Crystal structures of nematode (parasitic T. spiralis and free living C. elegans), compared to mammalian, thymidylate synthases (TS). Molecular docking and molecular dynamics simulations in search for nematode-specific inhibitors of TS.

PubMed

Jarmuła, Adam; Wilk, Piotr; Maj, Piotr; Ludwiczak, Jan; Dowierciał, Anna; Banaszak, Katarzyna; Rypniewski, Wojciech; Cieśla, Joanna; Dąbrowska, Magdalena; Frączyk, Tomasz; Bronowska, Agnieszka K; Jakowiecki, Jakub; Filipek, Sławomir; Rode, Wojciech

2017-10-01

Three crystal structures are presented of nematode thymidylate synthases (TS), including Caenorhabditis elegans (Ce) enzyme without ligands and its ternary complex with dUMP and Raltitrexed, and binary complex of Trichinella spiralis (Ts) enzyme with dUMP. In search of differences potentially relevant for the development of species-specific inhibitors of the nematode enzyme, a comparison was made of the present Ce and Ts enzyme structures, as well as binary complex of Ce enzyme with dUMP, with the corresponding mammalian (human, mouse and rat) enzyme crystal structures. To complement the comparison, tCONCOORD computations were performed to evaluate dynamic behaviors of mammalian and nematode TS structures. Finally, comparative molecular docking combined with molecular dynamics and free energy of binding calculations were carried out to search for ligands showing selective affinity to T. spiralis TS. Despite an overall strong similarity in structure and dynamics of nematode vs mammalian TSs, a pool of ligands demonstrating predictively a strong and selective binding to TsTS has been delimited. These compounds, the E63 family, locate in the dimerization interface of TsTS where they exert species-specific interactions with certain non-conserved residues, including hydrogen bonds with Thr174 and hydrophobic contacts with Phe192, Cys191 and Tyr152. The E63 family of ligands opens the possibility of future development of selective inhibitors of TsTS and effective agents against trichinellosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer

PubMed Central

Navarro-Teulon, Isabelle; Berthier-Vergnes, Odile; Fois, Giovanna; Zhu, Yingying; Besse, Sophie; Bawa, Olivia; Briat, Arnaud; Quintana, Mercedes; Pichard, Alexandre; Bonnet, Mathilde; Rubinstein, Eric; Pouget, Jean-Pierre; Opolon, Paule; Maigne, Lydia; Miot-Noirault, Elisabeth; Chezal, Jean-Michel

2017-01-01

Tetraspanin 8 (TSPAN8) overexpression is correlated with poor prognosis in human colorectal cancer (CRC). A murine mAb Ts29.2 specific for human TSPAN8 provided significant efficiency for immunotherapy in CRC pre-clinical models. We therefore evaluate the feasability of targeting TSPAN8 in CRC with radiolabeled Ts29.2. Staining of tissue micro-arrays with Ts29.2 revealed that TSPAN8 espression was restricted to a few human healthy tissues. DOTA-Ts29.2 was radiolabeled with 111In or 177Lu with radiochemical purities >95%, specific activity ranging from 300 to 600 MBq/mg, and radioimmunoreactive fractions >80%. The biodistribution of [111In]DOTA-Ts29.2 in nude mice bearing HT29 or SW480 CRC xenografts showed a high specificity of tumor localization with high tumor/blood ratios (HT29: 4.3; SW480-TSPAN8: 3.9 at 72h and 120h post injection respectively). Tumor-specific absorbed dose calculations for [177Lu]DOTA-Ts29.2 was 1.89 Gy/MBq, establishing the feasibility of using radioimmunotherapy of CRC with this radiolabeled antibody. A significant inhibition of tumor growth in HT29 tumor-bearing mice treated with [177Lu]DOTA-Ts29.2 was observed compared to control groups. Ex vivo experiments revealed specific DNA double strand breaks associated with cell apoptosis in [177Lu]DOTA-Ts29.2 treated tumors compared to controls. Overall, we provide a proof-of-concept for the use of [111In/177Lu]DOTA-Ts29.2 that specifically target in vivo aggressive TSPAN8-positive cells in CRC. PMID:28423546

Duct Diameter and Size of Stones Predict Successful Extracorporeal Shock Wave Lithotripsy and Endoscopic Clearance in Patients With Chronic Pancreatitis and Pancreaticolithiasis.

PubMed

Lapp, Robert T; Wolf, J Stuart; Faerber, Gary J; Roberts, William W; McCarthy, Sean T; Anderson, Michelle A; Wamsteker, Erik-Jan; Elta, Grace H; Scheiman, James M; Kwon, Richard S

2016-09-01

The need for endoscopic therapy before extracorporeal shock wave lithotripsy (SWL) to facilitate pancreatic duct stone removal is unclear. Predictive factors associated with successful fragmentation and subsequent complete duct clearance are variable. We hypothesize pancreatic duct strictures and large stones, but not pre-SWL endotherapy, correlate with successful fragmentation and complete duct clearance. A retrospective cohort study of patients with pancreaticolithiasis who underwent SWL and endoscopic retrograde cholangiopancreatography between January 2009 and June 2014 was evaluated. Thirty-seven patients were treated. Technical success (TS) of fragmentation was achieved in 22 patients (60%). Technical success was associated with fewer stones and SWL sessions and smaller stone and duct size. By multivariate logistic regression, only duct dilation was associated with TS. Endoscopic success of complete duct clearance was achieved in 29 patients (80%). Endoscopic success was more frequent with stones 12 mm or less and with successful TS. By multivariate logistic regression, stones greater than 12 mm were associated with endoscopic failure. Pre-SWL endotherapy does not affect stone fragmentation. Patients with a dilated duct (>8 mm) and pancreatic stones 12 mm or greater were associated with unsuccessful TS and endoscopic success, respectively, and may benefit from early referral for surgical decompression.

Reduced specificity of autobiographical memories in young people with tic disorders.

PubMed

Pile, Victoria; Robinson, Sally; Roberts, Elystan; Topor, Marta; Hedderly, Tammy; Lau, Jennifer Y F

2018-05-01

Depression is common in Tourette syndrome and Chronic Tic Disorders (TS/CTD) and contributes to significant impairment. The specificity of autobiographical memories is implicated in an individual's sense of self and their daily functioning but also in the onset and development of depression in the general population. Here, we examined whether memory specificity is reduced in young people with TS/CTD, relative to control participants, and whether memory specificity is associated with depression. Thirty young people with TS/CTD (14 females; age: x̅ = 11.31; SD = 1.66; 87% White British) and twenty-six (12 females; age: x̅ = 11.23; SD = 2.43; 77% White British) control participants completed the study. Participants completed the Autobiographical Memory Task, which asks participants to respond with a specific memory to cue words, and a questionnaire measure of depressive symptoms. There was no significant difference between the two groups in terms of age, gender, ethnicity, IQ and depressive symptomatology. Young people with TS/CTD had less specific autobiographical memories than their peers (p < 0.001, r = 0.49). Across both groups, increased memory specificity for positive cue words was associated with reduced depressive symptomatology (p < 0.001, R 2  = 0.51). Our findings indicate that autobiographical memory in young people with TS is characterised by a lack of specificity and, as with neurotypical peers, reduced memory specificity for positive words is associated with depressive symptoms. Autobiographical memory specificity could be an important factor in understanding mood symptoms that characterise young people with TS/CTD and may be an important cognitive target to reduce the development of depression in young people with TS/CTD. Copyright © 2018 Elsevier Inc. All rights reserved.

Costimulatory Effects of an Immunodominant Parasite Antigen Paradoxically Prevent Induction of Optimal CD8 T Cell Protective Immunity.

PubMed

Eickhoff, Christopher S; Zhang, Xiuli; Vasconcelos, Jose R; Motz, R Geoffrey; Sullivan, Nicole L; O'Shea, Kelly; Pozzi, Nicola; Gohara, David W; Blase, Jennifer R; Di Cera, Enrico; Hoft, Daniel F

2016-09-01

Trypanosoma cruzi infection is controlled but not eliminated by host immunity. The T. cruzi trans-sialidase (TS) gene superfamily encodes immunodominant protective antigens, but expression of altered peptide ligands by different TS genes has been hypothesized to promote immunoevasion. We molecularly defined TS epitopes to determine their importance for protection versus parasite persistence. Peptide-pulsed dendritic cell vaccination experiments demonstrated that one pair of immunodominant CD4+ and CD8+ TS peptides alone can induce protective immunity (100% survival post-lethal parasite challenge). TS DNA vaccines have been shown by us (and others) to protect BALB/c mice against T. cruzi challenge. We generated a new TS vaccine in which the immunodominant TS CD8+ epitope MHC anchoring positions were mutated, rendering the mutant TS vaccine incapable of inducing immunity to the immunodominant CD8 epitope. Immunization of mice with wild type (WT) and mutant TS vaccines demonstrated that vaccines encoding enzymatically active protein and the immunodominant CD8+ T cell epitope enhance subdominant pathogen-specific CD8+ T cell responses. More specifically, CD8+ T cells from WT TS DNA vaccinated mice were responsive to 14 predicted CD8+ TS epitopes, while T cells from mutant TS DNA vaccinated mice were responsive to just one of these 14 predicted TS epitopes. Molecular and structural biology studies revealed that this novel costimulatory mechanism involves CD45 signaling triggered by enzymatically active TS. This enhancing effect on subdominant T cells negatively regulates protective immunity. Using peptide-pulsed DC vaccination experiments, we have shown that vaccines inducing both immunodominant and subdominant epitope responses were significantly less protective than vaccines inducing only immunodominant-specific responses. These results have important implications for T. cruzi vaccine development. Of broader significance, we demonstrate that increasing breadth of T cell epitope responses induced by vaccination is not always advantageous for host immunity.

Physics and Engineering

ERIC Educational Resources Information Center

Jackson, G.

1972-01-01

Describes attempts in Britain to unite physics and technical studies in the new GCE A level engineering students (college bound). (Advocates more interdisciplinary efforts and greater use of mathematics.) (TS)

Application of dielectric constant measurement in microwave sludge disintegration and wastewater purification processes.

PubMed

Kovács, Petra Veszelovszki; Lemmer, Balázs; Keszthelyi-Szabó, Gábor; Hodúr, Cecilia; Beszédes, Sándor

2018-05-01

It has been numerously verified that microwave radiation could be advantageous as a pre-treatment for enhanced disintegration of sludge. Very few data related to the dielectric parameters of wastewater of different origins are available; therefore, the objective of our work was to measure the dielectric constant of municipal and meat industrial wastewater during a continuous flow operating microwave process. Determination of the dielectric constant and its change during wastewater and sludge processing make it possible to decide on the applicability of dielectric measurements for detecting the organic matter removal efficiency of wastewater purification process or disintegration degree of sludge. With the measurement of dielectric constant as a function of temperature, total solids (TS) content and microwave specific process parameters regression models were developed. Our results verified that in the case of municipal wastewater sludge, the TS content has a significant effect on the dielectric constant and disintegration degree (DD), as does the temperature. The dielectric constant has a decreasing tendency with increasing temperature for wastewater sludge of low TS content, but an adverse effect was found for samples with high TS and organic matter contents. DD of meat processing wastewater sludge was influenced significantly by the volumetric flow rate and power level, as process parameters of continuously flow microwave pre-treatments. It can be concluded that the disintegration process of food industry sludge can be detected by dielectric constant measurements. From technical purposes the applicability of dielectric measurements was tested in the purification process of municipal wastewater, as well. Determination of dielectric behaviour was a sensitive method to detect the purification degree of municipal wastewater.

Molecular cloning, characterization, and immunolocalization of two lactate dehydrogenase homologous genes from Taenia solium.

PubMed

Du, Wuying; Hu, Fengyu; Yang, Yabo; Hu, Dong; Hu, Xuchu; Yu, Xinbing; Xu, Jin; Dai, Jialin; Liao, Xinjiang; Huang, Jiang

2011-09-01

Two novel genes encoding lactate dehydrogenase A (LDHA) and B (LDHB) homologues, respectively, were identified from the cDNA libraries of adult Taenia solium (T. solium). The two deduced amino acid sequences both show more than 50% identity to the homologues for Danio rerio, Xenopus laevis, Schistosoma japonicum, Sus scrofa, Homo sapiens, et al. The identity of the amino acid sequence between TsLDHA and TsLDHB is 57.4%, and that of the nucleotide sequence is 61.5%. Recombinant TsLDHA homologue (rTsLDHA) and TsLDHB homologue (rTsLDHB) were expressed in Escherichia coli BL21/DE3 and purified. Though there were some differences in the sequence, the two LDH isozyme homologues show similarity in the conserved LDH domain, topological structure, primary immunological traits, localization on the tegument of T. solium adult, and partial physicochemical properties. The linear B-cell epitope analysis of TsLDHA and TsLDHB discovered a TsLDHA specific epitope. The purified rTsLDHA and rTsLDHB could be recognized by rat immuno-sera, serum from swine, or a patient infected with T. solium, respectively, but Western blot analysis showed cross-reactions, not only between these two LDH members but also with other common human tapeworms or helminths. The results suggested that the two LDH homologues are similar in the characteristics of LDH family, and they are not specific antigens for immunodiagnosis.

Face perception in women with Turner syndrome and its underlying factors.

PubMed

Anaki, David; Zadikov Mor, Tal; Gepstein, Vardit; Hochberg, Ze'ev

2016-09-01

Turner syndrome (TS) is a chromosomal condition that affects development in females. It is characterized by short stature, ovarian failure and other congenital malformations, due to a partial or complete absence of the sex chromosome. Women with TS frequently suffer from various physical and hormonal dysfunctions, along with impairments in visual-spatial processing and social cognition difficulties. Previous research has also shown difficulties in face and emotion perception. In the current study we examined two questions: First, whether women with TS, that are impaired in face perception, also suffer from deficits in face-specific processes. The second question was whether these face impairments in TS are related to visual-spatial perceptual dysfunctions exhibited by TS individuals, or to impaired social cognition skills. Twenty-six women with TS and 26 control participants were tested on various cognitive and psychological tests to assess visual-spatial perception, face and facial expression perception, and social cognition skills. Results show that women with TS were less accurate in face perception and facial expression processing, yet they exhibited normal face-specific processes (configural and holistic processing). They also showed difficulties in spatial perception and social cognition capacities. Additional analyses revealed that their face perception impairments were related to their deficits in visual-spatial processing. Thus, our results do not support the claim that the impairments in face processing observed in TS are related to difficulties in social cognition. Rather, our data point to the possibility that face perception difficulties in TS stem from visual-spatial impairments and may not be specific to faces. Copyright © 2016 Elsevier Ltd. All rights reserved.

The clinical and technical evaluation of a remote telementored telesonography system during the acute resuscitation and transfer of the injured patient.

PubMed

Dyer, Dianne; Cusden, Jane; Turner, Chris; Boyd, Jeff; Hall, Rob; Lautner, David; Hamilton, Douglas R; Shepherd, Lance; Dunham, Michael; Bigras, Andre; Bigras, Guy; McBeth, Paul; Kirkpatrick, Andrew W

2008-12-01

Ultrasound (US) has an ever increasing scope in the evaluation of trauma, but relies greatly on operator experience. NASA has refined telesongraphy (TS) protocols for traumatic injury, especially in reference to mentoring inexperienced users. We hypothesized that such TS might benefit remote terrestrial caregivers. We thus explored using real-time US and video communication between a remote (Banff) and central (Calgary) site during acute trauma resuscitations. A existing internet link, allowing bidirectional videoconferencing and unidirectional US transmission was used between the Banff and Calgary ERs. Protocols to direct or observe an extended focused assessment with sonography for trauma (EFAST) were adapted from NASA algorithms. A call rota was established. Technical feasibility was ascertained through review of completed checklists. Involved personnel were interviewed with a semistructured interview. In addition to three normal volunteers, 20 acute clinical examinations were completed. Technical challenges requiring solution included initiating US; audio and video communications; image freezing; and US transmission delays. FAST exams were completed in all cases and EFASTs in 14. The critical anatomic features of a diagnostic examination were identified in 98% of all FAST exams and a 100% of all EFASTs that were attempted. Enhancement of clinical care included confirmation of five cases of hemoperitoneum and two pneumothoraces (PTXs), as well as educational benefits. Remote personnel were appreciative of the remote direction particularly when instructions were given sequentially in simple, nontechnical language. The remote real-time guidance or observation of an EFAST using TS appears feasible. Most technical problems were quickly overcome. Further evaluation of this approach and technology is warranted in more remote settings with less experienced personnel.

L-lactic acid and sodium p-toluenesulfonate co-doped polypyrrole for high performance cathode in sodium ion battery

NASA Astrophysics Data System (ADS)

Liao, Qishu; Hou, Hongying; Liu, Xianxi; Yao, Yuan; Dai, Zhipeng; Yu, Chengyi; Li, Dongdong

2018-04-01

In this work, polypyrrole (PPy) was co-doped with L-lactic acid (LA) and sodium p-toluenesulfonate (TsONa) for high performance cathode in sodium ion battery (SIB) via facile one-step electropolymerization on Fe foil. The as-synthesized LA/TsONa co-doped PPy cathode was investigated in terms of scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), galvanostatic charge/discharge and cyclic voltammetry (CV). The results suggested that some oval-bud-like LA/TsONa co-doped PPy particles did form and tightly combine with the surface of Fe foil; furthermore, LA/TsONa co-doped PPy cathode also delivered higher electrochemical performances than TsONa mono-doped PPy cathode. For example, the initial specific discharge capacity was as high as about 124 mAh/g, and the reversible specific capacity still maintained at about 110 mAh/g even after 50 cycles, higher than those of TsONa mono-doped PPy cathode. The synergy effect of multi components of LA/TsONa co-doped PPy cathode should be responsible for high electrochemical performances.

Beryllium Health and Safety Committee Data Reporting Task Force White Paper #2 -- Uses of Uncensored Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacQueen, D H

2007-10-10

On December 8, 1999, the Department of Energy (DOE) published Title 10 CFR 850 (hereafter referred to as the Rule) to establish a chronic beryllium disease prevention program (CBDPP) to: (1) reduce the number of workers currently exposed to beryllium in the course of their work at DOE facilities managed by DOE or its contractors; (2) minimize the levels of, and potential for, exposure to beryllium; and (3) establish medical surveillance requirements to ensure early detection of the disease. On January 4, 2001, DOE issued DOE G 440.1-7A, Implementation Guide for use with 10 CFR 850, Chronic Beryllium Disease Preventionmore » Program, to assist line managers in meeting their responsibilities for implementing the CBDPP. That guide describes methods and techniques that DOE considers acceptable in complying with the Rule. In 2005 a draft DOE Technical Standard ''Management of Items and Areas Containing Low Levels of Beryllium'' (SAFT 0103; hereafter referred to as the ''TS'') was circulated for comment (http://www.hss.energy.gov/NuclearSafety/techstds/tsdrafts/saft-0103.pdf). DOE technical standards are voluntary consensus standards developed when industry standards do not exist (see http://www.hss.energy.gov/NuclearSafety/techstds/index.html for more information). DOE does not require its field elements to implement DOE technical standards, but field elements may choose to adopt these standards to meet specific needs. This beryllium TS is intended to provide best practices and lessons learned for manageing items and areas that contain low levels of beryllium, which has been a costly and technically challenging component of CBDPPs. The TS is also intended to provide guidance for determining if the Rule's housekeeping and release criteria are met. On challenge the TS addressed was the statistical interpretation of data sets with non-detected results, a topic for which no strong consensus exists. Among the many comments on the draft TS was a suggestion that certain of the statistical comparisons described in the TS could be better implemented if analytical results, even when below a reporting limit, were to be reported by analytical laboratories. See Appendix 1 for a review of terminology related to reporting limits. The Beryllium Health and Safety Committee (BHSC) formed a Sampling and Analysis Subcommittee (SAS) in 2003. The SAS established a working group on accreditation and reporting limits. By 2006 it had become evident that the issues extended to data reporting as a whole. The SAS proposed to the BHSC the formation of a Data Reporting Task Force (DRTF) to consider issues related to data reporting. The BHSC Board agreed, and requested that the DRTF generate a white paper, to be offered by the BHSC to potential interested parties such as the DOE policy office that is responsible for beryllium health and safety policy. It was noted that additional products could include detailed guidance and potentially a journal article in the future. The SAS proposed that DRTF membership represent the affected disciplines (chemists, industrial hygiene professionals and statisticians, and the DOE office that is responsible for beryllium health and safety policy). The BHSC Board decided that DRTF membership should come from DOE sites, since the focus would be on reporting in the context of the TS and the Rule. The DRTF came into existence in late 2006. The DRTF membership includes industrial hygienists, analytical chemists and laboratory managers, members of the regulatory and oversight community, and environmental statisticians. A first White Paper, ''Summary of Issues and Path Forward'', was reviewed by the BHSC in March 2007 and issued by the DRTF in June 2007. It describes the charter of the DRTF, introduces some basic terminology (reproduced here in Appendix 1), lays out the issues the DRTF is expected to address, and describes a path forward for the DRTF's work. This first White Paper is available through the BHSC web site. This White Paper presents recommendations developed by the DRTF following the process laid out in that first White Paper.« less

NEO Impact Hazard Scales in the Context of Other Hazard Scales

NASA Astrophysics Data System (ADS)

Chapman, C. R.; Mulligan, B. M.

2002-09-01

Astronomers are unaccustomed to practical matters like warning society about dangers. The NEO impact hazard has thrust new responsibilities upon us, which have been dealt with previously by other specialties, involving hurricanes, space weather, earthquakes, terrorism, etc. We discuss some lessons from the problems and successes of other warning scales. For example, a failing of the Torino Scale (TS) mirrors a failure of the Homeland Security Advisory System (HSAS, "terrorism scale"): it doesn't clearly tell ordinary folk what they should do; it says that TS=1 events merit "careful monitoring," a task for astronomers, not the public. The Red Cross has augmented the HSAS to separately advise individuals, families, neighborhoods, businesses, and schools what they should do; the TS could be similarly improved. The recent 2002 NT7 media scare was exacerbated by public use of the Palermo Technical Scale (PTS), which was not intended for such use, rather than the appropriate Torino Scale. Seismologists have more successfully avoided public confusion while internally debating different earthquake scales. Astronomers need to empathize with the needs of science journalists and communicators and with the low level of scientific comprehension by the public, who may be genuinely scared by mispresented cosmic hazards. A single warning scale should be used by all astronomers, should be very simple (e.g. one-dimensional), should have a public face that is consistent for years and decades (even if some fine-tuning is done behind the scenes in calculating values), and should suggest how a prudent person should react to a given hazard level. The TS has been used widely for several years by the popular media. It should remain the tool that we use to put particular impact predictions into context. While leaving the numbers and colors the same, we could augment and clarify the public advice. We could also make technical tweaks to how values are calculated. For example, it is possible to technically define Torino Scale values in a way more directly converted from PTS values.

Normal Performance in Non-Visual Social Cognition Tasks in Women with Turner Syndrome.

PubMed

Anaki, David; Zadikov-Mor, Tal; Gepstein, Vardit; Hochberg, Ze'ev

2018-01-01

Turner syndrome (TS) is a chromosomal disorder in women resulting from a partial or complete absence of the X chromosome. In addition to physical and hormonal dysfunctions, along with a unique neurocognitive profile, women with TS are reported to suffer from social functioning difficulties. Yet, it is unclear whether these difficulties stem from impairments in social cognition per se or from other deficits that characterize TS but are not specific to social cognition. Previous research that has probed social functioning in TS is equivocal regarding the source of these psychosocial problems since they have mainly used tasks that were dependent on visual-spatial skills, which are known to be compromised in TS. In the present study, we tested 26 women with TS and 26 matched participants on three social cognition tasks that did not require any visual-spatial capacities but rather relied on auditory-verbal skills. The results revealed that in all three tasks the TS participants did not differ from their control counterparts. The same TS cohort was found, in an earlier study, to be impaired, relative to controls, in other social cognition tasks that were dependent on visual-spatial skills. Taken together these findings suggest that the social problems, documented in TS, may be related to non-specific spatial-visual factors that affect their social cognition skills.

Cellular basis for neonatally induced T-suppressor activity. Primary B cell maturation is blocked by suppressor-helper interactions restricted by loci on chromosome 12

PubMed Central

1985-01-01

The cellular mechanism and genetic restriction of neonatally induced HA- specific suppressor T (Ts) cells have been examined. The in vivo effect of these Ts cells on antibody production, primary B cell proliferation, B cell surface marker changes, and helper T (Th) cell priming during primary responses to HA have been determined. The results indicate that, although antigen-induced B cell proliferative responses and surface marker changes occur in the presence of Ts cells, differentiation to Ig secretion, and long-lived memory B cell production are prevented. Further, antigen-specific Th cell priming is completely ablated by Ts cells, suggesting that Ts act by preventing the delivery of Th signals required for both the later stages of primary B cell maturation, and the formation of memory B cell populations. Finally, in vivo cell mixing experiments using congenic mice indicate that this Ts-Th interaction is restricted by loci on mouse chromosome 12. PMID:2580040

Generation and characterization of monoclonal antibodies specific for 18 kDa antigen from Taenia solium cysticerci.

PubMed

Zhang, Shaohua; Luo, Xuenong; Guo, Aijiang; Zhu, Xueliang; Cai, Xuepeng

2016-07-01

The gene encoding a mature 18 kDa glycoprotein of Taenia solium cysticerci (Ts18) was cloned and bacterially expressed with a His-tagged fusion protein. Monoclonal antibodies (MAbs) against the recombinant Ts18 antigen were generated in vitro by routine murine hybridoma technique of fusing splenocytes, from BALB/c mice immunized with the vesicular fluid of T. solium cysticerci (TsVF), with mouse myeloma cells (SP2/0). The reactivity and specificity of these MAbs were evaluated by indirect ELISA and immunoblotting techniques. Three stable hybridoma clones, namely 3B11, 6C5, and 6G4, were screened using His-Ts18-based ELISA, and these showed two IgG1 isotypes and one IgM isotype. All MAbs reacted with His-Ts18 at molecular weight (MW) 12.8 kDa and the native antigen at MW 18 kDa in TsVF and whole larval extracts (WLE). In a dot blotting test, MAbs 6C5 and 6G4 showed no obvious cross-reactivity with heterologous vesicular fluids from other taeniid species, including Taenia saginata (TsaVF), Taenia pisiformis (TpVF), Taenia hydatigena (ThVF), Taenia multiceps (TmVF), and Echinococcus granulosus (EgVF). Immunofluorescent assays showed that MAb 6C5 specifically reacted with the Ts18 expressed from pEGFP-N1-Ts18-transfected HeLa cells. Immunolocalization analysis, using MAb 6C5 as a probe, indicated that Ts18 was present at high concentrations in the region of the larval sucker and spiral canal. The results indicate that the Ts18 protein is an abundantly secreted parasite protein and MAbs against it might provide a step forward for improving the diagnosis of porcine cysticercosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping specificity landscapes of RNA-protein interactions by high throughput sequencing.

PubMed

Jankowsky, Eckhard; Harris, Michael E

2017-04-15

To function in a biological setting, RNA binding proteins (RBPs) have to discriminate between alternative binding sites in RNAs. This discrimination can occur in the ground state of an RNA-protein binding reaction, in its transition state, or in both. The extent by which RBPs discriminate at these reaction states defines RBP specificity landscapes. Here, we describe the HiTS-Kin and HiTS-EQ techniques, which combine kinetic and equilibrium binding experiments with high throughput sequencing to quantitatively assess substrate discrimination for large numbers of substrate variants at ground and transition states of RNA-protein binding reactions. We discuss experimental design, practical considerations and data analysis and outline how a combination of HiTS-Kin and HiTS-EQ allows the mapping of RBP specificity landscapes. Copyright © 2017 Elsevier Inc. All rights reserved.

75 FR 34181 - Connecticut Yankee Atomic Power Company, Haddam Neck Plant, Independent Spent Fuel Storage...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... Specification (TS) Surveillance Requirement 3.1.6.1 to verify the operability of the concrete cask heat removal... Specification (TS) Surveillance Requirement 3.1.6.1 to verify the operability of the concrete cask heat removal...

Technical, economic and environmental assessment of sludge treatment wetlands.

PubMed

Uggetti, Enrica; Ferrer, Ivet; Molist, Jordi; García, Joan

2011-01-01

Sludge treatment wetlands (STW) emerge as a promising sustainable technology with low energy requirements and operational costs. In this study, technical, economic and environmental aspects of STW are investigated and compared with other alternatives for sludge management in small communities (<2000 population equivalent). The performance of full-scale STW was characterised during 2 years. Sludge dewatering increased total solids (TS) concentration by 25%, while sludge biodegradation lead to volatile solids around 45% TS and DRI(24h) between 1.1 and 1.4 gO(2)/kgTS h, suggesting a partial stabilisation of biosolids. In the economic and environmental assessment, four scenarios were considered for comparison: 1) STW with direct land application of biosolids, 2) STW with compost post-treatment, 3) centrifuge with compost post-treatment and 4) sludge transport to an intensive wastewater treatment plant. According to the results, STW with direct land application is the most cost-effective scenario, which is also characterised by the lowest environmental impact. The life cycle assessment highlights that global warming is a significant impact category in all scenarios, which is attributed to fossil fuel and electricity consumption; while greenhouse gas emissions from STW are insignificant. As a conclusion, STW are the most appropriate alternative for decentralised sludge management in small communities. Copyright © 2010 Elsevier Ltd. All rights reserved.

75 FR 54390 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-07

... with the implementation of Nuclear Energy Institute (NEI) 04-10, ``Risk-Informed Technical... approved NEI 04-10, Rev. 1 in accordance with the TS SFCP. NEI [Nuclear Energy Institute] 04-10, Rev. 1...

Asthma-specific cognitions, self-focused attention, and fear of negative evaluation in adolescents and young adults diagnosed with childhood-onset asthma.

PubMed

Junghans-Rutelonis, Ashley N; Tackett, Alayna P; Suorsa, Kristina I; Chaney, John M; Mullins, Larry L

2018-01-01

The present study examined the impact of asthma-specific thought intrusion (TI) and thought suppression (TS) on two cognitive-affective variables (self-focused attention and fear of negative evaluation) among adolescents and young adults (AYAs) diagnosed with childhood-onset asthma. Participants were 290 AYAs who completed assessment questionnaires and participated in a written exercise electronically. Asthma-TI and TS were reported by participants following participation in a writing assignment. Asthma-TI was associated with increased private, public, and social anxiety self-focused attention, and greater fear of negative evaluation. Interestingly, asthma-TS was not associated with these same outcome variables. Findings suggest illness-specific cognitions are associated with cognitive-affective variables and it may be important to assess for illness-specific intrusive thoughts following asthma-focused medical appointments. Additionally, findings suggest the importance of assessing asthma-TI and TS separately in order to better understand thoughts about health and psychological functioning.

Application of Mutated miR-206 Target Sites Enables Skeletal Muscle-specific Silencing of Transgene Expression of Cardiotropic AAV9 Vectors

PubMed Central

Geisler, Anja; Schön, Christian; Größl, Tobias; Pinkert, Sandra; Stein, Elisabeth A; Kurreck, Jens; Vetter, Roland; Fechner, Henry

2013-01-01

Insertion of completely complementary microRNA (miR) target sites (miRTS) into a transgene has been shown to be a valuable approach to specifically repress transgene expression in non-targeted tissues. miR-122TS have been successfully used to silence transgene expression in the liver following systemic application of cardiotropic adeno-associated virus (AAV) 9 vectors. For miR-206–mediated skeletal muscle-specific silencing of miR-206TS–bearing AAV9 vectors, however, we found this approach failed due to the expression of another member (miR-1) of the same miR family in heart tissue, the intended target. We introduced single-nucleotide substitutions into the miR-206TS and searched for those which prevented miR-1–mediated cardiac repression. Several mutated miR-206TS (m206TS), in particular m206TS-3G, were resistant to miR-1, but remained fully sensitive to miR-206. All these variants had mismatches in the seed region of the miR/m206TS duplex in common. Furthermore, we found that some m206TS, containing mismatches within the seed region or within the 3′ portion of the miR-206, even enhanced the miR-206– mediated transgene repression. In vivo expression of m206TS-3G– and miR-122TS–containing transgene of systemically applied AAV9 vectors was strongly repressed in both skeletal muscle and the liver but remained high in the heart. Thus, site-directed mutagenesis of miRTS provides a new strategy to differentiate transgene de-targeting of related miRs. PMID:23439498

Expression and Regulatory Network Analysis of miR-140-3p, a New Potential Serum Biomarker for Autism Spectrum Disorder

PubMed Central

Cirnigliaro, Matilde; Barbagallo, Cristina; Gulisano, Mariangela; Domini, Carla N.; Barone, Rita; Barbagallo, Davide; Ragusa, Marco; Di Pietro, Cinzia; Rizzo, Renata; Purrello, Michele

2017-01-01

Given its prevalence and social impact, Autism Spectrum Disorder (ASD) is drawing much interest. Molecular basis of ASD is heterogeneous and only partially known. Many factors, including disorders comorbid with ASD, like TS (Tourette Syndrome), complicate ASD behavior-based diagnosis and make it vulnerable to bias. To further investigate ASD etiology and to identify potential biomarkers to support its precise diagnosis, we used TaqMan Low Density Array technology to profile serum miRNAs from ASD, TS, and TS+ASD patients, and unaffected controls (NCs). Through validation assays in 30 ASD, 24 TS, and 25 TS+ASD patients and 25 NCs, we demonstrated that miR-140-3p is upregulated in ASD vs.: NC, TS, and TS+ASD (Tukey's test, p-values = 0.03, = 0.01, < 0.0001, respectively). ΔCt values for miR-140-3p and YGTSS (Yale Global Tic Severity Scale) scores are positively correlated (Spearman r = 0.33; Benjamini-Hochberg p = 0.008) and show a linear relationship (p = 0.002). Network functional analysis showed that nodes controlled by miR-140-3p, especially CD38 and NRIP1 which are its validated targets, are involved in processes convergingly dysregulated in ASD, such as synaptic plasticity, immune response, and chromatin binding. Biomarker analysis proved that serum miR-140-3p can discriminate among: (1) ASD and NC (Area under the ROC curve, AUC: 0.70; sensitivity: 63.33%; specificity: 68%); (2) ASD and TS (AUC: 0.72; sensitivity: 66.66%; specificity: 70.83%); (3) ASD and TS+ASD (AUC: 0.78; sensitivity: 73.33%; specificity: 76%). Characterization of miR-140-3p network would contribute to further clarify ASD etiology. Serum miR-140-3p could represent a potential non-invasive biomarker for ASD, easy to test through liquid biopsy. PMID:28848387

DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

PubMed

Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

2015-10-01

The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (p<2.2e-16) than HK gene promoters. The entropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Installation Restoration Program Stage 3. Remedial Investigation/ Feasibility Study Elmendorf AFB, Alaska. Volume 2. Section 5 - Bibliography Text

DTIC Science & Technology

1990-05-01

ELME’IDORF AFB, AK UNITED STATES AIR FORCE OCCUPATIONAL & ENVIRONMENTAL HEALTH LABORATORY (AFSC) ilb(. IiCAL Sr.(VICES DIVISION (AFOEHLi £3) I BROOKS AIR...UNITED STATES AIR FORCE OCCUPATIONAL AND ENVIRONMENTAL HEALTH LABORATORY (AFSC) TECHNICAL SERVICES DIVISION (AFOEHL/TS) BROOKS AIR FORCE BASE, TEXAS...the following criteria: technical feasibility, institutional requirements, environmental impacts, public health impacts, and cost. This Alternative

CACDA Jiffy War Game Technical Manual. Part 1: Methodology

DTIC Science & Technology

1977-03-01

Systems Analysis Office (Mr Tyburski) Fort Monmout’.h, NJ 07703 Commander 1* USAISD ATTN: ATISE-TD-TS-CD (LT Boyer) Fort Deven , MASS 01433 Commander 2...Developments Activity Fort Leavenworth, Kansas 66027 CACDA JIFFY WAR GAME TECHNICAL MANUAL Part 1: Methodology by Timothy J. Bailey and Gerald A. Martin ACN...ComrbatDevelopments Activity (CACDA), Fort Leavenworth,i-Xsas," for scenario devel- opment and force structure evaluation. The Jiffy Game computer

Detection of Turner syndrome using X-chromosome inactivation specific differentially methylated CpG sites: A pilot study.

PubMed

Zhang, Qiang; Guo, Xiaohong; Tian, Tian; Wang, Teng; Li, Qiaoli; Wang, Lei; Liu, Yun; Xing, Qinghe; He, Lin; Zhao, Xinzhi

2017-05-01

Early diagnosis of Turner syndrome (TS) may improve preventive measures and treatment. X-chromosome inactivation specific differentially methylated CpG sites (XIDMSs) that are high methylated in inactive X chromosomes (Xi) and unmethylated in active X chromosomes (Xa) may be potential makers for TS detection. The candidate XIDMSs were screened from 9 male and 12 female DNA samples with normal karyotypes using the Illumina 450k array and validated by bisulfite sequencing PCR and pyrosequencing assay. X chromosome dosage was calculated according to the methylation level of multiple XIDMSs. Overall, 108 candidate XIDMSs were screened by the 450k array. Validations indicated that XIDMSs gathered and formed the X-chromosome inactivation specific differentially methylated regions (XIDMRs). Using 3 XIDMRs at SAT1, UXT and UTP14A loci, 36 TS, 22 normal female and 6 male samples were analyzed. Methylation levels of the 20 XIDMSs in the XIDMRs could distinguish between TS and normal female DNA samples, the X chromosome dosage was consistent with karyotyping data. Analyzing samples of 2 triple X syndrome and 3 Klinefelter syndrome patients suggested that this method could be used to detect X chromosome aneuploids other than TS. XIDMSs are widely spread along the X chromosome and might be effective markers for detection of TS and other X chromosome aneuploids. Copyright © 2017 Elsevier B.V. All rights reserved.

Tracking the mutual shaping of the technical and social dimensions of solar-powered mosquito trapping systems (SMoTS) for malaria control on Rusinga Island, western Kenya.

PubMed

Oria, Prisca A; Hiscox, Alexandra; Alaii, Jane; Ayugi, Margaret; Mukabana, Wolfgang Richard; Takken, Willem; Leeuwis, Cees

2014-11-18

There has been increasing effort in recent years to incorporate user needs in technology design and re-design. This project employed a bottom-up approach that engaged end users from the outset. Bottom-up approaches have the potential to bolster novel interventions and move them towards adaptive and evidence-based strategies. The present study concerns an innovative use of solar-powered mosquito trapping systems (SMoTS) to control malaria in western Kenya. Our paper highlights the co-dependence of research associated with the development of the SMoTS technology on one hand and research for enhancing the sustainable uptake of that very same intervention within the community on the other. During the pre-intervention year, we examined the design, re-design and piloting of a novel technology to generate lessons for malaria elimination on Rusinga Island. Initial ideas about many technological necessities were evaluated and re-designed following feedback from various sources, including technical and social research as well as broader interactions with the social environment. We documented the interlocking of the multiple processes and activities that took place through process observation and document reviews. We analysed the data within the conceptual framework of system innovation by identifying mutual shaping between technical and social factors. Our findings illustrate how various project stakeholders including project staff, collaborators, donor, and community members simultaneously pursued interdependent technological transformations and social interests. In the ongoing process, we observed how partial outcomes in the technological domain influenced social events at a later phase and vice versa. Looking at malaria intervention projects employing novel technologies as niches that may evolve towards system innovation, helps to reveal interrelations between the various technical and social aspects. Revealing these interrelations requires a different role for research and different perspective on innovation where innovation is more than the technical aspects. This approach therefore requires that research is designed in a way that enables obtaining feedback from both aspects.

Combining malaria control with house electrification: adherence to recommended behaviours for proper deployment of solar-powered mosquito trapping systems, Rusinga Island, western Kenya.

PubMed

Oria, Prisca A; Alaii, Jane; Ayugi, Margaret; Takken, Willem; Leeuwis, Cees

2015-08-01

To investigate community adherence to recommended behaviours for proper deployment of solar-powered mosquito trapping systems (SMoTS) after 3- to 10-week use. Solar-powered mosquito trapping system, which also provided power for room lighting and charging mobile phones, were installed in houses in Rusinga Island, western Kenya. We used a structured checklist for observations and a semi-structured questionnaire for interviews in 24 homesteads. We also analysed the subject of 224 community calls to the project team for technical maintenance of SMoTS. Most respondents cared for SMoTS by fencing, emptying and cleaning the trap. Our observations revealed that most traps were fenced, clean and in good working condition. A significantly higher proportion of community calls was lighting-related. Lighting was the main reason respondents liked SMoTS because it reduced or eliminated expenditure on kerosene. However, some respondents observed they no longer heard sounds of mosquitoes inside their houses. All respondents reportedly slept under insecticide-treated nets (ITNs) before receiving SMoTS. After receiving SMoTS, most respondents reportedly continued to use ITNs citing that the project advised them to do so. Some beach residents stopped using ITNs because they no longer heard mosquitoes or due to heat discomfort caused by lights. Electricity-related incentives played a greater role in encouraging adherence to recommended behaviours for proper deployment of SMoTS than the potential health benefits in the early stages of the intervention. Although energy-related financial incentives may play a role, they are insufficient to ensure adherence to health advice, even in the short term. Ongoing community engagement and research monitors and addresses adherence to recommended behaviours including continuation of current malaria control strategies. © 2015 John Wiley & Sons Ltd.

TS-Chemscore, a Target-Specific Scoring Function, Significantly Improves the Performance of Scoring in Virtual Screening.

PubMed

Wang, Wen-Jing; Huang, Qi; Zou, Jun; Li, Lin-Li; Yang, Sheng-Yong

2015-07-01

Most of the scoring functions currently used in structure-based drug design belong to 'universal' scoring functions, which often give a poor correlation between the calculated scores and experimental binding affinities. In this investigation, we proposed a simple strategy to construct target-specific scoring functions based on known 'universal' scoring functions. This strategy was applied to Chemscore, a widely used empirical scoring function, which led to a new scoring function, termed TS-Chemscore. TS-Chemscore was validated on 14 protein targets, which cover a wide range of biological target categories. The results showed that TS-Chemscore significantly improved the correlation between the calculated scores and experimental binding affinities compared with the original Chemscore. TS-Chemscore was then applied in virtual screening to retrieve novel JAK3 and YopH inhibitors. Top 30 compounds for each target were selected for experimental validation. Six active compounds for JAK3 and four for YopH were obtained. These compounds were out of the lists of top 30 compounds sorted by Chemscore. Collectively, TS-Chemscore established in this study showed a better performance in virtual screening than its counterpart Chemscore. © 2014 John Wiley & Sons A/S.

Centrality of prefrontal and motor preparation cortices to Tourette Syndrome revealed by meta-analysis of task-based neuroimaging studies.

PubMed

Polyanska, Liliana; Critchley, Hugo D; Rae, Charlotte L

2017-01-01

Tourette Syndrome (TS) is a neurodevelopmental condition characterized by chronic multiple tics, which are experienced as compulsive and 'unwilled'. Patients with TS can differ markedly in the frequency, severity, and bodily distribution of tics. Moreover, there are high comorbidity rates with attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), anxiety disorders, and depression. This complex clinical profile may account for apparent variability of findings across neuroimaging studies that connect neural function to cognitive and motor behavior in TS. Here we crystalized information from neuroimaging regarding the functional circuitry of TS, and furthermore, tested specifically for neural determinants of tic severity, by applying activation likelihood estimation (ALE) meta-analyses to neuroimaging (activation) studies of TS. Fourteen task-based studies (13 fMRI and one H2O-PET) met rigorous inclusion criteria. These studies, encompassing 25 experiments and 651 participants, tested for differences between TS participants and healthy controls across cognitive, motor, perceptual and somatosensory domains. Relative to controls, TS participants showed distributed differences in the activation of prefrontal (inferior, middle, and superior frontal gyri), anterior cingulate, and motor preparation cortices (lateral premotor cortex and supplementary motor area; SMA). Differences also extended into sensory (somatosensory cortex and the lingual gyrus; V4); and temporo-parietal association cortices (posterior superior temporal sulcus, supramarginal gyrus, and retrosplenial cortex). Within TS participants, tic severity (reported using the Yale Global Tic Severity Scale; YGTSS) selectively correlated with engagement of SMA, precentral gyrus, and middle frontal gyrus across tasks. The dispersed involvement of multiple cortical regions with differences in functional reactivity may account for heterogeneity in the symptomatic expression of TS and its comorbidities. More specifically for tics and tic severity, the findings reinforce previously proposed contributions of premotor and lateral prefrontal cortices to tic expression.

Characterization of HMA mixtures containing high reclaimed asphalt pavement content with crumb rubber additives : [technical summary].

DOT National Transportation Integrated Search

2013-03-01

With the increase in hot mix asphalt (HMA) mixtures prices continuously climbing, highway agencies and owners are continually : searching for methods to decrease material costs and maximize their benefi ts with no compromise in performance. One su...

Development and immunogenicity of recombinant GapA(+) Mycoplasma gallisepticum vaccine strain ts-11 expressing infectious bronchitis virus-S1 glycoprotein and chicken interleukin-6.

PubMed

Shil, Pollob K; Kanci, Anna; Browning, Glenn F; Markham, Philip F

2011-04-12

Mycoplasma gallisepticum (MG) is a major pathogen of poultry that causes chronic respiratory disease in chickens and infectious sinusitis in turkeys. A live attenuated vaccine, ts-11, has been used for the control of MG in several countries. The efficacy of this vaccine is highly dose dependent and the flock antibody response is weak. To improve the functionality of the vaccine and investigate its potential as a delivery vector for foreign antigens and immunomodulatory proteins, we developed a derivative of ts-11 expressing infectious bronchitis virus-S1 glycoprotein (IBV-S1) and releasing chicken interleukin-6 into the extracellular milieu (MG ts-11 C3 (+CS)) using a transposon-based delivery vector. Following administration of MG ts-11 C3 (+CS) to chickens by eye-drop, an antibody response to MG and IBV-S1, as determined by the rapid serum agglutination test (RSA) and Western blotting, respectively, could be detected. Birds inoculated with the recombinant vaccine had significantly enhanced weight gain and were partially protected against damage by pathogenic IBV. These results indicate that the ChIL-6 released by MG ts-11 C3 (+CS) may have had a non-specific effect on growth rate. They also suggest that ts-11 is a promising vaccine vector, capable of delivering heterologous protective antigens, and may also provide non-specific benefits when engineered to express immunomodulatory proteins. With some improvements in the expression system, it could be used to induce a targeted immune response against specific mucosal pathogens, and co-expression of several antigens would allow development of a novel multivalent vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

Modeling of space environment impact on nanostructured materials. General principles

NASA Astrophysics Data System (ADS)

Voronina, Ekaterina; Novikov, Lev

2016-07-01

In accordance with the resolution of ISO TC20/SC14 WG4/WG6 joint meeting, Technical Specification (TS) 'Modeling of space environment impact on nanostructured materials. General principles' which describes computer simulation methods of space environment impact on nanostructured materials is being prepared. Nanomaterials surpass traditional materials for space applications in many aspects due to their unique properties associated with nanoscale size of their constituents. This superiority in mechanical, thermal, electrical and optical properties will evidently inspire a wide range of applications in the next generation spacecraft intended for the long-term (~15-20 years) operation in near-Earth orbits and the automatic and manned interplanetary missions. Currently, ISO activity on developing standards concerning different issues of nanomaterials manufacturing and applications is high enough. Most such standards are related to production and characterization of nanostructures, however there is no ISO documents concerning nanomaterials behavior in different environmental conditions, including the space environment. The given TS deals with the peculiarities of the space environment impact on nanostructured materials (i.e. materials with structured objects which size in at least one dimension lies within 1-100 nm). The basic purpose of the document is the general description of the methodology of applying computer simulation methods which relate to different space and time scale to modeling processes occurring in nanostructured materials under the space environment impact. This document will emphasize the necessity of applying multiscale simulation approach and present the recommendations for the choice of the most appropriate methods (or a group of methods) for computer modeling of various processes that can occur in nanostructured materials under the influence of different space environment components. In addition, TS includes the description of possible approximations and limitations of proposed simulation methods as well as of widely used software codes. This TS may be used as a base for developing a new standard devoted to nanomaterials applications for spacecraft.

Melanoma detection. A prospective study comparing diagnosis with the naked eye, dermatoscopy and telespectrophotometry.

PubMed

Bono, Aldo; Bartoli, Cesare; Cascinelli, Natale; Lualdi, Manuela; Maurichi, Andrea; Moglia, Daniele; Tragni, Gabrina; Tomatis, Stefano; Marchesini, Renato

2002-01-01

Successful treatment of melanoma depends directly on early diagnosis. Such a diagnosis is based on clinical examination and dermatoscopy. Recently, automated instruments for melanoma detection are under development. To prospectively evaluate the diagnostic possibilities provided by clinical and dermatoscopic examinations and by a computerized telespectrophotometric system (TS). The study involves a consecutive series of 298 patients with 313 cutaneous pigmented lesions (66 melanomas and 247 non-melanoma lesions). Each lesion was subjected to the triple diagnostic evaluation, before surgery. Results were expressed in terms of sensitivity and specificity of each kind of evaluation. Clinical evaluation had sensitivity and specificity values of 86 and 77%, respectively, whereas dermatoscopy gave corresponding values of 91 and 74%. TS assessment resulted in a sensitivity of 80% and a specificity of 49%. Differences between clinical and dermatoscopic diagnoses lacked statistical significance (p = 0.22), whereas there was a significant difference comparing both clinical and TS evaluations (p < 0.01) and dermatoscopic and TS evaluations (p < 0.01). Combining clinical and dermatoscopic evaluations, a sensitivity of 97% was achieved. Addition of TS has not changed this figure. Results of this study confirm and stress the importance of dermatoscopy in the diagnosis of melanoma. Clinical evaluation coupled with dermatoscopy can be considered the cornerstone of such a diagnosis. Although TS is able to achieve interesting results, at present it cannot significantly compete with any of the other tested methods. Copyright 2002 S. Karger AG, Basel

Molecular characterization of 45 kDa aspartic protease of Trichinella spiralis.

PubMed

Park, Jong Nam; Park, Sang Kyun; Cho, Min Kyoung; Park, Mi-Kyung; Kang, Shin Ae; Kim, Dong-Hee; Yu, Hak Sun

2012-12-21

In a previous study, we identified an aspartic protease gene (Ts-Asp) from the Trichinella spiralis muscle stage larva cDNA library. The gene sequence of Ts-Asp was 1281 bp long and was found to encode a protein consisting of 405 amino acids, with a molecular mass of 45.248 kD and a pI of 5.95. The deduced Ts-Asp has a conserved catalytic motif with catalytic aspartic acid residues in the active site, a common characteristic of aspartic proteases. In addition, the deduced amino acid sequence of Ts-Asp was found to possess significant homology (above 50%) with aspartic proteases from nematode parasites. Results of phylogenetic analysis indicated a close relationship of Ts-Asp with cathepsin D aspartic proteases. For production of recombinant Ts-Asp (rTs-Asp), the pGEX4T expression system was used. Like other proteases, the purified rTs-Asp was able to digest collagen matrix in vitro. Abundant expression of Ts-Asp was observed in muscle stage larva. Ts-Asp was detected in ES proteins, and was able to elicit the production of specific antibodies. It is the first report of molecular characterization of aspartic protease isolated from T. spiralis. Copyright © 2012 Elsevier B.V. All rights reserved.

The Brave New World of Personality Disorder-Trait Specified: Effects of Additional Definitions on Coverage, Prevalence, and Comorbidity

PubMed Central

Clark, Lee Anna; Vanderbleek, Emily N.; Shapiro, Jaime L.; Nuzum, Hallie; Allen, Xia; Daly, Elizabeth; Kingsbury, Thomas J.; Oiler, Morgan; Ro, Eunyoe

2015-01-01

The alternative dimensional model for personality disorder (PD) in DSM-5, Section III (DSM-5-III) includes two main criteria: (A) personality-functioning impairment, and (B) personality-trait pathology; provides specific functioning-and-trait criteria for six PD-type diagnoses; and introduces PD-trait specified (PD-TS), which requires meeting the general PD criteria and not meeting criteria for any specific PD type. We termed this Simple PD-TS and developed two additional definitions: Mixed PD-TS, meeting criteria for one or two PD types and having five or more additional pathological traits; and Complex PD-TS, meeting criteria for three or more PD types. In a mixed sample of 165 outpatients and 215 community adults screened to be at high-risk for PD, we investigated the effect of these additional definitions on prevalence, coverage, comorbidity, and within-diagnosis heterogeneity, and conclude that eliminating the PD-type diagnoses and thus having PD-TS as the only PD diagnosis would be both more parsimonious and more useful clinically. PMID:26097740

A 6-year Follow-up survey of health status in middle-aged women with Turner syndrome.

PubMed

Fjermestad, Krister W; Naess, Eva E; Bahr, David; Gravholt, Claus H

2016-09-01

Studies suggest younger women with Turner syndrome (TS) have good quality of life. Less is known about everyday functioning in adults with TS. In a 6-year follow-up study, multiple areas of functioning were compared between TS women and controls. Women with TS and controls were mailed a self-report survey 6 years after a baseline study. Fifty-seven women with TS (M age 40·6 ± 11·1 years) and 101 controls (M age 38·8 ± 10·6 years, ns) responded. Measures of background information, experienced life strain and presence/impact of health conditions were developed for this study. The QPS Nordic measured perceived workload challenges. The LiSat-9 measured life satisfaction. The Rosenberg Self-Esteem Scale measured self-esteem. More TS women lived alone, fewer had biological children, and more had adoptive children. TS women reported fewer sex partners and less sexual confidence. Controls had higher education. There was no difference in employment status. More TS women received disability pensions. TS women reported their work as more physically challenging, less positively challenging and requiring less knowledge skills. TS women experienced more life strain in school, adolescence and late working life. Controls reported higher overall life satisfaction, with no difference between samples on specific domains. TS women reported lower self-esteem. For TS women only, physical health at baseline predicted length of education and mental health at baseline predicted self-esteem. Women with TS face more challenges than controls on several domains of functioning. Early physical and mental health may influence later educational achievement and self-esteem for women with TS. © 2016 John Wiley & Sons Ltd.

Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects.

PubMed

Stimac, Monika; Dolinsek, Tanja; Lampreht, Ursa; Cemazar, Maja; Sersa, Gregor

2015-01-01

Vascular targeted therapies, targeting specific endothelial cell markers, are promising approaches for the treatment of cancer. One of the targets is endoglin, transforming growth factor-β (TGF-β) co-receptor, which mediates proliferation, differentiation and migration of endothelial cells forming neovasculature. However, its specific, safe and long-lasting targeting remains the challenge. Therefore, in our study we evaluated the transfection efficacy, vascular targeted effects and therapeutic potential of the plasmid silencing endoglin with the tissue specific promoter, specific for endothelial cells marker endothelin-1 (ET) (TS plasmid), in comparison to the plasmid with constitutive promoter (CON plasmid), in vitro and in vivo. Tissue specificity of TS plasmid was demonstrated in vitro on several cell lines, and its antiangiogenic efficacy was demonstrated by reducing tube formation of 2H11 endothelial cells. In vivo, on a murine mammary TS/A tumor model, we demonstrated good antitumor effect of gene electrotransfer (GET) of either of both plasmids in treatment of smaller tumors still in avascular phase of growth, as well as on bigger tumors, already well vascularized. In support to the observations on predominantly vascular targeted effects of endoglin, histological analysis has demonstrated an increase in necrosis and a decrease in the number of blood vessels in therapeutic groups. A significant antitumor effect was observed in tumors in avascular and vascular phase of growth, possibly due to both, the antiangiogenic and the vascular disrupting effect. Furthermore, the study indicates on the potential use of TS plasmid in cancer gene therapy since the same efficacy as of CON plasmid was determined.

tRNA-Derived Small RNA: A Novel Regulatory Small Non-Coding RNA.

PubMed

Li, Siqi; Xu, Zhengping; Sheng, Jinghao

2018-05-10

Deep analysis of next-generation sequencing data unveils numerous small non-coding RNAs with distinct functions. Recently, fragments derived from tRNA, named as tRNA-derived small RNA (tsRNA), have attracted broad attention. There are mainly two types of tsRNAs, including tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived fragment (tRF), which differ in the cleavage position of the precursor or mature tRNA transcript. Emerging evidence has shown that tsRNAs are not merely tRNA degradation debris but have been recognized to play regulatory roles in many specific physiological and pathological processes. In this review, we summarize the biogeneses of various tsRNAs, present the emerging concepts regarding functions and mechanisms of action of tsRNAs, highlight the potential application of tsRNAs in human diseases, and put forward the current problems and future research directions.

Application of the multi-disciplinary thematic seminar method in two homecare cases - a comparative study.

PubMed

Scandurra, Isabella; Hägglund, Maria; Koch, Sabine

2008-01-01

A significant problem with current health information technologies is that they poorly support collaborative work of healthcare professionals, sometimes leading to a fragmentation of workflow and disruption of healthcare processes. This paper presents two homecare cases, both applying multi-disciplinary thematic seminars (MdTS) as a collaborative method for user needs elicitation and requirements specification. This study describes the MdTS application to elicit user needs from different perspectives to coincide with collaborative professions' work practices in two cases. Despite different objectives, the two cases validated that MdTS emphasized the "points of intersection" in cooperative work. Different user groups with similar, yet distinct needs reached a common understanding of the entire work process, agreed upon requirements and participated in the design of prototypes supporting cooperative work. MdTS was applicable in both exploratory and normative studies aiming to elicit the specific requirements in a cooperative environment.

CHARACTERIZING CONTAINERIZED MIXED LOW-LEVEL WASTE FOR TREATMENT - A WORKSHOP PROCEEDINGS

EPA Science Inventory

This report is the product of a technical workshop held in May 1993 in Las Vegas, Nevada addressing Mixed Low-Level Waste (MLLW). he workshop was conducted by the Environmental Protection Agency (EPA) and the Department of Energy (DOE). ts purpose was to define the characterizati...

Flight Technical Error for Category B Non-Precision Approaches and Missed Approaches Using Non-Differential GPS for Course Guidance

DOT National Transportation Integrated Search

1993-11-01

Twelve general aviation pilots flew a Beechcraft Baron on 93 non-precision instrument approaches using a nondifferential : GPS receiver nodifled to satisfy selected functional requirements specified in TS0-C129. : The purposes of the effort were to d...

RNA Structure Design Improves Activity and Specificity of trans-Splicing-Triggered Cell Death in a Suicide Gene Therapy Approach.

PubMed

Poddar, Sushmita; Loh, Pei She; Ooi, Zi Hao; Osman, Farhana; Eul, Joachim; Patzel, Volker

2018-06-01

Spliceosome-mediated RNA trans-splicing enables correction or labeling of pre-mRNA, but therapeutic applications are hampered by issues related to the activity and target specificity of trans-splicing RNA (tsRNA). We employed computational RNA structure design to improve both on-target activity and specificity of tsRNA in a herpes simplex virus thymidine kinase/ganciclovir suicide gene therapy approach targeting alpha fetoprotein (AFP), a marker of hepatocellular carcinoma (HCC) or human papillomavirus type 16 (HPV-16) pre-mRNA. While unstructured, mismatched target binding domains significantly improved 3' exon replacement (3'ER), 5' exon replacement (5'ER) correlated with the thermodynamic stability of the tsRNA 3' end. Alternative on-target trans-splicing was found to be a prevalent event. The specificity of trans-splicing with the intended target splice site was improved 10-fold by designing tsRNA that harbors secondary target binding domains shielding alternative on-target and blinding off-target splicing events. Such rationally designed suicide RNAs efficiently triggered death of HPV-16-transduced or hepatoblastoma-derived human tissue culture cells without evidence for off-target cell killing. Highest cell death activities were observed with novel dual-targeting tsRNAs programmed for trans-splicing toward AFP and a second HCC pre-mRNA biomarker. Our observations suggest trans-splicing represents a promising approach to suicide gene therapy. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome.

PubMed

Hirschtritt, M E; Darrow, S M; Illmann, C; Osiecki, L; Grados, M; Sandor, P; Dion, Y; King, R A; Pauls, D; Budman, C L; Cath, D C; Greenberg, E; Lyon, G J; Yu, D; McGrath, L M; McMahon, W M; Lee, P C; Delucchi, K L; Scharf, J M; Mathews, C A

2018-01-01

The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families. OCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed. EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders). Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flanagan, Sheryl A., E-mail: sflan@umich.edu; Cooper, Kristin S.; Mannava, Sudha

Purpose: To determine the effect of short hairpin ribonucleic acid (shRNA)-mediated suppression of thymidylate synthase (TS) on cytotoxicity and radiosensitization and the mechanism by which these events occur. Methods and Materials: shRNA suppression of TS was compared with 5-fluoro-2 Prime -deoxyuridine (FdUrd) inactivation of TS with or without ionizing radiation in HCT116 and HT29 colon cancer cells. Cytotoxicity and radiosensitization were measured by clonogenic assay. Cell cycle effects were measured by flow cytometry. The effects of FdUrd or shRNA suppression of TS on dNTP deoxynucleotide triphosphate imbalances and consequent nucleotide misincorporations into deoxyribonucleic acid (DNA) were analyzed by high-pressure liquidmore » chromatography and as pSP189 plasmid mutations, respectively. Results: TS shRNA produced profound ({>=}90%) and prolonged ({>=}8 days) suppression of TS in HCT116 and HT29 cells, whereas FdUrd increased TS expression. TS shRNA also produced more specific and prolonged effects on dNTPs deoxynucleotide triphosphates compared with FdUrd. TS shRNA suppression allowed accumulation of cells in S-phase, although its effects were not as long-lasting as those of FdUrd. Both treatments resulted in phosphorylation of Chk1. TS shRNA alone was less cytotoxic than FdUrd but was equally effective as FdUrd in eliciting radiosensitization (radiation enhancement ratio: TS shRNA, 1.5-1.7; FdUrd, 1.4-1.6). TS shRNA and FdUrd produced a similar increase in the number and type of pSP189 mutations. Conclusions: TS shRNA produced less cytotoxicity than FdUrd but was equally effective at radiosensitizing tumor cells. Thus, the inhibitory effect of FdUrd on TS alone is sufficient to elicit radiosensitization with FdUrd, but it only partially explains FdUrd-mediated cytotoxicity and cell cycle inhibition. The increase in DNA mismatches after TS shRNA or FdUrd supports a causal and sufficient role for the depletion of dTTP thymidine triphosphate and consequent DNA mismatches underlying radiosensitization. Importantly, shRNA suppression of TS avoids FP-mediated TS elevation and its negative prognostic role. These studies support the further exploration of TS suppression as a novel radiosensitizing strategy.« less

Incidence, puberty, and fertility in 45,X/47,XXX mosaicism: Report of a patient and a literature review.

PubMed

Lim, Han Hyuk; Kil, Hong Ryang; Koo, Sun Hoe

2017-05-09

Turner syndrome (TS), characterized by short stature and premature ovarian failure, is caused by chromosomal aberrations with total or partial loss of one of the two X chromosomes. Spontaneous puberty, menarche, and pregnancy occur in some patients depending on the abnormality of the X. Moreover, spontaneous pregnancy is uncommon (<0.5%) for TS with 45,X monosomy. Among TS patients, 45,X/47,XXX karyotype is extremely rare. Previous reports have demonstrated that TS with 45,X/47,XXX is less severe than common TS due to higher occurrence of puberty (83%), menarche (57-67%), and fertility (14%) and lower occurrence of congenital anomalies (<5%). However, TS mosaicism may not reduce the frequency of short stature. We diagnosed a 10-year-girl with TS with 45,X/47,XXX mosaicism who presented with short stature. She showed mild TS phenotype including short stature but had spontaneous puberty. Based on our case and previous reports, we expect that girls with 45,X/47,XXX mosaicism may progress through puberty normally, without estrogen therapy. Therefore, it is necessary to consider specific guidelines for clinical decisions surrounding pubertal development and fertility in TS with 45,X/47,XXX karyotype. © 2017 Wiley Periodicals, Inc.

Terson syndrome in aneurysmal subarachnoid hemorrhage-its relation to intracranial pressure, admission factors, and clinical outcome.

PubMed

Joswig, Holger; Epprecht, Lorenz; Valmaggia, Christophe; Leschka, Sebastian; Hildebrandt, Gerhard; Fournier, Jean-Yves; Stienen, Martin Nikolaus

2016-06-01

A large number of reports have not been able to clarify the pathophysiology of Terson syndrome (TS) in aneurysmal subarachnoid hemorrhage (aSAH). Prospective single-center study on aSAH patients. Fundoscopic and radiological signs of TS were assessed. The opening intracranial pressure (ICP) in patients who required a ventriculostomy was recorded with a manometer. Six out of 36 included patients had TS (16.7 %), which was associated with unfavorable admission scores. Twenty-nine patients (80.5 %) required ventriculostomy; TS was associated with higher ICP (median, 40 vs. 15 cm cmH2O, p = .003); all patients with TS had pathological ICP values of >20 cmH2O. Patients with a ruptured aneurysm of the anterior cerebral artery complex were ten times as likely to suffer from TS (OR 10.0, 95 % CI 1.03-97.50). Detection of TS on CT had a sensitivity of 50 %, a specificity of 98.4 %, a positive predictive value of 83.3 %, and a negative predictive value of 92.4 %. Mortality was 45 times as high in patients with TS (OR 45.0, 95 % CI 3.86-524.7) and neurologic morbidity up until 3 months post-aSAH was significantly higher in patients with TS (mRS 4-6; 100 vs. 17 %; p = .001). Our findings demonstrate an association between raised ICP and the incidence of TS. TS should be ruled out in aSAH patients presenting comatose or with raised ICP to ensure upfront ophthalmological follow-up. In alert patients without visual complaints and a TS-negative CT scan, the likelihood for the presence of TS is very low.

Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome

PubMed Central

Best, Tyler K.; Cramer, Nathan P.; Chakrabarti, Lina; Haydar, Tarik F.; Galdzicki, Zygmunt

2013-01-01

GABAergic dysfunction is implicated in hippocampal deficits of the Ts65Dn mouse model of Down syndrome (DS). Since Ts65Dn mice overexpress G-protein coupled inward-rectifying potassium (GIRK2) containing channels, we sought to evaluate whether increased GABAergic function disrupts the functioning of hippocampal circuitry. After confirming that GABAB/GIRK current density is significantly elevated in Ts65Dn CA1 pyramidal neurons, we compared monosynaptic inhibitory inputs in CA1 pyramidal neurons in response to proximal (stratum radiatum; SR) and distal (stratum lacunosum moleculare; SLM) stimulation of diploid and Ts65Dn acute hippocampal slices. Synaptic GABAB and GABAA mediated currents evoked by SR stimulation were generally unaffected in Ts65Dn CA1 neurons. However, the GABAB/GABAA ratios evoked by stimulation within the SLM of Ts65Dn hippocampus were significantly larger in magnitude, consistent with increased GABAB/GIRK currents after SLM stimulation. These results indicate that GIRK overexpression in Ts65Dn has functional consequences which affect the balance between GABAB and GABAA inhibition of CA1 pyramidal neurons, most likely in a pathway specific manner, and may contribute to cognitive deficits reported in these mice. PMID:22178330

A User-Oriented Methodology for DInSAR Time Series Analysis and Interpretation: Landslides and Subsidence Case Studies

NASA Astrophysics Data System (ADS)

Notti, Davide; Calò, Fabiana; Cigna, Francesca; Manunta, Michele; Herrera, Gerardo; Berti, Matteo; Meisina, Claudia; Tapete, Deodato; Zucca, Francesco

2015-11-01

Recent advances in multi-temporal Differential Synthetic Aperture Radar (SAR) Interferometry (DInSAR) have greatly improved our capability to monitor geological processes. Ground motion studies using DInSAR require both the availability of good quality input data and rigorous approaches to exploit the retrieved Time Series (TS) at their full potential. In this work we present a methodology for DInSAR TS analysis, with particular focus on landslides and subsidence phenomena. The proposed methodology consists of three main steps: (1) pre-processing, i.e., assessment of a SAR Dataset Quality Index (SDQI) (2) post-processing, i.e., application of empirical/stochastic methods to improve the TS quality, and (3) trend analysis, i.e., comparative implementation of methodologies for automatic TS analysis. Tests were carried out on TS datasets retrieved from processing of SAR imagery acquired by different radar sensors (i.e., ERS-1/2 SAR, RADARSAT-1, ENVISAT ASAR, ALOS PALSAR, TerraSAR-X, COSMO-SkyMed) using advanced DInSAR techniques (i.e., SqueeSAR™, PSInSAR™, SPN and SBAS). The obtained values of SDQI are discussed against the technical parameters of each data stack (e.g., radar band, number of SAR scenes, temporal coverage, revisiting time), the retrieved coverage of the DInSAR results, and the constraints related to the characterization of the investigated geological processes. Empirical and stochastic approaches were used to demonstrate how the quality of the TS can be improved after the SAR processing, and examples are discussed to mitigate phase unwrapping errors, and remove regional trends, noise and anomalies. Performance assessment of recently developed methods of trend analysis (i.e., PS-Time, Deviation Index and velocity TS) was conducted on two selected study areas in Northern Italy affected by land subsidence and landslides. Results show that the automatic detection of motion trends enhances the interpretation of DInSAR data, since it provides an objective picture of the deformation behaviour recorded through TS and therefore contributes to the understanding of the on-going geological processes.

Web-Based Mathematics: Some "Dos" and "Don'ts"

ERIC Educational Resources Information Center

Loong, Esther Yook-Kin

2011-01-01

This case study describes an "out of field" teacher's use of the Internet to teach a range of mathematical topics in a modified Year 8 mathematics class. It highlights the importance of three factors for implementing a discernible web-based teaching strategy: appropriate choice of web objects, effective "virtual" pedagogy, and technical support…

Improving the mixing performances of rice straw anaerobic digestion for higher biogas production by computational fluid dynamics (CFD) simulation.

PubMed

Shen, Fei; Tian, Libin; Yuan, Hairong; Pang, Yunzhi; Chen, Shulin; Zou, Dexun; Zhu, Baoning; Liu, Yanping; Li, Xiujin

2013-10-01

As a lignocellulose-based substrate for anaerobic digestion, rice straw is characterized by low density, high water absorbability, and poor fluidity. Its mixing performances in digestion are completely different from traditional substrates such as animal manures. Computational fluid dynamics (CFD) simulation was employed to investigate mixing performances and determine suitable stirring parameters for efficient biogas production from rice straw. The results from CFD simulation were applied in the anaerobic digestion tests to further investigate their reliability. The results indicated that the mixing performances could be improved by triple impellers with pitched blade, and complete mixing was easily achieved at the stirring rate of 80 rpm, as compared to 20-60 rpm. However, mixing could not be significantly improved when the stirring rate was further increased from 80 to 160 rpm. The simulation results agreed well with the experimental results. The determined mixing parameters could achieve the highest biogas yield of 370 mL (g TS)(-1) (729 mL (g TS(digested))(-1)) and 431 mL (g TS)(-1) (632 mL (g TS(digested))(-1)) with the shortest technical digestion time (T 80) of 46 days. The results obtained in this work could provide useful guides for the design and operation of biogas plants using rice straw as substrates.

The Evolution of Thyroid Function after Presenting with Hashimoto Thyroiditis Is Different between Initially Euthyroid Girls with and Those without Turner Syndrome.

PubMed

Wasniewska, Malgorzata; Salerno, Mariacarolina; Corrias, Andrea; Mazzanti, Laura; Matarazzo, Patrizia; Corica, Domenico; Aversa, Tommaso; Messina, Maria Francesca; De Luca, Filippo; Valenzise, Mariella

2016-01-01

To prospectively investigate, during a 5-year follow-up, whether the prognosis of thyroid function with Hashimoto thyroiditis (HT) is different in euthyroid girls with Turner syndrome (TS) than in euthyroid girls without TS. In 66 TS girls and 132 non-TS girls with euthyroid HT and similar thyroid functional test results at HT diagnosis, we followed up the evolution of thyroid status over time. At the end of follow-up, the TS girls exhibited higher TSH levels, lower fT4 levels, and lower prevalence rates of both euthyroidism and subclinical hypothyroidism, but higher prevalence rates of both overt hypothyroidism and hyperthyroidism, irrespective of the karyotype. An association with TS is able to impair the long-term prognosis of thyroid function in girls with HT. Such an effect occurs irrespective of thyroid functional test results at HT diagnosis and is not necessarily linked with a specific karyotype. © 2016 S. Karger AG, Basel.

Tourette syndrome and other neurodevelopmental disorders: a comprehensive review.

PubMed

Cravedi, Elena; Deniau, Emmanuelle; Giannitelli, Marianna; Xavier, Jean; Hartmann, Andreas; Cohen, David

2017-01-01

Gilles de la Tourette syndrome (TS) is a complex developmental neuropsychiatric condition in which motor manifestations are often accompanied by comorbid conditions that impact the patient's quality of life. In the DSM-5, TS belongs to the "neurodevelopmental disorders" group, together with other neurodevelopmental conditions, frequently co-occurring. In this study, we searched the PubMed database using a combination of keywords associating TS and all neurodevelopmental diagnoses. From 1009 original reports, we identified 36 studies addressing TS and neurodevelopmental comorbidities. The available evidence suggests the following: (1) neurodevelopmental comorbidities in TS are the rule, rather than the exception; (2) attention deficit/hyperactivity disorder (ADHD) is the most frequent; (3) there is a continuum from a simple (TS + ADHD or/and learning disorder) to a more complex phenotype (TS + autism spectrum disorder). We conclude that a prompt diagnosis and a detailed description of TS comorbidities are necessary not only to understand the aetiological basis of neurodevelopmental disorders but also to address specific rehabilitative and therapeutic approaches.

Self-reported emotion regulation in adults with Tourette's syndrome.

PubMed

Drury, Helena; Wilkinson, Verity; Robertson, Mary M; Channon, Shelley

2016-11-30

Recent work has reported mild impairments in social and emotional processing in Tourette's syndrome (TS), but deliberate attempts to use specific emotion regulation strategies have not been investigated previously. In the present study, adult participants with TS and no comorbidities (TS-alone) were compared to healthy control participants on several self-report measures assessing habitual use of reappraisal and suppression emotion regulation strategies. There were no group differences on measures of reappraisal, but the TS-alone group reported using suppression more frequently than the control group and this was true across a range of negative emotions. The groups did not differ on symptomatology scores of anxiety or depression, although more frequent use of suppression was associated with higher depressive symptomatology for the TS-alone group only. Further work is needed to examine potential factors that may influence emotion regulation in TS, including increased emotional reactivity or expertise in applying strategies to suppress tic symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Rolling blackout is required for bulk endocytosis in non-neuronal cells and neuronal synapses.

PubMed

Vijayakrishnan, Niranjana; Woodruff, Elvin A; Broadie, Kendal

2009-01-01

Rolling blackout (RBO) is a Drosophila EFR3 integral membrane lipase. A conditional temperature-sensitive (TS) mutant (rbo(ts)) displays paralysis within minutes following a temperature shift from 25 degrees C to 37 degrees C, an impairment previously attributed solely to blocked synaptic-vesicle exocytosis. However, we found that rbo(ts) displays a strong synergistic interaction with the Syntaxin-1A TS allele syx(3-69), recently shown to be a dominant positive mutant that increases Syntaxin-1A function. At neuromuscular synapses, rbo(ts) showed a strong defect in styryl-FM-dye (FM) endocytosis, and rbo(ts);syx(3-69) double mutants displayed a synergistic, more severe, endocytosis impairment. Similarly, central rbo(ts) synapses in primary brain culture showed severely defective FM endocytosis. Non-neuronal nephrocyte Garland cells showed the same endocytosis defect in tracer-uptake assays. Ultrastructurally, rbo(ts) displayed a specific defect in tracer uptake into endosomes in both neuronal and non-neuronal cells. At the rbo(ts) synapse, there was a total blockade of endosome formation via activity-dependent bulk endocytosis. Clathrin-mediated endocytosis was not affected; indeed, there was a significant increase in direct vesicle formation. Together, these results demonstrate that RBO is required for constitutive and/or bulk endocytosis and/or macropinocytosis in both neuronal and non-neuronal cells, and that, at the synapse, this mechanism is responsive to the rate of Syntaxin-1A-dependent exocytosis.

Short hairpin RNA suppression of thymidylate synthase produces DNA mismatches and results in excellent radiosensitization.

PubMed

Flanagan, Sheryl A; Cooper, Kristin S; Mannava, Sudha; Nikiforov, Mikhail A; Shewach, Donna S

2012-12-01

To determine the effect of short hairpin ribonucleic acid (shRNA)-mediated suppression of thymidylate synthase (TS) on cytotoxicity and radiosensitization and the mechanism by which these events occur. shRNA suppression of TS was compared with 5-fluoro-2'-deoxyuridine (FdUrd) inactivation of TS with or without ionizing radiation in HCT116 and HT29 colon cancer cells. Cytotoxicity and radiosensitization were measured by clonogenic assay. Cell cycle effects were measured by flow cytometry. The effects of FdUrd or shRNA suppression of TS on dNTP deoxynucleotide triphosphate imbalances and consequent nucleotide misincorporations into deoxyribonucleic acid (DNA) were analyzed by high-pressure liquid chromatography and as pSP189 plasmid mutations, respectively. TS shRNA produced profound (≥ 90%) and prolonged (≥ 8 days) suppression of TS in HCT116 and HT29 cells, whereas FdUrd increased TS expression. TS shRNA also produced more specific and prolonged effects on dNTPs deoxynucleotide triphosphates compared with FdUrd. TS shRNA suppression allowed accumulation of cells in S-phase, although its effects were not as long-lasting as those of FdUrd. Both treatments resulted in phosphorylation of Chk1. TS shRNA alone was less cytotoxic than FdUrd but was equally effective as FdUrd in eliciting radiosensitization (radiation enhancement ratio: TS shRNA, 1.5-1.7; FdUrd, 1.4-1.6). TS shRNA and FdUrd produced a similar increase in the number and type of pSP189 mutations. TS shRNA produced less cytotoxicity than FdUrd but was equally effective at radiosensitizing tumor cells. Thus, the inhibitory effect of FdUrd on TS alone is sufficient to elicit radiosensitization with FdUrd, but it only partially explains FdUrd-mediated cytotoxicity and cell cycle inhibition. The increase in DNA mismatches after TS shRNA or FdUrd supports a causal and sufficient role for the depletion of dTTP thymidine triphosphate and consequent DNA mismatches underlying radiosensitization. Importantly, shRNA suppression of TS avoids FP-mediated TS elevation and its negative prognostic role. These studies support the further exploration of TS suppression as a novel radiosensitizing strategy. Copyright © 2012 Elsevier Inc. All rights reserved.

GapA+ Mycoplasma gallisepticum ts-11 has improved vaccine characteristics.

PubMed

Shil, Pollob K; Kanci, Anna; Browning, Glenn F; Marenda, Marc S; Noormohammadi, Amir H; Markham, Philip F

2011-06-01

Mycoplasma gallisepticum (MG) is an important poultry pathogen that causes respiratory disease and loss of production worldwide, and is currently controlled with live attenuated vaccines. These vaccines have limitations as they vary in their pathogenicity, the protection afforded and their transmissibility, but have been shown to effectively reduce losses associated with challenge in the field. A live attenuated vaccine, ts-11, has been used for the control of M. gallisepticum in several countries. This vaccine is highly dose-dependent and the flock antibody response is weak. GapA is the primary cytadherence molecule in M. gallisepticum, and the absence of GapA expression has been observed in the vast majority of cells in the ts-11 vaccine strain. In this study the immunogenicity of a GapA(+) M. gallisepticum ts-11 vaccine was investigated in specific-pathogen-free chickens. Birds vaccinated with GapA(+) M. gallisepticum ts-11 were protected against clinical signs of disease following challenge with virulent M. gallisepticum, and GapA(+) M. gallisepticum ts-11 was shown to be non-pathogenic and more immunogenic at a lower dose than the currently available M. gallisepticum ts-11 vaccine. Thus, GapA(+) M. gallisepticum ts-11 appears to have improved potential as a vaccine candidate.

Calculation of the temperature in the container unit with a modified design for the production of {sup 99}Mo at the VVR-Ts research reactor facility (IVV.10M)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kazantsev, A. A., E-mail: kazantsevanatoly@gmail.com; Sergeev, V. V.; Kochnov, O. Yu.

The temperature regime is calculated for two different designs of containers with uranium-bearing material for the upgraded VVR-Ts research reactor facility (IVV.10M). The containers are to be used in the production of {sup 99}Mo. It is demonstrated that the modification of the container design leads to a considerable temperature reduction and an increase in the near-wall boiling margin and allows one to raise the amount of material loaded into the container. The calculations were conducted using the international thermohydraulic contour code TRAC intended to analyze the technical safety of water-cooled nuclear power units.

Evaluation of the egg transmission and pathogenicity of Mycoplasma gallisepticum isolates genotyped as ts-11.

PubMed

Armour, Natalie K; Ferguson-Noel, Naola

2015-01-01

Live Mycoplasma gallisepticum vaccines are used for the control of respiratory disease, egg production losses and egg transmission associated with M. gallisepticum infection in long-lived poultry. The first field case of apparent increased virulence and vertical transmission of ts-11, a live M. gallisepticum vaccine, has been reported. In that study a M. gallisepticum isolate from the broiler progeny of ts-11-vaccinated breeders was genotyped as ts-11 by sequence analysis of four different genetic targets and Random Amplified Polymorphic DNA and found to be significantly more virulent than ts-11 vaccine. The objective of the current study was to evaluate the rate of egg transmission and pathogenicity of ts-11 vaccine and isolates recovered from ts-11-vaccinated breeders (K6222B) and their broiler progeny (K6216D) which had been genotyped as ts-11. Groups of 28-week-old specific pathogen-free chickens at 87% average weekly egg production were inoculated with sterile broth media (negative controls), ts-11 vaccine, K6222B, K6216D or R strain (positive controls) by eye-drop and aerosol. K6216D transmitted via the egg at an average rate of 4.0% in the third and fourth weeks post-infection, while egg transmission of K6222B and ts-11 vaccine was not detected. M. gallisepticum was isolated from the air sacs, ovaries and oviducts of hens infected with K6216D and K6222B, but not from those infected with ts-11 vaccine. K6216D and K6222B both induced respiratory signs and significantly more tracheal colonization and more severe tracheal and air sac lesions than ts-11 vaccine (P ≤ 0.05). There were no substantial differences in the egg production of ts-11, K6216D and K6222B infected groups. These results provide the first conclusive evidence of transovarian transmission of an isolate genotyped as ts-11 and indicate that isolates genotyed as ts-11 vary in their virulence and ability to transmit via the egg.

A controlled study of Tourette syndrome. IV. Obsessions, compulsions, and schizoid behaviors.

PubMed Central

Comings, D E; Comings, B G

1987-01-01

To determine the frequency of obsessive, compulsive, and schizoid behaviors in Tourette syndrome (TS), we prospectively questioned 246 patients with TS, 17 with attention-deficit disorder (ADD), 15 with ADD due to a TS gene, and 47 random controls. The comparative frequency of obsessive, compulsive, and repetitive behaviors--such as obsessive unpleasant thoughts, obsessive silly thoughts, echolalia, palilalia, touching things excessively, touching things a specific number of times, touching others excessively, sexual touching, biting or hurting oneself, head banging, rocking, mimicking others, counting things, and occasional or frequent public exhibitionism--were significantly more common in TS patients than in controls. The frequency of each of these was much higher for grade 3 (severe) TS. Most of these behaviors also occurred significantly more often in individuals with ADD or in individuals with ADD secondary to TS (ADD 2(0) TS). When these features were combined into an obsessive-compulsive score, 45.4% of TS patients had a score of 4-15, whereas 8.5% of controls had a score of 4 or 5. These results indicate that obsessive-compulsive behaviors are an integral part of the expression of the TS gene and can be inherited as an autosomal dominant trait. Schizoid symptoms, such as thinking that people were watching them or plotting against them, were significantly more common in TS patients than in controls. Auditory hallucinations of hearing voices were present in 14.6% of TS patients, compared with 2.1% of controls (P = .02). These symptoms were absent in ADD patients but present in ADD 2(0) TS patients. These voices were often blamed for telling them to do bad things and were frequently identified with the devil. None of the controls had a total schizoid behavior score greater than 3, whereas 10.9% of the TS patients had scores of 4-10 (P = .02). This frequency increased to 20.6% in the grade 3 TS patients. These quantitative results confirm our clinical impression that some TS patients have paranoid ideations, often feel that people are out to get them, and hear voices. PMID:3479015

Comparison of the effects between animal-derived trypsin and recombinant trypsin on human skin cells proliferation, gene and protein expression.

PubMed

Manira, Maarof; Khairul Anuar, Khairoji; Seet, Wan Tai; Ahmad Irfan, Abd Wahab; Ng, Min Hwei; Chua, Kien Hui; Mohd Heikal, Mohd Yunus; Aminuddin, Bin Saim; Ruszymah, Bt Hj Idrus

2014-03-01

Animal-derivative free reagents are preferred in skin cell culture for clinical applications. The aim of this study was to compare the performance and effects between animal-derived trypsin and recombinant trypsin for skin cells culture and expansion. Full thickness human skin was digested in 0.6 % collagenase for 6 h to liberate the fibroblasts, followed by treatment with either animal-derived trypsin; Trypsin EDTA (TE) or recombinant trypsin; TrypLE Select (TS) to liberate the keratinocytes. Both keratinocytes and fibroblasts were then culture-expanded until passage 2. Trypsinization for both cell types during culture-expansion was performed using either TE or TS. Total cells yield was determined using a haemocytometer. Expression of collagen type I, collagen type III (Col-III), cytokeratin 10, and cytokeratin 14 genes were quantified via RT-PCR and further confirmed with immunocytochemical staining. The results of our study showed that the total cell yield for both keratinocytes and fibroblasts treated with TE or TS were comparable. RT-PCR showed that expression of skin-specific genes except Col-III was higher in the TS treated group compared to that in the TE group. Expression of proteins specific to the two cell types were confirmed by immunocytochemical staining in both TE and TS groups. In conclusion, the performance of the recombinant trypsin is comparable with the well-established animal-derived trypsin for human skin cell culture expansion in terms of cell yield and expression of specific cellular markers.

Technical Standards and Deaf and Hard of Hearing Medical School Applicants and Students: Interrogating Sensory Capacity and Practice Capacity.

PubMed

Argenyi, Michael

2016-10-01

Applicants to medical schools who are deaf and hard of hearing (DHoH) or who have other disabilities face significant barriers to medical school admission. One commonly cited barrier to admission is medical schools' technical standards (TS) for admission, advancement, and graduation. Ethical values of diversity and equity support altering the technical standards to be more inclusive of people with disabilities. Incorporating these values into admissions, advancement, and graduation considerations for DHoH and other students with disabilities can contribute to the physician workforce being more representative of the diverse patients it serves and better able to care for them. © 2016 American Medical Association. All Rights Reserved.

[Structure and characteristics of technical support that psychiatric social workers of prefectural governments provide for municipalities].

PubMed

Okada, Takashi

2017-01-01

Objectives　The support to municipalities by prefectural governments has become necessary in the fields of mental health and welfare. Therefore, psychiatric social workers (PSW) ordered from the prefectural governor has been providing technical support (TS) that promote community activities of the municipality and improve staff support for persons with mental disabilities. The purpose of this study was to identify empirical structure and characteristics of TS that PSW provide for municipality staff.Method　Semi-structured interviews were conducted with seven certified PSW randomly selected from the membership list of the National Psychiatric Social Worker Organization. Inclusion criteria required participants to have more than 10 years of experience at the prefectural government and experience providing TS in the last five years. Interviews focused on two situations: a casework and a project related to mental health. Interview data were analyzed using a qualitative content method, setting a framework for the consultation process.Results　The analysis included five categories < > and 15 subcategories [ ], which consisted of 37 concepts. In category with municipalities consisted of [complementary relationship] and [partnership]. The category included two subcategories, [analyze/judgment from the conditions spread in front of] and [analyze/judgment be the accumulated skills and knowledge in person]. In category , six policies were considered as important, including [problem solving and promoting action], [fostering person centered care perspective], [promoting the understanding of residents], [provide psychological support to the staff], [clarify responsibility as the municipal officials], and [coordinate to improve the environment]. Category consisted of both [support indirectly] and [support cooperatively]. The last category, included three subcategories, [lead to the maintenance and improvement of the system], [have the staff pleasure/contribute to the community], and [consider whether it can be applied to other regions]. The results showed that the characteristics of TS had a consultation function, and the support function utilized complementarity and collaboration between prefecture and municipality providing services to residents.Conclusion　This study has clarified the characteristics of TS, which have not been clarified in previous research. We should accumulate the knowledge and establish a method for spreading through various regions.

ESGE-ESGENA technical specification for process validation and routine testing of endoscope reprocessing in washer-disinfectors according to EN ISO 15883, parts 1, 4, and ISO/TS 15883-5.

PubMed

Beilenhoff, Ulrike; Biering, Holger; Blum, Reinhard; Brljak, Jadranka; Cimbro, Monica; Dumonceau, Jean-Marc; Hassan, Cesare; Jung, Michael; Neumann, Christiane; Pietsch, Michael; Pineau, Lionel; Ponchon, Thierry; Rejchrt, Stanislav; Rey, Jean-François; Schmidt, Verona; Tillett, Jayne; van Hooft, Jeanin

2017-12-01

1 Prerequisites. The clinical service provider should obtain confirmation from the endoscope washer-disinfector (EWD) manufacturer that all endoscopes intended to be used can be reprocessed in the EWD. 2 Installation qualification. This can be performed by different parties but national guidelines should define who has the responsibilities, taking into account legal requirements. 3 Operational qualification. This should include parametric tests to verify that the EWD is working according to its specifications. 4 Performance qualification. Testing of cleaning performance, microbiological testing of routinely used endoscopes, and the quality of the final rinse water should be considered in all local guidelines. The extent of these tests depends on local requirements. According to the results of type testing performed during EWD development, other parameters can be tested if local regulatory authorities accept this. Chemical residues on endoscope surfaces should be searched for, if acceptable test methods are available. 5 Routine inspections. National guidelines should consider both technical and performance criteria. Individual risk analyses performed in the validation and requalification processes are helpful for defining appropriate test frequencies for routine inspections. © Georg Thieme Verlag KG Stuttgart · New York.

The C-terminal Helix of Pseudomonas aeruginosa Elongation Factor Ts Tunes EF-Tu Dynamics to Modulate Nucleotide Exchange.

PubMed

De Laurentiis, Evelina Ines; Mercier, Evan; Wieden, Hans-Joachim

2016-10-28

Little is known about the conservation of critical kinetic parameters and the mechanistic strategies of elongation factor (EF) Ts-catalyzed nucleotide exchange in EF-Tu in bacteria and particularly in clinically relevant pathogens. EF-Tu from the clinically relevant pathogen Pseudomonas aeruginosa shares over 84% sequence identity with the corresponding elongation factor from Escherichia coli Interestingly, the functionally closely linked EF-Ts only shares 55% sequence identity. To identify any differences in the nucleotide binding properties, as well as in the EF-Ts-mediated nucleotide exchange reaction, we performed a comparative rapid kinetics and mutagenesis analysis of the nucleotide exchange mechanism for both the E. coli and P. aeruginosa systems, identifying helix 13 of EF-Ts as a previously unnoticed regulatory element in the nucleotide exchange mechanism with species-specific elements. Our findings support the base side-first entry of the nucleotide into the binding pocket of the EF-Tu·EF-Ts binary complex, followed by displacement of helix 13 and rapid binding of the phosphate side of the nucleotide, ultimately leading to the release of EF-Ts. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Variable (Tg, Ts) Measurements of Alkane Dissociative Sticking Coefficients

NASA Astrophysics Data System (ADS)

Valadez, Leticia; Dewitt, Kristy; Abbott, Heather; Kolasinski, Kurt; Harrision, Ian

2006-03-01

Dissociative sticking coefficients S(Tg, Ts) for CH4 and C2H6 on Pt(111) have been measured as a function of gas temperature (Tg) and surface temperature (Ts) using an effusive molecular beam. Microcanonical unimolecular rate theory (MURT) was employed to extract transition state characteristics [e.g., E0(CH4) = 52.5±3.5 kJ/mol-1 and E0(C2H6) = 26.5±3 kJ/mol-1]. MURT allows our S(Tg, Ts) values to be directly compared to other supersonic molecular beam and thermal equilibrium sticking measurements. The S(Tg, Ts) depend strongly on Ts, however, only for CH4 is a strong Tg dependence observed. The fairly weak Tg dependence for C2H6 suggests that vibrational mode specific behavior and/or molecular rotations play stronger roles in the dissociative chemisorption of C2H6 than they do for CH4. Interestingly, thermal S(Tg=Ts) predictions based on MURT modeling of our CH4/Pt(111) data are three orders of magnitude higher than recent thermal equilibrium measurements on supported Pt nanocrystallite catalysts [J. M. Wei, E. Iglesia, J. Phys. Chem. B 108, 4094 (2004)].

Evaluation of the immune response induced by DNA vaccines expressing MIF and MCD-1 genes of Trichinella spiralis in BALB/c mice.

PubMed

Tang, F; Xu, L; Yan, R; Song, X; Li, X

2012-12-01

Plasmids expressing macrophage migration inhibitory factor (MIF) of Trichinella spiralis (TsMIF), multi-cystatin-like domain protein (MCD-1) of T. spiralis (TsMCD-1), or co-expressing TsMIF and TsMCD-1 were constructed with a pVAX1 vector. Their ability to generate a protective immune response against T. spiralis infection was evaluated in BALB/c mice. Groups of mice were immunized twice at 2-week intervals with 100 μg of recombinant plasmids pVAX1-Tsmif, pVAX1-Tsmcd-1 or pVAX1-Tsmif-Tsmcd-1. Control animals were immunized with phosphate-buffered saline (PBS) or blank vector plasmid. Specific antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, IgA, IgE) against the recombinant protein TsMIF-TsMCD-1, serum cytokines (interferon (IFN)-γ, interleukin (IL)-4, IL-5, transforming growth factor (TGF)-β1 and IL-17) and CD4+/CD8+ T cells were monitored. Challenge infection was performed 2 weeks following the second immunization and worm burden was assayed at 35 days post-challenge. Vaccination with pVAX1-Tsmif induced moderate serum IFN-γ and increases of CD4+ and CD8+ T cells, but no specific immunoglobulin antibody response. Vaccination with pVAX1-Tsmcd-1 induced a predominant Th1 antibody (IgG2a and IgG2b) response and strong levels of serum IFN-γ, and increases of CD4+ T cells. Importantly, co-expression of TsMIF and TsMCD-1 in DNA immunization produced more serum IFN-γ and markedly enhanced CD4+ and CD8+ T cells than the single DNA vaccine of the two genes. Challenge infection demonstrated that immunization with pVAX1-Tsmif-Tsmcd-1 reduced worm burdens (by 23.17%; P < 0.05).

Comparing Military and Civilian Skill Training: Instruction and Program Evaluation. Final Report, October 1 - December 31, 1976.

ERIC Educational Resources Information Center

Gray, Burl B.; And Others

A questionnaire study was conducted to gather in-depth comparative data on job training practices in the Department of Defense (DOD), commercial business/institutions/industries (B/I/I), and proprietary trade/technical schools (T/TS). Detailed questionnaires requesting information on the management, conduct, and costs of twelve high-priority job…

Probability of Failure of Damaged Ship Structures - Phase 3

DTIC Science & Technology

2014-04-01

U. Akpan, B. Yuen, T. S. Koko , F. Lin, J. Wallace Martec Limited Prepared By: Martec Limited Suite 400, 1888 Brunswick St, Halifax, Nova Scotia, B3J...3J8 Martec Technical Report TR-13-15 Contract Project Manager: T.S. Koko , 902-425-5101 CSA: Malcolm J. Smith, Group Leader/ NPSS, 902-426-3100 ext 383

Specific arithmetic calculation deficits in children with Turner syndrome.

PubMed

Rovet, J; Szekely, C; Hockenberry, M N

1994-12-01

Study 1 compared arithmetic processing skills on the WRAT-R in 45 girls with Turner syndrome (TS) and 92 age-matched female controls. Results revealed significant underachievement by subjects with TS, which reflected their poorer performance on problems requiring the retrieval of addition and multiplication facts and procedural knowledge for addition and division operations. TS subjects did not differ qualitatively from controls in type of procedural error committed. Study 2, which compared the performance of 10 subjects with TS and 31 controls on the Keymath Diagnostic Arithmetic Test, showed that the TS group had less adequate knowledge of arithmetic, subtraction, and multiplication procedures but did not differ from controls on Fact items. Error analyses revealed that TS subjects were more likely to confuse component steps or fail to separate intermediate steps or to complete problems. TS subjects relied to a greater degree on verbal than visual-spatial abilities in arithmetic processing while their visual-spatial abilities were associated with retrieval of simple multidigit addition facts and knowledge of subtraction, multiplication, and division procedures. Differences between the TS and control groups increased with age for Keymath, but not WRAT-R, procedures. Discrepant findings are related to the different task constraints (timed vs. untimed, single vs. alternate versions, size of item pool) and the use of different strategies (counting vs. fact retrieval). It is concluded that arithmetic difficulties in females with TS are due to less adequate procedural skills, combined with poorer fact retrieval in timed testing situations, rather than to inadequate visual-spatial abilities.

Protective effect of the Japanese traditional medicine juzentaihoto on myelosuppression induced by the anticancer drug TS-1 and identification of a potential biomarker of this effect.

PubMed

Ogawa, Kazuo; Omatsu, Tatsushi; Matsumoto, Chinami; Tsuchiya, Naoko; Yamamoto, Masahiro; Naito, Yuji; Yoshikawa, Toshikazu

2012-08-09

TS-1 is an oral anticancer drug containing a 5-fluorouracil derivative (Tegafur) that is widely used in Japan for the treatment of cancer, especially gastrointestinal tumors. Frequently, however, TS-1 therapy has to be discontinued because of leukopenia. If it were possible to predict the development of bone marrow suppression before the white blood cell (WBC) count had actually decreased, treatment could be improved by strict dosage control and/or the prophylactic administration of hematopoietic drugs. Juzentaihoto (JTT), a traditional Japanese medicine (Kampo), has been reported to activate hematopoiesis and reduce the side effects associated with chemotherapy and radiotherapy. Here, we 1) evaluate the efficacy of JTT in alleviating myelosuppression induced by TS-1 therapy in mice, and 2) explore biomarkers that reflect both induction by TS-1 and alleviation by JTT of bone marrow suppression using a proteomics approach. Ten mg/kg of TS-1 was administered to Balb/c mice with or without 1 g/kg of oral JTT for 3, 5 and 7 days. WBC count and ratio of CD34+ bone marrow cells (BMCs) were estimated by flow cytometry. Plasma samples were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF-MS). A biomarker candidate from SELDI profiling was identified using a combination of cation exchange spin column purification, SDS-PAGE, enzymatic digestion and LC-MS/MS. After administration of TS-1, a significant decrease in WBC count and CD34+ BMC ratio were observed at days 5 and 3, respectively. JTT treatment improved WBC count on day 7 and CD34+ BMC ratio on days 5 and 7. SELDI analysis highlighted three protein peaks that had increased on day 3 after treatment with TS-1 but remained unchanged in mice co-treated with JTT. One of the three peaks, m/z 4223.1, was further investigated and identified as a specific C-terminal fragment of albumin. This study indicates that bone marrow suppression by treatment with TS-1 in mice might be improved by coadministration of JTT. A C-terminal fragment of albumin was identified as a candidate biomarker for predicting TS-1-induced myelosuppression. However, the sensitivity and specificity of the biomarker candidate must be validated in future clinical studies.

Functional neuroanatomy of tics.

PubMed

Neuner, Irene; Schneider, Frank; Shah, N Jon

2013-01-01

The therapeutic success of haloperidol in the treatment of Tourette syndrome (TS) put an end to the discussion about a "hysteric" or "neurotic" origin of TS. The cortico-striato-thalamo-cortical circuit has been identified as an underlying neurobiological correlate of TS. In this review we explore the main findings of structural alterations in TS including cortical areas, basal ganglia, hippocampus, amygdala, midbrain, and cerebellum. Based on the structural changes we examine the functional pattern described by the findings of fMRI and (15)O-PET/(18)FDG PET investigations. From the neuroimaging findings a cortical origin of the generation of tics is indicated. Future research on the neuronal footprint of TS should be directed towards addressing the question of which patterns of connectivity distinguish individuals in whom tics disappear during early adulthood from those in whom the tics persist. The understanding of this pathomechanism could provide a key on how to influence dysconnectivity in TS, for example, by more specific pharmaceutical intervention or by individually adopted EEG and/or fMRI neurofeedback. © 2013 Elsevier Inc. All rights reserved.

A DNA vaccine co-expressing Trichinella spiralis MIF and MCD-1 with murine ubiquitin induces partial protective immunity in mice.

PubMed

Tang, F; Xu, L; Yan, R; Song, X; Li, X

2013-03-01

Co-expression of Trichinella spiralis macrophage migration inhibitory factor (TsMIF) with T. spiralis cystatin-like domain protein (TsMCD-1) in a DNA vaccine induces a Th1 immune response and partial protection against T. spiralis infection. The present study evaluated whether co-expression of mouse ubiquitin (Ub) with TsMIF and TsMCD-1 might improve the immune response against T. spiralis infection. Groups of BALB/c mice were immunized twice at 2-week intervals with 100 μg of plasmid DNA encoding either a TsMIF-TsMCD-1 fusion protein (pVAX1-Tsmif-Tsmcd-1) or an Ub-co-expressing triple fusion protein Ub-TsMIF-TsMCD-1 (pVAX1-Ub-Tsmif-Tsmcd-1). Control animals were immunized with pVAX1-Ub or blank vector plasmid. Specific antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, IgA, IgE) against the recombinant protein TsMIF-TsMCD-1, serum cytokines (interferon (IFN)-γ, interleukin (IL)-4, IL-5, transforming growth factor (TGF)-β1 and IL-17), CD4+/CD8+ T cells and cytotoxic T lymphocyte (CTL) responses were monitored. Challenge infection was performed 2 weeks after the second immunization and worm burden was assayed at 35 days post-challenge. Antibody responses induced by pVAX1-Ub-Tsmif-Tsmcd-1 were significantly lower than for TsMIF-TsMCD-1, but the vaccine induced increased levels of Th1 cytokine (IFN-γ) and increased T-cell cytotoxicity. The reduction of worm burden (37.95%) following immunization with pVAX1-Ub-Tsmif-Tsmcd-1 was significantly greater than that induced by the pVAX1-Tsmif-Tsmcd-1 vaccine (23.17%; P< 0.05).

Evidence of a novel aggrecan-degrading activity in cartilage: Studies of mice deficient in both ADAMTS-4 and ADAMTS-5.

PubMed

Rogerson, Fraser M; Stanton, Heather; East, Charlotte J; Golub, Suzanne B; Tutolo, Leonie; Farmer, Pamela J; Fosang, Amanda J

2008-06-01

To characterize aggrecan catabolism and the overall phenotype in mice deficient in both ADAMTS-4 and ADAMTS-5 (TS-4/TS-5 Delta-cat) activity. Femoral head cartilage from the joints of TS-4/TS-5 Delta-cat mice and wild-type mice were cultured in vitro, and aggrecan catabolism was stimulated with either interleukin-1alpha (IL-1alpha) or retinoic acid. Total aggrecan release was measured, and aggrecanase activity was examined by Western blotting using neoepitope antibodies for detecting cleavage at EGE 373-374 ALG, SELE 1279-1280 GRG, FREEE 1467-1468 GLG, and AQE 1572-1573 AGEG. Aggrecan catabolism in vivo was examined by Western blotting of cartilage that had been extracted immediately ex vivo. TS-4/TS-5 Delta-cat mice were viable, fertile, and phenotypically normal. TS-4/TS-5 Delta-cat cartilage explants did not release aggrecan in response to IL-1alpha, and there was no detectable increase in aggrecanase neoepitopes. TS-4/TS-5 Delta-cat cartilage explants released aggrecan in response to retinoic acid. There was no retinoic acid-stimulated cleavage at either EGE 373-374 ALG or AQE 1572-1573 AGEG. There was a low level of cleavage at SELE 1279-1280 GRG and major cleavage at FREEE 1467-1468 GLG. Ex vivo, cleavage at FREEE 1467-1468 GLG was substantially reduced, but still present, in TS-4/TS-5 Delta-cat mouse cartilage compared with wild-type mouse cartilage. An aggrecanase other than ADAMTS-4 and ADAMTS-5 is expressed in mouse cartilage and is up-regulated by retinoic acid but not IL-1alpha. The novel aggrecanase appears to have different substrate specificity from either ADAMTS-4 or ADAMTS-5, cleaving E-G bonds but not E-A bonds. Neither ADAMTS-4 nor ADAMTS-5 is required for normal skeletal development or aggrecan turnover in cartilage.

Evaluation of the reported association of obsessive-compulsive symptoms or disorder with Tourette's disorder.

PubMed

Shapiro, A K; Shapiro, E

1992-01-01

This review evaluates the evidence reporting an association of obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) with Tourette's syndrome or disorder (TS). Published reports in the literature describing a relationship between OCS-OCD and TS provided the data for the review. The methodological adequacy of the studies are discussed and rated on five criteria: adequacy of the experimental sample, presence and adequacy of the control sample, whether tics are defined as OCS-OCD, whether blind procedures are used to diagnose OCS-OCD in subjects and controls, and evidence for the reliability and validity of OCS-OCD measures. Although there are considerable clinical indications suggesting an association of OCS-OCD with TS and chronic motor tic disorder (CMT), and a possible overlap between OSC-OCD and TS, our evaluation of the evidence does not provide adequate support for an association between these disorders. To meaningfully evaluate the possible relationship between OCS-OCD and TS requires development of specific criteria for classification of OCS-OCD-TS symptoms, use of adequate experimental and control samples, blind evaluation, reliable and valid measures of OCS-OCD-TS, and appropriate statistical analysis. If such studies are performed, it is possible that the strong relationship reported between OCS-OCD and TS is more likely to be artifact than fact, and recent bandwagon effect rather than the latest breakthrough.

Interrelations between orthostatic postural deviations and subjects' age, sex, malocclusion, and specific signs and symptoms of functional pathologies of the temporomandibular system: a preliminary correlation and regression study.

PubMed

Munhoz, Wagner Cesar; Hsing, Wu Tu

2014-07-01

Studies on the relationships between postural deviations and the temporomandibular system (TS) functional health are controversial and inconclusive. This study stems from the hypothesis that such inconclusiveness is due to authors considering functional pathologies of the TS (FPTS) as a whole, without taking into account subjects' specific FPTS signs and symptoms. Based on the author and collaborators' previous studies, the present study analyzed data on body posture from a sample of 50 subjects with (30) and without (20) FPTS. Correlation analyses were applied, taking as independent variables age, sex, Helkimo anamnestic, occlusal, and dysfunction indices, as well as FPTS specific signs and symptoms. Postural assessments of the head, cervical spine, shoulders, lumbar spine, and hips were the dependent variables. Linear regression equations were built that proved to partially predict the presence and magnitude of body posture deviations by drawing on subjects' characteristics and specific FPTS symptoms. Determination coefficients for these equations ranged from 0.082 to 0.199 in the univariate, and from 0.121 to 0.502 in the multivariate regression analyses. Results show that factors intrinsic to the subjects or the TS may potentially interfere in results of studies that analyze relationships between FPTS and body posture. Furthermore, a trend to specificity was found, e.g. the degree of cervical lordosis was found to correlate to age and FPTS degree of severity, suggesting that some TS pathological features, or malocclusion, age or sex, may be more strongly correlated than others with specific posture patterns.

Assessment of a solid-phase reagent for urinary specific gravity determination.

PubMed

Chu, S Y; Sparks, D

1984-02-01

We have compared the specific gravity (S.G.) determined by the N-Multistix method with that obtained from the Total Solids (TS) meter. Overall, 88.7% of the specific gravity results obtained with the reagent strip method were within 0.005 of those obtained with the TS meter. There was a good correlation between the methods and there was no bias for the group means obtained by either method. A good correlation was also found between the S.G. on the strip and osmolality (correlation coefficient of 0.955). The results obtained with the reagent strip for urinary specific gravity therefore appear acceptable for routine laboratory purposes.

Pancreas transplantation. An initial experience with systemic and portal drainage of pancreatic allografts.

PubMed Central

Rosenlof, L K; Earnhardt, R C; Pruett, T L; Stevenson, W C; Douglas, M T; Cornett, G C; Hanks, J B

1992-01-01

Pancreas transplantation has evolved dramatically since its introduction in 1966. As new centers for transplantation have developed, the evaluation of complications associated with pancreas transplantation has led to advances in surgical technique. Furthermore, surgical alterations of the pancreas resulting from transplantation (systemic release of insulin and denervation) are of unproven consequence on glucose metabolism. Since 1988, the authors have performed 21 transplants (16 combined pancreas/kidney, 3 pancreas alone, which includes 1 retransplantation, 1 pancreas after previous kidney transplant, and 1 "cluster") in 20 patients aged 18 to 49 years; mean, 35 +/- 1 years. Overall patient survival is 95%. Three pancreatic grafts failed within the first year because of technical failure; one additional pancreas was lost to an immunologic event on postoperative day 449, for an overall pancreatic graft survival of 81%. No renal grafts were lost. To evaluate causes of graft failure, demographic data were compared, which included age and sex of the donor and the recipient, operative time, intraoperative blood transfusion, and ischemic time of the graft. No statistically significant differences were found between groups except for ischemic time (11.7 +/- 6.4 hours for the technical success group versus 19.8 +/- 3.7 hours for the technical failure group; p less than 0.05 by unpaired Student's t test). Quadruple immunosuppression was used, which included prednisone, cyclosporine, azathioprine, and antilymphoblast globulin. A mean of 1.2 (range, 0 to 3) rejection episodes per patient occurred. Mean hospital stay was 24 +/- 11 days. Surgical and infectious complications were evaluated by comparing the technical success (TS) group (n = 17) with the technical failure (TF) group. Surgical complications in the TS group revealed a mean of 1.3 episodes per patient, whereas the TF group had 3.7 episodes per patient. The TS also had a reduced incidence of infectious complications compared with the TF (1.7 versus 4.3 episodes per patient). Cytomegalovirus was common in both groups, accounting for 11 infectious episodes, and occurred on a mean postoperative day of 38. Mean postoperative HbA1C levels dropped to 5 +/- 1% from 11 +/- 3%. The authors developed a new technique that incorporates portal drainage of the pancreatic venous effluent in three recipients. Preoperative metabolic studies disclosed a mean fasting glucose of 211 +/- 27 mg/dL and a mean stimulated glucose value of 434 +/- 41 mg/dL for all patients; the mean fasting insulin was 23 +/- 4 microU/mL.(ABSTRACT TRUNCATED AT 400 WORDS) Images FIG. 5. PMID:1632680

Development and genetics of brain temporal stability related to attention problems in adolescent twins.

PubMed

Smit, Dirk J A; Anokhin, Andrey P

2017-05-01

The brain continuously develops and reorganizes to support an expanding repertoire of behaviors and increasingly complex cognition. These processes may, however, also result in the appearance or disappearance of specific neurodevelopmental disorders such as attention problems. To investigate whether brain activity changed during adolescence, how genetics shape this change, and how these changes were related to attention problems, we measured EEG activity in 759 twins and siblings, assessed longitudinally in four waves (12, 14, 16, and 18years of age). Attention problems were assessed with the SWAN at waves 12, 14, and 16. To characterize functional brain development, we used a measure of temporal stability (TS) of brain oscillations over the recording time of 5min reflecting the tendency of a brain to maintain the same oscillatory state for longer or shorter periods. Increased TS may reflect the brain's tendency to maintain stability, achieve focused attention, and thus reduce "mind wandering" and attention problems. The results indicate that brain TS is increased across the scalp from 12 to 18. TS showed large individual differences that were heritable. Change in TS (alpha oscillations) was heritable between 12 and 14 and between 14 and 16 for the frontal brain areas. Absolute levels of brain TS at each wave were positively correlated with attention problems but not significantly. High and low attention problems subjects showed different developmental trajectories in TS, which was significant in a cluster of frontal leads. These results indicate that trajectories in brain TS development are a biomarker for the developing brain. TS in brain oscillations is highly heritable, and age-related change in TS is also heritable in selected brain areas. These results suggest that high and low attention problems subjects are at different stages of brain development. Copyright © 2016. Published by Elsevier B.V.

Health status in women with Turner syndrome: a questionnaire study on health status, education, work participation and aspects of sexual functioning.

PubMed

Naess, Eva Elisabeth; Bahr, David; Gravholt, Claus H

2010-05-01

Turner syndrome (TS) is a complex medical condition with specific cognitive and psychosocial characteristics and frequent medical morbidity. Few studies have investigated the influence this has on health status, education and ability to work. To explore health status, level of education, work participation, medical conditions, physical activity, satisfaction with life and aspects of sexual functioning in adult TS women and compare with a matched control group. A questionnaire was sent to 168 adult women with TS >18 years registered in a database of Frambu Resource Centre for Rare Disorders and The TS Association in Norway. We assessed health status with Short Form 36, education with Norwegian Standard Classification of Education, and employment with The General Nordic Questionnaire. Life satisfaction was measured with LiSat-9, and questions on psychological strain during life phases were included. Eighty women with TS (34.0 +/- 11.7 years) and 214 controls (32.9 +/- 10.6) responded. The TS group reported significantly more health problems and impaired health status in the two subscales "physical functioning" and "general health" (P < 0.001). Level of education and work participation was similar among TS and controls. TS moved away from their parents' home later than controls (20.4 +/- 4.0 vs. 18.7 +/- 2.1, P = 0.001). Age at sexual debut differed significantly (21.2 +/- 4.3 vs. 17.3 +/- 2.4 years, P < 0.001). TS attains the same level of education and level of employment as controls, they report more frequent occurrence of medical conditions, but scored lower on only two subscales in the SF-36. Despite considerable medical morbidity, TS seem to cope well with life.

Turner Syndrome: Genetic and Hormonal Factors Contributing to a Specific Learning Disability Profile

ERIC Educational Resources Information Center

Rovet, Joanne

2004-01-01

Turner Syndrome (TS) is a genetic disorder affecting primarily females. It arises from a loss of X-chromosome material, most usually one of the two X chromosomes. Affected individuals have a number of distinguishing somatic features, including short stature and ovarian dysgenesis. Individuals with TS show a distinct neurocognitive profile…

Russian Space Agency research and development program for Aerospace Plane combined propulsion systems ('OREL-2-1' R&D)

NASA Astrophysics Data System (ADS)

Lanshin, A.; Sosounov, V.

The 'OREL-2-1' R&D program - 'Development of Combined Propulsion Systems for Advanced Reusable Space Transportation Systems (RSTS) Using Atmospheric Air as an Oxidizer' is being conducted in 1993-1995 according to the order of the Russian Space Agency (RSA). This work is part of the complex 'OREL' R&D program - 'Complex Investigations for RSTS Development preferable Directions Basis and Making of the Scientific and Technical Experience for the RSTS Creation' at which the TsNIIMash, TsAGI and NIITP side by side the Central Institute of Aviation Motors (CIAM) are the lead organizations of the four work parts. The 'OREL-2-1' R&D program and some of its results of 1993 are described briefly in this paper.

Purification and kinetic analysis of cytosolic and mitochondrial thioredoxin glutathione reductase extracted from Taenia solium cysticerci.

PubMed

Plancarte, Agustin; Nava, Gabriela

2015-02-01

Thioredoxin glutathione reductases (TGRs) (EC 1.8.1.9) were purified to homogeneity from the cytosolic (cTsTGR) and mitochondrial (mTsTGR) fractions of Taenia solium, the agent responsible for neurocysticercosis, one of the major central nervous system parasitic diseases in humans. TsTGRs had a relative molecular weight of 132,000, while the corresponding value per subunit obtained under denaturing conditions, was of 62,000. Specific activities for thioredoxin reductase and glutathione reductase substrates for both TGRs explored were in the range or lower than values obtained for other platyhelminths and mammalian TGRs. cTsTGR and mTsTGR also showed hydroperoxide reductase activity using hydroperoxide as substrate. Km(DTNB) and Kcat(DTNB) values for cTsTGR and mTsTGR (88 µM and 1.9 s(-1); 45 µM and 12.6 s(-1), respectively) and Km(GSSG) and Kcat(GSSG) values for cTsTGR and mTsTGR (6.3 µM and 0.96 s(-1); 4 µM and 1.62 s(-1), respectively) were similar to or lower than those reported for mammalian TGRs. Mass spectrometry analysis showed that 12 peptides from cTsTGR and seven from mTsTGR were a match for gi|29825896 thioredoxin glutathione reductase [Echinococcus granulosus], confirming that both enzymes are TGRs. Both T. solium TGRs were inhibited by the gold compound auranofin, a selective inhibitor of thiol-dependent flavoreductases (I₅₀ = 3.25, 2.29 nM for DTNB and GSSG substrates, respectively for cTsTGR; I₅₀ = 5.6, 25.4 nM for mTsTGR toward the same substrates in the described order). Glutathione reductase activity of cTsTGR and mTsTGR exhibited hysteretic behavior with moderate to high concentrations of GSSG; this result was not observed either with thioredoxin, DTNB or NADPH. However, the observed hysteretic kinetics was suppressed with increasing amounts of both parasitic TGRs. These data suggest the existence of an effective substitute which may account for the lack of the detoxification enzymes glutathione reductase and thioredoxin reductase in T. solium, as has been described for very few other platyhelminths. Copyright © 2014 Elsevier Inc. All rights reserved.

"Not just right experiences" in patients with Tourette syndrome: complex motor tics or compulsions?

PubMed

Neal, Matthew; Cavanna, Andrea Eugenio

2013-12-15

Tourette syndrome (TS) is a chronic tic disorder often accompanied by specific obsessive-compulsive symptoms (OCS) or full-blown obsessive-compulsive disorder (OCD). Repetitive behaviours are commonly reported by patients with TS, who experience the urge to perform an action until it has been done "just right". This study investigated the clinical correlates of "not just right experiences" (NJREs) in this clinical population. A standardised battery of self-report psychometric measures was administered to 71 adult patients with TS recruited from a specialist TS clinic. NJREs were systematically screened for using the Not Just Right Experiences-Questionnaire Revised (NJRE-QR). The vast majority of patients in our clinical sample (n=57, 80%) reported at least one NJRE. Patients diagnosed with TS and co-morbid OCD/OCS (n=42, 59%) reported a significantly higher number of NJREs compared to TS patients without OCD/OCS. The strongest correlation was found between NJRE-QR scores and self-report measures of compulsivity. NJREs appear to be intrinsic to the clinical phenomenology of patients with TS and can present with higher frequency in the context of co-morbid OCD/OCS, suggesting they are more related to compulsions than tics. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Concerns about dose and underutilization of twelve-step programs: models, scales, and theory that inform treatment planning.

PubMed

Cloud, Richard N; Kingree, J B

2008-01-01

Researchers have observed that a majority of addicted persons who are encouraged and facilitated by treatment providers to attend twelve-step (TS) programs either drop out or sporadically use twelve-step programs following treatment. This is troubling given considerable evidence of TS program benefits associated with regular weekly attendance and ubiquitous reliance by treatment professionals on these programs to provide important support services. This chapter reviews and advances theory of TS utilization and dose that is supported by prior research, multivariate models, and scales that predict risk of TS meeting underutilization. Advancing theory should organize and clarify the process of initial utilization, guide intervention development, and improve adherence of TS program referrals, all of which should lead to improved treatment planning and better outcomes. Three theories are integrated to explain processes that may influence TS program dose: the health belief model, self-determination theory (motivational theory), and a person-in-organization cultural fit theory. Four multidimensional scales developed specifically to predict participation are described. Implications for practice and future research are considered in a final discussion. Information contained in this chapter raises awareness of the need for TS-focused treatments to focus on achieving weekly attendance during and after treatment.

Conventional and Electronic cigarettes dysregulate the expression of iron transporters and detoxifying enzymes at the brain vascular endothelium: In Vivo Evidence of a Gender-Specific Cellular Response to Chronic Cigarette Smoke Exposure.

PubMed

Kaisar, Mohammad A; Sivandzade, Farzane; Bhalerao, Aditya; Cucullo, Luca

2018-06-04

It is well established that tobacco smoking is associated with vascular endothelial dysfunction in a causative and dose dependent manner primarily related to the tobacco smoke (TS) content of reactive oxygen species (ROS), nicotine, and oxidative stress (OS) -driven inflammation. Preclinical studies have also shown that nicotine (the principal e-liquid's ingredient used in e-cigarettes (e-Cigs) can also cause OS, exacerbation of cerebral ischemia and secondary brain injury. Likewise, chronic e-Cig vaping could be prodromal to vascular endothelial dysfunctions. Herein, we provide direct evidence that similarly to TS, e-Cig promotes mitochondrial depolarization in primary brain vascular endothelial cells as well as the vascular endothelial cell line bEnd3. In addition, both TS and e-Cig exposure upregulated the transmembrane iron exporter Slc40a1 (crucial to maintain cellular iron and redox homeostasis) and that of porphyrin importer Abcb6 (linked to accelerated atherosclerosis). We then investigated in vivo whether gender plays a role in how chronic TS affect vascular endothelial functions. Our results clearly show chronic TS exposure differentially impacts the expression levels of Phase-II enzymes as well as the iron transporters previously investigated in vitro. Although the physiological implications of the gender-specific differential responses to TS are not fully clear, they do demonstrate that gender is a risk factor that needs to be investigated when assessing the potential impact of chronic smoking and perhaps e-Cig vaping. Copyright © 2018. Published by Elsevier B.V.

Cloning and characterization of EF-Tu and EF-Ts from Pseudomonas aeruginosa.

PubMed

Palmer, Stephanie O; Rangel, Edna Y; Montalvo, Alberto E; Tran, Alexis T; Ferguson, Kate C; Bullard, James M

2013-01-01

We have cloned genes encoding elongation factors EF-Tu and EF-Ts from Pseudomonas aeruginosa and expressed and purified the proteins to greater than 95% homogeneity. Sequence analysis indicated that P. aeruginosa EF-Tu and EF-Ts are 84% and 55% identical to E. coli counterparts, respectively. P. aeruginosa EF-Tu was active when assayed in GDP exchange assays. Kinetic parameters for the interaction of EF-Tu with GDP in the absence of EF-Ts were observed to be K M = 33 μM, k cat (obs) = 0.003 s(-1), and the specificity constant k cat (obs)/K M was 0.1 × 10(-3) s(-1) μM(-1). In the presence of EF-Ts, these values were shifted to K M = 2 μM, k cat (obs) = 0.005 s(-1), and the specificity constant k(cat)(obs)/K M was 2.5 × 10(-3) s(-1) μM(-1). The equilibrium dissociation constants governing the binding of EF-Tu to GDP (K GDP) were 30-75 nM and to GTP (K GTP) were 125-200 nM. EF-Ts stimulated the exchange of GDP by EF-Tu 10-fold. P. aeruginosa EF-Tu was active in forming a ternary complex with GTP and aminoacylated tRNA and was functional in poly(U)-dependent binding of Phe-tRNA(Phe) at the A-site of P. aeruginosa ribosomes. P. aeruginosa EF-Tu was active in poly(U)-programmed polyphenylalanine protein synthesis system composed of all P. aeruginosa components.

Expert Perspectives on Time Sensitivity and a Related Metric for Children Involved in Motor Vehicle Crashes.

PubMed

Doud, Andrea N; Schoell, Samantha L; Weaver, Ashley A; Talton, Jennifer W; Barnard, Ryan T; Petty, John K; Meredith, J Wayne; Stitzel, Joel D

2017-04-01

Advanced Automatic Crash Notification (AACN) uses vehicle telemetry data to predict risk of serious injury among motor vehicle crash occupants and can thus improve the accuracy with which injured children are triaged by first responders. To better define serious injury for AACN systems (which typically use Abbreviated Injury Scale [AIS] metrics), an age-specific approach evaluating severity, time sensitivity (TS), and predictability of injury has been developed. This study outlines the development of the TS score. The 95% most frequent AIS 2+ injuries in a national motor vehicle crash data set spanning 2000 to 2011 were determined for the following age groups: 0 to 4, 5 to 9, 10 to 14, and 15 to 18 years. For each age-specific injury, clinicians with pediatric trauma expertise were asked if treatment at a trauma center was required and were asked about the urgency of treatment. A TS score (range 0-1) was calculated by combining the mean trauma center decision and urgency scores. A total of 30 to 32 responses were obtained for each age-specific injury. The most frequent motor vehicle crash-induced injuries in the younger groups received significantly higher scores than those in the older groups (median TS score 0 to 4 years: 0.89, 5-9 years: 0.87, 10-14 years: 0.82, 15-18 years: 0.72, P < .001). Large variations in TS existed within each AIS severity level; for example, scores among AIS 2 injuries in 0- to 4-year-olds ranged from 0.12 to 0.98. The TS of common pediatric injuries varies on the basis of age and may not be accurately reflected by AIS metrics. AIS may not capture all aspects of injury that should be considered by AACN systems. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Tobacco Stem-Based Activated Carbons for High Performance Supercapacitors

NASA Astrophysics Data System (ADS)

Xia, Xiaohong; Liu, Hongbo; Shi, Lei; He, Yuede

2012-09-01

Tobacco stem-based activated carbons (TS-ACs) were prepared by simple KOH activation and their application as electrodes in the electrical double layer capacitor (EDLC) performed successfully. The BET surface area, pore volume, and pore size distribution of the TS-ACs were evaluated based on N2 adsorption isotherms at 77 K. The surface area of the obtained activated carbons varies over a wide range (1472.8-3326.7 m2/g) and the mesoporosity was enhanced significantly as the ratio of KOH to tobacco stem (TS) increased. The electrochemical behaviors of series TS-ACs were characterized by means of galvanostatic charging/discharging, cyclic voltammetry, and impedance spectroscopy. The correlation between electrochemical properties and pore structure was investigated. A high specific capacitance value as 190 F/g at 1 mA/cm2 was obtained in 1 M LiPF6-EC/DMC/DEC electrolyte solution. Furthermore, good performance is also achieved even at high current densities. A development of new use for TS into a valuable energy storage material is explored.

Antibody binding to neuronal surface in Sydenham chorea, but not in PANDAS or Tourette syndrome

PubMed Central

Merheb, V.; Ding, A.; Murphy, T.; Dale, R.C.

2011-01-01

Objective: To test the hypothesis that Sydenham chorea (SC) immunoglobulin G (IgG) autoantibodies bind to specific neuronal surface proteins, whereas IgG from patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) or Tourette syndrome (TS) do not bind to neuronal surface proteins. Methods: We used live differentiated SH-SY5Y cells, which have neuronal and dopaminergic characteristics. Using flow cytometry, we measured serum IgG cell surface binding in patients with SC (n = 11), PANDAS (n = 12), and TS (n = 11), and compared the findings to healthy controls (n = 11) and other neurologic controls (n = 11). In order to determine the specificity of binding to neuronal antigens, we also used a non-neuronal cell line, HEK 293. Results: The mean IgG cell surface binding was significantly higher in the SC group compared to all other groups (p < 0.001). By contrast, there was no difference between the PANDAS or TS groups and the controls. Using the non-neuronal HEK-293 cells, there was no significant difference in IgG cell surface binding between any groups. Conclusions: Serum autoantibodies that bind to neuronal cell surface antigens are present in SC, but not in PANDAS or TS. These findings strengthen the hypothesis that SC is due to a pathogenic autoantibody, but weaken the autoantibody hypothesis in PANDAS and TS. PMID:21411742

Antibody binding to neuronal surface in Sydenham chorea, but not in PANDAS or Tourette syndrome.

PubMed

Brilot, F; Merheb, V; Ding, A; Murphy, T; Dale, R C

2011-04-26

To test the hypothesis that Sydenham chorea (SC) immunoglobulin G (IgG) autoantibodies bind to specific neuronal surface proteins, whereas IgG from patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) or Tourette syndrome (TS) do not bind to neuronal surface proteins. We used live differentiated SH-SY5Y cells, which have neuronal and dopaminergic characteristics. Using flow cytometry, we measured serum IgG cell surface binding in patients with SC (n = 11), PANDAS (n = 12), and TS (n = 11), and compared the findings to healthy controls (n = 11) and other neurologic controls (n = 11). In order to determine the specificity of binding to neuronal antigens, we also used a non-neuronal cell line, HEK 293. The mean IgG cell surface binding was significantly higher in the SC group compared to all other groups (p < 0.001). By contrast, there was no difference between the PANDAS or TS groups and the controls. Using the non-neuronal HEK-293 cells, there was no significant difference in IgG cell surface binding between any groups. Serum autoantibodies that bind to neuronal cell surface antigens are present in SC, but not in PANDAS or TS. These findings strengthen the hypothesis that SC is due to a pathogenic autoantibody, but weaken the autoantibody hypothesis in PANDAS and TS.

Understanding tumor-stroma interplays for targeted therapies by armed mesenchymal stromal progenitors: the Mesenkillers

PubMed Central

Grisendi, Giulia; Bussolari, Rita; Veronesi, Elena; Piccinno, Serena; Burns, Jorge S; De Santis, Giorgio; Loschi, Pietro; Pignatti, Marco; Di Benedetto, Fabrizio; Ballarin, Roberto; Di Gregorio, Carmela; Guarneri, Valentina; Piccinini, Lino; Horwitz, Edwin M; Paolucci, Paolo; Conte, PierFranco; Dominici, Massimo

2011-01-01

A tumor represents a complex structure containing malignant cells strictly coupled with a large variety of surrounding cells constituting the tumor stroma (TS). In recent years, the importance of TS for cancer initiation, development, local invasion and metastases has become increasingly clear allowing the identification of TS as one of the possible ways to indirectly target tumors. Inside the heterogeneous stromal cell population, tumor associated fibroblasts (TAF) play a crucial role providing both functional and supportive environments. During both tumor and stroma development, several findings suggest that TAF could be recruited from different sources such as locally derived host fibroblasts, via epithelial/endothelial mesenchymal transitions or from circulating pools of fibroblasts deriving form mesenchymal progenitors, namely mesenchymal stem/stromal cells (MSC). These insights prompted scientists to identify multimodal approaches to target TS by biomolecules, monoclonal antibodies, and more recently via cell based strategies. These latter strategies appear extremely promising, although still associated with debated and unclear findings. This review discusses crosstalk between cancers and their stroma, dissecting specific tumor types, such as sarcoma, pancreatic and breast carcinoma, where stroma plays distinct paradigmatic roles. The recognition of these distinct stromal functions may help in planning effective and safer approaches aimed either to eradicate or to substitute TS by novel compounds and/or MSC having specific killing activities. PMID:22016827

Using support vector machines with tract-based spatial statistics for automated classification of Tourette syndrome children

NASA Astrophysics Data System (ADS)

Wen, Hongwei; Liu, Yue; Wang, Jieqiong; Zhang, Jishui; Peng, Yun; He, Huiguang

2016-03-01

Tourette syndrome (TS) is a developmental neuropsychiatric disorder with the cardinal symptoms of motor and vocal tics which emerges in early childhood and fluctuates in severity in later years. To date, the neural basis of TS is not fully understood yet and TS has a long-term prognosis that is difficult to accurately estimate. Few studies have looked at the potential of using diffusion tensor imaging (DTI) in conjunction with machine learning algorithms in order to automate the classification of healthy children and TS children. Here we apply Tract-Based Spatial Statistics (TBSS) method to 44 TS children and 48 age and gender matched healthy children in order to extract the diffusion values from each voxel in the white matter (WM) skeleton, and a feature selection algorithm (ReliefF) was used to select the most salient voxels for subsequent classification with support vector machine (SVM). We use a nested cross validation to yield an unbiased assessment of the classification method and prevent overestimation. The accuracy (88.04%), sensitivity (88.64%) and specificity (87.50%) were achieved in our method as peak performance of the SVM classifier was achieved using the axial diffusion (AD) metric, demonstrating the potential of a joint TBSS and SVM pipeline for fast, objective classification of healthy and TS children. These results support that our methods may be useful for the early identification of subjects with TS, and hold promise for predicting prognosis and treatment outcome for individuals with TS.

Physiological responses and time-motion characteristics of 4-a-side small-sided game in young soccer players: the influence of different team formation methods.

PubMed

Köklü, Yusuf; Ersöz, Gülfem; Alemdaroğlu, Utku; Aşç, Alper; Ozkan, Ali

2012-11-01

The purpose of this study was to examine the influence of different team formation methods on the physiological responses to and time-motion characteristics of 4-a-side small-sided games (SSG4) in young soccer players. Thirty-two young soccer players (age 16.2 ± 0.7 years; height 172.9 ± 6.1 cm; body mass 64.1 ± 7.7 kg) voluntarily participated in this study. Anthropometric measurements, technical tests, and maximum oxygen uptake (V[Combining Dot Above]O2max) tests were carried out on the players. The SSG4 teams were then created using 4 different methods: according to the coaches' subjective evaluation (CE), technical scores (TS), V[Combining Dot Above]O2max (AP), and V[Combining Dot Above]O2max multiplied by TSs (CG). The teams thus created played 4 bouts of SSG4 at 2-day intervals. During the SSG4, heart rate (HR) responses, distance covered, and time spent in HRmax zones were recorded. In addition, rating of perceived exertion (RPE) and blood lactate level (La) were determined at the end of the last bout of each SSG4. Percent of HRmax (%HRmax), La, and RPE responses during SSG4 were significantly higher for teams chosen according to AP and CG compared with that according to CE and TS (p < 0.05). In addition, teams chosen by AP and CG spent significantly more time in zone 4 (>90% HRmax ) and covered a greater distance in the high-intensity running zone (>18 km·h) than did teams formed according to TS. Moreover, AP teams covered significantly greater total distance than TS teams did (p < 0.05). In conclusion, to spend more time in both the high-intensity HR zone and the high-intensity running zone, the teams in SSG4 should be formed according to the players' V[Combining Dot Above]O2max values or the values calculated using both the V[Combining Dot Above]O2max and technique scores.

Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue.

PubMed

Alfaro, Clint M; Jarmusch, Alan K; Pirro, Valentina; Kerian, Kevin S; Masterson, Timothy A; Cheng, Liang; Cooks, R Graham

2016-08-01

Touch spray-mass spectrometry (TS-MS) is an ambient ionization technique (ionization of unprocessed samples in the open air) that may find intraoperative applications in quickly identifying the disease state of cancerous tissues and in defining surgical margins. In this study, TS-MS was performed on fresh kidney tissue (∼1-5 cm(3)), within 1 h of resection, from 21 human subjects afflicted by renal cell carcinoma (RCC). The preliminary diagnostic value of TS-MS data taken from freshly resected tissue was evaluated. Principal component analysis (PCA) of the negative ion mode (m/z 700-1000) data provided the separation between RCC (16 samples) and healthy renal tissue (13 samples). Linear discriminant analysis (LDA) on the PCA-compressed data estimated sensitivity (true positive rate) and specificity (true negative rate) of 98 and 95 %, respectively, based on histopathological evaluation. The results indicate that TS-MS might provide rapid diagnostic information in spite of the complexity of unprocessed kidney tissue and the presence of interferences such as urine and blood. Desorption electrospray ionization-MS imaging (DESI-MSI) in the negative ionization mode was performed on the tissue specimens after TS-MS analysis as a reference method. The DESI imaging experiments provided phospholipid profiles (m/z 700-1000) that also separated RCC and healthy tissue in the PCA space, with PCA-LDA sensitivity and specificity of 100 and 89 %, respectively. The TS and DESI loading plots indicated that different ions contributed most to the separation of RCC from healthy renal tissue (m/z 794 [PC 34:1 + Cl](-) and 844 [PC 38:4 + Cl](-) for TS vs. m/z 788 [PS 36:1 - H](-) and 810 [PS 38:4 - H](-) for DESI), while m/z 885 ([PI 38:4 - H](-)) was important in both TS and DESI. The prospect, remaining hurdles, and future work required for translating TS-MS into a method of intraoperative tissue diagnosis are discussed. Graphical abstract Touch spray-mass spectrometry used for lipid profiling of fresh human renal cell carcinoma. Left) Photograph of the touch spray probe pointed at the MS inlet. Right) Average mass spectra of healthy renal tissue (blue) and RCC (red).

Energy-positive sewage sludge pre-treatment with a novel ultrasonic flatbed reactor at low energy input.

PubMed

Lippert, Thomas; Bandelin, Jochen; Musch, Alexandra; Drewes, Jörg E; Koch, Konrad

2018-05-20

The performance of a novel ultrasonic flatbed reactor for sewage sludge pre-treatment was assessed for three different waste activated sludges. The study systematically investigated the impact of specific energy input (200 - 3,000 kJ/kg TS ) on the degree of disintegration (DD COD , i.e. ratio between ultrasonically and maximum chemically solubilized COD) and methane production enhancement. Relationship between DD COD and energy input was linear, for all sludges tested. Methane yields were significantly increased for both low (200 kJ/kg TS ) and high (2,000 - 3,000 kJ/kg TS ) energy inputs, while intermediate inputs (400 - 1,000 kJ/kg TS ) showed no significant improvement. High inputs additionally accelerated reaction kinetics, but were limited to similar gains as low inputs (max. 12%), despite the considerably higher DD COD values. Energy balance was only positive for 200 kJ/kg TS -treatments, with a maximum energy recovery of 122%. Results suggest that floc deagglomeration rather than cell lysis (DD COD =1% - 5% at 200 kJ/kg TS ) is the key principle of energy-positive sludge sonication. Copyright © 2018 Elsevier Ltd. All rights reserved.

Results obtained with a low cost software-based audiometer for hearing screening.

PubMed

Ferrari, Deborah Viviane; Lopez, Esteban Alejandro; Lopes, Andrea Cintra; Aiello, Camila Piccini; Jokura, Pricila Reis

2013-07-01

 The implementation of hearing screening programs can be facilitated by reducing operating costs, including the cost of equipment. The Telessaúde (TS) audiometer is a low-cost, software-based, and easy-to-use piece of equipment for conducting audiometric screening.  To evaluate the TS audiometer for conducting audiometric screening.  A prospective randomized study was performed. Sixty subjects, divided into those who did not have (group A, n = 30) and those who had otologic complaints (group B, n = 30), underwent audiometric screening with conventional and TS audiometers in a randomized order. Pure tones at 25 dB HL were presented at frequencies of 500, 1000, 2000, and 4000 Hz. A "fail" result was considered when the individual failed to respond to at least one of the stimuli. Pure-tone audiometry was also performed on all participants. The concordance of the results of screening with both audiometers was evaluated. The sensitivity, specificity, and positive and negative predictive values of screening with the TS audiometer were calculated.  For group A, 100% of the ears tested passed the screening. For group B, "pass" results were obtained in 34.2% (TS) and 38.3% (conventional) of the ears tested. The agreement between procedures (TS vs. conventional) ranged from 93% to 98%. For group B, screening with the TS audiometer showed 95.5% sensitivity, 90.4% sensitivity, and positive and negative predictive values equal to 94.9% and 91.5%, respectively.  The results of the TS audiometer were similar to those obtained with the conventional audiometer, indicating that the TS audiometer can be used for audiometric screening.

Parental mood during pregnancy and post-natally is associated with offspring risk of Tourette syndrome or chronic tics: prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC).

PubMed

Ben-Shlomo, Y; Scharf, J M; Miller, L L; Mathews, C A

2016-04-01

Little is known about risk factors for Tourette syndrome (TS) and chronic tic disorders (CT) but maternal psychological morbidity in pregnancy may be associated with TS/CT. We examined whether pre- and post-natal parental anxiety and/or depression are associated with risk of TS/CT in the Avon Longitudinal Study of Parents and Children. We compared self-reported anxiety and depression measures collected prospectively at four time points (18 and 32 weeks prenatally, and 8 weeks and 8 months post-natally) among parents of children who subsequently met criteria for TS/CT at 13 years of age as compared to other children from the cohort. We adjusted for various socioeconomic measures and tested both for time period-specific exposure and chronic exposure using multivariable logistic regression models. 122 children had TS/CT (50 TS, 72 CT) and 5968 children had no tics. In crude analyses, both pre- and post-natal maternal anxiety and depression, but only post-natal paternal depression at 8 months, showed associations with TS/CT. In the final, adjusted multivariable models, chronic maternal anxiety (odds ratio 2.17, 95% CI 1.23, 3.84, p = 0.007) and pre-natal maternal depression (odds ratio 1.86, 95% CI 1.02, 3.39, p = 0.04) showed associations with TS/CT though the latter was consistent with chance (p = 0.07) after adjustment for past maternal depression. We find associations between maternal psychological morbidity pre- and post-natally and risk of future TS/CT in offspring. These associations may reflect either shared genetic susceptibility or a pre-natal exposure. Further work is required to see if these findings can be replicated in larger datasets.

Identification of an anti-sperm auto-monoclonal antibody (Ts4)-recognized molecule in the mouse sperm acrosomal region and its inhibitory effect on fertilization in vitro.

PubMed

Yoshitake, Hiroshi; Oda, Risako; Yanagida, Mitsuaki; Kawasaki, Yu; Sakuraba, Mayumi; Takamori, Kenji; Hasegawa, Akiko; Fujiwara, Hiroshi; Araki, Yoshihiko

2016-06-01

We previously established an anti-mouse sperm auto-monoclonal antibody, Ts4, which shows immunoreactivity against several kinds of glycoproteins in the acrosomal region of epididymal spermatozoa, testicular germ cells, and early embryo, via binding to an epitope containing a common N-linked oligosaccharide (OS) chain on the molecules. In mice, we have already demonstrated that the OS chain in the epitope for Ts4 is a fucosylated agalacto-complex-type biantennary glycan carrying bisecting N-acetylglucosamine. In the testis, one of the specific OS chain-conjugated molecules is TEX101, a germ cell-marker glycoprotein, which is expressed in spermatocytes, spermatids, and testicular spermatozoa, but not in epididymal spermatozoa. In this study, we identified a Ts4-reactive glycoprotein in mouse cauda epididymal sperm. An immunoprecipitation method together with liquid chromatography-tandem mass spectrometry showed that alpha-N-acetylglucosaminidase (Naglu; a degradation enzyme of heparan sulfate) is one of the glycoproteins recognized by Ts4 in the epididymal spermatozoa. Western blot and immunohistochemical analyses revealed that mouse Naglu exists in two forms (82 and 77kDa) and is expressed in the acrosomal region and the flagellum of cauda epididymal sperm. Of the two Naglu-forms expressed in sperm, Ts4 immunoreacted against only the 82-kDa form located on the acrosomal region. The Ts4 mAb and anti-Naglu pAb negatively affected mouse fertilization in vitro. In addition, Ts4 inhibited sperm acrosome reaction induced by heparan sulfate. The Ts4-recognized fucosylated agalactobiantennary complex-type glycan with bisecting N-acetylglucosamine and Naglu on cauda epididymal spermatozoa may play a role in the process of fertilization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Trichinella spiralis Paramyosin Binds to C8 and C9 and Protects the Tissue-Dwelling Nematode from Being Attacked by Host Complement

PubMed Central

Zhang, Zhifei; Yang, Jing; Wei, Junfei; Yang, Yaping; Chen, Xiaoqin; Zhao, Xi; Gu, Yuan; Cui, Shijuan; Zhu, Xinping

2011-01-01

Background Paramyosin is a thick myofibrillar protein found exclusively in invertebrates. Evidence suggested that paramyosin from helminths serves not only as a structural protein but also as an immunomodulatory agent. We previously reported that recombinant Trichinella spiralis paramyosin (Ts-Pmy) elicited a partial protective immunity in mice. In this study, the ability of Ts-Pmy to bind host complement components and protect against host complement attack was investigated. Methods and Findings In this study, the transcriptional and protein expression levels of Ts-Pmy were determined in T. spiralis newborn larva (NBL), muscle larva (ML) and adult worm developmental stages by RT-PCR and western blot analysis. Expression of Ts-Pmy at the outer membrane was observed in NBL and adult worms using immunogold electron microscopy and immunofluorescence staining. Functional analysis revealed that recombinant Ts-Pmy(rTs-Pmy) strongly bound to complement components C8 and C9 and inhibited the polymerization of C9 during the formation of the membrane attack complex (MAC). rTs-Pmy also inhibited the lysis of rabbit erythrocytes (ER) elicited by an alternative pathway-activated complement from guinea pig serum. Inhibition of native Ts-Pmy on the surface of NBL with a specific antiserum reduced larvae viability when under the attack of complement in vitro. In vivo passive transfer of anti-Ts-Pmy antiserum and complement-treated larvae into mice also significantly reduced the number of larvae that developed to ML. Conclusion These studies suggest that the outer membrane form of T. spiralis paramyosin plays an important role in the evasion of the host complement attack. PMID:21750743

Comparison of surface temperature in 13-lined ground squirrel (Spermophilus tridecimlineatus) and yellow-bellied marmot (Marmota flaviventris) during arousal from hibernation.

PubMed

Phillips, P K; Heath, J E

2004-08-01

Surface temperatures (Ts) of eight 13-lined ground squirrels and seven yellow-bellied marmots were measured during arousal from hibernation using infrared thermography (IRT) and recorded on videotape. Animals aroused normally in 5 degrees C cold rooms. Body temperatures were recorded during arousal using both cheek pouch and interscapular temperature probes. Warming rate in arousal was exponential. Mean mass specific warming rates show the squirrels warm faster (69.76 degrees C/h/kg) than the marmots (4.49 degrees C/h/kg). Surface temperatures (Ts) for 11 regions were measured every few minutes during arousal. The smaller ground squirrel shows the ability to perfuse distal regions without compromising rise in deep body temperature (Tb). All squirrel Ts's remained low as Tb rose to 18 degrees C, at which point, eyes opened, squirrels became more active and all Ts's rose parallel to Tb. Marmot Ts remained low as Tb rose initially. Each marmot showed a plateau phase where Tb remained constant (mean Tb 20.3+/-1.0 degrees C, duration 9.4+/-4.1 min) during which time all Ts's rose, and then remained relatively constant as Tb again began to rise. An anterior to posterior Ts gradient was evident in the ground squirrel, both body and feet. This gradient was only evident in the feet of the marmots.

Thermosensitivity is reduced during fever induced by Staphylococcus aureus cells walls in rabbits.

PubMed

Tøien, Ø; Mercer, J B

1996-05-01

Thermosensitivity (TS) and threshold core temperature for metabolic cold defence were determined in six conscious rabbits before, and at seven different times after i.v. injection of killed Staphylococcus aureus (8 x 10(7) or 2 x 10(7) cell walls x kg(-1)) by exposure to short periods (5-10 min) of body cooling. Heat was extracted with a chronically implanted intravascular heat exchanger. TS was calculated by regression of metabolic heat production (M) and core temperature, as indicated by hypothalamic temperature. Threshold for cold defence (shivering threshold) was calculated as the core temperature at which the thermosensitivity line crossed preinjection resting M. The shivering thresholds followed the shape of the fever response. TS was significantly reduced (up to 49%) during the time course of fever induced by the highest dose of pyrogen only. At both high and low doses of pyrogen TS correlated negatively with shivering threshold (r = 0.66 and 0.79 respectively) with similar slopes. The reduction in TS during fever was thus associated with the increase in shivering threshold resulting from the pyrogen injection and not by the dose of pyrogen. Model considerations indicate, however, that changes in sensitivity of the thermosensory input to the hypothalamic controller may affect threshold changes but cause negligible TS changes. It is more likely that the reduction in TS is effected in the specific hypothalamic effector pathways.

Soil Temperature Variability in Complex Terrain measured using Distributed a Fiber-Optic Distributed Temperature Sensing

NASA Astrophysics Data System (ADS)

Seyfried, M. S.; Link, T. E.

2013-12-01

Soil temperature (Ts) exerts critical environmental controls on hydrologic and biogeochemical processes. Rates of carbon cycling, mineral weathering, infiltration and snow melt are all influenced by Ts. Although broadly reflective of the climate, Ts is sensitive to local variations in cover (vegetative, litter, snow), topography (slope, aspect, position), and soil properties (texture, water content), resulting in a spatially and temporally complex distribution of Ts across the landscape. Understanding and quantifying the processes controlled by Ts requires an understanding of that distribution. Relatively few spatially distributed field Ts data exist, partly because traditional Ts data are point measurements. A relatively new technology, fiber optic distributed temperature system (FO-DTS), has the potential to provide such data but has not been rigorously evaluated in the context of remote, long term field research. We installed FO-DTS in a small experimental watershed in the Reynolds Creek Experimental Watershed (RCEW) in the Owyhee Mountains of SW Idaho. The watershed is characterized by complex terrain and a seasonal snow cover. Our objectives are to: (i) evaluate the applicability of fiber optic DTS to remote field environments and (ii) to describe the spatial and temporal variability of soil temperature in complex terrain influenced by a variable snow cover. We installed fiber optic cable at a depth of 10 cm in contrasting snow accumulation and topographic environments and monitored temperature along 750 m with DTS. We found that the DTS can provide accurate Ts data (+/- .4°C) that resolves Ts changes of about 0.03°C at a spatial scale of 1 m with occasional calibration under conditions with an ambient temperature range of 50°C. We note that there are site-specific limitations related cable installation and destruction by local fauna. The FO-DTS provide unique insight into the spatial and temporal variability of Ts in a landscape. We found strong seasonal trends in Ts variability controlled by snow cover and solar radiation as modified by topography. During periods of spatially continuous snow cover Ts was practically homogeneous throughout. In the absence of snow cover, Ts is highly variable, with most of the variability attributable to different topographic units defined by slope and aspect. During transition periods when snow melts out, Ts is highly variable within the watershed and within topographic units. The importance of accounting for these relatively small scale effects is underscored by the fact that the overall range of Ts in study area 600 m long is similar to that of the much large RCEW with 900 m elevation gradient.

47 CFR 17.53 - Lighting equipment and paint.

Code of Federal Regulations, 2011 CFR

2011-10-01

... AC No. 150/5345-43B 4). 116-Watt lamp No. 116 A21/TS (6,000 h). 125-Watt lamp No. 125 A21/TS (6,000 h... Administration, 800 Independence Avenue SW., Washington, D.C. 20591. 4 Copies of Federal Aviation Administration... specifications, bulletins, and drawings (lamps are referred to by standard numbers): Outside white TT-P-102 1...

A Comprehensive Review of Tourette Syndrome and Complementary Alternative Medicine.

PubMed

Kumar, Ashutosh; Duda, L; Mainali, G; Asghar, S; Byler, D

2018-01-01

Tourette syndrome (TS) is a neuropsychiatric condition defined by both motor and phonic tics over a period of at least 1 year with the onset before 18 years of age. The purpose of this article is to review the use of complementary alternative medicine (CAM) in children and adults with Tourette syndrome with emphasis on recent research. Most patients do not tell their physician about the use of CAM unless if specifically asked. Of the studies reviewed, description of the treatment and the frequency of use were most often reported. Few studies examine the role or effectiveness of CAM in the treatment of TS specifically. Practitioners should be aware of current research regarding various CAM modalities used for TS patients, including efficacy, potential adverse effects, and interactions with medications. Robust data about the use of CAM, efficacy, and potential side effects is lacking and requires further research to clarify optimal use.

Tumor targeting profiling of hyaluronan-coated lipid based-nanoparticles

NASA Astrophysics Data System (ADS)

Mizrahy, Shoshy; Goldsmith, Meir; Leviatan-Ben-Arye, Shani; Kisin-Finfer, Einat; Redy, Orit; Srinivasan, Srimeenakshi; Shabat, Doron; Godin, Biana; Peer, Dan

2014-03-01

Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression. Low Mw (LMw, <10 kDa) HA has been reported to provoke inflammatory responses, such as induction of cytokines, chemokines, reactive nitrogen species and growth factors. Herein, we prepared and characterized two types of HA coated (LMw and HMw) lipid-based targeted and stabilized nanoparticles (tsNPs) and tested their binding to tumor cells expressing the HA receptor (CD44), systemic immunotoxicity, and biodistribution in tumor bearing mice. In vitro, the Mw of the surface anchored HA had a significant influence on the affinity towards CD44 on B16F10 murine melanoma cells. LMw HA-tsNPs exhibited weak binding, while binding of tsNPs coated with HMw HA was characterized by high binding. Both types of tsNPs had no measured effect on cytokine induction in vivo following intravenous administration to healthy C57BL/6 mice suggesting no immune activation. HMw HA-tsNPs showed enhanced circulation time and tumor targeting specificity, mainly by accumulating in the tumor and its vicinity compared with LMw HA-tsNPs. Finally, we show that methotrexate (MTX), a drug commonly used in cancer chemotherapy, entrapped in HMw HA-tsNPs slowly diffused from the particles with a half-life of 13.75 days, and improved the therapeutic outcome in a murine B16F10 melanoma model compared with NPs suggesting an active cellular targeting beyond the Enhanced Permeability and Retention (EPR) effect. Taken together, these findings have major implications for the use of high molecular weight HA in nanomedicine as a selective and safe active cellular targeting moiety.Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression. Low Mw (LMw, <10 kDa) HA has been reported to provoke inflammatory responses, such as induction of cytokines, chemokines, reactive nitrogen species and growth factors. Herein, we prepared and characterized two types of HA coated (LMw and HMw) lipid-based targeted and stabilized nanoparticles (tsNPs) and tested their binding to tumor cells expressing the HA receptor (CD44), systemic immunotoxicity, and biodistribution in tumor bearing mice. In vitro, the Mw of the surface anchored HA had a significant influence on the affinity towards CD44 on B16F10 murine melanoma cells. LMw HA-tsNPs exhibited weak binding, while binding of tsNPs coated with HMw HA was characterized by high binding. Both types of tsNPs had no measured effect on cytokine induction in vivo following intravenous administration to healthy C57BL/6 mice suggesting no immune activation. HMw HA-tsNPs showed enhanced circulation time and tumor targeting specificity, mainly by accumulating in the tumor and its vicinity compared with LMw HA-tsNPs. Finally, we show that methotrexate (MTX), a drug commonly used in cancer chemotherapy, entrapped in HMw HA-tsNPs slowly diffused from the particles with a half-life of 13.75 days, and improved the therapeutic outcome in a murine B16F10 melanoma model compared with NPs suggesting an active cellular targeting beyond the Enhanced Permeability and Retention (EPR) effect. Taken together, these findings have major implications for the use of high molecular weight HA in nanomedicine as a selective and safe active cellular targeting moiety. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr06102g

Statistical approach for the retrieval of phytoplankton community structures from in situ fluorescence measurements.

PubMed

Wang, Shengqiang; Xiao, Cong; Ishizaka, Joji; Qiu, Zhongfeng; Sun, Deyong; Xu, Qian; Zhu, Yuanli; Huan, Yu; Watanabe, Yuji

2016-10-17

Knowledge of phytoplankton community structures is important to the understanding of various marine biogeochemical processes and ecosystem. Fluorescence excitation spectra (F(λ)) provide great potential for studying phytoplankton communities because their spectral variability depends on changes in the pigment compositions related to distinct phytoplankton groups. Commercial spectrofluorometers have been developed to analyze phytoplankton communities by measuring the field F(λ), but estimations using the default methods are not always accurate because of their strong dependence on norm spectra, which are obtained by culturing pure algae of a given group and are assumed to be constant. In this study, we proposed a novel approach for estimating the chlorophyll a (Chl a) fractions of brown algae, cyanobacteria, green algae and cryptophytes based on a data set collected in the East China Sea (ECS) and the Tsushima Strait (TS), with concurrent measurements of in vivo F(λ) and phytoplankton communities derived from pigments analysis. The new approach blends various statistical features by computing the band ratios and continuum-removed spectra of F(λ) without requiring a priori knowledge of the norm spectra. The model evaluations indicate that our approach yields good estimations of the Chl a fractions, with root-mean-square errors of 0.117, 0.078, 0.072 and 0.060 for brown algae, cyanobacteria, green algae and cryptophytes, respectively. The statistical analysis shows that the models are generally robust to uncertainty in F(λ). We recommend using a site-specific model for more accurate estimations. To develop a site-specific model in the ECS and TS, approximately 26 samples are sufficient for using our approach, but this conclusion needs to be validated in additional regions. Overall, our approach provides a useful technical basis for estimating phytoplankton communities from measurements of F(λ).

Expression and prognostic significance of thymidylate synthase (TS) in pancreatic head and periampullary cancer.

PubMed

van der Zee, J A; van Eijck, C H J; Hop, W C J; van Dekken, H; Dicheva, B M; Seynhaeve, A L B; Koning, G A; Eggermont, A M M; Ten Hagen, T L M

2012-11-01

Pancreatic cancer has a dismal prognosis. Attempts have been made to improve outcome by several 5-FU based adjuvant treatment regimens. However, the results are conflicting. There seems to be a continental divide with respect to the use of 5-FU based chemoradiotherapy (CRT). Furthermore, evidence has been presented showing a different response of pancreatic head and periampullary cancer to 5-FU based CRT. Expression of thymidylate synthase (TS) has been associated with improved outcome following 5-FU based adjuvant treatment in gastrointestinal cancer. This prompted us to determine the differential expression and prognostic value of TS in pancreatic head and periampullary cancer. TS protein expression was studied by immunohistochemistry on original paraffin embedded tissue from 212 patients following microscopic radical resection (R0) of pancreatic head (n = 98) or periampullary cancer (n = 114). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS), and conventional prognostic factors. High cytosolic TS expression was present in 26% of pancreatic head tumours and 37% of periampullary tumours (p = .11). Furthermore, TS was an independent factor predicting favourable outcome following curative resection of pancreatic head cancer (p = .003, .001 and .001 for RFS, CSS and OS, respectively). In contrast, in periampullary cancer, TS was not associated with outcome (all p > .10). TS, was found to be poorly expressed in both pancreatic head and periampullary cancer and identified as an independent prognostic factor following curative resection of pancreatic head cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Correlation between thermostability of the xylanase EvXyn11(TS) and its N-terminal disulfide bridge].

PubMed

Min, Rou; Li, Jianfang; Gao, Shujuan; Zhang, Huimin; Wu, Jing; Wu, Minchen

2013-04-04

To reveal the correlation between thermostability of xylanase EvXyn11(TS) and its N-terminal disulfide bridge, an EvXyn11(TS)-encoding gene (Syxyn11) was synthesized and subjected to site-directed mutagenesis. Multiple homology alignment of protein primary structures between the EvXyn11(TS) and several GH family 11 xylanases displayed that, in their N-termini, only EvXyn11(TS) contained a disulfide bridge (Cys5-Cys32), whose effect on the xylanase thermostability was predicted by molecular dynamics simulation. We constructed a gene Syxyn11(M), encoding the mutated xylanase (EvXyn11(M)) without N-terminal disulfide bridge. Then, Syxyn11 and Syxyn11(M) were expressed in Pichia pastoris GS115, and temperature and pH properties of the expressed enzymes were analyzed. The analytical results displayed that the temperature optimum of EvXyn11(M) was 70 degrees C, which was 15 degrees C lower than that of EvXyn11(TS). The half-life (t1/2(90)) of EvXyn11(TS) at 90 degrees C was 32 min, while the t1/2(70) of EvXyn11(M) at 70 degrees C was only 8.0 min. The important role of the N-terminal disulfide bridge on the thermostability of EvXyn11(TS) was first predicted by molecular dynamics simulation, and confirmed by site-directed mutagenesis. This work provided a novel strategy to improve thermostabilities of the mesophilic family 11 xylanases with high specific activities.

Macrophages play an essential role in antigen-specific immune suppression mediated by T CD8⁺ cell-derived exosomes.

PubMed

Nazimek, Katarzyna; Ptak, Wlodzimierz; Nowak, Bernadeta; Ptak, Maria; Askenase, Philip W; Bryniarski, Krzysztof

2015-09-01

Murine contact sensitivity (CS) reaction could be antigen-specifically regulated by T CD8(+) suppressor (Ts) lymphocytes releasing microRNA-150 in antibody light-chain-coated exosomes that were formerly suggested to suppress CS through action on macrophages (Mφ). The present studies investigated the role of Mφ in Ts cell-exosome-mediated antigen-specific suppression as well as modulation of Mφ antigen-presenting function in humoral and cellular immunity by suppressive exosomes. Mice depleted of Mφ by clodronate liposomes could not be tolerized and did not produce suppressive exosomes. Moreover, isolated T effector lymphocytes transferring CS were suppressed by exosomes only in the presence of Mφ, demonstrating the substantial role of Mφ in the generation and action of Ts cell regulatory exosomes. Further, significant decrease of number of splenic B cells producing trinitrophenyl (TNP) -specific antibodies with the alteration of the ratio of serum titres of IgM to IgG was observed in recipients of exosome-treated, antigen-pulsed Mφ and the significant suppression of CS was demonstrated in recipients of exosome-treated, TNP-conjugated Mφ. Additionally, exosome-pulsed, TNP-conjugated Mφ mediated suppression of CS in mice pre-treated with a low-dose of cyclophosphamide, suggesting de novo induction of T regulatory (Treg) lymphocytes. Treg cell involvement in the effector phase of the studied suppression mechanism was proved by unsuccessful tolerization of DEREG mice depleted of Treg lymphocytes. Furthermore, the inhibition of proliferation of CS effector cells cultured with exosome-treated Mφ in a transmembrane manner was observed. Our results demonstrated the essential role of Mφ in antigen-specific immune suppression mediated by Ts cell-derived exosomes and realized by induction of Treg lymphocytes and inhibition of T effector cell proliferation. © 2015 John Wiley & Sons Ltd.

Psychometric properties of the Portuguese version of the Acceptance and Action Questionnaire-Trauma Specific (AAQ-TS): A study with Portuguese Colonial War Veterans.

PubMed

Pinto-Gouveia, José; Carvalho, Teresa; Cunha, Marina; Duarte, Joana; Walser, Robyn D

2015-10-01

The Acceptance and Action Questionnaire-Trauma Specific (AAQ-TS) is a self-report measure designed to assess-trauma-related psychological (in)flexibility, as conceptualized in Acceptance and Commitment Therapy. However, there are no studies to date regarding its psychometric properties. This study explores such properties in the Portuguese version of the AAQ-TS, in Portuguese Colonial War Veterans. A Principal Components Analysis (PCA) was conducted in a sample from the general population of war Veterans (N=371). Confirmatory Factor Analysis (CFA) as well as reliability and convergent validity studies were performed in a different sample from the same population (N=312). For the discriminant validity a clinical sample with a war-related PTSD (N=42) and a non-clinical sample without PTSD (N=44) were used. The CFA suggested a re-specified 15-item model with good global adjustment and factorial validity. The AAQ-TS showed internal consistency, a good temporal reliability, convergent validity with psychopathological symptoms (related to PTSD, anxiety, depression and stress) and peritraumatic dissociation (altered awareness and depersonalization/derealization). The questionnaire also discriminates between war Veterans with and without a PTSD diagnosis. The major limitation relates to the samples' characteristics and sampling methods, which can limit the generalization of results. The Portuguese version of the AAQ-TS is a reliable and valid measure to assess experiential avoidance related to trauma in Portuguese Colonial War Veterans. Copyright © 2015 Elsevier B.V. All rights reserved.

Improved immune response to an attenuated pseudorabies virus vaccine by ginseng stem-leaf saponins (GSLS) in combination with thimerosal (TS).

PubMed

Ni, Jingxuan; Bi, Shicheng; Xu, Wei; Zhang, Cenrong; Lu, Yisong; Zhai, Lijuan; Hu, Songhua

2016-08-01

Vaccination using attenuated vaccines remains an important method to control animal infectious diseases. The present study evaluated ginseng stem-leaf saponins (GSLS) and thimerosal (TS) for their adjuvant effect on an attenuated pseudorabies virus (aPrV) vaccine in mice. Compared to the group immunized with aPrV alone, the co-inoculation of GSLS and/or TS induced a higher antibody response. Particularly, when administered together with GSLS-TS, the aPrV vaccine provoked a higher serum gB-specific antibody, IgG1 and IgG2a levels, lymphocyte proliferative responses, as well as production of cytokines (IFN-γ, IL-12, IL-5 and IL-10) from lymphocytes, and more importantly provided an enhanced cytotoxicity of NK cells and protection against virulent field pseudorabies virus challenge. Additionally, the increased expression of miR-132, miR-146a, miR-147 and miR-155 was found in murine macrophages cultured with GSLS and/or TS. These data suggest that GSLS-TS as adjuvant improve the efficacy of aPrV vaccine in mouse model and have potential for the development of attenuated viral vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

JPRS Report, Science & Technology, USSR: Computers

DTIC Science & Technology

1987-09-29

Reliability of Protected Systems (L.S. Stoykova, O.A. Yushchenko; KIBERNETIKA, No 5, Sep-Oct 86) U Decision Making Based on Analysis of a Decision...34 published by the Central Scientific Research Institute for Information and Technoeconomic Research on Material and Technical Supply (TsNIITEIMS) of the...was said becomes clear after a subconscious analysis of the context. We have built our device according to the same pattern. In contrast to its

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dallman, Ann Renee; Neary, Vincent Sinclair

This report presents met - ocean data and wave energy characteristics at three U.S. wave energy converter (WEC) test and potential deployment sites . Its purpose is to enable the compari son of wave resource characteristics among sites as well as the select io n of test sites that are most suitable for a developer's device and that best meet their testing needs and objectives . It also provides essential inputs for the design of WEC test devices and planning WEC tests, including the planning of deployment and op eration s and maintenance. For each site, this report catalogues wavemore » statistics recommended in the (draft) International Electrotechnical Commission Technical Specification (IEC 62600 - 101 TS) on Wave Energy Characterization, as well as the frequency of oc currence of weather windows and extreme sea states, and statistics on wind and ocean currents. It also provides useful information on test site infrastructure and services .« less

Application of Tsallis Entropy to EEG: Quantifying the Presence of Burst Suppression After Asphyxial Cardiac Arrest in Rats

PubMed Central

Zhang, Dandan; Jia, Xiaofeng; Ding, Haiyan; Ye, Datian; Thakor, Nitish V.

2011-01-01

Burst suppression (BS) activity in EEG is clinically accepted as a marker of brain dysfunction or injury. Experimental studies in a rodent model of brain injury following asphyxial cardiac arrest (CA) show evidence of BS soon after resuscitation, appearing as a transitional recovery pattern between isoelectricity and continuous EEG. The EEG trends in such experiments suggest varying levels of uncertainty or randomness in the signals. To quantify the EEG data, Shannon entropy and Tsallis entropy (TsEn) are examined. More specifically, an entropy-based measure named TsEn area (TsEnA) is proposed to reveal the presence and the extent of development of BS following brain injury. The methodology of TsEnA and the selection of its parameter are elucidated in detail. To test the validity of this measure, 15 rats were subjected to 7 or 9 min of asphyxial CA. EEG recordings immediately after resuscitation from CA were investigated and characterized by TsEnA. The results show that TsEnA correlates well with the outcome assessed by evaluating the rodents after the experiments using a well-established neurological deficit score (Pearson correlation = 0.86, p ⪡ 0.01). This research shows that TsEnA reliably quantifies the complex dynamics in BS EEG, and may be useful as an experimental or clinical tool for objective estimation of the gravity of brain damage after CA. PMID:19695982

In situ hydrothermal synthesis of a novel hierarchically porous TS-1/modified-diatomite composite for methylene blue (MB) removal by the synergistic effect of adsorption and photocatalysis.

PubMed

Yuan, Weiwei; Yuan, Peng; Liu, Dong; Yu, Wenbin; Laipan, Minwang; Deng, Liangliang; Chen, Fanrong

2016-01-15

Hierarchically porous TS-1/modified-diatomite composites with high removal efficiency for methylene blue (MB) were prepared via a facile in situ hydrothermal route. The surface charge state of the diatomite was modified to enhance the electrostatic interactions, followed by in situ hydrothermal coating with TS-1 nanoparticles. The zeolite loading amount in the composites could be adjusted by changing the hydrothermal time. The highest specific surface area and micropore volume of the obtained composites were 521.3m(2)/g and 0.254cm(3)/g, respectively, with an optimized zeolite loading amount of 96.8%. Based on the synergistic effect of efficient adsorption and photocatalysis resulting from the newly formed hierarchically porous structure and improved dispersion of TS-1 nanoparticles onto diatomite, the composites' removal efficiency for MB reached 99.1% after 2h of photocatalytic reaction, even higher than that observed using pure TS-1 nanoparticles. Moreover, the superior MB removal kinetics of the composites were well represented by a pseudo-first-order model, with a rate constant (5.28×10(-2)min(-1)) more than twice as high as that of pure TS-1 nanoparticles (2.43×10(-2)min(-1)). The significant dye removal performance of this novel TS-1/modified-diatomite composite indicates that it is a promising candidate for use in waste water treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Analysis of PTPN22, ZFAT and MYO9B polymorphisms in Turner Syndrome and risk of autoimmune disease.

PubMed

Villanueva-Ortega, E; Ahedo, B; Fonseca-Sánchez, M A; Pérez-Durán, J; Garibay-Nieto, N; Macías-Galavíz, M T; Trujillo-Cabrera, Y; García-Latorre, E; Queipo, G

2017-08-01

Turner syndrome (TS) is one of the most common sexual chromosome abnormalities and is clearly associated with an increased risk of autoimmune diseases, particularly thyroid disease and coeliac disease (CD). Single-nucleotide polymorphism analyses have been shown to provide correlative evidence that specific genes are associated with autoimmune disease. Our aim was to study the functional polymorphic variants of PTPN22 and ZFAT in relation to thyroid disease and those of MYO9B in relation to CD. A cross-sectional comparative analysis was performed on Mexican mestizo patients with TS and age-matched healthy females. Our data showed that PTPN22 C1858T (considered a risk variant) is not associated with TS (X 2  = 3.50, p = .61, and OR = 0.33 [95% CI = 0.10-1.10]). Also, ZFAT was not associated with TS (X 2  = 1.2, p = .28, and OR = 1.22 [95% CI = 0.84-1.79]). However, for the first time, rs2305767 MYO9B was revealed to have a strong association with TS (X 2  = 58.6, p = .0001, and OR = 10.44 [95% C = 5.51-19.80]), supporting a high level of predisposition to CD among TS patients. This report addresses additional data regarding the polymorphic variants associated with autoimmune disease, one of the most common complications in TS. © 2017 John Wiley & Sons Ltd.

Muscle function in Turner syndrome: normal force but decreased power.

PubMed

Soucek, Ondrej; Lebl, Jan; Matyskova, Jana; Snajderova, Marta; Kolouskova, Stanislava; Pruhova, Stepanka; Hlavka, Zdenek; Sumnik, Zdenek

2015-02-01

Although hypogonadism and SHOX gene haploinsufficiency likely cause the decreased bone mineral density and increased fracture rate associated with Turner syndrome (TS), the exact mechanism remains unclear. We tested the hypothesis that muscle dysfunction in patients with TS contributes to increased fracture risk. The secondary aim was to determine whether menarche, hormone therapy duration, positive fracture history and genotype influence muscle function parameters in patients with TS. A cross-sectional study was conducted in a single university hospital referral centre between March 2012 and October 2013. Sixty patients with TS (mean age of 13·7 ± 4·5 years) were compared to the control group of 432 healthy girls. A Leonardo Mechanograph(®) Ground Reaction Force Platform was used to assess muscle force (Fmax ) by the multiple one-legged hopping test and muscle power (Pmax ) by the single two-legged jump test. While the Fmax was normal (mean weight-specific Z-score of 0·11 ± 0·77, P = 0·27), the Pmax was decreased in patients with TS (Z-score of -0·93 ± 1·5, P < 0·001) compared with healthy controls. The muscle function parameters were not significantly influenced by menarcheal stage, hormone therapy duration, fracture history or genotype (linear regression adjusted for age, weight and height; P > 0·05 for all). Fmax , a principal determinant of bone strength, is normal in patients with TS. Previously described changes in bone quality and structure in TS are thus not likely related to inadequate mechanical loading but rather represent a primary bone deficit. A decreased Pmax indicates impaired muscle coordination in patients with TS. © 2014 John Wiley & Sons Ltd.

Comparison of shoulder internal rotation test with the elbow flexion test in the diagnosis of cubital tunnel syndrome.

PubMed

Ochi, Kensuke; Horiuchi, Yukio; Tanabe, Aya; Morita, Kozo; Takeda, Kentaro; Ninomiya, Ken

2011-05-01

To compare the shoulder internal rotation test-a new, provocative test-with the elbow flexion test in the diagnosis of cubital tunnel syndrome (CubTS). Twenty-five patients with CubTS were examined before and after surgery with 10 seconds each of the elbow flexion and shoulder internal rotation tests. Fifty-four asymptomatic individuals and 14 neuropathy patients with a diagnosis other than CubTS were also examined as control cases. For the shoulder internal rotation test, the patient's upper extremity was kept at 90° abduction, maximum internal rotation, and 10° flexion at the shoulder, with 90° elbow flexion and neutral position of the forearm and wrist, with finger extension. Test results were considered positive if any slight symptom attributable to CubTS occurred within 10 seconds. Extraneural pressure inside the cubital tunnel was intraoperatively measured with the positions of both the elbow flexion and shoulder internal rotation tests, in 15 of the CubTS cases. Statistical analyses were performed using Student's t-test with a confidence level of 95%. The preoperative sensitivity in CubTS cases was 80% in the 10-second shoulder internal rotation test and 36% in the 10-second elbow flexion test, and these differences were significant. None of the control cases had positive results in either test. All the CubTS cases improved with surgery; after surgery, neither test provoked symptoms in any surgical patient. The extraneural pressure increased in both provocative positions with no significant difference. Positive results for the 10-second shoulder internal rotation test were more sensitive than that for the elbow flexion test of the same duration and seemed specific to CubTS. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

New View on the Initial Development Site and Radiographic Classification System of Osteoarthritis of the Knee Based on Radiographic Analysis

PubMed Central

Moon, Ki-Ho

2012-01-01

Introduction: Radiographic pathology of severe osteoarthritis of the knee (OAK) such as severe osteophyte at tibial spine (TS), compartment narrowing, marginal osteophyte, and subchondral sclerosis is well known. Kellgren-Lawrence grading system, which is widely used to diagnose OAK, describes narrowing-marginal osteophyte in 4-grades but uses osteophyte at TS only as evidence of OAK without detailed-grading. However, kinematically the knee employs medial TS as an axis while medial and lateral compartments carry the load, suggesting that early OAK would occur sooner at TS than at compartment. Then, Kellgren-Lawrence system may be inadequate to diagnose early-stage OAK manifested as a subtle osteophyte at TS without narrowing-marginal osteophyte. This undiagnosed-OAK will deteriorate becoming a contributing factor in an increasing incidence of OAK. Methods: This study developed a radiographic OAK-marker based on both osteophyte at TS and compartment narrowing-marginal osteophyte and graded as normal, mild, moderate, and severe. With this marker, both knee radiographs of 1,728 patients with knee pain were analyzed. Results: Among 611 early-stage mild OAK, 562 or 92% started at TS and 49 or 8% at compartment. It suggests the initial development site of OAK, helping develop new site-specific radiographic classification system of OAK accurately to diagnose all severity of OAK at early, intermediate, or late-stage. It showed that Kellgren-Lawrence system missed 92.0% of early-stage mild OAK from diagnosis. Conclusions: A subtle osteophyte at TS is the earliest radiographic sign of OAK. A new radiographic classification system of OAK was suggested for accurate diagnosis of all OAK in severity and at stage. PMID:23675278

New view on the initial development site and radiographic classification system of osteoarthritis of the knee based on radiographic analysis.

PubMed

Moon, Ki-Ho

2012-12-01

Radiographic pathology of severe osteoarthritis of the knee (OAK) such as severe osteophyte at tibial spine (TS), compartment narrowing, marginal osteophyte, and subchondral sclerosis is well known. Kellgren-Lawrence grading system, which is widely used to diagnose OAK, describes narrowing-marginal osteophyte in 4-grades but uses osteophyte at TS only as evidence of OAK without detailed-grading. However, kinematically the knee employs medial TS as an axis while medial and lateral compartments carry the load, suggesting that early OAK would occur sooner at TS than at compartment. Then, Kellgren-Lawrence system may be inadequate to diagnose early-stage OAK manifested as a subtle osteophyte at TS without narrowing-marginal osteophyte. This undiagnosed-OAK will deteriorate becoming a contributing factor in an increasing incidence of OAK. This study developed a radiographic OAK-marker based on both osteophyte at TS and compartment narrowing-marginal osteophyte and graded as normal, mild, moderate, and severe. With this marker, both knee radiographs of 1,728 patients with knee pain were analyzed. Among 611 early-stage mild OAK, 562 or 92% started at TS and 49 or 8% at compartment. It suggests the initial development site of OAK, helping develop new site-specific radiographic classification system of OAK accurately to diagnose all severity of OAK at early, intermediate, or late-stage. It showed that Kellgren-Lawrence system missed 92.0% of early-stage mild OAK from diagnosis. A subtle osteophyte at TS is the earliest radiographic sign of OAK. A new radiographic classification system of OAK was suggested for accurate diagnosis of all OAK in severity and at stage.

Belief and sign, true and false: the unique of false belief reasoning.

PubMed

Zhang, Ting; Zhang, Qin; Li, Yiyuan; Long, Changquan; Li, Hong

2013-11-01

For a long time, a controversy has been proposed that whether the process of theory of mind is a result of domain-specific or domain-general changes (Wellman in The handbook of childhood cognitive development. Blackwell Publication, New Jersey, 2011). This event-related potential study explored the neural time course of domain-general and domain-specific components in belief reasoning. Fourteen participants completed location transfer false belief (FB), true belief (TB), false sign (FS) and true sign (TS) tasks, in which two pictures told a story related to a dog that ran from a green into a red box. In the TB and FB tasks, a boy saw or did not see the transfer of the dog, respectively. In the FS and TS tasks, an arrow that pointed to the green box either altered its direction to the red box or did not alter following the transfer of the dog. Participants then inferred where the boy thought of, or the arrow indicated the location of the dog. FB and TB reasoning elicited lower N2 amplitudes than FS and TS reasoning, which is associated with domain-general components, the detection, and classification. The late slow wave (LSW) for FB was more positive at frontal, central, and parietal sites than FS because of the domain-specific component involved in FB reasoning. However, the LSW was less positive for TB than for FB but did not differ from the TS condition, which implies that mental representation might not be involved in TB reasoning.

Toward the Discovery of Effective Polycyclic Inhibitors of α-Synuclein Amyloid Assembly*

PubMed Central

Lamberto, Gonzalo R.; Torres-Monserrat, Valentina; Bertoncini, Carlos W.; Salvatella, Xavier; Zweckstetter, Markus; Griesinger, Christian; Fernández, Claudio O.

2011-01-01

The fibrillation of amyloidogenic proteins is a critical step in the etiology of neurodegenerative disorders such as Alzheimer and Parkinson diseases. There is major interest in the therapeutic intervention on such aberrant aggregation phenomena, and the utilization of polyaromatic scaffolds has lately received considerable attention. In this regard, the molecular and structural basis of the anti-amyloidogenicity of polyaromatic compounds, required to evolve this molecular scaffold toward therapeutic drugs, is not known in detail. We present here biophysical and biochemical studies that have enabled us to characterize the interaction of metal-substituted, tetrasulfonated phthalocyanines (PcTS) with α-synuclein (AS), the major protein component of amyloid-like deposits in Parkinson disease. The inhibitory activity of the assayed compounds on AS amyloid fibril formation decreases in the order PcTS[Ni(II)] ∼ PcTS > PcTS[Zn(II)] ≫ PcTS[Al(III)] ≈ 0. Using NMR and electronic absorption spectroscopies we demonstrated conclusively that the differences in binding capacity and anti-amyloid activity of phthalocyanines on AS are attributed to their relative ability to self-stack through π-π interactions, modulated by the nature of the metal ion bound at the molecule. Low order stacked aggregates of phthalocyanines were identified as the active amyloid inhibitory species, whose effects are mediated by residue specific interactions. Such sequence-specific anti-amyloid behavior of self-stacked phthalocyanines contrasts strongly with promiscuous amyloid inhibitors with self-association capabilities that act via nonspecific sequestration of AS molecules. The new findings reported here constitute an important contribution for future drug discovery efforts targeting amyloid formation. PMID:21795682

Financial Management Regulation. Volume 1. General Financial Management Information, Systems, and Requirements

DTIC Science & Technology

1993-05-01

20301-1100 DoD Components will be provided copies of this Volume of the Regulation through normal publication channels. Other Federal Agencies and the... public may obtain copies of this Volume from the National Technical Information Service, 5285 Port Royal Road, Springfield, VA 22161, (703) 487- 4650...SECTION 1 PARAGRAPH 1 SUtHI’ARAGRAIlTS ii DoD Financial Management Regulation Volume 1, Introductionp PUBLICATIONS SUPERSEDED This Volume of the

Comprehensive Employment and Training Act of 1973. Job Corps Health Program. A Working Document for Standing Orders. Part 1. Standing Orders for Health Personnel.

ERIC Educational Resources Information Center

Employment and Training Administration (DOL), Washington, DC.

Developed as the first of a two-part supplement to Technical Supplement Q for Standing Orders (TS-Q), this handbook of standing orders was designed to help health personnel at Comprehensive Employment and Training Act (CETA) Job Corps health centers meet the federal requirement that each center have a set of written standing orders on how to…

[Prokaryotic expression and histological localization of the Taenia solium CDC37 gene].

PubMed

Huang, Jiang; Li, Bo; Dai, Jia-Lin; Zhang, Ai-Hua

2013-02-01

To express Taenia solium gene encoding cell division cycle 37 protein (TsCDC37) and investigate its antigenicity and localization in adults of Taenia solium. The complete coding sequence of TsCDC37 was amplified by PCR based on the recombinant plasmid clone from the cDNA library of adult Taenia solium. The PCR product was cloned into a prokaryotic expression vector pET-28a (+). The recombinant expression plasmid was identified by PCR, double endonuclease digestion and sequencing. The recombinant plasmid was transformed into E. coli BL21/DE3 and followed by expression of the protein induced by IPTG. The mice were immunized subcutaneously with purified recombinant TsCDC37 formulated in Freund's adjuvant. The antigenicity of the recombinant protein was examined by Western blotting. The localization of TsCDC37 in adult worms was demonstrated by immunofluorescent technique. The recombinant expression vector was constructed successfully. The recombinant protein was about M(r) 52 000, it was then purified and specifically recognized by immuno sera of SD rats and sera from patients infected with Taenia solium, Taenia saginata or Taenia asiatica. The immunofluorescence assay revealed that TsCDC37 located at the tegument of T. solium adult and the eggs. TsCDC37 gene has been expressed with immunoreactivity. The recombinant protein is mainly expressed in tegument and egg, and is a common antigen of the three human taenia cestodes.

Refining Ovarian Cancer Test accuracy Scores (ROCkeTS): protocol for a prospective longitudinal test accuracy study to validate new risk scores in women with symptoms of suspected ovarian cancer

PubMed Central

Sundar, Sudha; Rick, Caroline; Dowling, Francis; Au, Pui; Rai, Nirmala; Champaneria, Rita; Stobart, Hilary; Neal, Richard; Davenport, Clare; Mallett, Susan; Sutton, Andrew; Kehoe, Sean; Timmerman, Dirk; Bourne, Tom; Van Calster, Ben; Gentry-Maharaj, Aleksandra; Deeks, Jon

2016-01-01

Introduction Ovarian cancer (OC) is associated with non-specific symptoms such as bloating, making accurate diagnosis challenging: only 1 in 3 women with OC presents through primary care referral. National Institute for Health and Care Excellence guidelines recommends sequential testing with CA125 and routine ultrasound in primary care. However, these diagnostic tests have limited sensitivity or specificity. Improving accurate triage in women with vague symptoms is likely to improve mortality by streamlining referral and care pathways. The Refining Ovarian Cancer Test Accuracy Scores (ROCkeTS; HTA 13/13/01) project will derive and validate new tests/risk prediction models that estimate the probability of having OC in women with symptoms. This protocol refers to the prospective study only (phase III). Methods and analysis ROCkeTS comprises four parallel phases. The full ROCkeTS protocol can be found at http://www.birmingham.ac.uk/ROCKETS. Phase III is a prospective test accuracy study. The study will recruit 2450 patients from 15 UK sites. Recruited patients complete symptom and anxiety questionnaires, donate a serum sample and undergo ultrasound scored as per International Ovarian Tumour Analysis (IOTA) criteria. Recruitment is at rapid access clinics, emergency departments and elective clinics. Models to be evaluated include those based on ultrasound derived by the IOTA group and novel models derived from analysis of existing data sets. Estimates of sensitivity, specificity, c-statistic (area under receiver operating curve), positive predictive value and negative predictive value of diagnostic tests are evaluated and a calibration plot for models will be presented. ROCkeTS has received ethical approval from the NHS West Midlands REC (14/WM/1241) and is registered on the controlled trials website (ISRCTN17160843) and the National Institute of Health Research Cancer and Reproductive Health portfolios. PMID:27507231

Evaluation and optimisation of indel detection workflows for ion torrent sequencing of the BRCA1 and BRCA2 genes.

PubMed

Yeo, Zhen Xuan; Wong, Joshua Chee Leong; Rozen, Steven G; Lee, Ann Siew Gek

2014-06-24

The Ion Torrent PGM is a popular benchtop sequencer that shows promise in replacing conventional Sanger sequencing as the gold standard for mutation detection. Despite the PGM's reported high accuracy in calling single nucleotide variations, it tends to generate many false positive calls in detecting insertions and deletions (indels), which may hinder its utility for clinical genetic testing. Recently, the proprietary analytical workflow for the Ion Torrent sequencer, Torrent Suite (TS), underwent a series of upgrades. We evaluated three major upgrades of TS by calling indels in the BRCA1 and BRCA2 genes. Our analysis revealed that false negative indels could be generated by TS under both default calling parameters and parameters adjusted for maximum sensitivity. However, indel calling with the same data using the open source variant callers, GATK and SAMtools showed that false negatives could be minimised with the use of appropriate bioinformatics analysis. Furthermore, we identified two variant calling measures, Quality-by-Depth (QD) and VARiation of the Width of gaps and inserts (VARW), which substantially reduced false positive indels, including non-homopolymer associated errors without compromising sensitivity. In our best case scenario that involved the TMAP aligner and SAMtools, we achieved 100% sensitivity, 99.99% specificity and 29% False Discovery Rate (FDR) in indel calling from all 23 samples, which is a good performance for mutation screening using PGM. New versions of TS, BWA and GATK have shown improvements in indel calling sensitivity and specificity over their older counterpart. However, the variant caller of TS exhibits a lower sensitivity than GATK and SAMtools. Our findings demonstrate that although indel calling from PGM sequences may appear to be noisy at first glance, proper computational indel calling analysis is able to maximize both the sensitivity and specificity at the single base level, paving the way for the usage of this technology for future clinical genetic testing.

In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the fucosyltransferase multigene family.

PubMed

Peterson, Nathan A; Anderson, Tavis K; Yoshino, Timothy P

2013-01-01

Fucosylated glycans of the parasitic flatworm Schistosoma mansoni play key roles in its development and immunobiology. In the present study we used a genome-wide homology-based bioinformatics approach to search for genes that contribute to fucosylated glycan expression in S. mansoni, specifically the α2-, α3-, and α6-fucosyltransferases (FucTs), which transfer L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. We identified and in silico characterized several novel schistosome FucT homologs, including six α3-FucTs and six α6-FucTs, as well as two protein O-FucTs that catalyze the unrelated transfer of L-fucose to serine and threonine residues of epidermal growth factor- and thrombospondin-type repeats. No α2-FucTs were observed. Primary sequence analyses identified key conserved FucT motifs as well as characteristic transmembrane domains, consistent with their putative roles as fucosyltransferases. Most genes exhibit alternative splicing, with multiple transcript variants generated. A phylogenetic analysis demonstrated that schistosome α3- and α6-FucTs form monophyletic clades within their respective gene families, suggesting multiple gene duplications following the separation of the schistosome lineage from the main evolutionary tree. Quantitative decreases in steady-state transcript levels of some FucTs during early larval development suggest a possible mechanism for differential expression of fucosylated glycans in schistosomes. This study systematically identifies the complete repertoire of FucT homologs in S. mansoni and provides fundamental information regarding their genomic organization, genetic variation, developmental expression, and evolutionary history.

Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins

PubMed Central

Cremonez, Caroline M.; Maiti, Mohitosh; Peigneur, Steve; Cassoli, Juliana Silva; Dutra, Alexandre A. A.; Waelkens, Etienne; Lescrinier, Eveline; Herdewijn, Piet; de Lima, Maria Elena; Pimenta, Adriano M. C.; Arantes, Eliane C.; Tytgat, Jan

2016-01-01

To date, several families of peptide toxins specifically interacting with ion channels in scorpion venom have been described. One of these families comprise peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202 KTxs have been reported, belonging to several subfamilies of KTxs (called α, β, γ, κ, δ, and λ-KTxs). Here we report on a previously described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out an in-depth structure-function analysis combining 3D structure elucidation of Ts11 and electrophysiological characterization of the toxin. The Ts11 structure is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely devoid of the classical secondary structure elements (α-helix and/or β-strand). This has, to the best of our knowledge, never been described before for scorpion toxins and therefore represents a novel, 6th type of structural fold for these scorpion peptides. On the basis of their preferred interaction with voltage-gated K channels, as compared to all the other targets tested, it can be postulated that Ts11 is the first member of a new subfamily, designated as ε-KTx. PMID:27706049

Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins.

PubMed

Cremonez, Caroline M; Maiti, Mohitosh; Peigneur, Steve; Cassoli, Juliana Silva; Dutra, Alexandre A A; Waelkens, Etienne; Lescrinier, Eveline; Herdewijn, Piet; de Lima, Maria Elena; Pimenta, Adriano M C; Arantes, Eliane C; Tytgat, Jan

2016-09-30

To date, several families of peptide toxins specifically interacting with ion channels in scorpion venom have been described. One of these families comprise peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202 KTxs have been reported, belonging to several subfamilies of KTxs (called α, β, γ, κ, δ, and λ-KTxs). Here we report on a previously described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out an in-depth structure-function analysis combining 3D structure elucidation of Ts11 and electrophysiological characterization of the toxin. The Ts11 structure is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely devoid of the classical secondary structure elements (α-helix and/or β-strand). This has, to the best of our knowledge, never been described before for scorpion toxins and therefore represents a novel, 6th type of structural fold for these scorpion peptides. On the basis of their preferred interaction with voltage-gated K channels, as compared to all the other targets tested, it can be postulated that Ts11 is the first member of a new subfamily, designated as ε-KTx.

Depletion of suppressor T cells by 2'-deoxyguanosine abrogates tolerance in mice fed ovalbumin and permits the induction of intestinal delayed-type hypersensitivity.

PubMed Central

Mowat, A M

1986-01-01

We have re-examined the role of suppressor T cells (Ts) in regulating immune responses to fed proteins by investigating the effect of 2'-deoxyguanosine (dGuo) on systemic and intestinal immunity in mice fed ovalbumin (OVA). Administration of dGuo for 10 days abrogated the suppression of systemic delayed-type hypersensitivity (DTH) and antibody responses normally found after feeding OVA, and also prevented the generation of OVA-specific Ts. In parallel, mice given dGuo and fed OVA developed sensitization to OVA in the gut-associated lymphoid tissues (GALT) after oral challenge with OVA and had increased intraepithelial lymphocyte (IEL) counts and crypt cell production rates (CCPR) in the jejunal mucosa, indicating the presence of a local DTH response. These findings confirm the importance of Ts in preventing hypersensitivity to dietary protein antigens and suggest that enteropathies associated with food hypersensitivity are due to a defect in Ts activity. PMID:2940171

Clinical Assessment of Tourette Syndrome and Tic Disorders

PubMed Central

Cohen, Stephanie; Leckman, James F.; Bloch, Michael H.

2013-01-01

Tourette Syndrome (TS) is a neuropsychiatric disorder involving multiple motor and phonic tics. Tics, which usually begin between the ages of 6 and 8, are sudden, rapid, stereotyped, and apparently purposeless movements or sounds that involve discrete muscle groups. Individuals with TS experience a variety of different sensory phenomena, including premonitory urges prior to tics and somatic hypersensitivity due to impaired sensorimotor gating. In addition to other conditions, stress, anxiety, fatigue, or other heightened emotional states tend to exacerbate tics, while relaxation, playing sports, and focused concentration on a specific task tend to alleviate tic symptoms. Ninety percent of children with TS also have comorbid conditions, such as Attention deficit hyperactivity disorder (ADHD), Obsessive-compulsive disorder (OCD), or an impulse control disorder. These disorders often cause more problems for the child both at home and at school than tics do alone. Proper diagnosis and treatment of TS involves appropriate evaluation and recognition, not only of tics, but also of these associated conditions. PMID:23206664

Phenomenology of tics and natural history of tic disorders.

PubMed

Leckman, James F

2003-12-01

Tic symptoms, the hallmark of Tourette's syndrome (TS), may simply be fragments of innate behavior. As such, the sensory urges that precede tics may illuminate some of the normal internal cues that are intimately involved in the assembly of behavioral sequences. The occurrence of tics in time appears to have fractal characteristics that may help to explain the waxing and waning course of tic disorders. Longitudinal studies are currently underway that should permit a close examination of the natural fluctuations in tic severity using valid and reliable clinician-rated scales of tic severity. The natural history of tics typically shows a marked decline during the course of adolescence. However, TS can also be associated with social, emotional, and academic difficulties in early adulthood. Comorbid attention deficit/hyperactivity disorder and obsessive-compulsive disorder are likely to influence the long-term adaptive outcomes of individuals with TS. Future progress may also be expected as endophenotypes, and possibly genetic markers, are identified that are associated with specific comorbid conditions and etiologically distinct forms of TS.

Lattice dynamics of A Sb2O6 (A =Cu , Co) with trirutile structure

NASA Astrophysics Data System (ADS)

Maimone, D. T.; Christian, A. B.; Neumeier, J. J.; Granado, E.

2018-03-01

Raman spectroscopy experiments on single crystals of CuSb2O6 and CoSb2O6 quasi-one-dimensional antiferromagnets with trirutile crystal structure were performed, with a focus on the first material. The observed Raman-active phonon modes and previously reported infrared-active modes were identified with the aid of ab initio lattice dynamics calculations. The structural transition between monoclinic β -CuSb2O6 and tetragonal α -CuSb2O6 phases at Ts=400 K is manifested in our spectra by a "repulsion" of two accidentally quasidegenerate symmetric modes below Ts, caused by a phonon mixing effect that is only operative in the monoclinic β -CuSb2O6 phase due to symmetry restrictions. Also, two specific phonons, associated with CuO6 octahedra rotation and with a Jahn-Teller elongation mode, soften and broaden appreciably as T →Ts . A crossover from a displacive to an order-disorder transition at Ts is inferred.

The influence of speed abilities and technical skills in early adolescence on adult success in soccer: A long-term prospective analysis using ANOVA and SEM approaches

PubMed Central

2017-01-01

Several talent development programs in youth soccer have implemented motor diagnostics measuring performance factors. However, the predictive value of such tests for adult success is a controversial topic in talent research. This prospective cohort study evaluated the long-term predictive value of 1) motor tests and 2) players’ speed abilities (SA) and technical skills (TS) in early adolescence. The sample consisted of 14,178 U12 players from the German talent development program. Five tests (sprint, agility, dribbling, ball control, shooting) were conducted and players’ height, weight as well as relative age were assessed at nationwide diagnostics between 2004 and 2006. In the 2014/15 season, the players were then categorized as professional (n = 89), semi-professional (n = 913), or non-professional players (n = 13,176), indicating their adult performance level (APL). The motor tests’ prognostic relevance was determined using ANOVAs. Players’ future success was predicted by a logistic regression threshold model. This structural equation model comprised a measurement model with the motor tests and two correlated latent factors, SA and TS, with simultaneous consideration for the manifest covariates height, weight and relative age. Each motor predictor and anthropometric characteristic discriminated significantly between the APL (p < .001; η2 ≤ .02). The threshold model significantly predicted the APL (R2 = 24.8%), and in early adolescence the factor TS (p < .001) seems to have a stronger effect on adult performance than SA (p < .05). Both approaches (ANOVA, SEM) verified the diagnostics’ predictive validity over a long-term period (≈ 9 years). However, because of the limited effect sizes, the motor tests’ prognostic relevance remains ambiguous. A challenge for future research lies in the integration of different (e.g., person-oriented or multilevel) multivariate approaches that expand beyond the “traditional” topic of single tests’ predictive validity and toward more theoretically founded issues. PMID:28806410

Teleost Fish-Specific Preferential Retention of Pigmentation Gene-Containing Families After Whole Genome Duplications in Vertebrates

PubMed Central

Lorin, Thibault; Brunet, Frédéric G.; Laudet, Vincent; Volff, Jean-Nicolas

2018-01-01

Vertebrate pigmentation is a highly diverse trait mainly determined by neural crest cell derivatives. It has been suggested that two rounds (1R/2R) of whole-genome duplications (WGDs) at the basis of vertebrates allowed changes in gene regulation associated with neural crest evolution. Subsequently, the teleost fish lineage experienced other WGDs, including the teleost-specific Ts3R before teleost radiation and the more recent Ss4R at the basis of salmonids. As the teleost lineage harbors the highest number of pigment cell types and pigmentation diversity in vertebrates, WGDs might have contributed to the evolution and diversification of the pigmentation gene repertoire in teleosts. We have compared the impact of the basal vertebrate 1R/2R duplications with that of the teleost-specific Ts3R and salmonid-specific Ss4R WGDs on 181 gene families containing genes involved in pigmentation. We show that pigmentation genes (PGs) have been globally more frequently retained as duplicates than other genes after Ts3R and Ss4R but not after the early 1R/2R. This is also true for non-pigmentary paralogs of PGs, suggesting that the function in pigmentation is not the sole key driver of gene retention after WGDs. On the long-term, specific categories of PGs have been repeatedly preferentially retained after ancient 1R/2R and Ts3R WGDs, possibly linked to the molecular nature of their proteins (e.g., DNA binding transcriptional regulators) and their central position in protein-protein interaction networks. Taken together, our results support a major role of WGDs in the diversification of the pigmentation gene repertoire in the teleost lineage, with a possible link with the diversity of pigment cell lineages observed in these animals compared to other vertebrates. PMID:29599177

Pediatric Autoimmune Disorders Associated with Streptococcal Infections and Tourette's Syndrome in Preclinical Studies

PubMed Central

Spinello, Chiara; Laviola, Giovanni; Macrì, Simone

2016-01-01

Accumulating evidence suggests that Tourette's Syndrome (TS) – a multifactorial pediatric disorder characterized by the recurrent exhibition of motor tics and/or vocal utterances – can partly depend on immune dysregulation provoked by early repeated streptococcal infections. The natural and adaptive antibody-mediated reaction to streptococcus has been proposed to potentially turn into a pathological autoimmune response in vulnerable individuals. Specifically, in conditions of increased permeability of the blood brain barrier (BBB), streptococcus-induced antibodies have been proposed to: (i) reach neuronal targets located in brain areas responsible for motion control; and (ii) contribute to the exhibition of symptoms. This theoretical framework is supported by indirect evidence indicating that a subset of TS patients exhibit elevated streptococcal antibody titers upon tic relapses. A systematic evaluation of this hypothesis entails preclinical studies providing a proof of concept of the aforementioned pathological sequelae. These studies shall rest upon individuals characterized by a vulnerable immune system, repeatedly exposed to streptococcus, and carefully screened for phenotypes isomorphic to the pathological signs of TS observed in patients. Preclinical animal models may thus constitute an informative, useful tool upon which conducting targeted, hypothesis-driven experiments. In the present review we discuss the available evidence in preclinical models in support of the link between TS and pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS), and the existing gaps that future research shall bridge. Specifically, we report recent preclinical evidence indicating that the immune responses to repeated streptococcal immunizations relate to the occurrence of behavioral and neurological phenotypes reminiscent of TS. By the same token, we discuss the limitations of these studies: limited evidence of behavioral phenotypes isomorphic to tics and scarce knowledge about the immunological phenomena favoring the transition from natural adaptive immunity to pathological outcomes. PMID:27445678

The technical communication practices of Russian and U.S. aerospace engineers and scientists

NASA Technical Reports Server (NTRS)

Pinelli, Thomas E.; Barclay, Rebecca O.; Keene, Michael L.; Flammia, Madelyn; Kennedy, John M.

1993-01-01

As part of Phase 4 of the NASA/DoD Aerospace Knowledge Diffusion Research Project, two studies were conducted that investigated the technical communication practices of Russian and U.S. aerospace engineers and scientists. Both studies had the same five objectives: first, to solicit the opinions of aerospace engineers and scientists regarding the importance of technical communication to their professions; second, to determine the use and production of technical communication by aerospace engineers and scientists; third, to seek their views about the appropriate content of the undergraduate course in technical communication; fourth, to determine aerospace engineers' and scientists' use of libraries, technical information centers, and on-line databases; and fifth, to determine the use and importance of computer and information technology to them. A self administered questionnaire was distributed to Russian aerospace engineers and scientists at the Central Aero-Hydrodynamic Institute (TsAGI) and to their U.S. counterparts at the NASA Ames Research Center and the NASA Langley Research Center. The completion rates for the Russian and U.S. surveys were 64 and 61 percent, respectively. Responses of the Russian and U.S. participants to selected questions are presented in this paper.

NASA/DOD Aerospace Knowledge Diffusion Research Project. Paper 16: A comparison of the technical communications practices of Russian and US aerospace engineers and scientists

NASA Technical Reports Server (NTRS)

Pinelli, Thomas E.; Kennedy, John M.; Barclay, Rebecca O.

1993-01-01

As part of Phase 4 of the NASA/DOD Aerospace Knowledge Diffusion Project, two studies were conducted that investigated the technical communications practices of Russian and U.S. aerospace engineers and scientists. Both studies have the same five objectives: first, to solicit the opinions of aerospace engineers and scientists regarding the importance of technical communications to their profession; second, to determine the use and production of technical communications by aerospace engineers and scientists; third, to seek their views about the appropriate content of an undergraduate course in technical communications; fourth, to determine aerospace engineers' and scientists' use of libraries, technical information centers, and on-line data bases; and fifth, to determine the use and importance of computer and information technology to them. A self-administered questionnaire was distributed to aerospace engineers and scientists at the Central Aero-Hydrodynamic Institute (TsAGI), NASA ARC, and NASA LaRC. The completion rates for the Russian and U.S. surveys were 64 and 61 percent, respectively. The responses of the Russian and U.S. participants, to selected questions, are presented in this report.

NASA/DOD Aerospace Knowledge Diffusion Research Project. Paper 28: The technical communication practices of Russian and US aerospace engineers and scientists

NASA Technical Reports Server (NTRS)

Pinelli, Thomas E.; Barclay, Rebecca O.; Keene, Michael L.; Flammia, Madelyn; Kennedy, John M.

1993-01-01

As part of Phase 4 of the NASA/DoD Aerospace Knowledge Diffusion Research Project, two studies were conducted that investigated the technical communication practices of Russian and U.S. aerospace engineers and scientists. Both studies had the same five objectives: first, to solicit the opinions of aerospace engineers and scientists regarding the importance of technical communication to their professions; second, to determine the use and production of technical communication by aerospace engineers and scientists; third, to seek their views about the appropriate content of the undergraduate course in technical communication; fourth, to determine aerospace engineers' and scientists' use of libraries, technical information centers, and on-line databases; and fifth, to determine the use and importance of computer and information technology to them. A self administered questionnaire was distributed to Russian aerospace engineers and scientists at the Central Aero-Hydrodynamic Institute (TsAGI) and to their U.S. counterparts at the NASA Ames Research Center and the NASA Langley Research Center. The completion rates for the Russian and U.S. surveys were 64 and 61 percent, respectively. Responses of the Russian and U.S. participants to selected questions are presented in this paper.

Startling Mosaicism of the Y-Chromosome and Tandem Duplication of the SRY and DAZ Genes in Patients with Turner Syndrome

PubMed Central

Premi, Sanjay; Srivastava, Jyoti; Panneer, Ganesan; Ali, Sher

2008-01-01

Presence of the human Y-chromosome in females with Turner Syndrome (TS) enhances the risk of development of gonadoblastoma besides causing several other phenotypic abnormalities. In the present study, we have analyzed the Y chromosome in 15 clinically diagnosed Turner Syndrome (TS) patients and detected high level of mosaicisms ranging from 45,XO:46,XY = 100:0% in 4; 45,XO:46,XY:46XX = 4:94:2 in 8; and 45,XO:46,XY:46XX = 50:30:20 cells in 3 TS patients, unlike previous reports showing 5–8% cells with Y- material. Also, no ring, marker or di-centric Y was observed in any of the cases. Of the two TS patients having intact Y chromosome in >85% cells, one was exceptionally tall. Both the patients were positive for SRY, DAZ, CDY1, DBY, UTY and AZFa, b and c specific STSs. Real Time PCR and FISH demonstrated tandem duplication/multiplication of the SRY and DAZ genes. At sequence level, the SRY was normal in 8 TS patients while the remaining 7 showed either absence of this gene or known and novel mutations within and outside of the HMG box. SNV/SFV analysis showed normal four copies of the DAZ genes in these 8 patients. All the TS patients showed aplastic uterus with no ovaries and no symptom of gonadoblastoma. Present study demonstrates new types of polymorphisms indicating that no two TS patients have identical genotype-phenotype. Thus, a comprehensive analysis of more number of samples is warranted to uncover consensus on the loci affected, to be able to use them as potential diagnostic markers. PMID:19030103

Tumor targeting profiling of hyaluronan-coated lipid based-nanoparticles.

PubMed

Mizrahy, Shoshy; Goldsmith, Meir; Leviatan-Ben-Arye, Shani; Kisin-Finfer, Einat; Redy, Orit; Srinivasan, Srimeenakshi; Shabat, Doron; Godin, Biana; Peer, Dan

2014-04-07

Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression. Low Mw (LMw, <10 kDa) HA has been reported to provoke inflammatory responses, such as induction of cytokines, chemokines, reactive nitrogen species and growth factors. Herein, we prepared and characterized two types of HA coated (LMw and HMw) lipid-based targeted and stabilized nanoparticles (tsNPs) and tested their binding to tumor cells expressing the HA receptor (CD44), systemic immunotoxicity, and biodistribution in tumor bearing mice. In vitro, the Mw of the surface anchored HA had a significant influence on the affinity towards CD44 on B16F10 murine melanoma cells. LMw HA-tsNPs exhibited weak binding, while binding of tsNPs coated with HMw HA was characterized by high binding. Both types of tsNPs had no measured effect on cytokine induction in vivo following intravenous administration to healthy C57BL/6 mice suggesting no immune activation. HMw HA-tsNPs showed enhanced circulation time and tumor targeting specificity, mainly by accumulating in the tumor and its vicinity compared with LMw HA-tsNPs. Finally, we show that methotrexate (MTX), a drug commonly used in cancer chemotherapy, entrapped in HMw HA-tsNPs slowly diffused from the particles with a half-life of 13.75 days, and improved the therapeutic outcome in a murine B16F10 melanoma model compared with NPs suggesting an active cellular targeting beyond the Enhanced Permeability and Retention (EPR) effect. Taken together, these findings have major implications for the use of high molecular weight HA in nanomedicine as a selective and safe active cellular targeting moiety.

High-Resolution Melting-Curve Analysis of obg Gene to Differentiate the Temperature-Sensitive Mycoplasma synoviae Vaccine Strain MS-H from Non-Temperature-Sensitive Strains

PubMed Central

Shahid, Muhammad A.; Markham, Philip F.; Marenda, Marc S.; Agnew-Crumpton, Rebecca; Noormohammadi, Amir H.

2014-01-01

Temperature-sensitive (ts +) vaccine strain MS-H is the only live attenuated M. synoviae vaccine commercially available for use in poultry. With increasing use of this vaccine to control M. synoviae infections, differentiation of MS-H from field M. synoviae strains and from rarely occurring non-temperature-sensitive (ts –) MS-H revertants has become important, especially in countries where local strains are indistinguishable from MS-H by sequence analysis of variable lipoprotein haemagglutinin (vlhA) gene. Single nucleotide polymorphisms (SNPs) in the obg of MS-H have been found to associate with ts phenotype. In this study, four PCRs followed by high-resolution melting (HRM)-curve analysis of the regions encompassing these SNPs were developed and evaluated for their potential to differentiate MS-H from 36 M. synoviae strains/isolates. The nested-obg PCR-HRM differentiated ts + MS-H vaccine not only from field M. synoviae strains/isolates but also from ts – MS-H revertants. The mean genotype confidence percentages, 96.9±3.4 and 8.8±11.2 for ts + and ts – strains, respectively, demonstrated high differentiating power of the nested-obg PCR-HRM. Using a combination of nested-obg and obg-F3R3 PCR-HRM, 97% of the isolates/strains were typed according to their ts phenotype with all MS-H isolates typed as MS-H. A set of respiratory swabs from MS-H vaccinated specific pathogen free chickens and M. synoviae infected commercial chicken flocks were tested using obg PCR-HRM system and results were consistent with those of vlhA genotyping. The PCR-HRM system developed in this study, proved to be a rapid and reliable tool using pure M. synoviae cultures as well as direct clinical specimens. PMID:24643035

Probing the structure of Leishmania donovani chagasi DHFR-TS: comparative protein modeling and protein-ligand interaction studies.

PubMed

Maganti, Lakshmi; Manoharan, Prabu; Ghoshal, Nanda

2010-09-01

Dihydrofolate reductase (DHFR) has been used successfully as a drug target in the area of anti-bacterial, anti-cancer and anti-malarial therapy. It also acts as a drug target for Leishmaniasis. Inhibition of DHFR leads to cell death through lack of thymine (nucleotide metabolism). Although the crystal structures of Leishmania major and Trypanosoma cruzi DHFR-thymidylate synthase (TS) have been resolved, to date there is no three-dimensional (3D)-structural information on DHFR-TS of Leishmania donovani chagasi, which causes visceral leishmaniasis. Our aim in this study was to model the 3D structure of L. donovani chagasi DHFR-TS, and to investigate the structural requirements for its inhibition. In this paper we describe a highly refined homology model of L. donovani chagasi DHFR-TS based on available crystallographic structures by using the Homology module of Insight II. Structural refinement and minimization of the generated L. donovani chagasi DHFR-TS model employed the Discover 3 module of Insight II and molecular dynamic simulations. The model was further validated through use of the PROCHECK, Verify_3D, PROSA, PSQS and ERRAT programs, which confirm that the model is reliable. Superimposition of the model structure with the templates L. major A chain, L. major B chain And T. cruzi A chain showed root mean square deviations of 0.69 A, 0.71 A and 1.11 A, respectively. Docking analysis of the L. donovani chagasi DHFR-TS model with methotrexate enabled us to identify specific residues, viz. Val156, Val30, Lys95, Lys75 and Arg97, within the L. donovani chagasi DHFR-TS binding pocket, that play an important role in ligand or substrate binding. Docking studies clearly indicated that these five residues are important determinants for binding as they have strong hydrogen bonding interactions with the ligand.

Thomson scattering diagnostic systems in ITER

NASA Astrophysics Data System (ADS)

Bassan, M.; Andrew, P.; Kurskiev, G.; Mukhin, E.; Hatae, T.; Vayakis, G.; Yatsuka, E.; Walsh, M.

2016-01-01

Thomson scattering (TS) is a proven diagnostic technique that will be implemented in ITER in three independent systems. The Edge TS will measure electron temperature Te and electron density ne profiles at high resolution in the region with r/a>0.8 (with a the minor radius). The Core TS will cover the region r/a<0.85 and shall be able to measure electron temperatures up to 40 keV . The Divertor TS will observe a segment of the divertor plasma more than 700 mm long and is designed to detect Te as low as 0.3 eV . The Edge and Core systems are primary contributors to Te and ne profiles. Both are installed in equatorial port 10 and very close together with the toroidal distance between the two laser beams of less than 600 mm at the first wall (~ 6° toroidal separation), a characteristic that should allow to reliably match the two profiles in the region 0.8

Metacarpophalangeal pattern profile analysis: useful diagnostic tool for differentiating between dyschondrosteosis, Turner syndrome, and hypochondroplasia.

PubMed

Laurencikas, E; Sävendahl, L; Jorulf, H

2006-06-01

To assess the value of the metacarpophalangeal pattern profile (MCPP) analysis as a diagnostic tool for differentiating between patients with dyschondrosteosis, Turner syndrome, and hypochondroplasia. Radiographic and clinical data from 135 patients between 1 and 51 years of age were collected and analyzed. The study included 25 patients with hypochondroplasia (HCP), 39 with dyschondrosteosis (LWD), and 71 with Turner syndrome (TS). Hand pattern profiles were calculated and compared with those of 110 normal individuals. Pearson correlation coefficient (r) and multivariate discriminant analysis were used for pattern profile analysis. Pattern variability index, a measure of dysmorphogenesis, was calculated for LWD, TS, HCP, and normal controls. Our results demonstrate that patients with LWD, TS, or HCP have distinct pattern profiles that are significantly different from each other and from those of normal controls. Discriminant analysis yielded correct classification of normal versus abnormal individuals in 84% of cases. Classification of the patients into LWD, TS, and HCP groups was successful in 75%. The correct classification rate was higher (85%) when differentiating two pathological groups at a time. Pattern variability index was not helpful for differential diagnosis of LWD, TS, and HCP. Patients with LWD, TS, or HCP have distinct MCPPs and can be successfully differentiated from each other using advanced MCPP analysis. Discriminant analysis is to be preferred over Pearson correlation coefficient because it is a more sensitive and specific technique. MCPP analysis is a helpful tool for differentiating between syndromes with similar clinical and radiological abnormalities.

Trypanosoma cruzi trans-sialidase: A potent and specific survival factor for human Schwann cells by means of phosphatidylinositol 3-kinase/Akt signaling

PubMed Central

Chuenkova, Marina V.; Furnari, Frank B.; Cavenee, Webster K.; Pereira, Miercio A.

2001-01-01

Patients infected with Trypanosoma cruzi may remain asymptomatic for decades and show signs of neuroregeneration in the peripheral nervous system (PNS). In the absence of such neuroregeneration, patients may die in part by extensive neuronal destruction in the gastrointestinal tract. Thus, T. cruzi may, despite their invasion of the PNS, directly prevent cell death to keep nerve destruction in check. Indeed, T. cruzi invasion of Schwann cells, their prime target in PNS, suppressed host-cell apoptosis caused by growth-factor deprivation. The trans-sialidase (TS) of T. cruzi and the Cys-rich domain of TS reproduced the antiapoptotic activity of the parasites at doses (≥3.0 nM) comparable or lower than those of bona fide mammalian growth factors. This effect was blocked by LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K). TS also activated Akt, a downstream effector of PI3K. Ectopic expression of TS in an unrelated parasite, Leishmania major, turned those parasites into activators of Akt in Schwann cells. In contrast, the Cys-rich domain of TS did not block apoptosis in Schwann cells overexpressing dominant-negative Akt or constitutively active PTEN, a negative regulator of PI3K/Akt signaling. The results demonstrate that T. cruzi, through its TS, triggers the survival of host Schwann cells via the PI3K/Akt pathway, suggesting a role for PI3K/Akt in the pathogenesis of Chagas' disease. PMID:11481434

Hot Press as a Sustainable Direct Recycling Technique of Aluminium: Mechanical Properties and Surface Integrity

PubMed Central

Lajis, Mohd Amri; Ahmad, Azlan

2017-01-01

Meltless recycling technique has been utilized to overcome the lack of primary resources, focusing on reducing the usage of energy and materials. Hot press was proposed as a novel direct recycling technique which results in astoundingly low energy usage in contrast with conventional recycling. The aim of this study is to prove the technical feasibility of this approach by characterizing the recycled samples. For this purpose, AA6061 aluminium chips were recycled by utilizing hot press process under various operating temperature (Ts = 430, 480, and 530 °C) and holding times (ts = 60, 90, and 120 min). The maximum mechanical properties of recycled chip are Ultimate tensile strength (UTS) = 266.78 MPa, Elongation to failure (ETF) = 16.129%, while, for surface integrity of the chips, the calculated microhardness is 81.744 HV, exhibited at Ts = 530 °C and ts = 120 min. It is comparable to theoretical AA6061 T4-temper where maximum UTS and microhardness is increased up to 9.27% and 20.48%, respectively. As the desired mechanical properties of forgings can only be obtained by means of a final heat treatment, T5-temper, aging after forging process was employed. Heat treated recycled billet AA6061 (T5-temper) are considered comparable with as-received AA6061 T6, where the value of microhardness (98.649 HV) at 175 °C and 120 min of aging condition was revealed to be greater than 3.18%. Although it is quite early to put a base mainly on the observations in experimental settings, the potential for significant improvement offered by the direct recycling methods for production aluminium scrap can be clearly demonstrated. This overtures perspectives for industrial development of solid state recycling processes as environmentally benign alternatives of current melting based practices. PMID:28771207

Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice.

PubMed

Samaddar, Sreyashi; Vazquez, Kizzy; Ponkia, Dipen; Toruno, Pedro; Sahbani, Karim; Begum, Sultana; Abouelela, Ahmed; Mekhael, Wagdy; Ahmed, Zaghloul

2017-02-01

Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords. NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a potential mechanism of action regarding the functional effects of applying direct current. Thus tsDCS may represent a novel method by which to manipulate the migration and cell number of adult newly born cells and restore functions following brain or spinal cord injury. Copyright © 2017 the American Physiological Society.

Bax and Bid act in synergy to bring about T11TS-mediated glioma apoptosis via the release of mitochondrial cytochrome c and subsequent caspase activation.

PubMed

Bhattacharjee, M; Acharya, S; Ghosh, A; Sarkar, P; Chatterjee, S; Kumar, P; Chaudhuri, S

2008-12-01

The specific apoptotic role of T11TS has been well established in glioma animal models. T11TS specifically induces the glioma cells to die an apoptotic death via immune cross-talk with the two intracranial immune competent cells-microglia and the brain-infiltrating lymphocytes. To unearth the molecular cascades operative within the glioma cells and to some extent in the two interacting immunocytes, we had initiated studies where preliminary findings not only had indicated the involvement of death receptors but had also hinted to the involvement of other apoptotic regulators. Hence, to identify the molecular pathway of apoptosis involving other apoptotic regulators in the three cell types, the cells were studied for the intrinsic apoptotic death regulators that were engaged to maintain the mitochondrial membrane integrity. The proteins that were selected could be divided into three broad classes-the Bcl-2 family of proteins-Bid, Bax and Bcl-2; the guardian of the genome p53 and the proteins downstream of mitochondria-Apaf-1, cytochrome c, caspase-9 and caspase-3. Activated Bid as well as maximal p53 expression was observed in the first dose of T11TS thus dually activating the pro-apoptotic Bax in the first and second dose in the glioma cells. Concurrently, the pro-survival protein Bcl-2's expression level was very much down-regulated in the same two doses favoring the internal microenvironment to proceed for apoptosis. High expression of cytochrome c and Apaf-1 and the presence of active caspase-9 and active caspase-3 in all the T11TS-treated tumor-bearing groups further adjudicated apoptosis of the glioma cells with clear involvement of mitochondrial death pathway in the T11TS-treated animals. Even though expression of the apoptotic regulators remained more or less the same indicating the involvement of mitochondria in the two interacting immunocytes, the intensity of expression of these proteins was much lower than the tumor cells. The present work focuses on the mechanistic approach of how T11TS mediates apoptosis and hence is the first approach of its kind in the field of immunology where the immunotherapeutic molecule's mode of action has been worked out.

Forced Two-Phase Helium Cooling Scheme for the Mu2e Transport Solenoid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tatkowski, G.; Cheban, S.; Dhanaraj, N.

2015-01-01

The Mu2e Transport Solenoid (TS) is an S-shaped magnet formed by two separate but similar magnets, TS-u and TS-d. Each magnet is quarter-toroid shaped with a centerline radius of approximately 3 m utilizing a helium cooling loop consisting of 25 to 27 horizontal-axis rings connected in series. This cooling loop configuration has been deemed adequate for cooling via forced single phase liquid helium; however it presents major challenges to forced two-phase flow such as “garden hose” pressure drop, concerns of flow separation from tube walls, difficulty of calculation, etc. Even with these disadvantages, forced two-phase flow has certain inherent advantagesmore » which make it a more attractive option than forced single phase flow. It is for this reason that the use of forced two-phase flow was studied for the TS magnets. This paper will describe the analysis using helium-specific pressure drop correlations, conservative engineering approach, helium properties calculated and updated at over fifty points, and how the results compared with those in literature. Based on the findings, the use of forced-two phase helium is determined to be feasible for steady-state cooling of the TS solenoids« less

Modified Anaerobic Digestion Model No.1 for dry and semi-dry anaerobic digestion of solid organic waste.

PubMed

Liotta, Flavia; Chatellier, Patrice; Esposito, Giovanni; Fabbricino, Massimiliano; Frunzo, Luigi; van Hullebusch, Eric D; Lens, Piet N L; Pirozzi, Francesco

2015-01-01

The role of total solids (TS) content in anaerobic digestion of selected complex organic matter, e.g. rice straw and food waste, was investigated. A range of TS from wet (4.5%) to dry (23%) was evaluated. A modified version of the Anaerobic Digestion Model No.1 for a complex organic substrate is proposed to take into account the effect of the TS content on anaerobic digestion. A linear function that correlates the kinetic constants of three specific processes (i.e. disintegration, acetate and propionate up-take) was included in the model. Results of biomethanation and volatile fatty acids production tests were used to calibrate the proposed model. Model simulations showed a good agreement between numerical and observed data.

Corrections to the Shapiro Equation used to Predict Sweating and Water Requirements

DTIC Science & Technology

2008-01-01

Nishi, Y., and A. P. Gagge. Effective temperature scale useful for hypobaric and hyperbaric environments. Aviat. Space Environ. Med. 48: 97-107, 1977...time series predictions of specific variables (35). Comparison of the original Shapiro equation predicting sweat loss and water requirements was...40 60 80 100 % O ff (+ ,m od el u nd er pr ed ic ts ;-, ov er pr ed ic ts ) It is clear from Figure 2’s plot of the residual values ( comparison

Sequential ultrasound and low-temperature thermal pretreatment: Process optimization and influence on sewage sludge solubilization, enzyme activity and anaerobic digestion.

PubMed

Neumann, Patricio; González, Zenón; Vidal, Gladys

2017-06-01

The influence of sequential ultrasound and low-temperature (55°C) thermal pretreatment on sewage sludge solubilization, enzyme activity and anaerobic digestion was assessed. The pretreatment led to significant increases of 427-1030% and 230-674% in the soluble concentrations of carbohydrates and proteins, respectively, and 1.6-4.3 times higher enzymatic activities in the soluble phase of the sludge. Optimal conditions for chemical oxygen demand solubilization were determined at 59.3kg/L total solids (TS) concentration, 30,500kJ/kg TS specific energy and 13h thermal treatment time using response surface methodology. The methane yield after pretreatment increased up to 50% compared with the raw sewage sludge, whereas the maximum methane production rate was 1.3-1.8 times higher. An energy assessment showed that the increased methane yield compensated for energy consumption only under conditions where 500kJ/kg TS specific energy was used for ultrasound, with up to 24% higher electricity recovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Common and specific impairments in attention functioning in girls with chromosome 22q11.2 deletion, fragile X or Turner syndromes

PubMed Central

2014-01-01

Background Chromosome 22q11.2 deletion syndrome (22q11.2DS), fragile X syndrome (FXS), and Turner syndrome (TS) are complex and variable developmental syndromes caused by different genetic abnormalities; yet, they share similar cognitive impairments in the domains of numbers, space, and time. The atypical development of foundational neural networks that underpin the attentional system is thought to result in further impairments in higher-order cognitive functions. The current study investigates whether children with similar higher-order cognitive impairments but different genetic disorders also show similar impairments in alerting, orienting, and executive control of attention. Methods Girls with 22q11.2DS, FXS, or TS and typically developing (TD) girls, aged 7 to 15 years, completed an attention network test, a flanker task with alerting and orienting cues. Exploration of reaction times and accuracy allowed us to test for potential commonalities in attentional functioning in alerting, orienting, and executive control. Linear regression models were used to test whether the predictors of group and chronological age were able to predict differences in attention indices. Results Girls with 22q11.2DS, FXS, or TS demonstrated unimpaired function of the alerting system and impaired function of the executive control system. Diagnosis-specific impairments were found such that girls with FXS made more errors and had a reduced orienting index, while girls with 22q11.2DS showed specific age-related deficits in the executive control system. Conclusions These results suggest that the control but not the implementation of attention is selectively impaired in girls with 22q11.2DS, TS or FXS. Additionally, the age effect on executive control in girls with 22q11.2DS implies a possible altered developmental trajectory. PMID:24628892

Using iron studies to predict HFE mutations in New Zealand: implications for laboratory testing.

PubMed

O'Toole, Rebecca; Romeril, Kenneth; Bromhead, Collette

2017-04-01

The diagnosis of hereditary haemochromatosis (HH) is not straightforward because symptoms are often absent or non-specific. Biochemical markers of iron-overloading may be affected by other conditions. To measure the correlation between iron studies and HFE genotype to inform evidence-based recommendations for laboratory testing in New Zealand. Results from 2388 patients genotyped for C282Y, H63D and S65C in Wellington, New Zealand from 2007 to 2013 were compared with their biochemical phenotype as quantified by serum ferritin (SF), transferrin saturation (TS), serum iron (SI) and serum transferrin (ST). The predictive power of these markers was evaluated by receiver operator characteristic (ROC) curve analysis, and if a statistically significant association for a variable was seen, sensitivity, specificity and predictive values were calculated. Test ordering patterns showed that 62% of HFE genotyping tests were ordered because of an elevated SF alone and only 11% of these had a C-reactive protein test to rule out an acute phase reaction. The association between SF and significant HFE genotypes SF was low. However, TS values ≥45% predicted HH mutations with the highest sensitivity and specificity. A SF of >1000 µg/L was found in one at-risk patient (C282Y homozygote) who had a TS <45%. Our analysis highlights the need for clear guidelines for investigation of hyperferritinaemia and HH in New Zealand. Using our findings, we developed an evidence-based laboratory testing algorithm based on a TS ≥45%, a SF ≥1000 µg/L and/or a family history of HH which identified all C282Y homozygotes in this study. © 2016 Royal Australasian College of Physicians.

Estimating Weight and Moments for Ship Control Design Technical Assessment Team Reviews

DTIC Science & Technology

2016-07-26

01 5/ 02 0 E st im at in g W ei gh t & M om en ts fo r S C D T ec hn ic al A ss es sm en t T ea m R ev ie w s NSWCCD-80-TR-2016/020...currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 07-26-2016 2. REPORT TYPE...10  3.4.2 Distributive Systems / Other Impacts

Installation Restoration Program. Phase II. Confirmation/Quantification. Stage 1 for Tinker AFB, Oklahoma. Volume 2. Appendices,

DTIC Science & Technology

1985-09-01

Special Olt 9-; ~ ~ ~ ~ ~ J -..-- w--- ’- V - V --y a - . . . . . . RADIAN APPENDIX A Definitions, Nomenclatures and Units A- i . -- 5. . -, - - STAGED...contaminatg ed 11 a thei±r~ iMei S-t.r-roundlin. Review the u f -r Ai Force investigationa. These *r-esu I.ts shall~ I & prvie une eatcvr B-5 -9 V q M I ...results or highly complicated nonlinear mathematical modeling , should * be precise, clear and technically defendable. This section should clearly

Technical Performance Assessment: Mission Success in Software Acquisition Management

DTIC Science & Technology

2010-04-27

Examples Design constraints make software acquisition and development t l iti lex reme y cr ca Application domain – Operational Flight Program, Air...environment – used to produce the software Ri k t t bli h d d i t i d i k ts managemen – es a s e an ma n a ne r s managemen systems Milestone reviews...Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that

WIAMan Technology Demonstrator Sensor Codes Conforming to International Organization for Standardization/Technical Standard (ISO/TS) 13499

DTIC Science & Technology

2016-03-01

in this report are not to be construed as an official Department of the Army position unless so designated by other authorized documents. Citation of...gravity, or pretest . 1 Approved for public release; distribution is unlimited. Fine Location 2 Code position 9–10: This substring represents the spacial...itself. For example, upper, pretest , or Hybrid III mid-sized male ATD. Physical dimension Code position 13–14: This substring represents the type of the

Annual Tropical Cyclone Report, 1982.

DTIC Science & Technology

1982-01-01

intensity forecast are made once each day by processed at AFGWC is recorded on-board applying the Dvorak technique (NOAA Technical the spacecraft as it...tropical cyclone. Season totals and the 700 mb pressure surface within the percentages are also indicated. vortex recorded in meters. 7 Z ;l__...16 TY GORDON 27 AUG - 5 SEP 10 39 100 944 2014 17 TS HOPE 4 SEP - 6 SEP 3 10 #0 979 630 18 TY IRVING 5 SEP - 16 SEP 12 44 90 952 1770 19 TY JUDY 5 SEP

Protective Coatings for Aluminum Torpedoes

DTIC Science & Technology

1983-06-01

Circeo it Cmader and Director of CERL, and Dr. L . R. Shaffer is Technical Director. 3 = -. =-e ° 𔄁 -i , i ..... rar DD FORM 1473 2 FOREWORD 3 LIST...Amerccat 9 Thinner 72 A12 Gas Chrouatogrm flughson VIS 3236-26 Wash Primer 73 L FIGURES (Cont’d) Number Page A13 .as Chroasatogram: Hughson TS 3236-23...intercoat adhesion problems providing the old surface is clean. A vinyl coating system manufactured by Ameron, 201 North Berry Street, Bret, CA 92621, was

Individual Low-Energy Toroidal Dipole State in Mg 24

NASA Astrophysics Data System (ADS)

Nesterenko, V. O.; Repko, A.; Kvasil, J.; Reinhard, P.-G.

2018-05-01

The low-energy dipole excitations in Mg 24 are investigated within the Skyrme quasiparticle random phase approximation for axial nuclei. The calculations with the force SLy6 reveal a remarkable feature: the lowest IπK =1-1 excitation (E =7.92 MeV ) in Mg 24 is a vortical toroidal state (TS) representing a specific vortex-antivortex realization of the well-known spherical Hill's vortex in a strongly deformed axial confinement. This is a striking example of an individual TS which can be much more easily discriminated in experiment than the toroidal dipole resonance embracing many states. The TS acquires the lowest energy due to the huge prolate axial deformation in Mg 24 . The result persists for different Skyrme parametrizations (SLy6, SVbas, SkM*). We analyze spectroscopic properties of the TS and its relation with the cluster structure of Mg 24 . Similar TSs could exist in other highly prolate light nuclei. They could serve as promising tests for various reactions to probe a vortical (toroidal) nuclear flow.

A cognitive characterization of dyscalculia in Turner syndrome.

PubMed

Bruandet, Marie; Molko, Nicolas; Cohen, Laurent; Dehaene, Stanislas

2004-01-01

Current theories of number processing postulate that the human abilities for arithmetic are based on cerebral circuits that are partially laid down under genetic control and later modified by schooling and education. This view predicts the existence of genetic diseases that interfere specifically with components of the number system. Here, we investigate whether Turner syndrome (TS) corresponds to this definition. TS is a genetic disorder which affects one woman in 2500 and is characterized by partial or complete absence of one X chromosome. In addition to well-characterized physical and hormonal dysfunction, TS patients exhibit cognitive deficits including dyscalculia. We tested 12 women with Turner syndrome and 13 control subjects on a cognitive battery including arithmetical tests (addition, subtraction, multiplication, division) as well as tests of the understanding of numerosity and quantity (cognitive estimation, estimation, comparison, bisection, subitizing/counting). Impairments were observed in cognitive estimation, subitizing, and calculation. We examine whether these deficits can be attributed to a single source, and discuss the possible implications of hormonal and genetic factors in the neuropsychological profile of TS patients.

Refining Ovarian Cancer Test accuracy Scores (ROCkeTS): protocol for a prospective longitudinal test accuracy study to validate new risk scores in women with symptoms of suspected ovarian cancer.

PubMed

Sundar, Sudha; Rick, Caroline; Dowling, Francis; Au, Pui; Snell, Kym; Rai, Nirmala; Champaneria, Rita; Stobart, Hilary; Neal, Richard; Davenport, Clare; Mallett, Susan; Sutton, Andrew; Kehoe, Sean; Timmerman, Dirk; Bourne, Tom; Van Calster, Ben; Gentry-Maharaj, Aleksandra; Menon, Usha; Deeks, Jon

2016-08-09

Ovarian cancer (OC) is associated with non-specific symptoms such as bloating, making accurate diagnosis challenging: only 1 in 3 women with OC presents through primary care referral. National Institute for Health and Care Excellence guidelines recommends sequential testing with CA125 and routine ultrasound in primary care. However, these diagnostic tests have limited sensitivity or specificity. Improving accurate triage in women with vague symptoms is likely to improve mortality by streamlining referral and care pathways. The Refining Ovarian Cancer Test Accuracy Scores (ROCkeTS; HTA 13/13/01) project will derive and validate new tests/risk prediction models that estimate the probability of having OC in women with symptoms. This protocol refers to the prospective study only (phase III). ROCkeTS comprises four parallel phases. The full ROCkeTS protocol can be found at http://www.birmingham.ac.uk/ROCKETS. Phase III is a prospective test accuracy study. The study will recruit 2450 patients from 15 UK sites. Recruited patients complete symptom and anxiety questionnaires, donate a serum sample and undergo ultrasound scored as per International Ovarian Tumour Analysis (IOTA) criteria. Recruitment is at rapid access clinics, emergency departments and elective clinics. Models to be evaluated include those based on ultrasound derived by the IOTA group and novel models derived from analysis of existing data sets. Estimates of sensitivity, specificity, c-statistic (area under receiver operating curve), positive predictive value and negative predictive value of diagnostic tests are evaluated and a calibration plot for models will be presented. ROCkeTS has received ethical approval from the NHS West Midlands REC (14/WM/1241) and is registered on the controlled trials website (ISRCTN17160843) and the National Institute of Health Research Cancer and Reproductive Health portfolios. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Circulating Prostate-Specific Antigen and Telomere Length in a Nationally Representative Sample of Men Without History of Prostate Cancer.

PubMed

Wulaningsih, Wahyu; Astuti, Yuliana; Matsuguchi, Tetsuya; Anggrandariyanny, Putri; Watkins, Johnathan

2017-01-01

We investigated the association of prostate-specific antigen (PSA) with leukocyte telomere length, which may be altered in preclinical prostate malignancies. This study was based on the 2001-2002 U.S. National Health and Nutrition Examination Survey (NHANES). A subsample of 1,127 men aged 40-85 years without prior history of prostate cancer who provided informed consent and blood samples were selected. Leukocyte telomere length (LTL) relative to standard DNA reference (T/S ratio) was quantified by polymerase chain reaction (PCR). Survey-weighted multivariable linear regression was performed to examine T/S ratio across quintiles of total and free PSA and free-to-total PSA ratio (%fPSA). A sensitivity analysis was performed by excluding men dying from prostate cancer during follow-up through to December 31, 2006. Stratification analyses were carried out to assess any effect modification by age group, race, body mass index (BMI), and levels of C-reactive protein (CRP), a marker of inflammation. Higher total PSA levels were associated to longer LTL, with approximately 8% increase in log-transformed T/S ratio (95% confidence interval [CI]: 2-13%) among men in the highest quintile of total PSA compared to the lowest in the fully adjusted model (P trend  = 0.01). No significant association was found for free PSA or %fPSA, although nonlinearity between all PSA measures and T/S ratio was indicated. Similar results were found after excluding men who died from prostate cancer during follow-up. We also found the associations between total PSA and T/S ratio to be strongest among non-Hispanic blacks, non-obese men (BMI <30 kg/m 2 ), and those with low CRP. However, a significant interaction was only found between total PSA and race/ethnicity (P interaction  = 0.01). Total PSA levels were strongly associated to LTL, particularly among non-Hispanic blacks. Our findings support a potential link between PSA and specific mechanisms contributing to prostate cancer development. Prostate 77:22-32, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Performance characteristics of an automated latex immunoturbidimetric assay [HemosIL® HIT-Ab(PF4-H)] for the diagnosis of immune heparin-induced thrombocytopenia.

PubMed

Warkentin, Theodore E; Sheppard, Jo-Ann I; Linkins, Lori-Ann; Arnold, Donald M; Nazy, Ishac

2017-05-01

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating anti-PF4/heparin antibodies. Given time-sensitive treatment considerations, a rapid and accurate laboratory test for HIT antibodies is needed. To determine operating characteristics for the HemosIL ® HIT-Ab (PF4/H) , a rapid, on-demand, fully-automated, latex immunoturbidimetric assay (LIA), for diagnosis of HIT. We evaluated LIA sensitivity, specificity, negative (NPV) and positive predictive value (PPV), negative (LR-) and positive likelihood ratio (LR+), using citrated-plasma from 429 patients (prospective cohort study of 4Ts scoring; HIT, n=31), and from consecutive HIT patients (n=125), using reference standard serotonin-release assay (SRA). Comparators included two PF4-dependent enzyme-immunoassays (EIAs). We used stratum-specific likelihood ratios (SSLRs) to determine how differing magnitudes of LIA-positivity influenced post-test probability of HIT. LIA operating characteristics were: sensitivity=97.4% (152/156); specificity=94.0% (374/398); PPV=55.6% (30/54); and NPV=99.7% (374/375). At manufacturers' cutoffs, LIA specificity and PPV were superior to the EIAs. Although a negative LIA pointed strongly against HIT (LR-, 0.034), the post-test probability was ~2% with high 4Ts score. The LIA's LR+ was high (16.0), with SSLRs rising substantially with greater LIA-positivity: 5.7 (1.0-4.9U/mL), 31 (5.0-15.9U/mL), and 128 (≥16U/mL). A LIA-positive result (at 1.0 cutoff) indicated at least 24% HIT probability (low 4Ts score), rising to 90% with high 4Ts score. Although approximately 1 in 40 SRA-positive patients tested LIA-negative, the LIA's high NPV and PPV indicate that this rapid assay is useful for the diagnostic evaluation of HIT, including in low pre-test situations. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Indian girls have higher bone mineral content per unit of lean body than boys through puberty.

PubMed

Khadilkar, Anuradha V; Sanwalka, Neha; Mughal, M Zulf; Chiplonkar, Shashi; Khadilkar, Vaman

2018-05-01

Our aim is to describe changes in the muscle-bone unit assessed as a ratio of bone mineral content (BMC) to lean body mass (LBM) through puberty at total body and various skeletal sites in Indian boys and girls. A cross-sectional study was conducted (888 children, 480 boys, aged 5-17 years) in Pune, India. Pubertal staging was assessed. BMC, LBM and fat percentage at the arms, legs, android, gynoid and total body (less the head) were assessed by dual energy X-ray absorptiometry. The amount of BMC per unit LBM (BMC/LBM) was computed. Changes in mean BMC/LBM at 5 Tanner (pubertal) stages after adjustment for age and fat percentage were calculated. In boys, adjusted BMC/LBM was significantly higher with successive Tanner stages [legs (TS-II vs TS-I), android (TS-III vs TS-II, TS-IV vs TS-III) and gynoid region (TS-III vs TS-II and TS-II vs TS-I) (p < 0.05)]. In girls, adjusted BMC/LBM was significantly higher with successive Tanner stages at total body, legs and gynoid (TS-III vs TS-II; TS-II vs TS-I; TS-V vs TS-IV), arms (TS-I to TS-V) and android regions (TS-V vs TS-IV) (p < 0.05). Boys had significantly higher adjusted BMC/LBM than girls at earlier Tanner stages (TS-I to TS-III), whereas girls had significantly higher adjusted BMC/LBM than boys at later Tanner stages (TS-IV, TS-V) (p < 0.05). Indian boys and girls showed higher total and regional body, and age- and fat percentage-adjusted BMC/LBM with successive pubertal stages. Girls had higher BMC/LBM than boys which may possibly act as a reservoir for later demands of pregnancy and lactation.

CHARACTERIZATION OF SPONTANEOUS AND INDUCED PUBERTY IN GIRLS WITH TURNER SYNDROME.

PubMed

Folsom, Lisal J; Slaven, James E; Nabhan, Zeina M; Eugster, Erica A

2017-07-01

To characterize puberty in girls with Turner syndrome (TS) and determine whether specific patient characteristics are associated with the timing of menarche. We also sought to compare spontaneous versus induced puberty in these patients. Medical records of girls followed in our Pediatric Endocrine clinic for TS from 2007 to 2015 were reviewed. Fifty-three girls were included, of whom 10 (19%) achieved menarche spontaneously and 43 (81%) received hormone replacement therapy (HRT). Of girls receiving HRT, a younger age at estrogen initiation correlated with a longer time to menarche (P = .02), and a mosaic karyotype was associated with a shorter time to menarche (P = .02), whereas no relationship was seen for body mass index, estrogen regimen, or maternal age at menarche. Nineteen girls (44%) receiving HRT had bleeding on estrogen alone at a wide dose range and were more likely to be on transdermal than oral preparations (P = .01). Girls with spontaneous puberty achieved menarche at a younger age (P<.01) and were more likely to have mosaic TS (P = .02). Significant variability in the timing of menarche exists among girls with TS. However, age at pubertal induction and karyotype were significantly correlated with age at menarche in our patients. A wide range of estrogen doses is seen in girls who bleed prior to progesterone, suggesting extreme variability in estrogen sensitivity among patients with TS. Girls achieving spontaneous menarche are younger and more likely to have a mosaic karyotype than those with induced menarche. Large-scale prospective studies are needed to confirm these results. BMI = body mass index; HRT = hormone replacement therapy; TS = Turner syndrome.

An unexpected target of spinal direct current stimulation: Interhemispheric connectivity in humans.

PubMed

Bocci, Tommaso; Caleo, Matteo; Vannini, Beatrice; Vergari, Maurizio; Cogiamanian, Filippo; Rossi, Simone; Priori, Alberto; Sartucci, Ferdinando

2015-10-30

Transcutaneous spinal Direct Current Stimulation (tsDCS) is a noninvasive technique based on the application of weak electrical currents over spinal cord. We studied the effects of tsDCS on interhemispheric motor connectivity and visual processing by evaluating changes in ipsilateral Silent Period (iSP), Transcallosal Conduction Time (TCT) and hemifield Visual Evoked Potentials (hVEPs), before (T0) and at a different intervals following sham, anodal and cathodal tsDCS (T9-T11 level, 2.0 mA, 20'). Motor Evoked Potentials (MEPs) were recorded from abductor pollicis brevis (APB), abductor hallucis (AH) and deltoid muscles. hVEPs were recorded bilaterally by reversal of a horizontal square wave grating with the display positioned in the right hemifield. Anodal tsDCS increased TCT (p < 0.001) and the interhemispheric delay for both the main VEP components (N1: p = 0.0003; P1: p < 0.0001), dampening at the same time iSP duration (APB: p < 0.0001; AH: p = 0.0005; deltoid: p < 0.0001), while cathodal stimulation elicited opposite effects (p < 0.0001). tsDCS modulates interhemispheric processing in a polarity-specific manner, with anodal stimulation leading to a functional disconnection between hemispheres. tsDCS would be a new promising therapeutic tool in managing a number of human diseases characterized by an impaired interhemispheric balance, or an early rehabilitation strategy in patients with acute brain lesions, when other non-invasive brain stimulation techniques (NIBS) are not indicated due to safety concerns. Copyright © 2015 Elsevier B.V. All rights reserved.

Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology.

PubMed

Isidori, A M; Balercia, G; Calogero, A E; Corona, G; Ferlin, A; Francavilla, S; Santi, D; Maggi, M

2015-01-01

We developed clinical practice guidelines to assess the individual risk-benefit profile of androgen replacement therapy in adult male hypogonadism (HG), defined by the presence of specific signs and symptoms and serum testosterone (T) below 12 nmol/L. The task force consisted of eight clinicians experienced in treating HG, selected by the Italian Society of Endocrinology (SIE). The authors received no corporate funding or remuneration. Consensus was guided by a systematic review of controlled trials conducted on men with a mean T < 12 nmol/L and by interactive discussions. The guidelines were reviewed and sequentially approved by the SIE Guidelines Commission and Executive Committee. We recommend T supplementation (TS) for adult men with severely reduced T levels (T < 8 nmol/L) to improve body composition and sexual function. We suggest that TS be offered to subjects with T < 12 nmol/L to improve glycaemic control, lipid profile, sexual function, bone mineral density, muscle mass and depressive symptoms, once major contraindications have been ruled out. We suggest that lifestyle changes and other available interventions (e.g. for erectile dysfunction) be suggested prior to TS. We suggest that TS should be combined with currently available treatments for individuals at high risk for complications, such as those with osteoporosis and/or metabolic disorders. We recommend against using TS to improve cardiac outcome and limited mobility. We recommend against using TS in men with prostate cancer, unstable cardiovascular conditions or elevated haematocrit. The task force places a high value on the timely treatment of younger and middle-aged subjects to prevent the long-term consequences of hypoandrogenism.

Influence of prenatal EGCG treatment and Dyrk1a dosage reduction on craniofacial features associated with Down syndrome.

PubMed

McElyea, Samantha D; Starbuck, John M; Tumbleson-Brink, Danika M; Harrington, Emily; Blazek, Joshua D; Ghoneima, Ahmed; Kula, Katherine; Roper, Randall J

2016-11-15

Trisomy 21 (Ts21) affects craniofacial precursors in individuals with Down syndrome (DS). The resultant craniofacial features in all individuals with Ts21 may significantly affect breathing, eating and speaking. Using mouse models of DS, we have traced the origin of DS-associated craniofacial abnormalities to deficiencies in neural crest cell (NCC) craniofacial precursors early in development. Hypothetically, three copies of Dyrk1a (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), a trisomic gene found in most humans with DS and mouse models of DS, may significantly affect craniofacial structure. We hypothesized that we could improve DS-related craniofacial abnormalities in mouse models using a Dyrk1a inhibitor or by normalizing Dyrk1a gene dosage. In vitro and in vivo treatment with Epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, modulated trisomic NCC deficiencies at embryonic time points. Furthermore, prenatal EGCG treatment normalized some craniofacial phenotypes, including cranial vault in adult Ts65Dn mice. Normalization of Dyrk1a copy number in an otherwise trisomic Ts65Dn mice normalized many dimensions of the cranial vault, but did not correct all craniofacial anatomy. These data underscore the complexity of the gene–phenotype relationship in trisomy and suggest that changes in Dyrk1a expression play an important role in morphogenesis and growth of the cranial vault. These results suggest that a temporally specific prenatal therapy may be an effective way to ameliorate some craniofacial anatomical changes associated with DS.

Associative learning and regional white matter deficits in mild cognitive impairment.

PubMed

Boespflug, Erin L; Eliassen, James; Welge, Jeffrey; Krikorian, Robert

2014-01-01

While diagnostic criteria for Alzheimer's disease (AD) include neuroimaging biomarkers, there remains no definitive biomarker of mild cognitive impairment (MCI). MCI is a risk factor for AD that may be amenable to early intervention. Early decline in white matter (WM) integrity identified by diffusion tensor imaging (DTI) is a predictor of future progression of neurodegeneration. Identify regionally specific WM differences between individuals with MCI and those with age-associated memory impairment (AAMI) and relationships with specific memory decrements. DTI and neuropsychological data were acquired from 38 participants (23 MCI and 15 AAMI). A region of interest approach was used to evaluate regional differences between groups and correlative relationships with performance on memory tasks. Fornix WM had higher mean (MD), radial (DR), and axial (DA) diffusivity in MCI participants relative to AAMI. Temporal stem (TS) WM had higher MD and DR in MCI than in AAMI. In MCI, TS MD and DR varied, while fornix MD and DR was uniformly high, and in AAMI, TS MD and DR were uniformly low and fornix MD and DR varied. In MCI, TS MD and DA were inversely associated with associative learning but not list learning. In addition to supporting prior evidence implicating the fornix in early AD pathology, these data implicate a profile of neurodegeneration associated with early MCI. Further, they suggest that associative learning tasks are more sensitive to early neurodegeneration and may be useful in identifying individuals at risk for AD.

Cell cycle phase dependent emergence of thymidylate synthase studied by monoclonal antibody (M-TS-4).

PubMed

Shibui, S; Hoshino, T; Iwasaki, K; Nomura, K; Jastreboff, M M

1989-05-01

A method of identifying thymidylate synthase (TS) at the cellular level was developed using anti-TS monoclonal antibody (M-TS-4), a monoclonal antibody created against purified TS from a HeLa cell line. In HeLa cells and four human glioma cell lines (U-251, U-87, 343-MGA, and SF-188), TS was identified primarily in the cytoplasm. Autoradiographic and flow cytometric studies showed that TS appeared mainly in the G1 phase and subsided early in the S phase; thus, the G1 phase can be divided into TS-positive and -negative fractions. Nuclear TS was not demonstrated unequivocally with M-TS-4, and the relationship between nuclear TS and DNA synthesis could not be determined. Although the percentage of TS-positive cells was larger than the S-phase fraction measured by autoradiography after a pulse of tritiated thymidine or by the immunoperoxidase method using BUdR, the ratios were within a similar range (1.2-1.4) in all cell lines studied. Therefore, the S-phase fraction can be estimated indirectly from the percentage of TS-positive cells measured by M-TS-4. Because the emergence of TS detected by our method is cell cycle dependent, M-TS-4 may be useful for biochemical studies of TS and for cytokinetic analysis.

Immunological mechanisms involved in the protection against intestinal taeniosis elicited by oral immunization with Taenia solium calreticulin.

PubMed

Leon-Cabrera, Sonia; Cruz-Rivera, Mayra; Mendlovic, Fela; Romero-Valdovinos, Mirza; Vaughan, Gilberto; Salazar, Ana María; Avila, Guillermina; Flisser, Ana

2012-11-01

Oral immunization with functional recombinant Taenia solium calreticulin (rTsCRT) induces 37% reduction in tapeworm burden in the experimental model of intestinal taeniosis in hamsters. Furthermore, tapeworms recovered from vaccinated animals exhibit diminished length, being frequently found in more posterior parts of the small intestine. The aim of this study was to analyze the immunological mechanisms involved in protection in response to rTsCRT oral immunization. Hamsters were orally immunized with rTsCRT using cholera toxin (CT) as adjuvant, weekly for 4 weeks. Fifteen days after the last boost animals were challenged with four T. solium cysticerci. Reduction in the adult worm recovery and increased transcription of mRNA for IL-4 and IFN-γ in the mucosa of rTsCRT+CT immunized animals were observed. Immunization also induced goblet cell hyperplasia in the mucosa surrounding the implantation site of the parasite. Specific IgG and IgA antibodies in serum and fecal supernatants were detected after the second immunization, being more pronounced after challenge. Our data suggest that oral vaccination with rTsCRT+CT regulates a local expression of IL-4 and IFN-γ, stimulating secretion of IgA that, together with the increase of goblet cells and mucin production, could result in an unfavorable environment for T. solium promoting an impaired tapeworm development. Copyright © 2012 Elsevier Inc. All rights reserved.

Alexithymia, emotion perception, and social assertiveness in adult women with Noonan and Turner syndromes.

PubMed

Roelofs, Renée L; Wingbermühle, Ellen; Freriks, Kim; Verhaak, Chris M; Kessels, Roy P C; Egger, Jos I M

2015-04-01

Noonan syndrome (NS) and Turner syndrome (TS) are associated with cognitive problems and difficulties in affective information processing. While both phenotypes include short stature, facial dysmorphisms, and a webbed neck, genetic etiology and neuropsychological phenotype differ significantly. The present study examines putative differences in affective information processing and social assertiveness between adult women with NS and TS. Twenty-six women with NS, 40 women with TS, and 40 female controls were matched on age and intelligence, and subsequently compared on (1) alexithymia, measured by the Bermond-Vorst Alexithymia Questionnaire, (2) emotion perception, evaluated by the Emotion Recognition Task, and (3) social assertiveness and social discomfort, assessed by the Scale for Interpersonal Behavior. Women with TS showed higher levels of alexithymia than women with NS and controls (P-values < 0.001), whereas women with NS had more trouble recognizing angry facial expressions in comparison with controls (P = 0.01). No significant group differences were found for the frequency of social assertiveness and the level of social discomfort. Women with NS and TS demonstrated different patterns of impairment in affective information processing, in terms of alexithymia and emotion perception. The present findings suggest neuropsychological phenotyping to be helpful for the diagnosis of specific cognitive-affective deficits in genetic syndromes, for the enhancement of genetic counseling, and for the development of personalized treatment plans. © 2015 Wiley Periodicals, Inc.

Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys.

PubMed

Akamizu, Takashi; Satoh, Tetsurou; Isozaki, Osamu; Suzuki, Atsushi; Wakino, Shu; Iburi, Tadao; Tsuboi, Kumiko; Monden, Tsuyoshi; Kouki, Tsuyoshi; Otani, Hajime; Teramukai, Satoshi; Uehara, Ritei; Nakamura, Yosikazu; Nagai, Masaki; Mori, Masatomo

2012-07-01

Thyroid storm (TS) is life threatening. Its incidence is poorly defined, few series are available, and population-based diagnostic criteria have not been established. We surveyed TS in Japan, defined its characteristics, and formulated diagnostic criteria, FINAL-CRITERIA1 and FINAL-CRITERIA2, for two grades of TS, TS1, and TS2 respectively. We first developed diagnostic criteria based on 99 patients in the literature and 7 of our patients (LIT-CRITERIA1 for TS1 and LIT-CRITERIA2 for TS2). Thyrotoxicosis was a prerequisite for TS1 and TS2 as well as for combinations of the central nervous system manifestations, fever, tachycardia, congestive heart failure (CHF), and gastrointestinal (GI)/hepatic disturbances. We then conducted initial and follow-up surveys from 2004 through 2008, targeting all hospitals in Japan, with an eight-layered random extraction selection process to obtain and verify information on patients who met LIT-CRITERIA1 and LIT-CRITERIA2. We identified 282 patients with TS1 and 74 patients with TS2. Based on these data and information from the Ministry of Health, Labor, and Welfare of Japan, we estimated the incidence of TS in hospitalized patients in Japan to be 0.20 per 100,000 per year. Serum-free thyroxine and free triiodothyroine concentrations were similar among patients with TS in the literature, Japanese patients with TS1 or TS2, and a group of patients with thyrotoxicosis without TS (Tox-NoTS). The mortality rate was 11.0% in TS1, 9.5% in TS2, and 0% in Tox-NoTS patients. Multiple organ failure was the most common cause of death in TS1 and TS2, followed by CHF, respiratory failure, arrhythmia, disseminated intravascular coagulation, GI perforation, hypoxic brain syndrome, and sepsis. Glasgow Coma Scale results and blood urea nitrogen (BUN) were associated with irreversible damages in 22 survivors. The only change in our final diagnostic criteria for TS as compared with our initial criteria related to serum bilirubin concentration >3 mg/dL. TS is still a life-threatening disorder with more than 10% mortality in Japan. We present newly formulated diagnostic criteria for TS and clarify its clinical features, prognosis, and incidence based on nationwide surveys in Japan. This information will help diagnose TS and in understanding the factors contributing to mortality and irreversible complications.

Phase 2 study of treatment selection based on tumor thymidylate synthase expression in previously untreated patients with metastatic colorectal cancer: A trial of the ECOG-ACRIN Cancer Research Group (E4203).

PubMed

Meropol, Neal J; Feng, Yang; Grem, Jean L; Mulcahy, Mary F; Catalano, Paul J; Kauh, John S; Hall, Michael J; Saltzman, Joel N; George, Thomas J; Zangmeister, Jeffrey; Chiorean, Elena G; Cheema, Puneet S; O'Dwyer, Peter J; Benson, Al B

2018-02-15

The authors hypothesized that patients with metastatic colorectal cancer (mCRC) who had tumors with low thymidylate synthase (TS-L) expression would have a higher response rate to combined 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab (FOLFOX/Bev) than those with high TS (TS-H) expression and that combined irinotecan and oxaliplatin (IROX) plus bevacizumab (IROX/Bev) would be more effective than FOLFOX/Bev in those with TS-H tumors. TS protein expression was determined in mCRC tissue. Patients who had TS-L tumors received FOLFOX/Bev, and those who had TS-H tumors were randomly assigned to receive either FOLFOX/Bev or IROX/Bev. The primary endpoint was the response rate (complete plus partial responses). In total, 211 of 247 patients (70% TS-H) were registered to the treatment phase. Efficacy analyses included eligible patients who had started treatment (N = 186). The response rates for patients who received IROX/Bev (TS-H), FOLFOX/Bev (TS-H), and FOLFOX/Bev (TS-L) were 33%, 38%, and 49%, respectively (P = nonsignificant). The median progression-free survival (PFS) was 10 months (95% confidence interval [CI], 9-12 months; 10 months in the IROX/Bev TS-H group, 9 months in the FOLFOX/Bev TS-H group, and 13 months in the FOLFOX/Bev TS-L group). The TS-L group had improved PFS compared with the TS-H group that received FOLFOX/Bev (hazard ratio, 1.6; 95% CI, 1.0%-2.4%; P = .04; Cox regression). The median overall survival (OS) was 22 months (95% CI, 20 29 months; 18 months in the IROX/Bev TS-H group, 21 months in the FOLFOX/Bev TS-H group, and 32 months in the TS-L group). OS comparisons for the 2 TS-H arms and for the FOLFOX/Bev TS-H versus TS-L arms were not significantly different. TS expression was prognostic: Patients with TS-L tumors who received FOLFOX/Bev had a longer PFS than those with TS-H tumors, along with a trend toward longer OS. Patients with TS-H tumors did not benefit more from IROX/Bev than from FOLFOX/Bev. Cancer 2018;124:688-97. © 2017 American Cancer Society. © 2017 American Cancer Society.

Oxidation and ozonation of waste activated sludge.

PubMed

Mines, Richard O; Northenor, C Brett; Murchison, Mitchell

2008-05-01

In this bench-scale study, the treatment of waste activated sludge (WAS) was evaluated using aerobic digestion and ozonation. Two, 2-L batch digesters, one aerated and the other one ozonated, were operated for 30 days in each phase of the study. The aerated digester simulated the aerobic digestion process and served as control to the ozonated digester. In Phase I, the aerated digester was supplied 810 mg O(2) min(- 1), whereas, the ozonated digester was supplied 0.88 mg O(3) min(- 1). In Phase II, the oxygenation rate to the aerobic digester was increased to 1,200 mg O(2) min(- 1) while the ozonation rate was reduced to 0.44 mg O(3) min(- 1). Ozone was more effective than air at oxidizing and reducing both total solids (TS) and volatile solids (VS) in the WAS. TS removals of 50% and 56% were observed for the ozonated digester versus TS removals of 23% and 35% for the aerated digester. VS removals of 40% and 42% were observed for the aerobic digester versus 57% and 74% for the ozonated digester. Aerobic digestion barely met the 38% reduction in VS required by the U.S. Environmental Protection Agency (EPA). The degradation rate constant (K(d)) based on degradable TS for the ozonated digester varied from 0.082 to 0.11 days(- 1) and from 0.067 to 0.09 days(- 1) for the aerobic digester. Total chemical oxygen demand (TCOD) removal in the aerobic digester increased from 30% to 40% from Phase I to Phase II. TCOD removal increased slightly from 57% to 58% in the ozonated digester from Phase I to Phase II. Soluble chemical oxygen demand (SCOD) concentrations in the sludge supernatant increased with digestion time, especially in the ozonated digester. Approximately 0.12 to 0.22 mg SCOD was produced per mg of TS destroyed during ozonation. The specific oxygen uptake rate (SOUR) was consistently below the EPA standard of 1.5 mg O(2) per hr per g TS, indicating that the sludge was well stabilized. The average quantity of oxygen required during aerobic digestion was 1.53 g O(2) per g of TS destroyed. Actual ozone consumption rates were 0.57 mg O(3) per mg TS destroyed and 1.09 mg O(3) per mg TS destroyed for Phase II and Phase I, respectively.

Binding Modes of Phthalocyanines to Amyloid β Peptide and Their Effects on Amyloid Fibril Formation.

PubMed

Valiente-Gabioud, Ariel A; Riedel, Dietmar; Outeiro, Tiago F; Menacho-Márquez, Mauricio A; Griesinger, Christian; Fernández, Claudio O

2018-03-13

The inherent tendency of proteins to convert from their native states into amyloid aggregates is associated with a range of human disorders, including Alzheimer's and Parkinson's diseases. In that sense, the use of small molecules as probes for the structural and toxic mechanism related to amyloid aggregation has become an active area of research. Compared with other compounds, the structural and molecular basis behind the inhibitory interaction of phthalocyanine tetrasulfonate (PcTS) with proteins such as αS and tau has been well established, contributing to a better understanding of the amyloid aggregation process in these proteins. We present here the structural characterization of the binding of PcTS and its Cu(II) and Zn(II)-loaded forms to the amyloid β-peptide (Aβ) and the impact of these interactions on the peptide amyloid fibril assembly. Elucidation of the PcTS binding modes to Aβ 40 revealed the involvement of specific aromatic and hydrophobic interactions in the formation of the Aβ 40 -PcTS complex, ascribed to a binding mode in which the planarity and hydrophobicity of the aromatic ring system in the phthalocyanine act as main structural determinants for the interaction. Our results demonstrated that formation of the Aβ 40 -PcTS complex does not interfere with the progression of the peptide toward the formation of amyloid fibrils. On the other hand, conjugation of Zn(II) but not Cu(II) at the center of the PcTS macrocyclic ring modified substantially the binding profile of this phthalocyanine to Aβ 40 and became crucial to reverse the effects of metal-free PcTS on the fibril assembly of the peptide. Overall, our results provide a firm basis to understand the structural rules directing phthalocyanine-protein interactions and their implications on the amyloid fibril assembly of the target proteins; in particular, our results contradict the hypothesis that PcTS might have similar mechanisms of action in slowing the formation of a variety of pathological aggregates. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Sensitivity and specificity of a new MRI method evaluating temporo-mandibular joint disc-condyle relationships: an in vivo study.

PubMed

Benbelaïd, R; Fleiter, B

2006-03-01

The aim of this study was to evaluate sensitivity and specificity of a new method to locate temporo-mandibular joint (TMJ) disc using magnetic resonance imaging (MRI) and analyze disc-condyle relationships, in asymptomatic subjects and patients with disc displacement. Twenty-nine sagittal MRI of 16 subjects, 8 asymptomatic volunteers and 8 subjects with anterior disc displacement, were carried out during controlled opening from intercuspal position up to a 25 mm opening. Selected sections were analyzed with a graphic computerized system of coordinates. The total surface area (TS) of disc section was separated into anterior surface area (AS) and posterior surface area. Areas were determined by computer. Two trained examiners drew images at random. The reliability of AS/TS ratio index was evaluated in a previous study. AS/TS ratio sensitivity (Se) and specificity (Sp) were calculated closed mouth, 5 mm open and 25 mm open mouth. Best sensitivity (Se=0.63) and specificity (Sp=0.81) were obtained when MRI was realized with closed mouth and 25 mm open mouth. Lower sensitivity was observed when MRI was performed either with closed mouth (Se=0.54) or 25 mm open mouth (Se=0.18). Lower specificity was observed with 5 mm open mouth (Sp=0.68). In conclusion, it was confirmed as well that MRI of anterior disc displacement should be performed with closed mouth and opened mouth. Thus, further studies are required to assess disc displacement and mechanical alterations and to evaluate the risk of direct damage on TMJ tissues.

Intensity Modulation: A Novel Approach to Percept Control in Spinal Cord Stimulation.

PubMed

Tan, Daniel; Tyler, Dustin; Sweet, Jennifer; Miller, Jonathan

2016-04-01

Spinal cord stimulation (SCS) can be effective for neuropathic pain, but clinical benefit is sometimes inadequate or is offset by stimulation-induced side-effects, and response can be inconsistent among patients. Intensity-modulated stimulation (IMS) is an alternative to tonic stimulation (TS) that involves continuous variation of stimulation intensity in a sinusoidal pattern between two different values, sequentially activating distinct axonal populations to produce an effect that resembles natural physiological signals. The purpose of this study is to evaluate the effect of IMS on the clinical effect of SCS. Seven patients undergoing a percutaneous SCS trial for postlaminectomy syndrome were enrolled. Thresholds for perception, pain relief, and discomfort were measured and used to create patient-specific models of axonal activation and charge delivery for both TS and IMS. All participants underwent three two-min periods of blinded stimulation using TS, IMS, and placebo, and were asked to describe the effect on quality of the sensory percept and pain relief. All participants perceived IMS differently from placebo, and five noted significant differences from TS that resulted in a more comfortable sensation. TS was described as electric and tingling, whereas IMS was described as producing a focal area of deep pressure with a sense of motion away from that focus. The anatomic location of coverage was similar between the two forms of stimulation, although one participant reported better lower back coverage with IMS. Computer modeling revealed that, compared with TS, IMS involved 36.4% less charge delivery and produced 78.7% less suprathreshold axonal activation. IMS for SCS is feasible, produces a more comfortable percept than conventional TS, and appears to provide a similar degree of pain relief with significantly lower energy requirements. Further studies are necessary to determine whether this represents an effective alternative to tonic SCS for treatment of neuropathic pain. © 2015 International Neuromodulation Society.

Effect of echo spacing and readout bandwidth on basic performances of EPI-fMRI acquisition sequences implemented on two 1.5 T MR scanner systems.

PubMed

Giannelli, Marco; Diciotti, Stefano; Tessa, Carlo; Mascalchi, Mario

2010-01-01

Although in EPI-fMRI analyses typical acquisition parameters (TR, TE, matrix, slice thickness, etc.) are generally employed, various readout bandwidth (BW) values are used as a function of gradients characteristics of the MR scanner. Echo spacing (ES) is another fundamental parameter of EPI-fMRI acquisition sequences but the employed ES value is not usually reported in fMRI studies. In the present work, the authors investigated the effect of ES and BW on basic performances of EPI-fMRI sequences in terms of temporal stability and overall image quality of time series acquisition. EPI-fMRI acquisitions of the same water phantom were performed using two clinical MR scanner systems (scanners A and B) with different gradient characteristics and functional designs of radiofrequency coils. For both scanners, the employed ES values ranged from 0.75 to 1.33 ms. The used BW values ranged from 125.0 to 250.0 kHz/64pixels and from 78.1 to 185.2 kHz/64pixels for scanners A and B, respectively. The temporal stability of EPI-fMRI sequence was assessed measuring the signal-to-fluctuation noise ratio (SFNR) and signal drift (DR), while the overall image quality was assessed evaluating the signal-to-noise ratio (SNR(ts)) and nonuniformity (NU(ts)) of the time series acquisition. For both scanners, no significant effect of ES and BW on signal drift was revealed. The SFNR, NU(ts) and SNR(ts) values of scanner A did not significantly vary with ES. On the other hand, the SFNR, NU(ts), and SNR(ts) values of scanner B significantly varied with ES. SFNR (5.8%) and SNR(ts) (5.9%) increased with increasing ES. SFNR (25% scanner A, 32% scanner B) and SNR(ts) (26.2% scanner A, 30.1% scanner B) values of both scanners significantly decreased with increasing BW. NU(ts) values of scanners A and B were less than 3% for all BW and ES values. Nonetheless, scanner A was characterized by a significant upward trend (3% percentage of variation) of time series nonuniformity with increasing BW while NU(ts) of scanner B significantly increased (19% percentage of variation) with increasing ES. Temporal stability (SFNR and DR) and overall image quality (NU(ts) and SNR(ts)) of EPI-fMRI time series can significantly vary with echo spacing and readout bandwidth. The specific pattern of variation may depend on the performance of each single MR scanner system in terms of gradients characteristics, EPI sequence calibrations (eddy currents, shimming, etc.), and functional design of radiofrequency coil. Our results indicate that the employment of low BW improves not only the signal-to-noise ratio of EPI-fMRI time series but also the temporal stability of functional acquisitions. The use of minimum ES values is not entirely advantageous when the MR scanner system is characterized by gradients with low performances and suboptimal EPI sequence calibration. Since differences in basic performances of MR scanner system are potential source of variability for fMRI activation, phantom measurements of SFNR, DR, NU(ts), and SNR(ts) can be executed before subjects acquisitions to monitor the stability of MR scanner performances in clinical group comparison and longitudinal studies.

A novel enolase from Taenia solium metacestodes and its evaluation as an immunodiagnostic antigen for porcine cysticercosis.

PubMed

Ponce, Reynaldo; León-Janampa, Nancy; Gilman, Robert H; Liendo, Ruddy; Roncal, Elisa; Luis, Sueline; Quiñones-Garcia, Stefany; Silverstein, Zach; García, Hector H; Gonzales, Armando; Sheen, Patricia; Zimic, Mirko; Pajuelo, Mónica

2018-06-06

Cysticercosis is a worldwide parasitic disease of humans and pigs principally caused by infection with the larvae of the pork tapeworm Taenia solium. Through the use of the recently-made-available T. solium genome, we identified a gene within a novel 1448 bp ORF that theoretically encodes for a 433 amino acid-long protein and predicted to be an α-enolase closely related to enolases of other flatworms. Additional bioinformatic analyses revealed a putative plasminogen-binding region on this protein, suggesting a potential role for this protein in pathogenesis. On this basis, we isolated the mRNA encoding for this presumptive enolase from T. solium metacestodes and reverse-transcribed it into cDNA before subsequently cloning and expressing it in both E. coli (rEnoTs) and insect cells (rEnoTsBac), in a 6xHis tagged manner. The molecular weights of these two recombinant proteins were ∼48 and ∼50 kDa, respectively, with the differences likely attributable to differential glycosylation. We used spectrophotometric assays to confirm the enolase nature of rEnoTs as well as to measure its enzymatic activity. The resulting estimates of specific activity (60.000 U/mg) and K m (0.091 mM) are quite similar to the catalytic characteristics of enolases of other flatworms. rEnoTs also exhibited high immunogenicity, eliciting a strong polyclonal antibody response in immunized rabbits. We subsequently employed rEnoTsBac for use in an ELISA aimed at discriminating between healthy pigs and those infected with T. solium. This diagnostic assay exhibited a sensitivity of 88.4% (95% CI, 74.92%-96.11%) and a specificity of 83.7% (95% CI: 69.29%-93.19%). In conclusión, this study reports on and enzymatically characterizes a novel enolase from T. solium metacestode, and shows a potential use as an immunodiagnostic for porcine cysticercosis. Copyright © 2018. Published by Elsevier Inc.

Diagnostic Criteria, Clinical Features, and Incidence of Thyroid Storm Based on Nationwide Surveys

PubMed Central

Satoh, Tetsurou; Isozaki, Osamu; Suzuki, Atsushi; Wakino, Shu; Iburi, Tadao; Tsuboi, Kumiko; Monden, Tsuyoshi; Kouki, Tsuyoshi; Otani, Hajime; Teramukai, Satoshi; Uehara, Ritei; Nakamura, Yosikazu; Nagai, Masaki; Mori, Masatomo

2012-01-01

Background Thyroid storm (TS) is life threatening. Its incidence is poorly defined, few series are available, and population-based diagnostic criteria have not been established. We surveyed TS in Japan, defined its characteristics, and formulated diagnostic criteria, FINAL-CRITERIA1 and FINAL-CRITERIA2, for two grades of TS, TS1, and TS2 respectively. Methods We first developed diagnostic criteria based on 99 patients in the literature and 7 of our patients (LIT-CRITERIA1 for TS1 and LIT-CRITERIA2 for TS2). Thyrotoxicosis was a prerequisite for TS1 and TS2 as well as for combinations of the central nervous system manifestations, fever, tachycardia, congestive heart failure (CHF), and gastrointestinal (GI)/hepatic disturbances. We then conducted initial and follow-up surveys from 2004 through 2008, targeting all hospitals in Japan, with an eight-layered random extraction selection process to obtain and verify information on patients who met LIT-CRITERIA1 and LIT-CRITERIA2. Results We identified 282 patients with TS1 and 74 patients with TS2. Based on these data and information from the Ministry of Health, Labor, and Welfare of Japan, we estimated the incidence of TS in hospitalized patients in Japan to be 0.20 per 100,000 per year. Serum-free thyroxine and free triiodothyroine concentrations were similar among patients with TS in the literature, Japanese patients with TS1 or TS2, and a group of patients with thyrotoxicosis without TS (Tox-NoTS). The mortality rate was 11.0% in TS1, 9.5% in TS2, and 0% in Tox-NoTS patients. Multiple organ failure was the most common cause of death in TS1 and TS2, followed by CHF, respiratory failure, arrhythmia, disseminated intravascular coagulation, GI perforation, hypoxic brain syndrome, and sepsis. Glasgow Coma Scale results and blood urea nitrogen (BUN) were associated with irreversible damages in 22 survivors. The only change in our final diagnostic criteria for TS as compared with our initial criteria related to serum bilirubin concentration >3 mg/dL. Conclusions TS is still a life-threatening disorder with more than 10% mortality in Japan. We present newly formulated diagnostic criteria for TS and clarify its clinical features, prognosis, and incidence based on nationwide surveys in Japan. This information will help diagnose TS and in understanding the factors contributing to mortality and irreversible complications. PMID:22690898

Thymidylate synthase (TS) gene expression in primary lung cancer patients: a large-scale study in Japanese population.

PubMed

Tanaka, F; Wada, H; Fukui, Y; Fukushima, M

2011-08-01

Previous small-sized studies showed lower thymidylate synthase (TS) expression in adenocarcinoma of the lung, which may explain higher antitumor activity of TS-inhibiting agents such as pemetrexed. To quantitatively measure TS gene expression in a large-scale Japanese population (n = 2621) with primary lung cancer, laser-captured microdissected sections were cut from primary tumors, surrounding normal lung tissues and involved nodes. TS gene expression level in primary tumor was significantly higher than that in normal lung tissue (mean TS/β-actin, 3.4 and 1.0, respectively; P < 0.01), and TS gene expression level was further higher in involved node (mean TS/β-actin, 7.7; P < 0.01). Analyses of TS gene expression levels in primary tumor according to histologic cell type revealed that small-cell carcinoma showed highest TS expression (mean TS/β-actin, 13.8) and that squamous cell carcinoma showed higher TS expression as compared with adenocarcinoma (mean TS/β-actin, 4.3 and 2.3, respectively; P < 0.01); TS gene expression was significantly increased along with a decrease in the grade of tumor cell differentiation. There was no significant difference in TS gene expression according to any other patient characteristics including tumor progression. Lower TS expression in adenocarcinoma of the lung was confirmed in a large-scale study.

Improved immunomagnetic enrichment of CD34(+) cells from umbilical cord blood using the CliniMACS cell separation system.

PubMed

Blake, Joseph M; Nicoud, Ian B; Weber, Daniel; Voorhies, Howard; Guthrie, Katherine A; Heimfeld, Shelly; Delaney, Colleen

2012-08-01

CD34(+) enrichment from cord blood units (CBU) is used increasingly in clinical applications involving ex vivo expansion. The CliniMACS instrument from Miltenyi Biotec is a current good manufacturing practice (cGMP) immunomagnetic selection system primarily designed for processing larger numbers of cells: a standard tubing set (TS) can process a maximum of 60 billion cells, while the larger capacity tubing set (LS) will handle 120 billion cells. In comparison, most CBU contain only 1-2 billion cells, raising a question regarding the optimal tubing set for CBU CD34(+) enrichment. We compared CD34(+) cell recovery and overall viability after CliniMACS processing of fresh CBU with either TS or LS. Forty-six freshly collected CBU (≤ 36 h) were processed for CD34(+) enrichment; 22 consecutive units were selected using TS and a subsequent 24 processed with LS. Cell counts and immunophenotyping were performed pre- and post-selection to assess total nucleated cells (TNC), viability and CD34(+) cell content. Two-sample t-tests of mean CD34(+) recovery and viability revealed significant differences in favor of LS (CD34(+) recovery, LS = 56%, TS = 45%, P = 0.003; viability, LS = 74%, TS = 59%, P = 0.011). Stepwise linear regression, considering pre-processing unit age, viability, TNC and CD34(+) purity, demonstrated statistically significant correlations only with the tubing set used and age of unit. For CD34(+) enrichment from fresh CBU, LS provided higher post-selection viability and more efficient recovery. In this case, a lower maximum TNC specification of TS was not predictive of better performance. The same may hold for smaller scale enrichment of other cell types with the CliniMACS instrument.

The temperature-sensitive mutants of Toxoplasma gondii and ocular toxoplasmosis.

PubMed

Lu, Fangli; Huang, Shiguang; Kasper, Lloyd H

2009-01-22

The risk of blindness caused by ocular toxoplasmosis supports efforts to improve our understanding for control of this disease. In this study, the involvement of CD8(+), CD4(+), B cell, and IL-10 gene in the immune response of primary ocular infection with the temperature-sensitive mutant (ts-4) of the RH Toxoplasma gondii strain, and in the protective immunity of ocular ts-4 vaccination and challenge with RH strain was investigated in murine models utilizing inbred C57BL/6 mice-deficient in CD4(+), CD8(+), B cells (microMT), or IL-10 gene. Compared to naive mice, all WT and mutant mice had different degree of ocular pathological changes after ts-4 ocular infection, in which both CD8 KO and IL-10 KO mice showed the most severe ocular lesions. Immunized by ts-4 intracameral (i.c.) inoculation, all mutant mice had partially decreased vaccine-induced resistance associated with increased ocular parasite burdens after RH strain challenge. A significant increase of the percentages of B cells and CD8(+) T cells in the draining lymph nodes were observed in WT and IL-10 KO mice after either infection or challenge. The levels of specific anti-toxoplasma IgG in both eye fluid and serum from all the mice were significantly increased after ts-4 i.c. immunization, except microMT mice. These results suggest that the avirulent ts-4 of T. gondii inoculated intracamerally can induce both ocular pathology and ocular protective immunity; CD4(+), CD8(+), B cell, and IL-10 gene are all necessary to the vaccine-induced resistance to ocular challenge by virulent RH strain, in which CD8(+) T cells are the most important component.

Prenatal risk factors for Tourette Syndrome: a systematic review.

PubMed

Chao, Ting-Kuang; Hu, Jing; Pringsheim, Tamara

2014-01-30

Tourette Syndrome (TS) appears to be an inherited disorder, although genetic abnormalities have been identified in less than 1% of patients, and the mode of inheritance is uncertain. Many studies have investigated environmental factors that might contribute to the onset and severity of tics and associated comorbidities such as obsessive compulsive disorder (OCD) and attention deficit hyperactive disorder (ADHD). A systematic review and qualitative analysis were performed to provide a broad view of the association between pre- and perinatal factors and TS. The Medline, Embase and PsycINFO databases were searched using terms specific to Tourette's syndrome and keywords such as "pregnancy", "prenatal", "perinatal", "birth" and "neonatal". Studies were limited to studies on human subjects published in English or French through October 2012. 22 studies were included. Studies were of limited methodological quality, with most samples derived from specialty clinics, and most exposures ascertained retrospectively. The majority of the results for demographic factors of parents, including age, education, socioeconomic status, and marital status, revealed no significant association with the onset of TS, or the presence of comorbidity. Many factors were reported to be significantly associated with the onset of TS, the presence of comorbidity and symptom severity, but the most consistently reported factors were maternal smoking and low birth weight. There are few studies evaluating the relationship between pre and perinatal events and TS, and existing studies have major limitations, including the use of clinic rather than epidemiologically derived samples, retrospective data collection on pre and perinatal events and multiple hypothesis testing without appropriate statistical correction. The mechanism by which prenatal and perinatal adversities could lead to TS onset or symptom severity is unknown, but may be related to changes in the dopaminergic system as a result of early brain injury.

Nontraditional roles for certified pharmacy technicians in a pharmaceutical company.

PubMed

Fung, Stacey M; Gilmour, Christine; McCracken, David; Shane, Korban; Matsuura, Gary

2006-01-01

To describe nontraditional roles for Certified Pharmacy Technicians (CPhTs) within pharmaceutical industry. Drug information department within a large biotechnology/pharmaceutical organization. The Medical Communications department within Genentech uses a skills-mix staffing model in which employees with varying educational and training backgrounds work as a team on meeting the informational needs of consumers and health professionals who contact the company. One position within the department is that of Medical Communications Associate, responsible primarily for managing product inquiries. Medical Communications Associates have degrees in life sciences or an equivalent combination of education and experience, including a minimum of 2 years of related experience in the health care industry. Currently, four of the seven Medical Communications Associates in the department are CPhTs. Not applicable. Ability to recruit CPhTs for Medical Communications Associate positions, and job satisfaction of those hired into these positions. Critical basic skills needed for the Medical Communications Associate position include strong computer literacy, ability to multitask, and ability to work in an environment with frequent interruptions. Strong oral and written communications skills, customer service skills, ability to deal with stressful situations, product-specific knowledge, ability to work on a daily basis with Medical Communications Pharmacists, and knowledge of medical terminology are also important. The skills set of CPhTs matches these requirements, as evidenced by the experiences of the four staff members who have worked in the department for a total of 17 person-years. This nontraditional role for CPhTs can be rewarding and beneficial to all, affording an unique opportunity within the pharmaceutical industry. The skill set and experience of CPhTs can be used in the nontraditional pharmacy practice setting of drug information.

Consistency of polyphenol oxidase (PPO) thermostability in ripening apricots (Prunus armeniaca L.): evidence for the presence of thermostable PPO forming and destabilizing mechanisms in apricots.

PubMed

Yemenicioğlu, Ahmet; Cemeroğlu, Bekir

2003-04-09

Destabilization of thermostable polyphenol oxidase (TS-PPO) during the ripening of peaches has been previously shown (Yemenicioğlu, A.; Cemeroğlu, B. Tr. J. Agric. For. 1998, 22, 261-265). This work studied the effect of ripening on thermal stability of apricot PPO for three different cultivars. Kabaaşi cultivar contained thermolabile PPO, whereas TS-PPO appeared in Hacihaliloğlu and Cataloğlu cultivars. The TS-PPO showed biphasic inactivation curves, and its D and z values between 60 and 90 degrees C varied in the ranges of 357-1.12 min and 11.9-12.7 degrees C, respectively. In Hacihaliloğlu cultivar the TS-PPO was very consistent and existed at all stages of ripening, whereas in Cataloğlu cultivar it appeared only at the half-ripe stage. The loss of consistent TS-PPO in Hacihaliloğlu apricots after partial purification by acetone precipitation and DEAE-cellulose chromatography suggested the non-covalent nature of its stabilization. The main purified fractions (F1 and F2) showed monophasic inactivation curves with similar thermal inactivation parameters (z(F1) = 10.4 degrees C, z(F2) = 10.1 degrees C). However, their kinetic properties against catechol (K(mF1) = 61 mM, K(mF2) = 122.7 mM) and substrate specificities were considerably different. The results of this study showed the presence of TS-PPO forming and destabilizing mechanisms in apricots. Further studies are needed for the solution of these mechanisms and to develop some new strategies that may be utilized by molecular techniques for a planned production of apricot cultivars provided with heat labile but normal PPO activity.

Electrophysiological correlates of purely temporal figure-ground segregation.

PubMed

Kandil, Farid I; Fahle, Manfred

2003-11-01

Inhomogenous displays, in contrast to homogenous ones, evoke a specific potential in the VEP (tsVEP) which appears across different classical visual stimulus dimensions defining figure-ground segregation, such as luminance, orientation, (first-order) motion, and stereoscopic depth. This negative potential has a peak latency of about 200-300 ms and a peak amplitude of about -3 to -10 microV [Doc Ophthalmol. 95 (1998) 335]. Previously, we demonstrated that human subjects reliably segregate figure from ground, even in the absence of the classical cues, leaving time of change as the only cue for segregation. The results of the present study demonstrate that also purely temporally defined checkerboards evoke a tsVEP resembling the motion-defined tsVEP regarding polarity (negative), latency (two peaks at 180 and 270 ms, respectively), amplitude of the first negativity (-5.6 microV), and overall form of its components.

Characteristics of Executive Functioning in a Small Sample of Children With Tourette Syndrome.

PubMed

Schwam, Dina M; King, Tricia Z; Greenberg, Daphne

2015-01-01

Tourette syndrome (TS) is a disorder that involves at least one vocal tic and two or more motor tics; however, associated symptoms of obsessive-compulsive disorder (OCD) and attention-deficit disorder or attention-deficit hyperactivity disorder (ADHD) are common. Many children with TS exhibit educational difficulties and one possible explanation may be deficits in executive functioning. The focus of this study was to look at the severity of symptoms often associated with TS (tics and OCD and ADHD symptoms) and its potential relationship with the Behavior Rating Inventory of Executive Function (BRIEF) Parent Form in 11 children diagnosed with TS aged 8 to 14 years old. The parent of the child completed the BRIEF along with symptom measures evaluating tics, OCD behaviors, and ADHD symptoms. Despite relatively low mean scores on the symptom measures and just a few children exhibiting clinically significant scores on the BRIEF indexes, at least half the children exhibited abnormal scores on the Working Memory, Inhibit, and Shift subscales of the BRIEF. Varying patterns of relationships were found on the BRIEF subscales for each symptom severity scale. Results suggest that the BRIEF may be useful in determining the specific areas of difficulty in a population with variable symptomatology.

How Accurate Are Transition States from Simulations of Enzymatic Reactions?

PubMed Central

2015-01-01

The rate expression of traditional transition state theory (TST) assumes no recrossing of the transition state (TS) and thermal quasi-equilibrium between the ground state and the TS. Currently, it is not well understood to what extent these assumptions influence the nature of the activated complex obtained in traditional TST-based simulations of processes in the condensed phase in general and in enzymes in particular. Here we scrutinize these assumptions by characterizing the TSs for hydride transfer catalyzed by the enzyme Escherichia coli dihydrofolate reductase obtained using various simulation approaches. Specifically, we compare the TSs obtained with common TST-based methods and a dynamics-based method. Using a recently developed accurate hybrid quantum mechanics/molecular mechanics potential, we find that the TST-based and dynamics-based methods give considerably different TS ensembles. This discrepancy, which could be due equilibrium solvation effects and the nature of the reaction coordinate employed and its motion, raises major questions about how to interpret the TSs determined by common simulation methods. We conclude that further investigation is needed to characterize the impact of various TST assumptions on the TS phase-space ensemble and on the reaction kinetics. PMID:24860275

Predictors of postoperative outcomes of cubital tunnel syndrome treatments using multiple logistic regression analysis.

PubMed

Suzuki, Taku; Iwamoto, Takuji; Shizu, Kanae; Suzuki, Katsuji; Yamada, Harumoto; Sato, Kazuki

2017-05-01

This retrospective study was designed to investigate prognostic factors for postoperative outcomes for cubital tunnel syndrome (CubTS) using multiple logistic regression analysis with a large number of patients. Eighty-three patients with CubTS who underwent surgeries were enrolled. The following potential prognostic factors for disease severity were selected according to previous reports: sex, age, type of surgery, disease duration, body mass index, cervical lesion, presence of diabetes mellitus, Workers' Compensation status, preoperative severity, and preoperative electrodiagnostic testing. Postoperative severity of disease was assessed 2 years after surgery by Messina's criteria which is an outcome measure specifically for CubTS. Bivariate analysis was performed to select candidate prognostic factors for multiple linear regression analyses. Multiple logistic regression analysis was conducted to identify the association between postoperative severity and selected prognostic factors. Both bivariate and multiple linear regression analysis revealed only preoperative severity as an independent risk factor for poor prognosis, while other factors did not show any significant association. Although conflicting results exist regarding prognosis of CubTS, this study supports evidence from previous studies and concludes early surgical intervention portends the most favorable prognosis. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Evaluation of passive transfer in captive greater kudu (Tragelaphus strepsiceros).

PubMed

Hammond, Elizabeth E; Fiorello, Christine V

2011-12-01

Failure of passive transfer (FPT) in captive greater kudu (Tragelaphus strepsiceros) calves can lead to increased morbidity and mortality. In this retrospective study, serum samples from neonatal kudu calves were tested for immunoglobulin using different tests validated for domestic ruminants, including measurement of gamma globulin (GG) measured by protein electrophoresis, total solids (TS) measured by calibrated refractometry, total protein (TP) and globulins measured by colorimetry, gamma glutamyltransferase (GGT), and the zinc sulfate turbidity test (ZSTT). In a logistic regression model, TP, TS, globulins, and the natural log transform of GGT were the only significant parameters associated with FPT. Various historic parameters related to the dam, as well as calf weight, sex, glucose, and packed cell volume, were not significant. Based on the results, FPT in greater kudu is defined as GG of < 0.5 g/dl, a value lower than that in domestic cattle. TS measured by refractometry has an 80% sensitivity and a 100% specificity for FPT in greater kudu. With FPT defined as GG < 0.5 g/dl, kudu calves with a TS < 4.8 g/dl and a negative ZSTT have an increased probability of requiring medical intervention and additional diagnostics may be warranted.

Thymidylate synthase (TS) protein expression as a prognostic factor in advanced colorectal cancer: a comparison with TS mRNA expression.

PubMed

Nakagawa, Tateo; Shimada, Mitsuo; Kurita, Nobuhiro; Iwata, Takashi; Nishioka, Masanori; Yoshikawa, Kozo; Higashijima, Jun; Utsunomiya, Tohru

2012-06-01

The role of intratumoral thymidylate synthase (TS) mRNA or protein expression is still controversial and little has been reported regarding relation of them in colorectal cancer. Forty-six patients with advanced colorectal cancer who underwent surgical resection were included. TS mRNA expression was determined by the Danenberg tumor profile method based on laser-captured micro-dissection of the tumor cells. TS protein expression was evaluated using immunohistochemical staining. TS mRNA expression tended to relate TS protein expression. Statistical significance was not found in overall survival between the TS mRNA high group and low group regardless of performing adjuvant chemotherapy. The overall survival in the TS protein negative group was significantly higher than that in positive group in all and the patients without adjuvant chemotherapy. Multivariate analysis showed TS protein expression was as an independent prognostic factor. TS protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.

Social cognition and self-other distinctions in neuropsychiatry: Insights from schizophrenia and Tourette syndrome.

PubMed

Eddy, Clare M

2018-03-02

Impairments in social cognition may reflect dysfunction of disorder specific or disorder general mechanisms. Although cross-disorder comparison may prove insightful, few studies have compared social cognition in different neuropsychiatric disorders. Parallel investigation of schizophrenia and Tourette syndrome (TS) is encouraged by similarities including the presence of problematic social behavior, echophenomena, emotional dysregulation and dopamine dysfunction. Focusing on tests of social cognition administered in both disorders, this review aims to summarize behavioral, neurophysiological and neuroimaging findings, before exploring how these may contribute to clinical symptoms. Studies investigating social cognition (imitation, emotion recognition, and understanding of beliefs or intentions) in patients with schizophrenia or TS were identified through Web of Science and PubMed searches. Although findings indicate that social cognitive deficits are more apparent in schizophrenia, adults with TS can exhibit similar task performance to patients with paranoia. In both disorders, behavioral and neuroimaging findings raise the possibility of increased internal simulation of others' actions and emotions, in combination with a relative under-application of mentalizing. More specifically, dysfunction in neurobiological substrates such as temporo-parietal junction and inferior frontal gyrus may underlie problems with self-other distinctions in both schizophrenia and TS. Difficulties in distinguishing between actions and mental states linked to the self and other may contribute to a range of psychiatric symptoms, including emotional dysregulation, paranoia, social anhedonia and socially disruptive urges. Comparing different patient populations could therefore reveal common neuro-cognitive risk factors for the development of problematic social behaviors, in addition to markers of resilience, coping strategies and potential neuro-compensation mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Hypoxia-inducible factor-targeting prodrug TOP3 combined with gemcitabine or TS-1 improves pancreatic cancer survival in an orthotopic model.

PubMed

Hoang, Ngoc Thi Hong; Kadonosono, Tetsuya; Kuchimaru, Takahiro; Kizaka-Kondoh, Shinae

2016-08-01

Pancreatic cancer is one of the most lethal digestive system cancers with a 5-year survival rate of 4-7%. Despite extensive efforts, recent chemotherapeutic regimens have provided only limited benefits to pancreatic cancer patients. Gemcitabine and TS-1, the current standard-of-care chemotherapeutic drugs for treatment of this severe cancer, have a low response rate. Hypoxia is one of the factors contributing to treatment resistance. Specifically, overexpression of hypoxia-inducible factor, a master transcriptional regulator of cell adaption to hypoxia, is strongly correlated with poor prognosis in many human cancers. TAT-ODD-procaspase-3 (TOP3) is a protein prodrug that is specifically processed and activated in hypoxia-inducible factor-active cells in cancers, leading to cell death. Here, we report combination therapies in which TOP3 was combined with gemcitabine or TS-1. As monotherapy, gemcitabine and TS-1 showed a limited effect on hypoxic and starved pancreatic cancer cells, whereas co-treatment with TOP3 successfully overcame this limitation in vitro. Furthermore, combination therapies of TOP3 with these drugs resulted in a significant improvement in survival of orthotopic pancreatic cancer models involving the human pancreatic cancer cell line SUIT-2. Overall, our study indicates that the combination of TOP3 with current chemotherapeutic drugs can significantly improve treatment outcome, offering a promising new therapeutic option for patients with pancreatic cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Temperature and food mediate long-term thermotactic behavioral plasticity by association-independent mechanisms in C. elegans.

PubMed

Chi, Cynthia A; Clark, Damon A; Lee, Stella; Biron, David; Luo, Linjiao; Gabel, Christopher V; Brown, Jeffrey; Sengupta, Piali; Samuel, Aravinthan D T

2007-11-01

Thermotactic behavior in the nematode Caenorhabditis elegans exhibits long-term plasticity. On a spatial thermal gradient, C. elegans tracks isotherms near a remembered set-point (T(S)) corresponding to its previous cultivation temperature. When navigating at temperatures above its set-point (T>T(S)), C. elegans crawls down spatial thermal gradients towards the T(S) in what is called cryophilic movement. The T(S) retains plasticity in the adult stage and is reset by approximately 4 h of sustained exposure to a new temperature. Long-term plasticity in C. elegans thermotactic behavior has been proposed to represent an associative learning of specific temperatures conditioned in the presence or absence of bacterial food. Here, we use quantitative behavioral assays to define the temperature and food-dependent determinants of long-term plasticity in the different modes of thermotactic behavior. Under our experimental conditions, we find that starvation at a specific temperature neither disrupts T(S) resetting toward the starvation temperature nor induces learned avoidance of the starvation temperature. We find that prolonged starvation suppresses the cryophilic mode of thermotactic behavior. The hen-1 and tax-6 genes have been reported to affect associative learning between temperature and food-dependent cues. Under our experimental conditions, mutation in the hen-1 gene, which encodes a secreted protein with an LDL receptor motif, does not significantly affect thermotactic behavior or long-term plasticity. Mutation in the tax-6 calcineurin gene abolishes thermotactic behavior altogether. In summary, we do not find evidence that long-term plasticity requires association between temperature and the presence or absence of bacterial food.

Characterization of ppGalNAc-T18, a member of the vertebrate-specific Y subfamily of UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases.

PubMed

Li, Xing; Wang, Jing; Li, Wei; Xu, Yingjiao; Shao, Dong; Xie, Yinyin; Xie, Wenxian; Kubota, Tomomi; Narimatsu, Hisashi; Zhang, Yan

2012-05-01

The first step of mucin-type O-glycosylation is catalyzed by members of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGalNAc-T; EC 2.4.1.41) family. Each member of this family has unique substrate specificity and expression profiles. In this report, we describe a new subfamily of ppGalNAc-Ts, designated the Y subfamily. The Y subfamily consists of four members, ppGalNAc-T8, -T9, -T17 and -T18, in which the conserved YDX(5)WGGENXE sequence in the Gal/GalNAc-T motif of ppGalNAc-Ts is mutated to LDX(5)YGGENXE. Phylogenetic analysis revealed that the Y subfamily members only exist in vertebrates. All four Y subfamily members lack in vitro GalNAc-transferase activity toward classical substrates possibly because of the UDP-GalNAc-binding pocket mutants. However, ppGalNAc-T18, the newly identified defining member, was localized in the endoplasmic reticulum rather than the Golgi apparatus in lung carcinoma cells. The knockdown of ppGalNAc-T18 altered cell morphology, proliferation potential and changed cell O-glycosylation. ppGalNAc-T18 can also modulate the in vitro GalNAc-transferase activity of ppGalNAc-T2 and -T10, suggesting that it may be a chaperone-like protein. These findings suggest that the new Y subfamily of ppGalNAc-Ts plays an important role in protein glycosylation; characterizing their functions will provide new insight into the role of ppGalNAc-Ts.

Program Manager: The Journal of the Defense Systems Management College. Volume 14, Number 1, January-February 1985,

DTIC Science & Technology

1985-02-01

world’s most re- its relationship to capital investment, act as a stimulus for decreasing weap- 0,ourcetul and technically capable commonly referred to...remove bar- other serious consequences, adver- an understanding (it what riers to a smooth flow. We need to sarial relationships lead to un- the...NOW?’ LHX VTXTS(T-45TS) ATF "WE CAN’T OFFEND OUR CUSTOMER ." AATWS JVX IEWS "WE CAN’T TAKE A CHANCE DURING THE COMPETI- PERSHING II CV IZ AWS TION

Characterization of Biopolymer Surfaces Using Scanning Microscopies

DTIC Science & Technology

1989-11-15

Final Technical Progress Report Contract N00014-88-K-0415 7/8 - 9/89 Chira ri atf ion of 51opolymor Aurfmann uTsIng ScAnning H~eroseon4e9: by J.D...J. C, in REFERENCES "Biocompatibilty of Clinical Implant NfatcriAl" (D. F. Williams , Ed.), Vol. 2, p. 3. CRC Press, I. Ilarisma, P. K.. and Tersof, .J...Pas model from Williams (191); the globular soluticn (10 ppm albumnn onto freshly domains at both ends my be elongated 190 .leaved H.PG and then the

High-Speed Solution of Spacecraft Trajectory Problems Using Taylor Series Integration

NASA Technical Reports Server (NTRS)

Scott, James R.; Martini, Michael C.

2010-01-01

It has been known for some time that Taylor series (TS) integration is among the most efficient and accurate numerical methods in solving differential equations. However, the full benefit of the method has yet to be realized in calculating spacecraft trajectories, for two main reasons. First, most applications of Taylor series to trajectory propagation have focused on relatively simple problems of orbital motion or on specific problems and have not provided general applicability. Second, applications that have been more general have required use of a preprocessor, which inevitably imposes constraints on computational efficiency. The latter approach includes the work of Berryman et al., who solved the planetary n-body problem with relativistic effects. Their work specifically noted the computational inefficiencies arising from use of a preprocessor and pointed out the potential benefit of manually coding derivative routines. In this Engineering Note, we report on a systematic effort to directly implement Taylor series integration in an operational trajectory propagation code: the Spacecraft N-Body Analysis Program (SNAP). The present Taylor series implementation is unique in that it applies to spacecraft virtually anywhere in the solar system and can be used interchangeably with another integration method. SNAP is a high-fidelity trajectory propagator that includes force models for central body gravitation with N X N harmonics, other body gravitation with N X N harmonics, solar radiation pressure, atmospheric drag (for Earth orbits), and spacecraft thrusting (including shadowing). The governing equations are solved using an eighth-order Runge-Kutta Fehlberg (RKF) single-step method with variable step size control. In the present effort, TS is implemented by way of highly integrated subroutines that can be used interchangeably with RKF. This makes it possible to turn TS on or off during various phases of a mission. Current TS force models include central body gravitation with the J2 spherical harmonic, other body gravitation, thrust, constant atmospheric drag from Earth's atmosphere, and solar radiation pressure for a sphere under constant illumination. The purpose of this Engineering Note is to demonstrate the performance of TS integration in an operational trajectory analysis code and to compare it with a standard method, eighth-order RKF. Results show that TS is 16.6 times faster on average and is more accurate in 87.5% of the cases presented.

Constructing Compact Takagi-Sugeno Rule Systems: Identification of Complex Interactions in Epidemiological Data

PubMed Central

Zhou, Shang-Ming; Lyons, Ronan A.; Brophy, Sinead; Gravenor, Mike B.

2012-01-01

The Takagi-Sugeno (TS) fuzzy rule system is a widely used data mining technique, and is of particular use in the identification of non-linear interactions between variables. However the number of rules increases dramatically when applied to high dimensional data sets (the curse of dimensionality). Few robust methods are available to identify important rules while removing redundant ones, and this results in limited applicability in fields such as epidemiology or bioinformatics where the interaction of many variables must be considered. Here, we develop a new parsimonious TS rule system. We propose three statistics: R, L, and ω-values, to rank the importance of each TS rule, and a forward selection procedure to construct a final model. We use our method to predict how key components of childhood deprivation combine to influence educational achievement outcome. We show that a parsimonious TS model can be constructed, based on a small subset of rules, that provides an accurate description of the relationship between deprivation indices and educational outcomes. The selected rules shed light on the synergistic relationships between the variables, and reveal that the effect of targeting specific domains of deprivation is crucially dependent on the state of the other domains. Policy decisions need to incorporate these interactions, and deprivation indices should not be considered in isolation. The TS rule system provides a basis for such decision making, and has wide applicability for the identification of non-linear interactions in complex biomedical data. PMID:23272108

The Roles of Phasic and Tonic Dopamine in Tic Learning and Expression.

PubMed

Maia, Tiago V; Conceição, Vasco A

2017-09-15

Tourette syndrome (TS) prominently involves dopaminergic disturbances, but the precise nature of those disturbances has remained elusive. A substantial body of empirical work and recent computational models have characterized the specific roles of phasic and tonic dopamine (DA) in action learning and selection, respectively. Using insights from this work and models, we suggest that TS involves increases in both phasic and tonic DA, which produce increased propensities for tic learning and expression, respectively. We review the evidence from reinforcement-learning and habit-learning studies in TS, which supports the idea that TS involves increased phasic DA responses; we also review the evidence that tics engage the habit-learning circuitry. On the basis of these findings, we suggest that tics are exaggerated, maladaptive, and persistent motor habits reinforced by aberrant, increased phasic DA responses. Increased tonic DA amplifies the tendency to execute learned tics and also provides a fertile ground of motor hyperactivity for tic learning. We review evidence suggesting that antipsychotics may counter both the increased propensity for tic expression, by increasing excitability in the indirect pathway, and the increased propensity for tic learning, by shifting plasticity in the indirect pathway toward long-term potentiation (and possibly also through more complex mechanisms). Finally, we review evidence suggesting that low doses of DA agonists that effectively treat TS decrease both phasic and tonic DA, thereby also reducing the propensity for both tic learning and tic expression, respectively. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Tic symptom dimensions and their heritabilities in Tourette's syndrome.

PubMed

de Haan, Marcel J; Delucchi, Kevin L; Mathews, Carol M; Cath, Danielle C

2015-06-01

Gilles de la Tourette's syndrome (TS) is both genotypically and phenotypically heterogeneous. Gene-finding strategies have had limited success, possibly because of symptom heterogeneity. This study aimed at specifically investigating heritabilities of tic symptom factors in a relatively large sample of TS patients and family members. Lifetime tic symptom data were collected in 494 diagnosed individuals in two cohorts of TS patients from the USA (n=273) and the Netherlands (n=221), and in 351 Dutch family members. Item-level factor analysis, using a tetrachoric correlation matrix in SAS (v9.2), was carried out on 23 tic symptoms from the Yale Global Tic Severity Scale. Three factors were identified explaining 49% of the total variance: factor 1, complex vocal tics and obscene behaviour; factor 2, body tics; and factor 3, head/neck tics. Using Sequential Oligogenic Linkage Analysis Routine, moderate heritabilities were found for factor 1 (h2r=0.21) and factor 3 (h2r=0.25). Lower heritability was found for overall tic severity (h2r=0.19). Bivariate analyses indicated no genetic associations between tic factors. These findings suggest that (i) three tic factors can be discerned with a distinct underlying genetic architecture and that (ii) considering the low tic heritabilities found, only focusing on the narrow-sense TS phenotype and leaving out comorbidities that are part of the broader sense tic phenotype may lead to missing heritability. Although these findings need replication in larger independent samples, they might have consequences for future genetic studies in TS.

Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

PubMed Central

Israelashvili, Michal; Loewenstern, Yocheved

2015-01-01

Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

Constructing compact Takagi-Sugeno rule systems: identification of complex interactions in epidemiological data.

PubMed

Zhou, Shang-Ming; Lyons, Ronan A; Brophy, Sinead; Gravenor, Mike B

2012-01-01

The Takagi-Sugeno (TS) fuzzy rule system is a widely used data mining technique, and is of particular use in the identification of non-linear interactions between variables. However the number of rules increases dramatically when applied to high dimensional data sets (the curse of dimensionality). Few robust methods are available to identify important rules while removing redundant ones, and this results in limited applicability in fields such as epidemiology or bioinformatics where the interaction of many variables must be considered. Here, we develop a new parsimonious TS rule system. We propose three statistics: R, L, and ω-values, to rank the importance of each TS rule, and a forward selection procedure to construct a final model. We use our method to predict how key components of childhood deprivation combine to influence educational achievement outcome. We show that a parsimonious TS model can be constructed, based on a small subset of rules, that provides an accurate description of the relationship between deprivation indices and educational outcomes. The selected rules shed light on the synergistic relationships between the variables, and reveal that the effect of targeting specific domains of deprivation is crucially dependent on the state of the other domains. Policy decisions need to incorporate these interactions, and deprivation indices should not be considered in isolation. The TS rule system provides a basis for such decision making, and has wide applicability for the identification of non-linear interactions in complex biomedical data.

Prognostic significance of thymidylate synthase (TS) expression in cutaneous malignant melanoma.

PubMed

Shimizu, A; Kaira, K; Yasuda, M; Asao, T; Ishikawa, O

2016-01-01

Thymidylate synthase (TS) plays an essential role in the pathogenesis and development of cancer, and TS-targeting agents have been widely used against different types of cancers. However, it remains still unclear whether or not TS is expressed in malignant melanoma. We conducted the clinicopathological study to investigate the prognostic significance of TS expression in cutaneous malignant melanoma. Ninety-nine patients with surgically resected cutaneous malignant melanoma were assessed. Tumor sections were stained by immunohistochemistry for TS, Ki-67, and microvessel density (MVD) determined by CD34. TS was positively expressed in 26% (26 out of 99). The expression of TS was significantly associated with T factor, cell proliferation (Ki-67) and MVD (CD34). By Spearman's rank test, TS expression was significantly correlated with Ki67 and CD34. By univariate analysis, ulceration, disease stage, TS, Ki-67 and CD34 had a significant relationship with survival. Multivariate analysis confirmed that TS was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The positive expression of TS could be a useful marker for predicting poor prognosis in patients with cutaneous malignant melanoma, and TS-targeting agents may be worth trying for the treatment of this dismal disease.

Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes.

PubMed

Stringer, Megan; Abeysekera, Irushi; Thomas, Jared; LaCombe, Jonathan; Stancombe, Kailey; Stewart, Robert J; Dria, Karl J; Wallace, Joseph M; Goodlett, Charles R; Roper, Randall J

2017-08-01

Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~10mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~20mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2-3mg per day (~40-60mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4mg/mL] or a water control, with treatments yielding average daily intakes of ~50mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)-which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking-and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis in the cerebellum. The lack of beneficial therapeutic behavioral effects and potentially detrimental skeletal effects of EGCG found in Ts65Dn mice emphasize the importance of identifying dosages of EGCG that reliably improve DS phenotypes and linking those effects to actions of EGCG (or EGCG-containing supplements) in specific targets in brain and bone. Copyright © 2017 Elsevier Inc. All rights reserved.

Final Technical Report for GO17004 Regulatory Logic: Codes and Standards for the Hydrogen Economy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakarado, Gary L.

The objectives of this project are to: develop a robust supporting research and development program to provide critical hydrogen behavior data and a detailed understanding of hydrogen combustion and safety across a range of scenarios, needed to establish setback distances in building codes and minimize the overall data gaps in code development; support and facilitate the completion of technical specifications by the International Organization for Standardization (ISO) for gaseous hydrogen refueling (TS 20012) and standards for on-board liquid (ISO 13985) and gaseous or gaseous blend (ISO 15869) hydrogen storage by 2007; support and facilitate the effort, led by the NFPA,more » to complete the draft Hydrogen Technologies Code (NFPA 2) by 2008; with experimental data and input from Technology Validation Program element activities, support and facilitate the completion of standards for bulk hydrogen storage (e.g., NFPA 55) by 2008; facilitate the adoption of the most recently available model codes (e.g., from the International Code Council [ICC]) in key regions; complete preliminary research and development on hydrogen release scenarios to support the establishment of setback distances in building codes and provide a sound basis for model code development and adoption; support and facilitate the development of Global Technical Regulations (GTRs) by 2010 for hydrogen vehicle systems under the United Nations Economic Commission for Europe, World Forum for Harmonization of Vehicle Regulations and Working Party on Pollution and Energy Program (ECE-WP29/GRPE); and to Support and facilitate the completion by 2012 of necessary codes and standards needed for the early commercialization and market entry of hydrogen energy technologies.« less

Neuropsychological functioning in children with Tourette syndrome (TS).

PubMed

Rasmussen, Carmen; Soleimani, Maryam; Carroll, Alan; Hodlevskyy, Oleksander

2009-11-01

We examined whether children with Tourette syndrome (TS) displayed a unique pattern of neuropsychological deficits on the CANTAB relative to control children. We also looked at whether children with TS and other comorbidities had more neuropsychological impairments than those with uncomplicated TS and how age was related to the profile of neuropsychological deficits in TS. Participants included 38 children with TS (aged 7 to 13 years) and 38 control children (aged 6 to 12 years). All children were administered 8 subtests from the CANTAB and parents and teachers completed the BRIEF rating scale on children in the TS group. Children with TS displayed deficits relative to control children on measures of visual memory, executive functioning, and attention from the CANTAB. Among the TS group, age was negatively correlated with performance on measures of executive functioning, speed of response and working memory. Identifying the pattern of neuropsychological deficits in children with TS on the CANTAB is important for highlighting areas of deficit that can be targeted for intervention and teaching strategies. With further research, the CANTAB may prove to be a useful resource in the assessment and treatment of children with TS.

Tuberous sclerosis: aberrant metabolism of ornithine, proline and glutamate in cultured fibroblasts.

PubMed

Tanaka, H; Nakazawa, K; Arima, M; Hayashi, A

1987-01-01

To investigate aberrant metabolism of proline (Pro) and its precursors in tuberous sclerosis (TS), 6, 7 and 5 strains of control, TS (normal skin) and TS (tumor) fibroblasts, respectively, were cultured in Eagle's MEM containing dialyzed fetal bovine serum with or without 0.1 mM ornithine (Orn). Ornithine aminotransferase (OAT) activity was decreased in TS, especially in TS (tumor) after mild sonication treatment. The yield of the OAT protein was inhibited in TS (tumor) when cultured without Orn. Free glutamate (Glu) in the medium was significantly increased in TS (tumor). Free proline (Pro) in cells was significantly decreased in TS (tumor) when cultured with Orn, but protein-bound Pro was not. The relative concentration of free Glu to glutamine (Gln) in the medium and that of free Glu to Pro in cells cultured with Orn were increased in TS (tumor). These results suggest that the requirement for Orn, increased turnover of Pro to Glu and increased elimination of Glu into the medium occur in TS (tumor). Aberrant regulation or turnover of Pro and Glu metabolism may occur in TS, especially in tumor cells.

A Comparison of Tropical Storm (TS) and Non-TS Gust Factors for Assessing Peak Wind Probabilities at the Eastern Range

NASA Technical Reports Server (NTRS)

Merceret, Francis J.; Crawford, Winifred C.

2010-01-01

Peak wind speed is an important forecast element to ensure the safety of personnel and flight hardware at Kennedy Space Center (KSC) and the Cape Canaveral Air Force Station (CCAFS) in East-Central Florida. The 45th Weather Squadron (45 WS), the organization that issues forecasts for the KSC/CCAFS area, finds that peak winds are more difficult to forecast than mean winds. This difficulty motivated the 45 WS to request two independent studies. The first (Merceret 2009) was the development of a reliable model for gust factors (GF) relating the peak to the mean wind speed in tropical storms (TS). The second (Lambert et al. 2008) was a climatological study of non-TS cool season (October-April) mean and peak wind speeds by the Applied Meteorology Unit (AMU; Bauman et al. 2004) without the use of GF. Both studies presented their statistics as functions of mean wind speed and height. Most of the few comparisons of TS and non-TS GF in the literature suggest that non-TS GF at a given height and mean wind speed are smaller than the corresponding TS GF. The investigation reported here converted the non-TS peak wind statistics calculated by the AMU to the equivalent GF statistics and compared them with the previous TS GF results. The advantage of this effort over all previously reported studies of its kind is that the TS and non-TS data were taken from the same towers in the same locations. This eliminates differing surface attributes, including roughness length and thermal properties, as a major source of variance in the comparison. The goal of this study is two-fold: to determine the relationship between the non-TS and TS GF and their standard deviations (GFSD) and to determine if models similar to those developed for TS data in Merceret (2009) could be developed for the non-TS environment. The results are consistent with the literature, but include much more detailed, quantitative information on the nature of the relationship between TS and non-TS GF and GFSD as a function of height and mean wind speed.

Noxious inhibition of temporal summation is impaired in chronic tension-type headache.

PubMed

Cathcart, Stuart; Winefield, Anthony H; Lushington, Kurt; Rolan, Paul

2010-03-01

To examine effects of stress on noxious inhibition and temporal summation (TS) in tension-type headache. Stress is the most commonly reported trigger of a chronic tension-type headache (CTH) episode; however, the mechanisms underlying this are unclear. Stress affects pain processing throughout the central nervous system, including, potentially, mechanisms of TS and diffuse noxious inhibitory controls (DNIC), both of which may be abnormal in CTH sufferers (CTH-S). No studies have examined TS of pressure pain or DNIC of TS in CTH-S to date. Similarly, effects of stress on TS or DNIC of TS have not been reported in healthy subjects or CTH-S to date. The present study measured TS and DNIC of TS in CTH-S and healthy controls (CNT) exposed to an hour-long stressful mental task, and in CTH-S exposed to an hour-long neutral condition. TS was elicited at finger and shoulder via 10 pulses from a pressure algometer, applied before and during stimulation from an occlusion cuff at painful intensity. Algometer pain ratings increased more in the CTH compared with the CNT group, and were inhibited during occlusion cuff more in the CNT compared with CTH groups. Task effects on TS or DNIC were not significant. The results indicate increased TS to pressure pain and impaired DNIC of TS in CTH-S. Stress does not appear to aggravate abnormal TS or DNIC mechanisms in CTH-S.

Development of ITS sequence based molecular marker to distinguish, Tribulus terrestris L. (Zygophyllaceae) from its adulterants.

PubMed

Balasubramani, Subramani Paranthaman; Murugan, Ramar; Ravikumar, Kaliamoorthy; Venkatasubramanian, Padma

2010-09-01

Tribulus terrestris L. (Zygophyllaceae) is one of the highly traded raw drugs and also used as a stimulative food additive in Europe and USA. While, Ayurvedic Pharmacopoeia of India recognizes T. terrestris as Goksura, Tribulus lanuginosus and T. subramanyamii are also traded by the same name raising issues of quality control. The nuclear ribosomal RNA genes and ITS (internal transcribed spacer) sequence were used to develop species-specific DNA markers. The species-specific markers efficiently amplified 295bp for T. terrestris (TT1F and TT1R), 300bp for T. lanuginosus (TL1F and TL1R) and 214bp for T. subramanyamii (TS1F and TS1R). These DNA markers can be used to distinguish T. terrestris from its adulterants. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Treatment with Biologicals in Rheumatoid Arthritis: An Overview.

PubMed

Rein, Philipp; Mueller, Ruediger B

2017-12-01

Management and therapy of rheumatoid arthritis (RA) has been revolutionized by the development and approval of the first biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumor necrosis factor (TNF) α at the end of the last century. Today, numerous efficacious agents with different modes of action are available and achievement of clinical remission or, at least, low disease activity is the target of therapy. Early therapeutic interventions aiming at a defined goal of therapy (treat to target) are supposed to halt inflammation, improving symptoms and signs, and preserving structural integrity of the joints in RA. Up to now, bDMARDs approved for therapy in RA include agents with five different modes of action: TNF inhibition, T cell co-stimulation blockade, IL-6 receptor inhibition, B cell depletion, and interleukin 1 inhibition. Furthermore, targeted synthetic DMARDs (tsDMARDs) inhibiting Janus kinase (JAK) and biosimilars also are approved for RA. The present review focuses on bDMARDs and tsDMARDS regarding similarities and possible drug-specific advantages in the treatment of RA. Furthermore, compounds not yet approved in RA and biosimilars are discussed. Following the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) recommendations, specific treatment of the disease will be discussed with respect to safety and efficacy. In particular, we discuss the question of favoring specific bDMARDs or tsDMARDs in the two settings of insufficient response to methotrexate and to the first bDMARD, respectively.

Evaluation of Biological Activity of Mastic Extracts Based on Chemotherapeutic Indices

PubMed Central

SUZUKI, RYUICHIRO; SAKAGAMI, HIROSHI; AMANO, SHIGERU; FUKUCHI, KUNIHIKO; SUNAGA, KATSUYOSHI; KANAMOTO, TAISEI; TERAKUBO, SHIGEMI; NAKASHIMA, HIDEKI; SHIRATAKI, YOSHIAKI; TOMOMURA, MINEKO; MASUDA, YOSHIKO; YOKOSE, SATOSHI; TOMOMURA, AKITO; WATANABE, HIROFUMI; OKAWARA, MASAKI; MATAHIRA, YOSHIHARU

2017-01-01

Background: Most previous mastic investigators have not considered its potent cytotoxicity that may significantly affect the interpretation of obtained data. In the present study, we re-evaluated several biological activities of mastic extracts, based on chemotherapeutic indexes. Materials and Methods: Pulverized mastic gum was extracted with n-hexane and then with ethyl acetate or independently with methanol or n-butanol. Tumor specificity (TS) of the extracts was determined by their cytotoxicity against human malignant and non-malignant cells. Antibacterial activity was determined by their cytotoxicity against bacteria and normal oral cells. Antiviral activity was determined by their protection of viral infection and cytotoxic activity. Cytochrome P-450 (CYP) 3A4 activity was measured by β-hydroxylation of testosterone. Results: Ethyl acetate extract showed slightly higher tumor specificity (TS=2.6) and one order higher antibacterial activity (selectivity index (SI)=0.813) than other extracts (TS=1.4-2.5; SI=0.030-0.063). All extracts showed no anti-human immunodeficiency virus (HIV) activity, but some anti-herpes simplex virus (HSV) activity, which was masked by potent cytotoxicity. They showed strong inhibitory activity against CYP3A4. Conclusion: Ethyl acetate extraction following the removal of cytotoxic and CYP3A4 inhibitory substances by n-hexane can enhance antitumor and antibacterial activity of mastic. PMID:28652425

Tourette Syndrome and Chronic Tic Disorders: The Clinical Spectrum Beyond Tics.

PubMed

Martino, Davide; Ganos, Christos; Pringsheim, Tamara M

2017-01-01

The clinical surveillance and active management of Tourette syndrome (TS) and other primary chronic tic disorders cannot be limited to tics, as these patients manifest a spectrum of sensory-, behavioral-, cognitive-, and sleep-related problems that have a major impact on their functioning and quality of life, influencing enormously clinical decision making on a routine basis. The sensory phenomena of primary tic disorders consist of premonitory urges and heightened sensitivity to external somatosensory and interoceptive stimuli. Recent evidence suggests that raised interoceptive awareness may be related to the classical premonitory urges associated with tics. The burden of behavioral comorbidities is very important in determining the degree of disability of patients with primary tic disorders. Only 10%-15% of these patients presents exclusively with a tic disorder. Obsessive-compulsive disorder (OCD) are common in TS, and the clinical distinction between compulsions and complex tics may be difficult in some cases. "Tic-related OCD" represents a phenomenologically characteristic subtype of OCD, also associated with "just right" phenomena. Probably the presence of comorbid attention deficit/hyperactivity disorder is the main determinant of cognitive dysfunction in TS patients and influences heavily also the risk of developing disruptive behaviors. Mood and anxiety disorders, impulse control disorders, rage attacks, "impulsive" tic-like behaviors (e.g., nonobscene socially inappropriate behaviors, and self-injurious behaviors), and autism spectrum disorders complete the wide psychopathological spectrum of primary chronic tic disorders. Moreover, specific sleep abnormalities have been reported in TS patients, although more research is needed on this specific clinical problem. As in other areas of clinical neuroscience, a comprehensive approach to both motor and nonmotor aspects of this group of disorders will help personalizing treatment interventions and, ultimately, improve quality of care. © 2017 Elsevier Inc. All rights reserved.

[Mobile geriatric rehabilitation in nursing homes, in short-term care facilities and private homes : Setting-specific analysis of nationwide treatment documentation (Part 2)].

PubMed

Pippel, Kristina; Meinck, M; Lübke, N

2017-06-01

Mobile geriatric rehabilitation can be provided in the setting of nursing homes, short-term care (STC) facilities and exclusively in private homes. This study analyzed the common features and differences of mobile rehabilitation interventions in various settings. Stratified by setting 1,879 anonymized mobile geriatric rehabilitation treatments between 2011 and 2014 from 11 participating institutions were analyzed with respect to patient, process and outcome-related features. Significant differences between the settings nursing home (n = 514, 27 %), STC (n = 167, 9 %) and private homes (n = 1198, 64 %) were evident for mean age (83 years, 83 years and 80 years, respectively), percentage of women (72 %, 64 % and 55 %), degree of dependency on pre-existing care (92 %, 76 % and 64 %), total treatment sessions (TS, 38 TS, 42 TS and 41 TS), treatment duration (54 days, 61 days and 58 days) as well as the Barthel index at the start of rehabilitation (34 points, 39 points and 46 points) and the gain in the Barthel index (15 points, 21 points and 18 points), whereby the gain in the capacity for self-sufficiency was significant in all settings. The setting-specific evaluation of mobile geriatric rehabilitation showed differences for relevant patient, process and outcome-related features. Compared to inpatient rehabilitation mobile rehabilitation in all settings made an above average contribution to the rehabilitation of patients with pre-existing dependency on care. The gains in the capacity for self-sufficiency achieved in all settings support the efficacy of mobile geriatric rehabilitation under the current prerequisites for applicability.

Neuropsychiatric Disorders Associated with Streptococcal Infection: A Case-Control Study among Privately Insured Children

PubMed Central

Leslie, Douglas L.; Kozma, Laura; Martin, Andrés; Landeros, Angeli; Katsovich, Liliya; King, Robert A.; Leckman, James F.

2009-01-01

Objective To assess whether antecedent streptococcal infection(s) increase the risk of subsequent diagnosis of obsessive-compulsive disorder (OCD), Tourette's syndrome (TS), other tic disorders, attention deficit hyperactivity disorder (ADHD) or major depressive disorder (MDD) in a national sample of privately insured children. Method Using health insurance claims data, we compared the prior-year occurrence of streptococcal infection in children aged 4–13 years with OCD, TS or tic disorder newly diagnosed between January 1998 and December 2004 to that of a cohort of matched controls. Conditional logistic regression models were used to determine the association of prior streptococcal sore throat or scarlet fever with a diagnosis of OCD, TS, or tic disorder. We repeated the analyses for two other infectious diseases (otitis media and sinusitis) and one non-infectious condition (migraine). We also investigated the potential specificity of this association by performing similar analyses focused on newly diagnosed attention deficit hyperactivity disorder (ADHD) and newly diagnosed major depressive disorder (MDD). Results Subjects with newly diagnosed OCD, TS, or tic disorder were more likely than controls to have had a diagnosis of streptococcal infection in the previous year (OR: 1.54, 95% CI: 1.29, 2.15). Prior streptococcal infection was also associated with incident diagnoses of ADHD (OR: 1.20, 95% CI: 1.06, 1.35) and MDD (OR=1.63, 95% CI: 1.12, 2.30). Conclusions These findings provide epidemiologic evidence that some pediatric onset neuropsychiatric disorders, including OCD, tic disorders, ADHD and MDD, may be temporally related to prior streptococcal infections. Whether this is the result of a non-specific stress response or secondary to an activation of the immune system remains to be determined. PMID:18724258

Anti-Taenia solium monoclonal antibodies for the detection of parasite antigens in body fluids from patients with neurocysticercosis.

PubMed

Paredes, Adriana; Sáenz, Patricia; Marzal, Miguel W; Orrego, Miguel A; Castillo, Yesenia; Rivera, Andrea; Mahanty, Siddhartha; Guerra-Giraldez, Cristina; García, Hector H; Nash, Theodore E

2016-07-01

Neurocysticercosis (NCC), an infection of the brain by Taenia solium (Ts) cysts, is the most common cause of adult-onset epilepsy in developing countries. Serological testing consists primarily of varying methods to detect antibodies in body fluids and more recently antigen (Ag) detection assays to identify individuals or animals with viable parasites. Antigen assays currently in use employ monoclonal antibodies (mAbs) raised against T. saginata, which have known cross reactivity to animal cestodes but are highly specific in human samples. We produced, characterized and tested 21 mAbs raised against T. solium whole cyst antigens, vesicular fluid or excretory secretory products. Reactivity of the TsmAbs against specific cyst structures was determined using immunofluorescence and immunohistochemistry on histological sections of Ts muscle cysts. Four TsmAbs reacted to vesicular space alone, 9 to the neck and cyst wall, one to the neck and vesicular space and 7 to the neck, cyst wall and vesicular space. An in-house ELISA assay to detect circulating Ts antigen, using the TsmAbs as capture antibodies and a rabbit polyclonal anti-Ts whole cyst antibody as a detector antibody demonstrated that eight of the 21 TsmAbs detected antigens in known NCC-positive human sera and three of these also in urine samples. Reactivity was expressed as normalized ratios of optical densities (OD positive control/OD negative control). Three TsmAbs had ratios >10 and five between 2 and 10. The TsmAbs have potential utility for the diagnosis and post-treatment monitoring of patients with viable NCC infections. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis of mesoporous TS-1 using a hybrid SiO{sub 2}–TiO{sub 2} xerogel for catalytic oxidative desulfurization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Seung-Tae; Jeong, Kwang-Eun; Jeong, Soon-Yong

2012-12-15

Graphical abstract: Display Omitted Highlights: ► Meso-TS-1 catalyst was synthesized using a SiO{sub 2}–TiO{sub 2} xerogel with an organosilane precursor. ► Hierarchical pore structure was confirmed by characterization of the materials. ► Catalytic activity was tested using oxidative desulfurization of the model sulfur compounds. ► Meso-TS-1 demonstrated significantly improved catalytic activity than TS-1. -- Abstract: Mesoporous TS-1 (M-TS-1) was synthesized using a hybrid SiO{sub 2}–TiO{sub 2} xerogel combined with an organosilane precursor. Prepared samples were characterized by XRD, UV–vis spectroscopy, SEM, and N{sub 2} adsorption–desorption measurement. M-TS-1, prepared in 2 days, showed high crystallinity and the best textural properties amongmore » the samples. The N{sub 2} adsorption–desorption isotherms of M-TS-1 exhibited a hysteresis loop at pressure higher than P/P{sub 0} = 0.4, clearly indicating the existence of mesopores. M-TS-1 has significantly larger mesopore volume (0.48 cm{sup 3}/g) than that of conventional TS-1 (0.07 cm{sup 3}/g), and showed a narrow peak centered at ca. 6.3 nm. In the oxidative desulfurization reaction, M-TS-1 was more active than conventional TS-1 at the same Ti-loading; M-TS-1 produced a dibenzothiophene (DBT) conversion of 96%, whereas conventional TS-1 produced a final DBT conversion of 5.6% after a reaction time of 180 min. Oxidative desulfurization over TS-1 was influenced both by electron density and steric hindrance in the sulfur compounds tested.« less

Standardizing procedures to study sensitization of human spinal nociceptive processes: comparing parameters for temporal summation of the nociceptive flexion reflex (TS-NFR).

PubMed

Terry, Ellen L; France, Christopher R; Bartley, Emily J; Delventura, Jennifer L; Kerr, Kara L; Vincent, Ashley L; Rhudy, Jamie L

2011-09-01

Temporal summation of pain (TS-pain) is the progressive increase in pain ratings during a series of noxious stimulations. TS-pain has been used to make inferences about sensitization of spinal nociceptive processes; however, pain report can be biased thereby leading to problems with this inference. Temporal summation of the nociceptive flexion reflex (TS-NFR, a physiological measure of spinal nociception) can potentially overcome report bias, but there have been few attempts (generally with small Ns) to standardize TS-NFR procedures. In this study, 50 healthy participants received 25 series of noxious electric stimulations to evoke TS-NFR and TS-pain. Goals were to: 1) determine the stimulation frequency that best elicits TS-NFR and reduces electromyogram (EMG) contamination from muscle tension, 2) determine the minimum number of stimulations per series before NFR summation asymptotes, 3) compare NFR definition intervals (90-150ms vs. 70-150ms post-stimulation), and 4) compare TS-pain and TS-NFR when different stimulation frequencies are used. Results indicated TS-NFR should be elicited by a series of three stimuli delivered at 2.0Hz and TS-NFR should be defined from a 70-150ms post-stimulation scoring interval. Unfortunately, EMG contamination from muscle tension was greatest during 2.0Hz series. Discrepancies were noted between TS-NFR and TS-pain which raise concerns about using pain ratings to infer changes in spinal nociceptive processes. And finally, some individuals did not have reliable NFRs when the stimulation intensity was set at NFR threshold during TS-NFR testing; therefore, a higher intensity is needed. Implications of findings are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of teeth clenching on the soleus H reflex during lower limb muscle fatigue.

PubMed

Mitsuyama, Akihiro; Takahashi, Toshiyuki; Ueno, Toshiaki

2017-04-01

We assessed whether the soleus H reflex was depressed or facilitated in association with voluntary teeth clenching during muscle fatigue. A total of 13 and 9 healthy adult subjects were instructed to perform right-side tiptoe standing for 5 (TS1) and 10min (TS2) to induce the soleus muscle fatigue. Electromyograms (EMGs) were recorded from the bilateral masseter as well as the right-side soleus muscles. H reflex was evoked using a surface electrode. The isometric muscle strength during plantar flexion was measured. We tested two dental occlusal conditions (1) with maximal voluntary teeth clenching (MVTC) and (2) at mandibular rest position (RP). H reflex was evoked before and after TS1 and TS2. The isometric muscle strength during plantar flexion was measured before and after TS1 and TS2. Mean amplitudes of H reflex with MVTC before and after TS1 were significantly larger than that with RP before and after TS1. The mean peak torque (PT) during isometric plantar flexion was observed significant differences in all subjects. The mean amplitude of H reflex with MVTC before TS2 was significantly larger than that with RP before TS2. No significant difference between RP after TS2 and MVTC after TS2. The mean PT with MVTC before TS2 was significantly larger than that with RP before TS2. There was no significant difference between RP and MVTC after TS2. The present study demonstrated that teeth clenching could facilitate H reflex regardless of the degree of muscle fatigue. Copyright © 2016 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

A population-based analysis of mortality in patients with Turner syndrome and hypoplastic left heart syndrome using the Texas Birth Defects Registry.

PubMed

Lara, Diego A; Ethen, Mary K; Canfield, Mark A; Nembhard, Wendy N; Morris, Shaine A

2017-01-01

Hypoplastic left heart syndrome (HLHS) is strongly associated with Turner syndrome (TS); outcome data when these conditions coexist is sparse. We aimed to investigate long-term survival and causes of death in this population. The Texas Birth Defects Registry was queried for all live born infants with HLHS during 1999-2007. We used Kaplan-Meier and Cox regression analyses to compare survival among patients with HLHS with TS (HLHS/TS+) to patients who had HLHS without genetic disorders or extracardiac birth defects (HLHS/TS-). Of the 542 patients with HLHS, 11 had TS (2.0%), 71 had other extracardiac birth defects or genetic disorders, and 463 had neither. The median follow-up time was 4.2 y (interquartile range [IQR] 2.1-6.5). Comparing those with HLHS/TS+ to HLHS/TS-, 100% versus 35% were female (P < .001), and median birth weight was 2140 g (IQR 1809-2650) versus 3196 g (IQR 2807-3540, P < .001). Neonatal mortality was 36% in HLHS/TS+ versus 27% in HLHS/TS- (log rank = 0.431). Ten of the 11 TS+ patients died during the study period for cumulative mortality of 91% versus 50% (hazard ratio (HR) for TS+: 2.90, 95% CI 1.53-5.48). Six patients died prior to surgery, 5 underwent Stage 1 palliation (S1P), 3 died after S1P, 2 survived past S2P, and one of these died at age 19 mo. The underlying cause of death was listed as congenital heart disease on all the death certificates of HLHS/TS+ patients. In multivariable analysis controlling for low birth weight (<2500 g), TS remained associated with significantly increased cumulative mortality, although females without TS had higher mortality than males (HR for TS+ versus males: 2.42, 95% CI 1.24-4.73; HR for TS- females versus males: 1.41, 95% CI 1.08-1.83). TS with HLHS is associated with significant mortality. The increased mortality in females without documented TS calls to question if TS is undetected in a portion of females with HLHS. © 2016 Wiley Periodicals, Inc.

Total solids content drives high solid anaerobic digestion via mass transfer limitation.

PubMed

Abbassi-Guendouz, Amel; Brockmann, Doris; Trably, Eric; Dumas, Claire; Delgenès, Jean-Philippe; Steyer, Jean-Philippe; Escudié, Renaud

2012-05-01

The role of the total solids (TS) content on anaerobic digestion was investigated in batch reactors. A range of TS contents from 10% to 35% was evaluated, four replicates were performed. The total methane production slightly decreased with TS concentrations increasing from 10% to 25% TS. Two behaviors were observed at 30% TS: two replicates had similar performances to that at 25% TS; for the two other replicates, the methane production was inhibited as observed at 35% TS. This difference suggested that 30% TS content corresponded to a threshold of the solids content, above which methanogenesis was strongly inhibited. The Anaerobic Digestion Model No. 1 (ADM1) was used to describe the experimental data. The effects of hydrolysis step and liquid/gas mass transfer were particularly investigated. The simulations showed that mass transfer limitation could explain the low methane production at high TS, and that hydrolysis rate constants slightly decreased with increasing TS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tic Related Activity Restriction as a Predictor of Emotional Functioning and Quality of Life

PubMed Central

Conelea, Christine A.; Busch, Andrew M.; Catanzaro, Mark A.; Budman, Cathy L.

2013-01-01

Objectives Tourette Syndrome (TS) is a chronic neuropsychiatric condition that frequently persists into adulthood. Existing research has identified demographic and symptom-level variables associated with psychopathology and poor quality of life in TS. However, behavior patterns associated with enhanced or adaptive psychological and global functioning among adults with TS have yet to be empirically identified. The current study examined whether tic-specific activity restriction is related to emotional functioning and quality of life in adults with TS. Methods Participants were 509 adults from the Tourette Syndrome Impact Survey who completed self-report measures of demographics, tic severity, emotional functioning, quality of life, and tic related general and social activity restriction. Results Partial correlations controlling for tic severity indicated that tic related general and social activity restriction were significantly correlated with lower quality of life and poorer emotional functioning. Hierarchical linear regression models indicated that activity restriction significantly predicted lower quality of life and poorer emotional functioning when controlling for tic severity and demographic variables. Conclusions Adults who restrict fewer activities due to tics, regardless of tic severity, experience greater quality of life and better emotional functioning. Clinically, adults with chronic tics may benefit from interventions focused on enhancing engagement in valued life activities. PMID:24156871

Synergism and foaming properties in binary mixtures of a biosurfactant derived from Camellia oleifera Abel and synthetic surfactants.

PubMed

Jian, Hong-lei; Liao, Xiao-xia; Zhu, Li-wei; Zhang, Wei-ming; Jiang, Jian-xin

2011-07-15

A biosurfactant, named tea saponin (TS), was isolated and purified from the defatted seed of Camellia oleifera Abel. The characterization of TS including molecular weight, glycosyl composition, and thermal behavior as well as the surface and foaming properties was conducted. The synergistic interactions of binary systems of CTAB-TS, SDS-TS, and Brij35-TS were investigated. The results show that TS had a weight-average molecular weight of 809.12 g mol(-1) and contained four aglycones of L-rhamnose, D-galactose, D-glucose, and D-glucuronic acid. The critical micelle concentration (cmc) of 2.242 mmol L(-1) and the minimum surface tension (γ(cmc)) of 43.5 mN m(-1) were determined for TS. Synergisms in surface tension reduction efficiency, in mixed micelle formation, and in surface tension reduction effectiveness were observed in CTAB-TS and SDS-TS systems, whereas that was not shown in Brij35-TS mixtures. The mixtures of TS with CTAB and SDS showed synergism in foaming efficiency, but this synergism did not exist in Brij35-TS system with respect to the surface properties. Nevertheless, there appears to be no significant correlation between foam stability and the surface properties. Copyright © 2011 Elsevier Inc. All rights reserved.

Are there distinct subtypes in Tourette syndrome? Pure-Tourette syndrome versus Tourette syndrome-plus, and simple versus complex tics

PubMed Central

Eapen, Valsamma; Robertson, Mary M

2015-01-01

This study addressed several questions relating to the core features of Tourette syndrome (TS) including in particular coprolalia (involuntary utterance of obscene words) and copropraxia (involuntary and inappropriate rude gesturing). A cohort of 400 TS patients was investigated. We observed that coprolalia occurred in 39% of the full cohort of 400 patients and copropraxia occurred in 20% of the cohort. Those with coprolalia had significantly higher Yale Global Tic Severity Scale (YGTSS) and Diagnostic Confidence Index (DCI) total scores and a significantly higher proportion also experienced copropraxia and echolalia. A subgroup of 222 TS patients with full comorbidity data available were also compared based on whether they had pure-TS (motor and vocal tics only) or associated comorbidities and co-existent psychopathologies (TS-plus). Pure-TS and TS-plus groups were compared across a number of characteristics including TS severity, associated clinical features, and family history. In this subgroup, 13.5% had pure-TS, while the remainder had comorbidities and psychopathologies consistent with TS-plus. Thirty-nine percent of the TS-plus group displayed coprolalia, compared to (0%) of the pure-TS group and the difference in proportions was statistically significant. The only other significant difference found between the two groups was that pure-TS was associated with no family history of obsessive compulsive disorder which is an interesting finding that may suggest that additional genes or environmental factors may be at play when TS is associated with comorbidities. Finally, differences between individuals with simple versus complex vocal/motor tics were evaluated. Results indicated that individuals with complex motor/vocal tics were significantly more likely to report premonitory urges/sensations than individuals with simple tics and TS. The implications of these findings for the assessment and understanding of TS are discussed. PMID:26089672

Therapeutic potential of larval excretory/secretory proteins of the pig whipworm Trichuris suis in allergic disease.

PubMed

Ebner, F; Hepworth, M R; Rausch, S; Janek, K; Niewienda, A; Kühl, A; Henklein, P; Lucius, R; Hamelmann, E; Hartmann, S

2014-11-01

Gastrointestinal nematodes are currently being evaluated as a novel therapeutic in the treatment of chronic human inflammatory disorders, due to their unique ability to induce immunoregulatory pathways in their hosts. In particular, administration of ova from the pig whipworm Trichuris suis (T. suis; TSO) has been proposed for the treatment of allergic, inflammatory and autoimmune disorders. Despite these advances, the biological pathways through which TSO therapy modulates the host immune system in the context of human disease remain undefined. We characterized the dominant proteins present in the excretory/secretory (E/S) products of first-stage (L1) T. suis larvae (Ts E/S) using LC-MS/MS analysis and examined the immunosuppressive properties of whole larval Ts E/S in vitro and in a murine model of allergic airway disease. Administration of larval Ts E/S proteins in vivo during the allergen sensitization phase was sufficient to suppress airway hyperreactivity, bronchiolar inflammatory infiltrate and allergen-specific IgE production. Three proteins in larval Ts E/S were unambiguously identified. The immunomodulatory function of larval Ts E/S was found to be partially dependent on the immunoregulatory cytokine IL-10. Taken together, these data demonstrate that the released proteins of larval T. suis have significant immunomodulatory capacities and efficiently dampen allergic airway hyperreactivity. Thus, the therapeutic potential of defined larval E/S proteins should be exploited for the treatment of human allergic disorders. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

New Late Gene, dar, Involved in DNA Replication of Bacteriophage T4 I. Isolation, Characterization, and Genetic Location.

PubMed

Wu, J R; Yeh, Y C

1975-05-01

Suppressors of gene 59-defective mutants were isolated by screening spontaneous, temperature-sensitive (ts) revertants of the amber mutant, amC5, in gene 59. Six ts revertants were isolated. No gene 59-defective ts recombinant was obtained by crossing each ts revertant with the wild type, T4D. However, suppressors of gene 59-defective mutants were obtained from two of these ts revertants. These suppressor mutants are referred to as dar (DNA arrested restoration). dar mutants specifically restored the abnormalities, both in DNA synthesis and burst size, caused by gene 59-defective mutants to normal levels. It is unlikely that dar mutants are nonsense suppressors since theý failed to suppress amber mutations in 11 other genes investigated. The genetic expression of dar is controlled by gene 55; therefore, dar is a late gene. The genetic location of dar has been mapped between genes 24 and 25, a region contiguous to late genes. dar appears to be another nonessential gene of T4 since burst sizes of dar were almost identical to those of the wild type. Mutations in dar did not affect genetic recombination and repair of UV-damaged DNA, but caused a sensitivity to hydroxyurea in progeny formation. The effect of the dar mutation on host DNA degradation cannot account for its hydroxyurea sensitivity. dar mutant alleles were recessive to the wild-type allele as judged by restoration of arrested DNA synthesis. The possible mechanisms for the suppression of defects in gene 59 are discussed.

Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study

PubMed Central

McGrath, Lauren M.; Yu, Dongmei; Marshall, Christian; Davis, Lea K.; Thiruvahindrapuram, Bhooma; Li, Bingbin; Cappi, Carolina; Gerber, Gloria; Wolf, Aaron; Schroeder, Frederick A.; Osiecki, Lisa; O’Dushlaine, Colm; Kirby, Andrew; Illmann, Cornelia; Haddad, Stephen; Gallagher, Patience; Fagerness, Jesen A.; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Cath, Danielle C.; Cavallini, Maria C.; Chouinard, Sylvain; Coric, Vladimir; Cullen, Bernadette; Delorme, Richard; Denys, Damiaan; Derks, Eske M.; Dion, Yves; Rosário, Maria C.; Eapen, Valsama; Evans, Patrick; Falkai, Peter; Fernandez, Thomas; Garrido, Helena; Geller, Daniel; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Heiman, Gary A.; Hemmings, Sian M.J.; Herrera, Luis D.; Hounie, Ana G.; Jankovic, Joseph; Kennedy, James L; King, Robert A.; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Lochner, Christine; Lowe, Thomas L.; Lyon, Gholson J.; Macciardi, Fabio; Maier, Wolfgang; McCracken, James T.; McMahon, William; Murphy, Dennis L.; Naarden, Allan L; Neale, Benjamin M; Nurmi, Erika; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark; Robertson, Mary M.; Rosenberg, David; Rouleau, Guy A.; Ruhrmann, Stephan; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Tischfield, Jay A.; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R.; Shugart, Yin Yao; Miguel, Euripedes C.; Nicolini, Humberto; Oostra, Ben A.; Moessner, Rainald; Wagner, Michael; Ruiz-Linares, Andres; Heutink, Peter; Nestadt, Gerald; Freimer, Nelson; Petryshen, Tracey; Posthuma, Danielle; Jenike, Michael A.; Cox, Nancy J.; Hanna, Gregory L.; Brentani, Helena; Scherer, Stephen W.; Arnold, Paul D.; Stewart, S. Evelyn; Mathews, Carol A.; Knowles, James A.; Cook, Edwin H.; Pauls, David L.; Wang, Kai; Scharf, Jeremiah M.

2014-01-01

Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable, neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method The primary analyses utilized a cross-disorder design for 2,699 patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p=.09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 patient deletions: 0 control deletions, p=0.08 in current study, p=0.025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support to the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in autism or schizophrenia (2–4%). Conclusion Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes. PMID:25062598

A Universal Ts-VI Triangle Method for the Continuous Retrieval of Evaporative Fraction From MODIS Products

NASA Astrophysics Data System (ADS)

Zhu, Wenbin; Jia, Shaofeng; Lv, Aifeng

2017-10-01

The triangle method based on the spatial relationship between remotely sensed land surface temperature (Ts) and vegetation index (VI) has been widely used for the estimates of evaporative fraction (EF). In the present study, a universal triangle method was proposed by transforming the Ts-VI feature space from a regional scale to a pixel scale. The retrieval of EF is only related to the boundary conditions at pixel scale, regardless of the Ts-VI configuration over the spatial domain. The boundary conditions of each pixel are composed of the theoretical dry edge determined by the surface energy balance principle and the wet edge determined by the average air temperature of open water. The universal triangle method was validated using the EF observations collected by the Energy Balance Bowen Ratio systems in the Southern Great Plains of the United States of America (USA). Two parameterization schemes of EF were used to demonstrate their applicability with Terra Moderate Resolution Imaging Spectroradiometer (MODIS) products over the whole year 2004. The results of this study show that the accuracy produced by both of these two parameterization schemes is comparable to that produced by the traditional triangle method, although the universal triangle method seems specifically suited to the parameterization scheme proposed in our previous research. The independence of the universal triangle method from the Ts-VI feature space makes it possible to conduct a continuous monitoring of evapotranspiration and soil moisture. That is just the ability the traditional triangle method does not possess.

Impact of Xist RNA on chromatin modifications and transcriptional silencing maintenance at different stages of imprinted X chromosome inactivation in vole Microtus levis.

PubMed

Shevchenko, Alexander I; Grigor'eva, Elena V; Medvedev, Sergey P; Zakharova, Irina S; Dementyeva, Elena V; Elisaphenko, Eugeny A; Malakhova, Anastasia A; Pavlova, Sophia V; Zakian, Suren M

2018-03-01

In vole Microtus levis, cells of preimplantation embryo and extraembryonic tissues undergo imprinted X chromosome inactivation (iXCI) which is triggered by a long non-coding nuclear RNA, Xist. At early stages of iXCI, chromatin of vole inactive X chromosome is enriched with the HP1 heterochromatin-specific protein, trimethylated H3K9 and H4K20 attributable to constitutive heterochromatin. In the study, using vole trophoblast stem (TS) cells as a model of iXCI, we further investigated chromatin of the inactive X chromosome of M. levis and tried to find out the role of Xist RNA. We demonstrated that chromatin of the inactive X chromosome in vole TS cells also contained the SETDB1 histone methyltransferase and KAP1 protein. In addition, we observed that Xist RNA did not contribute significantly to maintenance of X chromosome inactive state during iXCI in vole TS cells. Xist repression affected neither transcriptional silencing caused by iXCI nor maintenance of trimethylated H3K9 and H4K20 as well as HP1, KAP1, and SETDB1 on the inactive X chromosome. Moreover, the unique repertoire of chromatin modifications on the inactive X chromosome in vole TS cells could be disrupted by a chemical compound, DZNep, and then restored even in the absence of Xist RNA. However, Xist transcript was necessary for recruitment of an additional repressive histone modification, trimethylated H3K27, to the inactive X chromosome during vole TS cell differentiation.

From user needs to system specifications: multi-disciplinary thematic seminars as a collaborative design method for development of health information systems.

PubMed

Scandurra, I; Hägglund, M; Koch, S

2008-08-01

This paper presents a new multi-disciplinary method for user needs analysis and requirements specification in the context of health information systems based on established theories from the fields of participatory design and computer supported cooperative work (CSCW). Whereas conventional methods imply a separate, sequential needs analysis for each profession, the "multi-disciplinary thematic seminar" (MdTS) method uses a collaborative design process. Application of the method in elderly homecare resulted in prototypes that were well adapted to the intended user groups. Vital information in the points of intersection between different care professions was elicited and a holistic view of the entire care process was obtained. Health informatics-usability specialists and clinical domain experts are necessary to apply the method. Although user needs acquisition can be time-consuming, MdTS was perceived to efficiently identify in-context user needs, and transformed these directly into requirements specifications. Consequently the method was perceived to expedite the entire ICT implementation process.

Bearing-only Cooperative Localization: Simulation and Experimental Results

DTIC Science & Technology

2013-01-01

matrix Fi and Bi are the system jacobian with respect to state Xi and control ui, which are given below Fi = I3 + Ts ∂fi ∂Xi |Xi=Xi(k) =  1 0 − ViTs ...sinψ(k)0 1 ViTs cosψ(k) 0 0 1  , (8) Bi = Ts ∂fi ∂ui |ui=ui(k) Ts cosψk 0Ts sinψk 0 0 Ts  , (9) and Qi(k) = ( σ2vi 0 0 σ2ωi ) , where σvi and σωi

Effect of Hammerhead Ribozyme against Human Thymidylate Synthase on the Cytotoxicity of Thymidylate Synthase Inhibitors

PubMed Central

Takemura, Yuzuru; Miyachi, Hayato; Skelton, Lorraine; Jackman, Ann L.

1995-01-01

One of the resistance mechanisms to folate‐based thymidylate synthase (TS) inhibitors is the increase in TS activity in tumor cells. Human B lymphoblastoid cell line (W1L2) was made resistant to a lipophilic non‐polyglutamatable TS inhibitor (ZM249148), and the subline (W1L2:R179) showed a 20‐fold increase in TS enzyme activity with concomitant overexpression of TS mRNA. To overcome the resistance, we designed a ribozyme that can cleave the CUC sequences in a triple tandemly repeated sequence of TS mRNA. Expression of this ribozyme in W1L2:R179 cells transfected with Epstein Barr virus‐based expression vector resulted in sensitization to TS inhibitors concomitantly with a decrease of TS expression. The ribozyme expressed in transfectants was shown to be functional in cleaving artificial TS RNA in vitro. PMID:8567390

A New Green Ionic Liquid-Based Corrosion Inhibitor for Steel in Acidic Environments.

PubMed

Atta, Ayman M; El-Mahdy, Gamal A; Al-Lohedan, Hamad A; Ezzat, Abdel Rahman O

2015-06-17

This work examines the use of new hydrophobic ionic liquid derivatives, namely octadecylammonium tosylate (ODA-TS) and oleylammonium tosylate (OA-TS) for corrosion protection of steel in 1 M hydrochloric acid solution. Their chemical structures were determined from NMR analyses. The surface activity characteristics of the prepared ODA-TS and OA-TS were evaluated from conductance, surface tension and contact angle measurements. The data indicate the presence of a double bond in the chemical structure of OA-TS modified its surface activity parameters. Potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) measurements, scanning electron microscope (SEM), Energy dispersive X-rays (EDX) analysis and contact angle measurements were utilized to investigate the corrosion protection performance of ODA-TS and OA-TS on steel in acidic solution. The OA-TS and ODA-TS compounds showed good protection performance in acidic chloride solution due to formation of an inhibitive film on the steel surface.

Addressing the Complexity of Tourette's Syndrome through the Use of Animal Models

PubMed Central

Nespoli, Ester; Rizzo, Francesca; Boeckers, Tobias M.; Hengerer, Bastian; Ludolph, Andrea G.

2016-01-01

Tourette's syndrome (TS) is a neurodevelopmental disorder characterized by fluctuating motor and vocal tics, usually preceded by sensory premonitions, called premonitory urges. Besides tics, the vast majority—up to 90%—of TS patients suffer from psychiatric comorbidities, mainly attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The etiology of TS remains elusive. Genetics is believed to play an important role, but it is clear that other factors contribute to TS, possibly altering brain functioning and architecture during a sensitive phase of neural development. Clinical brain imaging and genetic studies have contributed to elucidate TS pathophysiology and disease mechanisms; however, TS disease etiology still is poorly understood. Findings from genetic studies led to the development of genetic animal models, but they poorly reflect the pathophysiology of TS. Addressing the role of neurotransmission, brain regions, and brain circuits in TS disease pathomechanisms is another focus area for preclinical TS model development. We are now in an interesting moment in time when numerous innovative animal models are continuously brought to the attention of the public. Due to the diverse and largely unknown etiology of TS, there is no single preclinical model featuring all different aspects of TS symptomatology. TS has been dissected into its key symptomst hat have been investigated separately, in line with the Research Domain Criteria concept. The different rationales used to develop the respective animal models are critically reviewed, to discuss the potential of the contribution of animal models to elucidate TS disease mechanisms. PMID:27092043

Allium compounds, dipropyl and dimethyl thiosulfinates as antiproliferative and differentiating agents of human acute myeloid leukemia cell lines.

PubMed

Merhi, Faten; Auger, Jacques; Rendu, Francine; Bauvois, Brigitte

2008-12-01

Epidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML) display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS), diallyl TS (All(2)TS), dipropyl TS (Pr(2)TS) and dimethyl TS (Me(2)TS), are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6) in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide). As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr(2)TS and Me(2)TS, but not All(2)TS and sulfides, 1) inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2) induced macrophage maturation, and 3) inhibited the levels of secreted MMP-9 (protein and activity) and TNF-alpha protein, without altering mRNA levels. By establishing for the first time that Pr(2)TS and Me(2)TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML.

Association of thymidylate synthase gene 3'-untranslated region polymorphism with sensitivity of non-small cell lung cancer to pemetrexed treatment: TS gene polymorphism and pemetrexed sensitivity in NSCLC.

PubMed

Wang, Xia; Wang, Yadi; Wang, Yue; Cheng, Jian; Wang, Yanyun; Ha, Minwen

2013-01-25

Thymidylate synthase (TS) is a key enzyme responsible for DNA synthesis and repair. Altered expression of TS protein or TS gene polymorphisms has been associated with cancer progression and treatment response. This study investigated the expressions of TS and its gene SNPs in non-small cell lung cancer (NSCLC), and then its association with sensitivity to pemetrexed treatment. Immunohistochemistry and qRT-PCR were performed on 160 resected NSCLC specimens and corresponding normal tissues to assess the expressions of TS protein and TS mRNA, and for associations with clinicopathological data. Blood samples of 106 lung adenocarcinoma patients were examined for polymorphisms of the TS gene 3'-UTR 1494del 6 bp, which was then investigated for associations with responses of the patients to pemetrexed treatment and survival. Expression of both TS protein and its mRNA was elevated in NSCLC tissues compared with matched normal tissues, and significantly higher in lung squamous cell carcinoma than in lung adenocarcinoma. TS expression was associated with poor tumor differentiation. Furthermore, the genotyping data showed that 56% of lung adenocarcinoma patients had the TS gene 3'-UTR 1494 bp (-6 bp/-6 bp) genotype and the rest had TS gene 3'-UTR 1494 bp (-6 bp/+6 bp). There was no TS 3'-UTR 1494 bp (+6 bp/+6 bp) genotype in any patients. Statistical analysis revealed that gender, tumor stage, and TS 3'-UTR 1494del 6 bp polymorphism were significant prognostic factors after short-term pemetrexed treatment. Log-rank analysis revealed that patients with the (-6 bp/-6 bp) genotype had significantly better progression-free and overall survival than patients with (-6 bp/+6 bp). This study showed that TS protein is highly expressed in NSCLC and that polymorphisms of TS 3'-UTR 1494del 6 bp are associated with sensitivity of lung adenocarcinoma patients to pemetrexed treatment. This suggests that TS gene polymorphisms should be further evaluated as prognostic markers for personalized therapy in lung adenocarcinoma.

Anaerobic biodegradability of Category 2 animal by-products: methane potential and inoculum source.

PubMed

Pozdniakova, Tatiana A; Costa, José C; Santos, Ricardo J; Alves, M M; Boaventura, Rui A R

2012-11-01

Category 2 animal by-products that need to be sterilized with steam pressure according Regulation (EC) 1774/2002 are studied. In this work, 2 sets of experiments were performed in mesophilic conditions: (i) biomethane potential determination testing 0.5%, 2.0% and 5.0% total solids (TS), using sludge from the anaerobic digester of a wastewater treatment plant as inoculum; (ii) biodegradability tests at a constant TS concentration of 2.0% and different inoculum sources (digested sludge from a wastewater treatment plant; granular sludge from an upflow anaerobic sludge blanket reactor; leachate from a municipal solid waste landfill; and sludge from the slaughterhouse wastewater treatment anaerobic lagoon) to select the more adapted inoculum to the substrate in study. The higher specific methane production was of 317 mL CH(4)g(-1) VS(substrate) for 2.0% TS. The digested sludge from the wastewater treatment plant led to the lowest lag-phase period and higher methane potential rate. Copyright © 2012 Elsevier Ltd. All rights reserved.

Temperature-sensitive mutations for live-attenuated Rift Valley fever vaccines: implications from other RNA viruses

PubMed Central

Nishiyama, Shoko; Ikegami, Tetsuro

2015-01-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to the African continent. RVF is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by the Rift Valley fever virus (RVFV: genus Phlebovirus, family Bunyaviridae). Vaccination is the only known effective strategy to prevent the disease, but there are no licensed RVF vaccines available for humans. A live-attenuated vaccine candidate derived from the wild-type pathogenic Egyptian ZH548 strain, MP-12, has been conditionally licensed for veterinary use in the U.S. MP-12 displays a temperature-sensitive (ts) phenotype and does not replicate at 41°C. The ts mutation limits viral replication at a specific body temperature and may lead to an attenuation of the virus. Here we will review well-characterized ts mutations for RNA viruses, and further discuss the potential in designing novel live-attenuated vaccines for RVF. PMID:26322023

Development and validation of the functional assessment of chronic illness therapy treatment satisfaction (FACIT TS) measures.

PubMed

Peipert, John D; Beaumont, Jennifer L; Bode, Rita; Cella, Dave; Garcia, Sofia F; Hahn, Elizabeth A

2014-04-01

To develop and validate a new functional assessment of chronic illness therapy (FACIT) measure of satisfaction with treatment for chronic illnesses such as cancer and HIV/AIDS. To define domains and generate items, a literature review informed creation of semi-structured interview guides for patients and an international expert panel of clinicians and researchers. Patients and experts also rated 15 areas of satisfaction for relevance. The final list of items underwent further refinement by the original expert panel and a new group of clinical experts. Items were tested in four studies (primarily lung cancer) and data were pooled for analysis. Exploratory and confirmatory factor analyses (CFA), and item response theory modeling were conducted to evaluate dimensionality. Internal consistency reliability and test-retest reliability were both evaluated. Validity was evaluated by correlating the FACIT subscale scores and measures of comparable concepts and by testing the scales' ability to distinguish people according to their overall treatment satisfaction. Two instruments were created: the FACIT TS-general (G), an overall evaluation of current treatment, and the FACIT TS-patient satisfaction (PS), a measure of patient satisfaction. CFA results were not optimal for a five-factor solution for PS. Internal consistency reliability met psychometric standards (≥0.70) for all PS subscales. Construct validity was established for the PS subscales: Physician Communication, Treatment Staff Communication, Technical Competence, Confidence and Trust, and Nurse Communication. The two instruments generated here offer a new way to assess several key dimensions of patient satisfaction with treatment, especially for people with lung cancer.

Two Stage Assessment of Thermal Hazard in An Underground Mine

NASA Astrophysics Data System (ADS)

Drenda, Jan; Sułkowski, Józef; Pach, Grzegorz; Różański, Zenon; Wrona, Paweł

2016-06-01

The results of research into the application of selected thermal indices of men's work and climate indices in a two stage assessment of climatic work conditions in underground mines have been presented in this article. The difference between these two kinds of indices was pointed out during the project entitled "The recruiting requirements for miners working in hot underground mine environments". The project was coordinated by The Institute of Mining Technologies at Silesian University of Technology. It was a part of a Polish strategic project: "Improvement of safety in mines" being financed by the National Centre of Research and Development. Climate indices are based only on physical parameters of air and their measurements. Thermal indices include additional factors which are strictly connected with work, e.g. thermal resistance of clothing, kind of work etc. Special emphasis has been put on the following indices - substitute Silesian temperature (TS) which is considered as the climatic index, and the thermal discomfort index (δ) which belongs to the thermal indices group. The possibility of the two stage application of these indices has been taken into consideration (preliminary and detailed estimation). Based on the examples it was proved that by the application of thermal hazard (detailed estimation) it is possible to avoid the use of additional technical solutions which would be necessary to reduce thermal hazard in particular work places according to the climate index. The threshold limit value for TS has been set, based on these results. It was shown that below TS = 24°C it is not necessary to perform detailed estimation.

78 FR 47010 - Proposed Safety Evaluation for Plant-Specific

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... to the existing SR on the reactor core isolation cooling system to maintain consistency within the... TS Bases are revised to reflect the change to the SRs. The proposed change captures the on-going...

Prenatal risk factors for Tourette Syndrome: a systematic review

PubMed Central

2014-01-01

Background Tourette Syndrome (TS) appears to be an inherited disorder, although genetic abnormalities have been identified in less than 1% of patients, and the mode of inheritance is uncertain. Many studies have investigated environmental factors that might contribute to the onset and severity of tics and associated comorbidities such as obsessive compulsive disorder (OCD) and attention deficit hyperactive disorder (ADHD). A systematic review and qualitative analysis were performed to provide a broad view of the association between pre- and perinatal factors and TS. Methods The Medline, Embase and PsycINFO databases were searched using terms specific to Tourette’s syndrome and keywords such as “pregnancy”, “prenatal”, “perinatal”, “birth” and “neonatal”. Studies were limited to studies on human subjects published in English or French through October 2012. Results 22 studies were included. Studies were of limited methodological quality, with most samples derived from specialty clinics, and most exposures ascertained retrospectively. The majority of the results for demographic factors of parents, including age, education, socioeconomic status, and marital status, revealed no significant association with the onset of TS, or the presence of comorbidity. Many factors were reported to be significantly associated with the onset of TS, the presence of comorbidity and symptom severity, but the most consistently reported factors were maternal smoking and low birth weight. Conclusions There are few studies evaluating the relationship between pre and perinatal events and TS, and existing studies have major limitations, including the use of clinic rather than epidemiologically derived samples, retrospective data collection on pre and perinatal events and multiple hypothesis testing without appropriate statistical correction. The mechanism by which prenatal and perinatal adversities could lead to TS onset or symptom severity is unknown, but may be related to changes in the dopaminergic system as a result of early brain injury. PMID:24479407

Experimental and Theoretical Approaches To Investigate the Immunogenicity of Taenia solium-Derived KE7 Antigen

PubMed Central

Bobes, Raúl J.; Navarrete-Perea, José; Ochoa-Leyva, Adrián; Anaya, Víctor Hugo; Hernández, Marisela; Cervantes-Torres, Jacquelynne; Estrada, Karel; Sánchez-Lopez, Filiberto; Soberón, Xavier; Rosas, Gabriela; Nunes, Cáris Maroni; García-Varela, Martín; Sotelo-Mundo, Rogerio Rafael; López-Zavala, Alonso Alexis; Gevorkian, Goar; Acero, Gonzalo; Laclette, Juan P.; Fragoso, Gladis

2017-01-01

ABSTRACT Taenia solium cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Taenia crassiceps. Both peptides have proven protective capacity against cysticercosis and are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated with membrane processes and may participate in several vital cell pathways. The aim of this study was to identify the T. solium KE7 (TsKE7) full-length protein and to determine its immunogenic properties. Recombinant TsKE7 (rTsKE7) was expressed in Escherichia coli Rosetta2 cells and used to obtain mouse polyclonal antibodies. Anti-rTsKE7 antibodies detected the expected native protein among the 350 spots developed from T. solium cyst vesicular fluid in a mass spectrometry-coupled immune proteomic analysis. These antibodies were then used to screen a phage-displayed 7-random-peptide library to map B-cell epitopes. The recognized phages displayed 9 peptides, with the consensus motif Y(F/Y)PS sequence, which includes YYYPS (named GK-1M, for being a GK-1 mimotope), exactly matching a part of GK-1. GK-1M was recognized by 58% of serum samples from cysticercotic pigs with 100% specificity but induced weak protection against murine cysticercosis. In silico analysis revealed a universal T-cell epitope(s) in native TsKE7 potentially capable of stimulating cytotoxic T lymphocytes and helper T lymphocytes under different major histocompatibility complex class I and class II mouse haplotypes. Altogether, these results provide a rationale for the efficacy of the KETc7, rTsKE7, and GK-1 peptides as vaccines. PMID:28923896

Experimental and Theoretical Approaches To Investigate the Immunogenicity of Taenia solium-Derived KE7 Antigen.

PubMed

Bobes, Raúl J; Navarrete-Perea, José; Ochoa-Leyva, Adrián; Anaya, Víctor Hugo; Hernández, Marisela; Cervantes-Torres, Jacquelynne; Estrada, Karel; Sánchez-Lopez, Filiberto; Soberón, Xavier; Rosas, Gabriela; Nunes, Cáris Maroni; García-Varela, Martín; Sotelo-Mundo, Rogerio Rafael; López-Zavala, Alonso Alexis; Gevorkian, Goar; Acero, Gonzalo; Laclette, Juan P; Fragoso, Gladis; Sciutto, Edda

2017-12-01

Taenia solium cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Taenia crassiceps Both peptides have proven protective capacity against cysticercosis and are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated with membrane processes and may participate in several vital cell pathways. The aim of this study was to identify the T. solium KE7 (TsKE7) full-length protein and to determine its immunogenic properties. Recombinant TsKE7 (rTsKE7) was expressed in Escherichia coli Rosetta2 cells and used to obtain mouse polyclonal antibodies. Anti-rTsKE7 antibodies detected the expected native protein among the 350 spots developed from T. solium cyst vesicular fluid in a mass spectrometry-coupled immune proteomic analysis. These antibodies were then used to screen a phage-displayed 7-random-peptide library to map B-cell epitopes. The recognized phages displayed 9 peptides, with the consensus motif Y(F/Y)PS sequence, which includes YYYPS (named GK-1M, for being a GK-1 mimotope), exactly matching a part of GK-1. GK-1M was recognized by 58% of serum samples from cysticercotic pigs with 100% specificity but induced weak protection against murine cysticercosis. In silico analysis revealed a universal T-cell epitope(s) in native TsKE7 potentially capable of stimulating cytotoxic T lymphocytes and helper T lymphocytes under different major histocompatibility complex class I and class II mouse haplotypes. Altogether, these results provide a rationale for the efficacy of the KETc7, rTsKE7, and GK-1 peptides as vaccines. Copyright © 2017 American Society for Microbiology.

Solar cycle dependence of the heliospheric shape deduced from a global MHD simulation of the interaction process between a nonuniform time-dependent solar wind and the local interstellar medium

NASA Astrophysics Data System (ADS)

Tanaka, T.; Washimi, H.

1999-06-01

The global structure of the solar wind/very local interstellar medium interaction is studied from a fully three-dimensional time-dependent magnetohydrodynamic model, in which the solar wind speed increases from 400 to 800 km/s in going from the ecliptic to pole and the heliolatitude of the low-high-speed boundary changes from 30° to 80° in going from the solar minimum to solar maximum. In addition, the interplanetary magnetic field (IMF) changes its polarity at the solar maximum. As a whole, the shapes of the terminal shock (TS) and heliopause (HP) are elongated along the solar polar axis owing to a high solar wind ram pressure over the poles. In the ecliptic plane, the heliospheric structure changes little throughout a solar cycle. The TS in this plane shows a characteristic bullet-shaped structure. In the polar plane, on the other hand, the shape of the TS exhibits many specific structures according to the stage of the solar cycle. These structures include the polygonal configuration of the polar TS seen around the solar minimum, the mesa- and terrace-shaped TSs in the high- and low-speed solar wind regions seen around the ascending phase, and the chimney-shaped TS in the high-speed solar wind region seen around the solar maximum. These structures are formed from different combinations of right-angle shock, oblique shock, and steep oblique shock so as to transport the heliosheath plasma most efficiently toward the heliotail (HT). In the HT, the hot and weakly-magnetized plasma from the high-heliolatitude TS invades as far as the ecliptic plane. A weakly time-dependent recirculation flow in the HT is a manifestation of invading flow. Distributions of magnetic field in the HT, which are a pile-up of the compressed MF over several solar cycles, are modified by the flow from high-heliolatitude.

A new weighted mean temperature model in China

NASA Astrophysics Data System (ADS)

Liu, Jinghong; Yao, Yibin; Sang, Jizhang

2018-01-01

The Global Positioning System (GPS) has been applied in meteorology to monitor the change of Precipitable Water Vapor (PWV) in atmosphere, transformed from Zenith Wet Delay (ZWD). A key factor in converting the ZWD into the PWV is the weighted mean temperature (Tm), which has a direct impact on the accuracy of the transformation. A number of Bevis-type models, like Tm -Ts and Tm -Ts,Ps type models, have been developed by statistics approaches, and are not able to clearly depict the relationship between Tm and the surface temperature, Ts . A new model for Tm , called weighted mean temperature norm model (abbreviated as norm model), is derived as a function of Ts , the lapse rate of temperature, δ, the tropopause height, htrop , and the radiosonde station height, hs . It is found that Tm is better related to Ts through an intermediate temperature. The small effects of lapse rate can be ignored and the tropopause height be obtained from an empirical model. Then the norm model is reduced to a simplified form, which causes fewer loss of accuracy and needs two inputs, Ts and hs . In site-specific fittings, the norm model performs much better, with RMS values reduced averagely by 0.45 K and the Mean of Absolute Differences (MAD) values by 0.2 K. The norm model is also found more appropriate than the linear models to fit Tm in a large area, not only with the RMS value reduced from 4.3 K to 3.80 K, correlation coefficient R2 increased from 0.84 to 0.88, and MAD decreased from 3.24 K to 2.90 K, but also with the distribution of simplified model values to be more reasonable. The RMS and MAD values of the differences between reference and computed PWVs are reduced by on average 16.3% and 14.27%, respectively, when using the new norm models instead of the linear model.

Monoacylglycerol Lipase Inhibitor JZL184 Improves Behavior and Neural Properties in Ts65Dn Mice, a Model of Down Syndrome

PubMed Central

Lysenko, Larisa V.; Kim, Jeesun; Henry, Cassandra; Tyrtyshnaia, Anna; Kohnz, Rebecca A.; Madamba, Francisco; Simon, Gabriel M.; Kleschevnikova, Natalia E.; Nomura, Daniel K.; Ezekowitz, R . Alan B.; Kleschevnikov, Alexander M.

2014-01-01

Genetic alterations or pharmacological treatments affecting endocannabinoid signaling have profound effects on synaptic and neuronal properties and, under certain conditions, may improve higher brain functions. Down syndrome (DS), a developmental disorder caused by triplication of chromosome 21, is characterized by deficient cognition and inevitable development of the Alzheimer disease (AD) type pathology during aging. Here we used JZL184, a selective inhibitor of monoacylglycerol lipase (MAGL), to examine the effects of chronic MAGL inhibition on the behavioral, biochemical, and synaptic properties of aged Ts65Dn mice, a genetic model of DS. In both Ts65Dn mice and their normosomic (2N) controls, JZL184-treatment increased brain levels of 2-arachidonoylglycerol (2-AG) and decreased levels of its metabolites such as arachidonic acid, prostaglandins PGD2, PGE2, PGFα, and PGJ2. Enhanced spontaneous locomotor activity of Ts65Dn mice was reduced by the JZL184-treatement to the levels observed in 2N animals. Deficient long-term memory was also improved, while short-term and working types of memory were unaffected. Furthermore, reduced hippocampal long-term potentiation (LTP) was increased in the JZL184-treated Ts65Dn mice to the levels observed in 2N mice. Interestingly, changes in synaptic plasticity and behavior were not observed in the JZL184-treated 2N mice suggesting that the treatment specifically attenuated the defects in the trisomic animals. The JZL184-treatment also reduced the levels of Aβ40 and Aβ42, but had no effect on the levels of full length APP and BACE1 in both Ts65Dn and 2N mice. These data show that chronic MAGL inhibition improves the behavior and brain functions in a DS model suggesting that pharmacological targeting of MAGL may be considered as a perspective new approach for improving cognition in DS. PMID:25474204

Analysis of 320 gastroenteropancreatic neuroendocrine tumors identifies TS expression as independent biomarker for survival.

PubMed

Lee, Hye Seung; Chen, Min; Kim, Ji Hun; Kim, Woo Ho; Ahn, Soyeon; Maeng, Kyungah; Allegra, Carmen J; Kaye, Frederic J; Hochwald, Steven N; Zajac-Kaye, Maria

2014-07-01

Thymidylate synthase (TS), a critical enzyme for DNA synthesis and repair, is both a potential tumor prognostic biomarker as well as a tumorigenic oncogene in animal models. We have now studied the clinical implications of TS expression in gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and compared these results to other cell cycle biomarker genes. Protein tissue arrays were used to study TS, Ki-67, Rb, pRb, E2F1, p18, p21, p27 and menin expression in 320 human GEP-NETs samples. Immunohistochemical expression was correlated with univariate and multivariate predictors of survival utilizing Kaplan Meier and Cox proportional hazards models. Real time RT-PCR was used to validate these findings. We found that 78 of 320 GEP-NETs (24.4%) expressed TS. NETs arising in the colon, stomach and pancreas showed the highest expression of TS (47.4%, 42.6% and 37.3%, respectively), whereas NETs of the appendix, rectum and duodenum displayed low TS expression (3.3%, 12.9% and 15.4%, respectively). TS expression in GEP-NETs was associated with poorly differentiated endocrine carcinoma, angiolymphatic invasion, lymph node metastasis and distant metastasis (p < 0.05). Patients with TS-positive NETs had markedly worse outcomes than TS-negative NETs as shown by univariate (p < 0.001) and multivariate (p = 0.01) survival analyses. Expression of p18 predicted survival in TS-positive patients that received chemotherapy (p = 0.015). In conclusion, TS protein expression was an independent prognostic biomarker for GEP-NETs. The strong association of increased TS expression with aggressive disease and early death supports the role of TS as a cancer promoting agent in these tumors. © 2013 UICC.

The relationship of periaortic fat thickness and cardiovascular risk factors in children with Turner syndrome.

PubMed

Akyürek, Nesibe; Atabek, Mehmet Emre; Eklioglu, Beray Selver; Alp, Hayrullah

2015-06-01

Children with Turner syndrome (TS) have a broad range of later health problems, including an increased risk of cardiovascular morbidity and mortality. The aim of this study was to evaluate the relationship between periaortic fat thickness (PAFT) and metabolic and cardiovascular profiles in children with TS. Twenty-nine TS and 29 healthy children and adolescents were enrolled in the study. Anthropometric measurements, pubertal staging, and blood pressure measurements were performed. Fasting serum glucose, insulin, and lipid profile were measured. Periaortic fat thickness was measured using an echocardiography method, which has not previously been applied in children with TS. No difference was found between TS and control subject (CS) in age, weight, waist/hip ratio, HDL cholesterol and LDL cholesterol levels. However, in TS subjects, total cholesterol (p = 0.045) was greater than that in controls. It was determined that 13.7 % (N: 4) of TS subjects had dyslipidemia. Mean fasting glucose, fasting insulin, QUICK-I, HOMA, and FGIR index were similar in TS and in CS, whereas 17.2 % (N: 5) of TS subjects had insulin resistance (IR) and 13.7 % (N: 4) had impaired glucose tolerance. Six subjects (20.6 %) were diagnosed as hypertensive. Periaortic fat thickness was significantly higher in the TS group (p < 0.001) (0.1694 ± 0.025 mm in the TS group and 0.1416 ± 0.014 mm in the CS group) In children with TS, PAFT was positively correlated with fasting insulin, body mass index, and diastolic blood pressure. Our results provide additional evidence for the presence of subclinical cardiovascular disease in TS. In addition to existing methods, we recommend the measurement of periaortic fat thickness in children with TS to reveal the presence of early atherosclerosis.

A Comparison of Tropical Storm (TS) and Non-TS Gust Factors for Assessing Peak Wind Probabilities at the Eastern Range

NASA Technical Reports Server (NTRS)

Merceret, Francis J.; Crawford, Winifred C.

2010-01-01

Knowledge of peak wind speeds is important to the safety of personnel and flight hardware at Kennedy Space Center (KSC) and the Cape Canaveral Air Force Station (CCAFS), but they are more difficult to forecast than mean wind speeds. Development of a reliable model for the gust factor (GF) relating the peak to the mean wind speed motivated a previous study of GF in tropical storms. The same motivation inspired a climatological study of non-TS peak wind speed statistics without the use of GF. Both studies presented their respective statistics as functions of mean wind speed and height. The few comparisons of IS and non-TS GF in the literature suggest that the non-TS GF at a given height and mean wind speed are smaller than the corresponding TS GF. The investigation reported here converted the non-TS peak wind statistics mentioned above to the equivalent GF statistics and compared the results with the previous TS GF results. The advantage of this effort over all previously reported studies of its kind is that the TS and non-TS data are taken from the same towers in the same locations. That eliminates differing surface attributes, including roughness length and thermal properties, as a major source of variance in the comparison. The results are consistent with the literature, but include much more detailed, quantitative information on the nature of the relationship between TS and non-TS GF as a function of height and mean wind speed. In addition, the data suggest the possibility of providing an operational model for non-TS GF as a function of height and wind speed in a manner similar to the one previously developed for TS GF.

Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET.

PubMed

Wong, Dean F; Brasić, James R; Singer, Harvey S; Schretlen, David J; Kuwabara, Hiroto; Zhou, Yun; Nandi, Ayon; Maris, Marika A; Alexander, Mohab; Ye, Weiguo; Rousset, Olivier; Kumar, Anil; Szabo, Zsolt; Gjedde, Albert; Grace, Anthony A

2008-05-01

Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-R's), dopamine transporter binding potential (BP), and amphetamine-induced dopamine release (DA(rel)) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DA rel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D(2)-R increase in left ventral striatum. SERT BP in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS-OCD). In three subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DA rel and 5-HT2A BP, when compared with TS-OCD subjects and normal controls. The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DA rel is a primary defect in TS. The finding of decreased SERT BP, and the possible elevation in 5-HT2AR in individuals with TS who had increased DA rel, suggest a condition of increased phasic DA rel modulated by low 5-HT in concomitant OCD.

Guide of good practices for occupational radiological protection in plutonium facilities

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1998-06-01

This Technical Standard (TS) does not contain any new requirements. Its purpose is to provide guides to good practice, update existing reference material, and discuss practical lessons learned relevant to the safe handling of plutonium. the technical rationale is given to allow US Department of Energy (DOE) health physicists to adapt the recommendations to similar situations throughout the DOE complex. Generally, DOE contractor health physicists will be responsible to implement radiation protection activities at DOE facilities and DOE health physicists will be responsible for oversight of those activities. This guidance is meant to be useful for both efforts. This TSmore » replaces PNL-6534, Health Physics Manual of Good Practices for Plutonium Facilities, by providing more complete and current information and by emphasizing the situations that are typical of DOE`s current plutonium operations; safe storage, decontamination, and decommissioning (environmental restoration); and weapons disassembly.« less

Comparison of Land Skin Temperature from a Land Model, Remote Sensing, and In-situ Measurement

NASA Technical Reports Server (NTRS)

Wang, Aihui; Barlage, Michael; Zeng, Xubin; Draper, Clara Sophie

2014-01-01

Land skin temperature (Ts) is an important parameter in the energy exchange between the land surface and atmosphere. Here hourly Ts from the Community Land Model Version 4.0, MODIS satellite observations, and in-situ observations in 2003 were compared. Compared with the in-situ observations over four semi-arid stations, both MODIS and modeled Ts show negative biases, but MODIS shows an overall better performance. Global distribution of differences between MODIS and modeled Ts shows diurnal, seasonal, and spatial variations. Over sparsely vegetated areas, the model Ts is generally lower than the MODIS observed Ts during the daytime, while the situation is opposite at nighttime. The revision of roughness length for heat and the constraint of minimum friction velocity from Zeng et al. [2012] bring the modeled Ts closer to MODIS during the day, and have little effect on Ts at night. Five factors contributing to the Ts differences between the model and MODIS are identified, including the difficulty in properly accounting for cloud cover information at the appropriate temporal and spatial resolutions, and uncertainties in surface energy balance computation, atmospheric forcing data, surface emissivity, and MODIS Ts data. These findings have implications for the cross-evaluation of modeled and remotely sensed Ts, as well as the data assimilation of Ts observations into Earth system models.

Research and Development for Novel Thermal Energy Storage Systems (TES) for Concentrating Solar Power (CSP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faghri, Amir; Bergman, Theodore L; Pitchumani, Ranga

2013-09-26

The overall objective was to develop innovative heat transfer devices and methodologies for novel thermal energy storage systems for concentrating solar power generation involving phase change materials (PCMs). Specific objectives included embedding thermosyphons and/or heat pipes (TS/HPs) within appropriate phase change materials to significantly reduce thermal resistances within the thermal energy storage system of a large-scale concentrating solar power plant and, in turn, improve performance of the plant. Experimental, system level and detailed comprehensive modeling approaches were taken to investigate the effect of adding TS/HPs on the performance of latent heat thermal energy storage (LHTES) systems.

Automatic Traffic Advisory and Resolution Service (ATARS) Algorithms Including Resolution-Advisory-Register Logic. Volume 1. Sections 1 through 11,

DTIC Science & Technology

1981-06-01

Donald Roberts contributed to the final design review and editing of this document as well as having overall project and technical management...and Reporting function 7. A Data Extraction function 1-5 2. SYSTEM OVERVIEW The basic concept of ATARS is very briefly reviewed here as background to...8-P30 PRM threatadvisorydeerination; If! ((SVECT1.CUNC 12 %P&LSZ jfl SV2c?t.ITSEQ 11 UNflQ) (SVUCT2.CUNC 12 SPILS2 LU SYICT2.&TS2Q j1, UIZQ)) TRS 2W

Prediction Methodology for Propulsive Induced Force and Moments of V/STOL Aircraft in Transition/STOL Flight. Volume 1. Technical Discussion.

DTIC Science & Technology

1979-07-31

VAPE ). - -5 (over) DD O, 73 1473 EDITION OF I NOVSS iS 1O.yTS/ Unclassified S/N 0102-LF-014-6601 SCCURIVV CLASWFICATION OF T1MI PAGS (When Dot&eta...S6nd) \\.- ,.t-*#,*’" Unclassified SECURITY CLASSIFICATION OF THiS PAGE ("on Date EntIe.4o The VAPE program is capable of evaluating: e- Effects of...Vought. This method will determine the pressures on the inlet face and nacelle inlet lips. The VAPE program will then utilize these pressures to

QM/MM Free Energy Simulations of Salicylic Acid Methyltransferase: Effects of Stabilization of TS-like Structures on Substrate Specificity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Jianzhuang; Xu, Qin; Chen, Feng

2010-01-01

Salicylic acid methyltransferases (SAMTs) synthesize methyl salicylate (MeSA) using salicylate as the substrate. MeSA synthesized in plants may function as an airborne signal to activate the expression of defense-related genes and could also be a critical mobile signaling molecule that travels from the site of plant infection to establish systemic immunity in the induction of disease resistance. Here the results of QM/MM free energy simulations for the methyl transfer process in Clarkia breweri SAMT (CbSAMT) are reported to determine the origin of the substrate specificity of SAMTs. The free energy barrier for the methyl transfer from S-adenosyl-l-methionine (AdoMet) to 4-hydroxybenzoatemore » in CbSAMT is found to be about 5 kcal/mol higher than that from AdoMet to salicylate, consistent with the experimental observations. It is suggested that the relatively high efficiency for the methylation of salicylate compared to 4-hydroxybenzoate is due, at least in part, to the reason that a part of the stabilization of the transition state (TS) configuration is already reflected in the reactant complex, presumably, through the binding. The results seem to indicate that the creation of the substrate complex (e.g., through mutagenesis and substrate modifications) with its structure closely resembling TS might be fruitful for improving the catalytic efficiency for some enzymes. The results show that the computer simulations may provide important insights into the origin of the substrate specificity for the SABATH family and could be used to help experimental efforts in generating engineered enzymes with altered substrate specificity.« less

Molecular, Immunological, and Biological Characterization of Tityus serrulatus Venom Hyaluronidase: New Insights into Its Role in Envenomation

PubMed Central

Oliveira-Mendes, Bárbara Bruna Ribeiro; do Carmo, Anderson Oliveira; Duarte, Clara Guerra; Felicori, Liza Figueiredo; Machado-de-Ávila, Ricardo Andrez; Chávez-Olórtegui, Carlos; Kalapothakis, Evanguedes

2014-01-01

Background Scorpionism is a public health problem in Brazil, and Tityus serrulatus (Ts) is primarily responsible for severe accidents. The main toxic components of Ts venom are low-molecular-weight neurotoxins; however, the venom also contains poorly characterized high-molecular-weight enzymes. Hyaluronidase is one such enzyme that has been poorly characterized. Methods and principal findings We examined clones from a cDNA library of the Ts venom gland and described two novel isoforms of hyaluronidase, TsHyal-1 and TsHyal-2. The isoforms are 83% identical, and alignment of their predicted amino acid sequences with other hyaluronidases showed conserved residues between evolutionarily distant organisms. We performed gel filtration followed by reversed-phase chromatography to purify native hyaluronidase from Ts venom. Purified native Ts hyaluronidase was used to produce anti-hyaluronidase serum in rabbits. As little as 0.94 µl of anti-hyaluronidase serum neutralized 1 LD50 (13.2 µg) of Ts venom hyaluronidase activity in vitro. In vivo neutralization assays showed that 121.6 µl of anti-hyaluronidase serum inhibited mouse death 100%, whereas 60.8 µl and 15.2 µl of serum delayed mouse death. Inhibition of death was also achieved by using the hyaluronidase pharmacological inhibitor aristolochic acid. Addition of native Ts hyaluronidase (0.418 µg) to pre-neutralized Ts venom (13.2 µg venom+0.94 µl anti-hyaluronidase serum) reversed mouse survival. We used the SPOT method to map TsHyal-1 and TsHyal-2 epitopes. More peptides were recognized by anti-hyaluronidase serum in TsHyal-1 than in TsHyal-2. Epitopes common to both isoforms included active site residues. Conclusions Hyaluronidase inhibition and immunoneutralization reduced the toxic effects of Ts venom. Our results have implications in scorpionism therapy and challenge the notion that only neurotoxins are important to the envenoming process. PMID:24551256

In Vivo Chromatin Targets of the Transcription Factor Yin Yang 2 in Trophoblast Stem Cells

PubMed Central

Pérez-Palacios, Raquel; Macías-Redondo, Sofía; Climent, María; Contreras-Moreira, Bruno; Muniesa, Pedro; Schoorlemmer, Jon

2016-01-01

Background Yin Yang 2 (YY2) is a zinc finger protein closely related to the well-characterized Yin Yang 1 (YY1). YY1 is a DNA-binding transcription factor, with defined functions in multiple developmental processes, such as implantation, cell differentiation, X inactivation, imprinting and organogenesis. Yy2 has been treated as a largely immaterial duplication of Yy1, as they share high homology in the Zinc Finger-region and similar if not identical in vitro binding sites. In contrast to these similarities, gene expression alterations in HeLa cells with attenuated levels of either Yy1 or Yy2 were to some extent gene-specific. Moreover, the chromatin binding sites for YY2, except for its association with transposable retroviral elements (RE) and Endogenous Retroviral Elements (ERVs), remain to be identified. As a first step towards defining potential Yy2 functions matching or complementary to Yy1, we considered in vivo DNA binding sites of YY2 in trophoblast stem (TS) cells. Results We report the presence of YY2 protein in mouse-derived embryonic stem (ES) and TS cell lines. Following up on our previous report on ERV binding by YY2 in TS cells, we investigated the tissue-specificity of REX1 and YY2 binding and confirm binding to RE/ERV targets in both ES cells and TS cells. Because of the higher levels of expression, we chose TS cells to understand the role of Yy2 in gene and chromatin regulation. We used in vivo YY2 association as a measure to identify potential target genes. Sequencing of chromatin obtained in chromatin-immunoprecipitation (ChIP) assays carried out with αYY2 serum allowed us to identify a limited number of chromatin targets for YY2. Some putative binding sites were validated in regular ChIP assays and gene expression of genes nearby was altered in the absence of Yy2. Conclusions YY2 binding to ERVs is not confined to TS cells. In vivo binding sites share the presence of a consensus binding motif. Selected sites were uniquely bound by YY2 as opposed to YY1, suggesting that YY2 exerts unique contributions to gene regulation. YY2 binding was not generally associated with gene promoters. However, several YY2 binding sites are linked to long noncoding RNA (lncRNA) genes and we show that the expression levels of a few of those are Yy2-dependent. PMID:27191592

Space Transportation System Liftoff Debris Mitigation Process Overview

NASA Technical Reports Server (NTRS)

Mitchell, Michael; Riley, Christopher

2011-01-01

Liftoff debris is a top risk to the Space Shuttle Vehicle. To manage the Liftoff debris risk, the Space Shuttle Program created a team with in the Propulsion Systems Engineering & Integration Office. The Shutt le Liftoff Debris Team harnesses the Systems Engineering process to i dentify, assess, mitigate, and communicate the Liftoff debris risk. T he Liftoff Debris Team leverages off the technical knowledge and expe rtise of engineering groups across multiple NASA centers to integrate total system solutions. These solutions connect the hardware and ana lyses to identify and characterize debris sources and zones contribut ing to the Liftoff debris risk. The solutions incorporate analyses sp anning: the definition and modeling of natural and induced environmen ts; material characterizations; statistical trending analyses, imager y based trajectory analyses; debris transport analyses, and risk asse ssments. The verification and validation of these analyses are bound by conservative assumptions and anchored by testing and flight data. The Liftoff debris risk mitigation is managed through vigilant collab orative work between the Liftoff Debris Team and Launch Pad Operation s personnel and through the management of requirements, interfaces, r isk documentation, configurations, and technical data. Furthermore, o n day of launch, decision analysis is used to apply the wealth of ana lyses to case specific identified risks. This presentation describes how the Liftoff Debris Team applies Systems Engineering in their proce sses to mitigate risk and improve the safety of the Space Shuttle Veh icle.

Differences in Medial and Lateral Posterior Tibial Slope: An Osteological Review of 1090 Tibiae Comparing Age, Sex, and Race.

PubMed

Weinberg, Douglas S; Williamson, Drew F K; Gebhart, Jeremy J; Knapik, Derrick M; Voos, James E

2017-01-01

Injuries to the anterior cruciate ligament (ACL) are common, and a number of knee morphological variables have been identified as risk factors for an ACL injury, including the posterior tibial slope (TS). However, limited data exist regarding innate population differences in the TS. To (1) establish normative values for the medial and lateral posterior TS; (2) determine what differences exist between ages, sexes, and races; and (3) determine how internal or external tibial rotation (as occurs during sagittal knee motion) influences the stereotactic perception of the TS. Cross-sectional study; Level of evidence, 3. A total of 545 cadaveric specimens (1090 tibiae) were obtained from the Hamann-Todd osteological collection. Specimens were leveled in the coronal, sagittal, and axial planes using a digital laser. Virtual representations of each bone were created with a 3-dimensional digitizer apparatus. The TS of the medial and lateral tibial plateaus were measured using techniques adapted from previous radiographic protocols. Medial and lateral TS were then again measured on 200 tibiae that were internally and externally rotated by 10° (axially). The mean (±SD) medial TS was 6.9° ± 3.7° posterior, which was greater than the mean lateral TS of 4.7° ± 3.6° posterior ( P < .001). Neither the medial nor lateral TS changed with age. Women had a greater mean TS compared with men on both the medial (7.5° ± 3.8° vs 6.8° ± 3.7°, respectively; P = .03) and lateral (5.2° ± 3.5° vs 4.6° ± 3.5°, respectively; P = .04) sides. Black specimens had a greater mean medial TS (8.7° ± 3.6° vs 5.8° ± 3.3°, respectively; P < .001) and lateral TS (5.9° ± 3.3° vs 3.8° ± 3.5°, respectively; P < .001) compared with white specimens. Axial rotation was shown to increase the perception of the medial and lateral TS ( P < .001). The medial TS was shown to be greater than the lateral TS. Important sex- and race-based differences exist in the TS. This study also highlights the role of axial rotation in measuring the TS.

Selected clinical features of the head and neck in women with Turner syndrome and the 45,X/46,XY karyotype.

PubMed

Frelich, Agnieszka; Frelich, Jakub; Jeż, Wacław; Irzyniec, Tomasz

2017-01-01

A 45,X/46,XY karyotype in women with Turner syndrome (TS) is very rare. The presence of a Y chromosome in the karyotype causes phenotypic differences and increased risk for neoplastic disease, compared to TS-women with other karyotypes. Our study addresses an issue: non-genital phenotypic differences between TS-patients with a Y-chromosome of their karyotype and TS-women without it. Results from patient history/physical examinations of the head and neck of eight TS-women and the 45,X/46,XY karyotype were compared with those observed in 164 TS-women and 30 controls. The heights of TS-groups: 142.5 ± 7.2 and 144.9 ± 7.2 cm were lower than controls (165.2 ± 6.6 cm). Participants were examined from 1995 to 2014. Among 28 study parameters, 15 were more frequently observed in TS women with the 45,X/46,XY karyotype compared to controls. Only abnormalities in the oral cavity and a history of childhood lymphoedema, differed significantly in the TS groups. With respect to the head and neck, the patient history and physical examination results of TS-women and the 45,X/46,XY karyotype and TS and other karyotypes revealed similar differences compared to controls. Compared to others TS patients, 45,X/46,XY individuals might more frequently have oral cavity soft tissue abnormalities and more rarely a history of childhood lymphoedema. (Endokrynol Pol 2017; 68 (1): 47-52).

Evaluation of a New IFN-γ Release Assay for Rapid Diagnosis of Active Tuberculosis in a High-Incidence Setting.

PubMed

Li, Gen; Li, Feng; Zhao, Hui-Min; Wen, Han-Li; Li, Hai-Cong; Li, Chun-Ling; Ji, Ping; Xu, Peng; Wu, Kang; Hu, Zhi-Dong; Lu, Shui-Hua; Lowrie, Douglas B; Lv, Jian-Xin; Fan, Xiao-Yong

2017-01-01

Blood-based interferon-gamma (IFN-γ) release assays (IGRAs) have been proven to be useful in the diagnosis of Mycobacterium tuberculosis ( Mtb ) infection. However, IGRAs have not been recommended for clinical practice in most low-income settings due to cost-intensive limitations and shortage of clinical data available. The established T-SPOT. TB assay containing Mtb -specific antigens ESAT-6 and CFP10 are widely used for immunodiagonsis of Mtb infection, but the high cost is one of the restricting factors against its clinical application in the developing countries. More recently, a cost-saving IGRA assay, TS-SPOT, was approved in China. This new assay contains an additional antigen Rv3615c. Rv3615c contains broadly recognized CD4 + and CD8 + epitopes, and T-cell responses to Rv3615c are as specific for Mtb infection as the responses to ESAT-6 and CFP10 in both Mtb -infected humans and M. bovis -infected cattle. Therefore, we assessed the likely effect of inclusion of Rv3615c as stimulus besides ESAT-6 and CFP10 in an IGRA assay and evaluated the performance of TS-SPOT for diagnosis of Mtb infection and active TB compared with T-SPOT. TB . We tested 155 active TB patients, 90 non-TB lung disease patients, and 55 healthy individuals. The results presented an improved positive rate for diagnosis of active TB and Mtb infection, that could be attributable to inclusion of Rv3615c in the mixture of stimulatory antigens. The diagnostic efficiency of TS-SPOT assay for active TB was as follows: sensitivity 80.00%, specificity 83.45%, positive predictive value (PPV) 83.78%, negative predictive value (NPV) 83.45%, positive likelihood ratio (LR+) 4.83, and negative likelihood ratio (LR-) 0.24. The results were similar to those of T-SPOT. TB , with an excellent agreement (κ = 0.91, 95% CI: 0.85-0.95) being observed between these two assays. The sensitivities of the TS-SPOT assay varied for patients with different forms of active TB, with the highest sensitivity for patients with culture-positive pulmonary TB (92.16%) and the lowest for those with tuberculosis meningitis (50.00%). Taken together, the current evidence indicates that this new TS-SPOT assay is a useful adjunct to the current tests for rapid diagnosis of active TB and Mtb infection in low-income and high-incidence settings due to its characteristics of cost-effectiveness and high-quality.

Modified natural porcine surfactant modulates tobacco smoke-induced stress response in human monocytes.

PubMed

Pinot, F; Bachelet, M; François, D; Polla, B S; Walti, H

1999-01-01

Tobacco smoke (TS) is a potent source of oxidants and oxidative stress is an important mechanism by which TS exerts its toxicity in the lung. We have shown that TS induces heat shock (HS)/stress protein (HSP) synthesis in human monocytes. Pulmonary surfactant (PS) whose major physiological function is to confer mechanical stability to alveoli, also modulates oxidative metabolism and other pro-inflammatory functions of monocytes-macrophages. In order to determine whether PS alters the stress response induced by TS, we incubated human peripheral blood monocytes overnight with modified natural porcine surfactant (Curosurf) (1 mg/ml) before exposure to TS. Curosurf decreased TS-induced, but not HS-induced, expression of the major cytosolic, inducible 72 kD HSP (Hsp70). Furthermore, TS-generated superoxide anions production was significantly decreased by Curosurf in an acellular system, suggesting a direct scavenging effect of PS. We also examined the effects of TS and PS on monocytes ultrastructure. Monocytes incubated with Curosurf presented smoother cell membranes than control monocytes, while TS-induced monocyte vacuolization was, at least in part, prevented by Curosurf. Taken together, our data suggest that PS plays a protective role against oxygen radical-mediated, TS-induced cellular stress responses.

Train surfing and other high voltage trauma: differences in injury-related mechanisms and operative outcomes after fasciotomy, amputation and soft-tissue coverage.

PubMed

Lumenta, David Benjamin; Vierhapper, Martin Friedrich; Kamolz, Lars-Peter; Keck, Maike; Frey, Manfred

2011-12-01

In the context of scarce reports on train surfers among high voltage electric injuries, we conducted a retrospective review between January 1994 and December 2008. After matching for inclusion criteria we reviewed patient records of 37 true high voltage injuries (12 train surfers [TS] and 25 other high voltage injuries [HV]). TS were significantly younger (TS 15.8 years vs. HV 33.3 years, p<0.0001), and had a greater %TBSA (TS 49.7%TBSA vs. HV 21.5%TBSA, p=0.0003) without affecting the median length-of-stay (TS 52 days vs. HV 49 days) or number of operations (TS 4 vs. HV 3). TS had different injury patterns, with a higher percentage of affected extremities (TS 72.9% vs. HV 52.0%, p=0.0468) and associated injuries (TS 58% vs. HV 20%, n.s.) than HV. Both groups demonstrated comparable fasciotomy (TS 71.4% vs. HV 55.8%) and amputation rates (TS 17.1% vs. HV 15.4%). While TS required less flaps (TS 3/12 vs. HV 18/25; p=0.0153), soft-tissue reconstruction revealed an overall low incidence of complication rates (one partial pedicled flap loss and two total free flap losses). Train surfers have proven to be a distinct group of patients among high-voltage injuries notably as a result of a younger age, a shorter electric contact duration and higher velocity-induced trauma. With a possibly declining trend of train surfing-related accidents in an aging society, it will be interesting to see if emerging economies will face comparable phenomena, for which prevention strategies remain key. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

Limits to TYMS and TP53 genes as predictive determinants for fluoropyrimidine sensitivity and further evidence for an RNA-based toxicity as a major influence

PubMed Central

Brody, Jonathan R.; Hucl, Tomas; Costantino, Christina L.; Eshleman, James; Gallmeier, Eike; Zhu, Heng; Heijden, Michael S. van der; Winter, Jordan M; Wikiewicz, Agnieszka K.; Yeo, Charles J.; Kern, Scott E.

2010-01-01

The major determinants of 5-flurouracil response would appear, based on accumulated literature, to be thymidylate synthase (TYMS, TS) expression levels, TS gene modifications, and TP53 status. We tested 5-fluorouracil sensitivity in yeast and human cancer cell models in which TS or TP53 alleles and expression were varied. Polymorphic TS tandem repeat status, TS expression levels reported, TS intragenic mutations, and TP53 status in outbred and experimental cancer cell lines did not predict 5-FU sensitivity or resistance. Novel observations included a dose-resistant persistence of unbound TS protein in many cancers and, upon 5-FU treatment of the colon cancer cell line, HCT116, evidence of allelic switching favoring transcripts of the mutant TS allele. The reported alleles having an intragenic mutation could not be causally associated with major degrees of 5-FU sensitivity. In yeast, TS protein was altered upon treatment with fluoro-deoxyuridine monophosphate, but 5-FU toxicity appeared largely to be RNA-based, being rescued by uridine rather than by thymidine. Cancer cell lines were also rescued from 5-FU toxicity with uridine rather than thymidine. Additionally, a TS (CDC21) knockout yeast strain, obviating any potential role for TS protein as a target, was hypersensitive to 5-FU. When denatured proteins from cancer cells treated with radio-labeled 5-FU were, labeled species with alternative molecular weights other than TS were visualized, providing further evidence for alternative 5-FU protein targets. These data emphasize that TS and TP53 status do not consistently explain the variance in responses of fluoropyrimidine-treated cancer cells, in part due to RNA-based toxicity. PMID:19155291

Morphology and Molecular Mechanisms of Hepatic Injury in Rats under Simulated Weightlessness and the Protective Effects of Resistance Training.

PubMed

Du, Fang; Ding, Ye; Zou, Jun; Li, Zhili; Tian, Jijing; She, Ruiping; Wang, Desheng; Wang, Huijuan; Lv, Dongqiang; Chang, Lingling

2015-01-01

This study investigated the effects of long-term simulated weightlessness on liver morphology, enzymes, glycogen, and apoptosis related proteins by using two-month rat-tail suspension model (TS), and liver injury improvement by rat-tail suspension with resistance training model (TS&RT). Microscopically the livers of TS rats showed massive granular degeneration, chronic inflammation, and portal fibrosis. Mitochondrial and endoplasmic reticulum swelling and loss of membrane integrity were observed by transmission electron microscopy (TEM). The similar, but milder, morphological changes were observed in the livers of TS&RT rats. Serum biochemistry analysis revealed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher (p<0.05) in TS rats than in controls. The levels of ALT and AST in TS&RT rats were slightly lower than in RT rats, but they were insignificantly higher than in controls. However, both TS and TS&RT rats had significantly lower levels (p<0.05) of serum glucose and hepatic glycogen than in controls. Immunohistochemistry demonstrated that the expressions of Bax, Bcl-2, and active caspase-3 were higher in TS rats than in TS&RT and control rats. Real-time polymerase chain reaction (real-time PCR) showed that TS rats had higher mRNA levels (P < 0.05) of glucose-regulated protein 78 (GRP78) and caspase-12 transcription than in control rats; whereas mRNA expressions of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) were slightly higher in TS rats. TS&RT rats showed no significant differences of above 4 mRNAs compared with the control group. Our results demonstrated that long-term weightlessness caused hepatic injury, and may trigger hepatic apoptosis. Resistance training slightly improved hepatic damage.

Morphology and Molecular Mechanisms of Hepatic Injury in Rats under Simulated Weightlessness and the Protective Effects of Resistance Training

PubMed Central

Zou, Jun; Li, Zhili; Tian, Jijing; She, Ruiping; Wang, Desheng; Wang, Huijuan; Lv, Dongqiang; Chang, Lingling

2015-01-01

This study investigated the effects of long-term simulated weightlessness on liver morphology, enzymes, glycogen, and apoptosis related proteins by using two-month rat-tail suspension model (TS), and liver injury improvement by rat-tail suspension with resistance training model (TS&RT). Microscopically the livers of TS rats showed massive granular degeneration, chronic inflammation, and portal fibrosis. Mitochondrial and endoplasmic reticulum swelling and loss of membrane integrity were observed by transmission electron microscopy (TEM). The similar, but milder, morphological changes were observed in the livers of TS&RT rats. Serum biochemistry analysis revealed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher (p<0.05) in TS rats than in controls. The levels of ALT and AST in TS&RT rats were slightly lower than in RT rats, but they were insignificantly higher than in controls. However, both TS and TS&RT rats had significantly lower levels (p<0.05) of serum glucose and hepatic glycogen than in controls. Immunohistochemistry demonstrated that the expressions of Bax, Bcl-2, and active caspase-3 were higher in TS rats than in TS&RT and control rats. Real-time polymerase chain reaction (real-time PCR) showed that TS rats had higher mRNA levels (P < 0.05) of glucose-regulated protein 78 (GRP78) and caspase-12 transcription than in control rats; whereas mRNA expressions of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) were slightly higher in TS rats. TS&RT rats showed no significant differences of above 4 mRNAs compared with the control group. Our results demonstrated that long-term weightlessness caused hepatic injury, and may trigger hepatic apoptosis. Resistance training slightly improved hepatic damage. PMID:26000905

Toe spatiotemporal differences between transition steps when ascending shorter flight stairways of different heights.

PubMed

Ajisafe, Toyin; Wu, Jianhua; Geil, Mark

2017-03-01

Studies have typically treated the first and second floor-to-stair transition steps (TS1 and TS2) as one stride. However, because the foot is devoid of plantar cutaneous input from the stair surface at TS1, these steps may have different toe spatiotemporal profiles, and resultantly, different susceptibilities to a trip and/or a fall. This study compared vertical toe clearance, forward velocity, and their respective variability magnitudes between TS1 and TS2 when ascending stairs of different heights. Twenty young adults (seven males and 13 females) (21.68 ± 2.49 years; 169.70 ± 9.56 cm; 63.91 ± 9.62 kg) negotiated an intervening three-step staircase placed midpoint on a 10 m walkway. There were three stair heights: low stairs (LS), medium stairs (MS), and high stairs (HS). Vertical toe clearance, forward velocity, and their variability magnitudes were calculated. Vertical toe clearance was only higher (P < 0.05) at TS1 than TS2 in the medium and high stairs. Vertical toe clearance was more variable (P < 0.05) in the low compared to medium stairs. Also, forward toe velocity was greater at TS1 than TS2, but was lower in the medium and high stairs. The locomotor system appeared cautious by exaggerating vertical toe clearance at both TS1 and TS2 only in low stairs, possibly due to higher forward toe velocity. If the exaggeration strategy consistently persists, this finding may suggest decreased trip or fall risk at both TS1 and TS2 only when transitioning onto low stairs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elucidating X chromosome influences on Attention Deficit Hyperactivity Disorder and executive function.

PubMed

Green, Tamar; Bade Shrestha, Sharon; Chromik, Lindsay C; Rutledge, Keetan; Pennington, Bruce F; Hong, David S; Reiss, Allan L

2015-09-01

To identify distinct behavioral and cognitive profiles associated with ADHD in Turner syndrome (TS), relative to idiopathic ADHD and neurotypical controls, in order to elucidate X-linked influences contributing to ADHD. We used a multilevel-model approach to compare 49 girls with TS to 37 neurotypical females, aged 5-12, on established measures of behavior (BASC-2) and neurocognitive function (NEPSY). We further compared girls with TS to BASC-2 and NEPSY age-matched reference data obtained from children with idiopathic ADHD. Within the TS group, 51% scored at or above the "at-risk" range for ADHD-associated behaviors on the BASC-2 (TS/+ADHD). The BASC-2 behavioral profile in this TS/+ADHD-subgroup was comparable to a reference group of boys with ADHD with respect to attentional problems and hyperactivity. However, the TS/+ADHD-subgroup had significantly higher hyperactivity scores relative to a reference sample of girls with ADHD (p = 0.016). The behavioral profile in TS was associated with significantly lower attention and executive function scores on the NEPSY relative to neurotypical controls (p = 0.015); but was comparable to scores from a reference sample of children with idiopathic ADHD. Deficits in attention and executive function were not observed in girls with TS having low levels of ADHD-associated behavior (TS/-ADHD). ADHD-associated behavioral and cognitive problems in TS are prevalent and comparable in severity to those found in children with idiopathic ADHD. The ADHD phenotype in TS also appears relatively independent of cognitive features typically associated with TS, like visuospatial weaknesses. These findings suggest that X-linked haploinsufficiency and downstream biological effects contribute to increased risk for ADHD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ts6 and Ts2 from Tityus serrulatus venom induce inflammation by mechanisms dependent on lipid mediators and cytokine production.

PubMed

Zoccal, Karina Furlani; Bitencourt, Claudia da Silva; Sorgi, Carlos Artério; Bordon, Karla de Castro Figueiredo; Sampaio, Suely Vilela; Arantes, Eliane Candiani; Faccioli, Lúcia Helena

2013-01-01

Inflammatory mediators are thought to be involved in the systemic and local immune response induced by the Tityus serrulatus scorpion envenomation. New functional aspects of lipid mediators have recently been described. Here, we examine the unreported role of lipid mediators in cell recruitment to the peritoneal cavity after an injection with Ts2 or Ts6 toxins isolated from the T. serrulatus scorpion venom. In this report, we demonstrate that following a single intraperitoneal (i.p.) injection of Ts2 or Ts6 (250 μg/kg) in mice, there was an induction of leukocytosis with a predominance of neutrophils observed at 4, 24, 48 and 96 h. Moreover, total protein, leukotriene (LT)B(4), prostaglandin (PG)E(2) and pro-inflammatory cytokine levels were increased. We also observed an increase of regulatory cytokines, including interleukin (IL)-10, after the Ts2 injection. Finally, we observed that Ts2 or Ts6 injection in 5-lipoxygenase (LO) deficient mice and in wild type (WT) 129sv mice pre-treated with LTs and PGs inhibitors (MK-886 and celecoxib, respectively) a reduction the influx of leukocytes occurs in comparison to WT. The recruitment of these cells demonstrated a phenotype characteristic of neutrophils, macrophages, CD4 and CD8 lymphocytes expressing GR1+, F4/80+, CD3+/CD4+ and CD3+/CD8+, respectively. In conclusion, our data demonstrate that Ts2 and Ts6 induce inflammation by mechanisms dependent on lipid mediators and cytokine production. Ts2 may play a regulatory role whereas Ts6 exhibits pro-inflammatory activity exclusively. Copyright © 2012 Elsevier Ltd. All rights reserved.

An epidemiologic study of Tourette's syndrome in a single school district.

PubMed

Comings, D E; Himes, J A; Comings, B G

1990-11-01

To evaluate the frequency of Gilles de la Tourette's syndrome (TS) in children, 3034 students in three schools in a single school district in greater Los Angeles were monitored frequently over a 2-year period by a school psychologist thoroughly familiar with the symptoms of the disorder. A portion of the cases were also evaluated in a TS clinic. A total of 14 males fulfilled the Tourette Syndrome Association research criteria for definite TS. When corrected for the number of students in special education classes in the monitored schools, the frequency of definite TS in males was 1 in 152. An additional 7 males who differed only in that they were not observed for a full year were termed definite TS less than 1 year. When the two groups were combined, the frequency of definite TS was 1 in 95 for males and 1 in 759 for females. These figures do not include an additional 10 males diagnosed as having definite transient tic disorder, 2 males diagnosed as having probable TS, and 10 males diagnosed as having possible TS. In addition to tics, most of these children had problems with attention span, obsessive compulsive behavior, and learning and/or conduct disorders. Seventy percent of the students with definite TS or definite TS less than 1 year were in special education classes. Twelve percent of the children in special education classes had definite TS or definite TS less than 1 year, and 28% were in one of the diagnostic categories of definite, probable, or possible. All of the 10 definite TS patients that were seen in the clinic had attention-deficit hyperactivity disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of mixture ratio, solids concentration and hydraulic retention time on the anaerobic digestion of the organic fraction of municipal solid waste.

PubMed

Fongsatitkul, Prayoon; Elefsiniotis, Panagiotis; Wareham, David G

2010-09-01

This paper describes how the degradation of the organic fraction of municipal solid waste (OFMSW) is affected through codigestion with varying amounts of return activated sludge (RAS). Solid waste that had its inorganic fraction selectively removed was mixed with RAS in ratios of 100% OFMSW, 50% OFMSW/50% RAS, and 25% OFMSW/75% RAS. The total solids (TS) concentration was held at 8% and three anaerobic digester systems treating the mixtures were held (for the first run) at a total hydraulic retention time (HRT) of 28 days. Increasing amounts of RAS did not however improve the mixture's digestability, as indicated by little change and/or a drop in the main performance indices [including percentage volatile solids (VS) removal and specific gas production]. The optimum ratio in this research therefore appeared to be 100% OFMSW with an associated 85.1 ± 0.6% VS removal and 0.72 ± 0.01 L total gas g(- 1) VS. In the second run, the effect of increasing percentage of TS (8, 12% and 15%) at a system HRT of 28 days was observed to yield no improvement in the main performance indices (i.e. percentage VS removal and specific gas production). Finally, during the third run, variations in the total system HRT were investigated at an 8% TS, again using 100% OFMSW. Of the HRTs explored (23, 28 and 33 days), the longest HRT yielded the best performance overall, particularly in terms of specific gas production (0.77 ± 0.01 L total gas g(-1) VS).

Does the Institution of a Statewide Trauma System Reduce Preventable Mortality and Yield a Positive Return on Investment for Taxpayers?

PubMed

Maxson, Todd; Mabry, Charles D; Sutherland, Michael J; Robertson, Ronald D; Booker, James O; Collins, Terry; Spencer, Horace J; Rinker, Charles F; Sanddal, Teri L; Sanddal, Nels D

2017-04-01

In July 2009, Arkansas began to annually fund $20 million for a statewide trauma system (TS). We studied injury deaths both pre-TS (2009) and post-TS (2013 to 2014), with attention to causes of preventive mortality, societal cost of those preventable mortality deaths, and benefit to tax payers of the lives saved. A multi-specialty trauma-expert panel met and reviewed records of 672 decedents (290 pre-TS and 382 post-TS) who met standardized inclusion criteria, were judged potentially salvageable, and were selected by a proportional sampling of the roughly 2,500 annual trauma deaths. Deaths were adjudicated into sub-categories of nonpreventable and preventable causes. The value of lives lost was calculated for those lives potentially saved in the post-TS period. Total preventable mortality was reduced from 30% of cases pre-TS to 16% of cases studied post-TS, a reduction of 14%. Extrapolating a 14% reduction of preventable mortality to the post-TS study period, using the same inclusion criteria of the post-TS, we calculate that 79 lives were saved in 2013 to 2014 due to the institution of a TS. Using a minimal standard estimate of $100,000 value for a life-year, a lifetime value of $2,365,000 per person was saved. This equates to an economic impact of the lives saved of almost $186 million annually, representing a 9-fold return on investment from the $20 million of annual state funding invested in the TS. The implementation of a TS in Arkansas during a 5-year period resulted in a reduction of the preventable death rate to 16% post-TS, and a 9-fold return on investment by the tax payer. Additional life-saving gains can be expected with ongoing financial support and additional system performance-improvement efforts. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Insights into Tan Spot and Stem Rust Resistance and Susceptibility by Studying the Pre-Green Revolution Global Collection of Wheat

PubMed Central

Abdullah, Sidrat; Sehgal, Sunish Kumar; Jin, Yue; Turnipseed, Brent; Ali, Shaukat

2017-01-01

Tan spot (TS), caused by the fungus Pyrenophora tritici-repentis (Died) Drechs, is an important foliar disease of wheat and has become a threat to world wheat production since the 1970s. In this study a globally diverse pre-1940s collection of 247 wheat genotypes was evaluated against Ptr ToxA, P. tritici-repentis race 1, and stem rust to determine if; (i) acquisition of Ptr ToxA by the P. tritici-repentis from Stagonospora nodorum led to increased pathogen virulence or (ii) incorporation of TS susceptibility during development stem rust resistant cultivars led to an increase in TS epidemics globally. Most genotypes were susceptible to stem rust; however, a range of reactions to TS and Ptr ToxA were observed. Four combinations of disease-toxin reactions were observed among the genotypes; TS susceptible-Ptr ToxA sensitive, TS susceptible-Ptr ToxA insensitive, TS resistant-Ptr ToxA insensitive, and TS resistant-Ptr ToxA toxin sensitive. A weak correlation (r = 0.14 for bread wheat and −0.082 for durum) was observed between stem rust susceptibility and TS resistance. Even though there were no reported epidemics in the pre-1940s, TS sensitive genotypes were widely grown in that period, suggesting that Ptr ToxA may not be an important factor responsible for enhanced prevalence of TS. PMID:28381959

A comparison of standard definitions and sagittal abdominal ...

EPA Pesticide Factsheets

Introduction: Metabolic syndrome (MeTS) is the cluster of several clinical symptoms that together represent the strongest risk factor for cardiovascular disease. The prevalence of MeTS in adolescents is difficult to estimate given that there are several, but no agreed upon definition of MeTS for this age group. It is important to estimate MeTS and identify at-risk adolescents early in order to provide effective interventions prior to the development of diabetes and coronary heart disease. Objective: Study objectives are to: (1) estimate the prevalence of MeTS in U.S. adolescents using three widely adopted definitions and (2) compare changes in prevalence of MeTS when utilizing sagittal abdominal diameter (SAD) as a component of MeTS. Methods: Data from U.S. adolescents ages 12–19 years (N=970) in the NHANES (2011–2014) were analyzed. MeTS standard definitions developed by Cook et al. (2003), deFerranti et al. (2007), and the International Disease Federation (IDF, 2007) were applied to estimate the sex-stratified, weighted prevalence of MeTS and its individual components (i.e., high waist circumference (WC), hypertension, blood lipid abnormalities, and high fasting blood glucose (FBG)). The definitions were modified by substituting SAD for WC, and weighted MeTS prevalence was re-estimated. Results: Regardless of gender and definition, abnormal blood lipids and high WC were the most prevalent MeTS components. For both sexes, estimated prevalence of componen

Homology modelling, molecular docking, and molecular dynamics simulations reveal the inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase enzyme by Withaferin-A.

PubMed

Vadloori, Bharadwaja; Sharath, A K; Prabhu, N Prakash; Maurya, Radheshyam

2018-04-16

Present in silico study was carried out to explore the mode of inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase (Ld DHFR-TS) enzyme by Withaferin-A, a withanolide isolated from Withania somnifera. Withaferin-A (WA) is known for its profound multifaceted properties, but its antileishmanial activity is not well understood. The parasite's DHFR-TS enzyme is diverse from its mammalian host and could be a potential drug target in parasites. A 3D model of Ld DHFR-TS enzyme was built and verified using Ramachandran plot and SAVES tools. The protein was docked with WA-the ligand, methotrexate (MTX)-competitive inhibitor of DHFR, and dihydrofolic acid (DHFA)-substrate for DHFR-TS. Molecular docking studies reveal that WA competes for active sites of both Hu DHFR and TS enzymes whereas it binds to a site other than active site in Ld DHFR-TS. Moreover, Lys 173 residue of DHFR-TS forms a H-bond with WA and has higher binding affinity to Ld DHFR-TS than Hu DHFR and Hu TS. The MD simulations confirmed the H-bonding interactions were stable. The binding energies of WA with Ld DHFR-TS were calculated using MM-PBSA. Homology modelling, molecular docking and MD simulations of Ld DHFR-TS revealed that WA could be a potential anti-leishmanial drug.

Formulation of intumescent flame retardant coatings containing natural-based tea saponin.

PubMed

Qian, Wei; Li, Xiang-Zhou; Wu, Zhi-Ping; Liu, Yan-Xin; Fang, Cong-Cong; Meng, Wei

2015-03-18

Natural product tea saponin (TS), extracted from the nutshell of camellia (Camellia oleifera Abel, Theaceae), was introduced into intumescent flame retardant formulations as blowing agent and carbon source. The formulations of the flame retardant system were optimized to get the optimum proportion of TS, and intumescent flame retardant coatings containing tea saponin (TS-IFRCs) were then prepared. It was found that TS can significantly affect the combustion behavior and the thermal stability of TS-IFRCs evaluated by cone calorimetry and simultaneous thermal analyzer, respectively. It was shown that TS, degraded to water vapor and carbon at high temperatures, can combine with other components to form a well-developed char layer. The char layer was supposed to inhibit erosion upon exposure to heat and oxygen and enhance the flame retardancy of TS-IFRCs. In addition, the smoke release of TS-IFRCs was also studied, which provided a low amount of smoke production.

A Qualitative Exploration of the Experiences of Children and Adolescents with Tourette Syndrome

PubMed Central

Edwards, Kim R.; Mendlowitz, Sandra; Jackson, Elana; Champigny, Claire; Specht, Matt; Arnold, Paul; Gorman, Daniel; Dimitropoulos, Gina

2017-01-01

Objective The purpose of this qualitative study was to explore the experiences of youth with Tourette Syndrome (TS). Method Thirteen participants with TS were recruited from a large tertiary care hospital to complete semi-structured interviews and two questionnaires pertaining to demographic information and tic severity. Thematic analysis was utilized to systematically analyze the data. Results Three main themes were identified: 1) beliefs about TS; 2) TS related distress and impairment; and, 3) coping with TS. Conclusion The findings from this study suggest that most participants were aware of their tics but unaware of the cause of tics/TS. The interviews also highlighted that, for most participants, TS caused emotional, social, physical, and/or occupational impairment. Despite their distress, participants provided several suggestions for coping with TS and for supporting those who are diagnosed with this condition. PMID:28331502

Observational Constraints on the Water Vapor Feedback Using GPS Radio Occultations

NASA Astrophysics Data System (ADS)

Vergados, P.; Mannucci, A. J.; Ao, C. O.; Fetzer, E. J.

2016-12-01

The air refractive index at L-band frequencies depends on the air's density and water vapor content. Exploiting these relationships, we derive a theoretical model to infer the specific humidity response to surface temperature variations, dq/dTs, given knowledge of how the air refractive index and temperature vary with surface temperature. We validate this model using 1.2-1.6 GHz Global Positioning System Radio Occultation (GPS RO) observations from 2007 to 2010 at 250 hPa, where the water vapor feedback on surface warming is strongest. Current research indicates that GPS RO data sets can capture the amount of water vapor in very dry and very moist air more efficiently than other observing platforms, possibly suggesting larger water vapor feedback than previously known. Inter-comparing the dq/dTs among different data sets will provide us with additional constraints on the water vapor feedback. The dq/dTs estimation from GPS RO observations shows excellent agreement with previously published results and the responses estimated using Atmospheric Infrared Sounder (AIRS) and NASA's Modern-Era Retrospective Analysis for Research and Applications (MERRA) data sets. In particular, the GPS RO-derived dq/dTs is larger by 6% than that estimated using the AIRS data set. This agrees with past evidence that AIRS may be dry-biased in the upper troposphere. Compared to the MERRA estimations, the GPS RO-derived dq/dTs is 10% smaller, also agreeing with previous results that show that MERRA may have a wet bias in the upper troposphere. Because of their high sensitivity to fractional changes in water vapor, and their inherent long-term accuracy, current and future GPS RO observations show great promise in monitoring climate feedbacks and their trends.

Differential impact of ionic and coordinate covalent chromium (Cr)-DNA binding on DNA replication.

PubMed

Fornsaglio, Jamie L; O'Brien, Travis J; Patierno, Steven R

2005-11-01

The reactive species produced by the reduction of Cr(VI), particularly Cr(III), can form both ionic and coordinate covalent complexes with DNA. These Cr(III)-DNA interactions consist of Cr-DNA monoadducts, Cr-DNA ternary adducts, and Cr-DNA interstrand cross-links (Cr-ICLs), the latter of which are DNA polymerase arresting lesions (PALs). We sought to determine the impact of Cr-DNA interactions on the formation of replication blocking lesions in S. cerevisiae using a PCR-based method. We found that target sequence (TS) amplification using DNA isolated from Cr(VI)-treated yeast actually increased as a function of Cr(VI) concentration. Moreover, the enhanced TS amplification was reproduced in vitro using Cr(III)-treated DNA. In contrast, PCR amplification of TS from DNA isolated from yeast exposed to equitoxic doses of the inorganic DNA cross-linking agent cisplatin (CDDP), was decreased in a concentration-dependent manner. This paradox suggested that a specific Cr-DNA interaction, such as an ionic Cr-DNA complex, was responsible for the enhanced TS amplification, thereby masking the replication-blocking effect of certain ternary Cr-DNA adducts (i.e. interstrand cross-links). To test this possibility, we removed ionically associated Cr from the DNA using salt extraction prior to PCR analysis. This procedure obviated the increased amplification and revealed a dose-dependent decrease in TS amplification and an increase in Cr-PALs. These data from DNA analyzed ex vivo after treatment of intact cells indicate that ionic interactions of Cr with DNA result in increased DNA amplification whereas coordinate-covalent Cr-DNA complexes lead to formation of Cr-PALs. Thus, these results suggest that treatment of living cells with Cr(VI) leads to two modes of Cr-binding, which may have conflicting effects on DNA replication.

Improvement of anaerobic digestion of sewage sludge through microwave pre-treatment.

PubMed

Serrano, A; Siles, J A; Martín, M A; Chica, A F; Estévez-Pastor, F S; Toro-Baptista, E

2016-07-15

Sewage sludge generated in the activated sludge process is a polluting waste that must be treated adequately to avoid important environmental impacts. Traditional management methods, such as landfill disposal or incineration, are being ruled out due to the high content in heavy metal, pathogens, micropolluting compounds of the sewage sludge and the lack of use of resources. Anaerobic digestion could be an interesting treatment, but must be improved since the biomethanisation of sewage sludge entails low biodegradability and low methane production. A microwave pre-treatment at pilot scale is proposed to increase the organic matter solubilisation of sewage sludge and enhance the biomethanisation yield. The operational variables of microwave pre-treatment (power and specific energy applied) were optimised by analysing the physicochemical characteristics of sewage sludge (both total and soluble fraction) under different pre-treatment conditions. According to the variation in the sCOD and TN concentration, the optimal operation variables of the pre-treatment were fixed at 20,000 J/g TS and 700 W. A subsequent anaerobic digestion test was carried out with raw and pre-treated sewage sludge under different conditions (20,000 J/g TS and 700 W; 20,000 J/g TS and 400 W; and 30,000 J/g TS and 400 W). Although stability was maintained throughout the process, the enhancement in the total methane yield was not high (up to 17%). Nevertheless, very promising improvements were determined for the kinetics of the process, where the rG and the OLR increased by 43% and 39%, respectively, after carrying out a pre-treatment at 20,000 J/g TS and 700 W. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antibodies and a cysteine-modifying reagent show correspondence of M current in neurons to KCNQ2 and KCNQ3 K+ channels

PubMed Central

Roche, John P; Westenbroek, Ruth; Sorom, Abraham J; Hille, Bertil; Mackie, Ken; Shapiro, Mark S

2002-01-01

KCNQ K+ channels are thought to underlie the M current of neurons. To probe if the KCNQ2 and KCNQ3 subtypes underlie the M current of rat superior cervical ganglia (SCG) neurons and of hippocampus, we raised specific antibodies against them and also used the cysteine-alkylating agent N-ethylmaleimide (NEM) as an additional probe of subunit composition. Tested on tsA-201 (tsA) cells transfected with cloned KCNQ1-5 subunits, our antibodies showed high affinity and selectivity for the appropriate subtype. The antibodies immunostained SCG neurons and hippocampal sections at levels similar to those for channels expressed in tsA cells, indicating that KCNQ2 and KCNQ3 are present in SCG and hippocampal neurons. Some hippocampal regions contained only KCNQ2 or KCNQ3 subunits, suggesting the presence of M currents produced by channels other than KCNQ2/3 heteromultimers. We found that NEM augmented M currents in SCG neurons and KCNQ2/3 currents in tsA cells via strong voltage-independent and modest voltage-dependent actions. Expression of individual KCNQ subunits in tsA cells revealed voltage-independent augmentation of KCNQ2, but not KCNQ1 nor KCNQ3, currents by NEM indicating that this action on SCG M currents likely localizes to KCNQ2. Much of the voltage-independent action is lost after the C242T mutation in KCNQ2. The correspondence of NEM effects on expressed KCNQ2/3 and SCG M currents, along with the antibody labelling, provide further evidence that KCNQ2 and KCNQ3 subunits strongly contribute to the M current of neurons. The site of NEM action may be important for treatment of diseases caused by under-expression of these channels. PMID:12466226

Ectopic Mineralization in the Middle Ear and Chronic Otitis Media with Effusion Caused by RPL38 Deficiency in the Tail-short (Ts) Mouse*

PubMed Central

Noben-Trauth, Konrad; Latoche, Joseph R.

2011-01-01

Inflammation of the middle ear cavity (otitis media) and the abnormal deposition of bone at the otic capsule are common causes of conductive hearing impairment in children and adults. Although a host of environmental factors can contribute to these conditions, a genetic predisposition has an important role as well. Here, we analyze the Tail-short (Ts) mouse, which harbors a spontaneous semi-dominant mutation that causes skeletal defects and hearing loss. By genetic means, we show that the Ts phenotypes arise from an 18-kb deletion/insertion of the Rpl38 gene, encoding a ribosomal protein of the large subunit. We show that Ts mutants exhibit significantly elevated auditory-brain stem response thresholds and reduced distortion-product otoacoustic emissions, in the presence of normal endocochlear potentials and typical inner ear histology suggestive of a conductive hearing impairment. We locate the cause of the hearing impairment to the middle ear, demonstrating over-ossification at the round window ridge, ectopic deposition of cholesterol crystals in the middle ear cavity, enlarged Eustachian tube, and chronic otitis media with effusion all beginning at around 3 weeks after birth. Using specific antisera, we demonstrate that Rpl38 is an ∼8-kDa protein that is predominantly expressed in mature erythrocytes. Finally, using an Rpl38 cDNA transgene, we rescue the Ts phenotypes. Together, these data present a previously uncharacterized combination of interrelated middle ear pathologies and suggest Rpl38 deficiency as a model to dissect the causative relationships between neo-ossification, cholesterol crystal deposition, and Eustachian tubes in the etiology of otitis media. PMID:21062742

U.S. EPA, Pesticide Product Label, DUPONT MATRIX HERBICIDE, 06/26/2007

EPA Pesticide Factsheets

2011-04-14

... Q\\Vn tOflla~~~§~9:ir~~ts~~~~ ilJl~~tra ... purse (Capsella bursa-pastoris) Wild Radish (Raphanus raphanistrum) ... t See Specific Weed Problems 9 ...

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

PubMed Central

Xu, Meiyu; Kobets, Andrew; Du, Jung-Chieh; Lennington, Jessica; Li, Lina; Banasr, Mounira; Duman, Ronald S.; Vaccarino, Flora M.; DiLeone, Ralph J.; Pittenger, Christopher

2015-01-01

Gilles de la Tourette syndrome (TS) is characterized by tics, which are transiently worsened by stress, acute administration of dopaminergic drugs, and by subtle deficits in motor coordination and sensorimotor gating. It represents the most severe end of a spectrum of tic disorders that, in aggregate, affect ∼5% of the population. Available treatments are frequently inadequate, and the pathophysiology is poorly understood. Postmortem studies have revealed a reduction in specific striatal interneurons, including the large cholinergic interneurons, in severe disease. We tested the hypothesis that this deficit is sufficient to produce aspects of the phenomenology of TS, using a strategy for targeted, specific cell ablation in mice. We achieved ∼50% ablation of the cholinergic interneurons of the striatum, recapitulating the deficit observed in patients postmortem, without any effect on GABAergic markers or on parvalbumin-expressing fast-spiking interneurons. Interneuron ablation in the dorsolateral striatum (DLS), corresponding roughly to the human putamen, led to tic-like stereotypies after either acute stress or d-amphetamine challenge; ablation in the dorsomedial striatum, in contrast, did not. DLS interneuron ablation also led to a deficit in coordination on the rotorod, but not to any abnormalities in prepulse inhibition, a measure of sensorimotor gating. These results support the causal sufficiency of cholinergic interneuron deficits in the DLS to produce some, but not all, of the characteristic symptoms of TS. PMID:25561540

Comparison between ozone and ultrasound disintegration on sludge anaerobic digestion.

PubMed

Braguglia, C M; Gianico, A; Mininni, G

2012-03-01

This paper deals with the comparison of ultrasound (mechanical) and ozone (chemical) pre-treatment on the performances of excess sludge semi-continuous digestion. Sludge solubilisation has been investigated by varying specific energy input. For each pre-treatment, long anaerobic digestion tests were carried out by two parallel digesters: one reactor, as control unit, was fed with untreated waste activated sludge, and the other one was fed with disintegrated sludge. To evaluate and compare the efficacy of both pre-treatments, the specific energy was maintained approximately the same. The digestion tests were carried out to investigate the feasibility of anaerobic digestion performance (total biogas production, volatile solids removal, sludge dewaterability) and to assess the heat balance. Results obtained from the digestion of sonicated sludge at 4% disintegration degree (≈ 2500 kJ/kg TS) showed that the ultrasound pre-treatment may be effective both in increasing VS destruction (+19%) and cumulative biogas production (+26%). On the contrary, the digestion test with ozonized sludge (ozone dose of 0.05 g O(3)/g TS corresponding to ≈ 2000 kJ/kg TS) did not indicate a significant improvement on the digestion performances. By doubling the ozone dose an improvement in the organics removal and cumulative biogas production was observed. Relevant differences in terms of colloidal charge and filterability were discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

Quantitative Structure-Cytotoxicity Relationship of Cinnamic Acid Phenetyl Esters.

PubMed

Uesawa, Yoshihiro; Sakagami, Hiroshi; Okudaira, Noriyuki; Toda, Kazuhiro; Takao, Koichi; Kagaya, Hajime; Sugita, Yoshiaki

2018-02-01

Many phenolic acid phenethyl esters possess diverse biological effects including antioxidant, cytoprotective, anti-inflammation and anti-tumor activities. However, most previous antitumor studies have not considered the cytotoxicity against normal cells. Ten cinnamic acid phenetyl esters were subjected to quantitative structure-activity relationship (QSAR) analysis, based on their cytotoxicity and tumor-specificity, in order to find their new biological activities. Cytotoxicity against four human oral squamous cell carcinoma cell lines and three oral normal mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC 50 ) against normal oral cells to that against human oral squamous cell carcinoma cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value by CC 50 against tumor cells. Apoptosis markers were detected by western blot analysis. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by force-field minimization. Western blot analysis demonstrated that [ 9 ] stimulated the cleavage of caspase-3, suggesting the induction of apoptosis. QSAR analysis demonstrated that TS values were correlated with shape, size and ionization potential. Chemical modification of the lead compound may be a potential choice for designing a new type of anticancer drugs. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Evaluation of Biological Activity of Mastic Extracts Based on Chemotherapeutic Indices.

PubMed

Suzuki, Ryuichiro; Sakagami, Hiroshi; Amano, Shigeru; Fukuchi, Kunihiko; Sunaga, Katsuyoshi; Kanamoto, Taisei; Terakubo, Shigemi; Nakashima, Hideki; Shirataki, Yoshiaki; Tomomura, Mineko; Masuda, Yoshiko; Yokose, Satoshi; Tomomura, Akito; Watanabe, Hirofumi; Okawara, Masaki; Matahira, Yoshiharu

2017-01-01

Most previous mastic investigators have not considered its potent cytotoxicity that may significantly affect the interpretation of obtained data. In the present study, we re-evaluated several biological activities of mastic extracts, based on chemotherapeutic indexes. Pulverized mastic gum was extracted with n-hexane and then with ethyl acetate or independently with methanol or n-butanol. Tumor specificity (TS) of the extracts was determined by their cytotoxicity against human malignant and non-malignant cells. Antibacterial activity was determined by their cytotoxicity against bacteria and normal oral cells. Antiviral activity was determined by their protection of viral infection and cytotoxic activity. Cytochrome P-450 (CYP) 3A4 activity was measured by β-hydroxylation of testosterone. Ethyl acetate extract showed slightly higher tumor specificity (TS=2.6) and one order higher antibacterial activity (selectivity index (SI)=0.813) than other extracts (TS=1.4-2.5; SI=0.030-0.063). All extracts showed no anti-human immunodeficiency virus (HIV) activity, but some anti-herpes simplex virus (HSV) activity, which was masked by potent cytotoxicity. They showed strong inhibitory activity against CYP3A4. Ethyl acetate extraction following the removal of cytotoxic and CYP3A4 inhibitory substances by n-hexane can enhance antitumor and antibacterial activity of mastic. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Combined (alkaline+ultrasonic) pretreatment effect on sewage sludge disintegration.

PubMed

Kim, Dong-Hoon; Jeong, Emma; Oh, Sae-Eun; Shin, Hang-Sik

2010-05-01

The individual effects of alkaline (pH 8-13) and ultrasonic (3750-45,000kJ/kg TS) pretreatments on the disintegration of sewage sludge were separately tested, and then the effect of combining these two methods at different intensity levels was investigated using response surface methodology (RSM). In the combined pretreatment, ultrasonic treatment was applied to the alkali-pretreated sludge. While the solubilization (SCOD/TCOD) increase was limited to 50% in individual pretreatments, it reached 70% in combined pretreatment, and the results clearly showed that preconditioning of sludge at high pH levels played a crucial role in enhancing the disintegration efficiency of the subsequent ultrasonic pretreatment. By applying regression analysis, the disintegration degree (DD) was fitted based on the actual value to a second order polynomial equation: Y=-172.44+29.82X(1)+5.30x10(-3)X(2)-7.53x10(-5)X(1)X(2)-1.10X(1)(2)-1.043x10(-7)X(2)(2), where X(1), X(2), and Y are pH, specific energy input (kJ/kg TS), and DD, respectively. In a 2D contour plot describing the tendency of DD with respect to pH and specific energy input, it was clear that DD increased as pH increased, but it seemed that DD decreased when the specific energy input exceeded about 20,000kJ/kg TS. This phenomenon tells us that there exists a certain point where additional energy input is ineffective in achieving further disintegration. A synergetic disintegration effect was also found in the combined pretreatment, with lower specific energy input in ultrasonic pretreatment yielding higher synergetic effect. Finally, in order to see the combined pretreatment effect in continuous operation, the sludge pretreated with low intensity alkaline (pH 9)/ultrasonic (7500kJ/kg TS) treatment was fed to a 3 L of anaerobic sequencing batch reactor after 70 days of control operation. CH(4) production yield significantly increased from 81.9+/-4.5mL CH(4)/g COD(added) to 127.3+/-5.0mL CH(4)/g COD(added) by pretreatment, and this enhanced performance was closely related to the solubilization increase of the sludge by pretreatment. However, enhanced anaerobic digestion resulted in 20% higher soluble N concentration in the reactor, which would be an additional burden in the subsequent nitrogen removal system.

Association of glutathione S-transferase P1 (GSTP1) polymorphism with Tourette syndrome in Taiwanese patients.

PubMed

Shen, Che-Piao; Chou, I-Ching; Liu, Hsin-Ping; Lee, Cheng-Chun; Tsai, Yuhsin; Wu, Bor-Tsang; Hsu, Ban-Dar; Lin, Wei-Yong; Tsai, Fuu-Jen

2014-01-01

The etiology of Tourette syndrome (TS) is multifactorial. TS vulnerability may be associated with genetic and environmental factors. From the genetic point of view, TS is heterogeneous. Previous studies showed that some single-nucleotide polymorphisms (SNPs) of the glutathione-S-transferase P1 (GSTP1) gene can affect cellular proliferation and apoptotic activity and TS is a neurodevelopmental disorder. We guessed that there was a relationship between TS and genetic variants of the GSTP1 gene. Therefore, in this study, we aimed to test the hypothesis that GSTP1 SNPs were associated with TS. We performed a case-control study. One hundred twenty-one TS children and 105 normal children were included in the study. Polymerase chain reaction was used to identify the GSTP1 gene polymorphism at position rs6591256 (A/G, promoter polymorphism) in TS patients and normal children. The polymorphism at position rs6591256 in the GSTP1 gene revealed significant differences in the allele (p=0.0135) and genotype (p=0.0159) distributions between the TS patients and the control group. The A allele was present at a higher frequency than the G allele in the TS patients compared with the control group (odds ratio [OR]=1.91, 95% confidence interval [CI]: 1.14-3.21). The AA genotype was associated with susceptibility to TS with an OR of 2.38 for the AA versus AG genotype (95% CI: 1.29-4.41). These findings suggest that variants in the GSTP1 gene may play a role in susceptibility to TS.

Temperature-sensitive mutants of influenza A virus. XIV. Production and evaluation of influenza A/Georgia/74-ts-1[E] recombinant viruses in human adults.

PubMed

Richman, D D; Murphy, B R; Belshe, R B; Rusten, H M; Chanock, R M; Blacklow, N R; Parrino, T A; Rose, F B; Levine, M M; Caplan, E

1977-08-01

The two temperature-sensitive (ts) lesions present in influenza A/Hong Kong/68-ts-1[E] (H3N2 68) virus were transferred via genetic reassortment to influenza A/Georgia/74 (H3N2 74) wild-type virus. A recombinant clone possessing both ts lesions and the shutoff temperature of 38 C of the Hong Kong/68 ts donor and the two surface antigens of the Georgia/74 wild-type virus was administered to 32 seronegative adult volunteers. Thirty-one volunteers were infected, of whom only five experienced mild afebrile upper respiratory tract illness. The wild-type recipient virus was a cloned population that induced illness in five of six infected volunteers. Therfore, the attenuation exhibited by the Georgia/74-ts-1[E] virus could reasonably be assumed to be due to the acquisition of the two ts-1[E] lesions by the Georgia/74 wild-type virus. The serum and nasal wash antibody responses of the ts-1[E] vaccinees were equivalent to those of the volunteers who received wild-type virus. The two ts lesions present in the Hong Kong/68-ts-1[E] virus have now been transferred three times to a wild-type virus bearing a new hemagglutinin, and in each instance the new ts recombination exhibited a similar, satisfactory level of attenuation and antigenicity for adults. It seems likely that the transfer of the ts-1[E] lesions to any new influenza virus will regularly result in attenuation of a recombinat virus possessing the new surface antigens.

Specific temperature-induced perturbations of secondary mRNA structures are associated with the cold-adapted temperature-sensitive phenotype of influenza A virus.

PubMed

Chursov, Andrey; Kopetzky, Sebastian J; Leshchiner, Ignaty; Kondofersky, Ivan; Theis, Fabian J; Frishman, Dmitrij; Shneider, Alexander

2012-10-01

For decades, cold-adapted, temperature-sensitive (ca/ts) strains of influenza A virus have been used as live attenuated vaccines. Due to their great public health importance it is crucial to understand the molecular mechanism(s) of cold adaptation and temperature sensitivity that are currently unknown. For instance, secondary RNA structures play important roles in influenza biology. Thus, we hypothesized that a relatively minor change in temperature (32-39°C) can lead to perturbations in influenza RNA structures and, that these structural perturbations may be different for mRNAs of the wild type (wt) and ca/ts strains. To test this hypothesis, we developed a novel in silico method that enables assessing whether two related RNA molecules would undergo (dis)similar structural perturbations upon temperature change. The proposed method allows identifying those areas within an RNA chain where dissimilarities of RNA secondary structures at two different temperatures are particularly pronounced, without knowing particular RNA shapes at either temperature. We identified such areas in the NS2, PA, PB2 and NP mRNAs. However, these areas are not identical for the wt and ca/ts mutants. Differences in temperature-induced structural changes of wt and ca/ts mRNA structures may constitute a yet unappreciated molecular mechanism of the cold adaptation/temperature sensitivity phenomena.

Multitiered and Cooperative Surveillance of Mitochondrial Phosphatidylserine Decarboxylase 1.

PubMed

Ogunbona, Oluwaseun B; Onguka, Ouma; Calzada, Elizabeth; Claypool, Steven M

2017-09-01

Phosphatidylserine decarboxylase 1 (Psd1p), an ancient enzyme that converts phosphatidylserine to phosphatidylethanolamine in the inner mitochondrial membrane, must undergo an autocatalytic self-processing event to gain activity. Autocatalysis severs the protein into a large membrane-anchored β subunit that noncovalently associates with the small α subunit on the intermembrane space side of the inner membrane. Here, we determined that a temperature sensitive ( ts ) PSD1 allele is autocatalytically impaired and that its fidelity is closely monitored throughout its life cycle by multiple mitochondrial quality control proteases. Interestingly, the proteases involved in resolving misfolded Psd1 ts vary depending on its autocatalytic status. Specifically, the degradation of a Psd1 ts precursor unable to undergo autocatalysis requires the unprecedented cooperative and sequential actions of two inner membrane proteases, Oma1p and Yme1p. In contrast, upon heat exposure postautocatalysis, Psd1 ts β subunits accumulate in protein aggregates that are resolved by Yme1p acting alone, while the released α subunit is degraded in parallel by an unidentified protease. Importantly, the stability of endogenous Psd1p is also influenced by Yme1p. We conclude that Psd1p, the key enzyme required for the mitochondrial pathway of phosphatidylethanolamine production, is closely monitored at several levels and by multiple mitochondrial quality control mechanisms present in the intermembrane space. Copyright © 2017 American Society for Microbiology.

Clinical and laboratory features of neuropathies with serum IgM binding to TS-HDS.

PubMed

Pestronk, Alan; Schmidt, Robert E; Choksi, Rati M; Sommerville, R Brian; Al-Lozi, Muhammad T

2012-06-01

In this investigation we studied clinical and laboratory features of polyneuropathies in patients with serum IgM binding to the trisulfated disaccharide IdoA2S-GlcNS-6S (TS-HDS). We retrospectively compared 58 patients with selective IgM binding to TS-HDS to 41 consecutive patients with polyneuropathies without TS-HDS binding. Patients with IgM vs. TS-HDS commonly had distal, sensory, axonal neuropathies. Weakness was associated with IgM M-proteins. Hand pain and serum IgM M-proteins were more common than in control neuropathy patients. TS-HDS antibody binding was often selectively κ class. Biopsies showed capillary pathology with thickened basal lamina and C5b9 complement deposition. IgM in sera with TS-HDS antibodies often bound to capillaries. Serum IgM binding to TS-HDS is associated with painful, sensory > motor, polyneuropathies with an increased frequency of persistent hand discomfort, serum IgM M-proteins, and capillary pathology. Serum IgM binding to TS-HDS suggests a possible immune etiology underlying some otherwise idiopathic sensory polyneuropathies. Copyright © 2011 Wiley Periodicals, Inc.

Tourette Syndrome and Stigma: A Place from Which Parents Advocate. Special Project in Sociology/Anthropology.

ERIC Educational Resources Information Center

Jeffery, Kelly

This paper presents a historical background and definition of Tourette Syndrome (TS), a review of the literature, and a view of the TS person as stigmatized in society. Social processes are examined through the eyes of the TS individual, and the impact of education on the TS person is examined. TS is viewed as the presence of motor or vocal tics,…

Effect of initial total solids concentration on volatile fatty acid production from food waste during anaerobic acidification.

PubMed

Wang, Quan; Jiang, Jianguo; Zhang, Yujing; Li, Kaimin

2015-01-01

The effect of initial total solids (TS) concentration on volatile fatty acid (VFAs) production from food waste under mesophilic conditions (35 °C) was determined. VFAs concentration and composition, biogas production, soluble chemical oxygen demand concentration, TS and volatile solids (VS) reduction, and ammonia nitrogen [Formula: see text] release were investigated. The VFAs concentrations were 26.10, 39.68, 59.58, and 62.64 g COD/L at TS contents of 40, 70, 100, and 130 g/L, respectively. While the VFAs' yields ranged from 0.467 to 0.799 g COD/g VSfed, decreased as initial TS increased. The percentage of propionate was not affected by TS concentration, accounting for 30.19-34.86% of the total VFAs, while a higher percentage of butyrate and lower percentage of acetate was achieved at a higher TS concentration. Biogas included mainly hydrogen and carbon dioxide and the maximum hydrogen yield of 148.9 ml/g VSfed was obtained at 130 g TS/L. [Formula: see text] concentration, TS and VS reductions increased as initial TS increased. Considering the above variables, we conclude that initial TS of 100 g/L shall be the most appropriate to VFAs production.

Predicting allergic contact dermatitis: a hierarchical structure activity relationship (SAR) approach to chemical classification using topological and quantum chemical descriptors

NASA Astrophysics Data System (ADS)

Basak, Subhash C.; Mills, Denise; Hawkins, Douglas M.

2008-06-01

A hierarchical classification study was carried out based on a set of 70 chemicals—35 which produce allergic contact dermatitis (ACD) and 35 which do not. This approach was implemented using a regular ridge regression computer code, followed by conversion of regression output to binary data values. The hierarchical descriptor classes used in the modeling include topostructural (TS), topochemical (TC), and quantum chemical (QC), all of which are based solely on chemical structure. The concordance, sensitivity, and specificity are reported. The model based on the TC descriptors was found to be the best, while the TS model was extremely poor.

Structural analyses of human thymidylate synthase reveal a site that may control conformational switching between active and inactive states.

PubMed

Chen, Dan; Jansson, Anna; Sim, Daniel; Larsson, Andreas; Nordlund, Pär

2017-08-11

Thymidylate synthase (TS) is the sole enzyme responsible for de novo biosynthesis of thymidylate (TMP) and is essential for cell proliferation and survival. Inhibition of human TS (hTS) has been extensively investigated for cancer chemotherapy, but several aspects of its activity and regulation are still uncertain. In this study, we performed comprehensive structural and biophysical studies of hTS using crystallography and thermal shift assay and provided the first detailed structural information on the conformational changes induced by ligand binding to the hTS active site. We found that upon binding of the antifolate agents raltitrexed and nolatrexed, the two insert regions in hTS, the functions of which are unclear, undergo positional shifts toward the catalytic center. We investigated the inactive conformation of hTS and found that the two insert regions are also involved in the conformational transition between the active and inactive state of hTS. Moreover, we identified a ligand-binding site in the dimer interface, suggesting that the cavity in the dimer interface could serve as an allosteric site of hTS to regulate the conformational switching between the active and inactive states. On the basis of these findings, we propose a regulatory mechanism of hTS activity that involves allosteric regulation of interactions of hTS with its own mRNA depending on cellular demands for TMP. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Proteomic differential display analysis for TS-1-resistant and -sensitive pancreatic cancer cells using two-dimensional gel electrophoresis and mass spectrometry.

PubMed

Yoshida, Kanako; Kuramitsu, Yasuhiro; Murakami, Kohei; Ryozawa, Shomei; Taba, Kumiko; Kaino, Seiji; Zhang, Xiulian; Sakaida, Isao; Nakamura, Kazuyuki

2011-06-01

TS-1 is an oral anticancer agent containing two biochemical modulators for 5-fluorouracil (5-FU) and tegafur (FT), a metabolically activated prodrug of 5-FU. TS-1 has been recognized as an effective anticancer drug using standard therapies for patients with advanced pancreatic cancer along with gemcitabine. However, a high level of inherent and acquired tumor resistance to TS-1 induces difficulty in the treatment. To identify proteins linked to the TS-1-resistance of pancreatic cancer, we profiled protein expression levels in samples of TS-1-resistant and -sensitive pancreatic cancer cell lines by using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The cytotoxicity of a 5-FU/5-chloro-2,4-dihydroxypyridine (CDHP) combination towards pancreatic cancer cell lines was evaluated by MTS assay. Panc-1, BxPC-3, MiaPaCa-2 and PK59 showed high sensitivity to the 5-FU/CDHP combination (TS-1-sensitive), whereas PK45p and KLM-1 were much less sensitive (TS-1-resistant). Proteomic analysis showed that eleven spots, including T-complex protein 1 subunit beta, ribonuclease inhibitor, elongation factor 1-delta, peroxiredoxin-2 and superoxide dismutase (Cu-Zn), appeared to be down-regulated, and 29 spots, including hypoxia up-regulated protein 1, lamin-A/C, endoplasmin, fascin and annexin A1, appeared to be up-regulated in TS-1-resistant cells compared with -sensitive cells. These results suggest that the identified proteins showing different expression between TS-1-sensitive and -resistant pancreatic cancer cells possibly relate to TS-1-sensitivity. These findings could be useful to overcome the TS-1-resistance of pancreatic cancer cells.

Influence of training status and eNOS haplotypes on plasma nitrite concentrations in normotensive older adults: a hypothesis-generating study.

PubMed

da Silva, Roberta Fernanda; Sertório, Jonas Tadeu Cau; Lacchini, Riccardo; Trapé, Atila Alexandre; Tanus-Santos, José Eduardo; Rush, James W E; Amaral, Sandra Lia; Zago, Anderson Saranz

2014-12-01

The purpose of this study was to evaluate the relationship between 3 eNOS gene polymorphisms and training status (TS) in affecting plasma nitrite concentration (NO2) in normotensive adults over 50 years old. Resting blood pressure (BP) was measured in all participants (n = 101). Plasma was taken to analyze: lipid profile, nitrite concentration (NO2) and lipid peroxide levels (T-BARS). Also, genomic DNA was extracted from plasma for genotyping NOS3 polymorphisms (-786T>C; 894G>T; and VNTR in intron 4). TS was determined by one-mile walk test and Functional Fitness Test Battery from AAHPERD (TS1-regular TS; TS2-good TS; and TS3-very good TS). BP was not influenced by TS, but NO2 was 15% higher in TS3 (123 ± 27 nM) compared to TS-2 (106 ± 22 nM). No differences were found in plasma NO2 in the haplotype analyses. However, the presence of the C allele (T-786C) and ASP allele (Glu298Asp) was found to enhance the correlation between TS and NO2 levels (r = 0.492 in C/4b/ASP haplotype and r = 0.855 in C/4a/ASP haplotype). This study thus identifies NOS3 polymorphism-dependent sensitivity to the effects of physical training on plasma NO2. Maintenance of good levels of training status, in carriers of C allele for T-786C polymorphism, combined with ASP allele for Glu298Asp polymorphism, may result in an increase in the NO2 plasma concentrations, which may reflect improved NO bioavailability in older adult normotensive individuals.

Identification of two heritable cross-disorder endophenotypes for Tourette Syndrome

PubMed Central

Darrow, Sabrina M.; Hirschtritt, Matthew E.; Davis, Lea K.; Illmann, Cornelia; Osiecki, Lisa; Grados, Marco; Sandor, Paul; Dion, Yves; King, Robert; Pauls, David; Budman, Cathy L.; Cath, Danielle C.; Greenberg, Erica; Lyon, Gholson J.; Yu, Dongmei; McGrath, Lauren M.; McMahon, William M.; Lee, Paul C.; Delucchi, Kevin L.; Scharf, Jeremiah M.; Mathews, Carol A.

2016-01-01

Objective Phenotypic heterogeneity in Tourette syndrome (TS) is partly due to complex genetic relationships between TS, obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts. Method 3494 individuals recruited for genetic studies were assessed for TS, OCD, and ADHD symptoms. Symptom-level factor and latent class analyses were conducted in TS families and replicated in an independent sample. Classes were characterized by comorbidity rates and proportion of parents. Heritability and TS-, OCD-, and ADHD-associated polygenic load were estimated. Results We identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high (disinhibition factor= 0.35, SE=0.03, p= 4.2 ×10−34; symmetry factor= 0.39, SE=0.03, p= 7.2 ×10−31; symmetry class=0.38, SE=0.10, p=0.001). Mothers of TS probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a TS genome-wide association study (GWAS) were associated with symmetry (p= 0.02), while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were associated with disinhibition (p =0.03), while TS and ADHD risk scores were not. Conclusions We identified two heritable TS-related endophenotypes that cross traditional diagnostic boundaries. The symmetry phenotype correlated with TS polygenic load, and was present in otherwise “TS-unaffected” mothers, suggesting that this phenotype may reflect additional TS (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses. PMID:27809572

Tourette Syndrome as an Independent Risk Factor for Subsequent Sleep Disorders in Children: A Nationwide Population-Based Case-Control Study.

PubMed

Lee, Wang-Tso; Huang, Hui-Ling; Wong, Lee Chin; Weng, Wen-Chin; Vasylenko, Tamara; Jong, Yuh-Jyh; Lin, Wei-Sheng; Ho, Shinn-Ying

2017-03-01

Tourette syndrome (TS) is associated with a variety of neuropsychiatric comorbidities. However, the relationship between TS and sleep disorders in children is less investigated. This nationwide population-based case-control study aimed to determine the correlation of TS and sleep disorders in children. Patients aged less than 18 years with newly diagnosed TS from 2001 to 2007 were collected (n = 1124) using data from Taiwan's National Health Insurance Research Database and were compared with a comparison cohort (n = 3372). The adjusted hazard ratio (aHR) for developing sleep disorders was calculated by multivariate Cox proportional hazards model. TS was more prevalent in boys, with a male to female ratio of 3.16:1. TS group also had significantly higher urbanization level of residence than controls (p < .001). The overall incidence rate of sleep disorders was 7.24‰ in children with TS, compared to 3.53‰ in controls. The TS group was associated with a significantly higher rate of sleep disorders, with a crude HR of 2.05 (95% confidence inerval [CI] = 1.43-2.95, p < .001). Among the comorbidities of TS, anxiety disorder was associated with the highest risk for sleep disorders (crude HR = 3.26, 95% CI = 1.52-7.00, p < .001). The aHR for TS cohort to develop sleep disorders was 1.72 (95% CI = 1.16-2.53, p = .007). The increased risk of sleep disorders in children with TS cannot be fully attributed to its comorbidities, and TS is an independent risk factor for sleep disorders in children. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Postural tachycardia syndrome is associated with significant symptoms and functional impairment predominantly affecting young women: a UK perspective

PubMed Central

McDonald, Claire; Koshi, Sharon; Busner, Lorna; Kavi, Lesley; Newton, Julia L

2014-01-01

Objective To examine a large UK cohort of patients with postural tachycardia syndrome (PoTS), to compare demographic characteristics, symptoms and treatment of PoTS at one centre compared to the largest patient group PoTS UK and to verify if their functional limitation is similar to patients with chronic fatigue syndrome (CFS). Design A cross-sectional study assessed the frequency of symptoms and their associated variables. Patients and setting Two PoTS cohorts were: (1) recruited via PoTS UK, (2) diagnosed at Newcastle Hospitals National Health Service (NHS) Foundation Trust 2009–2012. Patients with PoTS were then compared to a matched cohort with CFS. Main outcome measures Patients’ detailed demographics, time to diagnosis, education, disability, medications, comorbidity and precipitants. Symptom assessment tools captured, Fatigue Impact Scale, Epworth Sleepiness Scale, Orthostatic Grading Scale (OGS), Hospital Anxiety and Depression Scale, Health Assessment Questionnaire, Cognitive Failures Questionnaire. Results 136 patients with PoTS participated (84 members of PoTS UK (170 cohort; 50% return) and 52 (87 cohort; 60%) from Newcastle Clinics). The PoTS UK population was significantly younger than the clinic patients, with significantly fewer men (p=0.005). Over 60% had a university or postgraduate degree. Significantly more of the PoTS UK cohort were working, with hours worked being significantly higher (p=0.001). Time to diagnosis was significantly longer in the PoTS UK cohort (p=0.04). Symptom severity was comparable between cohorts. The PoTS total group was compared with a matched CFS cohort; despite comparable levels of fatigue and sleepiness, autonomic symptom burden (OGS) was statistically significantly higher. The most common treatment regime included β-blockers. Overall, 21 treatment combinations were described. Up to 1/3 were taking no treatment. Conclusions Patients with PoTS are predominantly women, young, well educated and have significant and debilitating symptoms that impact significantly on quality of life. Despite this, there is no consistent treatment. PMID:24934205

E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy.

PubMed

Sulzyc-Bielicka, Violetta; Domagala, Pawel; Bielicki, Dariusz; Safranow, Krzysztof; Rogowski, Wojciech; Domagala, Wenancjusz

2016-07-01

The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR = 3,78, P = 0,009) and DFS (HR = 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P = 0.008) and OS (P = 0.01). About 37 and 31 % difference in 3-year DFS and OS respectively were seen between patients with E2F1+TS+ vs. E2F1-TS- colon cancer immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU.

Electrostatic channeling in P. falciparum DHFR-TS: Brownian dynamics and Smoluchowski modeling.

PubMed

Metzger, Vincent T; Eun, Changsun; Kekenes-Huskey, Peter M; Huber, Gary; McCammon, J Andrew

2014-11-18

We perform Brownian dynamics simulations and Smoluchowski continuum modeling of the bifunctional Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (P. falciparum DHFR-TS) with the objective of understanding the electrostatic channeling of dihydrofolate generated at the TS active site to the DHFR active site. The results of Brownian dynamics simulations and Smoluchowski continuum modeling suggest that compared to Leishmania major DHFR-TS, P. falciparum DHFR-TS has a lower but significant electrostatic-mediated channeling efficiency (?15-25%) at physiological pH (7.0) and ionic strength (150 mM). We also find that removing the electric charges from key basic residues located between the DHFR and TS active sites significantly reduces the channeling efficiency of P. falciparum DHFR-TS. Although several protozoan DHFR-TS enzymes are known to have similar tertiary and quaternary structure, subtle differences in structure, active-site geometry, and charge distribution appear to influence both electrostatic-mediated and proximity-based substrate channeling.

Distinct contributions of replication and transcription to mutation rate variation of human genomes.

PubMed

Cui, Peng; Ding, Feng; Lin, Qiang; Zhang, Lingfang; Li, Ang; Zhang, Zhang; Hu, Songnian; Yu, Jun

2012-02-01

Here, we evaluate the contribution of two major biological processes--DNA replication and transcription--to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes. Copyright © 2012 Beijing Genomics Institute. Published by Elsevier Ltd. All rights reserved.

Action Recognition Using 3D Histograms of Texture and A Multi-Class Boosting Classifier.

PubMed

Zhang, Baochang; Yang, Yun; Chen, Chen; Yang, Linlin; Han, Jungong; Shao, Ling

2017-10-01

Human action recognition is an important yet challenging task. This paper presents a low-cost descriptor called 3D histograms of texture (3DHoTs) to extract discriminant features from a sequence of depth maps. 3DHoTs are derived from projecting depth frames onto three orthogonal Cartesian planes, i.e., the frontal, side, and top planes, and thus compactly characterize the salient information of a specific action, on which texture features are calculated to represent the action. Besides this fast feature descriptor, a new multi-class boosting classifier (MBC) is also proposed to efficiently exploit different kinds of features in a unified framework for action classification. Compared with the existing boosting frameworks, we add a new multi-class constraint into the objective function, which helps to maintain a better margin distribution by maximizing the mean of margin, whereas still minimizing the variance of margin. Experiments on the MSRAction3D, MSRGesture3D, MSRActivity3D, and UTD-MHAD data sets demonstrate that the proposed system combining 3DHoTs and MBC is superior to the state of the art.

Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation

NASA Astrophysics Data System (ADS)

Lira-Navarrete, Erandi; de Las Rivas, Matilde; Compañón, Ismael; Pallarés, María Carmen; Kong, Yun; Iglesias-Fernández, Javier; Bernardes, Gonçalo J. L.; Peregrina, Jesús M.; Rovira, Carme; Bernadó, Pau; Bruscolini, Pierpaolo; Clausen, Henrik; Lostao, Anabel; Corzana, Francisco; Hurtado-Guerrero, Ramon

2015-05-01

Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity and relies on a flexible linker located between the catalytic and the lectin domains. Our results also shed light on how GalNAc-Ts generate dense decoration of proteins with O-glycans.

Early Lineage Priming by Trisomy of Erg Leads to Myeloproliferation in a Down Syndrome Model

PubMed Central

Ng, Ashley P.; Hu, Yifang; Metcalf, Donald; Hyland, Craig D.; Ierino, Helen; Phipson, Belinda; Wu, Di; Baldwin, Tracey M.; Kauppi, Maria; Kiu, Hiu; Di Rago, Ladina; Hilton, Douglas J.; Smyth, Gordon K.; Alexander, Warren S.

2015-01-01

Down syndrome (DS), with trisomy of chromosome 21 (HSA21), is the commonest human aneuploidy. Pre-leukemic myeloproliferative changes in DS foetal livers precede the acquisition of GATA1 mutations, transient myeloproliferative disorder (DS-TMD) and acute megakaryocytic leukemia (DS-AMKL). Trisomy of the Erg gene is required for myeloproliferation in the Ts(1716)65Dn DS mouse model. We demonstrate here that genetic changes specifically attributable to trisomy of Erg lead to lineage priming of primitive and early multipotential progenitor cells in Ts(1716)65Dn mice, excess megakaryocyte-erythroid progenitors, and malignant myeloproliferation. Gene expression changes dependent on trisomy of Erg in Ts(1716)65Dn multilineage progenitor cells were correlated with those associated with trisomy of HSA21 in human DS hematopoietic stem and primitive progenitor cells. These data suggest a role for ERG as a regulator of hematopoietic lineage potential, and that trisomy of ERG in the context of DS foetal liver hemopoiesis drives the pre-leukemic changes that predispose to subsequent DS-TMD and DS-AMKL. PMID:25973911

A Temperature-Sensitive Lesion in the N-Terminal Domain of the Rotavirus Polymerase Affects Its Intracellular Localization and Enzymatic Activity

PubMed Central

McKell, Allison O.; LaConte, Leslie E. W.

2017-01-01

ABSTRACT Temperature-sensitive (ts) mutants of simian rotavirus (RV) strain SA11 have been previously created to investigate the functions of viral proteins during replication. One mutant, SA11-tsC, has a mutation that maps to the gene encoding the VP1 polymerase and shows diminished growth and RNA synthesis at 39°C compared to that at 31°C. In the present study, we sequenced all 11 genes of SA11-tsC, confirming the presence of an L138P mutation in the VP1 N-terminal domain and identifying 52 additional mutations in four other viral proteins (VP4, VP7, NSP1, and NSP2). To investigate whether the L138P mutation induces a ts phenotype in VP1 outside the SA11-tsC genetic context, we employed ectopic expression systems. Specifically, we tested whether the L138P mutation affects the ability of VP1 to localize to viroplasms, which are the sites of RV RNA synthesis, by expressing the mutant form as a green fluorescent protein (GFP) fusion protein (VP1L138P-GFP) (i) in wild-type SA11-infected cells or (ii) in uninfected cells along with viroplasm-forming proteins NSP2 and NSP5. We found that VP1L138P-GFP localized to viroplasms and interacted with NSP2 and/or NSP5 at 31°C but not at 39°C. Next, we tested the enzymatic activity of a recombinant mutant polymerase (rVP1L138P) in vitro and found that it synthesized less RNA at 39°C than at 31°C, as well as less RNA than the control at all temperatures. Together, these results provide a mechanistic basis for the ts phenotype of SA11-tsC and raise important questions about the role of leucine 138 in supporting key protein interactions and the catalytic function of the VP1 polymerase. IMPORTANCE RVs cause diarrhea in the young of many animal species, including humans. Despite their medical and economic importance, gaps in knowledge exist about how these viruses replicate inside host cells. Previously, a mutant simian RV (SA11-tsC) that replicates worse at higher temperatures was identified. This virus has an amino acid mutation in VP1, which is the enzyme responsible for copying the viral RNA genome. The mutation is located in a poorly understood region of the polymerase called the N-terminal domain. In this study, we determined that the mutation reduces the ability of VP1 to properly localize within infected cells at high temperatures, as well as reduced the ability of the enzyme to copy viral RNA in a test tube. The results of this study explain the temperature sensitivity of SA11-tsC and shed new light on functional protein-protein interaction sites of VP1. PMID:28100623

Reliability of temporal summation and diffuse noxious inhibitory control

PubMed Central

Cathcart, Stuart; Winefield, Anthony H; Rolan, Paul; Lushington, Kurt

2009-01-01

BACKGROUND: The test-retest reliability of temporal summation (TS) and diffuse noxious inhibitory control (DNIC) has not been reported to date. Establishing such reliability would support the possibility of future experimental studies examining factors affecting TS and DNIC. Similarly, the use of manual algometry to induce TS, or an occlusion cuff to induce DNIC of TS to mechanical stimuli, has not been reported to date. Such devices may offer a simpler method than current techniques for inducing TS and DNIC, affording assessment at more anatomical locations and in more varied research settings. METHOD: The present study assessed the test-retest reliability of TS and DNIC using the above techniques. Sex differences on these measures were also investigated. RESULTS: Repeated measures ANOVA indicated successful induction of TS and DNIC, with no significant differences across test-retest occasions. Sex effects were not significant for any measure or interaction. Intraclass correlations indicated high test-retest reliability for all measures; however, there was large interindividual variation between test and retest measurements. CONCLUSION: The present results indicate acceptable within-session test-retest reliability of TS and DNIC. The results support the possibility of future experimental studies examining factors affecting TS and DNIC. PMID:20011713

Precursor effect on the property and catalytic behavior of Fe-TS-1 in butadiene epoxidation

NASA Astrophysics Data System (ADS)

Wu, Mei; Zhao, Huahua; Yang, Jian; Zhao, Jun; Song, Huanling; Chou, Lingjun

2017-11-01

The effect of iron precursor on the property and catalytic behavior of iron modified titanium silicalite molecular sieve (Fe-TS-1) catalysts in butadiene selective epoxidation has been studied. Three Fe-TS-1 catalysts were prepared, using iron nitrate, iron chloride and iron sulfate as precursors, which played an important role in adjusting the textural properties and chemical states of TS-1. Of the prepared Fe-TS-1 catalysts, those modified by iron nitrate (FN-TS-1) exhibited a significant enhanced performance in butadiene selective epoxidation compared to those derived from iron sulfate (FS-TS-1) or iron chloride (FC-TS-1) precursors. To obtain a deep understanding of their structure-performance relationship, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Temperature programmed desorption of NH3 (NH3-TPD), Diffuse reflectance UV-Vis spectra (DR UV-Vis), Fourier transformed infrared spectra (FT-IR) and thermal gravimetric analysis (TGA) were conducted to characterize Fe-TS-1 catalysts. Experimental results indicated that textural structures and acid sites of modified catalysts as well as the type of Fe species influenced by the precursors were all responsible for the activity and product distribution.

Holocene Tsunami Deposits From Large Tsunamis Along the Kuril Subduction Zone, Northeast Japan

NASA Astrophysics Data System (ADS)

Nanayama, F.; Furukawa, R.; Satake, K.; Soeda, Y.; Shigeno, K.

2003-12-01

Holocene tsunami deposits in eastern Hokkaido between Nemuro and Tokachi show that the Kuril subduction zone repeatedly produced earthquakes and tsunamis larger than those recorded in this region since AD 1804 (Nanayama et al., Nature, 424, 660-663, 2003). Twenty-two postulated tsunami sand layers from the past 9500 years are preserved on lake bottom near Kushiro City, and about ten postulated tsunami sand layers from the past 3000 years are preserved in peat layers on the coastal marsh of Kiritappu. We dated these ten tsunami deposits (named Ts1 to Ts10 from shallower to deeper) in peat layers by radiocarbon and tephrochronology, correlated them with historical earthquakes and tsunamis, and surveyed their spatial distribution to estimate the tsunamisO inland inundation limits. Ts10 and Ts9 are under regional tephra Ta-c2 (ca. 2.5 ka) and represent prehistorical events. Ts8 to Ts5 are between two regional tephra layers Ta-c2 and B-Tm (ca. 9th century). In particular, Ts5 is found just below B-Tm, so it is dated 9th century (Heian era). Ts4 is dated ca 13th century (Kamakura era), while Ts3, found just below Us-b and Ta-b (AD 1667-1663), is dated 17th century (Edo era). Ts2 is dated 19th century (Edo era) and may correspond to the AD 1843 Tempo Tokachi-oki earthquake (Mt 8.0) recorded in a historical document Nikkanki of Kokutai-ji temple at Akkeshi. Ts1 is inferred 20th century and may correspond to the tsunami from the AD 1960 Chilean earthquake (M 9.5) or the AD 1952 Tokachi-oki earthquake (Mt 8.2). Our detailed surveys indicate that Ts3 and Ts4 can be traced more than 3 km from the present coast line in Kirittapu marsh, much longer than the limits (< 1 km) of recent deposits Ts1 and Ts2 or documented inundation of the 19th and 20th century tsunamis. The recurrence intervals of great tsunami inundation are about 400 to 500 years, longer than that of typical interplate earthquakes along the Kuril subduction zone. The longer interval and the apparent large tsunami inundation indicate unusual origin of these tsunamis.

The mechanism and high-free-energy transition state of lac repressor–lac operator interaction

PubMed Central

Sengupta, Rituparna; Capp, Michael W.; Shkel, Irina A.

2017-01-01

Abstract Significant, otherwise-unavailable information about mechanisms and transition states (TS) of protein folding and binding is obtained from solute effects on rate constants. Here we characterize TS for lac repressor(R)–lac operator(O) binding by analyzing effects of RO-stabilizing and RO-destabilizing solutes on association (ka) and dissociation (kd) rate constants. RO-destabilizing solutes (urea, KCl) reduce ka comparably (urea) or more than (KCl) they increase kd, demonstrating that they destabilize TS relative to reactants and RO, and that TS exhibits most of the Coulombic interactions between R and O. Strikingly, three solutes which stabilize RO by favoring burial/dehydration of amide oxygens and anionic phosphate oxygens all reduce kd without affecting ka significantly. The lack of stabilization of TS by these solutes indicates that O phosphates remain hydrated in TS and that TS preferentially buries aromatic carbons and amide nitrogens while leaving amide oxygens exposed. In our proposed mechanism, DNA-binding-domains (DBD) of R insert in major grooves of O pre-TS, forming most Coulombic interactions of RO and burying aromatic carbons. Nucleation of hinge helices creates TS, burying sidechain amide nitrogens. Post-TS, hinge helices assemble and the DBD-hinge helix-O-DNA module docks on core repressor, partially dehydrating phosphate oxygens and tightening all interfaces to form RO. PMID:29036376

Toona sinensis Inhibits Murine Leukemia WEHI-3 Cells and Promotes Immune Response In Vivo.

PubMed

Yang, Hsin-Ling; Thiyagarajan, Varadharajan; Liao, Jiunn-Wang; Chu, Yu-Lin; Chang, Chia-Ting; Huang, Pei-Jane; Hsu, Chih-Jung; Hseu, You-Cheng

2017-09-01

Toona sinensis (TS) is one of the most popular vegetarian dishes in Taiwan. It has been shown to exhibit antioxidant, antiangiogenic, antiatherosclerotic, and anticancer properties. In this study, we demonstrated the ability of aqueous leaf extracts from TS to promote immune responses in BALB/c mice and to exhibit anti-leukemia activity in murine WEHI-3 cells. BALB/c mice were injected intravenously with WEHI-3 cells and then treated orally with TS (50 mg/kg). In vivo study showed that TS treatment reduced liver and spleen enlargement in WEHI-3 bearing mice compared with the untreated group. Furthermore, TS also decreased white blood cells (WBC), indicating inhibition of differentiation of the precursor of macrophages in WEHI-3 bearing mice. Treatment of WEHI-3 cells with TS (0-75 μg/mL for 24 hours) significantly reduced cell viability. Furthermore, TS treatment-induced late apoptosis was confirmed by Annexin-V/PI staining. Western blot analyses revealed that treatment of WEHI-3 cells with TS statistically increased the protein expression level of cytochrome c in the cytoplasm and activates caspase-3. Notably, TS treatment caused a dramatic reduction in Bcl-2 and increase in Bax protein levels. TS may disturb the Bcl-2 and Bax protein ratio and induce apoptosis. This reports confirms the antitumor activity of this nutritious vegetable potentially against leukemia.

Leaving Group Ability Observably Affects Transition State Structure in a Single Enzyme Active Site.

PubMed

Roston, Daniel; Demapan, Darren; Cui, Qiang

2016-06-15

A reaction's transition state (TS) structure plays a critical role in determining reactivity and has important implications for the design of catalysts, drugs, and other applications. Here, we explore TS structure in the enzyme alkaline phosphatase using hybrid Quantum Mechanics/Molecular Mechanics simulations. We find that minor perturbations to the substrate have major effects on TS structure and the way the enzyme stabilizes the TS. Substrates with good leaving groups (LGs) have little cleavage of the phosphorus-LG bond at the TS, while substrates with poor LGs have substantial cleavage of that bond. The results predict nonlinear free energy relationships for a single rate-determining step, and substantial differences in kinetic isotope effects for different substrates; both trends were observed in previous experimental studies, although the original interpretations differed from the present model. Moreover, due to different degrees of phosphorus-LG bond cleavage at the TS for different substrates, the LG is stabilized by different interactions at the TS: while a poor LG is directly stabilized by an active site zinc ion, a good LG is mainly stabilized by active site water molecules. Our results demonstrate the considerable plasticity of TS structure and stabilization in enzymes. Furthermore, perturbations to reactivity that probe TS structure experimentally (i.e., substituent effects) may substantially perturb the TS they aim to probe, and thus classical experimental approaches such as free energy relations should be interpreted with care.

Toona sinensis Inhibits Murine Leukemia WEHI-3 Cells and Promotes Immune Response In Vivo

PubMed Central

Yang, Hsin-Ling; Thiyagarajan, Varadharajan; Liao, Jiunn-Wang; Chu, Yu-Lin; Chang, Chia-Ting; Huang, Pei-Jane; Hsu, Chih-Jung; Hseu, You-Cheng

2016-01-01

Toona sinensis (TS) is one of the most popular vegetarian dishes in Taiwan. It has been shown to exhibit antioxidant, antiangiogenic, antiatherosclerotic, and anticancer properties. In this study, we demonstrated the ability of aqueous leaf extracts from TS to promote immune responses in BALB/c mice and to exhibit anti-leukemia activity in murine WEHI-3 cells. BALB/c mice were injected intravenously with WEHI-3 cells and then treated orally with TS (50 mg/kg). In vivo study showed that TS treatment reduced liver and spleen enlargement in WEHI-3 bearing mice compared with the untreated group. Furthermore, TS also decreased white blood cells (WBC), indicating inhibition of differentiation of the precursor of macrophages in WEHI-3 bearing mice. Treatment of WEHI-3 cells with TS (0-75 μg/mL for 24 hours) significantly reduced cell viability. Furthermore, TS treatment–induced late apoptosis was confirmed by Annexin-V/PI staining. Western blot analyses revealed that treatment of WEHI-3 cells with TS statistically increased the protein expression level of cytochrome c in the cytoplasm and activates caspase-3. Notably, TS treatment caused a dramatic reduction in Bcl-2 and increase in Bax protein levels. TS may disturb the Bcl-2 and Bax protein ratio and induce apoptosis. This reports confirms the antitumor activity of this nutritious vegetable potentially against leukemia. PMID:27151590

In vivo imaging of tumour angiogenesis in mice with the alpha(v)beta (3) integrin-targeted tracer 99mTc-RAFT-RGD.

PubMed

Sancey, Lucie; Ardisson, Valérie; Riou, Laurent M; Ahmadi, Mitra; Marti-Batlle, Danièle; Boturyn, Didier; Dumy, Pascal; Fagret, Daniel; Ghezzi, Catherine; Vuillez, Jean-Philippe

2007-12-01

The molecular imaging of tumour neoangiogenesis currently represents a major field of research for the diagnostic and treatment strategy of solid tumours. Endothelial cells from tumour neovessels overexpress the alpha(v)beta(3) integrin, which selectively binds to Arg-Gly-Asp (RGD)-containing peptides. We evaluated the potential of the novel radiotracer (99m)Tc-RAFT-RGD for the non-invasive molecular imaging of alpha(v)beta(3) integrin expression in mice models of tumour development. (99m)Tc-RAFT-RGD, (99m)Tc-cRGD (specific control) and (99m)Tc-RAFT-RAD (non-specific control) were injected intravenously to mice bearing B16F0 or TS/A-pc tumours. In vivo whole-body tomographic imaging and post-mortem biodistribution studies were performed 60 min following tracer injection. Adjacent tumour slices were used to compare the localisation of neovessels from immunostaining and the pattern of (99m)Tc-RAFT-RGD uptake from autoradiographic ex vivo imaging. Biodistribution studies indicated that (99m)Tc-RAFT-RGD tumour uptake was significantly higher than that of (99m)Tc-RAFT-RAD in B16F0 (2.4+/-0.5 vs 1.0+/-0.1%ID/g, respectively) and in TS/A-pc tumours (2.7+/-0.8 vs 0.7+/-0.1%ID/g, respectively). Immunohistochemical and autoradiographic studies indicated that (99m)Tc-RAFT-RGD intratumoural uptake preferentially occurred in angiogenic areas. Tomographic imaging allowed tumour visualisation following injection of (99m)Tc-RAFT-RGD and (99m)Tc-cRGD with similar tumour-to-contralateral muscle (T/CM) ratios in B16F0 and in TS/A-pc tumours whereas (99m)Tc-RAFT-RAD T/CM ratios did not allow tumour imaging. In accordance with the higher level of alpha(v)beta(3) integrin expression on TS/A-pc tumours than on B16F0 tumours as determined from western blot and immunoprecipitation analyses, the (99m)Tc-RAFT-RGD T/CM ratio was significantly higher in TS/A-pc than in B16F0 tumours. (99m)Tc-RAFT-RGD allowed the in vivo imaging of alpha(v)beta(3) integrin tumour expression.

Prevalence of diverse complications and its association with karyotypes in Japanese adult women with Turner syndrome-a questionnaire survey by the Foundation for Growth Science.

PubMed

Hanew, Kunihiko; Tanaka, Toshiaki; Horikawa, Reiko; Hasegawa, Tomonobu; Yokoya, Susumu

2018-05-28

The reported prevalence of complications in Turner Syndrome (TS) was highly variable because of the rarity and the limited numbers analyzed. Again, possible presence of other complications that are not described as specific for TS, is also speculated. To resolve these issues, a questionnaire survey was conducted in hGH treated 492 patients with adult TS (17-42 years). The possible association with these complications and karyotypes were also analyzed. The complications and their prevalence were as follows: chronic thyroiditis (25.2%), inflammatory bowel disease (1.8%), congenital cardiovascular anomaly (11.8%), urinary tract malformation (11.8%), low bone mineral density (BMD) (42.9%), scoliosis (8.4%), hearing loss (6.2%), epilepsy (2.8%) and schizophrenia (0.9%). The majority of prevalence of these diseases in TS was higher than in the general population. In distribution, the most frequent karyotype was 45,X monosomy (28.9%), followed by 45,X/46,X,Xi (16.9%), 46,X,Xi (9.1%), and 45,X/46,XX (6.3%), while other mosaic 45,X was noted in 29.9%. Regarding the karyotype, cardiovascular anomaly was more frequent in the 45,X group and less in the 46,X,Xi group. Urinary tract malformation and epilepsy were frequently associated with the chromosome 45,X. The prevalence of low BMD was noticed more in the chromosome 46,X,Xi and 45,X/46,X,Xi, and less in other mosaic 45,X. In conclusion, the more exact prevalence of diverse complications was clarified and it exceeded the prevalence of the majority of complications in general population. As novel findings, it was observed that the prevalence of epilepsy was significantly high, and epilepsy and low BMD were frequently associated with the specific karyotypes.

Adrenalectomy for Cushing's syndrome: do's and don'ts.

PubMed

Paduraru, D N; Nica, A; Carsote, M; Valea, A

2016-01-01

Aim. To present specific aspects of adrenalectomy for Cushing's syndrome (CS) by introducing well established aspects ("do's") and less known aspects ("don'ts"). Material and Method. This is a narrative review. Results. The "do's" for laparoscopic adrenalectomy (LA) are the following: it represents the "gold standard" for secretor and non-secretor adrenal tumors and the first line therapy for CS with an improvement of cardio-metabolic co-morbidities; the success rate depending on the adequate patients' selection and the surgeon's skills. The "don'ts" are large (>6-8 centimeters), locally invasive, malignant tumors requiring open adrenalectomy (OA). Robotic adrenalectomy is a new alternative for LA, with similar safety and conversion rate and lower pain drugs use. The "don'ts" are the following: lack of randomized controlled studies including oncologic outcome, different availability at surgical centers. Related to the sub-types of CS, the "do's" are the following: adrenal adenomas which are cured by LA, while adrenocortical carcinoma (ACC) requires adrenalectomy as first line therapy and adjuvant mitotane therapy; synchronous bilateral adrenalectomy (SBA) is useful for Cushing's disease (only cases refractory to pituitary targeted therapy), for ectopic Cushing's syndrome (cases with unknown or inoperable primary site), and for bilateral cortisol producing adenomas. The less established aspects are the following: criteria of skilled surgeon to approach ACC; the timing of surgery in subclinical CS; the need for adrenal vein catheterization (which is not available in many centers) to avoid unnecessary SBA. Conclusion. Adrenalectomy for CS is a dynamic domain; LA overstepped the former OA area. The future will improve the knowledge related to RA while the cutting edge is represented by a specific frame of intervention in SCS, children and pregnant women. Abbreviations: ACC = adrenocortical carcinoma, ACTH = Adrenocorticotropic Hormone, CD = Cushing's disease, CS = Cushing's syndrome, ECS = Ectopic Cushing's syndrome, LA = laparoscopic adrenalectomy, OA = open adrenalectomy, PA = partial adrenalectomy, RA = robotic adrenalectomy, SCS = subclinical Cushing' syndrome.

GPi Oscillatory Activity Differentiates Tics from the Resting State, Voluntary Movements, and the Unmedicated Parkinsonian State

PubMed Central

Jimenez-Shahed, Joohi; Telkes, Ilknur; Viswanathan, Ashwin; Ince, Nuri F.

2016-01-01

Background: Deep brain stimulation (DBS) is an emerging treatment strategy for severe, medication-refractory Tourette syndrome (TS). Thalamic (Cm-Pf) and pallidal (including globus pallidus interna, GPi) targets have been the most investigated. While the neurophysiological correlates of Parkinson's disease (PD) in the GPi and subthalamic nucleus (STN) are increasingly recognized, these patterns are not well characterized in other disease states. Recent findings indicate that the cross-frequency coupling (CFC) between beta band and high frequency oscillations (HFOs) within the STN in PD patients is pathologic. Methods: We recorded intraoperative local field potentials (LFPs) from the postero-ventrolateral GPi in three adult patients with TS at rest, during voluntary movements, and during tic activity and compared them to the intraoperative GPi-LFP activity recorded from four unmedicated PD patients at rest. Results: In all PD patients, we noted excessive beta band activity (13–30 Hz) at rest which consistently modulated the amplitude of the co-existent HFOs observed between 200 and 400 Hz, indicating the presence of beta-HFO CFC. In all 3TS patients at rest, we observed theta band activity (4–7 Hz) and HFOs. Two patients had beta band activity, though at lower power than theta oscillations. Tic activity was associated with increased high frequency (200–400 Hz) and gamma band (35–200 Hz) activity. There was no beta-HFO CFC in TS patients at rest. However, CFC between the phase of 5–10 Hz band activity and the amplitude of HFOs was found in two TS patients. During tics, this shifted to CFC between the phase of beta band activity and the amplitude of HFOs in all subjects. Conclusions: To our knowledge this is the first study that shows that beta-HFO CFC exists in the GPi of TS patients during tics and at rest in PD patients, and suggests that this pattern might be specific to pathologic/involuntary movements. Furthermore, our findings suggest that during tics, resting state 5–10 Hz-HFO CFC shifts to beta-HFO CFC which can be used to trigger stimulation in a closed loop system when tics are present. PMID:27733815

Producer estimates of prevalence and perceived importance of lameness in dairy herds with tiestalls, freestalls, and automated milking systems.

PubMed

Cutler, J H Higginson; Rushen, J; de Passillé, A M; Gibbons, J; Orsel, K; Pajor, E; Barkema, H W; Solano, L; Pellerin, D; Haley, D; Vasseur, E

2017-12-01

Lameness is one of the most important welfare and productivity concerns in the dairy industry. Our objectives were to obtain producers' estimates of its prevalence and their perceptions of lameness, and to investigate how producers monitor lameness in tiestall (TS), freestall with milking parlor (FS), and automated milking system (AMS) herds. Forty focal cows per farm in 237 Canadian dairy herds were scored for lameness by trained researchers. On the same day, the producers completed a questionnaire. Mean herd-level prevalence of lameness estimated by producers was 9.0% (±0.9%; ±SE), whereas the researchers observed a mean prevalence of 22.2% (±0.9%). Correlation between producer- and researcher-estimated lameness prevalence was low (r = 0.19) and mean researcher prevalence was 1.6, 1.8, and 4.1 times higher in AMS, FS, and TS farms, respectively. A total of 48% of producers thought lameness was a moderate or major problem in their herds (TS = 34%; AMS =53%; FS = 59%). One third of producers considered lameness the highest ranked health problem they were trying to control, whereas two-thirds of producers (TS = 43%; AMS = 63%; FS = 71%) stated that they had made management changes to deal with lameness in the past 2 yr. Almost all producers (98%) stated they routinely check cows to identify new cases of lameness; however, 40% of producers did not keep records of lameness (AMS = 24%; FS = 23%; TS = 60%). A majority (69%) of producers treated lame cows themselves immediately after detection, whereas 13% relied on hoof-trimmer or veterinarians to plan treatment. Producers are aware of lameness as an issue in dairy herds and almost all monitor lameness as part of their daily routine. However, producers underestimate lameness prevalence, which highlights that lameness detection continues to be difficult in in all housing systems, especially in TS herds. Training to improve detection, record keeping, identification of farm-specific risk factors, and treatment planning for lame cows is likely to help decrease lameness prevalence. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

New Insights into Clinical Characteristics of Gilles de la Tourette Syndrome: Findings in 1032 Patients from a Single German Center.

PubMed

Sambrani, Tanvi; Jakubovski, Ewgeni; Müller-Vahl, Kirsten R

2016-01-01

Gilles de la Tourette syndrome (TS) is a complex neuropsychiatric disorder defined by the presence of motor and phonic tics, but often associated with psychiatric comorbidities. The main objective of this study was to explore the clinical presentation and comorbidities of TS. We analyzed clinical data obtained from a large sample (n = 1032; 529 children and 503 adults) of patients with tic disorders from one single German TS center assessed by one investigator. Data was collected with the help of an expert-reviewed semi-structured interview, designed to assess tic severity and certain comorbidities. Group comparisons were carried out via independent sample t-tests and chi-square tests. The main findings of the study are: (1) tic severity is associated with the presence of premonitory urges (PU), copro-, echo-, and paliphenomena and the number of comorbidities, but not age at tic onset; it is higher in patients with comorbid obsessive-compulsive disorder (OCD) than in patients with comorbid attention deficit/hyperactivity disorder (ADHD). (2) PU were found to be highly associated with "not just right experiences" and to emerge much earlier than previously thought alongside with the ability to suppress tics (PU in >60% and suppressibility in >75% at age 8-10 years). (3) Self-injurious behavior (SIB) is highly associated with complex motor tics and coprophenomena, but not with OCD/obsessive-compulsive behavior (OCB). While comorbid ADHD is associated with a lower ability to suppress tics, comorbid depression is associated with sleeping problems. Our results demonstrate that tic severity is not influenced by age at onset. From our data, it is suggested that PU represent a specific type of "not just right experience" that is not a prerequisite for tic suppression. Comorbid ADHD reduces patients' ability of successful tic suppression. Our data suggest that SIB belongs to the coprophenomena spectrum and hence should be conceptualized as a complex tic rather than a compulsion. Finally, this study strongly supports the hypothesis that TS+OCD is a more severe form of TS and that comorbid OCD/OCB, depression, and anxiety belong to the TS spectrum, while ADHD should be better conceptualized as a separate problem.

Do cervical collars and cervicothoracic orthoses effectively stabilize the injured cervical spine? A biomechanical investigation.

PubMed

Ivancic, Paul C

2013-06-01

In vitro biomechanical study. Our objective was to determine the effectiveness of cervical collars and cervicothoracic orthoses for stabilizing clinically relevant, experimentally produced cervical spine injuries. Most previous in vitro studies of cervical orthoses used a simplified injury model with all ligaments transected at a single spinal level, which differs from real-life neck injuries. Human volunteer studies are limited to measuring only sagittal motions or 3-dimensional motions only of the head or 1 or 2 spinal levels. Three-plane flexibility tests were performed to evaluate 2 cervical collars (Vista Collar and Vista Multipost Collar) and 2 cervicothoracic orthoses (Vista TS and Vista TS4) using a skull-neck-thorax model with 8 injured cervical spine specimens (manufacturer of orthoses: Aspen Medical Products Inc, Irvine, CA). The injuries consisted of flexion-compression at the lower cervical spine and extension-compression at superior spinal levels. Pair-wise repeated measures analysis of variance (P < 0.05) and Bonferroni post hoc tests determined significant differences in average range of motions of the head relative to the base, C7 or T1, among experimental conditions. RESULTS.: All orthoses significantly reduced unrestricted head/base flexion and extension. The orthoses allowed between 8.4% and 25.8% of unrestricted head/base motion in flexion/extension, 57.8% to 75.5% in axial rotation, and 53.8% to 73.7% in lateral bending. The average percentages of unrestricted motion allowed by the Vista Collar, Vista Multipost Collar, Vista TS, and Vista TS4 were: 14.0, 9.7, 6.1, and 4.7, respectively, for middle cervical spine extension and 13.2, 11.8, 3.3, and 0.4, respectively, for lower cervical spine flexion. Successive increases in immobilization were observed from Vista Collar to Vista Multipost Collar, Vista TS, and Vista TS4 in extension at the injured middle cervical spine and in flexion at the injured lower cervical spine. Our results may assist clinicians in selecting the most appropriate orthosis based upon patient-specific cervical spine injuries.

Conducting polymer coated neural recording electrodes.

PubMed

Harris, Alexander R; Morgan, Simeon J; Chen, Jun; Kapsa, Robert M I; Wallace, Gordon G; Paolini, Antonio G

2013-02-01

Neural recording electrodes suffer from poor signal to noise ratio, charge density, biostability and biocompatibility. This paper investigates the ability of conducting polymer coated electrodes to record acute neural response in a systematic manner, allowing in depth comparison of electrochemical and electrophysiological response. Polypyrrole (Ppy) and poly-3,4-ethylenedioxythiophene (PEDOT) doped with sulphate (SO4) or para-toluene sulfonate (pTS) were used to coat iridium neural recording electrodes. Detailed electrochemical and electrophysiological investigations were undertaken to compare the effect of these materials on acute in vivo recording. A range of charge density and impedance responses were seen with each respectively doped conducting polymer. All coatings produced greater charge density than uncoated electrodes, while PEDOT-pTS, PEDOT-SO4 and Ppy-SO4 possessed lower impedance values at 1 kHz than uncoated electrodes. Charge density increased with PEDOT-pTS thickness and impedance at 1 kHz was reduced with deposition times up to 45 s. Stable electrochemical response after acute implantation inferred biostability of PEDOT-pTS coated electrodes while other electrode materials had variable impedance and/or charge density after implantation indicative of a protein fouling layer forming on the electrode surface. Recording of neural response to white noise bursts after implantation of conducting polymer-coated electrodes into a rat model inferior colliculus showed a general decrease in background noise and increase in signal to noise ratio and spike count with reduced impedance at 1 kHz, regardless of the specific electrode coating, compared to uncoated electrodes. A 45 s PEDOT-pTS deposition time yielded the highest signal to noise ratio and spike count. A method for comparing recording electrode materials has been demonstrated with doped conducting polymers. PEDOT-pTS showed remarkable low fouling during acute implantation, inferring good biostability. Electrode impedance at 1 kHz was correlated with background noise and inversely correlated with signal to noise ratio and spike count, regardless of coating. These results collectively confirm a potential for improvement of neural electrode systems by coating with conducting polymers.

Conducting polymer coated neural recording electrodes

NASA Astrophysics Data System (ADS)

Harris, Alexander R.; Morgan, Simeon J.; Chen, Jun; Kapsa, Robert M. I.; Wallace, Gordon G.; Paolini, Antonio G.

2013-02-01

Objective. Neural recording electrodes suffer from poor signal to noise ratio, charge density, biostability and biocompatibility. This paper investigates the ability of conducting polymer coated electrodes to record acute neural response in a systematic manner, allowing in depth comparison of electrochemical and electrophysiological response. Approach. Polypyrrole (Ppy) and poly-3,4-ethylenedioxythiophene (PEDOT) doped with sulphate (SO4) or para-toluene sulfonate (pTS) were used to coat iridium neural recording electrodes. Detailed electrochemical and electrophysiological investigations were undertaken to compare the effect of these materials on acute in vivo recording. Main results. A range of charge density and impedance responses were seen with each respectively doped conducting polymer. All coatings produced greater charge density than uncoated electrodes, while PEDOT-pTS, PEDOT-SO4 and Ppy-SO4 possessed lower impedance values at 1 kHz than uncoated electrodes. Charge density increased with PEDOT-pTS thickness and impedance at 1 kHz was reduced with deposition times up to 45 s. Stable electrochemical response after acute implantation inferred biostability of PEDOT-pTS coated electrodes while other electrode materials had variable impedance and/or charge density after implantation indicative of a protein fouling layer forming on the electrode surface. Recording of neural response to white noise bursts after implantation of conducting polymer-coated electrodes into a rat model inferior colliculus showed a general decrease in background noise and increase in signal to noise ratio and spike count with reduced impedance at 1 kHz, regardless of the specific electrode coating, compared to uncoated electrodes. A 45 s PEDOT-pTS deposition time yielded the highest signal to noise ratio and spike count. Significance. A method for comparing recording electrode materials has been demonstrated with doped conducting polymers. PEDOT-pTS showed remarkable low fouling during acute implantation, inferring good biostability. Electrode impedance at 1 kHz was correlated with background noise and inversely correlated with signal to noise ratio and spike count, regardless of coating. These results collectively confirm a potential for improvement of neural electrode systems by coating with conducting polymers.

75 FR 36449 - Yankee Atomic Electric Co.; Yankee Atomic Independent Spent Fuel Storage Installation; Issuance...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-25

... Specification (TS) Surveillance Requirement 3.1.6.1 to verify the operability of the concrete cask heat removal....6.1 to verify the operability of the concrete cask heat removal system to maintain safe storage...

Exercise Do's and Don'ts: Guidelines for Fitness Activities.

ERIC Educational Resources Information Center

Burgess, Sharon

Many common exercises are contraindicated due to their potential for injury relative to benefit produced. Specific contraindicated exercises are discussed, and safer, more effective exercises are recommended. Current stretching and toning guidelines are also given which apply to all fitness activities. (Author)

The directed migration of gonadal distal tip cells in Caenorhabditis elegans requires NGAT-1, a ß1,4-N-acetylgalactosaminyltransferase enzyme

PubMed Central

Veyhl, Joseph; Dunn, Robert J.; Johnston, Wendy L.; Bennett, Alexa; Zhang, Lijia W.; Dennis, James W.; Schachter, Harry

2017-01-01

Glycoproteins such as growth factor receptors and extracellular matrix have well-known functions in development and cancer progression, however, the glycans at sites of modification are often heterogeneous molecular populations which makes their functional characterization challenging. Here we provide evidence for a specific, discrete, well-defined glycan modification and regulation of a stage-specific cell migration in Caenorhabditis elegans. We show that a chain-terminating, putative null mutation in the gene encoding a predicted β1,4-N-acetylgalactosaminyltransferase, named ngat-1, causes a maternally rescued temperature sensitive (ts) defect in the second phase of the three phase migration pattern of the posterior, but not the anterior, hermaphrodite Distal Tip Cell (DTC). An amino-terminal partial deletion of ngat-1 causes a similar but lower penetrance ts phenotype. The existence of multiple ts alleles with distinctly different molecular DNA lesions, neither of which is likely to encode a ts protein, indicates that NGAT-1 normally prevents innate temperature sensitivity for phase 2 DTC pathfinding. Temperature shift analyses indicate that the ts period for the ngat-1 mutant defect ends by the beginning of post-embryonic development–nearly 3 full larval stages prior to the defective phase 2 migration affected by ngat-1 mutations. NGAT-1 homologs generate glycan-terminal GalNAc-β1-4GlcNAc, referred to as LacdiNAc modifications, on glycoproteins and glycolipids. We also found that the absence of the GnT1/Mgat1 activity [UDP-N-acetyl-D-glucosamine:α-3-D-mannoside β-1,2-N-acetylglucosaminyltransferase 1 (encoded by C. elegans gly-12, gly-13, and gly-14 and homologous to vertebrate GnT1/Mgat1)], causes a similar spectrum of DTC phenotypes as ngat-1 mutations–primarily affecting posterior DTC phase 2 migration and preventing manifestation of the same innate ts period as ngat-1. GnT1/Mgat1 is a medial Golgi enzyme known to modify mannose residues and initiate N-glycan branching, an essential step in the biosynthesis of hybrid, paucimannose and complex-type N-glycans. Quadruple mutant animals bearing putative null mutations in ngat-1 and the three GnT genes (gly-12, gly-13, gly-14) were not enhanced for DTC migration defects, suggesting NGAT-1 and GnT1 act in the same pathway. These findings suggest that GnTI generates an N-glycan substrate for NGAT-1 modification, which is required at restrictive temperature (25°C) to prevent, stabilize, reverse or compensate a perinatal thermo-labile process (or structure) causing late larval stage DTC phase 2 migration errors. PMID:28817611

Properties of Nanocrystalline Cubic Silicon Carbide Thin Films Prepared by Hot-Wire Chemical Vapor Deposition Using SiH4/CH4/H2 at Various Substrate Temperatures

NASA Astrophysics Data System (ADS)

Tabata, Akimori; Komura, Yusuke; Hoshide, Yoshiki; Narita, Tomoki; Kondo, Akihiro

2008-01-01

Silicon carbide (SiC) thin films were prepared by hot-wire chemical vapor deposition from SiH4/CH4/H2 gases, and the influence of substrate temperature, Ts (104 < Ts < 434 °C), on the properties of the SiC thin films was investigated. X-ray diffraction patterns and Raman scattering spectra revealed that nanocrystalline cubic SiC (nc-3C-SiC) films grew at Ts above 187 °C, while completely amorphous films grew at Ts = 104 °C. Fourier transform infrared absorption spectra revealed that the crystallinity of the nc-3C-SiC was improved with increasing Ts up to 282 °C and remained almost unchanged with a further increase in Ts from 282 to 434 °C. The spin density was reduced monotonically with increasing Ts.

Neurofunctional Differences Associated with Arithmetic Processing in Turner Syndrome

PubMed Central

Kesler, Shelli R.; Menon, Vinod; Reiss, Allan L.

2011-01-01

Turner syndrome (TS) is a neurogenetic disorder characterized by the absence of one X chromosome in a phenotypic female. Individuals with TS are at risk for impairments in mathematics. We investigated the neural mechanisms underlying arithmetic processing in TS. Fifteen subjects with TS and 15 age-matched typically developing controls were scanned using functional MRI while they performed easy (two-operand) and difficult (three-operand) versions of an arithmetic processing task. Both groups activated fronto-parietal regions involved in arithmetic processing during the math tasks. Compared with controls, the TS group recruited additional neural resources in frontal and parietal regions during the easier, two-operand math task. During the more difficult three-operand task, individuals with TS demonstrated significantly less activation in frontal, parietal and subcortical regions than controls. However, the TS group’s performance on both math tasks was comparable to controls. Individuals with TS demonstrate activation differences in fronto-parietal areas during arithmetic tasks compared with controls. They must recruit additional brain regions during a relatively easy task and demonstrate a potentially inefficient response to increased task difficulty compared with controls. PMID:16135780

Fermentation of wet-exploded corn stover for the production of volatile fatty acids.

PubMed

Murali, Nanditha; Fernandez, Sebastian; Ahring, Birgitte Kiaer

2017-03-01

Volatile fatty acids (VFA) have been used as platform molecules for production of biofuels and bioproducts. In the current study, we examine the VFA production from wet-exploded corn stover through anaerobic fermentation using rumen bacteria. The total VFA yield (acetic acid equivalents) was found to increase from 22.8g/L at 2.5% total solids (TS) to 40.8g/L at 5% TS. It was found that the acetic acid concentration increased from 10g/L to 22g/L at 2.5% and 5% TS, respectively. An increased propionic acid production was seen between day 10 and 20 at 5% TS. Valeric acid (4g/L) was produced at 5% TS and not at 2.5% TS. Composition analysis showed that 50% of the carbohydrates were converted to VFA at 5% TS and 33% at 2.5% TS. Our results show that rumen fermentation of lignocellulosic biomass after wet explosion can produce high concentrations of VFA without addition of external enzymes of importance for the process economics of lignocellulosic biorefineries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of Estimated Training Status on Anti and Pro-Oxidant Activity, Nitrite Concentration, and Blood Pressure in Middle-Aged and Older Women

PubMed Central

Jacomini, André M.; Dias, Danielle da Silva; Brito, Janaina de Oliveira; da Silva, Roberta F.; Monteiro, Henrique L.; Llesuy, Susana; De Angelis, Kátia; Amaral, Sandra L.; Zago, Anderson S.

2017-01-01

The purpose of this study was to compare the association between anti and pro-oxidant activity, nitrite concentration, and blood pressure (BP) in middle-aged and older women with different levels of estimated training status (TS). The sample consisted of 155 females (50–84 years) who were submitted to a physical examination to evaluate estimated TS through the “Functional Fitness Battery Test,” BP measurements, and plasma blood samples to evaluate pro-oxidant and antioxidant activity and nitrite concentrations. Participants were separated by age into a middle-aged group (<65 years) and an older (≥65 years) group and then subdivided in each group according to TS. Blood biochemistry was similar between groups. On the other hand, protein oxidation was lower in participants with higher TS, independent of age. Older females with higher TS presented higher nitrite concentrations, lower lipoperoxidation, and lower values of BP compared with those with lower TS. Lower GPx activity was observed in participants with higher TS compared with middle-aged with lower TS. Thus, our results suggest that good levels of TS may be associated with lower oxidative stress and higher nitrite concentration and may contribute to maintain normal or reduced blood pressure values. PMID:28326041

[The expression of thymidylate synthase (TS) and excision repair complementing-1 (ERCC-1) protein in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy].

PubMed

Ishibashi, Keiichiro; Okada, Norimichi; Ishiguro, Toru; Kuwabara, Kouki; Ohsawa, Tomonori; Yokoyama, Masaru; Kumamoto, Kensuke; Haga, Norihiro; Mori, Takashi; Yamada, Hirofumi; Miura, Ichiro; Tamaru, Junichi; Itoyama, Shinji; Ishida, Hideyuki

2010-11-01

Thymidylate synthase (TS) and excision repair complementing-1 (ERCC-1) were known to be important biomarkers to predict a tumor response to 5-fluorouracil (5-FU) and oxaliplatin, but the relationship between these expressions and tumor response were still unclear. The aim of this study was to determine whether the expression of TS and ERCC-1 protein predict a tumor response in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy as first-line treatment. Fifty patients with unresectable colorectal cancer treated with mFOLFOX6 therapy were enrolled in this study. The expression of TS and ERCC-1 protein in primary cancer cells were examined using immunohistochemistry. There were no significant differences between response rate and the expression of TS or ERCC-1 protein (TS: p>0.99, ERCC-1: p= 0.50). There were no significant differences between progression-free survival time and the expression of TS or ERCC-1 protein (TS: p=0.60, ERCC-1: p=0.60). In this study, the expression TS and ERCC-1 protein may not be useful for the prediction of tumor response in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy.

Influence of Estimated Training Status on Anti and Pro-Oxidant Activity, Nitrite Concentration, and Blood Pressure in Middle-Aged and Older Women.

PubMed

Jacomini, André M; Dias, Danielle da Silva; Brito, Janaina de Oliveira; da Silva, Roberta F; Monteiro, Henrique L; Llesuy, Susana; De Angelis, Kátia; Amaral, Sandra L; Zago, Anderson S

2017-01-01

The purpose of this study was to compare the association between anti and pro-oxidant activity, nitrite concentration, and blood pressure (BP) in middle-aged and older women with different levels of estimated training status (TS). The sample consisted of 155 females (50-84 years) who were submitted to a physical examination to evaluate estimated TS through the "Functional Fitness Battery Test," BP measurements, and plasma blood samples to evaluate pro-oxidant and antioxidant activity and nitrite concentrations. Participants were separated by age into a middle-aged group (<65 years) and an older (≥65 years) group and then subdivided in each group according to TS. Blood biochemistry was similar between groups. On the other hand, protein oxidation was lower in participants with higher TS, independent of age. Older females with higher TS presented higher nitrite concentrations, lower lipoperoxidation, and lower values of BP compared with those with lower TS. Lower GPx activity was observed in participants with higher TS compared with middle-aged with lower TS. Thus, our results suggest that good levels of TS may be associated with lower oxidative stress and higher nitrite concentration and may contribute to maintain normal or reduced blood pressure values.

Electrophysiological correlates of reinforcement learning in young people with Tourette syndrome with and without co-occurring ADHD symptoms.

PubMed

Shephard, Elizabeth; Jackson, Georgina M; Groom, Madeleine J

2016-06-01

Altered reinforcement learning is implicated in the causes of Tourette syndrome (TS) and attention-deficit/hyperactivity disorder (ADHD). TS and ADHD frequently co-occur but how this affects reinforcement learning has not been investigated. We examined the ability of young people with TS (n=18), TS+ADHD (N=17), ADHD (n=13) and typically developing controls (n=20) to learn and reverse stimulus-response (S-R) associations based on positive and negative reinforcement feedback. We used a 2 (TS-yes, TS-no)×2 (ADHD-yes, ADHD-no) factorial design to assess the effects of TS, ADHD, and their interaction on behavioural (accuracy, RT) and event-related potential (stimulus-locked P3, feedback-locked P2, feedback-related negativity, FRN) indices of learning and reversing the S-R associations. TS was associated with intact learning and reversal performance and largely typical ERP amplitudes. ADHD was associated with lower accuracy during S-R learning and impaired reversal learning (significantly reduced accuracy and a trend for smaller P3 amplitude). The results indicate that co-occurring ADHD symptoms impair reversal learning in TS+ADHD. The implications of these findings for behavioural tic therapies are discussed. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Constitutive expression of thymidylate synthase from LCDV-C induces a transformed phenotype in fish cells.

PubMed

Zhao, Zhe; Shi, Yan; Ke, Fei; Wei, Sun; Gui, Jianfang; Zhang, Qiya

2008-03-01

Thymidylate synthase (TS), an essential enzyme in DNA synthesis and repair, plays a key role in the events of cell cycle regulation and tumor formation. Here, an investigation was presented about subcellular location and biological function of viral TS from lymphocystis disease virus from China (LCDV-C) in fish cells. Fluorescence microscopy revealed that LCDV-C TS was predominantly localized in the cytoplasm in fish cells. Cell cycle analysis demonstrated that LCDV-C TS promoted cell cycle progression into S and G2/M phase in the constitutive expressed cells. As a result, the cells have a faster growth rate compared with the control cells as revealed by cell growth curves. For foci assay, the TS-expressed cells gave rise to foci 4-5 weeks after incubation. Microscopic examination of the TS-induced foci revealed multilayered growth and crisscross morphology characteristic of transformed cells. Moreover, LCDV-C TS predisposed the transfected cells to acquire an anchorage-independent phenotype and could grow in 0.3% soft agar. So the data reveal LCDV-C TS is sufficient to induce a transformed phenotype in fish cells in vitro and exhibits its potential ability in cell transformation. To our knowledge, it is the first report on viral TS sequences associated with transforming activity.

TS Gene Polymorphisms Correlate with Susceptibility to Acute Lymphocytic Leukemia in Children.

PubMed

Zou, Runyin; He, Xiangling; Wu, Yanpeng; Tian, Xin; You, Yalan; Zheng, Mincui; Li, Wanli; Zou, Hui; Liu, Hua; Zhu, Xiujuan; Zhu, Chengguang

2017-06-24

BACKGROUND Acute lymphocytic leukemia (ALL) in children is a clonal disease of bone marrow hematopoietic stem cells. This study aimed to explore the associations between MTHFR or TS genetic polymorphisms and susceptibility to acute lymphocytic leukemia (ALL) in children. MATERIAL AND METHODS This case-control study included 79 ALL patients (case group) and 102 non-ALL patients (control group). Post-PCR genomic DNA sequencing revealed MTHFR C677T and MTHFR A1298C genotypes and TS polymorphisms. The χ² test was used to compare differences in MTHFR and TS polymorphisms (including genotypic and allelic distributions) between groups. Logistic regression analysis was used to determine genetic polymorphisms and ALL risk associations. RESULTS The results indicated that TS 3R allele frequency was significantly higher in the case group than in the control group (χ²=7.45, P<0.05). The MTHFR C677T and MTHFR A1298C polymorphisms were not associated with ALL risk. Compared to the TS 2R/2R genotype, subjects carrying TS 2R/3R were twice as likely to develop ALL, and the TS 3R/3R+3R/4R genotype carried a 4-fold higher risk of developing ALL (OR=1.96, CI: 1.14-3.36). CONCLUSIONS The TS genetic polymorphisms increase the ALL risk. The TS 3R allele was a risk factor for ALL. There were no associations between MTHFR C677T or MTHFR A1298C polymorphisms and ALL susceptibility.

Abscisic acid content and the expression of genes related to its metabolism during maturation of triticale grains of cultivars differing in pre-harvest sprouting susceptibility.

PubMed

Fidler, Justyna; Zdunek-Zastocka, Edyta; Prabucka, Beata; Bielawski, Wiesław

2016-12-01

Abscisic acid (ABA) is a plant hormone that plays a predominant role in the onset and maintenance of primary dormancy. Peak ABA accumulation in embryos of triticale grains was observed before any significant loss of water and was higher in Fredro, a cultivar less susceptible to pre-harvest sprouting (PHS), than in Leontino, a cultivar more sensitive to PHS. At full maturity, embryonic ABA content in Fredro was twice as high as in Leontino. Two full-length cDNAs of 9-cis-epoxycarotenoid dioxygenase (TsNCED1, TsNCED2), an enzyme involved in ABA biosynthesis, and two full-length cDNAs of ABA 8'-hydroxylase (TsABA8'OH1 and TsABA8'OH2), an enzyme involved in ABA catabolism, were identified in triticale grains and characterized. The maximum transcript level of both TsNCED1 and TsNCED2 preceded the peak of ABA accumulation, suggesting that both TsNCEDs contribute to reach this peak, although the expression of TsNCED1 was significantly higher in Fredro than in Leontino. High expression of TsABA8'OH2 and TsABA8'OH1 was observed long before and at the end of the ABA accumulation peak, respectively, but no differences were observed between cultivars. The obtained results suggest that mainly TsNCED1 might be related to the higher ABA content and higher resistance of Fredro to PHS. However, Fredro embryos not only have higher ABA content, but also exhibit greater sensitivity to ABA, which may also have a significant effect on grain dormancy and lower susceptibility to PHS for grains of this cultivar. Copyright © 2016 Elsevier GmbH. All rights reserved.

Inversion of AMSR-E observations for land surface temperature estimation: 2. Global comparison with infrared satellite temperature

NASA Astrophysics Data System (ADS)

Ermida, S. L.; Jiménez, C.; Prigent, C.; Trigo, I. F.; DaCamara, C. C.

2017-03-01

A comparison of land surface temperature (Ts) derived from the Advanced Microwave Scanning Radiometer-Earth Observing System (AMSR-E) with infrared Ts is presented. The infrared Ts include clear-sky estimates from the Moderate Resolution Imaging Spectroradiometer (MODIS), the Spinning Enhanced Visible and Infrared Imager, the Geostationary Operational Environmental Satellite (GOES) Imager, and the Japanese Meteorological Imager. The higher discrepancies between AMSR-E and MODIS are observed over deserts and snow-covered areas. The former seems to be associated with Ts underestimation by MODIS, whereas the latter is mostly related to uncertainties in microwave emissivity over snow/ice. Ts differences between AMSR-E and MODIS are significantly reduced after masking out snow and deserts, with a bias change from 2.6/4.6 K to 3.0/1.4 K for daytime/nighttime and a standard deviation (STD) decrease from 7.3/7.9 K to 5.1/3.9 K. When comparing with all infrared sensors, the STD of the differences between microwave and infrared Ts is generally higher than between IR retrievals. However, the biases between microwave and infrared Ts are, in some cases, of the same order as the ones observed between infrared products. This is the case for GOES, with daytime biases with respect to AMSR-E and MODIS of 0.45 K and 0.60 K, respectively. While the infrared Ts are clear-sky estimates, AMSR-E also provides Ts under cloudy conditions. For frequently cloudy regions, this results in a large increase of available Ts estimates (>250%), making the microwave Ts a very powerful complement of the infrared estimates.

Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients.

PubMed

Paradiso, A; Simone, G; Petroni, S; Leone, B; Vallejo, C; Lacava, J; Romero, A; Machiavelli, M; De Lena, M; Allegra, C J; Johnston, P G

2000-02-01

The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated-5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53- cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively; P < 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P < 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34-1.01; two-sided P < 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85-1.26; two-sided P < 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy.

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats.

PubMed

Lee, JooBuom; Lee, Kyungsun; Choe, Keunbum; Jung, Hyunseob; Cho, Hyunseok; Choi, Kiseok; Kim, Taegon; Kim, Seojin; Lee, Hyeong-Seok; Cha, Mi-Jin; Song, Si-Whan; Lee, Chul Kyu; Chun, Gie-Taek

2015-12-01

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 μg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 μg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 μg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 μg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 μg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

PubMed Central

Lee, JooBuom; Lee, Kyungsun; Choe, Keunbum; Jung, Hyunseob; Cho, Hyunseok; Choi, Kiseok; Kim, Taegon; Kim, Seojin; Lee, Hyeong-Seok; Cha, Mi-Jin; Song, Si-Whan; Lee, Chul Kyu; Chun, Gie-Taek

2015-01-01

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 μg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 μg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 μg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 μg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 μg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats. PMID:26877840

Intelligent ensemble T-S fuzzy neural networks with RCDPSO_DM optimization for effective handling of complex clinical pathway variances.

PubMed

Du, Gang; Jiang, Zhibin; Diao, Xiaodi; Yao, Yang

2013-07-01

Takagi-Sugeno (T-S) fuzzy neural networks (FNNs) can be used to handle complex, fuzzy, uncertain clinical pathway (CP) variances. However, there are many drawbacks, such as slow training rate, propensity to become trapped in a local minimum and poor ability to perform a global search. In order to improve overall performance of variance handling by T-S FNNs, a new CP variance handling method is proposed in this study. It is based on random cooperative decomposing particle swarm optimization with double mutation mechanism (RCDPSO_DM) for T-S FNNs. Moreover, the proposed integrated learning algorithm, combining the RCDPSO_DM algorithm with a Kalman filtering algorithm, is applied to optimize antecedent and consequent parameters of constructed T-S FNNs. Then, a multi-swarm cooperative immigrating particle swarm algorithm ensemble method is used for intelligent ensemble T-S FNNs with RCDPSO_DM optimization to further improve stability and accuracy of CP variance handling. Finally, two case studies on liver and kidney poisoning variances in osteosarcoma preoperative chemotherapy are used to validate the proposed method. The result demonstrates that intelligent ensemble T-S FNNs based on the RCDPSO_DM achieves superior performances, in terms of stability, efficiency, precision and generalizability, over PSO ensemble of all T-S FNNs with RCDPSO_DM optimization, single T-S FNNs with RCDPSO_DM optimization, standard T-S FNNs, standard Mamdani FNNs and T-S FNNs based on other algorithms (cooperative particle swarm optimization and particle swarm optimization) for CP variance handling. Therefore, it makes CP variance handling more effective. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pathogenesis of tropical sprue: A pilot study of antroduodenal manometry, duodenocaecal transit time & fat-induced ileal brake

PubMed Central

Ghoshal, Uday C.; Kumar, Sunil; Misra, Asha; Choudhuri, Gourdas

2013-01-01

Background & objectives: Small intestinal bacterial overgrowth (SIBO) due to ileal brake-induced hypomotility may cause tropical sprue (TS). We evaluated effect of infusion of fat or placebo in duodenum randomly in patients with TS and healthy controls on antroduodenal manometry (ADM) and mediators of ileal brake, and duodenocaecal transit time (DCTT). Methods: ADM and DCTT (lactulose hydrogen breath test, HBT) were evaluated with placebo and fat in eight controls and 13 patients with TS (diagnostic criteria: tests showing malabsorption of two unrelated substances, abnormal duodenal histology, absence of other causes, response to antibiotics and folate). Results: Patients with TS (6 had SIBO by glucose HBT) were similar in age and gender with controls. After fat infusion, proximal gut motility index (MI) was reduced compared to fasting state in TS, and DCTT was longer in TS than controls (200 min, 120-380 vs. 130, 70-160, P=0.001), though comparable after placebo (70 min, 30-140 vs. 60, 40-90). TS patients had higher PYY and neurotensin than controls after fat infusion. DCTT after fat infusion correlated with plasma level of PYY in TS but not in controls. Post-fat PYY and neurotensin levels were higher in TS with lower BMI (<16 kg/m2) than those with higher BMI. Parameters of ileal brake (post-fat DCTT, PYY and neurotensin) were higher in patients with than without SIBO. Interpretation & conclusions: Fat infusion reduced proximal gut MI, increased DCTT, PYY, and neurotensin among patients with TS. Malabsorbed fat might cause exaggerated ileal brake reducing gut motility, promoting SIBO and bacterial colonization and malabsorption in TS. PMID:23481053

Cognition, Emotion and Behavior in Children with Tourette’s Syndrome and Children with ADHD-Combined Subtype—A Two-Year Follow-Up Study

PubMed Central

Hovik, Kjell Tore; Plessen, Kerstin J.; Cavanna, Andrea E.; Skogli, Erik Winther; Andersen, Per Normann; Øie, Merete

2015-01-01

Objective This two-year follow-up study investigates the course of and association among measures of cognitive control, focused attention, decision-making and symptom severity (anxiety, depression and behavior) in children and adolescents with Tourette’s Syndrome (TS) or Attention-Deficit/Hyperactivity Disorder-Combined subtype (ADHD-C). Method 19 children with TS, 33 with ADHD-C, and 50 typically developing children (TDC) were examined with a battery of psychometric measures and rating forms at baseline and two-years later. Results All three groups improved likewise in measures of cognitive control over time, whereas only the TDC improved in focused attention. The group of children with TS with comorbidities performed more similar to the children with ADHD-C in cognitive control at T1 and T2, whereas the children with TS without comorbidities performed more similar to the TDC in cognitive control at T1 and T2. In the decision-making task, the children with TS (with or without comorbidities) preferred a safer strategy in selecting advantageous choices than the children with ADHD-C and the TDC at T2. Children with TS and children with ADHD-C showed higher symptoms of anxiety and depression and more problems with emotional control compared with TDC at both time points. Finally, children with ADHD-C self-reported more depression symptoms than those with TS at both assessments. For the TS group, safer decision-making was related to better emotional control, and this relationship was stronger for the TS subgroup without comorbidities. Conclusion This study emphasizes the importance of addressing symptoms of anxiety and depression in children with TS or ADHD-C, identifying the effect of comorbidities in children with TS, and that children with TS or ADHD-C likely differ in their sensitivity to reinforcement contingencies. PMID:26673612

Development of the embryonic heat shock response and the impact of repeated thermal stress in early stage lake whitefish (Coregonus clupeaformis) embryos.

PubMed

Whitehouse, Lindy M; McDougall, Chance S; Stefanovic, Daniel I; Boreham, Douglas R; Somers, Christopher M; Wilson, Joanna Y; Manzon, Richard G

2017-10-01

Lake whitefish (Coregonus clupeaformis) embryos were exposed to thermal stress (TS) at different developmental stages to determine when the heat shock response (HSR) can be initiated and if it is altered by exposure to repeated TS. First, embryos were subject to one of three different TS temperatures (6, 9, or 12°C above control) at 4 points in development (21, 38, 60 and 70 days post-fertilisation (dpf)) for 2h followed by a 2h recovery to understand the ontogeny of the HSR. A second experiment explored the effects of repeated TS on the HSR in embryos from 15 to 75 dpf. Embryos were subjected to one of two TS regimes; +6°C TS for 1h every 6 days or +9°C TS for 1h every 6 days. Following a 2h recovery, a subset of embryos was sampled. Our results show that embryos could initiate a HSR via upregulation of heat shock protein 70 (hsp70) mRNA at all developmental ages studied, but that this response varied with age and was only observed with a TS of +9 or +12°C. In comparison, when embryos received multiple TS treatments, hsp70 was not induced in response to the 1h TS and 2h recovery, and a downregulation was observed at 39 dpf. Downregulation of hsp47 and hsp90α mRNA was also observed in early age embryos. Collectively, these data suggest that embryos are capable of initiating a HSR at early age and throughout embryogenesis, but that repeated TS can alter the HSR, and may result in either reduced responsiveness or a downregulation of inducible hsps. Our findings warrant further investigation into both the short- and long-term effects of repeated TS on lake whitefish development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Peroxiredoxin 3 Is a Redox-Dependent Target of Thiostrepton in Malignant Mesothelioma Cells

PubMed Central

Newick, Kheng; Cunniff, Brian; Preston, Kelsey; Held, Paul; Arbiser, Jack; Pass, Harvey; Mossman, Brooke; Shukla, Arti; Heintz, Nicholas

2012-01-01

Thiostrepton (TS) is a thiazole antibiotic that inhibits expression of FOXM1, an oncogenic transcription factor required for cell cycle progression and resistance to oncogene-induced oxidative stress. The mechanism of action of TS is unclear and strategies that enhance TS activity will improve its therapeutic potential. Analysis of human tumor specimens showed FOXM1 is broadly expressed in malignant mesothelioma (MM), an intractable tumor associated with asbestos exposure. The mechanism of action of TS was investigated in a cell culture model of human MM. As for other tumor cell types, TS inhibited expression of FOXM1 in MM cells in a dose-dependent manner. Suppression of FOXM1 expression and coincidental activation of ERK1/2 by TS were abrogated by pre-incubation of cells with the antioxidant N-acetyl-L-cysteine (NAC), indicating its mechanism of action in MM cells is redox-dependent. Examination of the mitochondrial thioredoxin reductase 2 (TR2)-thioredoxin 2 (TRX2)-peroxiredoxin 3 (PRX3) antioxidant network revealed that TS modifies the electrophoretic mobility of PRX3. Incubation of recombinant human PRX3 with TS in vitro also resulted in PRX3 with altered electrophoretic mobility. The cellular and recombinant species of modified PRX3 were resistant to dithiothreitol and SDS and suppressed by NAC, indicating that TS covalently adducts cysteine residues in PRX3. Reduction of endogenous mitochondrial TRX2 levels by the cationic triphenylmethane gentian violet (GV) promoted modification of PRX3 by TS and significantly enhanced its cytotoxic activity. Our results indicate TS covalently adducts PRX3, thereby disabling a major mitochondrial antioxidant network that counters chronic mitochondrial oxidative stress. Redox-active compounds like GV that modify the TR2/TRX2 network may significantly enhance the efficacy of TS, thereby providing a combinatorial approach for exploiting redox-dependent perturbations in mitochondrial function as a therapeutic approach in mesothelioma. PMID:22761781

Testosterone supplementation and sexual function: a meta-analysis study.

PubMed

Corona, Giovanni; Isidori, Andrea M; Buvat, Jaques; Aversa, Antonio; Rastrelli, Giulia; Hackett, Geoff; Rochira, Vincenzo; Sforza, Alessandra; Lenzi, Andrea; Mannucci, Edoardo; Maggi, Mario

2014-06-01

The role of testosterone supplementation (TS) as a treatment for male sexual dysfunction remains questionable. The aim of this study was to attempt a meta-analysis on the effect of TS on male sexual function and its synergism with the use of phosphodiesterase type 5 inhibitor (PDE5i). An extensive Medline, Embase, and Cochrane search was performed. All randomized controlled trials (RCTs) comparing the effect of TS vs. placebo or the effect of TS as add on to PDE5is on sexual function were included. Data extraction was performed independently by two of the authors (A. M. Isidori and G. Corona), and conflicts resolved by the third investigator (M. Maggi). Out of 1,702 retrieved articles, 41 were included in the study. In particular, 29 compared TS vs. placebo, whereas 12 trials evaluated the effect of TS as add on to PDE5is. TS is able to significantly ameliorate erectile function and to improve other aspects of male sexual response in hypogonadal patients. However, the presence of possible publication bias was detected. After applying "trim and fill" method, the positive effect of TS on erectile function and libido components retained significance only in RCTs partially or completely supported by pharmaceutical companies (confidence interval [0.04-0.53] and [0.12; 0.52], respectively). In addition, we also report that TS could be associated with an improvement in PDE5i outcome. These results were not confirmed in placebo-controlled studies. The majority of studies, however, included mixed eugonadal/hypogonadal subjects, thus imparting uncertainty to the statistical analyses. TS plays positive effects on male sexual function in hypogonadal subjects. The role of TS is uncertain in men who are not clearly hypogonadal. The apparent difference between industry-supported and independent studies could depend on trial design more than on publication bias. New RCTs exploring the effect of TS in selected cases of PDE5i failure that persistently retain low testosterone levels are advisable. © 2014 International Society for Sexual Medicine.

Effects of Tityus serrulatus scorpion venom and its toxin TsTX-V on neurotransmitter uptake in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cecchini, Alessandra L.; Vollum Institute, Oregon Health Sciences University, Portland, Oregon 9701; Vasconcelos, Flavio

2006-12-01

Scorpion neurotoxins targeting the Na{sub v} channel can be classified into two classes: {alpha}- and {beta}-neurotoxins and are reported as highly active in mammalian brain. In this work, we evaluate the effects of Tityus serrulatus venom (Ts venom) and its {alpha}-neurotoxin TsTX-V on {gamma}-aminobutyric acid (GABA), dopamine (DA) and glutamate (Glu) uptake in isolated rat brain synaptosomes. TsTX-V was isolated from Ts venom by ion exchange chromatography followed by reverse-phase (C18) high-performance liquid chromatography. Neither Ts venom nor TsTX-V was able to affect {sup 3}H-Glu uptake. On the other hand, Ts venom (0.13 {mu}g/mg) significantly inhibited both {sup 3}H-GABA andmore » {sup 3}H-DA uptake ({approx} 50%). TsTX-V showed IC{sub 5} values of 9.37 {mu}M and 22.2 {mu}M for the inhibition of {sup 3}H-GABA and {sup 3}H-DA uptake, respectively. These effects were abolished by pre-treatment with tetrodotoxin (TTX, 1 {mu}M), indicating the involvement of voltage-gated Na{sup +} channels in this process. In the absence of Ca{sup 2+}, and at low Ts venom concentrations, the reduction of {sup 3}H-GABA uptake was not as marked as in the presence of Ca{sup 2+}. TsTX-V did not reduce {sup 3}H-GABA uptake in COS-7 cells expressing the GABA transporters GAT-1 and GAT-3, suggesting that this toxin indirectly reduces the transport. The reduced {sup 3}H-GABA uptake by synaptosomes might be due to rapid cell depolarization as revealed by confocal microscopy of C6 glioma cells. Thus, TsTX-V causes a reduction of {sup 3}H-GABA and {sup 3}H-DA uptake in a Ca{sup 2+}-dependent manner, not directly affecting GABA transporters, but, in consequence of depolarization, involving voltage-gated Na{sup +} channels.« less

Down-regulation of Jab1, HIF-1alpha, and VEGF by Moloney murine leukemia virus-ts1 infection: a possible cause of neurodegeneration.

PubMed

Lungu, Gina F; Stoica, George; Wong, Paul K Y

2008-05-01

Moloney murine leukemia virus-temperature sensitive (MoMuLV-ts1)-mediated neuronal death is a result of both loss of glial support and release of cytokines and neurotoxins from ts1-infected glial cells. Here the authors propose vascular endothelial growth factor (VEGF) down-regulation as another contributory factor in neuronal degeneration induced by ts1 infection. To determine how ts1 affects VEGF expression in ts1-infected brain, the authors examined the expression of several proteins that are important in regulating the expression of VEGF. The authors found significant decreases in Jun-activating domain-binding protein 1 (Jab1), hypoxia-inducible factor (HIF)-1alpha, and VEGF levels and increases in p53 protein levels in ts1-infected brains compared to noninfected control brains. The authors suggest that a decrease Jab1 expression in ts1 infection leads to accumulation of p53, which binds to HIF-1alpha to accelerate its degradation. A rapid degradation of HIF-1alpha leads to decreased VEGF production and secretion. Considering that endothelial cells are the most conspicuous in virus replication and production in ts1 infection, but are not killed by the infection, the authors examined the expression of these proteins using infected and noninfected mouse cerebrovascular endothelial (CVE) cells. The ts1- infected CVE cells showed decreased Jab1, HIF-1alpha, and VEGF mRNA and protein levels and increased p53 protein levels compared with noninfected cells, consistent with the results found in vivo. These results confirm that ts1 infection results in insufficient secretion of VEGF from endothelial cells and may result in decreased neuroprotection. This study suggested that ts1-mediated neuropathology in mice may result from changes in expression and activity of Jab1, p53, and HIF-1alpha, with a final target on VEGF expression and neuronal degeneration.

A rice chloroplast transit peptide sequence does not alter the cytoplasmic localization of sheep serotonin N-acetyltransferase expressed in transgenic rice plants.

PubMed

Byeon, Yeong; Lee, Hyoung Yool; Lee, Kyungjin; Back, Kyoungwhan

2014-09-01

Ectopic overexpression of melatonin biosynthetic genes of animal origin has been used to generate melatonin-rich transgenic plants to examine the functional roles of melatonin in plants. However, the subcellular localization of these proteins expressed in the transgenic plants remains unknown. We studied the localization of sheep (Ovis aries) serotonin N-acetyltransferase (OaSNAT) and a translational fusion of a rice SNAT transit peptide to OaSNAT (TS:OaSNAT) in plants. Laser confocal microscopy analysis revealed that both OaSNAT and TS:OaSNAT proteins were localized to the cytoplasm even with the addition of the transit sequence to OaSNAT. Transgenic rice plants overexpressing the TS:OaSNAT fusion transgene exhibited high SNAT enzyme activity relative to untransformed wild-type plants, but lower activity than transgenic rice plants expressing the wild-type OaSNAT gene. Melatonin levels in both types of transgenic rice plant corresponded well with SNAT enzyme activity levels. The TS:OaSNAT transgenic lines exhibited increased seminal root growth relative to wild-type plants, but less than in the OaSNAT transgenic lines, confirming that melatonin promotes root growth. Seed-specific OaSNAT expression under the control of a rice prolamin promoter did not confer high levels of melatonin production in transgenic rice seeds compared with seeds from transgenic plants expressing OaSNAT under the control of the constitutive maize ubiquitin promoter. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mindfulness-based stress reduction for Tourette Syndrome and Chronic Tic Disorder: a pilot study.

PubMed

Reese, Hannah E; Vallejo, Zayda; Rasmussen, Jessica; Crowe, Katherine; Rosenfield, Elizabeth; Wilhelm, Sabine

2015-03-01

In this pilot study we sought to develop and test a modified form of mindfulness-based stress reduction (MBSR-tics) for the treatment of Tourette Syndrome (TS) and Chronic Tic Disorder (CTD). Our specific aims were: 1) To determine the feasibility and acceptability of an 8-week trial of MBSR-tics in individuals 16 and older with TS or CTD and 2) To determine the efficacy of an 8-week trial of MBSR-tics in individuals 16 and older with TS or CTD. Eighteen individuals age 16-67 completed an uncontrolled open trial of MBSR-tics. The intervention consisted of 8 weekly 2-hour classes and one 4hour retreat in the fifth or sixth week of the program. Symptomatic assessments were performed at baseline, post-treatment, and one-month follow-up. MBSR-tics proved to be a feasible and acceptable intervention. It resulted in significant improvement in tic severity and tic-related impairment. 58.8% of subjects were deemed treatment responders. Therapeutic gains were maintained at 1-month follow-up. Improvements in tic severity were correlated with increases in self-reported levels of mindfulness. This small open pilot study provides preliminary support for the feasibility, acceptability, and efficacy of MBSR-tics for individuals 16 or older with TS or CTD. A larger randomized controlled trial with blind assessment is necessary to confirm these initial, promising findings. Trial Registration Partners Clinical Trials Registry Number 2011P000606 (clinicaltrials.partners.org). Copyright © 2014 Elsevier Inc. All rights reserved.

Temperature-Induced Protein Secretion by Leishmania mexicana Modulates Macrophage Signalling and Function

PubMed Central

Hassani, Kasra; Antoniak, Elisabeth; Jardim, Armando; Olivier, Martin

2011-01-01

Protozoan parasites of genus Leishmania are the causative agents of leishmaniasis. These digenetic microorganisms undergo a marked environmental temperature shift (TS) during transmission from the sandfly vector (ambient temperature, 25–26°C) to the mammalian host (37°C). We have observed that this TS induces a rapid and dramatic increase in protein release from Leishmania mexicana (cutaneous leishmaniasis) within 4 h. Proteomic identification of the TS-induced secreted proteins revealed 72 proteins, the majority of which lack a signal peptide and are thus thought to be secreted via nonconventional mechanisms. Interestingly, this protein release is accompanied by alterations in parasite morphology including an augmentation in the budding of exovesicles from its surface. Here we show that the exoproteome of L. mexicana upon TS induces cleavage and activation of the host protein tyrosine phosphatases, specifically SHP-1 and PTP1-B, in a murine bone-marrow-derived macrophage cell line. Furthermore, translocation of prominent inflammatory transcription factors, namely NF-κB and AP-1 is altered. The exoproteome also caused inhibition of nitric oxide production, a crucial leishmanicidal function of the macrophage. Overall, our results provide strong evidence that within early moments of interaction with the mammalian host, L. mexicana rapidly releases proteins and exovesicles that modulate signalling and function of the macrophage. These modulations can result in attenuation of the inflammatory response and deactivation of the macrophage aiding the parasite in the establishment of infection. PMID:21559274

Understanding the molecular mechanism of substrate channeling and domain communication in protozoal bifunctional TS-DHFR.

PubMed

Anderson, Karen S

2017-03-01

Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. In contrast, several parasitic protozoa, including Leishmania major (Lm), Plasmodium falciparum (Pf), Toxoplasma gondii (Tg) and Cryptosporidium hominis (Ch), contain a unique bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) having the two sequential catalytic activities contained on a single polypeptide chain. It has been suggested that the bifunctional nature of the two catalytic activities may enable substrate channeling. The 3D structures for each of these enzymes reveals distinct features for each species. While three of the four species (Pf, Tg and Ch) contain a junctional region linking the two domains, this is lacking in Lm. The Lm and Pf contain N-terminal amino acid extensions. A multidisciplinary approach using structural studies and transient kinetic analyses combined with mutational analysis has investigated the roles of these unique structural features for each enzyme. Additionally, the possibility of substrate channeling behavior was explored. These studies have identified unique, functional regions in both the TS and DHFR domains that govern efficient catalysis for each species. Surprisingly, even though there are structural similarities among the species, each is regulated in a distinct manner. This structural and mechanistic information was also used to exploit species-specific inhibitor design. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

An efficient strategy for producing a stable, replaceable, highly efficient transgene expression system in silkworm, Bombyx mori

PubMed Central

Long, Dingpei; Lu, Weijian; Zhang, Yuli; Bi, Lihui; Xiang, Zhonghuai; Zhao, Aichun

2015-01-01

We developed an efficient strategy that combines a method for the post-integration elimination of all transposon sequences, a site-specific recombination system, and an optimized fibroin H-chain expression system to produce a stable, replaceable, highly efficient transgene expression system in the silkworm (Bombyx mori) that overcomes the disadvantages of random insertion and post-integration instability of transposons. Here, we generated four different transgenic silkworm strains, and of one the transgenic strains, designated TS1-RgG2, with up to 16% (w/w) of the target protein in the cocoons, was selected. The subsequent elimination of all the transposon sequences from TS1-RgG2 was completed by the heat-shock-induced expression of the transposase in vivo. The resulting transgenic silkworm strain was designated TS3-g2 and contained only the attP-flanked optimized fibroin H-chain expression cassette in its genome. A phiC31/att-system-based recombinase-mediated cassette exchange (RMCE) method could be used to integrate other genes of interest into the same genome locus between the attP sites in TS3-g2. Controlling for position effects with phiC31-mediated RMCE will also allow the optimization of exogenous protein expression and fine gene function analyses in the silkworm. The strategy developed here is also applicable to other lepidopteran insects, to improve the ecological safety of transgenic strains in biocontrol programs. PMID:25739894

The influence of sex chromosome aneuploidy on brain asymmetry.

PubMed

Rezaie, Roozbeh; Daly, Eileen M; Cutter, William J; Murphy, Declan G M; Robertson, Dene M W; DeLisi, Lynn E; Mackay, Clare E; Barrick, Thomas R; Crow, Timothy J; Roberts, Neil

2009-01-05

The cognitive deficits present in individuals with sex chromosome aneuploidies suggest that hemispheric differentiation of function is determined by an X-Y homologous gene [Crow (1993); Lancet 342:594-598]. In particular, females with Turner's syndrome (TS) who have only one X-chromosome exhibit deficits of spatial ability whereas males with Klinefelter's syndrome (KS) who possess a supernumerary X-chromosome are delayed in acquiring words. Since spatial and verbal abilities are generally associated with right and left hemispheric function, such deficits may relate to anomalies of cerebral asymmetry. We therefore applied a novel image analysis technique to investigate the relationship between sex chromosome dosage and structural brain asymmetry. Specifically, we tested Crow's prediction that the magnitude of the brain torque (i.e., a combination of rightward frontal and leftward occipital asymmetry) would, as a function of sex chromosome dosage, be respectively decreased in TS women and increased in KS men, relative to genotypically normal controls. We found that brain torque was not significantly different in TS women and KS men, in comparison to controls. However, TS women exhibited significantly increased leftward brain asymmetry, restricted to the posterior of the brain and focused on the superior temporal and parietal-occipital association cortex, while KS men showed a trend for decreased brain asymmetry throughout the frontal lobes. The findings suggest that the number of sex chromosomes influences the development of brain asymmetry not simply to modify the torque but in a complex pattern along the antero-posterior axis. 2008 Wiley-Liss, Inc.

Effect of Lower and Upper Body High Intensity Training on Genes Associated with Cellular Stress Response

PubMed Central

Kochanowicz, Andrzej; Kochanowicz, Kazimierz; Mieszkowski, Jan; Niespodziński, Bartłomiej; Sawczyn, Stanisław

2017-01-01

This study aimed to compare the effect of upper and lower body high intensity exercise (HIE) on select gene expression in athletes. Fourteen elite male artistic gymnasts (age 20.9 ± 2.6 years; weight 68.6 ± 7.2 kg; fat free mass 63.6 ± 6.7 kg; height 1.70 ± 0.04 m) performed lower and upper body 30 s Wingate Tests (WAnTs) before and after eight weeks of specific HIIT. Two milliliters of blood was collected before and after (5, 30 min, resp.) lower and upper body WAnTs, and select gene expression was determined by PCR. Eight weeks of HIIT caused a significant increase in maximal power (722 to 751 Wat), relative peak power in the lower body WAnTs (10.1 to 11 W/kg), mean power (444 to 464 W), and relative mean power (6.5 to 6.8 W/kg). No significant differences in lower versus upper body gene expression were detected after HIIT, and a significant decrease in the IL6/IL10 ratio was observed after lower (−2∧0.57 p = 0.0019) and upper (−2∧0.5 p = 0.03) WAnTs following eight weeks of HIIT. It is hypothesized that a similar adaptive response to exercise may be obtained by lower and upper body exercise. PMID:28589135

High-resolution melting genotyping of Enterococcus faecium based on multilocus sequence typing derived single nucleotide polymorphisms.

PubMed

Tong, Steven Y C; Xie, Shirley; Richardson, Leisha J; Ballard, Susan A; Dakh, Farshid; Grabsch, Elizabeth A; Grayson, M Lindsay; Howden, Benjamin P; Johnson, Paul D R; Giffard, Philip M

2011-01-01

We have developed a single nucleotide polymorphism (SNP) nucleated high-resolution melting (HRM) technique to genotype Enterococcus faecium. Eight SNPs were derived from the E. faecium multilocus sequence typing (MLST) database and amplified fragments containing these SNPs were interrogated by HRM. We tested the HRM genotyping scheme on 85 E. faecium bloodstream isolates and compared the results with MLST, pulsed-field gel electrophoresis (PFGE) and an allele specific real-time PCR (AS kinetic PCR) SNP typing method. In silico analysis based on predicted HRM curves according to the G+C content of each fragment for all 567 sequence types (STs) in the MLST database together with empiric data from the 85 isolates demonstrated that HRM analysis resolves E. faecium into 231 "melting types" (MelTs) and provides a Simpson's Index of Diversity (D) of 0.991 with respect to MLST. This is a significant improvement on the AS kinetic PCR SNP typing scheme that resolves 61 SNP types with D of 0.95. The MelTs were concordant with the known ST of the isolates. For the 85 isolates, there were 13 PFGE patterns, 17 STs, 14 MelTs and eight SNP types. There was excellent concordance between PFGE, MLST and MelTs with Adjusted Rand Indices of PFGE to MelT 0.936 and ST to MelT 0.973. In conclusion, this HRM based method appears rapid and reproducible. The results are concordant with MLST and the MLST based population structure.

Total gastrectomy increases the incidence of grade III and IV toxicities in patients with gastric cancer receiving adjuvant TS-1 treatment.

PubMed

Chou, Wen-Chi; Chang, Chia-Lun; Liu, Keng-Hao; Hsu, Jun-Te; Cheng, Wei Hong; Hsu, Hung-Chih; Shen, Wen-Chi; Hung, Yu-Shin; Chen, Jen-Shi

2013-11-01

We aimed to evaluate the safety and efficacy of TS-1 adjuvant chemotherapy in Taiwanese patients with gastric cancer. We included in this study patients with locally advanced gastric cancer who received adjuvant TS-1 or 5-fluorouracil chemotherapy after curative surgery and extended lymph node dissection between 1 June 2008 and 31 December 2012 at Chang Gung Memorial Hospital. Patient characteristics, tumor features, safety profiles and compliance with TS-1 treatment were retrospectively analyzed from medical charts. Forty patients received adjuvant chemotherapy with TS-1 and 193 with 5-fluorouracil within the study period. The 1- and 2-year overall survival rates were 90.6% and 87% in the TS-1 group and 95.4% and 86.8% in the 5-fluorouracil group (P = 0.34). The 1- and 2-year disease-free survival rates were 90.6% and 74.7% in the TS-1 group and 88% and 75.7% in the 5-fluorouracil group (P = 0.66). In the TS-1 group, tumor recurrence was more frequent in those with >15 metastatic lymph nodes than ≤15. Overall, 78.9%, 74.3%, 62.1% and 56% of patients underwent TS-1 treatment for at least 3, 6, 9 and 12 months, respectively. The most common adverse events of TS-1 were skin hyperpigmentation (55%), diarrhea (27.5%), dizziness (27.5%) and leucopenia (20%). Severe adverse events (SAEs; grade III or IV toxicity) were diarrhea (7.5%), stomatitis (7.5%), leukopenia (5%), vomiting (2.5%), anorexia (2.5%) and dizziness (2.5%). Patients who underwent total gastrectomy had a significantly greater risk of TS-1-related SAEs than patients who underwent subtotal gastrectomy (40% versus 8%, P = 0.014). The incidence of SAEs during TS-1 therapy was more common in Taiwanese patients with gastric cancer who underwent total gastrectomy compared with those who underwent subtotal gastrectomy. Clinicians must be aware of and able to manage these SAEs to maximize patient compliance with adjuvant TS-1.

A paleolatitude approach to assessing surface temperature history for use in burial heating models

USGS Publications Warehouse

Barker, Charles E.

2000-01-01

Calculations using heat flow theory as well as case histories show that over geologic time scales (106 years), changes in mean annual surface temperature (Ts) on the order of 10°C penetrate kilometers deep into the crust. Thus, burial heating models of sedimentary basins, which typically span kilometers in depth and persist over geological time frames, should consider Ts history to increase their accuracy. In any case, Ts history becomes important when it changes enough to be detected by a thermal maturation index like vitrinite reflectance, a parameter widely used to constrain burial heating models. Assessment of the general temperature conditions leading to petroleum generation indicates that changes in Ts as small as 6°C can be detected by vitrinite reflectance measurements. This low temperature threshold indicates that oil and gas windows can be significantly influenced by Ts history. A review of paleoclimatic factors suggests the significant and geologically resolvable factors affecting Ts history are paleolatitude, long-term changes between cool and warm geological periods (climate mode), the degree to which a basin is removed from the sea (geographic isolation), and elevation or depth relative to sea level. Case studies using geologically realistic data ranges or different methods of estimating Ts in a burial heating model indicate a significant impact of Ts when: (1) continental drift, subduction, tectonism and erosion significantly change paleolatitude, paleoaltitude, or paleogeography; (2) strata are at, or near, maximum burial, and changes in Ts directly influence maximum burial temperature; and (3), when a significant change in Ts occurs near the opening or closing of the oil or gas windows causing petroleum generation to begin or cease. Case studies show that during the burial heating and petroleum generation phase of basin development changes in climate mode alone can influence Ts by about 15°C. At present, Ts changes from the poles to the equator by about 50°C. Thus, in extreme cases, continental drift alone can seemingly produce Ts changes on the order of 50°C over a time frame of 107 years.

Plankton Production Biology

DTIC Science & Technology

2013-09-30

kind. It will permit the study of stage-specific population dynamics (growth rate, production, mortality) of copepod larvae in mixed populations...will be picked up. 4. The translation and distribution of Sazhina’s keys will permit the study of stage-specific population dynamics (growth rate...of the 1987 Russian original, edited by K. Banse) Petipa, T.S. (ed.) (1986) Ecological Systems in Dynamically Active Zones of the Indian Ocean

Structural and Binding Properties of Two Paralogous Fatty Acid Binding Proteins of Taenia solium Metacestode

PubMed Central

Yang, Hyun-Jong; Shin, Joo-Ho; Diaz-Camacho, Sylvia Paz; Nawa, Yukifumi; Kang, Insug; Kong, Yoon

2012-01-01

Background Fatty acid (FA) binding proteins (FABPs) of helminths are implicated in acquisition and utilization of host-derived hydrophobic substances, as well as in signaling and cellular interactions. We previously demonstrated that secretory hydrophobic ligand binding proteins (HLBPs) of Taenia solium metacestode (TsM), a causative agent of neurocysticercosis (NC), shuttle FAs in the surrounding host tissues and inwardly transport the FAs across the parasite syncytial membrane. However, the protein molecules responsible for the intracellular trafficking and assimilation of FAs have remained elusive. Methodology/Principal Findings We isolated two novel TsMFABP genes (TsMFABP1 and TsMFABP2), which encoded 133- and 136-amino acid polypeptides with predicted molecular masses of 14.3 and 14.8 kDa, respectively. They shared 45% sequence identity with each other and 15–95% with other related-members. Homology modeling demonstrated a characteristic β-barrel composed of 10 anti-parallel β-strands and two α-helices. TsMFABP2 harbored two additional loops between β-strands two and three, and β-strands six and seven, respectively. TsMFABP1 was secreted into cyst fluid and surrounding environments, whereas TsMFABP2 was intracellularly confined. Partially purified native proteins migrated to 15 kDa with different isoelectric points of 9.2 (TsMFABP1) and 8.4 (TsMFABP2). Both native and recombinant proteins bound to 11-([5-dimethylaminonaphthalene-1-sulfonyl]amino)undecannoic acid, dansyl-DL-α-amino-caprylic acid, cis-parinaric acid and retinol, which were competitively inhibited by oleic acid. TsMFABP1 exhibited high affinity toward FA analogs. TsMFABPs showed weak binding activity to retinol, but TsMFABP2 showed relatively high affinity. Isolation of two distinct genes from an individual genome strongly suggested their paralogous nature. Abundant expression of TsMFABP1 and TsMFABP2 in the canal region of worm matched well with the histological distributions of lipids and retinol. Conclusions/Significance The divergent biochemical properties, physiological roles and cellular distributions of the TsMFABPs might be one of the critical mechanisms compensating for inadequate de novo FA synthesis. These proteins might exert harmonized or independent roles on lipid assimilation and intracellular signaling. The specialized distribution of retinol in the canal region further implies that cells in this region might differentiate into diverse cell types during metamorphosis into an adult worm. Identification of bioactive systems pertinent to parasitic homeostasis may provide a valuable target for function-related drug design. PMID:23150743

Association of Survival With Shorter Time to Radiation Therapy After Surgery for US Patients With Head and Neck Cancer.

PubMed

Harris, Jeremy P; Chen, Michelle M; Orosco, Ryan K; Sirjani, Davud; Divi, Vasu; Hara, Wendy

2018-04-01

Shortening the time from surgery to the start of radiation (TS-RT) is a consideration for physicians and patients. Although the National Comprehensive Cancer Network recommends radiation to start within 6 weeks, a survival benefit with this metric remains controversial. To determine the association of delayed TS-RT with overall survival (OS) using a large cancer registry. In this observational cohort study, 25 216 patients with nonmetastatic stages III to IV head and neck cancer were identified from the National Cancer Database (NCDB). Patients received definitive surgery followed by adjuvant radiation therapy, with an interval duration defined as TS-RT. Overall survival as a function of TS-RT and the effect of clinicopathologic risk factors and accelerated fractionation. We identified 25 216 patients with nonmetastatic squamous cell carcinoma of the head and neck. There were 18 968 (75%) men and 6248 (25%) women and the mean (SD) age of the cohort was 59 (10.9) years. Of the 25 216 patients, 9765 (39%) had a 42-days or less TS-RT and 4735 (19%) had a 43- to 49-day TS-RT. Median OS was 10.5 years (95% CI, 10.0-11.1 years) for patients with a 42-days or less TS-RT, 8.2 years (95% CI, 7.4-8.6 years; absolute difference, -2.4 years, 95% CI, -1.5 to -3.2 years) for patients with a 43- to 49-day TS-RT, and 6.5 years (95% CI, 6.1-6.8 years; absolute difference, -4.1 years, 95% CI, -3.4 to -4.7 years) for those with a 50-days or more TS-RT. Multivariable analysis found that compared with a 42-days or less TS-RT, there was not a significant increase in mortality with a 43- to 49-day TS-RT (HR, 0.98; 95% CI, 0.93-1.04), although there was for a TS-RT of 50 days or more (HR, 1.07; 95% CI, 1.02-1.12). A significant interaction was identified between TS-RT and disease site. Subgroup effect modeling found that a delayed TS-RT of 7 days resulted in significantly worse OS for patients with tonsil tumors (HR, 1.22; 95% CI, 1.05-1.43) though not other tumor subtypes. Accelerated fractionation of 5.2 fractions or more per week was associated with improved survival (HR, 0.93; 95% CI, 0.87-0.99) compared with standard fractionation. Delayed TS-RT of 50 days or more was associated with worse overall survival. The multidisciplinary care team should focus on shortening TS-RT to improve survival. Unavoidable delays may be an indication for accelerated fractionation or other dose intensification strategies.

The temperature-sensitive and attenuation phenotypes conferred by mutations in the influenza virus PB2, PB1, and NP genes are influenced by the species of origin of the PB2 gene in reassortant viruses derived from influenza A/California/07/2009 and A/WSN/33 viruses.

PubMed

Broadbent, Andrew J; Santos, Celia P; Godbout, Rachel A; Subbarao, Kanta

2014-11-01

Live attenuated influenza vaccines in the United States are derived from a human virus that is temperature sensitive (ts), characterized by restricted (≥ 100-fold) replication at 39 °C. The ts genetic signature (ts sig) has been mapped to 5 loci in 3 genes: PB1 (391 E, 581 G, and 661 T), PB2 (265 S), and NP (34 G). However, when transferred into avian and swine influenza viruses, only partial ts and attenuation phenotypes occur. To investigate the reason for this, we introduced the ts sig into the human origin virus A/WSN/33 (WSN), the avian-origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple-reassortant 2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene segments from human, avian, and swine viruses. The VN04(ts sig) and CA07(ts sig) viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39 °C, but the replication of WSN(ts sig) was restricted ≥ 100-fold compared to that at 33 °C. Reassortant CA07(ts sig) viruses were generated with individual polymerase gene segments from WSN, and vice versa. Only ts sig viruses with a PB2 gene segment derived from WSN were restricted in replication ≥ 100-fold at 39 °C. In ferrets, the CA07(ts sig) virus replicated in the upper and lower respiratory tract, but the replication of a reassortant CA07(ts sig) virus with a WSN PB2 gene was severely restricted in the lungs. Taken together, these data suggest that the origin of the PB2 gene segment influences the ts phenotype in vitro and attenuation in vivo. This could have implications for the design of novel live vaccines against animal origin influenza viruses. Live attenuated influenza vaccines (LAIVs) on temperature-sensitive (ts) backbones derived from animal origin influenza viruses are being sought for use in the poultry and swine industries and to protect people against animal origin influenza. However, inserting the ts genetic signature from a licensed LAIV backbone fails to fully attenuate these viruses. Our data indicate this is associated with the presence of a PB2 gene segment derived from an avian influenza virus. We show that a reassortant 2009 pandemic H1N1 virus with the ts signature from a licensed LAIV donor virus is ts in vitro and attenuated in vivo when the PB2 gene is derived from a human origin virus but not from an avian virus. Our study provides information that could benefit the rational design of alternative LAIV backbones against animal origin influenza viruses. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Accuracy of increased thyroid activity during pertechnetate scintigraphy by subcutaneous injection for diagnosing hyperthyroidism in cats.

PubMed

Page, Richard B; Scrivani, Peter V; Dykes, Nathan L; Erb, Hollis N; Hobbs, Jeff M

2006-01-01

Our purpose was to determine the accuracy of increased thyroid activity for diagnosing hyperthyroidism in cats suspected of having that disease during pertechnetate scintigraphy using subcutaneous rather than intravenous radioisotope administration. Increased thyroid activity was determined by two methods: the thyroid:salivary ratio (T:S) and visual inspection. These assessments were made on the ventral scintigram of the head and neck. Scintigraphy was performed by injecting sodium pertechnetate (111 MBq, SQ) in the right-dorsal-lumbar region; static-acquisition images were obtained 20 min after injection. We used 49 cats; 34 (69%) had hyperthyroidism based on serum-chemistry analysis. Using a Wilcoxon's rank-sum test, a significant difference (P < 0.0001) was detected in the T:S between cats with and without hyperthyroidism. Using a decision criterion of 2.0 for the T:S, the test accurately predicted hyperthyroidism in 32/34 cats (sensitivity, 94%; 95% confidence interval (CI), 85-100%) and correctly predicted that hyperthyroidism was absent in 15/15 cats (specificity, 100%; CI, 97-100%). Using visual inspection, the test accurately predicted hyperthyroidism in 34/34 cats (sensitivity, 100%; CI, 99-100%) and correctly predicted that hyperthyroidism was absent in 12/15 cats (specificity, 80%; CI, 56-100%). The positive and negative predictive values were high for a wide range of prevalence of hyperthyroidism. And, the test had excellent agreement within and between examiners. Therefore, detecting increased thyroid activity during pertechnetate scintigraphy by subcutaneous injection is an accurate and reproducible test for feline hyperthyroidism.

78 FR 53134 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

... and Uses: Require the collection of specific information on prospective Air Force contract flight... DEPARTMENT OF DEFENSE Department of the Air Force [Docket ID: USAF-2013-0034] Proposed Collection; Comment Request AGENCY: Air Education and Training Command (AETC/A5TS), Department of the Air Force...

The Pre-Employment Inquiry Guide.

ERIC Educational Resources Information Center

Koen, Clifford M., Jr.

1980-01-01

Contains a list of "do's" and "don'ts" concerning what an interviewer may or may not ask a prospective employee during an interview. Discusses various government directives and touches specifically on issues concerning discrimination due to age, sex, race, religion, handicap, marital status, and political affiliation. (CT)

Development and evaluation of porcine cysticercosis QuickELISA in Triturus EIA analyzer.

PubMed

Handali, Sukwan; Pattabhi, Sowmya; Lee, Yeuk-Mui; Silva-Ibanez, Maria; Kovalenko, Victor A; Levin, Andrew E; Gonzalez, Armando E; Roberts, Jacquelin M; Garcia, Hector H; Gilman, Robert H; Hancock, Kathy; Tsang, Victor C W

2010-01-01

We evaluated three diagnostic antigens (recombinant GP50, recombinant T24H, and synthetic Ts18var1) for cysticercosis and found that all three performed well in detecting cysticercosis in humans and pigs in several assay formats. These antigens were adapted to a new antibody detection format (QuickELISA). With one single incubation step which involves all reactants except the enzyme substrate, the QuickELISA is particularly suited for automation. We formatted the QuickELISA for the Triturus EIA analyzer for testing large numbers of samples. We found that in QuickELISA formats rGP50 and rT24H have better sensitivity and specificity than sTs18var1 for detecting porcine cysticercosis.

Addiction, 12-Step Programs, and Evidentiary Standards for Ethically and Clinically Sound Treatment Recommendations: What Should Clinicians Do?

PubMed

Mendola, Annette; Gibson, Richard L

2016-06-01

Addiction is a complex phenomenon characterized by a loss of control and compulsive, habitual behavior. Since there is no single, specific cause for addiction, there is no single, standard treatment for it. A variety of approaches are used, including counseling, psychotherapy, medications, and mutual help groups (MHG). The best known and most widely available approach to addiction is 12-step (TS) programs of recovery, a variety of MHG. These have been lauded as lifesaving by some and criticized by others. We argue that TS programs are an appropriate mode of help for those seeking to quit an addiction but should not be the only approach considered. © 2016 American Medical Association. All Rights Reserved. ISSN 2376-6980.

Comparison study of thickness swell performance of commercial oriented strandboard flooring products

Treesearch

Hongmei Gu; Siqun Wang; Trairat Neimsuwan; Sunguo Wang

2005-01-01

The multiple layer structure of oriented strandboard (OSB) has a significant influence on its performance, including thickness swell (TS). TS is recognized as an important performance property for OSB products. Optimization of TS through layer property ma- nipulation to achieve the lowest total TS while maintaining acceptable mechanical properties is attainable if the...

TS mRNA levels can predict pemetrexed and raltitrexed sensitivity in colorectal cancer.

PubMed

Zhang, Qun; Shen, Jie; Wang, Hao; Hu, Jing; Yu, Lixia; Xie, Li; Wei, Jia; Liu, Baorui; Guan, Wenxian; Qian, Xiaoping

2014-02-01

The purpose of the study is to analyze the relationship between tumor thymidylate synthase (TS) mRNA expression levels and raltitrexed/pemetrexed/5-FU sensitivity. We collected freshly removed colorectal tumor specimens from 50 patients. Chemosensitivities to anticancer drugs were evaluated by histoculture drug response assay. We adopted quantitative reverse transcription polymerase chain reaction for TS mRNA detection and immunohistochemical staining for assessing TS expression in tumor tissues. There is a significant relationship between TS mRNA expression levels and in vitro chemosensitivity of freshly removed colorectal tumor specimens to pemetrexed (P < 0.001)/raltitrexed (P = 0.004)/5-FU (P = 0.007). TS mRNA expression levels can predict pemetrexed and raltitrexed sensitivity in colorectal cancer.

Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis.

PubMed

De Savi, Chris; Pape, Andrew; Sawyer, Yvonne; Milne, David; Davies, Chris; Cumming, John G; Ting, Attilla; Lamont, Scott; Smith, Peter D; Tart, Jonathon; Page, Ken; Moore, Peter

2011-06-01

A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure-activity and structure-property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This led to the identification of a pre-clinical candidate with excellent bioavailability across three species and predicting once daily dosing kinetics. Copyright © 2011 Elsevier Ltd. All rights reserved.

Towards an estimation of water masses formation areas from SMOS-based TS diagrams

NASA Astrophysics Data System (ADS)

Klockmann, Marlene; Sabia, Roberto; Fernandez-Prieto, Diego; Donlon, Craig; Font, Jordi

2014-05-01

Temperature-Salinity (TS) diagrams emphasize the mutual variability of ocean temperature and salinity values, relating them to the corresponding density. Canonically used in oceanography, they provide a means to characterize and trace ocean water masses. In [1], a first attempt to estimate surface-layer TS diagrams based on satellite measurements has been performed, profiting from the recent availability of spaceborne salinity data. In fact, the Soil Moisture and Ocean Salinity (SMOS, [2]) and the Aquarius/SAC-D [3] satellite missions allow to study the dynamical patterns of Sea Surface Salinity (SSS) for the first time on a global scale. In [4], given SMOS and Aquarius salinity estimates, and by also using Sea Surface Temperature (SST) from the Operational Sea Surface Temperature and Sea Ice Analysis (OSTIA, [5]) effort, experimental satellite-based TS diagrams have been routinely derived for the year 2011. They have been compared with those computed from ARGO-buoys interpolated fields, referring to a customised partition of the global ocean into seven regions, according to the water masses classification of [6]. In [7], moreover, besides using TS diagrams as a diagnostic tool to evaluate the temporal variation of SST and SSS (and their corresponding density) as estimated by satellite measurements, the emphasis was on the interpretation of the geographical deviations with respect to the ARGO baseline (aiming at distinguishing between the SSS retrieval errors and the additional information contained in the satellite data with respect to ARGO). In order to relate these mismatches to identifiable oceanographic structures and processes, additional satellite datasets of ocean currents, evaporation/precipitation fluxes, and wind speed have been super-imposed. Currently, the main focus of the study deals with the exploitation of these TS diagrams as a prognostic tool to derive water masses formation areas. Firstly, following the approach described in [8], the surface density flux (i.e., the change in density induced by surface heat and freshwater fluxes) is computed, characterizing how the buoyancy of a water parcel is being transformed, by increasing or decreasing its density. Afterwards, integrating over a certain time/space and deriving with respect to density, the formation (in Sv) of water masses themselves can be computed, pinpointing the range of SST and SSS in the TS diagrams where a specific water mass is formed. A geographical representation of these points, ultimately, allows to provide a relevant temporal series of the spatial extent of the water masses formation areas (in the specific test zones chosen). This can be then extended over challenging ocean regions, also evaluating the sensitivity of the performances to the datasets used. With this approach, known water masses can be identified and their formation traced in time and space. Longer time series will give further insights by helping to identify inter-annual water mass formation variability and trends in the TS/geographical domains. Future work aims at exploring additional datasets and at connecting the surface information to the vertical structure and to buoyancy-driven ocean circulation processes. References [1] Sabia, R., J. Ballabrera, G. Lagerloef, E. Bayler, M. Talone, Y. Chao, C. Donlon, D. Fernández-Prieto, J. Font, "Derivation of an Experimental Satellite-based T-S Diagram", In Proceedings of IGARSS '12 , Munich, Germany, pp. 5760-5763, 2012. [2] Font, J., A. Camps, A. Borges, M. Martín-Neira, J. Boutin, N. Reul, Y. H. Kerr, A. Hahne, and S. Mecklenburg, "SMOS: The challenging sea surface salinity measurement from space," Proceedings of the IEEE, vol. 98, pp. 649-665, 2010. [3] Le Vine, D.M.; Lagerloef, G.S.E.; Torrusio, S.E.; "Aquarius and Remote Sensing of Sea Surface Salinity from Space," Proceedings of the IEEE , vol.98, no.5, pp.688-703, May 2010, doi: 10.1109/JPROC.2010.2040550. [4] Sabia, R., M. Klockmann, D. Fernández-Prieto, C. Donlon, E. Bayler, J. Font, G. Lagerloef, "Satellite-based T/S Diagrams and Surface Ocean Water Masses", SMOS-Aquarius Science Workshop, Brest, France, April 2013. [5] Donlon, C. J., M. Martin, J. D. Stark, J. Roberts-Jones, E. Fiedler and W. Wimmer, "The Operational Sea Surface Temperature and Sea Ice analysis (OSTIA)", Remote Sensing of the Environment. doi: 10.1016/j.rse.2010.10.017 2011. [6] Emery, W. J., "Water Types and Water Masses", Ocean Circulation, Elsevier science, pp 1556-1567, 2003. [7] Sabia, R., M. Klockmann, C. Donlon, D. Fernández-Prieto, M. Talone, J. Ballabrera, "Satellite-based T-S Diagrams: a prospective diagnostic tool to trace ocean water masses", Living Planet Symposium 2013, Edinburgh, UK, September 2013. [8] Speer, K., E. Tzipermann, "Rates of Water Mass Transformation in the North Atlantic", Journal of Physical Oceanography, 22, 93 - 104, 1992.

Impact of Tourette Syndrome on School Measures in a Nationally Representative Sample.

PubMed

Claussen, Angelika H; Bitsko, Rebecca H; Holbrook, Joseph R; Bloomfield, Jeanette; Giordano, Kathy

2018-05-01

Children with Tourette syndrome (TS) are at risk for a variety of co-occurring conditions and learning and school problems. The purpose of this study was to determine the impact of TS and co-occurring conditions on school measures. Parent-reported data from the 2007-2008 and 2011-2012 National Survey of Children's Health were combined (n = 129,353 children aged 6-17 yrs). Parent report of health care provider diagnosis of TS; co-occurring mental, emotional, and behavioral conditions; learning and language conditions; and school measures were assessed. School measures included type of school, individual education plan (IEP), number of school days missed, school problems, doing well in school, doing homework, and repeating a grade. Children with TS were compared with those who never had TS on school measures accounting for co-occurring conditions. After adjusting for demographics, compared with children without TS, children currently with TS were more likely to have an IEP, have a parent contacted about school problems, and not complete homework. After further adjusting for co-occurring conditions, only IEP status remained statistically significant. Compared with children with mild TS, children with moderate or severe TS were more likely to have an IEP, repeat a grade, encounter school problems, and not care about doing well in school. Tourette syndrome severity and co-occurring conditions are associated with school challenges and educational service needs. Awareness among health care providers, teachers and parents of the potential challenges related to both TS and co-occurring conditions would help to best support the child's education.

Diffusion tractography and graph theory analysis reveal the disrupted rich-club organization of white matter structural networks in early Tourette Syndrome children

NASA Astrophysics Data System (ADS)

Wen, Hongwei; Liu, Yue; Wang, Shengpei; Zhang, Jishui; Peng, Yun; He, Huiguang

2017-03-01

Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder. At present, the topological disruptions of the whole brain white matter (WM) structural networks remain poorly understood in TS children. Considering the unique position of the topologically central role of densely interconnected brain hubs, namely the rich club regions, therefore, we aimed to investigate whether the rich club regions and their related connections would be particularly vulnerable in early TS children. In our study, we used diffusion tractography and graph theoretical analyses to explore the rich club structures in 44 TS children and 48 healthy children. The structural networks of TS children exhibited significantly increased normalized rich club coefficient, suggesting that TS is characterized by increased structural integrity of this centrally embedded rich club backbone, potentially resulting in increased global communication capacity. In addition, TS children showed a reorganization of rich club regions, as well as significantly increased density and decreased number in feeder connections. Furthermore, the increased rich club coefficients and feeder connections density of TS children were significantly positively correlated to tic severity, indicating that TS may be characterized by a selective alteration of the structural connectivity of the rich club regions, tending to have higher bridging with non-rich club regions, which may increase the integration among tic-related brain circuits with more excitability but less inhibition for information exchanges between highly centered brain regions and peripheral areas. In all, our results suggest the disrupted rich club organization in early TS children and provide structural insights into the brain networks.

Tobacco smoke modulates ozone-induced toxicity in rat lungs and central nervous system.

PubMed

Bhoopalan, Vanitha; Han, Sung Gu; Shah, Mrudang M; Thomas, David M; Bhalla, Deepak K

2013-01-01

Adult Sprague-Dawley (SD) male rats were exposed for a single 3 h period to air, ozone (O₃) or O₃) followed by tobacco smoke (O₃/TS). For pulmonary effects, bronchoalveolar lavage (BAL) cells and fluid were analyzed. Data revealed a significant increase in polymorphonuclear leukocytes (PMN), total protein and albumin concentrations in the O₃ group, reflecting inflammatory and toxic responses. A subsequent exposure to TS attenuated PMN infiltration into the airspaces and their recovery in the BAL. A similar reduction was observed for BAL protein and albumin in the O₃/TS group, but it was not statistically significant. We also observed a significant increase in BAL total antioxidant capacity following O₃ exposure, suggesting development of protective mechanisms for oxidative stress damage from O₃. Exposure to TS attenuated the levels of total antioxidant capacity. Lung tissue protein analysis showed a significant reduction of extracellular superoxide dismutase (EC-SOD) in the O₃ or O₃/TS group and catalase in the O₃/TS group. TS further altered O₃-induced EC-SOD and catalase protein expression, but the reductions were not significant. For effects in the central nervous system (CNS), we measured striatal dopamine levels by HPLC with electrochemical detection. O₃ exposure produced a nonsignificant decrease in the striatal dopamine content. The effect was partially reversed in the O₃/TS group. Overall, the results show that the toxicity of O₃ in the lung is modulated by TS exposure, and the attenuating trend, though nonsignificant in many cases, is contrary to the synergistic toxicity predicted for TS and O₃, suggesting limited cross-tolerance following such exposures.

Age and gender differences in mechanically induced intraoral temporal summation and conditioned pain modulation in healthy subjects.

PubMed

Khan, Junad; Korczeniewska, Olga; Benoliel, Rafael; Kalladka, Mythili; Eliav, Eli; Nasri-Heir, Cibelle

2018-04-13

The aim of this study was to investigate intraoral temporal summation (TS) and conditioned pain modulation (CPM) and compare the outcome with TS and CPM induced in the forearm. In addition, we aimed to study the effect of age and gender on intraoral and forearm TS and CPM. Mechanical stimulation was induced with # 5.46 von Frey filament applying 26 grams of force. A single stimulus, followed by a train of 30 successive stimuli, was applied intraorally and to the dominant forearm. CPM was assessed with the TS test as the painful stimulus and with immersion of the nondominant hand in a hot water bath as the conditioning stimulus. Gender was significantly associated with TS but not with CPM measures. Females had significantly lower mean TS measured in the face and in the dominant forearm compared with males. Age was significantly associated with CPM, but not with TS measures. In both sites examined, older patients had significantly lower mean CPM compared with younger patients. Mechanical TM elicited in the oral cavity can be used as test stimulus for CPM testing. Intraoral modulation, both TS and CPM, has an extent similar to that of the standard cutaneous extremity. TS was lower in females, and CPM was reduced with age. Copyright © 2018 Elsevier Inc. All rights reserved.

Elongation factor Ts directly facilitates the formation and disassembly of the Escherichia coli elongation factor Tu·GTP·aminoacyl-tRNA ternary complex.

PubMed

Burnett, Benjamin J; Altman, Roger B; Ferrao, Ryan; Alejo, Jose L; Kaur, Navdep; Kanji, Joshua; Blanchard, Scott C

2013-05-10

Aminoacyl-tRNA (aa-tRNA) enters the ribosome in a ternary complex with the G-protein elongation factor Tu (EF-Tu) and GTP. EF-Tu·GTP·aa-tRNA ternary complex formation and decay rates are accelerated in the presence of the nucleotide exchange factor elongation factor Ts (EF-Ts). EF-Ts directly facilitates the formation and disassociation of ternary complex. This system demonstrates a novel function of EF-Ts. Aminoacyl-tRNA enters the translating ribosome in a ternary complex with elongation factor Tu (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state fluorescence methods that enabled us to quantitatively explore the kinetic features of Escherichia coli ternary complex formation and decay. The data obtained suggest that both processes are controlled by a nucleotide-dependent, rate-determining conformational change in EF-Tu. Unexpectedly, we found that this conformational change is accelerated by elongation factor Ts (EF-Ts), the guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non-hydrolyzable GTP analogs. These results suggest that EF-Ts serves an unanticipated role in the cell of actively regulating the abundance and stability of ternary complex in a manner that contributes to rapid and faithful protein synthesis.

The portrayal of Tourette Syndrome in film and television.

PubMed

Calder-Sprackman, Samantha; Sutherland, Stephanie; Doja, Asif

2014-03-01

To determine the representation of Tourette Syndrome (TS) in fictional movies and television programs by investigating recurrent themes and depictions. Television and film can be a source of information and misinformation about medical disorders. Tourette Syndrome has received attention in the popular media, but no studies have been done on the accuracy of the depiction of the disorder. International internet movie databases were searched using the terms "Tourette's", "Tourette's Syndrome", and "tics" to generate all movies, shorts, and television programs featuring a character or scene with TS or a person imitating TS. Using a grounded theory approach, we identified the types of characters, tics, and co-morbidities depicted as well as the overall representation of TS. Thirty-seven television programs and films were reviewed dating from 1976 to 2010. Fictional movies and television shows gave overall misrepresentations of TS. Coprolalia was overrepresented as a tic manifestation, characters were depicted having autism spectrum disorder symptoms rather than TS, and physicians were portrayed as unsympathetic and only focusing on medical therapies. School and family relationships were frequently depicted as being negatively impacted by TS, leading to poor quality of life. Film and television are easily accessible resources for patients and the public that may influence their beliefs about TS. Physicians should be aware that TS is often inaccurately represented in television programs and film and acknowledge misrepresentations in order to counsel patients accordingly.

ENVIRONMENTAL TECHNOLOGY VERIFICATION: JOINT (NSF-EPA) VERIFICATION STATEMENT AND REPORT: TRITON SYSTEMS, LLC SOLID BOWL CENTRIFUGE, MODEL TS-5000

EPA Science Inventory

Verification testing of the Triton Systems, LLC Solid Bowl Centrifuge Model TS-5000 (TS-5000) was conducted at the Lake Wheeler Road Field Laboratory Swine Educational Unit in Raleigh, North Carolina. The TS-5000 was 48" in diameter and 30" deep, with a bowl capacity of 16 ft3. ...

Gilles de la Tourette syndrome in a cohort of deaf people.

PubMed

Robertson, M M; Roberts, S; Pillai, S; Eapen, V

2015-10-01

We present six patients with Gilles de la Tourette syndrome (TS) who are also deaf. TS has been observed previously, but rarely reported in deaf people, and to date, so called "unusual" phenomenology has been highlighted. TS occurs almost worldwide and in all cultures, and the clinical phenomenology is virtually identical. In our cohort of deaf patients (we suggest another culture) with TS, the phenomenology is the same as in hearing people, and as in all other cultures, with classic motor and vocal/phonic tics, as well as associated phenomena including echo-phenomena, pali-phenomena and rarer copro-phenomena. When "words" related to these phenomenon (e.g. echolalia, palilalia, coprolalia or mental coprolalia) are elicited in deaf people, they occur usually in British Sign Language (BSL): the more "basic" vocal/phonic tics such as throat clearing are the same phenomenologically as in hearing TS people. In our case series, there was a genetic predisposition to TS in all cases. We would argue that TS in deaf people is the same as TS in hearing people and in other cultures, highlighting the biological nature of the disorder. Copyright © 2015 Elsevier B.V. All rights reserved.

Expression of thymidylate synthase (TS) and its prognostic significance in patients with cutaneous angiosarcoma.

PubMed

Shimizu, A; Kaira, K; Okubo, Y; Utsumi, D; Bolag, A; Yasuda, M; Takahashi, K; Ishikawa, O

2017-01-01

Cutaneous angiosarcoma (CA) is extremely rare, and little is known about the biological significance of possible biomarkers for chemotherapeutic agents. Thymidylate synthase (TS) is an attractive target for cancer treatment in various human neoplasms. It remains unclear whether the expression of TS is associated with the clinicopathological features of CA patients. The aim of this study was to elucidate the relationship between TS expression and the clinicopathological significance in CA patients. Fifty-one patients with CA were included in this study. TS expression and Ki-67 labeling index were examined using immunohistochemical analysis. TS was positively expressed in 39% (20/51) of CA patients. No statistically significant prognostic factor was identified as a predictor of overall survival (OS) for all patients by univariate analysis, whereas a significant prognostic variable for progression free survival (PFS) was found to be the clinical stage. In addition, both univariate and multivariate analyses confirmed that positive expression of TS was a significant predictor of worse PFS in CA patients of clinical stage 1. Positive TS expression in CA was identified as a significant predictor of worse outcome in patients of clinical stage 1.

Total solids content: a key parameter of metabolic pathways in dry anaerobic digestion

PubMed Central

2013-01-01

Background In solid-state anaerobic digestion (AD) bioprocesses, hydrolytic and acidogenic microbial metabolisms have not yet been clarified. Since these stages are particularly important for the establishment of the biological reaction, better knowledge could optimize the process performances by process parameters adjustment. Results This study demonstrated the effect of total solids (TS) content on microbial fermentation of wheat straw with six different TS contents ranging from wet to dry conditions (10 to 33% TS). Three groups of metabolic behaviors were distinguished based on wheat straw conversion rates with 2,200, 1,600, and 1,400 mmol.kgVS-1 of fermentative products under wet (10 and 14% TS), dry (19 to 28% TS), and highly dry (28 to 33% TS) conditions, respectively. Furthermore, both wet and dry fermentations showed acetic and butyric acid metabolisms, whereas a mainly butyric acid metabolism occurred in highly dry fermentation. Conclusion Substrate conversion was reduced with no changes of the metabolic pathways until a clear limit at 28% TS content, which corresponded to the threshold value of free water content of wheat straw. This study suggested that metabolic pathways present a limit of TS content for high-solid AD. PMID:24261971

DESCRIBING LYMPHEDEMA IN FEMALES WITH TURNER SYNDROME.

PubMed

Rothbauer, J; Driver, S; Callender, L

2015-09-01

Turner syndrome (TS) is a chromosomal condition affecting an estimated 1 in 2,500 girls where the second X chromosome is missing, or partially formed. This abnormality affects multiple body systems and can lead to short stature, cardiac, neural, and renal abnormalities. Due to the chronic, non-life threatening nature of lymphedema in comparison to other symptoms of TS, it is often ignored by girls and women with TS and their physicians. Consequently, little is known about how lymphedema affects girls and women with TS across the lifespan. Therefore, the objective of the study was to deliver an online survey for females with TS and caregivers in the US, UK, and Canada to provide a worldwide perspective on their current experience with lymphedema within the spectrum of TS. There were 219 participants who completed the survey, and we were able to identify incidence and characteristics of lymphedema across the lifespan. In addition, we found that females with 45,X karyotyping were more likely to report lymphedema symptoms. Lymphedema is not the most significant concern of females with TS, but education, physician evaluation, and assistance with referrals for treatment and management would improve the ease of managing lymphedema in girls and women with TS.

Mechanical Behavior of Spray-Coated Metallic Laminates

NASA Astrophysics Data System (ADS)

Vackel, Andrew; Nakamura, Toshio; Sampath, Sanjay

2016-06-01

Thermal spray (TS) coatings have been extensively utilized for various surface modifications such as enhancing wear/erosion resistance and thermal protection. In the present study, a new function of TS material is explored by studying its load-carrying capability. Due to the inherent microstructures containing voids and interfaces, it has been presumed TS materials were not suitable to bear loads. However, the recent advances in TS technology to manufacture near fully dense TS coatings have expanded their potential applications. In the current experiments, TS nickel coatings are deposited onto metallic substrates, and their mechanical behaviors are closely examined. Based on the measured data, the estimated elastic modulus of TS Ni is about 130 GPa (35% less than bulk value), and the maximum tensile strength is about 500 MPa (comparable to bulk value). It was found that such a high value is attainable because the coating is deposited onto a substrate, enabling a load-transfer mechanism and preventing coating failure at a much lower stress level. Three distinct deformation stages are identified to describe this behavior. Such a clarification is critical for enabling TS process to restore structural parts as well as to additively manufacture load-bearing components.

Structural Characteristics and Function of a New Kind of Thermostable Trehalose Synthase from Thermobaculum terrenum.

PubMed

Wang, Junqing; Ren, Xudong; Wang, Ruiming; Su, Jing; Wang, Feng

2017-09-06

Trehalose has important applications in the food industry and pharmaceutical manufacturing. The thermostable enzyme trehalose synthase from Thermobaculum terrenum (TtTS) catalyzes the reversible interconversion of maltose and trehalose. Here, we investigated the structural characteristics of TtTS in complex with the inhibitor TriS. TtTS exhibits the typical three domain glycoside hydrolase family 13 structure. The catalytic cleft consists of Asp202-Glu244-Asp310 and various conserved substrate-binding residues. However, among trehalose synthases, TtTS demonstrates obvious thermal stability. TtTS has more polar (charged) amino acids distributed on its protein structure surface and more aromatic amino acids buried within than other mesophilic trehalose synthases. Furthermore, TtTS structural analysis revealed four potential metal ion-binding sites rather than the two in a homologous structure. These factors may render TtTS relatively more thermostable among mesophilic trehalose synthases. The detailed thermophilic enzyme structure provided herein may provide guidance for further protein engineering in the design of stabilized enzymes.

Human body temperature and new approaches to constructing temperature-sensitive bacterial vaccines

PubMed Central

White, Matthew D.; Bosio, Catharine M.; Duplantis, Barry N.

2012-01-01

Many of the live human and animal vaccines that are currently in use are attenuated by virtue of their temperature-sensitive (TS) replication. These vaccines are able to function because they can take advantage of sites in mammalian bodies that are cooler than the core temperature, where TS vaccines fail to replicate. In this article, we discuss the distribution of temperature in the human body, and relate how the temperature differential can be exploited for designing and using TS vaccines. We also examine how one of the coolest organs of the body, the skin, contains antigen-processing cells that can be targeted to provoke the desired immune response from a TS vaccine. We describe traditional approaches to making TS vaccines, and highlight new information and technologies that are being used to create a new generation of engineered TS vaccines. We pay particular attention to the recently described technology of substituting essential genes from Arctic bacteria for their homologues in mammalian pathogens as a way of creating TS vaccines. PMID:21626408

Human body temperature and new approaches to constructing temperature-sensitive bacterial vaccines.

PubMed

White, Matthew D; Bosio, Catharine M; Duplantis, Barry N; Nano, Francis E

2011-09-01

Many of the live human and animal vaccines that are currently in use are attenuated by virtue of their temperature-sensitive (TS) replication. These vaccines are able to function because they can take advantage of sites in mammalian bodies that are cooler than the core temperature, where TS vaccines fail to replicate. In this article, we discuss the distribution of temperature in the human body, and relate how the temperature differential can be exploited for designing and using TS vaccines. We also examine how one of the coolest organs of the body, the skin, contains antigen-processing cells that can be targeted to provoke the desired immune response from a TS vaccine. We describe traditional approaches to making TS vaccines, and highlight new information and technologies that are being used to create a new generation of engineered TS vaccines. We pay particular attention to the recently described technology of substituting essential genes from Arctic bacteria for their homologues in mammalian pathogens as a way of creating TS vaccines.

Enhancing anaerobic digestion of waste activated sludge by pretreatment: effect of volatile to total solids.

PubMed

Wang, Xiao; Duan, Xu; Chen, Jianguang; Fang, Kuo; Feng, Leiyu; Yan, Yuanyuan; Zhou, Qi

2016-01-01

In this study the effect of volatile to total solids (VS/TS) on anaerobic digestion of waste activated sludge (WAS) pretreated by alkaline, thermal and thermal-alkaline strategies was studied. Experimental results showed that the production of methane from sludge was increased with VS/TS. When anaerobic digesters were fed with sludge pretreated by the thermal-alkaline method, the average methane yield was improved from 2.8 L/d at VS/TS 0.35 to 4.7 L/d at VS/TS 0.56. Also, the efficiency of VS reduction during sludge anaerobic digestion varied between 18.9% and 45.6%, and increased gradually with VS/TS. Mechanism investigation of VS/TS on WAS anaerobic digestion suggested that the general activities of anaerobic microorganisms, activities of key enzymes related to sludge hydrolysis, acidification and methanogenesis, and the ratio of Archaea to Bacteria were all increased with VS/TS, showing good agreement with methane production.

Hybrid water flow-like algorithm with Tabu search for traveling salesman problem

NASA Astrophysics Data System (ADS)

Bostamam, Jasmin M.; Othman, Zulaiha

2016-08-01

This paper presents a hybrid Water Flow-like Algorithm with Tabu Search for solving travelling salesman problem (WFA-TS-TSP).WFA has been proven its outstanding performances in solving TSP meanwhile TS is a conventional algorithm which has been used since decades to solve various combinatorial optimization problem including TSP. Hybridization between WFA with TS provides a better balance of exploration and exploitation criteria which are the key elements in determining the performance of one metaheuristic. TS use two different local search namely, 2opt and 3opt separately. The proposed WFA-TS-TSP is tested on 23 sets on the well-known benchmarked symmetric TSP instances. The result shows that the proposed WFA-TS-TSP has significant better quality solutions compared to WFA. The result also shows that the WFA-TS-TSP with 3-opt obtained the best quality solution. With the result obtained, it could be concluded that WFA has potential to be further improved by using hybrid technique or using better local search technique.

A Temperature-Sensitive Lesion in the N-Terminal Domain of the Rotavirus Polymerase Affects Its Intracellular Localization and Enzymatic Activity.

PubMed

McKell, Allison O; LaConte, Leslie E W; McDonald, Sarah M

2017-04-01

Temperature-sensitive ( ts ) mutants of simian rotavirus (RV) strain SA11 have been previously created to investigate the functions of viral proteins during replication. One mutant, SA11- ts C, has a mutation that maps to the gene encoding the VP1 polymerase and shows diminished growth and RNA synthesis at 39°C compared to that at 31°C. In the present study, we sequenced all 11 genes of SA11- ts C, confirming the presence of an L138P mutation in the VP1 N-terminal domain and identifying 52 additional mutations in four other viral proteins (VP4, VP7, NSP1, and NSP2). To investigate whether the L138P mutation induces a ts phenotype in VP1 outside the SA11- ts C genetic context, we employed ectopic expression systems. Specifically, we tested whether the L138P mutation affects the ability of VP1 to localize to viroplasms, which are the sites of RV RNA synthesis, by expressing the mutant form as a green fluorescent protein (GFP) fusion protein (VP1 L138P -GFP) (i) in wild-type SA11-infected cells or (ii) in uninfected cells along with viroplasm-forming proteins NSP2 and NSP5. We found that VP1 L138P -GFP localized to viroplasms and interacted with NSP2 and/or NSP5 at 31°C but not at 39°C. Next, we tested the enzymatic activity of a recombinant mutant polymerase (rVP1 L138P ) in vitro and found that it synthesized less RNA at 39°C than at 31°C, as well as less RNA than the control at all temperatures. Together, these results provide a mechanistic basis for the ts phenotype of SA11- ts C and raise important questions about the role of leucine 138 in supporting key protein interactions and the catalytic function of the VP1 polymerase. IMPORTANCE RVs cause diarrhea in the young of many animal species, including humans. Despite their medical and economic importance, gaps in knowledge exist about how these viruses replicate inside host cells. Previously, a mutant simian RV (SA11- ts C) that replicates worse at higher temperatures was identified. This virus has an amino acid mutation in VP1, which is the enzyme responsible for copying the viral RNA genome. The mutation is located in a poorly understood region of the polymerase called the N-terminal domain. In this study, we determined that the mutation reduces the ability of VP1 to properly localize within infected cells at high temperatures, as well as reduced the ability of the enzyme to copy viral RNA in a test tube. The results of this study explain the temperature sensitivity of SA11- ts C and shed new light on functional protein-protein interaction sites of VP1. Copyright © 2017 American Society for Microbiology.

The "Youth Lens": Analyzing Adolescence/ts in Literary Texts

ERIC Educational Resources Information Center

Petrone, Robert; Sarigianides, Sophia Tatiana; Lewis, Mark A.

2014-01-01

Drawing from interdisciplinary scholarship that re-conceptualizes adolescence as a cultural construct, this article introduces a "Youth Lens." A "Youth Lens" comprises an approach to textual analysis that examines how ideas about adolescence and youth get formed, circulated, critiqued, and revised. Focused specifically on its…

Interaction between paliperidone extended release and TS-1(®), an oral anticancer drug containing a 5-fluorouracil derivative, in a schizophrenic patient.

PubMed

Yasui-Furukori, Norio; Hashimoto, Kojiro; Kubo, Kazutoshi; Tomita, Tetsu

2013-01-01

Until now there has been no information available on drug interaction between paliperidone and TS-1(®), an oral anticancer drug containing a 5-fluorouracil derivative. The patient in the case presented here was a 39-year-old man with a 15-year history of schizophrenia. The patient's usual treatment of 2 mg/day of risperidone was changed to 3 mg/day of paliperidone extended release. He experienced worsening psychotic symptoms after switching from risperidone to paliperidone while he was also receiving TS-1. Retrospective analyses showed plasma concentration of paliperidone was consistently lower during the treatment with TS-1 than without TS-1. This case suggests there is drug interaction between paliperidone extended-release tablets and TS-1.

Transactional Sex: Supply and Demand Among European Men Who have Sex with Men (MSM) in the Context of Local Laws

PubMed Central

Berg, Rigmor C.; Schmidt, Axel J.; Weatherburn, Peter; The EMIS Network

2015-01-01

ABSTRACT Objectives: Transactional sex (TS) is generally defined as the trading of sex for material goods. Cast within the broader context of prostitution laws, we examined variations in the sociodemographic profile of men who have sex with men engaging in TS by payment direction (buying/selling). Methods: The data were collected as part of the 38-country European Men who have sex with men Internet Survey project, conducted in 2010. Results: About 12% of respondents reported engaging in TS in the past year. TS was associated with laws, age, education, employment, and residence. Conclusions: The striking sociodemographic differences in TS by payment direction suggest a power differential and a leading role of socioeconomic factors in TS. PMID:26430474

The Temperature-Sensitive and Attenuation Phenotypes Conferred by Mutations in the Influenza Virus PB2, PB1, and NP Genes Are Influenced by the Species of Origin of the PB2 Gene in Reassortant Viruses Derived from Influenza A/California/07/2009 and A/WSN/33 Viruses

PubMed Central

Broadbent, Andrew J.; Santos, Celia P.; Godbout, Rachel A.

2014-01-01

ABSTRACT Live attenuated influenza vaccines in the United States are derived from a human virus that is temperature sensitive (ts), characterized by restricted (≥100-fold) replication at 39°C. The ts genetic signature (ts sig) has been mapped to 5 loci in 3 genes: PB1 (391E, 581G, and 661T), PB2 (265S), and NP (34G). However, when transferred into avian and swine influenza viruses, only partial ts and attenuation phenotypes occur. To investigate the reason for this, we introduced the ts sig into the human origin virus A/WSN/33 (WSN), the avian-origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple-reassortant 2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene segments from human, avian, and swine viruses. The VN04ts sig and CA07ts sig viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39°C, but the replication of WSNts sig was restricted ≥100-fold compared to that at 33°C. Reassortant CA07ts sig viruses were generated with individual polymerase gene segments from WSN, and vice versa. Only ts sig viruses with a PB2 gene segment derived from WSN were restricted in replication ≥100-fold at 39°C. In ferrets, the CA07ts sig virus replicated in the upper and lower respiratory tract, but the replication of a reassortant CA07ts sig virus with a WSN PB2 gene was severely restricted in the lungs. Taken together, these data suggest that the origin of the PB2 gene segment influences the ts phenotype in vitro and attenuation in vivo. This could have implications for the design of novel live vaccines against animal origin influenza viruses. IMPORTANCE Live attenuated influenza vaccines (LAIVs) on temperature-sensitive (ts) backbones derived from animal origin influenza viruses are being sought for use in the poultry and swine industries and to protect people against animal origin influenza. However, inserting the ts genetic signature from a licensed LAIV backbone fails to fully attenuate these viruses. Our data indicate this is associated with the presence of a PB2 gene segment derived from an avian influenza virus. We show that a reassortant 2009 pandemic H1N1 virus with the ts signature from a licensed LAIV donor virus is ts in vitro and attenuated in vivo when the PB2 gene is derived from a human origin virus but not from an avian virus. Our study provides information that could benefit the rational design of alternative LAIV backbones against animal origin influenza viruses. PMID:25122786

Edge Thomson scattering diagnostic on COMPASS tokamak: Installation, calibration, operation, improvements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bohm, P., E-mail: bohm@ipp.cas.cz; Bilkova, P.; Melich, R.

2014-11-15

The core Thomson scattering diagnostic (TS) on the COMPASS tokamak was put in operation and reported earlier. Implementation of edge TS, with spatial resolution along the laser beam up to ∼1/100 of the tokamak minor radius, is presented now. The procedure for spatial calibration and alignment of both core and edge systems is described. Several further upgrades of the TS system, like a triggering unit and piezo motor driven vacuum window shutter, are introduced as well. The edge TS system, together with the core TS, is now in routine operation and provides electron temperature and density profiles.

Hydroacoustics for the discovery and quantification of Nassau grouper ( Epinephelus striatus) spawning aggregations

NASA Astrophysics Data System (ADS)

Egerton, J. P.; Johnson, A. F.; Le Vay, L.; McCoy, C. M.; Semmens, B. X.; Heppell, S. A.; Turner, J. R.

2017-06-01

Fish spawning aggregations (FSAs) are vital life-history events that need to be monitored to determine the health of aggregating populations; this is especially true of the endangered Nassau grouper ( Epinephelus striatus). Hydroacoustics were used to locate Nassau grouper FSAs at sites on the west end of Little Cayman (LCW), and east ends of Grand Cayman (GCE) and Cayman Brac (CBE). Fish abundance and biomass at each FSA were estimated via echo integration and FSA extent. Acoustic mean fish abundance estimates (±SE) on the FSA at LCW (893 ± 459) did not differ significantly from concurrent SCUBA estimates (1150 ± 75). Mean fish densities (number 1000 m-3) were significantly higher at LCW (33.13 ± 5.62) than at the other sites (GCE: 7.01 ± 2.1, CBE: 4.61 ± 1.16). We investigate different acoustic post-processing options to obtain target strength (TS), and we examine the different TS to total length (TL) formulas available. The SCUBA surveys also provided measures of TL through the use of laser callipers allowing development of an in situ TS to TL formula for Nassau grouper at the LCW FSA. Application of this formula revealed mean fish TL was significantly higher at LCW (65.4 ± 0.7 cm) than GCE (60.7 ± 0.4 cm), but not CBE (61.1 ± 2.5 cm). Use of the empirical TS to TL formula resulted in underestimation of fish length in comparison with diver measurements, highlighting the benefits of secondary length data and deriving specific TS to TL formulas for each population. FSA location examined with reference to seasonal marine protected areas (Designated Grouper Spawning Areas) showed FSAs were partially outside these areas at GCE and very close to the boundary at CBE. As FSAs often occur at the limits of safe diving operations, hydroacoustic technology provides an alternative method to monitor and inform future management of aggregating fish species.

Presence of a consensus DNA motif at nearby DNA sequence of the mutation susceptible CG nucleotides.

PubMed

Chowdhury, Kaushik; Kumar, Suresh; Sharma, Tanu; Sharma, Ankit; Bhagat, Meenakshi; Kamai, Asangla; Ford, Bridget M; Asthana, Shailendra; Mandal, Chandi C

2018-01-10

Complexity in tissues affected by cancer arises from somatic mutations and epigenetic modifications in the genome. The mutation susceptible hotspots present within the genome indicate a non-random nature and/or a position specific selection of mutation. An association exists between the occurrence of mutations and epigenetic DNA methylation. This study is primarily aimed at determining mutation status, and identifying a signature for predicting mutation prone zones of tumor suppressor (TS) genes. Nearby sequences from the top five positions having a higher mutation frequency in each gene of 42 TS genes were selected from a cosmic database and were considered as mutation prone zones. The conserved motifs present in the mutation prone DNA fragments were identified. Molecular docking studies were done to determine putative interactions between the identified conserved motifs and enzyme methyltransferase DNMT1. Collective analysis of 42 TS genes found GC as the most commonly replaced and AT as the most commonly formed residues after mutation. Analysis of the top 5 mutated positions of each gene (210 DNA segments for 42 TS genes) identified that CG nucleotides of the amino acid codons (e.g., Arginine) are most susceptible to mutation, and found a consensus DNA "T/AGC/GAGGA/TG" sequence present in these mutation prone DNA segments. Similar to TS genes, analysis of 54 oncogenes not only found CG nucleotides of the amino acid Arg as the most susceptible to mutation, but also identified the presence of similar consensus DNA motifs in the mutation prone DNA fragments (270 DNA segments for 54 oncogenes) of oncogenes. Docking studies depicted that, upon binding of DNMT1 methylates to this consensus DNA motif (C residues of CpG islands), mutation was likely to occur. Thus, this study proposes that DNMT1 mediated methylation in chromosomal DNA may decrease if a foreign DNA segment containing this consensus sequence along with CG nucleotides is exogenously introduced to dividing cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

EVALUATION OF QUANTITATIVE THYROID SCINTIGRAPHY FOR DIAGNOSIS AND STAGING OF DISEASE SEVERITY IN CATS WITH HYPERTHYROIDISM: COMPARISON OF THE PERCENT THYROIDAL UPTAKE OF PERTECHNETATE TO THYROID-TO-SALIVARY RATIO AND THYROID-TO-BACKGROUND RATIOS.

PubMed

Peterson, Mark E; Guterl, Jade N; Rishniw, Mark; Broome, Michael R

2016-07-01

Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid-to-salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid-to-background ratios (T/B) or percent thyroidal uptake of (99m) TcO(-) 4 (TcTU) has only been reported in a few studies. The purpose of this prospective, cross-sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T4 ), triiodothyronine (T3 ), free T4 (fT4 ), and thyroid-stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T4 (r = 0.76 vs. 0.64), T3 (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland. © 2016 American College of Veterinary Radiology.

LIDAR TS for ITER core plasma. Part II: simultaneous two wavelength LIDAR TS

NASA Astrophysics Data System (ADS)

Gowers, C.; Nielsen, P.; Salzmann, H.

2017-12-01

We have shown recently, and in more detail at this conference (Salzmann et al) that the LIDAR approach to ITER core TS measurements requires only two mirrors in the inaccessible port plug area of the machine. This leads to simplified and robust alignment, lower risk of mirror damage by plasma contamination and much simpler calibration, compared with the awkward and vulnerable optical geometry of the conventional imaging TS approach, currently under development by ITER. In the present work we have extended the simulation code used previously to include the case of launching two laser pulses, of different wavelengths, simultaneously in LIDAR geometry. The aim of this approach is to broaden the choice of lasers available for the diagnostic. In the simulation code it is assumed that two short duration (300 ps) laser pulses of different wavelengths, from an Nd:YAG laser are launched through the plasma simultaneously. The temperature and density profiles are deduced in the usual way but from the resulting combined scattered signals in the different spectral channels of the single spectrometer. The spectral response and quantum efficiencies of the detectors used in the simulation are taken from catalogue data for commercially available Hamamatsu MCP-PMTs. The response times, gateability and tolerance to stray light levels of this type of photomultiplier have already been demonstrated in the JET LIDAR system and give sufficient spatial resolution to meet the ITER specification. Here we present the new simulation results from the code. They demonstrate that when the detectors are combined with this two laser, LIDAR approach, the full range of the specified ITER core plasma Te and ne can be measured with sufficient accuracy. So, with commercially available detectors and a simple modification of a Nd:YAG laser similar to that currently being used in the design of the conventional ITER core TS design mentioned above, the ITER requirements can be met.

Influences of recovery from wildfire and thinning on soil respiration of a Mediterranean mixed forest.

PubMed

López-Serrano, F R; Rubio, E; Dadi, T; Moya, D; Andrés-Abellán, M; García-Morote, F A; Miettinen, H; Martínez-García, E

2016-12-15

The ecosystem recovery after wildfire and thinning practices are both key processes that have great potential to influence fluxes and storage of carbon within Mediterranean semiarid ecosystems. In this study, started 7years after a wildfire, soil respiration (SR) patterns measured from 2008 to 2010 were compared between an unmanaged-undisturbed mature forest stand (UB site) and a naturally regenerated post-wildfire stand (B site) in a Mediterranean mixed forest in Spain. The disturbed stand included a control zone (unthinned forest, BUT site) and a thinned zone (BT site). Our results indicated that SR was lower at naturally regenerated after fire sites (BUT and BT) than at unburnt one. Soil under the canopy layer of pine and oak trees exhibited higher SR rates than bare or herbaceous layer soils, regardless of the site. The effect of thinning was only manifest, with a significant increase of SR, during the 1st year after thinning practices. SR showed a clear soil temperature-dependent seasonal pattern, which was strongly modulated by soil water content (SWC), especially in summer. Site-specific polynomial regression models were defined to describe SR responses, being mainly controlled by both soil temperature (Ts) and SWC at UB site, or Ts at burnt sites. The sensitivity of SR rate to Ts variations (Q 10 ) ranged between 0.20 and 6.89, with mean annual values varying between 0.92 and 1.35. Q 10 values were higher at BT than at UB-BUT sites. The results revealed a significant, non-linear dependence, of Q 10 on both Ts and SWC at UB site, and on Ts at both burnt sites. This study contributes to (i) improve the understanding of how natural recovery and management practices affect soil respiration in a Mediterranean forest during their early stages after fire disturbance and (ii) highlight the importance of Q 10 values <1 which emphasizes drought stress effect on SR temperature sensitivity. Copyright © 2016 Elsevier B.V. All rights reserved.

Transfrontal and Transsphenoidal Approaches to Pediatric Craniopharyngioma: A National Perspective.

PubMed

Lin, Yimo; Hansen, Daniel; Sayama, Christina M; Pan, I-Wen; Lam, Sandi

2017-01-01

This study compared transsphenoidal (TS) and transfrontal (TF) approaches to craniopharyngioma utilizing a national database. The Kids' Inpatient Database (2003, 2006, and 2009) was surveyed for patients with a diagnosis of craniopharyngioma who underwent a subset of surgical interventions to compare TS and TF surgery. Demographics, hospital variables, and complications/comorbidities were analyzed with multivariate regression. 314 admissions (TS = 104, TF = 210) were identified. The mean age was 14.8 (TS) versus 9.8 (TF) years (p < 0.001). The mean number of diagnoses was 4.6 (TS) versus 6.2 (TF) (p < 0.001). Diabetes insipidus was associated with 38% (TS) and 69% (TF). Cerebrospinal fluid (CSF) leak affected 19% TS and 4% TF resections. Other complications and comorbidities included postoperative stroke (2% TS vs. 5% TF), panhypopituitarism (5 vs. 8%), death (0 vs. 1%), cranial nerve deficits (1 vs. 6%), thrombotic events (7 vs. 17%), and seizures (0 vs. 12%). 98% of patients were discharged home after a mean 6-day length of stay (LOS) after TS, whereas 90% of TF patients had a LOS of 12 days. TS cases were more likely to be privately insured (68%) and from higher income brackets (61%) than TF ones (56 and 2%, respectively) (p < 0.05). In multivariate regression models adjusting for age, sex, race, number of diagnoses, surgical approach, hospital volume, and insurance type, the TS approach was associated with an increased incidence of CSF leak (OR 10, p < 0.001). More documented diagnoses (OR 16-60, p < 0.01) and TF approach (OR 2.6, p < 0.01) were associated with an increased incidence of other complications and comorbidities. Age younger than 10 (β-coefficient 2.3, p = 0.01), more diagnoses (β-coefficient 1.2, p < 0.001), and TF approach (β- coefficient 3.0, p < 0.01) were associated with increased LOS. A higher number of diagnoses were associated with nonhome discharge destinations (β-coefficient 1.29, p < 0.001). TS surgery was associated with an increased incidence of CSF leak but shorter LOS; TF surgery was associated with an increased incidence of other complications. Patients undergoing TS surgery were more likely to have private insurance and a higher family income bracket. © 2017 S. Karger AG, Basel.

Engineering Temperature Sensitive Live Attenuated Influenza Vaccines from Emerging Viruses

PubMed Central

Zhou, Bin; Li, Yan; Speer, Scott D.; Subba, Anju; Lin, Xudong; Wentworth, David E.

2012-01-01

The licensed live attenuated influenza A vaccine (LAIV) in the United States is created by making a reassortant containing six internal genes from a cold-adapted master donor strain (ca A/AA/6/60) and two surface glycoprotein genes from a circulating/emerging strain (e.g., A/CA/7/09 for the 2009/2010 H1N1 pandemic). Technologies to rapidly create recombinant viruses directly from patient specimens were used to engineer alternative LAIV candidates that have genomes composed entirely of vRNAs from pandemic or seasonal strains. Multiple mutations involved in the temperature-sensitive (ts) phenotype of the ca A/AA/6/60 master donor strain were introduced into a 2009 H1N1 pandemic strain rA/New York/1682/2009 (rNY1682-WT) to create rNY1682-TS1, and additional mutations identified in other ts viruses were added to rNY1682-TS1 to create rNY1682-TS2. Both rNY1682-TS1 and rNY1682-TS2 replicated efficiently at 30°C and 33°C. However, rNY1682-TS1 was partially restricted, and rNY1682-TS2 was completely restricted at 39°C. Additionally, engineering the TS1 or TS2 mutations into a distantly related human seasonal H1N1 influenza A virus also resulted pronounced restriction of replication in vitro. Clinical symptoms and virus replication in the lungs of mice showed that although rNY1682-TS2 and the licensed FluMist®-H1N1pdm LAIV that was used to combat the 2009/2010 pandemic were similarly attenuated, the rNY1682-TS2 was more protective upon challenge with a virulent mutant of pandemic H1N1 virus or a heterologous H1N1 (A/PR/8/1934) virus. This study demonstrates that engineering key temperature sensitive mutations (PB1-K391E, D581G, A661T; PB2-P112S, N265S, N556D, Y658H) into the genomes of influenza A viruses attenuates divergent human virus lineages and provides an alternative strategy for the generation of LAIVs. PMID:22449422

40 CFR Table 21 to Subpart G of... - Average Storage Temperature (Ts) as a Function of Tank Paint Color

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 10 2012-07-01 2012-07-01 false Average Storage Temperature (Ts) as a..., and Wastewater Pt. 63, Subpt. G, Table 21 Table 21 to Subpart G of Part 63—Average Storage Temperature (Ts) as a Function of Tank Paint Color Tank Color Average Storage Temperature (Ts) White TA a = 0...

40 CFR Table 21 to Subpart G of... - Average Storage Temperature (Ts) as a Function of Tank Paint Color

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Average Storage Temperature (Ts) as a..., and Wastewater Pt. 63, Subpt. G, Table 21 Table 21 to Subpart G of Part 63—Average Storage Temperature (Ts) as a Function of Tank Paint Color Tank Color Average Storage Temperature (Ts) White TA a = 0...

40 CFR Table 21 to Subpart G of... - Average Storage Temperature (Ts) as a Function of Tank Paint Color

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 10 2013-07-01 2013-07-01 false Average Storage Temperature (Ts) as a..., and Wastewater Pt. 63, Subpt. G, Table 21 Table 21 to Subpart G of Part 63—Average Storage Temperature (Ts) as a Function of Tank Paint Color Tank Color Average Storage Temperature (Ts) White TA a = 0...

40 CFR Table 21 to Subpart G of... - Average Storage Temperature (Ts) as a Function of Tank Paint Color

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 9 2011-07-01 2011-07-01 false Average Storage Temperature (Ts) as a..., and Wastewater Pt. 63, Subpt. G, Table 21 Table 21 to Subpart G of Part 63—Average Storage Temperature (Ts) as a Function of Tank Paint Color Tank Color Average Storage Temperature (Ts) White TA a = 0...

40 CFR Table 21 to Subpart G of... - Average Storage Temperature (Ts) as a Function of Tank Paint Color

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 10 2014-07-01 2014-07-01 false Average Storage Temperature (Ts) as a..., and Wastewater Pt. 63, Subpt. G, Table 21 Table 21 to Subpart G of Part 63—Average Storage Temperature (Ts) as a Function of Tank Paint Color Tank Color Average Storage Temperature (Ts) White TA a = 0...

Comparative genomic analysis reveals a novel mitochondrial isoform of human rTS protein and unusual phylogenetic distribution of the rTS gene

PubMed Central

Liang, Ping; Nair, Jayakumar R; Song, Lei; McGuire, John J; Dolnick, Bruce J

2005-01-01

Background The rTS gene (ENOSF1), first identified in Homo sapiens as a gene complementary to the thymidylate synthase (TYMS) mRNA, is known to encode two protein isoforms, rTSα and rTSβ. The rTSβ isoform appears to be an enzyme responsible for the synthesis of signaling molecules involved in the down-regulation of thymidylate synthase, but the exact cellular functions of rTS genes are largely unknown. Results Through comparative genomic sequence analysis, we predicted the existence of a novel protein isoform, rTS, which has a 27 residue longer N-terminus by virtue of utilizing an alternative start codon located upstream of the start codon in rTSβ. We observed that a similar extended N-terminus could be predicted in all rTS genes for which genomic sequences are available and the extended regions are conserved from bacteria to human. Therefore, we reasoned that the protein with the extended N-terminus might represent an ancestral form of the rTS protein. Sequence analysis strongly predicts a mitochondrial signal sequence in the extended N-terminal of human rTSγ, which is absent in rTSβ. We confirmed the existence of rTS in human mitochondria experimentally by demonstrating the presence of both rTSγ and rTSβ proteins in mitochondria isolated by subcellular fractionation. In addition, our comprehensive analysis of rTS orthologous sequences reveals an unusual phylogenetic distribution of this gene, which suggests the occurrence of one or more horizontal gene transfer events. Conclusion The presence of two rTS isoforms in mitochondria suggests that the rTS signaling pathway may be active within mitochondria. Our report also presents an example of identifying novel protein isoforms and for improving gene annotation through comparative genomic analysis. PMID:16162288

Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients

PubMed Central

Paradiso, A; Simone, G; Petroni, S; Leone, B; Vallejo, C; Lacava, J; Romero, A; Machiavelli, M; Lena, M De; Allegra, C J; Johnston, P G

2000-01-01

The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated–5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53– cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively;P< 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P< 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34–1.01; two-sided P< 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85–1.26; two-sided P< 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy. © 2000 Cancer Research Campaign PMID:10682666

Psychogenetics of Turner syndrome: an investigation of 28 subjects and respective controls using the Bender test and Piagetian scales.

PubMed

Ricardi, F C F; Zaia, L L; Pellegrino-Rosa, I; Rosa, J T; Mantovani de Assis, O Z; Saldanha, P H

2010-08-31

Piagetian scales and the Bender visual motor gestalt test (BT) were applied to 28 subjects with universal 45,X Turner syndrome (TS), and their respective controls, in order to investigate their cognitive performance. Dermatoglyphics were also analyzed to obtain clues concerning embryological changes that may have appeared during development of the nervous system and could be associated with cognitive performance of TS patients. Dermatoglyphic pattern distribution was similar to that reported in previous studies of TS individuals: ulnar loops in the digital patterns and finger ridge, a-b, and A'-d counts were more frequent, while arch and whorl patterns were less frequent compared to controls. However, we did not find higher frequencies of hypothenar pattern, maximum atd angle, and ulnarity index in our TS subjects, unlike other investigations. Furthermore, we found significant differences between TS and control T line index values. The BT scores were also lower in probands, as has been previously reported, revealing a neurocognitive deficit of visual motor perception in TS individuals, which could be due to an absence of, or deficiency in, cerebral hemispheric lateralization. However, TS subjects seemed to improve their performance on BT with age. Cognitive performance of the TS subjects was not significantly different from that of controls, confirming a previous study in which TS performance was found to be similar to that of the normal Brazilian population. There were significant correlations between BT scores and Piagetian scale levels with dermatoglyphic parameters. This association could be explained by changes in the common ectodermal origin of the epidermis and the central nervous system. TS subjects seem to succeed in compensating their spatial impairments in adapting their cognitive and social contacts. We concluded that genetic counseling should consider cognitive and psychosocial difficulties presented by TS subjects, providing appropriate treatment and orientation for them and their families.

Un-catalyzed peptide bond formation between two monomers of glycine, alanine, serine, threonine, and aspartic acid in gas phase: a density functional theory study

NASA Astrophysics Data System (ADS)

Bhunia, Snehasis; Singh, Ajeet; Ojha, Animesh K.

2016-05-01

In the present report, un-catalyzed peptide bond formation between two monomers of glycine (Gly), alanine (Ala), serine (Ser), threonine (Thr), and aspartic acid (Asp) has been investigated in gas phase via two steps reaction mechanism and concerted mechanism at B3LYP/6-31G(d,p) and M062X/6-31G(d,p) level of theories. The peptide bond is formed through a nucleophilic reaction via transition states, TS1 and TS2 in stepwise mechanism. The TS1 reveals formation of a new C-N bond while TS2 illustrate the formation of C=O bond. In case of concerted mechanism, C-N bond is formed by a single four-centre transition state (TS3). The energy barrier is used to explain the involvement of energy at each step of the reaction. The energy barrier (20-48 kcal/mol) is required for the transformation of reactant state R1 to TS1 state and intermediate state I1 to TS2 state. The large value of energy barrier is explained in terms of distortion and interaction energies for stepwise mechanism. The energy barrier of TS3 in concerted mechanism is very close to the energy barrier of the first transition state (TS1) of the stepwise mechanism for the formation of Gly-Gly and Ala-Ala di- peptide. However, in case of Ser-Ser, Thr-Thr and Asp-Asp di-peptide, the energy barrier of TS3 is relatively high than that of the energy barrier of TS1 calculated at B3LYP/6-31G(d,p) and M062X/6-31G(d,p) level of theories. In both the mechanisms, the value of energy barrier calculated at B3LYP/6-31G(d,p) level of theory is greater than that of the value calculated at M062X/6-31G(d,p) level of theory.

Comparative analysis of COPD associated with tobacco smoking, biomass smoke exposure or both.

PubMed

Olloquequi, Jordi; Jaime, Sergio; Parra, Viviana; Cornejo-Córdova, Elizabeth; Valdivia, Gonzalo; Agustí, Àlvar; Silva O, Rafael

2018-01-18

Exposure to noxious gases and particles contained in both tobacco smoking (TS) and biomass smoke (BS) are well recognized environmental risk factors for chronic obstructive pulmonary disease (COPD). COPD is characterized by an abnormal inflammatory response, both in the pulmonary and systemic compartments. The differential effects of TS, BS or their combined exposure have not been well characterized yet. This study sought to compare the lung function characteristics and systemic inflammatory response in COPD patients exposed to TS, BS or their combination. Sociodemographic, clinical and lung functional parameters were compared across 49 COPD patients with a history of smoking and no BS exposure (TS COPD), 31 never-smoker COPD patients with BS exposure (BS COPD), 46 COPD patients with a combined exposure (TS + BS COPD) and 52 healthy controls (HC) who have never been exposed neither to TS or BS. Blood cell counts, C-reactive protein (CRP), fibrinogen and immunoglobulin E (IgE) levels were quantified in all four groups. TS + BS COPD patients exhibited significantly lower oxygen saturation than the rest of groups (p < 0.01). Spirometry and diffusing capacity were significantly higher in BS than in TS or TS + BS patients. CRP levels were significantly higher in TS COPD patients than in BS COPD group (p < 0.05), whereas fibrinogen was raised in COPD patients with a history of smoking (TS and TS + BS) when compared to control subjects (p < 0.01). Finally, COPD patients with BS exposure (BS and BS + TS groups) showed higher IgE levels than TS and HC (p < 0.05). There are significant physiological and inflammatory differences between COPD patients with TS, BS and TS + BS exposures. The latter had worse blood oxygenation, whereas the raised levels of IgE in BS exposed patients suggests a differential Th2 systemic inflammatory pattern triggered by this pollutant.

Cell death in response to antimetabolites directed at thymidylate synthase.

PubMed

Barbour, Karen W; Berger, Franklin G

2008-02-01

Thymidylate synthase (TS) is an indispensable enzyme in the de novo biosynthesis of TMP during DNA replication and cell growth, and has, therefore, been an important target for several classes of antimetabolites used in cancer chemotherapy. While most investigations of the action of TS-directed agents have focused on apoptosis as the primary means of cell death, little is known regarding the role, if any, of non-apoptotic mechanisms. In the present study, we have examined the mode of cell death induced by several TS inhibitors. Apoptosis and necrosis in response to TS inhibitors was assessed. The roles of caspases and the transcriptional regulator nuclear factor kappa B (NFkappaB) in drug-induced cell death were analyzed. Finally, drug-mediated changes in expression of several proteins involved in regulation of apoptosis were analyzed. Though human colon tumor cells exposed to TS inhibitors undergo classical apoptosis, it is not the predominant mechanism of response; rather, a necrosis-like mechanism prevails. The apoptotic response to TS inhibitors is caspase-dependent, and is promoted by NFkappaB. In contrast, the necrosis-like response is independent of both caspases and NFkappaB. Exposure to TS inhibitors induces PARP cleavage, but does not alter expression of the pro or activated forms of caspases-3 or caspases-8, Fas, or FasL. Treatment with the death-inducing cytokine TNFalpha, like TS inhibitors, results in a limited extent of apoptosis that is both caspase- and NFkappaB-dependent; however, unlike TS inhibitors, the cytokine does not induce necrosis. Classical apoptosis occurs to a limited extent in human colon tumor cells exposed to TS inhibitors, with caspase-independent necrosis being the prinicipal mechanism of cell death. We suggest that the role of necrosis and necrosis-like mechanisms should be considered in future studies of the action of TS-directed antimetabolites, as well as other chemotherapeutic agents.

Potential utility of three-dimensional temperature and salinity fields estimated from satellite altimetry and Argo data for improving mesoscale reproducibility in regional ocean modeling

NASA Astrophysics Data System (ADS)

Kanki, R.; Uchiyama, Y.; Miyazaki, D.; Takano, A.; Miyazawa, Y.; Yamazaki, H.

2014-12-01

Mesoscale oceanic structure and variability are required to be reproduced as accurately as possible in realistic regional ocean modeling. Uchiyama et al. (2012) demonstrated with a submesoscale eddy-resolving JCOPE2-ROMS downscaling oceanic modeling system that the mesoscale reproducibility of the Kuroshio meandering along Japan is significantly improved by introducing a simple restoration to data which we call "TS nudging" (a.k.a. robust diagnosis) where the prognostic temperature and salinity fields are weakly nudged four-dimensionally towards the assimilative JCOPE2 reanalysis (Miyazawa et al., 2009). However, there is not always a reliable reanalysis for oceanic downscaling in an arbitrary region and at an arbitrary time, and therefore alternative dataset should be prepared. Takano et al. (2009) proposed an empirical method to estimate mesoscale 3-D thermal structure from the near real-time AVISO altimetry data along with the ARGO float data based on the two-layer model of Goni et al. (1996). In the present study, we consider the TS data derived from this method as a candidate. We thus conduct a synoptic forward modeling of the Kuroshio using the JCOPE2-ROMS downscaling system to explore potential utility of this empirical TS dataset (hereinafter TUM-TS) by carrying out two runs with the T-S nudging towards 1) the JCOPE2-TS and 2) TUM-TS fields.　An example of the comparison between the two ROMS test runs is shown in the attached figure showing the annually averaged surface EKE. Both of TUM-TS and JCOPE2-TS are found to help reproducing the mesoscale variance of the Koroshio and its extension as well as its mean paths, surface KE and EKE reasonably well. Therefore, the AVISO-ARGO derived empirical 3-D TS estimation is potentially exploitable for the dataset to conduct the T-S nudging to reproduce mesoscale oceanic structure.

Mouse-based genetic modeling and analysis of Down syndrome

PubMed Central

Xing, Zhuo; Li, Yichen; Pao, Annie; Bennett, Abigail S.; Tycko, Benjamin; Mobley, William C.; Yu, Y. Eugene

2016-01-01

Introduction Down syndrome (DS), caused by human trisomy 21 (Ts21), can be considered as a prototypical model for understanding the effects of chromosomal aneuploidies in other diseases. Human chromosome 21 (Hsa21) is syntenically conserved with three regions in the mouse genome. Sources of data A review of recent advances in genetic modeling and analysis of DS. Using Cre/loxP-mediated chromosome engineering, a substantial number of new mouse models of DS have recently been generated, which facilitates better understanding of disease mechanisms in DS. Areas of agreement Based on evolutionary conservation, Ts21 can be modeled by engineered triplication of Hsa21 syntenic regions in mice. The validity of the models is supported by the exhibition of DS-related phenotypes. Areas of controversy Although substantial progress has been made, it remains a challenge to unravel the relative importance of specific candidate genes and molecular mechanisms underlying the various clinical phenotypes. Growing points Further understanding of mechanisms based on data from mouse models, in parallel with human studies, may lead to novel therapies for clinical manifestations of Ts21 and insights to the roles of aneuploidies in other developmental disorders and cancers. PMID:27789459

Growth, microstructure and electrical properties of sputter-deposited hafnium oxide (HfO2) thin films grown using HfO2 ceramic target

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aguirre, B.; Vemuri, R. S.; Zubia, David

2011-01-01

Hafnium oxide (HfO₂) thin films have been made by radio-frequency (rf) magnetron-sputtering onto Si(100) substrates under varying growth temperature (Ts). HfO₂ ceramic target has been employed for sputtering while varying the Ts from room temperature to 500⁰C during deposition. The effect of Ts on the growth and microstructure of deposited HfO₂ films has been studied using grazing incidence x-ray diffraction (GIXRD), X-ray photoelectron spectroscopy (XPS), and high-resolution scanning electron microscopy (HR-SEM) coupled with energy dispersive x-ray spectrometry (EDS). The results indicate that the effect of Ts is significant on the growth, surface and interface structure, morphology and chemical composition ofmore » the HfO₂ films. Structural characterization indicates that the HfO₂ films grown at Ts<200 ⁰C are amorphous while films grown at Ts>200 ⁰C are nanocrystalline. An amorphous-to-crystalline transition occurs at Ts=200 ⁰C. Nanocrystalline HfO₂ films crystallized in a monoclinic structure with a (-111) orientation. XPS measurements indicated the high surface-chemical quality and stoichiometric nature of the grown HfO₂ films. An interface layer (IL) formation occurs due to reaction at the HfO₂-Si interface for HfO₂ films deposited at Ts>200 ⁰C. The thickness of IL increases with increasing Ts. XPS and EDS at the HfO₂-Si cross-section indicate the IL is a (Hf, Si)-O compound. The electrical characterization using capacitance-voltage measurements indicate that the dielectric constant decreases from 25 to 16 with increasing Ts.« less

Relationship Between the DPD and TS mRNA Expression and the Response to S-1-Based Chemotherapy and Prognosis in Patients with Advanced Gastric Cancer.

PubMed

Shen, Xiao-Ming; Zhou, Chong; Lian, Lian; Li, Li-Qun; Li, Wei; Tao, Min

2015-04-01

The aim was to determine changes in dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) mRNAs in the blood of advanced gastric cancer (AGC) patients to see whether these enzymes affected the patients' response to S-1-based chemotherapy and prognosis. For this purpose, pretreatment DPD/TS mRNA expressions were determined in 40 AGC patients using RT-PCR. The patients were then administered with S-1-based regimen (S-1 + cisplatin) and toxicities were recorded. The relationship between the DPD/TS mRNA expressions and the chemotherapy response, drug resistance, and prognosis was analyzed. The data show that DPD mRNA expression correlated significantly with Lauren type while TS mRNA expression correlated with distant metastasis. Patients with higher DPD and/or TS mRNA expression(s) showed poor response, while those with low DPD mRNA expression showed better response to the chemotherapy. Pooled analysis showed that the patients with low DPD/TS mRNA expressions had better therapeutic response. The incidence of bone marrow suppression, diarrhea, and oral mucositis was high in patients with low DPD mRNA expression. Median overall survival (OS) in 40 patients was 13.5 months. It was 17 months for low and 10 months for high DPD (P = 0.044) and TS mRNA expression (P = 0.047). Pooled analysis showed that the patients with both low DPD/TS mRNA expressions had longer OS (P = 0.001). In conclusion, the detection of DPD and/or TS mRNA expression can be used to predict the response to S-1-based chemotherapy, drug resistance, and prognosis in AGC patients as well as to help guide the individualized treatment of gastric cancer.

Disrupted topological organization of structural networks revealed by probabilistic diffusion tractography in Tourette syndrome children.

PubMed

Wen, Hongwei; Liu, Yue; Rekik, Islem; Wang, Shengpei; Zhang, Jishui; Zhang, Yue; Peng, Yun; He, Huiguang

2017-08-01

Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder. Although previous TS studies revealed structural abnormalities in distinct corticobasal ganglia circuits, the topological alterations of the whole-brain white matter (WM) structural networks remain poorly understood. Here, we used diffusion MRI probabilistic tractography and graph theoretical analysis to investigate the topological organization of WM networks in 44 drug-naive TS children and 41 age- and gender-matched healthy children. The WM networks were constructed by estimating inter-regional connectivity probability and the topological properties were characterized using graph theory. We found that both TS and control groups showed an efficient small-world organization in WM networks. However, compared to controls, TS children exhibited decreased global and local efficiency, increased shortest path length and small worldness, indicating a disrupted balance between local specialization and global integration in structural networks. Although both TS and control groups showed highly similar hub distributions, TS children exhibited significant decreased nodal efficiency, mainly distributed in the default mode, language, visual, and sensorimotor systems. Furthermore, two separate networks showing significantly decreased connectivity in TS group were identified using network-based statistical (NBS) analysis, primarily composed of the parieto-occipital cortex, precuneus, and paracentral lobule. Importantly, we combined support vector machine and multiple kernel learning frameworks to fuse multiple levels of network topological features for classification of individuals, achieving high accuracy of 86.47%. Together, our study revealed the disrupted topological organization of structural networks related to pathophysiology of TS, and the discriminative topological features for classification are potential quantitative neuroimaging biomarkers for clinical TS diagnosis. Hum Brain Mapp 38:3988-4008, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome.

PubMed

Corrales, Andrea; Parisotto, Eduardo B; Vidal, Verónica; García-Cerro, Susana; Lantigua, Sara; Diego, Marian; Wilhem Filho, Danilo; Sanchez-Barceló, Emilio J; Martínez-Cué, Carmen; Rueda, Noemí

2017-09-15

Melatonin administered during adulthood induces beneficial effects on cognition and neuroprotection in the Ts65Dn (TS) mouse model of Down syndrome. Here, we investigated the effects of pre- and post-natal melatonin treatment on behavioral and cognitive abnormalities and on several neuromorphological alterations (hypocellularity, neurogenesis impairment and increased oxidative stress) that appear during the early developmental stages in TS mice. Pregnant TS females were orally treated with melatonin or vehicle from the time of conception until the weaning of the offspring, and the pups continued to receive the treatment from weaning until the age of 5 months. Melatonin administered during the pre- and post-natal periods did not improve the cognitive impairment of TS mice as measured by the Morris Water maze or fear conditioning tests. Histological alterations, such as decreased proliferation (Ki67+ cells) and hippocampal hypocellularity (DAPI+ cells), which are typical in TS mice, were not prevented by melatonin. However, melatonin partially regulated brain oxidative stress by modulating the activity of the primary antioxidant enzymes (superoxide dismutase in the cortex and catalase in the cortex and hippocampus) and slightly decreasing the levels of lipid peroxidation in the hippocampus of TS mice. These results show the inability of melatonin to prevent cognitive impairment in TS mice when it is administered at pre- and post-natal stages. Additionally, our findings suggest that to induce pro-cognitive effects in TS mice during the early stages of development, in addition to attenuating oxidative stress, therapies should aim to improve other altered processes, such as hippocampal neurogenesis and/or hypocellularity. Copyright © 2017 Elsevier B.V. All rights reserved.

Takotsubo syndrome and estrogen receptor genes: partners in crime?

PubMed

Pizzino, Gabriele; Bitto, Alessandra; Crea, Pasquale; Khandheria, Bijoy; Vriz, Olga; Carerj, Scipione; Squadrito, Francesco; Minisini, Rosalba; Citro, Rodolfo; Cusmà-Piccione, Maurizio; Madaffari, Antonio; Andò, Giuseppe; Altavilla, Domenica; Zito, Concetta

2017-04-01

We aimed to analyze genetic polymorphism of estrogen receptor (ESR) 1 and ESR2 in a series of postmenopausal women with Takotsubo syndrome (TS). In total, 81 consecutive white women were prospectively enrolled: 22 with TS (TS group; mean age 71.2 ± 9.8 years), 22 with acute myocardial infarction (MI group; mean age 73.2 ± 8 years), and 37 asymptomatic healthy controls (CTRL group; mean age 69 ± 4.2 years). Genotyping of ESR1 -397C>T (rs2234693) and -351A>G (rs9340799) and ESR2 -1839G>T (rs 1271572) and 1082G>A (rs1256049) genetic variants was performed. We estimated the odds ratio (OR) between the genotype of each examined locus with the occurrence of TS or MI. The risk of experiencing TS was higher for those study participants carrying the T allele at the rs2234693 locus of the ESR1 gene [OR: 2.0, 95% confidence interval (CI): 0.973-4.11, P = 0.04, TS vs. MI + CTRL; OR: 2.79, 95% CI: 1.17-6.64, P = 0.016, TS vs. MI alone]. Women carrying a T allele at the rs1271572 locus of the ESR2 gene demonstrated an even higher risk (OR: 3.23, 95% CI: 1.55-6.73, P = 0.0019, TS vs. MI + CTRL; OR: 9.13, 95% CI: 2.78-29.9, P = 0.0001, TS vs. MI alone). The study reports preliminary findings suggesting a possible link between ESR polymorphisms and the occurrence of TS. Larger studies are needed to confirm our results.

Biochemical characterization of the triticale TsPAP1, a new type of plant prolyl aminopeptidase, and its impact on proline content and flowering time in transgenic Arabidopsis plants.

PubMed

Zdunek-Zastocka, Edyta; Grabowska, Agnieszka; Branicki, Tomasz; Michniewska, Beata

2017-07-01

Proline aminopeptidase (PAP, EC 3.4.11.5) is the only enzyme that effectively releases proline from the N-termini of peptides. The amino acid sequence of the PAP from Triticosecale, TsPAP1, comprises conserved regions, characteristic of the monomeric forms of PAP found in bacteria but not yet identified in plants. Therefore, we aimed to obtain and biochemically characterize the TsPAP1 protein. The recombinant TsPAP1 protein was received through heterologous expression of the TsPAP1 coding sequence in a bacterial expression system and purified with affinity chromatography. Gel filtration chromatography and SDS electrophoresis revealed that TsPAP1 is a monomer with a molecular mass of 37.5 kDa. TsPAP1 prefers substrates with proline at the N-terminus but is also capable of hydrolyzing β-naphthylamides of hydroxyproline and alanine. Among the peptides tested, the most preferred were di- and tripeptides, especially those with glycine in the Y position. The use of diagnostic inhibitors indicated that TsPAP1 is a serine peptidase; however, further characterization revealed that the SH residues are also important for maintaining its activity. To examine the role of TsPAP1 under physiological conditions, we developed transgenic Arabidopsis plants overexpressing TsPAP1. Compared with wild-type plants, the transgenic lines accumulated more proline, flowered an average of 3.5 days earlier, and developed more siliques than did untransformed controls. Our paper is the first to describe the biochemical properties of a novel monomeric plant PAP and contributes to the functional characterization of PAP proteins in plants. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Neurosurgical strategies for Gilles de la Tourette’s syndrome

PubMed Central

Mukhida, Karim; Bishop, Matthew; Hong, Murray; Mendez, Ivar

2008-01-01

Tourette’s syndrome (TS) is a neurological disorder characterized by motor and vocal tics that typically begin in childhood and often are accompanied by psychiatric comorbidities. Symptoms of TS may be socially disabling and cause secondary medical complications. Pharmacological therapies remain the mainstay of symptom management. For the subset of patients in whom TS symptoms are medically recalcitrant and do not dissipate by adulthood, neurosurgery may offer an alternative treatment strategy. Greater understanding of the neuroanatomic and pathophysiologic basis of TS has facilitated the development of surgical procedures that aim to ameliorate TS symptoms by lesions or deep brain stimulation of cerebral structures. Herein, the rationale for the surgical management of TS is discussed and neurosurgical experiences since the 1960s are reviewed. The necessity for neurosurgical strategies to be performed with appropriate ethical considerations is highlighted. PMID:19337454

Increased detection of co-morbidities with evaluation at a dedicated adult Turner syndrome clinic.

PubMed

Vincent, A J; Nguyen, H H; Ranasinha, S; Vollenhoven, B

2017-10-01

Turner syndrome (TS), resulting from complete/partial X chromosomal monosomy, is associated with multiple co-morbidities and increased mortality. Although multidisciplinary management is recommended, TS women's health care is sub-optimal. This study evaluates a multidisciplinary adult TS service. Retrospective cohort study of 82 patients attending the quarterly TS clinic from December 2003 to December 2014. Evaluation included (1) demographics, (2) TS standardized co-morbidity screening, and (3) estrogen therapy use. Data analysis involved frequency statistics, T tests and polychoric correlation analysis. Median age at TS diagnosis was 14 years (range 0-65 years), with 12% of women aged >18 years. Median age at initial consultation was 31 years (range 16-65 years). Only 14% of patients were transition program referrals. XO karyotype occurred in 30%. Primary amenorrhea predominated; however, 37% of TS women were not taking estrogen therapy. The proportion of patients not previously screened (44-76%) and those with positive screening diagnoses (5-53%) varied according to co-morbidity. The mean (± standard deviation) number of co-morbidities identified increased following TS clinic screening (7.0 ± 2.6 post-screening vs. 4.4 ± 2.3 pre-screening; p < 0.0001). Polychoric correlation analysis identified particular co-morbidity groupings (including metabolism-related) and increased co-morbidities with primary amenorrhea. A multidisciplinary adult TS clinic improves health surveillance with increased identification of co-morbidities and initiation of estrogen therapy.

The Study of Stability of Compression-loaded Multispan Composite Panel Upon Failure of elements Binding it to Panel Supports

NASA Technical Reports Server (NTRS)

Zamula, G. N.; Ierusalimsky, K. M.; Fomin, V. P.; Grishin, V. I.; Kalmykova, G. S.

1999-01-01

The present document is a final technical report under the NCC-1-233 research program (dated September 15, 1998; see Appendix 5) carried out within co-operation between United States'NASA Langley RC and Russia's Goskomoboronprom in aeronautics, and continues similar programs, NCCW-73, NCC-1-233 and NCCW 1-233 accomplished in 1996, 1997, and 1998, respectively. The report provides results of "The study of stability of compression-loaded multispan composite panels upon failure of elements binding it to panel supports"; these comply with requirements established at TsAGI on 24 March 1998 and at NASA on 15 September 1998.

Utilization of a ts-sacB selection system for the generation of a Mycobacterium avium serovar-8 specific glycopeptidolipid allelic exchange mutant

PubMed Central

Irani, Vida R; Lee, Sun-Hwa; Eckstein, Torsten M; Inamine, Julia M; Belisle, John T; Maslow, Joel N

2004-01-01

Background Mycobacterium avium are ubiquitous environmental organisms and a cause of disseminated infection in patients with end-stage AIDS. The glycopeptidolipids (GPL) of M. avium are proposed to participate in the pathogenesis of this organism, however, establishment of a clear role for GPL in disease production has been limited by the inability to genetically manipulate M. avium. Methods To be able to study the role of the GPL in M. avium pathogenesis, a ts-sacB selection system, not previously used in M. avium, was employed as a means to achieve homologous recombination for the rhamnosyltransferase (rtfA) gene of a pathogenic serovar 8 strain of M. avium to prevent addition of serovar-specific sugars to rhamnose of the fatty acyl-peptide backbone of GPL. The genotype of the resultant rtfA mutant was confirmed by polymerase chain reaction and southern hybridization. Disruption in the proximal sugar of the haptenic oligosaccharide resulted in the loss of serovar specific GPL with no change in the pattern of non-serovar specific GPL moieties as shown by thin layer chromatography and gas chromatography/mass spectrometry. Complementation of wild type (wt) rtfA in trans through an integrative plasmid restored serovar-8 specific GPL expression identical to wt serovar 8 parent strain. Results In this study, we affirm our results that rtfA encodes an enzyme responsible for the transfer of Rha to 6d-Tal and provide evidence of a second allelic exchange mutagenesis system suitable for M. avium. Conclusion We report the second allelic exchange system for M. avium utilizing ts-sacB as double-negative and xylE as positive counter-selection markers, respectively. This system of allelic exchange would be especially useful for M. avium strains that demonstrate significant isoniazid (INH) resistance despite transformation with katG. Through the construction of mutants in GPL or other mycobacterial components, their roles in M. avium pathogenesis, biosynthesis, or drug resistance can be studied in a consistent manner. PMID:15458565

Divalent counterion-induced condensation of triple-strand DNA.

PubMed

Qiu, Xiangyun; Parsegian, V Adrian; Rau, Donald C

2010-12-14

Understanding and manipulation of the forces assembling DNA/RNA helices have broad implications for biology, medicine, and physics. One subject of significance is the attractive force between dsDNA mediated by polycations of valence ≥ 3. Despite extensive studies, the physical origin of the "like-charge attraction" remains unsettled among competing theories. Here we show that triple-strand DNA (tsDNA), a more highly charged helix than dsDNA, is precipitated by alkaline-earth divalent cations that are unable to condense dsDNA. We further show that our observation is general by examining several cations (Mg(2+), Ba(2+), and Ca(2+)) and two distinct tsDNA constructs. Cation-condensed tsDNA forms ordered hexagonal arrays that redissolve upon adding monovalent salts. Forces between tsDNA helices, measured by osmotic stress, follow the form of hydration forces observed with condensed dsDNA. Probing a well-defined system of point-like cations and tsDNAs with more evenly spaced helical charges, the counterintuitive observation that the more highly charged tsDNA (vs. dsDNA) is condensed by cations of lower valence provides new insights into theories of polyelectrolytes and the biological and pathological roles of tsDNA. Cations and tsDNAs also hold promise as a model system for future studies of DNA-DNA interactions and electrostatic interactions in general.

Seasonal variations in behaviour of thermoregulation in juveniles and adults Liolaemus lutzae (Squamata, Liolaemidae) in a remnant of Brazilian restinga.

PubMed

Maia-Carneiro, Thiago; Rocha, Carlos Frederico Duarte

2013-11-01

Adaptations of lizards inhabiting hot arid environments should include mechanisms of behavioural thermoregulation. In contrast, in environments with lower temperatures lizards tend to behave as thermoconformers. Herein we aim to infer thermoregulatory behaviours exhibited by Liolaemus lutzae (a lizard species endemic to restingas in the coast of the state of Rio de Janeiro, Brazil) in two different seasonal thermal environments. In the dry season, the body temperatures (Tb) of the lizards were higher than air temperature (Ta) and similar to substrate temperature (Ts), suggesting thermoconformer thermoregulatory behaviour using Ts. During the rainy season, the higher percentage of negative values of ΔTs (=Tb-Ts) and ΔTa (=Tb-Ta) and the tendency for lower Tb compared to Ts suggest a more active behavioural thermoregulation in that season. The ΔTs was higher for juveniles in the rainy season, suggesting that youngest lizards tended to thermoregulate more actively regarding to Ts than adults. L. lutzae probably survives under high Ts due to the behaviour of the individuals sheltering inside burrows or under detritus and burying themselves into the sand. This behavioural flexibility may potentially reduce variations in Tb of active lizards in changing thermal environments both during the daily cycle and between seasons. Copyright © 2013 Elsevier B.V. All rights reserved.

Fundamental study on micro calcification detection using twinkling sign (TS): the effect of stiffness of surrounding tissue on the appearance of TS.

PubMed

Liu, Lei; Funamoto, Kenichi; Tanabe, Masayuki; Hayase, Toshiyuki

2013-01-01

The twinkling sign (TS) observed in ultrasound imaging (e.g., color flow mode and pulse Doppler mode) has been reported in previous researches as a potential phenomenon to detect micro calcification in soft tissue. However, the mechanism of the twinkling sign has not been clearly understood yet. The authors investigated the effect of stiffness of surrounding tissue on the appearance of TS using the soft tissue-mimicking phantoms and a medical ultrasound device. The author used Poly (vinyl alcohol) hydro (PVA-H) gel as the material of phantom and developed three phantoms with different PVA concentration; 8 %wt, 10 %wt and 15 %wt those correspond to Young's modulus (E) as 50 kPa, 100 kPa and 230 kPa, respectively. Micro glass and CaCO3 particles were embedded in the phantoms as pseudo micro calcification. The authors observed TS in each phantom and analyzed the temporal average of TS. The temporal average of TS was largest in the 8 %wt (E = 50 kPa) PVA-H gel phantom, and decreased with increasing the phantom stiffness. The result indicated that the micro oscillation of the particles had a close relationship with the occurrence of TS.

Excitatory amino acid transporters tonically restrain nTS synaptic and neuronal activity to modulate cardiorespiratory function

PubMed Central

2015-01-01

The nucleus tractus solitarii (nTS) is the initial central termination site for visceral afferents and is important for modulation and integration of multiple reflexes including cardiorespiratory reflexes. Glutamate is the primary excitatory neurotransmitter in the nTS and is removed from the extracellular milieu by excitatory amino acid transporters (EAATs). The goal of this study was to elucidate the role of EAATs in the nTS on basal synaptic and neuronal function and cardiorespiratory regulation. The majority of glutamate clearance in the central nervous system is believed to be mediated by astrocytic EAAT 1 and 2. We confirmed the presence of EAAT 1 and 2 within the nTS and their colocalization with astrocytic markers. EAAT blockade with dl-threo-β-benzyloxyaspartic acid (TBOA) produced a concentration-related depolarization, increased spontaneous excitatory postsynaptic current (EPSC) frequency, and enhanced action potential discharge in nTS neurons. Solitary tract-evoked EPSCs were significantly reduced by EAAT blockade. Microinjection of TBOA into the nTS of anesthetized rats induced apneic, sympathoinhibitory, depressor, and bradycardic responses. These effects mimicked the response to microinjection of exogenous glutamate, and glutamate responses were enhanced by EAAT blockade. Together these data indicate that EAATs tonically restrain nTS excitability to modulate cardiorespiratory function. PMID:26719090

Conservation and Role of Electrostatics in Thymidylate Synthase.

PubMed

Garg, Divita; Skouloubris, Stephane; Briffotaux, Julien; Myllykallio, Hannu; Wade, Rebecca C

2015-11-27

Conservation of function across families of orthologous enzymes is generally accompanied by conservation of their active site electrostatic potentials. To study the electrostatic conservation in the highly conserved essential enzyme, thymidylate synthase (TS), we conducted a systematic species-based comparison of the electrostatic potential in the vicinity of its active site. Whereas the electrostatics of the active site of TS are generally well conserved, the TSs from minimal organisms do not conform to the overall trend. Since the genomes of minimal organisms have a high thymidine content compared to other organisms, the observation of non-conserved electrostatics was surprising. Analysis of the symbiotic relationship between minimal organisms and their hosts, and the genetic completeness of the thymidine synthesis pathway suggested that TS from the minimal organism Wigglesworthia glossinidia (W.g.b.) must be active. Four residues in the vicinity of the active site of Escherichia coli TS were mutated individually and simultaneously to mimic the electrostatics of W.g.b TS. The measured activities of the E. coli TS mutants imply that conservation of electrostatics in the region of the active site is important for the activity of TS, and suggest that the W.g.b. TS has the minimal activity necessary to support replication of its reduced genome.

Ts1Cje Down syndrome model mice exhibit environmental stimuli-triggered locomotor hyperactivity and sociability concurrent with increased flux through central dopamine and serotonin metabolism.

PubMed

Shimohata, Atsushi; Ishihara, Keiichi; Hattori, Satoko; Miyamoto, Hiroyuki; Morishita, Hiromasa; Ornthanalai, Guy; Raveau, Matthieu; Ebrahim, Abdul Shukkur; Amano, Kenji; Yamada, Kazuyuki; Sago, Haruhiko; Akiba, Satoshi; Mataga, Nobuko; Murphy, Niall P; Miyakawa, Tsuyoshi; Yamakawa, Kazuhiro

2017-07-01

Ts1Cje mice have a segmental trisomy of chromosome 16 that is orthologous to human chromosome 21 and display Down syndrome-like cognitive impairments. Despite the occurrence of affective and emotional impairments in patients with Down syndrome, these parameters are poorly documented in Down syndrome mouse models, including Ts1Cje mice. Here, we conducted comprehensive behavioral analyses, including anxiety-, sociability-, and depression-related tasks, and biochemical analyses of monoamines and their metabolites in Ts1Cje mice. Ts1Cje mice showed enhanced locomotor activity in novel environments and increased social contact with unfamiliar partners when compared with wild-type littermates, but a significantly lower activity in familiar environments. Ts1Cje mice also exhibited some signs of decreased depression like-behavior. Furthermore, Ts1Cje mice showed monoamine abnormalities, including increased extracellular dopamine and serotonin, and enhanced catabolism in the striatum and ventral forebrain. This study constitutes the first report of deviated monoamine metabolism that may help explain the basis for abnormal behaviors, including the environmental stimuli-triggered hyperactivity, increased sociability and decreased depression-like behavior in Ts1Cje mice. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of local terminologies in electronic health records. The HEGP experience.

PubMed

Daniel-Le Bozec, Christel; Steichen, Olivier; Dart, Thierry; Jaulent, Marie-Christine

2007-01-01

Despite decades of work, there is no universally accepted standard medical terminology and no generally usable terminological tools have yet emerged. The local dictionary of concepts of the Georges Pompidou European Hospital (HEGP) is a Terminological System (TS) designed to support clinical data entry. It covers 93 data entry forms and contains definitions and synonyms of more than 5000 concepts, sometimes linked to reference terminologies such as ICD-10. In this article, we evaluate to which extend SNOMED CT could fully replace or rather be mapped to the local terminology system. We first describe the local dictionary of concepts of HEGP according to some published TS characterization framework. Then we discuss the specific role that a local terminology system plays with regards to reference terminologies.

Tourette Syndrome

MedlinePlus

... and arranging. People with TS have also reported problems with depression or anxiety disorders, as well as other difficulties ... possible that neurobehavioral disorders such as ADHD, OCD, depression, generalized ... with TS? Although students with TS often function well in the regular ...

Uniform TiO2-SiO2 hollow nanospheres: Synthesis, characterization and enhanced adsorption-photodegradation of azo dyes and phenol

NASA Astrophysics Data System (ADS)

Guo, Na; Liang, Yimai; Lan, Shi; Liu, Lu; Ji, Guijuan; Gan, Shucai; Zou, Haifeng; Xu, Xuechun

2014-06-01

TiO2-SiO2 hollow nanospheres with remarkable enhanced photocatalytic performance have been fabricated by sol-gel method. The hollow sphere possesses both high phototcatalytic activity and adsorption capability. The as-prepared samples were characterized by XRD, SEM, TEM, FTIR, XPS, BJH and TGA/DSC. The experiment results show that, the photocatalyst calcined at 500 °C with Ti/Si ratio of 5:1 (denoted as 5T/S-500) displayed superiorities in both textural and functional properties with the enhanced degradation efficiency on azo dyes (methylene blue, methyl orange) and phenol. The high adsorption capability of organic poisonous contaminants onto 5T/S-500 in aqueous solution demonstrated that the photocatalyst can remove the contaminants from water effectively even without illumination. The TEM and SEM morphologies demonstrated unique hollow and coarse structure of 5T/S-500. Structural analysis showed that Si was doped into the lattice of TiO2 and SiO2 nanoparticles can work as a surface modifier on TiO2. The surface area of 5T/S-500 is 1105 m2/g, 14.5 times as great as that of the pure hollow TiO2 nanosphere, confirms the effect of SiO2 on the improvement of specific surface area. The high photocatalytic activities and high adsorption ability for organic poisonous contaminants demonstrate that the nanocomposite of TiO2-SiO2 is a promising candidate material for future treatment of contaminated water.

Animal models of tic disorders: A translational perspective

PubMed Central

Godar, Sean C.; Mosher, Laura J.; Di Giovanni, Giuseppe; Bortolato, Marco

2014-01-01

Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. PMID:25244952

Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation.

PubMed

Guidine, Patrícia Alves Maia; Cash, Diana; Drumond, Luciana Estefani; de Souza E Rezende, Gustavo Henrique; Massensini, André Ricardo; Williams, Steve Charles Rees; Moraes-Santos, Tasso; Moraes, Márcio Flávio Dutra; Mesquita, Michel Bernanos Soares

2014-01-01

Severe scorpion envenoming (SSE) is more frequent in children and is characterized by systemic dysfunctions with a mortality rate of up to 9%. Recent evidence shows that the central nervous system (CNS) plays a key role in triggering the cascade of symptoms present in SSE. The age-dependent role of the CNS in SSE lethality may be summarized in 3 hypotheses: (1) the shown increased blood brain barrier permeability of infants to the toxins would especially and primarily compromise neurovegetative control areas, (2) the neurons within these areas have high affinity to the toxins, and (3) the neurovascular interaction is such that SSE metabolically compromises proper function of toxin-targeted areas. A pharmacological magnetic resonance imaging paradigm was used to evaluate localized hemodynamic changes in relative cerebral blood volume (rCBV) for 30 min after the injection of TsTX, the most lethal toxin from the venom of the Tityus serrulatus scorpion. The brainstem showed significant rCBV reduction 1 min after TsTX administration, whereas rostral brain areas had delayed increase in rCBV (confirmed by laser Doppler measurements of cortical cerebral blood flow). Moreover, metabolic activity by 14C-2-deoxyglucose autoradiography showed the highest relative increase at the brainstem. To test whether TsTX has high affinity to brainstem neurons, the lateral ventricle was injected with Alexa Fluor 568 TsTX. Although some neurons showed intense fluorescence, the labeling pattern suggests that specific neurons were targeted. Altogether, these results suggest that brainstem areas involved in neurovegetative control are most likely within the primary structures triggering the cascade of symptoms present in SSE.

Phenotype in girls and women with Turner syndrome: Association between dysmorphic features, karyotype and cardio-aortic malformations.

PubMed

Noordman, Iris; Duijnhouwer, Anthonie; Kapusta, Livia; Kempers, Marlies; Roeleveld, Nel; Schokking, Michiel; Smeets, Dominique; Freriks, Kim; Timmers, Henri; van Alfen-van der Velden, Janiëlle

2018-06-01

Turner syndrome (TS) is a genetic disorder characterized by the (partial) absence or a structural aberration of the second sex chromosome and is associated with a variety of phenotypes with specific physical features and cardio-aortic malformations. The objective of this study was to gain a better insight into the differences in dysmorphic features between girls and women with TS and to explore the association between these features, karyotype and cardio-aortic malformations. This prospective study investigated 14 dysmorphic features of TS girls and women using a checklist. Three major phenotypic patterns were recognized (severe phenotype, lymphatic phenotype and skeletal phenotype). Patient data including karyotype and cardio-aortic malformations (bicuspid aortic valve (BAV) and aortic coarctation (COA)) were collected. Associations between the prevalence of dysmorphic features, karyotype and cardio-aortic malformations were analysed using chi 2 -test and odds ratios. A total of 202 patients (84 girls and 118 women) were analysed prospectively. Differences in prevalence of dysmorphic features were found between girls and women. A strong association was found between monosomy 45,X and the phenotypic patterns. Furthermore, an association was found between COA and lymphatic phenotype, but no association was found between karyotype and cardio-aortic malformations. This study uncovered a difference in dysmorphic features between girls and women. Monosomy 45,X is associated with a more severe phenotype, lymphatic phenotype and skeletal phenotype. All patients with TS should be screened for cardio-aortic malformations, because in contrast to previous reports, karyotype and cardio-aortic malformations showed no significant association. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Disruption of the APC gene by t(5;7) translocation in a Turcot family.

PubMed

Sahnane, Nora; Bernasconi, Barbara; Carnevali, Ileana; Furlan, Daniela; Viel, Alessandra; Sessa, Fausto; Tibiletti, Maria Grazia

2016-03-01

Turcot syndrome (TS) refers to the combination of colorectal polyps and primary tumours of the central nervous system. TS is a heterogeneous genetic condition due to APC and/or mismatch repair germline mutations. When APC is involved the vast majority of mutations are truncating, but in approximately 20%-30% of patients with familial polyposis no germline mutation can be found. A 30-year-old Caucasian woman with a positive pedigree for TS was referred to our Genetic Counselling Service. She was negative for APC and MUTYH but showed a reciprocal balanced translocation t(5;7)(q22;p15) at chromosome analysis. FISH analysis using specific BAC probes demonstrated that 5q22 breakpoint disrupted the APC gene. Transcript analysis by MLPA and digital PCR revealed that the cytogenetic rearrangement involving the 3' end of the APC gene caused a defective expression of a truncated transcript. This result allowed cytogenetic analysis to be offered to all the other family members and segregation analysis clearly demonstrated that all the carriers were affected, whereas non-carriers did not have the polyposis. A cytogenetic approach permitted the identification of the mutation-causing disease in this family, and the segregation analysis together with the transcript study supported the pathogenetic role of this mutation. Karyotype analysis was used as a predictive test in all members of this family. This family suggests that clinically positive TS and FAP cases, which test negative with standard molecular analysis, could be easily and cost-effectively resolved by a classical and molecular cytogenetic approach. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of total solids content and temperature on the rheological behaviour of reconstituted whole milk concentrates.

PubMed

Trinh, Binh; Trinh, Khanh Tuoc; Haisman, Derek

2007-02-01

This work investigated the combined effect of solids content, heating and storage temperatures on the rheological behaviour of reconstituted whole milk concentrates. The powder was reconstituted at 35 degrees C in a custom built recombination rig to various total solids content (TS) from 10-48% TS. The concentrates were then heated to 45-85 degrees C and stored at the heating temperature. The rheological behaviour shifter from Newtonian behaviour (below 30% TS) to power law (below 40% TS), with the yield stress observed from 40% TS upwards and time-dependent behaviour was noticed above 44% TS. Higher heating temperatures tend to promote non-Newtonian behaviour at lower solids content. The viscosity-solid content curve showed an exponential relationship, while the viscosity-temperature curve exhibited a minimum at 65-75 degrees C above 46% TS. During age thickening, the yield stress and the consistency coefficient increased, while the flow behaviour index decreased with storage time. This indicated that the milk concentrates deviated away from Newtonian behaviour during age thickening.

Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of d-Glucose Conformers.

PubMed

Satoh, Hiroko; Oda, Tomohiro; Nakakoji, Kumiyo; Uno, Takeaki; Tanaka, Hiroaki; Iwata, Satoru; Ohno, Koichi

2016-11-08

This paper describes our approach that is built upon the potential energy surface (PES)-based conformational analysis. This approach automatically deduces a conformational transition network, called a conformational reaction route map (r-map), by using the Scaled Hypersphere Search of the Anharmonic Downward Distortion Following method (SHS-ADDF). The PES-based conformational search has been achieved by using large ADDF, which makes it possible to trace only low transition state (TS) barriers while restraining bond lengths and structures with high free energy. It automatically performs sampling the minima and TS structures by simply taking into account the mathematical feature of PES without requiring any a priori specification of variable internal coordinates. An obtained r-map is composed of equilibrium (EQ) conformers connected by reaction routes via TS conformers, where all of the reaction routes are already confirmed during the process of the deduction using the intrinsic reaction coordinate (IRC) method. The postcalculation analysis of the deduced r-map is interactively carried out using the RMapViewer software we have developed. This paper presents computational details of the PES-based conformational analysis and its application to d-glucose. The calculations have been performed for an isolated glucose molecule in the gas phase at the RHF/6-31G level. The obtained conformational r-map for α-d-glucose is composed of 201 EQ and 435 TS conformers and that for β-d-glucose is composed of 202 EQ and 371 TS conformers. For the postcalculation analysis of the conformational r-maps by using the RMapViewer software program we have found multiple minimum energy paths (MEPs) between global minima of 1 C 4 and 4 C 1 chair conformations. The analysis using RMapViewer allows us to confirm the thermodynamic and kinetic predominance of 4 C 1 conformations; that is, the potential energy of the global minimum of 4 C 1 is lower than that of 1 C 4 (thermodynamic predominance) and that the highest energy of those of all the TS structures along a route from 4 C 1 to 1 C 4 is lower than that of 1 C 4 to 4 C 1 (kinetic predominance).

New Insights into Clinical Characteristics of Gilles de la Tourette Syndrome: Findings in 1032 Patients from a Single German Center

PubMed Central

Sambrani, Tanvi; Jakubovski, Ewgeni; Müller-Vahl, Kirsten R.

2016-01-01

Background: Gilles de la Tourette syndrome (TS) is a complex neuropsychiatric disorder defined by the presence of motor and phonic tics, but often associated with psychiatric comorbidities. The main objective of this study was to explore the clinical presentation and comorbidities of TS. Method: We analyzed clinical data obtained from a large sample (n = 1032; 529 children and 503 adults) of patients with tic disorders from one single German TS center assessed by one investigator. Data was collected with the help of an expert-reviewed semi-structured interview, designed to assess tic severity and certain comorbidities. Group comparisons were carried out via independent sample t-tests and chi-square tests. Results: The main findings of the study are: (1) tic severity is associated with the presence of premonitory urges (PU), copro-, echo-, and paliphenomena and the number of comorbidities, but not age at tic onset; it is higher in patients with comorbid obsessive-compulsive disorder (OCD) than in patients with comorbid attention deficit/hyperactivity disorder (ADHD). (2) PU were found to be highly associated with “not just right experiences” and to emerge much earlier than previously thought alongside with the ability to suppress tics (PU in >60% and suppressibility in >75% at age 8–10 years). (3) Self-injurious behavior (SIB) is highly associated with complex motor tics and coprophenomena, but not with OCD/obsessive-compulsive behavior (OCB). While comorbid ADHD is associated with a lower ability to suppress tics, comorbid depression is associated with sleeping problems. Discussion: Our results demonstrate that tic severity is not influenced by age at onset. From our data, it is suggested that PU represent a specific type of “not just right experience” that is not a prerequisite for tic suppression. Comorbid ADHD reduces patients' ability of successful tic suppression. Our data suggest that SIB belongs to the coprophenomena spectrum and hence should be conceptualized as a complex tic rather than a compulsion. Finally, this study strongly supports the hypothesis that TS+OCD is a more severe form of TS and that comorbid OCD/OCB, depression, and anxiety belong to the TS spectrum, while ADHD should be better conceptualized as a separate problem. PMID:27672357

Tourette's syndrome is not associated with interleukin-10 receptor 1 variants on chromosome 11q23.3.

PubMed

Kindler, Jochen; Schosser, Alexandra; Stamenkovic, Mara; Schloegelhofer, Monika; Leisch, Friedrich; Hornik, Kurt; Aschauer, Harald; Gasche, Christoph

2008-01-15

Interleukin-10 receptor 1 (IL-10R1) single nucleotide polymorphisms, located on chromosome 11q23 - a strong candidate for linkage with Tourette's syndrome (TS) - have been investigated for association with TS. DNA of 77 patients with a DSM-IV (Diagnostic and Statistical Manual IV) diagnosis of TS and 250 healthy controls was genotyped. IL-10R1 was not associated with TS.

Interhemispheric Connectivity and Executive Functioning in Adults With Tourette Syndrome

PubMed Central

Margolis, Amy; Donkervoort, Mireille; Kinsbourne, Marcel; Peterson, Bradley S.

2008-01-01

The prefrontal cortex (PFC) is relatively smaller, and the corpus callosum (CC) larger, in adults with Tourette syndrome (TS). The authors explored the possible roles of the PFC and the CC in mediating interhemispheric interference and coordination in TS adults. They measured performance on M. Kinsbourne and J. Cook's (1971) verbal–manual interference task and on the bimanual Purdue Pegboard in 38 adults with TS and 34 healthy adults. Compared with controls, TS subjects were impaired on the bimanual Purdue Pegboard. On the dual task, right-hand performance did not differ between groups, but the normally expected left-hand advantage (opposite hemisphere condition) was absent in TS subjects. In the control group only, better left-hand performance accompanied larger PFC volumes but not CC cross-sectional area. PFC dysfunction might have precluded executive control of interference in the TS group. PMID:16460223

Thin stillage supplementation greatly enhances bacterial cellulose production by Gluconacetobacter xylinus.

PubMed

Wu, Jyh-Ming; Liu, Ren-Han

2012-09-01

Thin stillage (TS), a wastewater from rice wine distillery can well sustain the growth of Gluconacetobacter xylinus for production of bacterial cellulose (BC). When used as a supplement to the traditional BC production medium (Hestrin and Schramm medium), the enhancement of BC production increased with the amount of TS supplemented in a static culture of G. xylinus. When TS was employed to replace distilled water for preparing HS medium (100%TS-HS medium), the BC production in this 100%TS-HS medium was enhanced 2.5-fold to a concentration of 10.38 g/l with sugar to BC conversion yield of 57% after 7 days cultivation. The cost-free TS as a supplement in BC production medium not only can greatly enhance the BC production, but also can effectively dispose the nuisance wastewater of rice wine distillery. Copyright © 2012 Elsevier Ltd. All rights reserved.

A novel mechanism of vascular endothelial growth factor, leptin and transforming growth factor-beta2 sequestration in a subpopulation of human ovarian follicle cells.

PubMed

Antczak, M; Van Blerkom, J; Clark, A

1997-10-01

This study describes the occurrence of a highly specialized subpopulation of granulosa and cumulus oophorus cells that accumulate and sequester specific growth factors by a novel mechanism. These cells are characterized by multiple balloon-like processes tethered to the cell by means of a slender stalk of plasma membrane. Time-lapse analyses demonstrate that these tethered structures (TS) form in minutes and frequently detach from the cell with the bulbous portion remaining motile on the cell surface. Serial section reconstruction of transmission electron microscopic images shows a specific and stable intracellular organization in which an apparent secretory compartment composed of densely packed vacuoles, vesicles, and cisternae is separated by a thick filamentous network from a nuclear compartment containing mitochondria, polyribosomes, lipid inclusions, and rough-surfaced endoplasmic reticulum. Immunofluorescent analysis performed during the formation of these structures showed a progressive accumulation of vascular endothelial growth factor, leptin, and transforming growth factor-beta2 in the bulbous region. TS were identified in newly aspirated masses of granulosa and cumulus oophorus, and their production persists for months in culture. Observations of TS-forming cells made over several days of culture indicates that their production is episodic and factor release from these cells may be pulsatile. The findings suggest that a novel method of growth factor storage and release by an apparent apocrine-like mechanism occurs in the human ovarian follicle. The results are discussed with respect to possible roles in pre- and post-ovulatory follicular development.

Functional analysis of fruitless gene expression by transgenic manipulations of Drosophila courtship

PubMed Central

Villella, Adriana; Ferri, Sarah L.; Krystal, Jonathan D.; Hall, Jeffrey C.

2005-01-01

A gal4-containing enhancer–trap called C309 was previously shown to cause subnormal courtship of Drosophila males toward females and courtship among males when driving a conditional disrupter of synaptic transmission (shiTS). We extended these manipulations to analyze all features of male-specific behavior, including courtship song, which was almost eliminated by driving shiTS at high temperature. In the context of singing defects and homosexual courtship affected by mutations in the fru gene, a tra-regulated component of the sex-determination hierarchy, we found a C309/traF combination also to induce high levels of courtship between pairs of males and “chaining” behavior in groups; however, these doubly transgenic males sang normally. Because production of male-specific FRUM protein is regulated by TRA, we hypothesized that a fru-derived transgene encoding the male (M) form of an Inhibitory RNA (fruMIR) would mimic the effects of traF; but C309/fruMIR males exhibited no courtship chaining, although they courted other males in single-pair tests. Double-labeling of neurons in which GFP was driven by C309 revealed that 10 of the 20 CNS clusters containing FRUM in wild-type males included coexpressing neurons. Histological analysis of the developing CNS could not rationalize the absence of traF or fruMIR effects on courtship song, because we found C309 to be coexpressed with FRUM within the same 10 neuronal clusters in pupae. Thus, we hypothesize that elimination of singing behavior by the C309/shiTS combination involves neurons acting downstream of FRUM cells PMID:16179386

Abnormal gastric myoelectrical activity in postural tachycardia syndrome.

PubMed

Seligman, William H; Low, David A; Asahina, Masato; Mathias, Christopher J

2013-04-01

Postural tachycardia syndrome (PoTS) is an important cause of orthostatic intolerance resulting from cardiovascular autonomic dysfunction. In addition to postural symptoms, PoTS patients may have allied features, including gastrointestinal (GI) symptoms, which have not yet been thoroughly investigated. We evaluated gastric myoelectrical activity in PoTS patients. Using cutaneous electrogastrography (EGG), we recorded gastric myoelectrical activity before and after standard liquid meal ingestion in 15 PoTS patients (age 27 ± 4 years); including 7 with and 8 without GI symptoms, and in 11 healthy individuals (age 23 ± 7 years). We performed spectral analysis of EGG recordings to obtain the dominant frequency of gastric pacemaker rhythm (DF), instability coefficient of DF (ICDF), and low (LFR%), normal (NFR%), and high (HFR%) range power percentages of the total power. Instability coefficient of DF, an index of variability of gastric pacemaker rhythm, was significantly elevated both pre- and post-prandially (30-45 min after the meal) in the PoTS group (8.8 ± 6, 10.0 ± 8 %) compared with controls (4.0 ± 3, 4.0 ± 3 %; both p < 0.05). Patients with GI symptoms had significantly higher post-prandial ICDF (15.0 ± 5 %) than those without GI symptoms (5.6 ± 4 %; p < 0.05). There were no significant differences in DF, LFR%, NFR% and HFR% before and after the meal between the PoTS and control groups, or between PoTS patients with and without GI symptoms. Our study revealed increased variability of gastric pacemaker rhythm in PoTS, and these findings might be related to pathophysiology of functional GI symptoms in PoTS.

Triangles, tricks and tics: Hyper-mentalizing in response to animated shapes in Tourette syndrome.

PubMed

Eddy, Clare M; Cavanna, Andrea E

2015-10-01

Tourette syndrome (TS) can feature complex tics involving socially inappropriate behaviours. Adults with TS can also demonstrate differences to healthy controls when reasoning about mental states. This study investigated spontaneous mentalizing in TS. Twenty adults with TS and twenty healthy controls completed the animations task. Participants were asked to watch short ambiguous animations involving two triangles and describe what was happening. Some animations featured random movement of the triangles, while others depicted social interactions that were simple (e.g., dancing) or more complex (e.g., one triangle tricking the other). Measures were taken of executive functions, alexithymia and clinical symptoms. Individuals with TS responded similarly to controls when viewing animations featuring simple and complex interactions, demonstrating intact mentalizing ability. However, significant group differences were apparent for the random movement animations. TS was associated with a greater tendency to attribute mental states during this condition, and to describe random movements as motivated actions guided by the intentions of the triangles. There were no group differences for the alexithymia scale, but TS was associated with mild executive deficits. No relationships were apparent between animation responses and other measures. Our findings suggest that TS is associated with a propensity to adopt the intentional stance. Hyper-mentalizing in TS could be linked to both dopamine dysfunction and altered social behaviour, whereby amplified salience of social cues could contribute to the complex interplay between environmental context and tic expression. These observations may offer further insight into the potential effects of dopamine dysfunction on social cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

The training and learning process of transseptal puncture using a modified technique.

PubMed

Yao, Yan; Ding, Ligang; Chen, Wensheng; Guo, Jun; Bao, Jingru; Shi, Rui; Huang, Wen; Zhang, Shu; Wong, Tom

2013-12-01

As the transseptal (TS) puncture has become an integral part of many types of cardiac interventional procedures, its technique that was initial reported for measurement of left atrial pressure in 1950s, continue to evolve. Our laboratory adopted a modified technique which uses only coronary sinus catheter as the landmark to accomplishing TS punctures under fluoroscopy. The aim of this study is prospectively to evaluate the training and learning process for TS puncture guided by this modified technique. Guided by the training protocol, TS puncture was performed in 120 consecutive patients by three trainees without previous personal experience in TS catheterization and one experienced trainer as a controller. We analysed the following parameters: one puncture success rate, total procedure time, fluoroscopic time, and radiation dose. The learning curve was analysed using curve-fitting methodology. The first attempt at TS crossing was successful in 74 (82%), a second attempt was successful in 11 (12%), and 5 patients failed to puncture the interatrial septal finally. The average starting process time was 4.1 ± 0.8 min, and the estimated mean learning plateau was 1.2 ± 0.2 min. The estimated mean learning rate for process time was 25 ± 3 cases. Important aspects of learning curve can be estimated by fitting inverse curves for TS puncture. The study demonstrated that this technique was a simple, safe, economic, and effective approach for learning of TS puncture. Base on the statistical analysis, approximately 29 TS punctures will be needed for trainee to pass the steepest area of learning curve.

Characterization of a Thioredoxin-1 Gene from Taenia solium and Its Encoding Product

PubMed Central

Jiménez, Lucía; Rodríguez-Lima, Oscar; Ochoa-Sánchez, Alicia; Landa, Abraham

2015-01-01

Taenia solium thioredoxin-1 gene (TsTrx-1) has a length of 771 bp with three exons and two introns. The core promoter gene presents two putative stress transcription factor binding sites, one putative TATA box, and a transcription start site (TSS). TsTrx-1 mRNA is expressed higher in larvae than in adult. This gene encodes a protein of 107 amino acids that presents the Trx active site (CGPC), the classical secondary structure of the thioredoxin fold, and the highest degree of identity with the Echinococcus granulosus Trx. A recombinant TsTrx-1 (rTsTrx-1) was produced in Escherichia coli with redox activity. Optimal activity for rTsTrx-1 was at pH 6.5 in the range of 15 to 25°C. The enzyme conserved activity for 3 h and lost it in 24 h at 37°C. rTsTrx-1 lost 50% activity after 1 h and lost activity completely in 24 h at temperatures higher than 55°C. Best storage temperature for rTsTrx-1 was at −70°C. It was inhibited by high concentrations of H2O2 and methylglyoxal (MG), but it was inhibited neither by NaCl nor by anti-rTsTrx-1 rabbit antibodies that strongly recognized a ~12 kDa band in extracts from several parasites. These TsTrx-1 properties open the opportunity to study its role in relationship T. solium-hosts. PMID:26090410

Tityus serrulatus venom--A lethal cocktail.

PubMed

Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro Junior, Ernesto Lopes; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Cordeiro, Francielle Almeida; Longhim, Heloisa Tavoni; Cremonez, Caroline Marroni; Oliveira, Guilherme Honda; Arantes, Eliane Candiani

2015-12-15

Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts venom in vitro, in animals and in humans (a total of 151 references). Copyright © 2015 Elsevier Ltd. All rights reserved.

Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Scott-McKean, Jonah J.; Roque, Adriano L.; Surewicz, Krystyna; Johnson, Mark W.; Surewicz, Witold K.

2018-01-01

The Ts65Dn mouse is the most studied animal model of Down syndrome. Past research has shown a significant reduction in CA1 hippocampal long-term potentiation (LTP) induced by theta-burst stimulation (TBS), but not in LTP induced by high-frequency stimulation (HFS), in slices from Ts65Dn mice compared with euploid mouse-derived slices. Additionally, therapeutically relevant doses of the drug memantine were shown to rescue learning and memory deficits in Ts65Dn mice. Here, we observed that 1 μM memantine had no detectable effect on HFS-induced LTP in either Ts65Dn- or control-derived slices, but it rescued TBS-induced LTP in Ts65Dn-derived slices to control euploid levels. Then, we assessed LTP induced by four HFS (4xHFS) and found that this form of LTP was significantly depressed in Ts65Dn slices when compared with LTP in euploid control slices. Memantine, however, did not rescue this phenotype. Because 4xHFS-induced LTP had not yet been characterized in Ts65Dn mice, we also investigated the effects of picrotoxin, amyloid beta oligomers, and soluble recombinant human prion protein (rPrP) on this form of LTP. Whereas ≥10 μM picrotoxin increased LTP to control levels, it also caused seizure-like oscillations. Neither amyloid beta oligomers nor rPrP had any effect on 4xHFS-induced LTP in Ts65Dn-derived slices. PMID:29849573

EDC Cross-linking of Decellularized Tissue: A Promising Approach?

PubMed

Lehmann, Nadine; Christ, Torsten; Daugs, Aila; Bloch, Oliver; Holinski, Sebastian

2017-07-01

Decellularization of xenogenous cardiovascular structures is a promising approach to create scaffolds for tissue engineering. Unfortunately, handling and pliability of the unfixed tissue is challenging. N-(3-dimethylaminopropyl)-N9-ethylcarbodiimide (EDC) is an alternative cross-linking agent to glutaraldehyde (GA). Applied in native tissue, it provides biocompatibility and shows no potential for calcification. In addition, EDC can be used to link growth factors (GFs) to tissue scaffolds after decellularization. EDC cross-linking could thereby help to improve decellularized tissue without the toxicity of GA. Porcine aortic wall tissue specimens (TS) were decellularized, treated with EDC, and coated with fibroblast growth factor (FGF) or vascular endothelial growth factor (VEGF). Afterward, TS were subcutaneously implanted in 36 Lewis rats along with one decellularized TS without EDC treatment. After 2, 4, and 6 weeks TS were explanted from 12 rats, respectively. Vital cells were evaluated by RNA quantification, general cellular infiltration by hematoxylin and eosin staining (H&E), macrophage infiltration by CD68 staining, calcification by Von-Kossa staining, and tissue degradation by measurement of TS thickness. Quantification of vital cells showed reduced reseeding of EDC-treated TS compared to noncross-linked TS after 2 (p < 0.05) and 4 weeks (p < 0.05), while after 6 weeks only EDC+VEGF showed fewer viable cells (p < 0.01). Histological evaluation confirmed a reduced infiltration of EDC-treated TS. Macrophage infiltration decreased in all groups from 2 to 6 weeks, with the smallest population in EDC+VEGF-treated TS (p > 0.05). In EDC+FGF-treated TS, macrophages were reduced after 2 weeks compared to noncross-linked TS (p < 0.05), while after 4 and 6 weeks no significant difference was found (p > 0.05). Von-Kossa staining revealed no calcification in any of the specimens. Thickness of noncross-linked and EDC+FGF-treated TS was not different at the respective times of explantation, but decreased in both groups toward 6 weeks. EDC cross-linking combined with GF coating of decellularized aortic wall tissue showed encouraging results. The treatment did not impair the advantages of decellularized tissue such as long-term recellularization, absence of calcification, and tissue integrity. Based on the low macrophage infiltration and minimal tissue degradation, treatment with EDC and VEGF could be useful after decellularization. However, further research is necessary to verify these findings in models, including mechanical stress.

A survey of dental hygienists in the United Kingdom in 2011. Part 1--demographics and working patterns as dental hygienists.

PubMed

Eaton, K A; Harris, M; Ross, M K; Arevalo, C

2012-11-01

The aims of this survey were to establish the demographic profile of dental hygienists (DHs) and dental hygienist/therapists (DH/Ts) in the United Kingdom in 2011 and their patterns of practice as DHs. A 10% sample of all those registered with the General Dental Council as DHs or DH/Ts in April 2011 were sent a pre-piloted questionnaire, explanatory letter and stamped addressed envelope. The questionnaire contained a total of 100 questions, 24 of which related to demographics and working patterns. All 100 questions were solely on tasks/work performed by DH, none related to other types of work performed by DH/Ts. Three mailings were distributed between May and July 2011. The resulting data were entered into an Excel spreadsheet. Where appropriate, differences between the responses from DHs and DH/Ts were statistically tested with the chi-squared test. Five hundred and sixty-one DHs and DH/Ts were sent the questionnaire, by the third mailing 371 (66.1%) had responded and returned completed questionnaires. The respondents were 288 DHs, 79 DH/Ts and 4 who did not specify which category they were. The mean year of qualification of the DHs was 1990 and for the DH/Ts 2005. One hundred and twenty-four (33%) reported that they worked full-time, 235 (63%) part-time and the remainder that they were not working as DHs or DH/Ts or had retired. The average number of clinical hours worked per week was reported as 24.6 hours for DHs and 25 hours for DH/Ts, but there were regional variations. For DHs the mean percentage of patients treated under NHS contract was 15.5% and for DH/Ts it was 40.2%. Again there were regional variations and in Scotland these figures were 45.5% for DHs and 70% for DH/Ts. Two hundred and forty-eight (69%) of all respondents were either fully or partly self-employed and 221 (62.7%) worked in two or more locations. The results of this study provide a snapshot of the demographics and practice patterns of DHs and DH/Ts in the UK in the summer of 2011. They confirm the results of a survey that was conducted in England in early 2011 and of a survey that took place in Scotland in 2009.

Design of Ag/ and Pt/TiO2-SiO2 nanomaterials for the photocatalytic degradation of phenol under solar irradiation.

PubMed

Matos, Juan; Llano, Biviana; Montaña, Ricmary; Poon, Po S; Hidalgo, Maria C

2018-05-01

The design of hybrid mesoporous TiO 2 -SiO 2 (TS1) materials decorated with Ag and Pt nanoparticles was performed. The photocatalytic degradation of phenol under artificial solar irradiation was studied and the activity and selectivity of the intermediate products were verified. TiO 2 -SiO 2 was prepared by sol-gel method while Ag- and Pt-based photocatalysts (TS1-Ag and TS1-Pt) were prepared by photodeposition of the noble metals on TS1. Two series of photocatalysts were prepared varying Ag and Pt contents (0.5 and 1.0 wt%). An increase in the photocatalytic activity up to two and five times higher than TS1 was found on TS1-Ag-1.0 and TS1-Pt-1.0, respectively. Changes in the intermediate products were detected on Ag- and Pt-based photocatalysts with an increase in the catechol formation up to 3.3 and 6.6 times higher than that observed on TS1, respectively. A two-parallel reaction mechanism for the hydroquinone and catechol formation is proposed. A linear correlation between the photocatalytic activity and the surface concentration of noble metals was found indicating that the electron affinity of noble metals is the driven force for both the increase in the photoactivity and for the remarkable changes in the selectivity of products.

Evaluation of the effect of different stretching patterns on force decay and tensile properties of elastomeric ligatures

PubMed Central

Aminian, Amin; Nakhaei, Samaneh; Agahi, Raha Habib; Rezaeizade, Masoud; Aliabadi, Hamed Mirzazadeh; Heidarpour, Majid

2015-01-01

Background: There have been numerous researches on elastomeric ligatures, but clinical conditions in different stages of treatment are not exactly similar to laboratory conditions. The aim of this in vitro study was to simulate clinical conditions and evaluate the effect of three stretching patterns on the amount of force, tensile strength (TS) and extension to TS of the elastomers during 8 weeks. Materials and Methods: Forces, TS and extension to TS of two different brands of elastomers were measured at initial, 24 h and 2, 4, and 8-week intervals using a testing machine. During the study period, the elastomers were stored in three different types of jig (uniform stretching, 1 and 3 mm point stretching) designed by the computer-aided design and computer-aided manufacturing technique in order to simulate the different stages of orthodontic treatment. Results: The elastomeric ligatures under study exhibited a similar force decay pattern. The maximum force decay occurred during the first 24 h (49.9% ± 15%) and the amount of force decay was 75.7% ± 8% after 8 weeks. In general, the TS decreased during the study period, and the amount of extension to TS increased. Conclusion: Although the elastic behavior of all ligatures under study was similar, the amount of residual force, TS and extension to TS increased in elastomers under point stretching pattern. PMID:26759597

TS expression predicts postoperative recurrence in adenocarcinoma of the lung.

PubMed

Shimokawa, Hidehiko; Uramoto, Hidetaka; Onitsuka, Takamitsu; Iwata, Teruo; Nakagawa, Makoto; Ono, Kenji; Hanagiri, Takeshi

2011-06-01

Not all patients with lung cancer require postoperative adjuvant chemotherapy after a complete resection. However, no useful markers for either selecting appropriate candidates or for predicting clinical recurrence exist. Tumor specimens were collected from 183 consecutive patients who underwent a complete resection for lung adenocarcinoma from 2003 to 2007 in our department. We analyzed the thymidylate synthase (TS) and dihydrofolate reductase (DHFR) expressions in the primary lung adenocarcinoma by immunohistochemisty. The strong expression of TS and DHFR was identified in 39 (21.3%) and 120 (65.6%) patients, respectively. The strong TS expression was identified in 11 (39.3%) of 28 patients and 28 (18.1%) of 155 patients in patients with and without recurrence, respectively (p=0.012). The strong DHFR expression was also identified in 23 (82.1%) and 97 (62.6%) of the patients with and without recurrence, respectively (p=0.045). Logistic regression models indicated the strong TS expression to be an independent factor for tumor recurrence. The strong TS and DHFR expression was associated with a poorer disease-free survival (DFS) according to the survival analysis. A multivariate analysis demonstrated the strong TS expression to be independently associated with an increased risk for poor DFS. The strong TS expression may be a useful marker for predicting postoperative recurrence in patients with lung adenocarcinoma following surgery. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Assembly of Q{beta} viral RNA polymerase with host translational elongation factors EF-Tu and -Ts.

PubMed

Takeshita, Daijiro; Tomita, Kozo

2010-09-07

Replication and transcription of viral RNA genomes rely on host-donated proteins. Qbeta virus infects Escherichia coli and replicates and transcribes its own genomic RNA by Qbeta replicase. Qbeta replicase requires the virus-encoded RNA-dependent RNA polymerase (beta-subunit), and the host-donated translational elongation factors EF-Tu and -Ts, as active core subunits for its RNA polymerization activity. Here, we present the crystal structure of the core Qbeta replicase, comprising the beta-subunit, EF-Tu and -Ts. The beta-subunit has a right-handed structure, and the EF-Tu:Ts binary complex maintains the structure of the catalytic core crevasse of the beta-subunit through hydrophobic interactions, between the finger and thumb domains of the beta-subunit and domain-2 of EF-Tu and the coiled-coil motif of EF-Ts, respectively. These hydrophobic interactions are required for the expression and assembly of the Qbeta replicase complex. Thus, EF-Tu and -Ts have chaperone-like functions in the maintenance of the structure of the active Qbeta replicase. Modeling of the template RNA and the growing RNA in the catalytic site of the Qbeta replicase structure also suggests that structural changes of the RNAs and EF-Tu:Ts should accompany processive RNA polymerization and that EF-Tu:Ts in the Qbeta replicase could function to modulate the RNA folding and structure.

Tourette syndrome and excitatory substances: is there a connection?

PubMed

Zou, Li-Ping; Wang, Ying; Zhang, Li-Ping; Zhao, Jian-Bo; Lu, Jin-Fang; Liu, Qun; Wang, Hang-Yan

2011-05-01

The objective of this study is to investigate the relationship between excitatory substances by testing the urine in children with Tourette syndrome (TS). We performed a control study involving 44 patients with TS and 44 normal children by investigating the children's daily eating habits. We used the gas chromatograph-mass spectrometer and liquid chromatograph-mass spectrometer from Agilent. Substances for detection included 197 excitatory substances prohibited by the International Olympic Committee and other substances with similar chemical structures or biological functions for urine samples. Forty-four patients who did not take any drugs in the past 2 weeks enrolled in the study. The positive rate in the experiment group was three cases, while it was negative in the control group. The level of 1-testosterone increased in one extremely severe TS patient who ate large amounts of puffed food and drank an average of 350 ml of cola per day. Cathine and other substances with similar chemical constitution or similar biological effects increased in one severe TS patient who ate bags of instant noodles daily, according to the high score of the Yale Global Tic Severity Scale. An increase in ephedrine type, testosterone, and stimulants may be related to the pathogenesis of TS. Unhealthy food possibly causes TS. The relationship between excitatory substances and TS needs to be explored with the goal of providing more information on diagnosing and treating TS.

Early tumor shrinkage is independently associated with improved overall survival among patients with metastatic renal cell carcinoma: a validation study using the COMPARZ cohort.

PubMed

Grünwald, Viktor; Dietrich, Marion; Pond, Gregory R

2018-04-13

Early tumor shrinkage (eTS) has prognostic value in metastatic renal cell carcinoma (mRCC). We aimed to validate the role of eTS in first line treatment from the COMPARZ study (NCT00720941). 1100 patients treated with sunitinib or pazopanib were analyzed for tumor response according to RECIST 1.0. eTS was defined as tumor shrinkage by ≥ 10%. A landmark analysis was performed on day (d) 42 and 90 and Cox proportional hazards regression was computed for the prognostic effect of eTS. In patients with eTS median OS was 34.1 [CI 95% 28.4; not reached (NR)] and 33.6 (CI 95% 30.1; NR) months (mo) at d 42 and 90, respectively, compared to 19.6 (CI 95% 14.0; 28.9) and 15.1 (CI 95% 12.4; 18.7) mo for patients without eTS. There was no interaction between type of treatment and eTS (d 42 p = 0.79; d 90 p = 0.37). eTS ≥ 10% remained an independent prognostic marker in multivariable analyses at both d 42 and 90. Similar results were found for eTS at the 42 and 90 days landmarks. eTS ≥ 10% has prognostic relevance in mRCC and reflects a putative tool to guide future clinical treatment.

Impact of co-morbid attention-deficit and hyperactivity disorder on cognitive function in male children with Tourette syndrome: A controlled study.

PubMed

Termine, Cristiano; Luoni, Chiara; Fontolan, Stefania; Selvini, Claudia; Perego, Livia; Pavone, Francesca; Rossi, Giorgio; Balottin, Umberto; Cavanna, Andrea E

2016-09-30

Tourette syndrome (TS) and attention-deficit and hyperactivity disorder (ADHD) are co-morbid neurodevelopmental conditions affecting more commonly male patients. We set out to determine the impact of co-morbid ADHD on cognitive function in male children with TS by conducting a controlled study. Participants included four matched groups of unmedicated children (age range 6-15 years): TS (n=13), TS+ADHD (n=8), ADHD (n=39), healthy controls (n=66). Following clinical assessment, each participant completed a battery of tests from the Wechsler Intelligence Scale for Children-III, the Italian Battery for ADHD, the Tower of London test, the Corsi test, and the Digit Span test. All patient groups reported significantly lower scores than healthy controls across the neuropsychological tests involving executive functions. The TS+ADHD group was the most severely affected, followed by the ADHD group and the TS group, particularly in the tests assessing planning ability, inhibitory function, working memory and visual attention, but not auditory attention. Problems in executive functions are more common in patients with neurodevelopmental disorders than controls. Deficits in planning ability, inhibitory function, working memory and visual attention reported by children with TS appear to be more strongly related to the presence of co-morbid ADHD symptoms than core TS symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of the effect of different stretching patterns on force decay and tensile properties of elastomeric ligatures.

PubMed

Aminian, Amin; Nakhaei, Samaneh; Agahi, Raha Habib; Rezaeizade, Masoud; Aliabadi, Hamed Mirzazadeh; Heidarpour, Majid

2015-01-01

There have been numerous researches on elastomeric ligatures, but clinical conditions in different stages of treatment are not exactly similar to laboratory conditions. The aim of this in vitro study was to simulate clinical conditions and evaluate the effect of three stretching patterns on the amount of force, tensile strength (TS) and extension to TS of the elastomers during 8 weeks. Forces, TS and extension to TS of two different brands of elastomers were measured at initial, 24 h and 2, 4, and 8-week intervals using a testing machine. During the study period, the elastomers were stored in three different types of jig (uniform stretching, 1 and 3 mm point stretching) designed by the computer-aided design and computer-aided manufacturing technique in order to simulate the different stages of orthodontic treatment. The elastomeric ligatures under study exhibited a similar force decay pattern. The maximum force decay occurred during the first 24 h (49.9% ± 15%) and the amount of force decay was 75.7% ± 8% after 8 weeks. In general, the TS decreased during the study period, and the amount of extension to TS increased. Although the elastic behavior of all ligatures under study was similar, the amount of residual force, TS and extension to TS increased in elastomers under point stretching pattern.

Economic Assessment and Budgetary Impact of a Telemedicine Procedure and Spirometry Quality Control in the Primary Care Setting.

PubMed

Marina, Nuria; Bayón, Juan Carlos; López de Santa María, Elena; Gutiérrez, Asunción; Inchausti, Marta; Bustamante, Victor; Gáldiz, Juan B

2016-01-01

To evaluate the economic impact of a telemedicine procedure designed to improve the quality of lung function testing (LFT) in primary care in a public healthcare system, compared with the standard method. The economic impact of 9,039 LFTs performed in 51 health centers (2010-2013) using telespirometry (TS) compared to standard spirometry (SS) was studied. TS costs more per unit than SS (€47.80 vs. €39.70) (2013), but the quality of the TS procedure is superior (84% good quality, compared to 61% using the standard procedure). Total cost of TS was €431,974 (compared with €358,306€ for SS), generating an economic impact of €73,668 (2013). The increase in cost for good quality LFT performed using TS was €34,030 (2010) and €144,295 (2013), while the costs of poor quality tests fell by €15,525 (2010) and 70,627€ (2013). The cost-effectiveness analysis concludes that TS is 23% more expensive and 46% more effective. Healthcare costs consequently fall as the number of LFTs performed by TS rises. Avoiding poor quality, invalid LFTs generates savings that compensate for the increased costs of performing LFTs with TS, making it a cost-effective method. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Biogas production from oil palm empty fruit bunches of post mushroom cultivation media

NASA Astrophysics Data System (ADS)

Purnomo, Agus; Suprihatin; Romli, M.; Hasanudin, Udin

2018-03-01

The Empty fruit bunches are one of the palm oil industry wastes, which can be used for mushroom cultivation. Post-cultivation of mushroom from former EFB-mushroom media (EFBMM) has the potential to be processed into biogas. The purpose of this research was to examine optimum co-digestion conditions for biogas production of EFBMM.The research was carried out in an anaerobic digester with three different conditions - dry fermentation (Water content (WC)/Total Solid (TS) ratio 1.5 - 3.5), semi-wet fermentation (WC/TS ratio = 4.0 - 5.7) and wet fermentation (WC/TS ratio> 9.0) conditions. Digester of capacity 50L was used. Fermentation was done using 20% cow feces as inoculum which then added with circulation system for 70 days. The results showed that optimum biogas production were produced in semi-wet fermentation conditions (WC/TS ratio = 4). It was produced 37.462 liters (2.420 liters CH4/Kg Volatile Solid (VS)) of biogas with methane contain about 26.231%. Total volume of inoculum during process was 19.6 liters (1: 4 w/v) with absorbed TS inoculum ratio, TS/I = 0.4 (1:2.5 w/v). The result of research also showed that biogas which was produced from control about 2.865 liters (0.041 liters CH4/KgVS), with TS absorbed inoculum ratio, TS/I = 0.5 (1: 5w/v).

Difficulties experienced by young people with Tourette syndrome in secondary school: a mixed methods description of self, parent and staff perspectives.

PubMed

Wadman, Ruth; Glazebrook, Cris; Beer, Charlotte; Jackson, Georgina M

2016-01-20

Tourette syndrome (TS) is a neurodevelopmental disorder characterised by motor and vocal tics. These involuntary movements and vocalizations can have a negative impact in the school environment. The paper presents a mixed methods description of the difficulties experienced by UK students with TS in secondary school, drawing on multiple perspectives. Thirty-five young people with TS (11 to 18 years), their parents (n = 35) and key members of school staff (n = 54) took part in semi-structured interviews about TS-related difficulties in secondary school. Theme analysis was used to identify school difficulties reported by the young people, before moving on to analysis of the parents' and staff members' transcripts. The most frequently occurring themes from the young people's accounts were then quantified in order to examine the level of agreement between informants and the association with clinical symptom severity. A range of TS-related difficulties with academic work, and social and emotional well-being in school were reported by young people, parents and staff. Three superordinate themes are described: 1) TS makes school work more difficult, 2) Negative response to TS from staff and fellow students and 3) TS makes it more difficult to manage emotions in school. The three difficulties most frequently reported by the young people were problems concentrating in class, unhelpful responses by school staff to tics and difficulties with other students such as name-calling and mimicking tics. Additional difficulties reported by more than a quarter of young people related to homework, examinations, writing, anxiety and managing anger in school. Having more severe motor tics was associated with reporting difficulties with homework and handwriting, whereas having more severe phonic tics was associated with reporting unhelpful responses from staff. Young people and parents agreed more strongly with each other than they did with staff regarding school difficulties faced by individuals, and staff generally reported fewer TS-related difficulties. TS can present a barrier to learning in several ways and can also affect interactions with others and emotional experiences in secondary school. Implications for supporting secondary school-aged students with TS are considered.

Phthalocyanine tetrasulfonates affect the amyloid formation and cytotoxicity of alpha-synuclein.

PubMed

Lee, Eui-Nam; Cho, Hyun-Ju; Lee, Choong-Hwan; Lee, Daekyun; Chung, Kwang Chul; Paik, Seung R

2004-03-30

Alpha-synuclein is a pathological component of Parkinson's disease by constituting the filamentous component of Lewy bodies. Phthalocyanine (Pc) effects on the amyloidosis of alpha-synuclein have been examined. The copper complex of phthalocyanine tetrasulfonate (PcTS-Cu(2+)) caused the self-oligomerization of alpha-synuclein while Pc-Cu(2+) did not affect the protein, indicating that introduction of the sulfonate groups was critical for the selective protein interaction. The PcTS-Cu(2+) interaction with alpha-synuclein has occurred predominantly at the N-terminal region of the protein with a K(d) of 0.83 microM apart from the hydrophobic NAC (non-Abeta component of Alzheimer's disease amyloid) segment. Phthalocyanine tetrasulfonate (PcTS) lacking the intercalated copper ion also showed a considerable affinity toward alpha-synuclein with a K(d) of 3.12 microM, and its binding site, on the other hand, was located at the acidic C-terminus. These mutually exclusive interactions between PcTS and PcTS-Cu(2+) toward alpha-synuclein resulted in distinctive features on the kinetics of protein aggregation, morphologies of the final aggregates, and their in vitro cytotoxicities. The PcTS actually suppressed the fibrous amyloid formation of alpha-synuclein, but it produced the chopped-wood-looking protein aggregates. The aggregates showed rather low toxicity (9.5%) on human neuroblastoma cells (SH-SY5Y). In fact, the PcTS was shown to effectively rescue the cell death of alpha-synuclein overexpressing cells caused by the lactacystin treatment as a proteasome inhibitor. The anti-aggregative and anti-amyloidogenic properties of PcTS were also demonstrated with alcohol dehydrogenase, glutathione S-transferase, and amyloid beta/A4 protein under their aggregative conditions. The PcTS-Cu(2+), on the other hand, promoted the protein aggregation of alpha-synuclein, which gave rise to the fibrillar protein aggregates whose cytotoxicity became significant to 35.8%. Taken together, the data provided in this study indicate that PcTS/PcTS-Cu(2+) could be considered as possible candidates for the development of therapeutic or prophylactic strategies against the alpha-synuclein-related neurodegenerative disorders.

Effects of tea saponin on glucan conversion and bonding behaviour of cellulolytic enzymes during enzymatic hydrolysis of corncob residue with high lignin content

PubMed Central

2013-01-01

Background Recently, interest in the utilization of corncob residue (CCR, with high lignin of 45.1%) as a feedstock for bioethanol has been growing. Surfactants have been one of the most popular additives intended to prevent the inhibitory effect of lignin on cellulolytic enzymes, thereby improving hydrolysis. In this study, the effects of biosurfactant tea saponin (TS) on the enzymatic hydrolysis of CCR and the bonding behavior of cellulolytic enzymes to the substrate were investigated. The surface tension in the supernatant was also detected to obtain information about the characteristics and stability of TS. Results The glucose concentration was 17.15 mg/mL at 120 hours of hydrolysis with the low loading of cellulolytic enzymes (7.0 FPU/g cellulose and 10.5 BGU/g cellulose) and 5% CCR. The optimal dosage of TS was its critical micelle concentration (cmc, 1.80 mg/mL). The glucose yield was enhanced from 34.29 to 46.28 g/100 g dry matter by TS. The results indicate that TS can promote the adsorption of cellulolytic enzymes on the substrate and mediate the release of adsorbed enzymes. Meanwhile, TS improves the recovery of the cellulolytic enzymes after a hydrolysis cycle and prevents deactivation of the enzymes during the intense shaking process. The surface tension in supernatants of digested CCR with TS remained at 50.00 mN/m during the course of hydrolysis. It is interesting to note that biosurfactant TS can maintain the surface tension in supernatants, despite its digestibility by cellulolytic enzymes. Conclusions Serving as an accelerant of lignocellulose hydrolysis, TS can also be degraded by the cellulolytic enzymes and release glucose while retaining stability, which reduces the cost of both the cellulolytic enzymes and the additive. As the glucose from the TS could be utilized by yeast, further efforts will investigate the mechanism of function and the application of TS in the production of ethanol by simultaneous saccharification and fermentation (SSF). PMID:24225035

Molecular Cloning of a cDNA Encoding for Taenia solium TATA-Box Binding Protein 1 (TsTBP1) and Study of Its Interactions with the TATA-Box of Actin 5 and Typical 2-Cys Peroxiredoxin Genes.

PubMed

Rodríguez-Lima, Oscar; García-Gutierrez, Ponciano; Jiménez, Lucía; Zarain-Herzberg, Ángel; Lazzarini, Roberto; Landa, Abraham

2015-01-01

TATA-box binding protein (TBP) is an essential regulatory transcription factor for the TATA-box and TATA-box-less gene promoters. We report the cloning and characterization of a full-length cDNA that encodes a Taenia solium TATA-box binding protein 1 (TsTBP1). Deduced amino acid composition from its nucleotide sequence revealed that encodes a protein of 238 residues with a predicted molecular weight of 26.7 kDa, and a theoretical pI of 10.6. The NH2-terminal domain shows no conservation when compared with to pig and human TBP1s. However, it shows high conservation in size and amino acid identity with taeniids TBP1s. In contrast, the TsTBP1 COOH-terminal domain is highly conserved among organisms, and contains the amino acids involved in interactions with the TATA-box, as well as with TFIIA and TFIIB. In silico TsTBP1 modeling reveals that the COOH-terminal domain forms the classical saddle structure of the TBP family, with one α-helix at the end, not present in pig and human. Native TsTBP1 was detected in T. solium cysticerci´s nuclear extract by western blot using rabbit antibodies generated against two synthetic peptides located in the NH2 and COOH-terminal domains of TsTBP1. These antibodies, through immunofluorescence technique, identified the TBP1 in the nucleus of cells that form the bladder wall of cysticerci of Taenia crassiceps, an organism close related to T. solium. Electrophoretic mobility shift assays using nuclear extracts from T. solium cysticerci and antibodies against the NH2-terminal domain of TsTBP1 showed the interaction of native TsTBP1 with the TATA-box present in T. solium actin 5 (pAT5) and 2-Cys peroxiredoxin (Ts2-CysPrx) gene promoters; in contrast, when antibodies against the anti-COOH-terminal domain of TsTBP1 were used, they inhibited the binding of TsTBP1 to the TATA-box of the pAT5 promoter gene.