Merkel Cell Carcinoma Metastatic to Pleural Fluid: A Case Report.

PubMed

Rhee, Ye-Young; Kim, Soo Hee; Kim, Eun Kyung; Kim, Se Hoon

2018-05-01

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine carcinoma of the skin that shows locoregional or distant metastasis. Metastasis of MCC to body cavity effusion is extremely rare; only three cases have been reported so far. Metastatic MCC in effusion cytology shows small blue round cells with fine stippled chromatin like other small blue round cell tumors such as small cell lung carcinoma or lymphoma. The diagnosis of metastatic MCC can grant patients good chances at recently advanced therapeutic options. Here, we present a case of metastatic MCC to pleural effusion with characteristic single file-like pattern.

Reviewing the current evidence supporting early B-cells as the cellular origin of Merkel cell carcinoma.

PubMed

Sauer, C M; Haugg, A M; Chteinberg, E; Rennspiess, D; Winnepenninckx, V; Speel, E-J; Becker, J C; Kurz, A K; Zur Hausen, A

2017-08-01

Merkel cell carcinoma (MCC) is a highly malignant skin cancer characterized by early metastases and poor survival. Although MCC is a rare malignancy, its incidence is rapidly increasing in the U.S. and Europe. The discovery of the Merkel cell polyomavirus (MCPyV) has enormously impacted our understanding of its etiopathogenesis and biology. MCCs are characterized by trilinear differentiation, comprising the expression of neuroendocrine, epithelial and B-lymphoid lineage markers. To date, it is generally accepted that the initial assumption of MCC originating from Merkel cells (MCs) is unlikely. This is owed to their post-mitotic character, absence of MCPyV in MCs and discrepant protein expression pattern in comparison to MCC. Evidence from mouse models suggests that epidermal/dermal stem cells might be of cellular origin in MCC. The recently formulated hypothesis of MCC originating from early B-cells is based on morphology, the consistent expression of early B-cell lineage markers and the finding of clonal immunoglobulin chain rearrangement in MCC cells. In this review we elaborate on the cellular ancestry of MCC, the identification of which could pave the way for novel and more effective therapeutic regimens. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Avelumab: A Review in Metastatic Merkel Cell Carcinoma.

PubMed

Shirley, Matt

2018-05-24

Avelumab (Bavencio ® ) is a fully human IgG1 monoclonal antibody that is directed against programmed cell death ligand 1 (PD-L1). Avelumab functions as an immune checkpoint inhibitor and has recently been approved in the USA, the EU and Japan for the treatment of metastatic Merkel cell carcinoma (MCC). It is thus the first therapeutic agent specifically approved for use in this indication, and is approved for use independent of line of treatment. Approval for avelumab in metastatic MCC was based on the two-part, single-arm, phase II trial, JAVELIN Merkel 200. In Part A of the study, confirmed objective responses were observed in approximately one-third of patients with chemotherapy-refractory metastatic MCC treated with avelumab. The responses were observed early and appeared to be durable, with an estimated 74% of responses having a duration ≥ 12 months. Furthermore, interim results from a separate cohort of patients (Part B) indicate an objective response rate for avelumab of > 60% in patients who were chemotherapy-naïve in the metastatic disease setting. Avelumab is associated with a risk of immune-related adverse events but, overall, has an acceptable and manageable safety and tolerability profile. In conclusion, currently available data suggest that avelumab presents a clinically beneficial new treatment option for metastatic MCC, a rare but aggressive cancer associated with a poor prognosis.

Detection of the Merkel cell polyomavirus in the neuroendocrine component of combined Merkel cell carcinoma.

PubMed

Kervarrec, Thibault; Samimi, Mahtab; Gaboriaud, Pauline; Gheit, Tarik; Beby-Defaux, Agnès; Houben, Roland; Schrama, David; Fromont, Gaëlle; Tommasino, Massimo; Le Corre, Yannick; Hainaut-Wierzbicka, Eva; Aubin, Francois; Bens, Guido; Maillard, Hervé; Furudoï, Adeline; Michenet, Patrick; Touzé, Antoine; Guyétant, Serge

2018-05-01

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. The main etiological agent is Merkel cell polyomavirus (MCPyV), detected in 80% of cases. About 5% of cases, called combined MCC, feature an admixture of neuroendocrine and non-neuroendocrine tumor cells. Reports of the presence or absence of MCPyV in combined MCC are conflicting, most favoring the absence, which suggests that combined MCC might have independent etiological factors and pathogenesis. These discrepancies might occur with the use of different virus identification assays, with different sensitivities. In this study, we aimed to determine the viral status of combined MCC by a multimodal approach. We histologically reviewed 128 cases of MCC and sub-classified them as "combined" or "conventional." Both groups were compared by clinical data (age, sex, site, American Joint Committee on Cancer [AJCC] stage, immunosuppression, risk of recurrence, and death during follow-up) and immunochemical features (cytokeratin 20 and 7, thyroid transcription factor 1 [TTF1], p53, large T antigen [CM2B4], CD8 infiltrates). After a first calibration step with 12 conventional MCCs and 12 cutaneous squamous cell carcinomas as controls, all eight cases of combined MCC were investigated for MCPyV viral status by combining two independent molecular procedures. Furthermore, on multiplex genotyping assay, the samples were examined for the presence of other polyoma- and papillomaviruses. Combined MCC differed from conventional MCC in earlier AJCC stage, increased risk of recurrence and death, decreased CD8 infiltrates, more frequent TTF1 positivity (5/8), abnormal p53 expression (8/8), and frequent lack of large T antigen expression (7/8). With the molecular procedure, half of the combined MCC cases were positive for MCPyV in the neuroendocrine component. Beta papillomaviruses were detected in 5/8 combined MCC cases and 9/12 conventional MCC cases. In conclusion, the detection of MCPyV DNA in half of the combined MCC cases suggests similar routes of carcinogenesis for combined and conventional MCC.

Huntingtin-interacting protein 1: a Merkel cell carcinoma marker that interacts with c-Kit.

PubMed

Ames, Heather M; Bichakjian, Christopher K; Liu, Grace Y; Oravecz-Wilson, Katherine I; Fullen, Douglas R; Verhaegen, Monique E; Johnson, Timothy M; Dlugosz, Andrzej A; Ross, Theodora S

2011-10-01

Merkel cell carcinoma (MCC) is a neoplasm thought to originate from the neuroendocrine Merkel cells of the skin. Although the prevalence of MCC has been increasing, treatments for this disease remain limited because of a paucity of information regarding MCC biology. We have found that the endocytic oncoprotein Huntingtin-interacting protein 1 (HIP1) is expressed at high levels in ∼90% of MCC tumors and serves as a more reliable histological cytoplasmic stain than the gold standard, cytokeratin 20. Furthermore, high anti-HIP1 antibody reactivity in the sera of a cohort of MCC patients predicts the presence of metastases. Another protein that is frequently expressed at high levels in MCC tumors is the stem cell factor (SCF) receptor tyrosine kinase, c-Kit. In working toward an understanding of how HIP1 might contribute to MCC tumorigenesis, we have discovered that HIP1 interacts with SCF-activated c-Kit. These data not only identify HIP1 as a molecular marker for management of MCC patients but also show that HIP1 interacts with and slows the degradation of c-Kit.

Merkel cell carcinoma: is this a true carcinoma?

PubMed

Jankowski, Marek; Kopinski, Piotr; Schwartz, Robert; Czajkowski, Rafal

2014-11-01

Recent years have brought an enhanced understanding of Merkel cell carcinoma (MCC) biology, especially with regard to the Merkel cell polyoma virus as a causative agent. Differences between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative MCC in morphology; gene expression, miRNA profiles and prognosis have been reported. Origin of MCC is controversial. Presence of neurosecretory granules has suggested that these carcinomas originate from one of the neurocrest derivatives, most probably Merkel cells; the name Merkel cell carcinoma is now widely accepted. Expression of PGP 9.5, chromogranin A and several neuropeptides, initially regarded as specific markers for neural and neuroendocrine cells, has recently been shown in a subset of lymphomas. MCC commonly expresses terminal deoxynucleotidyl transferase and PAX5. Their co-expression under physiologic circumstances is restricted to pro/pre-B cells and pre-B cells. These findings lead to the hypothesis by zur Hausen et al. that MCC originates from early B cells. This review was intended to critically appraise zur Hausen's hypothesis and discuss the possibility that MCC is a heterogenous entity with distinct subtypes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intraepidermal Merkel cell carcinoma: A case series of a rare entity with clinical follow up.

PubMed

Jour, George; Aung, Phyu P; Rozas-Muñoz, Eduardo; Curry, Johnathan L; Prieto, Victor; Ivan, Doina

2017-08-01

Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous carcinoma. MCC typically involves dermis and although epidermotropism has been reported, MCC strictly intraepidermal or in situ (MCCIS) is exceedingly rare. Most of the cases of MCCIS described so far have other associated lesions, such as squamous or basal cell carcinoma, actinic keratosis and so on. Herein, we describe 3 patients with MCC strictly in situ, without a dermal component. Our patients were elderly. 2 of the lesions involved the head and neck area and 1 was on a finger. All tumors were strictly intraepidermal in the diagnostic biopsies, and had histomorphologic features and an immunohistochemical profile supporting the diagnosis of MCC. Excisional biopsies were performed in 2 cases and failed to reveal dermal involvement by MCC or other associated malignancies. Our findings raise the awareness that MCC strictly in situ does exist and it should be included in the differential diagnosis of Paget's or extramammary Paget's disease, pagetoid squamous cell carcinoma, melanoma and other neoplasms that typically show histologically pagetoid extension of neoplastic cells. Considering the limited number of cases reported to date, the diagnosis of isolated MCCIS should not warrant a change in management from the typical MCC. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Update on Merkel Cell Carcinoma.

PubMed

Harms, Paul W

2017-09-01

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine malignancy. Merkel cell polyomavirus, a tumorigenic DNA virus, is present in most MCC tumors, with implications for tumor biology, diagnosis, and management. Merkel cell polyomavirus-negative tumors have a high burden of UV-signature mutations, similar to melanoma. The histopathologic diagnosis of MCC requires immunohistochemistry to exclude morphologically similar entities. Therapies for advanced disease are currently lacking. Here, the features of MCC are reviewed, including recent molecular discoveries with implications for improved therapy for advanced disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Huntingtin Interacting Protein 1: a Merkel Cell Carcinoma Marker That Interacts with c-Kit

PubMed Central

Ames, Heather M.; Bichakjian, Christopher K.; Liu, Grace Y.; Oravecz-Wilson, Katherine I.; Fullen, Douglas R.; Verhaegen, Monique; Johnson, Timothy M.; Dlugosz, Andrzej A.; Ross, Theodora S.

2011-01-01

Merkel Cell Carcinoma (MCC) is a neoplasm thought to originate from the neuroendocrine Merkel cells of the skin. While the prevalence of MCC has been increasing, treatments for this disease remain limited due to a paucity of information regarding MCC biology. We have found that the endocytic oncoprotein Huntingtin interacting protein 1 (HIP1) is expressed at high levels in close to 90% of MCC tumors and serves as a more reliable histological cytoplasmic stain than the gold standard, cytokeratin 20 (CK20). Furthermore, high anti-HIP1 antibody reactivity in the sera of a cohort of MCC patients predicts the presence of metastases. Another protein that is frequently expressed at high levels in MCC tumors is the stem cell factor (SCF) receptor tyrosine kinase, c-Kit. In working towards an understanding of how HIP1 might contribute to MCC tumorigenesis, we have discovered that HIP1 interacts with SCF activated c-Kit. These data not only identify HIP1 as a molecular marker for management of MCC patients but also show that HIP1 interacts with and slows the degradation of c-Kit. PMID:21697888

A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

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

Min, Kyung-Won; Zhang, Xiaobo; College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi, 712100

2012-09-01

MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found thatmore » MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down-regulation in a PPARγ dependent manner. ► To our knowledge, this is the first report that MCC-555 affects anti-proliferative activity in pancreatic cancer cells, along with multiple targets.« less

RB1 is the crucial target of the Merkel cell polyomavirus Large T antigen in Merkel cell carcinoma cells.

PubMed

Hesbacher, Sonja; Pfitzer, Lisa; Wiedorfer, Katharina; Angermeyer, Sabrina; Borst, Andreas; Haferkamp, Sebastian; Scholz, Claus-Jürgen; Wobser, Marion; Schrama, David; Houben, Roland

2016-05-31

The pocket protein (PP) family consists of the three members RB1, p107 and p130 all possessing tumor suppressive properties. Indeed, the PPs jointly control the G1/S transition mainly by inhibiting E2F transcription factors. Notably, several viral oncoproteins are capable of binding and inhibiting PPs. Merkel cell polyomavirus (MCPyV) is considered as etiological factor for Merkel cell carcinoma (MCC) with expression of the viral Large T antigen (LT) harboring an intact PP binding domain being required for proliferation of most MCC cells. Therefore, we analyzed the interaction of MCPyV-LT with the PPs. Co-IP experiments indicate that MCPyV-LT binds potently only to RB1. Moreover, MCPyV-LT knockdown-induced growth arrest in MCC cells can be rescued by knockdown of RB1, but not by p107 or p130 knockdown. Accordingly, cell cycle arrest and E2F target gene repression mediated by the single PPs can only in the case of RB1 be significantly reverted by MCPyV-LT expression. Moreover, data from an MCC patient indicate that loss of RB1 rendered the MCPyV-positive MCC cells LT independent. Thus, our results suggest that RB1 is the dominant tumor suppressor PP in MCC, and that inactivation of RB1 by MCPyV-LT is largely sufficient for its growth supporting function in established MCPyV-positive MCC cells.

Molecular and cytogenetic analysis of human diploid fibroblast cells transformed by simian virus 40: What causes immortalization

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

Patsalis, P.C.

1993-01-01

Transformation of human diploid fibroblasts (HF) with SV40 can result in extension of life span beyond the normal limit of senescence and in a minority of cases, immortalization. This study used comparison of matched parental (diploid) and immortalized cell lines to determine if any single genetic factor could be related to the immortalization phenomena. The integration site of SV40 was shown to be at chromosome 5q21 by cytologic hybridization. A comparison of mortal and immortal cells showed no alterations involving the integrated SV40 genome per se. Karyotypic analysis of matched cell lines identified a specific chromosomal breakpoint (6q21) in immortalizedmore » cells that was not present in the parental line. Hybridization analysis confirmed that sequences on the distal portion of 6q are lost in immortalized cells. Two single copy DNAs which flank the breakpoint were identified and used to further define the exact breakpoint on 6q13. FISH analysis demonstrated the region 6q13 [yields] 21 as belonging to another chromosome and confirmed the 6q13 breakpoint. A survey of random translocations and other anomalies occurring in the immortalized lines was also made. Some of these are regions known to contain oncogenes and transforming proteins. The MCC tumor suppressor gene was rearranged and deregulated. The genes DCC, Bel-2, APC were also found to be deregulated. The authors propose that deletion of specific sequences due to breakage of chromosome 6q represent one of the mutational events responsible for immortalization of SV40 transformed HF. In addition, the MCC and possibly other genes are involved in the progression of immortalization.« less

Merkel Cell Polyomavirus: A New DNA Virus Associated with Human Cancer.

PubMed

MacDonald, Margo; You, Jianxin

2017-01-01

Merkel cell polyomavirus (MCPyV or MCV) is a novel human polyomavirus that has been discovered in Merkel cell carcinoma (MCC), a highly aggressive skin cancer. MCPyV infection is widespread in the general population. MCPyV-associated MCC is one of the most aggressive skin cancers, killing more patients than other well-known cancers such as cutaneous T-cell lymphoma and chronic myelogenous leukemia (CML). Currently, however, there is no effective drug for curing this cancer. The incidence of MCC has tripled over the past two decades. With the widespread infection of MCPyV and the increase in MCC diagnoses, it is critical to better understand the biology of MCPyV and its oncogenic potential. In this chapter, we summarize recent discoveries regarding MCPyV molecular virology, host cellular tropism, mechanisms of MCPyV oncoprotein-mediated oncogenesis, and current therapeutic strategies for MCPyV-associated MCC. We also present epidemiological evidence for MCPyV infection in HIV patients and links between MCPyV and non-MCC human cancers.

FAST TRACK COMMUNICATION: The origin of Bohm diffusion, investigated by a comparison of different modelling methods

NASA Astrophysics Data System (ADS)

Bultinck, E.; Mahieu, S.; Depla, D.; Bogaerts, A.

2010-07-01

'Bohm diffusion' causes the electrons to diffuse perpendicularly to the magnetic field lines. However, its origin is not yet completely understood: low and high frequency electric field fluctuations are both named to cause Bohm diffusion. The importance of including this process in a Monte Carlo (MC) model is demonstrated by comparing calculated ionization rates with particle-in-cell/Monte Carlo collisions (PIC/MCC) simulations. A good agreement is found with a Bohm diffusion parameter of 0.05, which corresponds well to experiments. Since the PIC/MCC method accounts for fast electric field fluctuations, we conclude that Bohm diffusion is caused by fast electric field phenomena.

Merkel cell carcinoma: Do you know your guidelines?

PubMed

Miles, Brett A; Goldenberg, David

2016-05-01

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy that exhibits clinically aggressive features and is associated with a poor prognosis. The incidence of MCC seems to be increasing for reasons unknown, and is estimated to be 0.32/100,000 in the United States. This article will review the current literature and National Comprehensive Cancer Network practice guidelines in the treatment of MCC. Resection of MCC with negative margins remains the mainstay of therapy. Positive nodal disease should be treated with neck dissection and adjuvant radiotherapy. High-risk patients should undergo adjuvant radiotherapy, which improves oncologic outcomes. The role of chemotherapy is less clear and is currently reserved for advanced-stage MCC and palliative therapy. The pathogenesis of MCC has recently been impacted with the discovery of the Merkel cell polyomavirus (MCPyV). Research to establish targeted and immunologic therapeutic options are ongoing. © 2015 Wiley Periodicals, Inc.

Merkel Cell Carcinoma Therapeutic Update.

PubMed

Cassler, Nicole M; Merrill, Dean; Bichakjian, Christopher K; Brownell, Isaac

2016-07-01

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Early-stage disease can be cured with surgical resection and radiotherapy (RT). Sentinel lymph node biopsy (SLNB) is an important staging tool, as a microscopic MCC is frequently identified. Adjuvant RT to the primary excision site and regional lymph node bed may improve locoregional control. However, newer studies confirm that patients with biopsy-negative sentinel lymph nodes may not benefit from regional RT. Advanced MCC currently lacks a highly effective treatment as responses to chemotherapy are not durable. Recent work suggests that immunotherapy targeting the programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) checkpoint holds great promise in treating advanced MCC and may provide durable responses in a portion of patients. At the same time, high-throughput sequencing studies have demonstrated significant differences in the mutational profiles of tumors with and without the Merkel cell polyomavirus (MCV). An important secondary endpoint in the ongoing immunotherapy trials for MCC will be determining if there is a response difference between the virus-positive MCC tumors that typically lack a large mutational burden and the virus-negative tumors that have a large number of somatic mutations and predicted tumor neoantigens. Interestingly, sequencing studies have failed to identify a highly recurrent activated driver pathway in the majority of MCC tumors. This may explain why targeted therapies can demonstrate exceptional responses in case reports but fail when treating all comers with MCC. Ultimately, a precision medicine approach may be more appropriate for treating MCC, where identified driver mutations are used to direct targeted therapies. At a minimum, stratifying patients in future clinical trials based on tumor viral status should be considered as virus-negative tumors are more likely to harbor activating driver mutations.

High load of Merkel cell polyomavirus DNA detected in the normal skin of Japanese patients with Merkel cell carcinoma.

PubMed

Hashida, Yumiko; Nakajima, Kimiko; Nakajima, Hideki; Shiga, Takeo; Tanaka, Moe; Murakami, Masanao; Matsuzaki, Shigenobu; Naganuma, Seiji; Kuroda, Naoki; Seki, Yasutaka; Katano, Harutaka; Sano, Shigetoshi; Daibata, Masanori

2016-09-01

Although Merkel cell polyomavirus (MCPyV) has the potential to cause Merkel cell carcinoma (MCC), it is also found in the normal skin of healthy individuals. However, the mechanism for transformation of MCPyV to an oncogenic form is unknown. To investigate the levels of MCPyV infection in the normal skin patients with MCC compared with those in a control cohort. We studied a total of six Japanese patients with cutaneous MCC. Sun-exposed and sun-unexposed skin swabs were obtained and analyzed for MCPyV loads using quantitative real-time polymerase chain reaction. At first, we found a patient with MCC carrying an extremely high load of MCPyV DNA in normal skin. This unique case prompted us to further explore the levels of MCPyV as skin microbiota in patients with MCC. We showed that MCPyV DNA levels were significantly higher in swabs obtained from normal skin samples of six patients with MCC compared with those from 30 age-matched healthy individuals and 19 patients with other cutaneous cancers. Whereas MCPyV strains obtained from the normal skin of patients with MCC had gene sequences without structural alterations, sequences of the tumor-derived strains showed truncating mutations or deletions. Although the number of patients with MCC studied was small, our findings suggest that MCC may occur with a background of high MCPyV load in the skin, and are expected to stimulate further studies on whether such skin virome levels could be one of predictive markers for the development of MCC. Copyright © 2016 Elsevier B.V. All rights reserved.

Merkel cell carcinoma: Epidemiology, prognosis, therapy and unmet medical needs.

PubMed

Schadendorf, Dirk; Lebbé, Céleste; Zur Hausen, Axel; Avril, Marie-Françoise; Hariharan, Subramanian; Bharmal, Murtuza; Becker, Jürgen C

2017-01-01

Merkel cell carcinoma (MCC) is a rare skin cancer that is associated with Merkel cell polyomavirus infection in most cases. Incidence rates of MCC have increased in past decades. Risk factors for MCC include ultraviolet light exposure, immunosuppression and advanced age. MCC is an aggressive malignancy with frequent recurrences and a high mortality rate, although patient outcomes are generally more favourable if the patient is referred for treatment at an early stage. Although advances have been made recently in the MCC field, large gaps remain with regard to definitive biomarkers and prognostic indicators. Although MCC is chemosensitive, responses in advanced stages are mostly of short duration, and the associated clinical benefit on overall survival is unclear. Recent nonrandomised phase 2 clinical trials with anti-PD-L1/PD-1 antibodies have demonstrated safety and efficacy; however, there are still no approved treatments for patients with metastatic MCC. Patients with advanced disease are encouraged to participate in clinical trials for treatment, indicating the largely unmet need for durable, safe treatment within this population. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

An unusual case of diffuse Merkel cell carcinoma successfully treated with low dose radiotherapy.

PubMed

Chatzinasiou, Foteini; Papadavid, Euaggelia; Korkolopoulou, Penelope; Levidou, Georgia; Panayiotides, Ioannis; Theodoropoulos, Konstadinos; Pogka, Vasiliki; Asimakopoulos, Charalampos; Rigopoulos, Dimitrios

2015-01-01

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of the skin. MCC should be included in the diagnosis of a rapidly growing infiltrating mass and histology as well as laboratory investigations such as Merkel cell polyoma virus (MCPyV) detection are valuable in its diagnosis. We present an unusual case of giant MCC-positive MCPyV in a Greek woman located on the lower leg. Our patient is very unusual in terms of her extensive MCC and her rapid and complete response to radiotherapy. © 2015 Wiley Periodicals, Inc.

Simultaneous Wastewater Treatment, Algal Biomass Production and Electricity Generation in Clayware Microbial Carbon Capture Cells.

PubMed

Jadhav, Dipak A; Jain, Sumat C; Ghangrekar, Makarand M

2017-11-01

Performance of microbial carbon capture cells (MCCs), having a low-cost clayware separator, was evaluated in terms of wastewater treatment and electricity generation using algae Chlorella pyrenoidosa in MCC-1 and Anabaena ambigua in MCC-2 and without algae in a cathodic chamber of MCC-3. Higher power production was achieved in MCC-1 (6.4 W/m 3 ) compared to MCC-2 (4.29 W/m 3 ) and MCC-3 (3.29 W/m 3 ). Higher coulombic efficiency (15.23 ± 1.30%) and biomass production (66.4 ± 4.7 mg/(L*day)) in MCC-1 indicated the superiority of Chlorella over Anabaena algae for carbon capture and oxygen production to facilitate the cathodic reduction. Algal biofilm formation on the cathode surface of MCC-1 increased dissolved oxygen in the catholyte and decreased the cathodic charge transfer resistance with increase in reduction current. Electrochemical analyses revealed slow cathodic reactions and increase in internal resistance in MCC-2 (55 Ω) than MCC-1 (30 Ω), due to lower oxygen produced by Anabaena algae. Thus, biomass production in conjunction with wastewater treatment, CO 2 sequestration and electricity generation can be achieved using Chlorella algal biocathode in MCC.

Avelumab: a new standard for treating metastatic Merkel cell carcinoma.

PubMed

Baker, Mairead; Cordes, Lisa; Brownell, Isaac

2018-04-01

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Although MCC is chemosensitive, responses to traditional chemotherapeutic agents are not durable. Avelumab, a novel anti-PD-L1 immune checkpoint inhibitor, recently became the first FDA-approved agent for the treatment of metastatic MCC and represents a new option to improve patient survival. Areas covered: This article presents an overview of MCC and summarizes the development of avelumab in the treatment of metastatic MCC. Preclinical studies, phase 1 and phase 2 clinical trials, and the safety profile of avelumab are reviewed. Future perspectives and ongoing studies are also discussed. Expert commentary: Avelumab demonstrated rapid and durable responses and a manageable safety profile in the treatment of metastatic MCC. Patient outcomes are favorable when compared to historical responses to standard chemotherapy. Ongoing clinical trials will continue to characterize avelumab and its optimal use in MCC therapy.

Tropomyosin Receptor Kinase A Expression on Merkel Cell Carcinoma Cells.

PubMed

Wehkamp, Ulrike; Stern, Sophie; Krüger, Sandra; Hauschild, Axel; Röcken, Christoph; Egberts, Friederike

2017-11-01

Merkel cell carcinoma (MCC) is a malignant neuroendocrine skin tumor frequently associated with the Merkel cell polyomavirus. Immune checkpoint therapy showed remarkable results, although not all patients are responsive to this therapy. Anti-tropomyosin receptor kinase A (TrkA)-targeted treatment has shown promising results in several tumor entities. To determine TrkA expression in MCC as a rationale for potential targeted therapy. This case series study investigated the MCC specimens of 55 patients treated at the Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany, from January 1, 2005, through December 31, 2015. Thirty-nine of the 55 samples were suitable for further histopathologic examination. Expression of TrkA was explored by immunohistochemical analysis. Diagnosis of MCC was confirmed by staining positive for cytokeratin 20 (CK20) and synaptophysin. Expression of TrkA on the tumor cells. Specimens of 39 patients (21 women and 18 men; mean [SD] age, 75.0 [7.8] years) underwent immunohistochemical investigation. Thirty-eight of 38 specimens expressed CK20 and synaptophysin on the MCC tumor cells (100% expression). Merkel cell polyomavirus was detected in 32 of 38 specimens (84%). Tropomyosin receptor kinase A was found in all 36 evaluable specimens on the tumor cells; 34 (94%) showed a weak and 2 (6%) showed a strong cytoplasmic expression. In addition, strongly positive perinuclear dots were observed in 30 of 36 specimens (83%). Tropomyosin receptor kinase A was expressed on MCC tumor cells in 100% of evaluable specimens. This result may lead to the exploration of new targeted treatment options in MCC, especially for patients who do not respond to anti-programmed cell death protein 1 treatment.

Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF.

PubMed

Rotondo, John Charles; Bononi, Ilaria; Puozzo, Andrea; Govoni, Marcello; Foschi, Valentina; Lanza, Giovanni; Gafà, Roberta; Gaboriaud, Pauline; Touzé, Françoise Antoine; Selvatici, Rita; Martini, Fernanda; Tognon, Mauro

2017-07-15

Purpose: The purpose of this investigation was to characterize Merkel cell carcinomas (MCC) arisen in patients affected by autoimmune diseases and treated with biologic drugs. Experimental Design: Serum samples from patients with MCC were analyzed for the presence and titer of antibodies against antigens of the oncogenic Merkel cell polyomavirus (MCPyV). IgG antibodies against the viral oncoproteins large T (LT) and small T (ST) antigens and the viral capsid protein-1 were analyzed by indirect ELISA. Viral antigens were recombinant LT/ST and virus-like particles (VLP), respectively. MCPyV DNA sequences were studied using PCR methods in MCC tissues and in peripheral blood mononuclear cells (PBMC). Immunohistochemical (IHC) analyses were carried out in MCC tissues to reveal MCPyV LT oncoprotein. Results: MCPyV DNA sequences identified in MCC tissues showed 100% homology with the European MKL-1 strain. PBMCs from patients tested MCPyV-negative. Viral DNA loads in the three MCC tissues were in the 0.1 to 30 copy/cell range. IgG antibodies against LT/ST were detected in patients 1 and 3, whereas patient 2 did not react to the MCPyV LT/ST antigen. Sera from the three patients with MCC contained IgG antibodies against MCPyV VP1. MCC tissues tested MCPyV LT-antigen-positive in IHC assays, with strong LT expression with diffuse nuclear localization. Normal tissues tested MCPyV LT-negative when employed as control. Conclusions: We investigated three new MCCs in patients affected by rheumatologic diseases treated with biologic drugs, including TNF. A possible cause-effect relationship between pharmacologic immunosuppressive treatment and MCC onset is suggested. Indeed, MCC is associated with MCPyV LT oncoprotein activity. Clin Cancer Res; 23(14); 3929-34. ©2017 AACR . ©2017 American Association for Cancer Research.

Recent Insights and Advances in the Management of Merkel Cell Carcinoma.

PubMed

Banks, Patricia D; Sandhu, Shahneen; Gyorki, David E; Johnston, Meredith L; Rischin, Danny

2016-07-01

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy with a propensity for recurrence and a poor prognosis. Incidence of MCC is on the rise and is known to increase with advanced age, immunosuppression, and UV exposure. Merkel cell polyomavirus is implicated in the pathogenesis of virus-positive MCC and accounts for 80% of MCCs in the northern hemisphere and 25% in southern latitudes. In contrast, tumorigenesis of virus-negative MCC is linked to UV-induced DNA damage. Interplay between ubiquitous Merkel cell polyomavirus skin infections that commonly occur in healthy skin and other established risk factors, such as immunosuppression and UV exposure, remains poorly understood. Surgery and radiotherapy achieves excellent locoregional control; however, invariably, a significant proportion of patients develop disseminated disease that is incurable. Chemotherapy offers a high response rate for metastatic disease, but responses are short-lived and the impact on survival is not established. Recent advances in our understanding of the genetic landscape and immunobiology of MCC has led to investigation of novel treatments, including immune checkpoint inhibitors, which are likely to rapidly transform the way we manage these patients. We review epidemiologic, clinical, and histopathologic features of MCC; describe recent insights in MCC biology; and discuss novel therapeutic approaches. Copyright © 2016 by American Society of Clinical Oncology.

Merkel cell polyomavirus small T antigen initiates Merkel cell carcinoma-like tumor development in mice

PubMed Central

Verhaegen, Monique E.; Mangelberger, Doris; Harms, Paul W.; Eberl, Markus; Wilbert, Dawn M.; Meireles, Julia; Bichakjian, Christopher K.; Saunders, Thomas L.; Wong, Sunny Y.; Dlugosz, Andrzej A.

2017-01-01

Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a non-proliferative population of neuroendocrine cells which arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor’s cell of origin, are unknown. Using a panel of pre-term transgenic mice, we show that epidermis-targeted co-expression of sT and the cell fate determinant atonal bHLH transcription factor 1 (Atoh1) leads to development of widespread cellular aggregates with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Co-expression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with Atoh1. MCPyV sT, when co-expressed with Atoh1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. PMID:28512245

Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice.

PubMed

Verhaegen, Monique E; Mangelberger, Doris; Harms, Paul W; Eberl, Markus; Wilbert, Dawn M; Meireles, Julia; Bichakjian, Christopher K; Saunders, Thomas L; Wong, Sunny Y; Dlugosz, Andrzej A

2017-06-15

Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12); 3151-7. ©2017 AACR . ©2017 American Association for Cancer Research.

Update on Merkel Cell Carcinoma: Epidemiology, Etiopathogenesis, Clinical Features, Diagnosis, and Staging.

PubMed

Llombart, B; Requena, C; Cruz, J

2017-03-01

Merkel cell carcinoma (MCC) is a rare, highly aggressive tumor, and local or regional disease recurrence is common, as is metastasis. MCC usually develops in sun-exposed skin in patients of advanced age. Its incidence has risen 4-fold in recent decades as the population has aged and immunohistochemical techniques have led to more diagnoses. The pathogenesis of MCC remains unclear but UV radiation, immunosuppression, and the presence of Merkel cell polyomavirus in the tumor genome seem to play key roles. This review seeks to update our understanding of the epidemiology, etiology, pathogenesis, and clinical features of MCC. We also review histologic and immunohistochemical features required for diagnosis. MCC staging is discussed, given its great importance in establishing a prognosis for these patients. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Strategy for eliciting antigen-specific CD8+ T cell-mediated immune response against a cryptic CTL epitope of merkel cell polyomavirus large T antigen

PubMed Central

2012-01-01

Background Merkel cell carcinoma (MCC) is a relatively new addition to the expanding category of oncovirus-induced cancers. Although still comparably rare, the number of cases has risen dramatically in recent years. Further complicating this trend is that MCC is an extremely aggressive neoplasm with poor patient prognosis and limited treatment options for advanced disease. The causative agent of MCC has been identified as the merkel cell polyomavirus (MCPyV). The MCPyV-encoded large T (LT) antigen is an oncoprotein that is theorized to be essential for virus-mediated tumorigenesis and is therefore, an excellent MCC antigen for the generation of antitumor immune responses. As a foreign antigen, the LT oncoprotein avoids the obstacle of immune tolerance, which normally impedes the development of antitumor immunity. Ergo, it is an excellent target for anti-MCC immunotherapy. Since tumor-specific CD8+ T cells lead to better prognosis for MCC and numerous other cancers, we have generated a DNA vaccine that is capable of eliciting LT-specific CD8+ T cells. The DNA vaccine (pcDNA3-CRT/LT) encodes the LT antigen linked to a damage-associated molecular pattern, calreticulin (CRT), as it has been demonstrated that the linkage of CRT to antigens promotes the induction of antigen-specific CD8+ T cells. Results The present study shows that DNA vaccine-induced generation of LT-specific CD8+ T cells is augmented by linking CRT to the LT antigen. This is relevant since the therapeutic effects of the pcDNA3-CRT/LT DNA vaccine is mediated by LT-specific CD8+ T cells. Mice vaccinated with the DNA vaccine produced demonstrably more LT-specific CD8+ T cells. The DNA vaccine was also able to confer LT-specific CD8+ T cell-mediated protective and therapeutic effects to prolong the survival of mice with LT-expressing tumors. In the interest of determining the LT epitope which most MCC-specific CD8+ T cells recognize, we identified the amino acid sequence of the immunodominant LT epitope as aa19-27 (IAPNCYGNI) and found that it is H-2kb-restricted. Conclusion The results of this study can facilitate the development of other modes of MCC treatment such as peptide-based vaccines and adoptive transfer of LT-specific CD8+ T cells. Likewise, the MCC DNA vaccine has great potential for clinical translation as the immunologic specificity is high and the treatment strategy can be exported to address other virus-induced tumors. PMID:23095249

Evaluation of mast cell counts and microvessel density in reactive lesions of the oral cavity.

PubMed

Kouhsoltani, Maryam; Moradzadeh Khiavi, Monir; Tahamtan, Shabnam

2016-01-01

Background. Reliable immunohistochemical assays to assess the definitive role of mast cells (MCs) and angiogenesis in the pathogenesis of oral reactive lesions are generally not available. The aim of the present study was to evaluate mast cell counts (MCC) and microvessel density (MVD) in oral reactive lesions and determine the correlation between MCC and MVD. Methods. Seventy-five cases of reactive lesions of the oral cavity, including pyogenic granuloma, fibroma, peripheral giant cell granuloma, inflammatory fibrous hyperplasia, peripheral ossifying fibroma (15 for each category) were immunohisto-chemically stained with MC tryptase and CD31. Fifteen cases of normal gingival tissue were considered as the control group. The mean MCC and MVD in superficial and deep connective tissues were assessed and total MCC and MVD was computed for each lesion. Results . Statistically significant differences were observed in MCC and MVD between the study groups (P < 0.001). MC tryptase and CD31 expression increased in the superficial connective tissue of each lesion in comparison to the deep con-nective tissue. A significant negative correlation was not found between MCC and MVD in oral reactive lesions (P < 0.001, r = -0.458). Conclusion. Although MCs were present in the reactive lesions of the oral cavity, a direct correlation between MCC and MVD was not found in these lesions. Therefore, a significant interaction between MCs and endothelial cells and an active role for MCs in the growth of oral reactive lesions was not found in this study.

Basal cell carcinoma: CD56 and cytokeratin 5/6 staining patterns in the differential diagnosis with Merkel cell carcinoma.

PubMed

Panse, Gauri; McNiff, Jennifer M; Ko, Christine J

2017-06-01

Basal cell carcinoma (BCC) can resemble Merkel cell carcinoma (MCC) on histopathological examination and while CK20 is a useful marker in this differential, it is occasionally negative in MCC. CD56, a sensitive marker of neuroendocrine differentiation, is sometimes used to identify MCC, but has been reportedly variably positive in BCC as well. In contrast, CK5/6 consistently labels BCC but is not expressed in neuroendocrine tumors. We evaluated 20 cases of BCC for the pattern of CD56 and cytokeratin 5/6 (CK5/6) staining, hypothesizing that these 2 stains could differentiate BCC from MCC in difficult cases. Seventeen cases of MCC previously stained with CD56 were also examined. All BCCs showed patchy expression of CD56 except for 2 cases, which showed staining of greater than 70% of tumor. CK5/6 was diffusely positive in all cases of BCC. Fifteen of 17 MCCs were diffusely positive for CD56. The difference in the pattern of CD56 expression between MCC and BCC (diffuse vs patchy, respectively) was statistically significant (P < .05). BCC typically shows patchy CD56 expression and diffuse CK5/6 positivity. These 2 markers can be used to distinguish between BCC and MCC in challenging cases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Complete Spontaneous Regression of Merkel Cell Carcinoma After Biopsy: A Case Report and Review of the Literature.

PubMed

Ahmadi Moghaddam, Parnian; Cornejo, Kristine M; Hutchinson, Lloyd; Tomaszewicz, Keith; Dresser, Karen; Deng, April; OʼDonnell, Patrick

2016-11-01

Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine tumor that typically occurs on the head and neck of the elderly and follows an aggressive clinical course. Merkel cell polyomavirus (MCPyV) has been identified in up to 80% of cases and has been shown to participate in MCC tumorigenesis. Complete spontaneous regression of MCC has been rarely reported in the literature. We describe a case of a 79-year-old man that presented with a rapidly growing, 3-cm mass on the left jaw. An incisional biopsy revealed MCC. Additional health issues were discovered in the preoperative workup of this patient which delayed treatment. One month after the biopsy, the lesion showed clinical regression in the absence of treatment. Wide excision of the biopsy site with sentinel lymph node dissection revealed no evidence of MCC 2 months later. The tumor cells in the patient's biopsy specimen were negative for MCPyV by polymerase chain reaction and immunohistochemistry (CM2B4 antibody, Santa Cruz, CA). The exact mechanism for complete spontaneous regression in MCC is unknown. To our knowledge, only 2 previous studies evaluated the presence of MCPyV by polymerase chain reaction in MCC with spontaneous regression. Whether the presence or absence of MCPyV correlates with spontaneous regression warrants further investigation.

Immune evasion mechanisms and immune checkpoint inhibition in advanced merkel cell carcinoma.

PubMed

Schadendorf, Dirk; Nghiem, Paul; Bhatia, Shailender; Hauschild, Axel; Saiag, Philippe; Mahnke, Lisa; Hariharan, Subramanian; Kaufman, Howard L

2017-01-01

Merkel cell carcinoma (MCC) is a rare skin cancer caused by Merkel cell polyomavirus (MCPyV) infection and/or ultraviolet radiation-induced somatic mutations. The presence of tumor-infiltrating lymphocytes is evidence that an active immune response to MCPyV and tumor-associated neoantigens occurs in some patients. However, inhibitory immune molecules, including programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), within the MCC tumor microenvironment aid in tumor evasion of T-cell-mediated clearance. Unlike chemotherapy, treatment with anti-PD-L1 (avelumab) or anti-PD-1 (pembrolizumab) antibodies leads to durable responses in MCC, in both virus-positive and virus-negative tumors. As many tumors are established through the evasion of infiltrating immune-cell clearance, the lessons learned in MCC may be broadly relevant to many cancers.

Diversity in the antibacterial potential of probiotic cultures Bacillus licheniformis MCC2514 and Bacillus licheniformis MCC2512.

PubMed

Shobharani, Papanna; Padmaja, Radhakrishnan J; Halami, Prakash M

2015-01-01

The aim of the present study was to investigate the characteristic diversity and stability of antimicrobial compounds produced by two probiotic strains of Bacillus licheniformis (MCC2514 and MCC2512). Antimicrobial compounds from the two strains notably varied, related to stability and potency. The inhibitory spectrum of B. licheniformis MCC2512 was higher than MCC2514, but, related to the effect on Micrococcus luteus ATCC9341, MCC2514 (LD50 = 450 AU ml(-1)) was more potent than MCC2512 (LD50 = 750 AU ml(-1)). The compounds were thermo-resistant and stable at a wide range of pH and exhibited considerable resistance to digestive enzymes and bile salts (anionic biological detergents), contributing to their appropriate application in various food systems. The isolate B. licheniformis MCC2512 gave a positive response to Bacillus subtilis-based biosensors BSF2470 and BS168.BS2, confirming the mode of action on the cell wall and subtilin-type, respectively. For B. licheniformis MCC2514, the mode of action was characterized by constructing B. subtilis reporters that interfered in five major biosynthetic pathways, i.e., biosynthesis of DNA, RNA, protein, the cell wall and fatty acids. B. licheniformis MCC2514 responded to the yvgS reporter, indicating it as an RNA synthesis inhibitor. Overall, the investigation reveals variability of the antimicrobial compounds from B. licheniformis of different origins and for their possible application as biopreservative agents. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial.

PubMed

Kaufman, Howard L; Russell, Jeffery S; Hamid, Omid; Bhatia, Shailender; Terheyden, Patrick; D'Angelo, Sandra P; Shih, Kent C; Lebbé, Céleste; Milella, Michele; Brownell, Isaac; Lewis, Karl D; Lorch, Jochen H; von Heydebreck, Anja; Hennessy, Meliessa; Nghiem, Paul

2018-01-19

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with poor survival outcomes in patients with distant metastatic disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2, prospective, open-label, single-arm trial in mMCC, avelumab-a human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody-showed promising efficacy and a safety profile that was generally manageable and tolerable. Here, we report the efficacy of avelumab after ≥1 year of follow-up in patients with distant mMCC that had progressed following prior chemotherapy for metastatic disease. Patients received avelumab 10 mg/kg by 1-h intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was best overall response. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Patients (N = 88) were followed for a minimum of 12 months. The confirmed objective response rate was 33.0% (95% CI, 23.3%-43.8%; complete response: 11.4%). An estimated 74% of responses lasted ≥1 year, and 72.4% of responses were ongoing at data cutoff. Responses were durable, with the median DOR not yet reached (95% CI, 18.0 months-not estimable), and PFS was prolonged; 1-year PFS and OS rates were 30% (95% CI, 21%-41%) and 52% (95% CI, 41%-62%), respectively. Median OS was 12.9 months (95% CI, 7.5-not estimable). Subgroup analyses suggested a higher probability of response in patients receiving fewer prior lines of systemic therapy, with a lower baseline disease burden, and with PD-L1-positive tumors; however, durable responses occurred irrespective of baseline factors, including tumor Merkel cell polyomavirus status. With longer follow-up, avelumab continues to show durable responses and promising survival outcomes in patients with distant mMCC whose disease had progressed after chemotherapy. Clinicaltrials.gov identifier: NCT02155647.

Rationale for immune-based therapies in Merkel polyomavirus-positive and -negative Merkel cell carcinomas.

PubMed

Vandeven, Natalie; Nghiem, Paul

2016-07-01

Merkel cell carcinoma (MCC) is a rare but often deadly skin cancer that is typically caused by the Merkel cell polyomavirus (MCPyV). Polyomavirus T-antigen oncoproteins are persistently expressed in virus-positive MCCs (˜80% of cases), while remarkably high numbers of tumor-associated neoantigens are detected in virus-negative MCCs, suggesting that both MCC subsets may be immunogenic. Here we review mechanisms by which these immunogenic tumors evade multiple levels of host immunity. Additionally, we summarize the exciting potential of diverse immune-based approaches to treat MCC. In particular, agents blocking the PD-1 axis have yielded strikingly high response rates in MCC as compared with other solid tumors, highlighting the potential for immune-mediated treatment of this disease.

Aberrant Promoter Hypermethylation of RASSF Family Members in Merkel Cell Carcinoma

PubMed Central

Richter, Antje M.; Haag, Tanja; Walesch, Sara; Herrmann-Trost, Peter; Marsch, Wolfgang C.; Kutzner, Heinz; Helmbold, Peter; Dammann, Reinhard H.

2013-01-01

Merkel cell carcinoma (MCC) is one of the most aggressive cancers of the skin. RASSFs are a family of tumor suppressors that are frequently inactivated by promoter hypermethylation in various cancers. We studied CpG island promoter hypermethylation in MCC of RASSF2, RASSF5A, RASSF5C and RASSF10 by combined bisulfite restriction analysis (COBRA) in MCC samples and control tissue. We found RASSF2 to be methylated in three out of 43 (7%), RASSF5A in 17 out of 39 (44%, but also 43% in normal tissue), RASSF5C in two out of 26 (8%) and RASSF10 in 19 out of 84 (23%) of the cancer samples. No correlation between the methylation status of the analyzed RASSFs or between RASSF methylation and MCC characteristics (primary versus metastatic, Merkel cell polyoma virus infection, age, sex) was found. Our results show that RASSF2, RASSF5C and RASSF10 are aberrantly hypermethylated in MCC to a varying degree and this might contribute to Merkel cell carcinogenesis. PMID:24252868

Merkel cell carcinoma - recent advances in the biology, diagnostics and treatment.

PubMed

Czapiewski, Piotr; Biernat, Wojciech

2014-08-01

Merkel cell carcinoma (MCC) is an uncommon primary cutaneous carcinoma with neuroendocrine differentiation. Since recent discovery of MCCs strong association with Merkel cell polyomavirus (MCPyV), there has been a rapid increase in the understanding of the carcinomas genetics, molecular biology and pathogenesis. In our study, we reviewed recent advances and controversies concerning MCC histogenesis, epidemiology, diagnostic and prognostic markers. We analyzed the association of MCPyV with MCC and the possible new targets for therapy. We also examined English-based literature regarding MCC pathogenesis published between 2008 and 2013, which lead to a deeper understanding of the topic. Our study showed that the association of MCPyV strongly influences the course of MCC. Additionally, it has been shown that a immunological response to MCPyV may in the future give hope to identify new therapeutic strategies in treatment of this fatal malignancy. This article is part of a Directed Issue entitled: Rare Cancers. Copyright © 2014 Elsevier Ltd. All rights reserved.

Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus

PubMed Central

Stakaitytė, Gabrielė; Wood, Jennifer J.; Knight, Laura M.; Abdul-Sada, Hussein; Adzahar, Noor Suhana; Nwogu, Nnenna; Macdonald, Andrew; Whitehouse, Adrian

2014-01-01

A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC. PMID:24978434

Detection and quantification of Merkel cell polyomavirus. Analysis of Merkel cell carcinoma cases from 1977 to 2015.

PubMed

Álvarez-Argüelles, Marta E; Melón, Santiago; Rojo, Susana; Fernandez-Blázquez, Ana; Boga, Jose A; Palacio, Ana; Vivanco, Blanca; de Oña, María

2017-12-01

This study investigates the presence of Merkel cell polyomavirus (MCPyV) in skin lesions of patients with Merkel cell carcinoma (MCC). MCPyV was quantified using quantitative Real-Time-PCR (qRT-PCR) in 34 paraffinized MCC samples (resected/biopsied) originally taken between 1977 and 2015, and six non-MCC samples. In 31 (91.2%) MCC-individuals, MCPyV was detected. No virus was observed in any non-MCC tumor. Average age at diagnosis was 78.2 ± 9.35 (55-97) years for women (n = 19) and 69.5 ± 14.7 (45-91) for men (n = 15) (P = 0.04). MCC tumor location, known in 25 cases, was: 11 (44%) in the head region, 6 (24%) in upper limbs, 4 (16%) in lower limbs, and 4 (16%) in the trunk. All but one patient had received some sort of treatment: 15 (45.45%) underwent both radio and chemotherapy, 13 (39.39%) only surgery, 2 (6.06%) surgery, plus radio and chemotherapy, 2 (6.06%) surgery and chemotherapy, and 1 (3.03%) only radiotherapy. Follow up data were available for 21/34 patients: recurrence was recorded for 4 (19.04%), and metastasis for 13 (61.9%). Recorded data showed that 10 men and 5 women (total 44.1%) died during follow up, 7 (46.7%) of them within 2 years of diagnosis. Viral load was 5.8 ± 1.4 log copies/10 5 cells (3.1-8.6), independent of any variable. MCPyV was very frequent in MCC. It was principally associated with head and limb tumors, it more commonly affected men, who in this study were, on average, younger than women, and had high rates of recurrence and mortality. The amplification techniques described here are easily applied and suitable for detecting the presence of MCPyV virus in MCC. © 2017 Wiley Periodicals, Inc.

Merkel cell carcinoma with fingolimod treatment for multiple sclerosis: A case report.

PubMed

Mahajan, Kedar R; Ko, Jennifer S; Tetzlaff, Michael T; Hudgens, Courtney W; Billings, Steven D; Cohen, Jeffrey A

2017-10-01

Neoplasms and reactivation of latent viruses have been observed in individuals taking fingolimod. Merkel cell carcinoma (MCC), a rare neuroendocrine skin cancer, is associated with immunosuppression and can be triggered by the oncogenic Merkel cell polyoma virus (MCPyV). We report a case of a 61-year-old man with multiple sclerosis who developed MCPyV-positive MCC 4 years after starting fingolimod. This is the second report of MCC associated with MCPyV in an individual on fingolimod. Copyright © 2017 Elsevier B.V. All rights reserved.

Bifidobacterium breve MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect

PubMed Central

MURATA, Kozue; TOMOSADA, Yohsuke; VILLENA, Julio; CHIBA, Eriko; SHIMAZU, Tomoyuki; ASO, Hisashi; IWABUCHI, Noriyuki; XIAO, Jin-zhong; SAITO, Tadao; KITAZAWA, Haruki

2014-01-01

Bifidobacterium breve MCC-117 is able to significantly reduce the expression of inflammatory cytokines in porcine intestinal epithelial (PIE) cells and to improve IL-10 levels in CD4+CD25high Foxp3+ lymphocytes in response to heat-stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular patterns (PAMPs), while the immunoregulatory effect of B. adolescentis ATCC15705 was significantly lower than that observed for the MCC-117 strain. Considering the different capacities of the two bifidobacterium strains to activate toll-like receptor (TLR)-2 and their differential immunoregulatory activities in PIE and immune cells, we hypothesized that comparative studies with both strains could provide important information regarding the molecular mechanism(s) involved in the anti-inflammatory activity of bifidobacteria. In this work, we demonstrated that the anti-inflammatory effect of B. breve MCC-117 was achieved by a complex interaction of multiple negative regulators of TLRs as well as inhibition of multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable ETEC PAMP-induced NF-κB, p38 MAPK and PI3 K activation and expression of pro-inflammatory cytokines in PIE cells. In addition, we demonstrated that B. breve MCC-117 may activate TLR2 synergistically and cooperatively with one or more other pattern recognition receptors (PRRs), and that interactions may result in a coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and SIGIRR. Upregulation of these negative regulators could have an important physiological impact on maintaining or reestablishing homeostatic TLR signals in PIE cells. Therefore, in the present study, we gained insight into the molecular mechanisms involved in the immunoregulatory effect of B. breve MCC-117. PMID:24936377

PD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma.

PubMed

Gaiser, Maria Rita; Bongiorno, Michelle; Brownell, Isaac

2018-04-01

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that lacks durable responses to traditional chemotherapy. Areas covered: After MCC was shown to be an immunogenic tumor, small trials revealed high objective response rates to PD-1/PD-L1 checkpoint inhibitors. The JAVELIN Merkel 200 (NCT02155647) trial tested the use of avelumab, a human IgG1 monoclonal antibody against PD-L1, in metastatic MCC. Avelumab recently became the first approved drug for metastatic MCC. Expert commentary: By conducting broad phase I studies assessing the safety of avelumab and a small phase II study demonstrating efficacy in this rare orphan tumor type, avelumab gained accelerated approval for the treatment of metastatic MCC. Additional studies are needed to determine how the antibody-dependent cellular cytotoxicity (ADCC) competent Fc region of avelumab contributes to disease control. Remaining questions: Longer follow-up will determine the durability of checkpoint blockade in controlling metastatic MCC. Additional studies will assess the utility and safety of adjuvant checkpoint blockade in patients with excised MCC. How to increase response rates by combining PD-1/PD-L1 blockade with other treatment approaches needs to be explored. In addition, treatment options for MCC patients who fail or do not respond to avelumab need to be identified.

Avelumab and other recent advances in Merkel cell carcinoma.

PubMed

Bommareddy, Praveen K; Kaufman, Howard L

2017-12-01

Merkel cell carcinoma (MCC) is a rare but aggressive form of skin cancer that occurs in the elderly, is associated with UV radiation and immunosuppression. Initial treatment consists of wide excision with adjuvant radiation. Although the tumor is sensitive to chemotherapy, long-term survival is unusual and there had been no US FDA-approved drugs prior to 2017. The recognition that MCC is associated with the Merkel cell polyomavirus occurs more commonly in immune-compromised patients and tumors express PD-L1 suggested testing immunotherapy. A study of an anti-PD-L1 antibody, avelumab, in chemotherapy-refractory MCC demonstrated a response rate of 31.8% resulting in FDA approval in March 2017 and EMA in September 2017. This review will discuss the disease, role of avelumab and other emerging treatment strategies for MCC.

Advances in Merkel cell carcinoma from a pathologist's perspective.

PubMed

Barksdale, Sarah Kay

2017-10-01

Merkel cell carcinoma (MCC) is a rarely made but potentially devastating diagnosis. While local disease might be cured by surgery and radiotherapy, advanced disease is usually rapidly progressive and fatal. Until very recently, the only approach to metastatic MCC was cytotoxic chemotherapy with results so disappointing that current treatment guidelines discourage its use and recommend clinical trial as a more viable treatment option. Fortunately, recent advances in the understanding of the molecular pathogenesis of this tumour have produced a wide variety of experimental treatments for MCC, some of which are quite promising. The most current information regarding the diagnosis, staging, management of this tumour is briefly presented as well as new insights into the molecular basis of MCC and therapeutic approaches to MCC. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Merkel cell carcinoma with seborrheic keratosis: A unique association.

PubMed

Anand, Murthy S; Krishnamurthy, Shantha; Ravindranath, Suvarna; Ranganathan, Jyothi

2018-01-01

Merkel cell carcinoma (MCC) is a rare, clinically aggressive neuroendocrine carcinoma of the skin; MCC is 40 times less common as compared to melanoma. The most frequently reported sites have been the head and neck, extremities, and trunk. Potential mimics include malignant melanoma, lymphoma, or metastatic small cell (neuroendocrine) carcinomas. Histopathology of MCC resembles small cell carcinoma both morphologically and on IHC. The possible cell of origin was proposed as the Merkel cell, which functions as a mechanoreceptor. It has a high chance of local recurrence, regional and distant spread. In recent times, Merkel cell polyomavirus has been implicated as the causative agent for this tumor. The same agent has a reported etiologic association with other skin lesions, including seborrheic keratosis.

Living with Merkel Cell Carcinoma (MCC): Development of a Conceptual Model of MCC Based on Patient Experiences.

PubMed

Kaufman, Howard L; Dias Barbosa, Carla; Guillemin, Isabelle; Lambert, Jérémy; Mahnke, Lisa; Bharmal, Murtuza

2018-03-06

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with limited treatment options at advanced stages. There is a paucity of data available regarding the impact of MCC and its management on patients' lives. This study aimed to address this gap by interviewing patients with metastatic MCC entering a trial of an immunotherapy (avelumab). In a single-arm, open-label, international, phase 2 trial in patients with stage IV, chemotherapy-refractory, histologically confirmed MCC, patients were invited to participate in semi-structured phone interviews. These were conducted before avelumab administration. Interview transcripts were analysed qualitatively to identify concepts important to patients relating to their experience of metastatic MCC and its management. Nineteen patients were interviewed. Most reported MCC to be painless and asymptomatic. They reported being often misdiagnosed and described a long process before receiving the correct diagnosis. They also reported a feeling of "shock" after being informed of the severity and seriousness of their cancer. Overall, patients did not report impaired physical and cognitive capacities or impact on daily lives, either before or after diagnosis. However, patients and their relatives reported feelings of "worry" and "fear" about the unknown outcome of the disease. Chemotherapy and radiotherapy negatively affected patients physically and psychologically in their everyday lives. MCC disease was not perceived by the interviewed patients to result in severe functional limitations or to severely impact everyday activities, but was associated with substantial negative psychological impact. In contrast, chemotherapy and radiotherapy for MCC are highly debilitating and disrupt patients' lives. CLINICALTRIALS. NCT02155647.

Merkel cell polyomavirus and Merkel cell carcinoma.

PubMed

DeCaprio, James A

2017-10-19

Merkel cell polyomavirus (MCPyV) causes the highly aggressive and relatively rare skin cancer known as Merkel cell carcinoma (MCC). MCPyV also causes a lifelong yet relatively innocuous infection and is one of 14 distinct human polyomaviruses species. Although polyomaviruses typically do not cause illness in healthy individuals, several can cause catastrophic diseases in immunocompromised hosts. MCPyV is the only polyomavirus clearly associated with human cancer. How MCPyV causes MCC and what oncogenic events must transpire to enable this virus to cause MCC is the focus of this essay.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).

Merkel cell carcinoma: Current US incidence and projected increases based on changing demographics.

PubMed

Paulson, Kelly G; Park, Song Youn; Vandeven, Natalie A; Lachance, Kristina; Thomas, Hannah; Chapuis, Aude G; Harms, Kelly L; Thompson, John A; Bhatia, Shailender; Stang, Andreas; Nghiem, Paul

2018-03-01

Merkel cell carcinoma (MCC) incidence rates are rising and strongly age-associated, relevant for an aging population. Determine MCC incidence in the United States and project incident cases through the year 2025. Registry data were obtained from the SEER-18 Database, containing 6600 MCC cases. Age- and sex-adjusted projections were generated using US census data. During 2000-2013, the number of reported solid cancer cases increased 15%, melanoma cases increased 57%, and MCC cases increased 95%. In 2013, the MCC incidence rate was 0.7 cases/100,000 person-years in the United States, corresponding to 2488 cases/year. MCC incidence increased exponentially with age, from 0.1 to 1.0 to 9.8 (per 100,000 person-years) among age groups 40-44 years, 60-64 years, and ≥85 years, respectively. Due to aging of the Baby Boomer generation, US MCC incident cases are predicted to climb to 2835 cases/year in 2020 and 3284 cases/year in 2025. We assumed that the age-adjusted incidence rate would stabilize, and thus, the number of incident cases we projected might be an underestimate. An aging population is driving brisk increases in the number of new MCC cases in the United States. This growing impact combined with the rapidly evolving therapeutic landscape warrants expanded awareness of MCC diagnosis and management. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Alternative site of implantation affects tumor malignancy and metastatic potential in mice: its comparison to the flank model.

PubMed

Speroni, Lucia; Bustuoabad, Victoria de Los Angeles; Gasparri, Julieta; Chiaramoni, Nadia Silvia; Taira, María Cristina; Ruggiero, Raúl Alejandro; Alonso, Silvia Del Valle

2009-02-01

MC-C fibrosarcoma and B16F0 melanoma tumors were implanted intradermally in the dorsal region of the foot of mice. Tumor progression was compared to standard implantation in the flank. Although foot tumors only reached 13% (MC-C) and 25% (B16F0) of the mean volume of flank tumors, a more malignant phenotype in terms of histology and survival rate was observed in this type of tumors. Moreover, lung metastases were only detected in hosts bearing foot tumors, in contrast to MC-C and B16F0 populations with tumors growing in the flank. In addition, cellular influx and local immune reaction were higher in the dorsal region of the foot. According to our results, the dermis of the flank allows excessive tumor growth due to its low reactivity. Thus, differences in innate and adaptive immune effectors between the evaluated tumor microenvironments would account for the differences in tumor malignancy. Due to its striking differences with the standard flank inoculation, the tumor implantation model herein introduced could be a valuable tool to study the metastatic potential of different cell lines and the microenvironment components affecting tumor growth.

PD-L1 blockade with avelumab: A new paradigm for treating Merkel cell carcinoma.

PubMed

Barkdull, Savannah; Brownell, Isaac

2017-12-02

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer. Until recently, no durable treatment options were available for patients with advanced disease. As an immunogenic cancer, MCC was hypothesized to be a candidate for PD-L1/PD-1 targeted therapy. On March 23, 2017 the US Food and Drug Administration granted accelerated approval for avelumab, an anti-PD-L1 monoclonal antibody, for the treatment of metastatic MCC on the basis of the JAVELIN Merkel 200 trial. Here we examine the results and implications of this pivotal study, published in Lancet Oncology by Kaufman et al., as well as current developments in the use of immune-checkpoint therapies for treating patients with MCC.

Balanced and Unbalanced Circulations in a Primitive Equation Simulation of a Midlatitude MCC. Part I: The Numerical Simulation.

NASA Astrophysics Data System (ADS)

Olsson, Peter Q.; Cotton, William R.

1997-02-01

A midlatitude mesoscale convective complex (MCC), which occurred over the central United States on 23-24 June 1985, was simulated using the Regional Atmospheric Modeling System (RAMS). The multiply nested-grid simulation agreed reasonably well with surface, upper-air, and satellite observations and ground-based radar plots. The simulated MCC had a typical structure consisting of a leading line of vigorous convection and a trailing region of less intense stratiform rainfall. Several other characteristic MCC circulations were also simulated: a divergent cold pool in the lower troposphere, midlevel convergence coupled with a relatively cool descending rear-inflow jet, and relatively warm updraft structure, and a cold divergent anticyclone in the tropopause region. Early in the MCC simulation, a mesoscale convectively induced vortex (MCV) formed on the eastern edge of the convective line. While frequently associated with MCCs and other mesoscale convective systems (MCSs), MCVs are more typically reported in the mature and decaying stages of the life cycle. Several hours later, a second MCV formed near the opposite end of the convective line, and by the mature phase of the MCC, these MCVs were embedded within a more complex system-wide vortical flow in the lower troposphere.Analysis of the first MCV during its incipient phase indicates that the vortex initially formed near the surface by convergence/stretching of the large low-level ambient vertical vorticity in this region. Vertical advection appeared largely responsible for the upward extension of this MCV to about 3.5 km above the surface, with tilting of horizontal vorticity playing a secondary role. This mechanism of MCV formation is in contrast to recent idealized high-resolution squall line simulations, where MCVs were found to result from the tilting into the vertical of storm-induced horizontal vorticity formed near the top of the cold pool.Another interesting aspect of the simulation was the development of a banded vorticity structure at midtropospheric levels. These bands were found to be due to the apparent vertical transport of zonal momentum by the descending rear-to-front circulation, or rear-inflow jet. An equivalent alternative viewpoint of this process, deformation of horizontal vorticity filaments by the convective updrafts and rear-inflow jet, is discussed.Part II of this work presents a complementary approach to the analysis presented here, demonstrating that the circulations seen in this MCC simulation are, to a large degree, contained within the nonlinear balance approximation, the related balanced omega equation, and the PV as analyzed from the PE model results.

Study of multi-kilowatt solar arrays for Earth orbit applications

NASA Technical Reports Server (NTRS)

Patterson, R. E.

1983-01-01

A miniaturized Cassegrainian concentrator (MCC) solar array concept is being developed with the objective of significantly reducing the recurring cost of multikilowatt solar arrays. The desired cost reduction is obtained as a result of using very small high efficiency solar cells in conjuction with low cost optics. The MCC single element concept incident slar radiation is reflected rom a primary parabolic reflector to a secondary hyperbolic reflector and finally to a 4 millimeter diameter solar cell. A light catcher cone is used to improve off axis performance. The solar cell is mounted to a heat fin. An element is approximately 13 millimeters thick which permits efficient launch stowage of the concentrator system panels without complex optical component deployments or retractions. The MCC elements are packed in bays within graphite epoxy frames and are electrically connected into appropriate series-parallel circuits. A MCC sngle element with a 21 sq cm entrance aperture and a 20 efficient, 0.25 sq cm gallium arsenide solar cell has the same power output as 30 sq cm of 11-percent efficiency (at 68 C) silicon solar cells.

Design, fabrication and delivery of a miniature Cassegrainian concentrator solar array system

NASA Technical Reports Server (NTRS)

Kruer, Mark A.

1987-01-01

The optical design of the miniature Cassegrainian concentrator (MCC) element was improved for both offpoint and onpoint power capability. The cell stack design has shown no losses under the high short term thermal stresses imposed by component level test and is projected to be capable of greater than five years thermal cycle life in low Earth orbit. The structural design met all requirements for stiffness and flatness and requires adjustable inserts for fine tuning of the GFRP structure to meet flatness goals. The completed, fully populated small and large MCC panels deliverable under this contract perform electrically as expected. A solid acceptance inspection program to guarantee quality of all purchased parts, and continued manufacturing process improvements will make the MCC design a viable low cost alternative to standard flat panel technology. Minor improvements to the cell stack design of the MCC element can make significant improvements in both the performance and manufacturability of the MCC system.

Demographics and Outcomes of Stage I-II Merkel Cell Carcinoma Treated with Mohs Micrographic Surgery Compared with Wide Local Excision in the National Cancer Data Base.

PubMed

Singh, Babu; Qureshi, Muhammad M; Truong, Minh Tam; Sahni, Debjani

2018-02-03

The optimal surgical approach (wide local excision (WLE) vs. Mohs micrographic surgery (MOHS)) for treating Merkel cell carcinoma (MCC) is yet to be determined. To compare survival outcomes in patients with early stage MCC treated with MOHS versus WLE. A retrospective review of all cases in the National Cancer Data Base (NCDB) of MCC of clinical Stage I-II MCC treated with WLE or MOHS was performed. 1,795 cases of Stage I-II MCC were identified who underwent WLE (N=1,685) or MOHS (N=110). There was no difference in residual tumor on surgical margins between the two treatment groups (p=0.588). On multivariate analysis, there was no difference in overall survival between the treatment modalities (adjusted HR 1.02; 95% CI 0.72-1.45, p=0.897). There was no difference in overall survival between the two groups on propensity score matched analysis. Disease specific survival was not reported as this data in not available in the NCDB. MOHS appears to be as effective as WLE in treating early stage MCC. Copyright © 2018. Published by Elsevier Inc.

The effects of particle recycling on the divertor plasma: A particle-in-cell with Monte Carlo collision simulation

NASA Astrophysics Data System (ADS)

Chang, Mingyu; Sang, Chaofeng; Sun, Zhenyue; Hu, Wanpeng; Wang, Dezhen

2018-05-01

A Particle-In-Cell (PIC) with Monte Carlo Collision (MCC) model is applied to study the effects of particle recycling on divertor plasma in the present work. The simulation domain is the scrape-off layer of the tokamak in one-dimension along the magnetic field line. At the divertor plate, the reflected deuterium atoms (D) and thermally released deuterium molecules (D2) are considered. The collisions between the plasma particles (e and D+) and recycled neutral particles (D and D2) are described by the MCC method. It is found that the recycled neutral particles have a great impact on divertor plasma. The effects of different collisions on the plasma are simulated and discussed. Moreover, the impacts of target materials on the plasma are simulated by comparing the divertor with Carbon (C) and Tungsten (W) targets. The simulation results show that the energy and momentum losses of the C target are larger than those of the W target in the divertor region even without considering the impurity particles, whereas the W target has a more remarkable influence on the core plasma.

History of chronic inflammatory disorders increases the risk of Merkel cell carcinoma, but does not correlate with Merkel cell polyomavirus infection.

PubMed

Sahi, Helka; Sihto, Harri; Artama, Miia; Koljonen, Virve; Böhling, Tom; Pukkala, Eero

2017-01-17

We aimed to assess the connection between chronic inflammatory disorders (CIDs) and Merkel cell carcinoma (MCC). Merkel cell carcinoma cases diagnosed in 1978-2009 were extracted from the Finnish Cancer Registry and controls from the Population Registry. Information on reimbursed CIDs was linked to clinicopathological data including Merkel cell polyomavirus (MCV) status by qPCR and immunohistochemistry for the large T antigen of MCV (LTA), Ki-67 and tumour-infiltrating lymphocytes. Chronic inflammatory disorders increased the risk of MCC significantly (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.03-1.88), specifically connective tissue/systemic diseases (OR 1.75, 95% CI 1.09-1.80) and diabetic conditions (OR 1.51, 95% CI 1.03-2.22). Chronic inflammatory disorders associated with larger tumour diameter (P=0.02) and higher Ki-67 expression (P=0.005). The expression of LTA was seen significantly more often in the absence of CIDs (P=0.05). Patients with CID are at significantly higher risk for aggressive MCC. Merkel cell polyomavirus positivity is more common in MCC patients unafflicted by CID.

Is this the end of cytotoxic chemotherapy in Merkel cell carcinoma?

PubMed Central

Rabinowits, Guilherme

2017-01-01

Although cytotoxic chemotherapy has been used often in the management of Merkel cell carcinoma (MCC), its benefit remains uncertain. Despite being considered a chemosensitive disease, the duration of response is generally short, and the survival benefit is unclear. With the recent FDA approval of the anti-programmed cell death ligand 1 (PD-L1) antibody avelumab for patients with advanced MCC and the limited and controversial data on chemotherapy, it is important to put in perspective whether conventional chemotherapy should remain an option for these patients. Here, we review the evidence and controversies around chemotherapy in MCC as well as two recent studies on immunotherapy that changed the treatment paradigm for this disease. PMID:29033592

Characterization and Properties of Micro-arc Composite Ceramic Coatings on Magnesium Alloys

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

Zhang, Long; Jiang, Bailing; Ge, Yanfeng

2013-05-21

Magnesium alloys are of growing interest for many industrial applications due to their favorable strength-to-weight ratio and excellent cast ability. However, one of the limiting factors in the use of magnesium on production vehicles is its poor corrosion resistance. Micro-arc Composite Ceramic (MCC) coatings on AZ91D magnesium alloys were prepared in combination with Micro-arc Oxidation (MAO) and electrophoresis technologies. The microstructure, corrosion resistance, abrasion resistance, stone impact resistance, thermal shock resistance and adhesion of MCC coating were studied, respectively. The surface and cross-section morphologies of MAO and MCC coating showed that the outer organic coating filled the holes on themore » surface of the MAO coating. It acted as a shelter on the MAO coating surface when the MCC coatings were exposed to corrosive environments. The corrosion resistance of the MCC coating was characterized by a copper-accelerated acetic acid salt spray test. The testing results showed that the creep back from scribe lines was less than 1mm and completely fit the evaluation standard. The composite structure of the MCC coating vastly improved the corrosion resistance of Mg alloys. According to testing standards, the resistance to abrasion, stone impact resistance, thermal shock resistance and adhesion of MCC coatings completely met the evaluation standard requirements. The MCC coated AZ91D magnesium alloys possessed excellent properties; this is a promising corrosion and wear resistance surface treatment technology on magnesium alloys for production vehicles.« less

Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study.

PubMed

Paulson, Kelly G; Lewis, Christopher W; Redman, Mary W; Simonson, William T; Lisberg, Aaron; Ritter, Deborah; Morishima, Chihiro; Hutchinson, Kathleen; Mudgistratova, Lola; Blom, Astrid; Iyer, Jayasri; Moshiri, Ata S; Tarabadkar, Erica S; Carter, Joseph J; Bhatia, Shailender; Kawasumi, Masaoki; Galloway, Denise A; Wener, Mark H; Nghiem, Paul

2017-04-15

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases per year in the United States, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV oncoprotein (T-antigens) have been correlated with MCC tumor burden. The present study assesses the clinical utility of MCPyV-oncoprotein antibody titers for MCC prognostication and surveillance. MCPyV-oncoprotein antibody detection was optimized in a clinical laboratory. A cohort of 219 patients with newly diagnosed MCC were followed prospectively (median follow-up, 1.9 years). Among the seropositive patients, antibody titer and disease status were serially tracked. Antibodies to MCPyV oncoproteins were rare among healthy individuals (1%) but were present in most patients with MCC (114 of 219 patients [52%]; P < .01). Seropositivity at diagnosis independently predicted decreased recurrence risk (hazard ratio, 0.58; P = .04) in multivariate analyses adjusted for age, sex, stage, and immunosuppression. After initial treatment, seropositive patients whose disease did not recur had rapidly falling titers that became negative by a median of 8.4 months. Among seropositive patients who underwent serial evaluation (71 patients; 282 time points), an increasing oncoprotein titer had a positive predictive value of 66% for clinically evident recurrence, whereas a decreasing titer had a negative predictive value of 97%. Determination of oncoprotein antibody titer assists in the clinical management of patients with newly diagnosed MCC by stratifying them into a higher risk seronegative cohort, in which radiologic imaging may play a more prominent role, and into a lower risk seropositive cohort, in which disease status can be tracked in part by oncoprotein antibody titer. Cancer 2017;123:1464-1474. © 2016 American Cancer Society. © 2016 American Cancer Society.

Examining Merkel Cell Polyomavirus Minor Capsid Proteins | Center for Cancer Research

Cancer.gov

Merkel cell polyomavirus (MCV or MCPyV) is a recently discovered member of the viral family Polyomaviridae. It is a skin-dwelling polyomavirus species that appears to cause a rare but highly lethal form of skin cancer called Merkel cell carcinoma (MCC). Despite MCC being uncommon, chronic MCV infection of human skin is widespread, and most infected people have no known

Identification of Key Amino Acid Residues Modulating Intracellular and In vitro Microcin E492 Amyloid Formation

PubMed Central

Aguilera, Paulina; Marcoleta, Andrés; Lobos-Ruiz, Pablo; Arranz, Rocío; Valpuesta, José M.; Monasterio, Octavio; Lagos, Rosalba

2016-01-01

Microcin E492 (MccE492) is a pore-forming bacteriocin produced and exported by Klebsiella pneumoniae RYC492. Besides its antibacterial activity, excreted MccE492 can form amyloid fibrils in vivo as well as in vitro. It has been proposed that bacterial amyloids can be functional playing a biological role, and in the particular case of MccE492 it would control the antibacterial activity. MccE492 amyloid fibril’s morphology and formation kinetics in vitro have been well-characterized, however, it is not known which amino acid residues determine its amyloidogenic propensity, nor if it forms intracellular amyloid inclusions as has been reported for other bacterial amyloids. In this work we found the conditions in which MccE492 forms intracellular amyloids in Escherichia coli cells, that were visualized as round-shaped inclusion bodies recognized by two amyloidophilic probes, 2-4′-methylaminophenyl benzothiazole and thioflavin-S. We used this property to perform a flow cytometry-based assay to evaluate the aggregation propensity of MccE492 mutants, that were designed using an in silico prediction of putative aggregation hotspots. We established that the predicted amino acid residues 54–63, effectively act as a pro-amyloidogenic stretch. As in the case of other amyloidogenic proteins, this region presented two gatekeeper residues (P57 and P59), which disfavor both intracellular and in vitro MccE492 amyloid formation, preventing an uncontrolled aggregation. Mutants in each of these gatekeeper residues showed faster in vitro aggregation and bactericidal inactivation kinetics, and the two mutants were accumulated as dense amyloid inclusions in more than 80% of E. coli cells expressing these variants. In contrast, the MccE492 mutant lacking residues 54–63 showed a significantly lower intracellular aggregation propensity and slower in vitro polymerization kinetics. Electron microscopy analysis of the amyloids formed in vitro by these mutants revealed that, although with different efficiency, all formed fibrils morphologically similar to wild-type MccE492. The physiological implication of MccE492 intracellular amyloid formation is probably similar to the inactivation process observed for extracellular amyloids, and could be used as a mean of sequestering potentially toxic species inside the cell when this bacteriocin is produced in large amounts. PMID:26858708

Incidence and survival for Merkel cell carcinoma in Queensland, Australia, 1993-2010.

PubMed

Youlden, Danny R; Soyer, H Peter; Youl, Philippa H; Fritschi, Lin; Baade, Peter D

2014-08-01

Merkel cell carcinoma (MCC) is an uncommon but highly invasive form of skin cancer. The mechanisms that cause MCC are yet to be fully determined. To compare the incidence and survival rates of MCC in Queensland, Australia, known to be a high-risk area, with MCC incidence and survival elsewhere in the world. We also analyzed incidence trends and differences in survival by key demographic and clinical characteristics. Retrospective cohort study of population-based administrative data for MCC collected by the Queensland Cancer Registry and supplemented with detailed histopathologic data. Deidentified records were obtained of all Queensland residents diagnosed as having MCC during the period from 1993 to 2010. A subsample of histopathologic records were reviewed by a senior dermatopathologist to determine the potential for misclassification. A total of 879 eligible cases of MCC were included in the study. Incidence rates were directly age standardized to the 2000 United States Standard Population. Trends were examined using Joinpoint software with results expressed in terms of the annual percentage change. The period method was used to calculate 5-year relative survival, and adjusted hazard ratios were obtained from multivariate Poisson models. There were 340 cases of MCC diagnosed in Queensland between 2006 and 2010, corresponding to an incidence rate of 1.6 per 100,000 population. Men (2.5 per 100,000) had higher incidence than women (0.9 per 100,000), and rates peaked at 20.7 per 100,000 for persons 80 years or older. The overall incidence of MCC increased by an average of 2.6% per year from 1993 onwards. Relative survival was 41% after 5 years, with significantly better survival found for those younger than 70 years at diagnosis (56%-60%), those with tumors on the face or ears (51%), and those with stage I lesions (49%). Incidence rates for MCC in Queensland are at least double those of any that have been previously published elsewhere in the world. It is likely that Queensland's combination of a predominantly white population, outdoor lifestyle, and exposure to sunlight has played a role in this unwanted result. Interventions are required to increase awareness of MCC among clinicians and the public.

Tumor-Infiltrating Merkel Cell Polyomavirus-Specific T Cells Are Diverse and Associated with Improved Patient Survival. | Office of Cancer Genomics

Cancer.gov

Tumor-infiltrating CD8+ T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8+ T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome.

Correlation of Merkel cell polyomavirus positivity with PDGFRα mutations and survivin expression in Merkel cell carcinoma.

PubMed

Batinica, M; Akgül, B; Silling, S; Mauch, C; Zigrino, P

2015-07-01

Merkel cell carcinoma (MCC) is a neuroendocrine cancer of the skin postulated to originate through Merkel cell polyomavirus (MCPyV) oncogenesis and/or by mutations in molecules implicated in the regulation of cell growth and survival. Despite the fact that MCPvV is detected more broadly within the population, only a part of the infected people also develop MCC. It is thus conceivable that together, virus and for example mutations, are necessary for disease development. However, apart from a correlation between MCPyV positivity or mutations and MCC development, less is known about the association of these factors with progressive disease. To analyze MCPyV positivity, load and integration in MCC as well as presence of mutations in PDGFRα and TP53 genes and correlate these with clinical features and disease progression to identify features with prognostic value for clinical progression. This is a study on a MCC population group of 64 patients. MCPyV positivity, load and integration in parallel to mutations in the PDGFRα and TP53 were analyzed on genomic DNA from MCC specimens. In addition, expression of PDGFRα, survivin and p53 proteins was analyzed by immunodetection in tissues specimens. All these parameters were analyzed as function of patient's disease progression status. 83% of MCCs were positive for the MCPyV and among these 36% also displayed virus-T integration. Viral load ranged from 0.006 to 943 viral DNA copies/β-globin gene and was highest in patients with progressive disease. We detected more than one mutation within the PDGFRα gene and identified two new SNPs in 36% of MCC patients, whereas no mutations were found in TP53 gene. Survivin was expressed in 78% of specimens. We could not correlate either mutations in PDGFR or expression of PDGFR, p53 and surviving either to the disease progression or to the MCPyV positivity. In conclusion, our data indicate that the viral positivity when associated with high viral load, correlates with poor disease outcome. Frequent mutations in the PDGFRα gene and high survivin expression were found in MCC independent of the viral positivity. These data suggest that these three factors independently contribute to Merkel cell carcinoma development and that only the viral load can be used as indicator of disease progression in virus positive patients. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Fission Yeast Apc15 Stabilizes MCC-Cdc20-APC/C Complexes, Ensuring Efficient Cdc20 Ubiquitination and Checkpoint Arrest.

PubMed

May, Karen M; Paldi, Flora; Hardwick, Kevin G

2017-04-24

During mitosis, cells must segregate the replicated copies of their genome to their daughter cells with extremely high fidelity. Segregation errors lead to an abnormal chromosome number (aneuploidy), which typically results in disease or cell death [1]. Chromosome segregation and anaphase onset are initiated through the action of the multi-subunit E3 ubiquitin ligase known as the anaphase-promoting complex or cyclosome (APC/C [2]). The APC/C is inhibited by the spindle checkpoint in the presence of kinetochore attachment defects [3, 4]. Here we demonstrate that two non-essential APC/C subunits (Apc14 and Apc15) regulate association of spindle checkpoint proteins, in the form of the mitotic checkpoint complex (MCC), with the APC/C. apc14Δ mutants display increased MCC association with the APC/C and are unable to silence the checkpoint efficiently. Conversely, apc15Δ mutants display reduced association between the MCC and APC/C, are defective in poly-ubiquitination of Cdc20, and are checkpoint defective. In vitro reconstitution studies have shown that human MCC-APC/C can contain two molecules of Cdc20 [5-7]. Using a yeast strain expressing two Cdc20 genes with different epitope tags, we show by co-immunoprecipitation that this is true in vivo. MCC binding to the second molecule of Cdc20 is mediated via the C-terminal KEN box in Mad3. Somewhat surprisingly, complexes containing both molecules of Cdc20 accumulate in apc15Δ cells, and the implications of this observation are discussed. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Reliability of 46,XX results on miscarriage specimens: a review of 1,222 first-trimester miscarriage specimens.

PubMed

Lathi, Ruth B; Gustin, Stephanie L F; Keller, Jennifer; Maisenbacher, Melissa K; Sigurjonsson, Styrmir; Tao, Rosina; Demko, Zach

2014-01-01

To examine the rate of maternal contamination in miscarriage specimens. Retrospective review of 1,222 miscarriage specimens submitted for chromosome testing with detection of maternal cell contamination (MCC). Referral centers requesting genetic testing of miscarriage specimens at a single reference laboratory. Women with pregnancy loss who desire complete chromosome analysis of the pregnancy tissue. Analysis of miscarriage specimens using single-nucleotide polymorphism (SNP) microarray technology with bioinformatics program to detect maternal cell contamination. Chromosome content of miscarriages and incidence of 46,XX results due to MCC. Of the 1,222 samples analyzed, 592 had numeric chromosomal abnormalities, and 630 were normal 46,XX or 46,XY (456 and 187, respectively). In 269 of the 46,XX specimens, MCC with no embryonic component was found. With the exclusion of maternal 46,XX results, the chromosomal abnormality rate increased from 48% to 62%, and the ratio for XX to XY results dropped from 2.6 to 1.0. Over half of the normal 46,XX results in miscarriage specimens were due to MCC. The use of SNPs in MCC testing allows for precise identification of chromosomal abnormalities in miscarriage as well as MCC, improving the accuracy of products of conception testing. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: a case series.

PubMed

Xu, Melody J; Wu, Susan; Daud, Adil I; Yu, Siegrid S; Yom, Sue S

2018-05-30

Patients with metastatic Merkel cell carcinoma (mMCC) who experience disease progression on immunotherapy have limited additional standard options. Given evidence of synergism between radiation therapy (RT) and immunotherapy, two patients progressing on PD-1 inhibition were referred for short-course RT. Two patients were found to have progressive mMCC on PD-1 inhibitor therapy and were treated with single-fraction palliative RT. Both patients were observed to have local control at irradiated regions, as well as durable abscopal response at unirradiated, out-of-field, sites of metastatic disease. Short-course RT is a compelling strategy that could be a means to augment response in patients with mMCC who show progression on immune checkpoint blockade. Ongoing clinical trials are investigating the relationship between RT and immunotherapy in mMCC.

Intraepidermal proliferation of Merkel cells within a seborrheic keratosis: Merkel cell carcinoma in situ or Merkel cell hyperplasia?

PubMed

McFalls, Jeanne; Okon, Lauren; Cannon, Sarah; Lee, Jason B

2017-05-01

Intradepidermal proliferation of Merkel cells without any dermal component has been interpreted as either a hyperplastic process secondary to chronic ultraviolet radiation or a neoplastic process, namely Merkel cell carcinoma (MCC) in situ. The recent criteria that have been proffered to diagnose MCC in situ, unfortunately, are identical to those that have been applied to Merkel cell hyperplasia in the past, posing a diagnostic quandary when faced with an intraepidermal proliferation of Merkel cells. Most previously reported cases of MCC in situ have occurred within associated epithelial lesion that includes solar (actinic) keratosis and squamous-cell carcinoma in situ. Similarly, Merkel cell hyperplasia has been reported to occur in association with a variety of epithelial lesions as well as on chronically sun-damaged skin. Herein, a case of an intraepidermal proliferation of Merkel cells within a seborrheic keratosis is presented accompanied by a discussion on whether the proliferation represents another case of Merkel cell carcinoma in situ or an incidental hyperplastic process on chronically sun-damaged skin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Merkel Cell Polyomavirus Small T Antigen Drives Cell Motility via Rho-GTPase-Induced Filopodium Formation.

PubMed

Stakaitytė, Gabrielė; Nwogu, Nnenna; Dobson, Samuel J; Knight, Laura M; Wasson, Christopher W; Salguero, Francisco J; Blackbourn, David J; Blair, G Eric; Mankouri, Jamel; Macdonald, Andrew; Whitehouse, Adrian

2018-01-15

Cell motility and migration is a complex, multistep, and multicomponent process intrinsic to progression and metastasis. Motility is dependent on the activities of integrin receptors and Rho family GTPases, resulting in the remodeling of the actin cytoskeleton and formation of various motile actin-based protrusions. Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high likelihood of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases, and MCPyV-induced tumorigenesis largely depends on the expression of the small tumor antigen (ST). Since the discovery of MCPyV, a number of mechanisms have been suggested to account for replication and tumorigenesis, but to date, little is known about potential links between MCPyV T antigen expression and the metastatic nature of MCC. Previously, we described the action of MCPyV ST on the microtubule network and how it impacts cell motility and migration. Here, we demonstrate that MCPyV ST affects the actin cytoskeleton to promote the formation of filopodia through a mechanism involving the catalytic subunit of protein phosphatase 4 (PP4C). We also show that MCPyV ST-induced cell motility is dependent upon the activities of the Rho family GTPases Cdc42 and RhoA. In addition, our results indicate that the MCPyV ST-PP4C interaction results in the dephosphorylation of β 1 integrin, likely driving the cell motility pathway. These findings describe a novel mechanism by which a tumor virus induces cell motility, which may ultimately lead to cancer metastasis, and provides opportunities and strategies for targeted interventions for disseminated MCC. IMPORTANCE Merkel cell polyomavirus (MCPyV) is the most recently discovered human tumor virus. It causes the majority of cases of Merkel cell carcinoma (MCC), an aggressive skin cancer. However, the molecular mechanisms implicating MCPyV-encoded proteins in cancer development are yet to be fully elucidated. This study builds upon our previous observations, which demonstrated that the MCPyV ST antigen enhances cell motility, providing a potential link between MCPyV protein expression and the highly metastatic nature of MCC. Here, we show that MCPyV ST remodels the actin cytoskeleton, promoting the formation of filopodia, which is essential for MCPyV ST-induced cell motility, and we also implicate the activity of specific Rho family GTPases, Cdc42 and RhoA, in these processes. Moreover, we describe a novel mechanism for the activation of Rho-GTPases and the cell motility pathway due to the interaction between MCPyV ST and the cellular phosphatase catalytic subunit PP4C, which leads to the specific dephosphorylation of β1 integrin. These findings may therefore provide novel strategies for therapeutic intervention for disseminated MCC. Copyright © 2018 Stakaitytė et al.

Association between mast cell chymase genotype and atopic eczema: comparison between patients with atopic eczema alone and those with atopic eczema and atopic respiratory disease.

PubMed

Tanaka, K; Sugiura, H; Uehara, M; Sato, H; Hashimoto-Tamaoki, T; Furuyama, J

1999-06-01

It has remained unclear whether genetic background of patients with atopic eczema (AE) alone is identical to that of patients with both AE and atopic respiratory disease. We aimed to assess whether there is a genetic difference between these two groups of AE patients. We determined the genotype with regard to an allelic polymorphism in the gene for mast cell chymase (MCC; a serine protease secreted from mast cells) in 169 AE patients. MCC genotype was significantly associated with pure AE patients who did not have a predisposition to atopic respiratory disease and whose serum IgE concentration was < 500 IU/mL. The distribution of MCC genotypes also differed significantly between the latter patients and those AE patients with bronchial asthma and a serum IgE concentration of > 2000 IU/mL. These results suggest that pure AE is associated with genetic variants of MCC, and that the genetic basis of pure AE differs from that of AE associated with atopic asthma.

Mad2, Bub3, and Mps1 regulate chromosome segregation and mitotic synchrony in Giardia intestinalis, a binucleate protist lacking an anaphase-promoting complex

PubMed Central

Vicente, Juan-Jesus; Cande, W. Zacheus

2014-01-01

The binucleate pathogen Giardia intestinalis is a highly divergent eukaryote with a semiopen mitosis, lacking an anaphase-promoting complex/cyclosome (APC/C) and many of the mitotic checkpoint complex (MCC) proteins. However, Giardia has some MCC components (Bub3, Mad2, and Mps1) and proteins from the cohesin system (Smc1 and Smc3). Mad2 localizes to the cytoplasm, but Bub3 and Mps1 are either located on chromosomes or in the cytoplasm, depending on the cell cycle stage. Depletion of Bub3, Mad2, or Mps1 resulted in a lowered mitotic index, errors in chromosome segregation (including lagging chromosomes), and abnormalities in spindle morphology. During interphase, MCC knockdown cells have an abnormal number of nuclei, either one nucleus usually on the left-hand side of the cell or two nuclei with one mislocalized. These results suggest that the minimal set of MCC proteins in Giardia play a major role in regulating many aspects of mitosis, including chromosome segregation, coordination of mitosis between the two nuclei, and subsequent nuclear positioning. The critical importance of MCC proteins in an organism that lacks their canonical target, the APC/C, suggests a broader role for these proteins and hints at new pathways to be discovered. PMID:25057014

Multiple Primary Merkel Cell Carcinomas Presenting as Pruritic, Painful Lower Leg Tumors

PubMed Central

Blumenthal, Laura; VandenBoom, Timothy; Melian, Edward; Peterson, Anthony; Hutchens, Kelli A.

2015-01-01

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine tumor of the skin which almost exclusively presents as a solitary tumor. It is most often seen on sun-exposed regions, historically almost exclusively on the head and neck, with only rare case reports on the extremities. Although recent studies have shown increased incidence with up to 20% on the extremities, here we present one of these rare emerging presentations, with the addition of a unique treatment option. Our patient is an 80-year-old male with a 3-month history of multiple raised, rapidly enlarging tumors on the right ankle. Two separate biopsies were performed and demonstrated sheets and clusters of small blue cells filling the dermis with scant cytoplasm, dusty chromatin, and nuclear molding. Subsequent immunohistochemical stains confirmed the diagnosis of multiple primary MCC. Despite the characteristic immunohistochemical profile of primary MCC, the possibility of a metastatic neuroendocrine carcinoma from an alternate primary site was entertained, given his unusual clinical presentation. A complete clinical workup including CT scans of the chest, abdomen, and pelvis showed no evidence of disease elsewhere. Instead of amputation, the patient opted for nonsurgical treatment with radiation therapy alone, resulting in a rapid and complete response. This case represents an unusual presentation of primary MCC and demonstrates further evidence that radiation as monotherapy is an effective local treatment option for inoperable MCC. PMID:26594171

Mucociliary clearance and submucosal gland secretion in the ex vivo ferret trachea.

PubMed

Jeong, Jin Hyeok; Joo, Nam Soo; Hwang, Peter H; Wine, Jeffrey J

2014-07-01

In many species submucosal glands are an important source of tracheal mucus, but the extent to which mucociliary clearance (MCC) depends on gland secretion is unknown. To explore this relationship, we measured basal and agonist-stimulated MCC velocities in ex vivo tracheas from adult ferrets and compared the velocities with previously measured rates of ferret glandular mucus secretion (Cho HJ, Joo NS, Wine JJ. Am J Physiol Lung Cell Mol Physiol 299: L124-L136, 2010). Stimulated MCC velocities (mm/min, means ± SE for 10- to 35-min period poststimulation) were as follows: 1 μM carbachol: 19.1 ± 3.3 > 10 μM phenylephrine: 15.3 ± 2.4 ≈ 10 μM isoproterenol: 15.0 ± 1.9 ≈ 10 μM forskolin: 14.6 ± 3.1 > 1 μM vasoactive intestinal peptide (VIP): 10.2 ± 2.2 > basal (t15): 1.8 ± 0.3; n = 5-10 for each condition. Synergistic stimulation of MCC was observed between low concentrations of carbachol (100 nM) and isoproterenol (300 nM). Bumetanide inhibited carbachol-stimulated MCC by ~70% and abolished the increase in MCC stimulated by forskolin + VIP, whereas HCO3 (-)-free solutions did not significantly inhibit MCC to either intracellular Ca(2+) concentration or intracellular cAMP concentration ([cAMP]i)-elevating agonists. Stimulation and inhibition of MCC and gland secretion differed in several respects: most importantly, elevating [cAMP]i increased MCC much more effectively than expected from its effects on gland secretion, and bumetanide almost completely inhibited [cAMP]i-stimulated MCC while it had a smaller effect on gland secretion. We conclude that changes in glandular fluid secretion are complexly related to MCC and discuss possible reasons for this. Copyright © 2014 the American Physiological Society.

Merkel cell carcinoma: histopathologic and prognostic features according to the immunohistochemical expression of Merkel cell polyomavirus large T antigen correlated with viral load.

PubMed

Leroux-Kozal, Valérie; Lévêque, Nicolas; Brodard, Véronique; Lesage, Candice; Dudez, Oriane; Makeieff, Marc; Kanagaratnam, Lukshe; Diebold, Marie-Danièle

2015-03-01

Merkel cell carcinoma (MCC) is a neuroendocrine skin malignancy frequently associated with Merkel cell polyomavirus (MCPyV), which is suspected to be oncogenic. In a series of MCC patients, we compared clinical, histopathologic, and prognostic features according to the expression of viral large T antigen (LTA) correlated with viral load. We evaluated the LTA expression by immunohistochemistry using CM2B4 antibody and quantified viral load by real-time polymerase chain reaction. We analyzed formalin-fixed, paraffin-embedded (FFPE) tissue samples (n = 36) and corresponding fresh-frozen biopsies when available (n = 12), of the primary tumor and/or metastasis from 24 patients. MCPyV was detected in 88% and 58% of MCC patients by real-time polymerase chain reaction and immunohistochemistry, respectively. The relevance of viral load measurements was demonstrated by the strong consistency of viral load level between FFPE and corresponding frozen tissues as well as between primary tumor and metastases. From FFPE samples, 2 MCC subgroups were distinguished based on a viral load threshold defined by the positivity of CM2B4 immunostaining. In the LTA-negative subgroup with no or low viral load (nonsignificant), tumor cells showed more anisokaryosis (P = .01), and a solar elastosis around the tumor was more frequently observed (P = .03). LTA-positive MCCs with significant viral load had a lower proliferation index (P = .03) and a longer survival of corresponding patients (P = .008). Depending on MCPyV involvement, 2 MCC subgroups can be distinguished on histopathologic criteria, and the CM2B4 antibody is able to differentiate them reliably. Furthermore, the presence of a significant viral load in tumors is predictive of better prognosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Epidemiological, Clinicopathological and Virological Features of Merkel Cell Carcinomas in Medical Center of University of Pécs, Hungary (2007-2012).

PubMed

Horváth, Katalin Barbara; Pankovics, Péter; Kálmán, Endre; Kádár, Zsolt; Battyáni, Zita; Lengyel, Zsuzsanna; Reuter, Gábor

2016-01-01

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin tumour. In 2008, a Merkel cell polyomavirus (MC) was identified in MCCs as a potential etiological factor of MCC. The aims of this retrospective study were to investigate the epidemiological, clinicopathological and virological features of MCCs. Between 2007 and 2012, 11 patients had been diagnosed with MCC by histological methods in University of Pécs, Hungary. In eight MCC cases MC was tested by PCR (in primary skin lesions, lymph nodes/cutan metastases, MCC neighboring carcinomas). Clinicopathological characteristics (age, histological pattern, lymphovascular invasion, co-morbidities) of MC-positive and MC-negative cases were compared. MC was detected in three (37.5%) out of eight patients' primary tumour or metastasis. The average age was 73.8 (64.3 in MC-positive group). Except the youngest, 55 year-old patient (the primary tumour appeared on his leg), all tumours were found at the head and neck region. Immunosuppression (steroid therapy, chronic lymphoid leukaemia, chronic obstructive pulmonary disease) and/or old age were characteristic for all cases. Histological pattern was different in MC-positive and in MC-negative groups: MCCs with MC showed more homogeneous histological pattern, lack of lymphovascular invasion and were associated with better prognosis (mortality rate: 33% versus 80%). MCC associated with oncogenic virus is a newly recognized clinical entity. However, MC could not be detected in all histologically proven MCCs. The well-defined selection of patients/disease groups and better characterization of differences between MC-positive and negative cases is an important step towards the recognition of the etiology and pathogenesis of all MCCs.

Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma.

PubMed

Starrett, Gabriel J; Marcelus, Christina; Cantalupo, Paul G; Katz, Joshua P; Cheng, Jingwei; Akagi, Keiko; Thakuria, Manisha; Rabinowits, Guilherme; Wang, Linda C; Symer, David E; Pipas, James M; Harris, Reuben S; DeCaprio, James A

2017-01-03

Merkel cell polyomavirus is the primary etiological agent of the aggressive skin cancer Merkel cell carcinoma (MCC). Recent studies have revealed that UV radiation is the primary mechanism for somatic mutagenesis in nonviral forms of MCC. Here, we analyze the whole transcriptomes and genomes of primary MCC tumors. Our study reveals that virus-associated tumors have minimally altered genomes compared to non-virus-associated tumors, which are dominated by UV-mediated mutations. Although virus-associated tumors contain relatively small mutation burdens, they exhibit a distinct mutation signature with observable transcriptionally biased kataegic events. In addition, viral integration sites overlap focal genome amplifications in virus-associated tumors, suggesting a potential mechanism for these events. Collectively, our studies indicate that Merkel cell polyomavirus is capable of hijacking cellular processes and driving tumorigenesis to the same severity as tens of thousands of somatic genome alterations. A variety of mutagenic processes that shape the evolution of tumors are critical determinants of disease outcome. Here, we sequenced the entire genome of virus-positive and virus-negative primary Merkel cell carcinomas (MCCs), revealing distinct mutation spectra and corresponding expression profiles. Our studies highlight the strong effect that Merkel cell polyomavirus has on the divergent development of viral MCC compared to the somatic alterations that typically drive nonviral tumorigenesis. A more comprehensive understanding of the distinct mutagenic processes operative in viral and nonviral MCCs has implications for the effective treatment of these tumors. Copyright © 2017 Starrett et al.

Differential effects of cyclic and constant stress on ATP release and mucociliary transport by human airway epithelia

PubMed Central

Button, Brian; Picher, Maryse; Boucher, Richard C

2007-01-01

In the lungs, the first line of defence against bacterial infection is the thin layer of airway surface liquid (ASL) lining the airway surface. The superficial airway epithelium exhibits complex regulatory pathways that blend ion transport to adjust ASL volume to maintain proper mucociliary clearance (MCC). We hypothesized that stresses generated by airflow and transmural pressures during breathing govern ASL volume by regulating the rate of epithelial ATP release. Luminal ATP, via interactions with apical membrane P2-purinoceptors, regulates the balance of active ion secretion versus absorption to maintain ASL volume at optimal levels for MCC. In this study we tested the hypothesis that cyclic compressive stress (CCS), mimicking normal tidal breathing, regulates ASL volume in airway epithelia. Polarized tracheobronchial epithelial cultures from normal and cystic fibrosis (CF) subjects responded to a range of CCS by increasing the rate of ATP release. In normal airway epithelia, the CCS-induced increase in ASL ATP concentration was sufficient to induce purinoceptor-mediated increases in ASL height and MCC, via inhibition of epithelial Na+-channel-mediated Na+ absorption and stimulation of Cl− secretion through CFTR and the Ca2+-activated chloride channels. In contrast, static, non-oscillatory stress did not stimulate ATP release, ion transport or MCC, emphasizing the importance of rhythmic mechanical stress for airway defence. In CF airway cultures, which exhibit basal ASL depletion, CCS was partially effective, producing less ASL volume secretion than in normal cultures, but a level sufficient to restore MCC. The present data suggest that CCS may (1) regulate ASL volume in the normal lung and (2) improve clearance in the lungs of CF patients, potentially explaining the beneficial role of exercise in lung defence. PMID:17317749

Increased expression of EZH2 in Merkel cell carcinoma is associated with disease progression and poorer prognosis.

PubMed

Harms, Kelly L; Chubb, Heather; Zhao, Lili; Fullen, Douglas R; Bichakjian, Christopher K; Johnson, Timothy M; Carskadon, Shannon; Palanisamy, Nallasivam; Harms, Paul W

2017-09-01

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing. Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that has a high risk of disease progression with nodal and distant metastases. Here, we evaluated EZH2 expression by immunohistochemistry in a cohort of 85 MCC tumors (29 primary tumors, 41 lymph node metastases, 13 in-transit metastases, and 2 distant metastases) with clinical follow-up. We show strong/moderate EZH2 expression in 54% of tumors. Importantly, weak expression of EZH2 in the primary tumor, but not nodal metastases, correlated with improved prognosis compared to moderate/strong EZH2 expression (5-year MCC-specific survival of 68% versus 22%, respectively, P=.024). In addition, EZH2 was expressed at higher levels in nodal metastases compared to primary tumors (P=.005). Our data demonstrate that EZH2 has prognostic value and may play an oncogenic role in MCC. Copyright © 2017 Elsevier Inc. All rights reserved.

The diagnostic utility of Merkel cell polyomavirus immunohistochemistry in a fine needle aspirate of metastatic Merkel cell carcinoma of unknown primary to the pancreas.

PubMed

Li, Long; Molberg, Kyle; Cheedella, Naga; Thibodeaux, Joel; Hinson, Stacy; Lucas, Elena

2018-01-01

Merkel cell carcinoma (MCC) is an aggressive skin tumor with a high tendency for metastases. We report a case of MCC initially presenting as axillary and pancreatic metastases. A 33-year-old HIV-positive Hispanic male presented with a history of a rapidly growing axillary mass. A needle core biopsy demonstrated an epithelioid neoplasm composed of small to medium-sized cells with high nuclear-cytoplasmic ratio, nuclear molding, and frequent mitotic figures. A subsequent PET scan revealed a 1.5 cm FDG avid mass in the pancreas. Endoscopic ultrasound-guided FNA of the pancreatic mass showed neoplastic cells with similar morphology to those of the axillary mass. The tumor cells were positive with pancytokeratin AE1/AE3, CK20, CD56, synatophysin, chromogranin, and Merkel cell polyomavirus (MCPyV). This case of MCC most likely originated from a resolved primary skin lesion drained by the involved axillary lymph node with subsequent metastases to the pancreas and distant lymph nodes. © 2017 Wiley Periodicals, Inc.

Emerging and Mechanism-Based Therapies for Recurrent or Metastatic Merkel Cell Carcinoma

PubMed Central

Miller, Natalie J.; Bhatia, Shailender; Parvathaneni, Upendra; Iyer, Jayasri G.; Nghiem, Paul

2013-01-01

Opinion statement Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer with a disease-specific mortality of approximately 40 %. The association of MCC with a recently discovered polyomavirus, combined with the increased incidence and mortality of MCC among immunocompromised patients, highlight the importance of the immune system in controlling this cancer. Initial management of MCC is summarized within the NCCN guidelines and in recently published reviews. The high rate of recurrent and metastatic disease progression in MCC, however, presents a major challenge in a cancer that lacks mechanism-based, disease-specific therapies. Traditional treatment approaches have focused on cytotoxic chemotherapy that, despite frequent initial efficacy, rarely provides durable responses and has high morbidity among the elderly. In addition, the immunosuppressive nature of chemotherapy is of concern when treating a virus-associated cancer for which survival is unusually tightly linked to immune function. With a median survival of 9.6 months after development of an initial metastasis (n=179, described herein), and no FDA-approved agents for this cancer, there is an urgent need for more effective treatments. We review diverse management options for patients with advanced MCC, with a focus on emerging and mechanism-based therapies, some of which specifically target persistently expressed viral antigens. These treatments include single-dose radiation and novel immunotherapies, some of which are in clinical trials. Due to their encouraging efficacy, low toxicity, and lack of immune suppression, these therapies may offer viable alternatives to traditional cytotoxic chemotherapy. PMID:23436166

Pedunculated and telangiectatic merkel cell carcinoma: an unusual clinical presentation.

PubMed

Errichetti, Enzo; Piccirillo, Angelo; Ricciuti, Federico; Ricciuti, Francesco

2013-05-01

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect.

Intraoperative imprint cytology for evaluation of sentinel lymph nodes from Merkel cell carcinoma.

PubMed

Wong, S Lindsey; Young, Yorke D; Geisinger, Kim R; Shen, Perry; Stewart, John H; Sangueza, Omar; Pichardo-Geisinger, Rita; Levine, Edward A

2009-07-01

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy. Intraoperative imprint cytology (IIC) can potentially avoid second operations for completion lymphadenectomy when nodal metastases are found during nodal staging with sentinel lymph node biopsy (SLN). This represents the first series of IIC for MCC we are aware of and our initial experience. Patients with biopsy-proven MCC underwent SLN (at the time of wide excision) using a double indicator technique with 99technetium sulfur colloid and isosulfan blue. SLN were identified and bisected and touch imprints of each half were made. One half was air-dried and stained with Diff-Quick and the other was fixed with 95 per cent alcohol and stained with hematoxylin and eosin (H&E). Paraffin-embedded sections were examined by H&E. Eighteen patients underwent successful SLN mapping procedures. IIC was negative in 84.2 per cent (16) cases. Three false-negatives occurred with IIC, but there were no false-positives, making the sensitivity 33 per cent and the specificity 100 per cent. Two of four patients with positive pathology-confirmed SLN also had positive IIC. SLN mapping has usefulness in patients with MCC. IIC is feasible and accurate in evaluating the SLN. IIC is a practical diagnostic tool when intraoperative analysis of SLN biopsy is desired for MCC.

Molecular basis of APC/C regulation by the spindle assembly checkpoint

PubMed Central

Zhang, Ziguo; Yang, Jing; Maslen, Sarah; Skehel, Mark; Barford, David

2016-01-01

In the dividing eukaryotic cell the spindle assembly checkpoint (SAC) ensures each daughter cell inherits an identical set of chromosomes. The SAC coordinates the correct attachment of sister chromatid kinetochores to the mitotic spindle with activation of the anaphase-promoting complex/cyclosome (APC/C), the E3 ubiquitin ligase that initiates chromosome separation. In response to unattached kinetochores, the SAC generates the mitotic checkpoint complex (MCC), a multimeric assembly that inhibits the APC/C, delaying chromosome segregation. Here, using cryo-electron microscopy we determined the near-atomic resolution structure of an APC/C-MCC complex (APC/CMCC). We reveal how degron-like sequences of the MCC subunit BubR1 block degron recognition sites on Cdc20, the APC/C coactivator subunit (Cdc20APC/C) responsible for substrate interactions. BubR1 also obstructs binding of UbcH10 (APC/C’s initiating E2) to repress APC/C ubiquitination activity. Conformational variability of the complex allows for UbcH10 association, and we show from a structure of APC/CMCC in complex with UbcH10 how the Cdc20 subunit intrinsic to the MCC (Cdc20MCC) is ubiquitinated, a process that results in APC/C reactivation when the SAC is silenced. PMID:27509861

Convective cell development and propagation in a mesoscale convective complex

NASA Technical Reports Server (NTRS)

Ahn, Yoo-Shin; Brundidge, Kenneth C.

1987-01-01

A case study was made of the mesoscale convective complex (MCC) which occurred over southern Oklahoma and northern Texas on 27 May 1981. This storm moved in an eastsoutheasterly direction and during much of its lifetime was observable by radars at Oklahoma City, Ok. and Stephenville, Tx. It was found that the direction of cell (VIP level 3 or more reflectivity) propagation was somewhat erratic but approximately the same as the system (VIP level 1 reflectivity) movement and the ambient wind. New cells developed along and behind the gust front make it appear that once the MCC is initiated, a synergistic relationship exists between the gust front and the MCC. The relationship between rainfall patterns and amounts and the infrared (IR) temperature field in the satellite imagery were examined. The 210 K isotherm of GOES IR imagery was found to encompass the rain area of the storm. The heaviest rainfall was in the vicinity of the VIP level 3 cells and mostly contained within the 205 K isotherm of GOES IR imagery.

Comprehensive genetic analysis of cytarabine sensitivity in a cell-based model identifies polymorphisms associated with outcome in AML patients

PubMed Central

Gamazon, Eric R.; Lamba, Jatinder K.; Pounds, Stanley; Stark, Amy L.; Wheeler, Heather E.; Cao, Xueyuan; Im, Hae K.; Mitra, Amit K.; Rubnitz, Jeffrey E.; Ribeiro, Raul C.; Raimondi, Susana; Campana, Dario; Crews, Kristine R.; Wong, Shan S.; Welsh, Marleen; Hulur, Imge; Gorsic, Lidija; Hartford, Christine M.; Zhang, Wei; Cox, Nancy J.; Dolan, M. Eileen

2013-01-01

A whole-genome approach was used to investigate the genetic determinants of cytarabine-induced cytotoxicity. We performed a meta-analysis of genome-wide association studies involving 523 lymphoblastoid cell lines (LCLs) from individuals of European, African, Asian, and African American ancestry. Several of the highest-ranked single-nucleotide polymorphisms (SNPs) were within the mutated in colorectal cancers (MCC) gene. MCC expression was induced by cytarabine treatment from 1.7- to 26.6-fold in LCLs. A total of 33 SNPs ranked at the top of the meta-analysis (P < 10−5) were successfully tested in a clinical trial of patients randomized to receive low-dose or high-dose cytarabine plus daunorubicin and etoposide; of these, 18 showed association (P < .05) with either cytarabine 50% inhibitory concentration in leukemia cells or clinical response parameters (minimal residual disease, overall survival (OS), and treatment-related mortality). This count (n = 18) was significantly greater than expected by chance (P = .016). For rs1203633, LCLs with AA genotype were more sensitive to cytarabine-induced cytotoxicity (P = 1.31 × 10−6) and AA (vs GA or GG) genotype was associated with poorer OS (P = .015), likely as a result of greater treatment-related mortality (P = .0037) in patients with acute myeloid leukemia (AML). This multicenter AML02 study trial was registered at www.clinicaltrials.gov as #NCT00136084. PMID:23538338

Pedunculated and Telangiectatic Merkel Cell Carcinoma: An Unusual Clinical Presentation

PubMed Central

Errichetti, Enzo; Piccirillo, Angelo; Ricciuti, Federico; Ricciuti, Francesco

2013-01-01

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect. PMID:23723504

Merkel Cell Polyomavirus Large T Antigen Has Growth-Promoting and Inhibitory Activities

PubMed Central

Cheng, Jingwei; Rozenblatt-Rosen, Orit; Paulson, Kelly G.; Nghiem, Paul

2013-01-01

Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. In at least 80% of all MCC, Merkel cell polyomavirus (MCPyV) DNA has undergone clonal integration into the host cell genome, and most tumors express the MCPyV large and small T antigens. In all cases of MCC reported to date, the integrated MCPyV genome has undergone mutations in the large T antigen. These mutations result in expression of a truncated large T antigen that retains the Rb binding or LXCXE motif but deletes the DNA binding and helicase domains. However, the transforming functions of full-length and truncated MCPyV large T antigen are unknown. We compared the transforming activities of full-length, truncated, and alternatively spliced 57kT forms of MCPyV large T antigen. MCPyV large T antigen could bind to Rb but was unable to bind to p53. Furthermore, MCPyV-truncated large T antigen was more effective than full-length and 57kT large T antigen in promoting the growth of human and mouse fibroblasts. In contrast, expression of the MCPyV large T antigen C-terminal 100 residues could inhibit the growth of several different cell types. These data imply that the deletion of the C terminus of MCPyV large T antigen found in MCC serves not only to disrupt viral replication but also results in the loss of a distinct growth-inhibitory function intrinsic to this region. PMID:23514892

Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma.

PubMed

Henderson, Samuel A; Tetzlaff, Michael T; Pattanaprichakul, Penvadee; Fox, Patricia; Torres-Cabala, Carlos A; Bassett, Roland L; Prieto, Victor G; Richards, Hunter W; Curry, Jonathan L

2014-11-01

High mitotic figure count (MFC) correlates with low survival rate in Merkel cell carcinoma (MCC). However, the prognostic impact of histone biomarkers as surrogates of MFC in MCC is unknown. We evaluated the prognostic significance of the immunodetection of mitotic figures and of G2+ tumor nuclei with histone-associated mitotic markers H3K79me3T80ph (H3KT) and phosphohistone H3 (PHH3) in MCC. Immunohistochemical analyses of H3KT and PHH3 and proliferative marker Ki-67 were performed in a series of 21 cases of MCC. The significance of the pathologic data and immunoreactivity with these markers was evaluated with Pearson correlation and paired Student t-test. Univariate Cox proportional hazards regression models were performed to assess the relationships between these markers and survival. H3KT detected a higher number of mitotic figure (p<0.0001) and G2+ tumor nuclei (p<0.0052) than did PHH3. Furthermore, the MFC combined with G2+ tumor nuclei detected with H3KT compared to PHH3 and manual MFC was a significant predictor of impaired survival in patients with MCC (p=0.035; HR=1.0172), corresponding to a 1.72% increased risk of death for each unit increase in H3KT. Biomarker analysis of proliferative rates with histone markers may have relevance in stratifying risk in patients with MCC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Merkel cell carcinoma: An algorithm for multidisciplinary management and decision-making.

PubMed

Prieto, Isabel; Pérez de la Fuente, Teresa; Medina, Susana; Castelo, Beatriz; Sobrino, Beatriz; Fortes, Jose R; Esteban, David; Cassinello, Fernando; Jover, Raquel; Rodríguez, Nuria

2016-02-01

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Therapeutic approach is often unclear, and considerable controversy exists regarding MCC pathogenesis and optimal management. Due to its rising incidence and poor prognosis, it is imperative to establish the optimal therapy for both the tumor and the lymph node basin, and for treatment to include sentinel node biopsy. Sentinel node biopsy is currently the most consistent predictor of survival for MCC patients, although there are conflicting views and a lack of awareness regarding node management. Tumor and node management involve different specialists, and their respective decisions and interventions are interrelated. No effective systemic treatment has been made available to date, and therefore patients continue to experience distant failure, often without local failure. This review aims to improve multidisciplinary decision-making by presenting scientific evidence of the contributions of each team member implicated in MCC management. Following this review of previously published research, the authors conclude that multidisciplinary team management is beneficial for care, and propose a multidisciplinary decision algorithm for managing this tumor. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma.

PubMed

Joseph, Jocelyn; Zobniw, Chrystia; Davis, Jennifer; Anderson, Jaime; Trinh, Van Anh

2018-04-01

To summarize the clinical development of avelumab and its clinical relevance in metastatic Merkel cell carcinoma (MCC). An English-language literature search using PubMed was performed using the terms avelumab, anti-PD-1, anti-PD-L1, and MCC from January of 1950 to March 2018. Data were also obtained from package inserts, meeting abstracts, and clinical registries. All relevant published articles of avelumab were reviewed. Clinical trial registries and meeting abstracts were used for information about ongoing trials. Avelumab is a fully human monoclonal antibody that inhibits programmed death ligand-1, which reverses T-cell exhaustion and induces antitumor responses. Avelumab is safe and effective in previously treated metastatic MCC based on a phase II trial of previously treated patients with objective response rates in 28 of 88 patients, including 10 complete responses and 19 partial responses. Median overall survival (OS) was 12.9 months, and 1-year progression-free survival and OS were 30% and 52%, respectively. Grade 3 treatment-related side effects included lymphopenia (2 patients), serum creatine phosphokinase increase (1 patient), aminotransferase elevation (1 patient), and serum cholesterol increase (1 patient). Relevance to Patient Care and Clinical Practice: This review outlines the pharmacology and clinical trial data for avelumab in metastatic MCC and guides clinicians on avelumab's place in therapy. Avelumab is the first Food and Drug Administration-approved medication for metastatic MCC and provides an advantage of durable responses and possibly improved tolerability compared with traditional platinum-based chemotherapy. Clinical trials are under way to expand its utility into the adjuvant and frontline settings.

Phosphohistone-H3 (PHH3) is prognostic relevant in Merkel cell carcinomas but Merkel cell polyomavirus is a more powerful prognostic factor than AJCC clinical stage, PHH3, Ki-67 or mitotic indices.

PubMed

Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Kato, Masako; Nagata, Keiko; Murakami, Ichiro; Hayashi, Kazuhiko

2015-08-01

Merkel cell carcinomas (MCCs) associated with Merkel cell polyomavirus (MCPyV) have better prognosis than those without MCPyV. The relationship between mitotic index (MI) and MCC outcome has remained elusive because of the difficulty in differentiating mitotic cells from apoptotic ones. We evaluated the role of phosphohistone-H3 (PHH3) (Ser10), a new mitotic count biomarker, in MCPyV-positive or -negative MCC patients, and assessed its prognostic value in comparison to Ki-67 labeling index or MI using hematoxylin and eosin (HE) staining. We compared the prognostic value of PHH3 mitotic index with that of MI by HE in 19 MCPyV-positive and 9 MCPyV-negative MCC patients. PHH3-positive immunoreactivity was mostly observed in mitotic figures. Multivariate analysis significantly showed that MCPyV status (HR, 0.004; 95% CI 0.0003-0.058) and the American Joint Committee of Cancer (AJCC) stage (HR, 5.02; 95% CI 1.23-20.51) were observed as significantly independent prognostic factors for OS. PHH3-positive cell counts/10 HPF was a slightly significant independent prognostic factor for OS (HR, 4.96; 95% CI 0.93-26.55). PHH3-positive MI and MCPyV status in MCC patients are useful in prognostication, although MCPyV-infection is a more powerful prognostic factor in MCCs than the AJCC scheme on proliferation or mitotic indices. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice.

PubMed

Mridha, Auvro R; Wree, Alexander; Robertson, Avril A B; Yeh, Matthew M; Johnson, Casey D; Van Rooyen, Derrick M; Haczeyni, Fahrettin; Teoh, Narci C-H; Savard, Christopher; Ioannou, George N; Masters, Seth L; Schroder, Kate; Cooper, Matthew A; Feldstein, Ariel E; Farrell, Geoffrey C

2017-05-01

NOD-like receptor protein 3 (NLRP3) inflammasome activation occurs in Non-alcoholic fatty liver disease (NAFLD). We used the first small molecule NLRP3 inhibitor, MCC950, to test whether inflammasome blockade alters inflammatory recruitment and liver fibrosis in two murine models of steatohepatitis. We fed foz/foz and wild-type mice an atherogenic diet for 16weeks, gavaged MCC950 or vehicle until 24weeks, then determined NAFLD phenotype. In mice fed an methionine/choline deficient (MCD) diet, we gavaged MCC950 or vehicle for 6weeks and determined the effects on liver fibrosis. In vehicle-treated foz/foz mice, hepatic expression of NLRP3, pro-IL-1β, active caspase-1 and IL-1β increased at 24weeks, in association with cholesterol crystal formation and NASH pathology; plasma IL-1β, IL-6, MCP-1, ALT/AST all increased. MCC950 treatment normalized hepatic caspase 1 and IL-1β expression, plasma IL-1β, MCP-1 and IL-6, lowered ALT/AST, and reduced the severity of liver inflammation including designation as NASH pathology, and liver fibrosis. In vitro, cholesterol crystals activated Kupffer cells and macrophages to release IL-1β; MCC950 abolished this, and the associated neutrophil migration. MCD diet-fed mice developed fibrotic steatohepatitis; MCC950 suppressed the increase in hepatic caspase 1 and IL-1β, lowered numbers of macrophages and neutrophils in the liver, and improved liver fibrosis. MCC950, an NLRP3 selective inhibitor, improved NAFLD pathology and fibrosis in obese diabetic mice. This is potentially attributable to the blockade of cholesterol crystal-mediated NLRP3 activation in myeloid cells. MCC950 reduced liver fibrosis in MCD-fed mice. Targeting NLRP3 is a logical direction in pharmacotherapy of NASH. Fatty liver disease caused by being overweight with diabetes and a high risk of heart attack, termed non-alcoholic steatohepatitis (NASH), is the most common serious liver disease with no current treatment. There could be several causes of inflammation in NASH, but activation of a protein scaffold within cells termed the inflammasome (NLRP3) has been suggested to play a role. Here we show that cholesterol crystals could be one pathway to activate the inflammasome in NASH. We used a drug called MCC950, which has already been shown to block NLRP3 activation, in an attempt to reduce liver injury in NASH. This drug partly reversed liver inflammation, particularly in obese diabetic mice that most closely resembles the human context of NASH. In addition, such dampening of liver inflammation in NASH achieved with MCC950 partly reversed liver scarring, the process that links NASH to the development of cirrhosis. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Microcin Amyloid Fibrils A Are Reservoir of Toxic Oligomeric Species

PubMed Central

Shahnawaz, Mohammad; Soto, Claudio

2012-01-01

Microcin E492 (Mcc), a low molecular weight bacteriocin produced by Klebsiella pneumoniae RYC492, has been shown to exist in two forms: soluble forms that are believed to be toxic to the bacterial cell by forming pores and non-toxic fibrillar forms that share similar biochemical and biophysical properties with amyloids associated with several human diseases. Here we report that fibrils polymerized in vitro from soluble forms sequester toxic species that can be released upon changing environmental conditions such as pH, ionic strength, and upon dilution. Our results indicate that basic pH (≥8.5), low NaCl concentrations (≤50 mm), and dilution (>10-fold) destabilize Mcc fibrils into more soluble species that are found to be toxic to the target cells. Additionally, we also found a similar conversion of non-toxic fibrils into highly toxic oligomers using Mcc aggregates produced in vivo. Moreover, the soluble protein released from fibrils is able to rapidly polymerize into amyloid fibrils under fibril-forming conditions and to efficiently seed aggregation of monomeric Mcc. Our findings indicate that fibrillar forms of Mcc constitute a reservoir of toxic oligomeric species that is released into the medium upon changing the environmental conditions. These findings may have substantial implications to understand the dynamic process of interconversion between toxic and non-toxic aggregated species implicated in protein misfolding diseases. PMID:22337880

Method to improve near-field nonlinearity of a high-power diode laser array on a microchannel cooler

NASA Astrophysics Data System (ADS)

Zhang, Hongyou; Jia, Yangtao; Cai, Wanshao; Tao, Chunhua; Zah, Chung-en; Liu, Xingsheng

2018-03-01

Due to thermal stress, each emitter in a semiconductor laser bar or array is vertically displaced along the p-n junction; the result is that each emitter is not in a line, called near-field nonlinearity. Near-field nonlinearity along a laser bar (also known as "SMILE" effect) degrades the laser beam brightness, which causes an adverse effect on optical coupling and beam shaping. A large SMILE value causes a large divergence angle after collimation and a wider line after collimation and focusing. We simulate the factors affecting the SMILE value of a high-power diode laser array on a microchannel cooler (MCC). According to the simulation results, we have fabricated a series of laser bars bonded on MCCs with lower SMILE value. After simulation and experiment analysis, we found the key factor to affect SMILE is the deformation of the thin MCC because of the distribution of strain and stress in it. We also decreased the SMILE value of 1-cm-wide full bar AuSn bonded on MCCs from 12 to 1 μm by balancing force on MCC to minimize the deformation.

Quantitative analysis of mast cell count and density in chronic periodontal disease.

PubMed

Rathod, Surekha; Raj, Anubha; Wanikar, Ishita

2018-01-01

Mast cells play a crucial role in activation of acquired immune response to inflammatory conditions of periodontal diseases. They promote inflammation by releasing pro-inflammatory mediators and bring about angiogenesis, degeneration of the extracellular matrix, and tissue remodeling. Since there is little literature regarding the role of mast cells in periodontitis, the present study was aimed to evaluate mast cell count (MCC) and density in periodontitis. A total of eighty participants, Group I ( n = 40) healthy participants and Group II ( n = 40) participants with moderate chronic periodontitis, were included in the study. Tissue samples of 5 micron were obtained from each participant and were fixed in 10% formalin. Inflammation assessment was carried out after staining the sections with hematoxylin/eosin (H and E) followed by toluidine blue and mast cells were counted. MCC in healthy group (1.32 ± 0.43) was significantly smaller than periodontitis group (10.28 ± 1.15) and also mast cell density in healthy group (98.08 ± 37.40) was smaller than periodontitis group (803.43 ± 89.94) with P < 0.0001. It could be concluded that participants with chronic periodontitis have a higher MCC and density when compared with healthy participants.

Avelumab: First Global Approval.

PubMed

Kim, Esther S

2017-05-01

Avelumab (Bavencio ® ) is an intravenously administered programmed cell death ligand-1-blocking human antibody initially developed by EMD Serono Inc. (the biopharmaceutical division of Merck KGaA, Darmstadt, Germany) [now jointly developed and commercialized by EMD Serono Inc. and Pfizer] for the treatment of various tumours. It has received accelerated approval in the USA for the treatment of metastatic Merkel cell carcinoma (mMCC) in adults and paediatric patients aged ≥12 years. The marketing authorization application for avelumab in the treatment of mMCC is undergoing regulatory review in the EU, the biologics license application for avelumab in the treatment of urothelial carcinoma is undergoing priority review by the FDA, and avelumab is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of avelumab leading to this first approval for mMCC.

Merkel Cell Carcinoma.

PubMed

Pulitzer, Melissa

2017-06-01

Merkel cell carcinoma (MCC) encompasses neuroendocrine carcinomas primary to skin and occurs most commonly in association with clonally integrated Merkel cell polyomavirus with related retinoblastoma protein sequestration or in association with UV radiation-induced alterations involving the TP53 gene and mutations, heterozygous deletion, and hypermethylation of the Retinoblastoma gene. Molecular genetic signatures may provide therapeutic guidance. Morphologic features, although patterned, are associated with predictable diagnostic pitfalls, usually resolvable by immunohistochemistry. Therapeutic options for MCC, traditionally limited to surgical intervention and later chemotherapy and radiation, are growing, given promising early results of immunotherapeutic regimens. Copyright © 2017 Elsevier Inc. All rights reserved.

Morphometric study of the fibrosis and mast cell count in the circular colon musculature of chronic Chagas patients with and without megacolon.

PubMed

Pinheiro, Simone Wanderley; Rua, Adilha Misson de Oliveira; Etchebehere, Renata Margarida; Cançado, Cristiane Gobbo; Chica, Javier Em lio Lazo; Lopes, Edison Reis; Adad, Sheila Jorge

2003-01-01

A morphometric study of the circular colon musculature was performed, in which the mast cell count was determined and the connective fibrous tissue in this layer was measured. The objective was to gain better understanding of Chagas megacolon morphology and contribute towards the knowledge of fibrosis pathogenesis in Chagas megas. An evaluation was made of 15 distal sigmoid rings from Chagas patients with megacolon (MCC), 15 without megacolon (CSMC) and 15 non-Chagas patients (NC). The rings were fixed in formol, embedded in paraffin, and 7mm thick sections were cut and stained using Azan-Heidenhain and Giemsa. The mast cell count and fibrosis were greater in the MCC group than in the CSMC and NC groups (p< 0,05; Kruskal-Wallis test) and there was no significant difference between the latter two. The fibrosis and increased mast cell count in the colon musculature of the MCC group possibly indicates that there is a relationship between mastocytosis and fibrosis, as has already been demonstrated in other pathologies.

A Trojan-Horse Peptide-Carboxymethyl-Cytidine Antibiotic from Bacillus amyloliquefaciens.

PubMed

Serebryakova, Marina; Tsibulskaya, Darya; Mokina, Olga; Kulikovsky, Alexey; Nautiyal, Manesh; Van Aerschot, Arthur; Severinov, Konstantin; Dubiley, Svetlana

2016-12-07

Microcin C and related antibiotics are Trojan-horse peptide-adenylates. The peptide part is responsible for facilitated transport inside the sensitive cell, where it gets processed to release a toxic warhead-a nonhydrolyzable aspartyl-adenylate, which inhibits aspartyl-tRNA synthetase. Adenylation of peptide precursors is carried out by MccB THIF-type NAD/FAD adenylyltransferases. Here, we describe a novel microcin C-like compound from Bacillus amyloliquefaciens. The B. amyloliquefaciens MccB demonstrates an unprecedented ability to attach a terminal cytidine monophosphate to cognate precursor peptide in cellular and cell free systems. The cytosine moiety undergoes an additional modification-carboxymethylation-that is carried out by the C-terminal domain of MccB and the MccS enzyme that produces carboxy-SAM, which serves as a donor of the carboxymethyl group. We show that microcin C-like compounds carrying terminal cytosines are biologically active and target aspartyl-tRNA synthetase, and that the carboxymethyl group prevents resistance that can occur due to modification of the warhead. The results expand the repertoire of known enzymatic modifications of peptides that can be used to obtain new biological activities while avoiding or limiting bacterial resistance.

In vitro characterization of DNA gyrase inhibition by microcin B17 analogs with altered bisheterocyclic sites

PubMed Central

Zamble, Deborah B.; Miller, Deborah A.; Heddle, Jonathan G.; Maxwell, Anthony; Walsh, Christopher T.; Hollfelder, Florian

2001-01-01

Microcin B17 (MccB17) is a 3.1-kDa Escherichia coli antibiotic that contains thiazole and oxazole heterocycles in a peptide backbone. MccB17 inhibits its cellular target, DNA gyrase, by trapping the enzyme in a complex that is covalently bound to double-strand cleaved DNA, in a manner similar to the well-known quinolone drugs. The identification of gyrase as the target of MccB17 provides an opportunity to analyze the relationship between the structure of this unusual antibiotic and its activity. In this report, steady-state parameters are used to describe the induction of the cleavable complex by MccB17 analogs containing modified bisheterocyclic sites. The relative potency of these analogs corresponds to the capacity of the compounds to prevent growth of sensitive cells. In contrast to previously reported experiments, inhibition of DNA gyrase supercoiling activity by wild-type MccB17 also was observed. These results suggest that DNA gyrase is the main intracellular target of MccB17. This study probes the structure-function relationship of a new class of gyrase inhibitors and demonstrates that these techniques could be used to analyze compounds in the search for clinically useful antibiotics that block DNA gyrase. PMID:11427730

Clinical impact of targeted therapies in patients with metastatic clear-cell renal cell carcinoma

PubMed Central

Nerich, Virginie; Hugues, Marion; Paillard, Marie Justine; Borowski, Laëtitia; Nai, Thierry; Stein, Ulrich; Nguyen Tan Hon, Thierry; Montcuquet, Philippe; Maurina, Tristan; Mouillet, Guillaume; Kleinclauss, François; Pivot, Xavier; Limat, Samuel; Thiery-Vuillemin, Antoine

2014-01-01

Introduction The aim of this retrospective clinical study was to assess, in the context of the recent evolution of systemic therapies, the potential effect of targeted therapies on overall survival (OS) of patients with metastatic clear-cell renal cell carcinoma (mccRCC) in daily practice. Patients and methods All consecutive patients with histologically confirmed mccRCC who received systemic therapy between January 2000 and December 2010 in two oncology treatment centers in our Franche-Comté region in eastern France were included in the analysis. The primary end point was OS. The analysis of prognostic factors was performed using a two-step approach: univariate then multivariate analysis with a stepwise Cox proportional hazards regression model. Results For the entire cohort of 111 patients, the median OS was 17 months (95% confidence interval [CI]; 13–22 months) and the two-year OS was 39%. Three prognostic factors were independent predictors of long survival: prior nephrectomy (hazard ratio =0.38 [0.22–0.64], P<0.0001); systemic therapy by targeted therapy (hazard ratio =0.50 [0.31–0.80], P=0.005); and lack of liver metastasis (hazard ratio =0.43 [0.22–0.82], P=0.002). Median OS was 21 months [14–29 months] for patients who received at least one targeted therapy compared with 12 months [7–15 months] for patients who were treated only by immunotherapy agents (P=0.003). Conclusion Our results suggest that targeted therapies are associated with improved OS in comparison with cytokines, which is in line with other publications. PMID:24600236

Association of VAMP5 and MCC genetic polymorphisms with increased risk of Hirschsprung disease susceptibility in Southern Chinese children.

PubMed

Zhao, Jinglu; Xie, Xiaoli; Yao, Yuxiao; He, Qiuming; Zhang, Ruizhong; Xia, Huimin; Zhang, Yan

2018-04-25

Hirschsprung disease (HSCR) is a genetic disorder characterized by the absence of neural crest cells in parts of the intestine. This study aims to investigate the association of vesicle-associated membrane protein 5 ( VAMP5 ) and mutated in colorectal cancer ( MCC ) genetic polymorphisms and their correlated risks with HSCR. We examined the association in four polymorphisms (rs10206961, rs1254900 and rs14242 in VAMP5 , rs11241200 in MCC ) and HSCR susceptibility in a Southern Chinese population composed of 1473 cases and 1469 controls. Two variants in VAMP5 were replicated as associated with HSCR. Interestingly, we clarified SNPs rs10206961 and rs1254900 in VAMP5 are more essential for patients with long-segment aganglionosis (LHSCR). Relatively high expression correlation was observed between VAMP5 and MCC using data from public database showing there may exist potential genetic interactions. SNP interaction was cross-examined by logistic regression and multifactor dimensionality reduction analysis revealing that VAMP5 rs1254900 and MCC rs11241200 were interacting significantly, thereby contributing to the risk of HSCR. The results suggest that significant associations of the rs10206961 and rs14242 in VAMP5 with an increased risk of HSCR in Southern Chinese, especially in LHSCR patients. This study provided new evidence of epistatic association of VAMP5 and MCC with increased risk of HSCR.

Polyomavirus-Negative Merkel Cell Carcinoma: A More Aggressive Subtype Based on Analysis of 282 Cases Using Multimodal Tumor Virus Detection.

PubMed

Moshiri, Ata S; Doumani, Ryan; Yelistratova, Lola; Blom, Astrid; Lachance, Kristina; Shinohara, Michi M; Delaney, Martha; Chang, Oliver; McArdle, Susan; Thomas, Hannah; Asgari, Maryam M; Huang, Meei-Li; Schwartz, Stephen M; Nghiem, Paul

2017-04-01

Previous studies have reached conflicting conclusions regarding the proportion of Merkel cell carcinomas (MCCs) that contain the Merkel cell polyomavirus (MCPyV) and the clinical significance of tumor viral status. To address these controversies, we detected MCPyV large T antigen using immunohistochemistry with two distinct antibodies and MCPyV DNA using quantitative PCR. Tumors were called MCPyV-positive if two or more of these three assays indicated presence of this virus. A total of 53 of 282 (19%) MCC tumors in this cohort were virus-negative using this multimodal system. Immunohistochemistry with the CM2B4 antibody had the best overall performance (sensitivity = 0.882, specificity = 0.943) compared with the multimodal classification. Multivariate analysis including age, sex, and immunosuppression showed that, relative to MCC patients with virus-positive tumors, virus-negative MCC patients had significantly increased risk of disease progression (hazard ratio = 1.77, 95% confidence interval = 1.20-2.62) and death from MCC (hazard ratio = 1.85, 95% confidence interval = 1.19-2.89). We confirm that approximately 20% of MCCs are not driven by MCPyV and that such virus-negative MCCs, which can be quite reliably identified by immunohistochemistry using the CM2B4 antibody alone, represent a more aggressive subtype that warrants closer clinical follow-up. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Immunotherapy in Merkel cell carcinoma: role of Avelumab.

PubMed

Palla, Amruth R; Doll, Donald

2018-01-01

Merkel cell carcinoma (MCC), a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer.

Radiotherapy is associated with significant improvement in local and regional control in Merkel cell carcinoma

PubMed Central

2012-01-01

Introduction Merkel cell carcinoma (MCC) is a rare tumour of skin. This study is a retrospective audit of patients with MCC from St Vincent’s and Mater Hospital, Sydney, Australia. The aim of this study was to investigate the influence of radiotherapy (RT) on the local and regional control of MCC lesions and survival of patients with MCC. Method The data bases in anatomical pathology, RT and surgery. We searched for patients having a diagnosis of MCC between 1996 and 2007. Patient, tumour and treatment characteristics were collected and analysed. Univariate survival analysis of categorical variables was conducted with the Kaplan-Meier method together with the Log-Rank test for statistical significance. Continuous variables were assessed using the Cox regression method. Multivariate analysis was performed for significant univariate results. Results Sixty seven patients were found. Sixty two who were stage I-III and were treated with radical intent were analysed. 68% were male. The median age was 74 years. Forty-two cases (68%) were stage I or II, and 20 cases (32%) were stage III. For the subset of 42 stage I and II patients, those that had RT to their primary site had a 2-year local recurrence free survival of 89% compared with 36% for patients not receiving RT (p<0.001). The cumulative 2-year regional recurrence free survival for patients having adjuvant regional RT was 84% compared with 43% for patients not receiving this treatment (p<0.001). Immune status at initial surgery was a significant predictor for OS and MCCSS. In a multivariate analysis combining macroscopic size (mm) and immune status at initial surgery, only immune status remained a significant predictor of overall survival (HR=2.096, 95% CI: 1.002-4.385, p=0.049). Conclusions RT is associated with significant improvement in local and regional control in Merkel cell carcinoma. Immunosuppression is an important factor in overall survival. PMID:23075308

Evaluation of Mucociliary Clearance by Three Dimension Micro-CT-SPECT in Guinea Pig: Role of Bitter Taste Agonists.

PubMed

Ortiz, Jose Luis; Ortiz, Amparo; Milara, Javier; Armengot, Miguel; Sanz, Celia; Compañ, Desamparados; Morcillo, Esteban; Cortijo, Julio

2016-01-01

Different image techniques have been used to analyze mucociliary clearance (MCC) in humans, but current small animal MCC analysis using in vivo imaging has not been well defined. Bitter taste receptor (T2R) agonists increase ciliary beat frequency (CBF) and cause bronchodilation but their effects in vivo are not well understood. This work analyzes in vivo nasal and bronchial MCC in guinea pig animals using three dimension (3D) micro-CT-SPECT images and evaluates the effect of T2R agonists. Intranasal macroaggreggates of albumin-Technetium 99 metastable (MAA-Tc99m) and lung nebulized Tc99m albumin nanocolloids were used to analyze the effect of T2R agonists on nasal and bronchial MCC respectively, using 3D micro-CT-SPECT in guinea pig. MAA-Tc99m showed a nasal mucociliary transport rate of 0.36 mm/min that was increased in presence of T2R agonist to 0.66 mm/min. Tc99m albumin nanocolloids were homogeneously distributed in the lung of guinea pig and cleared with time-dependence through the bronchi and trachea of guinea pig. T2R agonist increased bronchial MCC of Tc99m albumin nanocolloids. T2R agonists increased CBF in human nasal ciliated cells in vitro and induced bronchodilation in human bronchi ex vivo. In summary, T2R agonists increase MCC in vivo as assessed by 3D micro-CT-SPECT analysis.

Emerging differential roles of the pRb tumor suppressor in trichodysplasia spinulosa-associated polyomavirus and Merkel cell polyomavirus pathogeneses.

PubMed

Wu, Julie H; Simonette, Rebecca A; Nguyen, Harrison P; Doan, Hung Q; Rady, Peter L; Tyring, Stephen K

2016-03-01

Merkel cell carcinoma (MCC) and trichodysplasia spinulosa (TS) are two proliferative cutaneous diseases caused by the Merkel cell polyomavirus (MCPyV) and trichodysplasia spinulosa-associated polyomavirus (TSPyV) respectively. Recently, studies have elucidated a key role of the small tumor (sT) antigen in the proliferative pathogenic mechanisms of MCPyV and likely TSPyV. While both sT antigens have demonstrated a capacity in regulating cellular pathways, it remains unknown whether MCPyV and TSPyV sT antigens contribute similarly or differentially to cell proliferation. The present study aims to explore the proliferative potential of MCPyV and TSPyV sT antigens by investigating their regulatory effects on the retinoblastoma protein (pRb) tumor suppressor. Inducible cell lines expressing MCPyV sT or TSPyV sT were created using a lentiviral packaging system. Cellular proteins were extracted and subjected to SDS-PAGE followed by Western blot detection and densitometric analysis. Expression of TSPyV sT markedly enhanced the phosphorylation of pRb in Western blot experiments. In contrast, expression of MCPyV sT did not alter pRb phosphorylation under the same experimental conditions. Densitometric analysis revealed that TSPyV sT antigen expression nearly doubled the ratio of phosphorylated to total pRb (P<0.001, Student's T-test), while MCPyV sT antigen expression did not cause significant change in pRb phosphorylation status. Given that hyperphosphorylation of pRb is associated with dysregulation of the cell cycle, S-phase induction, and increased cell proliferation, our findings support an important role of TSPyV-mediated pRb deactivation in the development of TS. The observation that the pRb tumor suppressor is inactivated by TSPyV sT but not MCPyV sT provides further insights into the distinct pathobiological mechanisms of MCC and TS. Copyright © 2016 Elsevier B.V. All rights reserved.

Multiciliated Cells in Animals.

PubMed

Meunier, Alice; Azimzadeh, Juliette

2016-12-01

Many animal cells assemble single cilia involved in motile and/or sensory functions. In contrast, multiciliated cells (MCCs) assemble up to 300 motile cilia that beat in a coordinate fashion to generate a directional fluid flow. In the human airways, the brain, and the oviduct, MCCs allow mucus clearance, cerebrospinal fluid circulation, and egg transportation, respectively. Impairment of MCC function leads to chronic respiratory infections and increased risks of hydrocephalus and female infertility. MCC differentiation during development or repair involves the activation of a regulatory cascade triggered by the inhibition of Notch activity in MCC progenitors. The downstream events include the simultaneous assembly of a large number of basal bodies (BBs)-from which cilia are nucleated-in the cytoplasm of the differentiating MCCs, their migration and docking at the plasma membrane associated to an important remodeling of the actin cytoskeleton, and the assembly and polarization of motile cilia. The direction of ciliary beating is coordinated both within cells and at the tissue level by a combination of planar polarity cues affecting BB position and hydrodynamic forces that are both generated and sensed by the cilia. Herein, we review the mechanisms controlling the specification and differentiation of MCCs and BB assembly and organization at the apical surface, as well as ciliary assembly and coordination in MCCs. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

Immunotherapy in Merkel cell carcinoma: role of Avelumab

PubMed Central

Palla, Amruth R; Doll, Donald

2018-01-01

Merkel cell carcinoma (MCC), a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer. PMID:29535979

Examining Merkel Cell Polyomavirus Minor Capsid Proteins | Center for Cancer Research

Cancer.gov

Merkel cell polyomavirus (MCV or MCPyV) is a recently discovered member of the viral family Polyomaviridae. It is a skin-dwelling polyomavirus species that appears to cause a rare but highly lethal form of skin cancer called Merkel cell carcinoma (MCC). Despite MCC being uncommon, chronic MCV infection of human skin is widespread, and most infected people have no known symptoms. The surface of polyomavirus virions is made up of pentameric knobs of the major capsid protein VP1. VP1 enables attachment of the virus to the cell surface, permitting infectious entry and delivery of the viral genome to host cells. The VP1 protein of previously studied polyomaviruses, such as simian virus 40 and murine polyomavirus, associates with two minor capsid proteins, VP2 and VP3, which are considered to play important roles during the infectious entry process.

High-Affinity Rb Binding, p53 Inhibition, Subcellular Localization, and Transformation by Wild-Type or Tumor-Derived Shortened Merkel Cell Polyomavirus Large T Antigens

PubMed Central

Borchert, Sophie; Czech-Sioli, Manja; Neumann, Friederike; Schmidt, Claudia; Wimmer, Peter; Dobner, Thomas

2014-01-01

ABSTRACT Interference with tumor suppressor pathways by polyomavirus-encoded tumor antigens (T-Ags) can result in transformation. Consequently, it is thought that T-Ags encoded by Merkel cell polyomavirus (MCPyV), a virus integrated in ∼90% of all Merkel cell carcinoma (MCC) cases, are major contributors to tumorigenesis. The MCPyV large T-Ag (LT-Ag) has preserved the key functional domains present in all family members but has also acquired unique regions that flank the LxCxE motif. As these regions may mediate unique functions, or may modulate those shared with T-Ags of other polyomaviruses, functional studies of MCPyV T-Ags are required. Here, we have performed a comparative study of full-length or MCC-derived truncated LT-Ags with regard to their biochemical characteristics, their ability to bind to retinoblastoma (Rb) and p53 proteins, and their transforming potential. We provide evidence that full-length MCPyV LT-Ag may not directly bind to p53 but nevertheless can significantly reduce p53-dependent transcription in reporter assays. Although early region expression constructs harboring either full-length or MCC-derived truncated LT-Ag genes can transform primary baby rat kidney cells, truncated LT-Ags do not bind to p53 or reduce p53-dependent transcription. Interestingly, shortened LT-Ags exhibit a very high binding affinity for Rb, as shown by coimmunoprecipitation and in vitro binding studies. Additionally, we show that truncated MCPyV LT-Ag proteins are expressed at higher levels than those for the wild-type protein and are able to partially relocalize Rb to the cytoplasm, indicating that truncated LT proteins may have gained additional features that distinguish them from the full-length protein. IMPORTANCE MCPyV is one of the 12 known polyomaviruses that naturally infect humans. Among these, it is of particular interest since it is the only human polyomavirus known to be involved in tumorigenesis. MCPyV is thought to be causally linked to MCC, a rare skin tumor. In these tumors, viral DNA is monoclonally integrated into the genome of the tumor cells in up to 90% of all MCC cases, and the integrated MCV genomes, furthermore, harbor signature mutations in the so-called early region that selectively abrogate viral replication while preserving cell cycle deregulating functions of the virus. This study describes comparative studies of early region T-Ag protein characteristics, their ability to bind to Rb and p53, and their transforming potential. PMID:24371076

Impact of Resolution on Simulation of Closed Mesoscale Cellular Convection Identified by Dynamically Guided Watershed Segmentation

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

Martini, Matus N.; Gustafson, William I.; Yang, Qing

2014-11-18

Organized mesoscale cellular convection (MCC) is a common feature of marine stratocumulus that forms in response to a balance between mesoscale dynamics and smaller scale processes such as cloud radiative cooling and microphysics. We use the Weather Research and Forecasting model with chemistry (WRF-Chem) and fully coupled cloud-aerosol interactions to simulate marine low clouds during the VOCALS-REx campaign over the southeast Pacific. A suite of experiments with 3- and 9-km grid spacing indicates resolution-dependent behavior. The simulations with finer grid spacing have smaller liquid water paths and cloud fractions, while cloud tops are higher. The observed diurnal cycle is reasonablymore » well simulated. To isolate organized MCC characteristics we develop a new automated method, which uses a variation of the watershed segmentation technique that combines the detection of cloud boundaries with a test for coincident vertical velocity characteristics. This ensures that the detected cloud fields are dynamically consistent for closed MCC, the most common MCC type over the VOCALS-REx region. We demonstrate that the 3-km simulation is able to reproduce the scaling between horizontal cell size and boundary layer height seen in satellite observations. However, the 9-km simulation is unable to resolve smaller circulations corresponding to shallower boundary layers, instead producing invariant MCC horizontal scale for all simulated boundary layers depths. The results imply that climate models with grid spacing of roughly 3 km or smaller may be needed to properly simulate the MCC structure in the marine stratocumulus regions.« less

Genetic control of flame retardancy in white lint cotton (gossypium hirsutum)

USDA-ARS?s Scientific Manuscript database

Varieties of cotton (Gossypium hirsutum L.) exhibit differences in fiber combustion properties and flame retardancy (FR) as measured by microscale combustion calorimetry (MCC) and standardized flammability testing. Some naturally colored brown lint cotton lines produce fibers that can create self-ex...

Particle in cell/Monte Carlo collision analysis of the problem of identification of impurities in the gas by the plasma electron spectroscopy method

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

Kusoglu Sarikaya, C.; Rafatov, I., E-mail: rafatov@metu.edu.tr; Kudryavtsev, A. A.

2016-06-15

The work deals with the Particle in Cell/Monte Carlo Collision (PIC/MCC) analysis of the problem of detection and identification of impurities in the nonlocal plasma of gas discharge using the Plasma Electron Spectroscopy (PLES) method. For this purpose, 1d3v PIC/MCC code for numerical simulation of glow discharge with nonlocal electron energy distribution function is developed. The elastic, excitation, and ionization collisions between electron-neutral pairs and isotropic scattering and charge exchange collisions between ion-neutral pairs and Penning ionizations are taken into account. Applicability of the numerical code is verified under the Radio-Frequency capacitively coupled discharge conditions. The efficiency of the codemore » is increased by its parallelization using Open Message Passing Interface. As a demonstration of the PLES method, parallel PIC/MCC code is applied to the direct current glow discharge in helium doped with a small amount of argon. Numerical results are consistent with the theoretical analysis of formation of nonlocal EEDF and existing experimental data.« less

Secondary metabolism in simulated microgravity

NASA Technical Reports Server (NTRS)

Demain, A. L.; Fang, A.

2001-01-01

We have studied microbial secondary metabolism in a simulated microgravity (SMG) environment provided by NASA rotating-wall bioreactors (RWBs). These reactors were designed to simulate some aspects of actual microgravity that occur in space. Growth and product formation were observed in SMG in all cases studied, i.e., Bacillus brevis produced gramicidin S (GS), Streptomyces clavuligerus made beta-lactam antibiotics, Streptomyces hygroscopicus produced rapamycin, and Escherichia coli produced microcin B17 (MccB17). Of these processes, only GS production was unaffected by SMG; production of the other three products was inhibited. This was determined by comparison with performance in an RWB positioned in a different mode to provide a normal gravity (NG) environment. Carbon source repression by glycerol of the GS process, as observed in shaken flasks, was not observed in the RWBs, whether operated in the SMG or NG mode. The same phenomenon occurred in the case of MccB17 production, with respect to glucose repression. Thus, the negative effects of carbon source on GS and beta-lactam formation are presumably dependent on shear, turbulence, and/or vessel geometry, but not on gravity. Stimulatory effects of phosphate and the precursor L-lysine on beta-lactam antibiotic production, as observed in flasks, also occurred in SMG. An almost complete shift in the localization of produced MccB17 from cells to extracellular medium was observed when E. coli was grown in the RWB under SMG or NG. If a plastic bead was placed in the RWB, accumulation became cellular, as it is in shaken flasks, indicating that sheer stress favors a cellular location. In the case of rapamycin, the same type of shift was observed, but it was less dramatic, i.e., growth in the RWB under SMG shifted the distribution of produced rapamycin from 2/3 cellular:1/3 extracellular to 1/3 cellular:2/3 extracellular. Stress has been shown to induce or promote secondary metabolism in a number of other microbial systems. RWBs provide a low stress SMG environment, which, however, supports only poor production of MccB17, as compared to production in shaken flasks. We wondered whether the poor production in RWBs under SMG is due to the low level of stress, and whether increasing stress in the RWBs would raise the amount of MccB17 formed. We found that increasing shear stress by adding a single Teflon bead to the RWB improved MccB17 production. Although shear stress seems to have a marked positive effect on MccB17 production in SMG, addition of various concentrations of ethanol to RWBs (or to shaken flasks) failed to increase MccB17 production. Ethanol stress merely decreased production and, at higher concentrations, inhibited growth. Interestingly, cells growing in the RWB were much more resistant to the growth- and production-inhibitory effects of ethanol than cells growing in shaken flasks. With respect to S. hygroscopicus, addition of Teflon beads to the RWB reversed the inhibition of growth, but rapamycin production was still markedly inhibited, and the distribution did not revert back to a preferential cellular site.

Identifying Meteorological Controls on Open and Closed Mesoscale Cellular Convection Associated with Marine Cold Air Outbreaks

NASA Astrophysics Data System (ADS)

McCoy, Isabel L.; Wood, Robert; Fletcher, Jennifer K.

2017-11-01

Mesoscale cellular convective (MCC) clouds occur in large-scale patterns over the ocean and have important radiative effects on the climate system. An examination of time-varying meteorological conditions associated with satellite-observed open and closed MCC clouds is conducted to illustrate the influence of large-scale meteorological conditions. Marine cold air outbreaks (MCAO) influence the development of open MCC clouds and the transition from closed to open MCC clouds. MCC neural network classifications on Moderate Resolution Imaging Spectroradiometer (MODIS) data for 2008 are collocated with Clouds and the Earth's Radiant Energy System (CERES) data and ERA-Interim reanalysis to determine the radiative effects of MCC clouds and their thermodynamic environments. Closed MCC clouds are found to have much higher albedo on average than open MCC clouds for the same cloud fraction. Three meteorological control metrics are tested: sea-air temperature difference (ΔT), estimated inversion strength (EIS), and a MCAO index (M). These predictive metrics illustrate the importance of atmospheric surface forcing and static stability for open and closed MCC cloud formation. Predictive sigmoidal relations are found between M and MCC cloud frequency globally and regionally: negative for closed MCC cloud and positive for open MCC cloud. The open MCC cloud seasonal cycle is well correlated with M, while the seasonality of closed MCC clouds is well correlated with M in the midlatitudes and EIS in the tropics and subtropics. M is found to best distinguish open and closed MCC clouds on average over shorter time scales. The possibility of a MCC cloud feedback is discussed.

Multicapillary Gas Chromatography-Temperature Modulated Metal Oxide Semiconductor Sensors Array Detector for Monitoring of Volatile Organic Compounds in Closed Atmosphere Using Gaussian Apodization Factor Analysis.

PubMed

Alinoori, Amir Hossein; Masoum, Saeed

2018-05-22

A unique metal oxide semiconductor sensor (MOS) array detector with eight sensors was designed and fabricated in a PTFE chamber as an interface for coupling with multicapillary gas chromatography. This design consists of eight transfer lines with equal length between the multicapillary columns (MCC) and sensors. The deactivated capillary columns were passed through each transfer line and homemade flow splitter to distribute the same gas flow on each sensor. Using the eight ports flow splitter design helps us to equal the length of carrier gas path and flow for each sensor, minimizing the dead volume of the sensor's chamber and increasing chromatographic resolution. In addition to coupling of MCC to MOS array detector and other considerations in hardware design, modulation of MOS temperature was used to increase sensitivity and selectivity, and data analysis was enhanced with adapted Gaussian apodization factor analysis (GAFA) as a multivariate curve resolution algorithm. Continues air sampling and injecting system (CASI) design provides a fast and easily applied method for continues injection of air sample with no additional sample preparation. The analysis cycle time required for each run is less than 300 s. The high sample load and sharp injection with the fast separation by MCC decrease the peak widths and improve detection limits. This homemade customized instrument is an alternative to other time-consuming and expensive technologies for continuous monitoring of outgassing in air samples.

Multiple Chronic Conditions and Healthcare Costs among Adults

PubMed Central

Sambamoorthi, Usha; Tan, Xi; Deb, Arijita

2015-01-01

The prevalence of multiple chronic conditions (MCC) is increasing among individuals of all ages. MCC are associated with poor health outcomes. The presence of MCC has profound healthcare utilization and cost implications for public and private insurance payers, individuals, and families. Investigators have used a variety of definitions for MCC to evaluate costs associated with MCC. The objective of this article is to examine the current literature in estimating excess costs associated with MCC among adults. The discussion highlights some of the theoretical and technical merits of various MCC definitions and models used to estimate the excess costs associated with MCC. PMID:26400220

Evaluation of De-O-Acetylated Meningococcal C Polysaccharide-Tetanus Toxoid Conjugate Vaccine in Infancy: Reactogenicity, Immunogenicity, Immunologic Priming, and Bactericidal Activity against O-Acetylated and De-O-Acetylated Serogroup C Strains

PubMed Central

Richmond, Peter; Borrow, Ray; Findlow, Jamie; Martin, Sarah; Thornton, Carol; Cartwright, Keith; Miller, Elizabeth

2001-01-01

The polysaccharide capsule of serogroup C Neisseria meningitidis (MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O-acetylated (OAc+) form of polysaccharide. Some MenC strains have de-O-acetylated (OAc−) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio immunization in 83 infants at 2, 3, and 4 months of age. Serum bactericidal activities (SBA) against OAc+ and OAc− MenC strains and OAc+ and OAc− polysaccharide-specific immunoglobulin G (IgG) levels were evaluated. MCC-TT vaccine was well tolerated. All infants produced SBA titers of ≥8 after a single dose at 2 months of age. The SBA geometric mean titer for OAc+ strain C11 increased from 2.7 (95% confidence interval [CI] 2.2 to 3.2) to 320 (95% CI, 237 to 432), 773 (95% CI, 609 to 982), and 1,063 (95% CI, 856 to 1319) after one, two, and three doses of MCC-TT, respectively. OAc− IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SBA was significantly higher against the OAc− MenC strain. Antibody responses to booster vaccination with either OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 14 months of age provided evidence of immunologic memory. The acetylation status of the booster vaccine influenced the specificity of the response, with significantly higher OAc− IgG levels and SBA after MCC-TT vaccine compared to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highly immunogenic and primes for immunologic memory against OAc+ and OAc− MenC strains in infancy. PMID:11254596

CO2 Fixation, Lipid Production, and Power Generation by a Novel Air-Lift-Type Microbial Carbon Capture Cell System.

PubMed

Hu, Xia; Liu, Baojun; Zhou, Jiti; Jin, Ruofei; Qiao, Sen; Liu, Guangfei

2015-09-01

An air-lift-type microbial carbon capture cell (ALMCC) was constructed for the first time by using an air-lift-type photobioreactor as the cathode chamber. The performance of ALMCC in fixing high concentration of CO2, producing energy (power and biodiesel), and removing COD together with nutrients was investigated and compared with the traditional microbial carbon capture cell (MCC) and air-lift-type photobioreactor (ALP). The ALMCC system produced a maximum power density of 972.5 mW·m(-3) and removed 86.69% of COD, 70.52% of ammonium nitrogen, and 69.24% of phosphorus, which indicate that ALMCC performed better than MCC in terms of power generation and wastewater treatment efficiency. Besides, ALMCC demonstrated 9.98- and 1.88-fold increases over ALP and MCC in the CO2 fixation rate, respectively. Similarly, the ALMCC significantly presented a higher lipid productivity compared to those control reactors. More importantly, the preliminary analysis of energy balance suggested that the net energy of the ALMCC system was significantly superior to other systems and could theoretically produce enough energy to cover its consumption. In this work, the established ALMCC system simultaneously achieved the high level of CO2 fixation, energy recycle, and municipal wastewater treatment effectively and efficiently.

Mast cells in Canine parvovirus-2-associated enteritis with crypt abscess.

PubMed

Woldemeskel, M W; Saliki, J T; Blas-Machado, U; Whittington, L

2013-11-01

The role of mast cells (MCs) in allergic reactions and parasitic infections is well established. Their involvement in host immune response against bacterial and viral infections is reported. In this study, investigation is made to determine if MCs are associated with Canine parvovirus-2 (CPV-2)-induced enteritis with crypt abscess (ECA). Mast cell count (MCC) was made on toluidine blue-stained intestinal sections from a total of 34 dogs. These included 16 dogs exhibiting ECA positive for CPV-2 and negative for Canine distemper virus and Canine coronavirus by immunohistochemistry and fluorescent antibody test, 12 dogs with inflammatory bowel disease (IBD), and 6 non-ECA/non-IBD (control) dogs. The average total MCC per high-power field in ECA (40.8 ± 2.2) and IBD (24.7 ± 2.1) was significantly higher (P < .05) than in the control (3.4 ± 0.6). Although not significant (P > .05), MCC was also higher in ECA than in IBD. The present study for the first time has documented significantly increased MCs in CPV-2-associated ECA as was previously reported for IBD, showing that MCs may also play an important role in CPV-2-associated ECA. Further studies involving more CPV-infected dogs are recommended to substantiate the findings.

Cellular and Matrix Response of the Mandibular Condylar Cartilage to Botulinum Toxin

PubMed Central

Dutra, Eliane H.; O’ Brien, Mara H.; Lima, Alexandro; Kalajzic, Zana; Tadinada, Aditya; Nanda, Ravindra; Yadav, Sumit

2016-01-01

Objectives To evaluate the cellular and matrix effects of botulinum toxin type A (Botox) on mandibular condylar cartilage (MCC) and subchondral bone. Materials and Methods Botox (0.3 unit) was injected into the right masseter of 5-week-old transgenic mice (Col10a1-RFPcherry) at day 1. Left side masseter was used as intra-animal control. The following bone labels were intraperitoneally injected: calcein at day 7, alizarin red at day 14 and calcein at day 21. In addition, EdU was injected 48 and 24 hours before sacrifice. Mice were sacrificed 30 days after Botox injection. Experimental and control side mandibles were dissected and examined by x-ray imaging and micro-CT. Subsequently, MCC along with the subchondral bone was sectioned and stained with tartrate resistant acid phosphatase (TRAP), EdU, TUNEL, alkaline phosphatase, toluidine blue and safranin O. In addition, we performed immunohistochemistry for pSMAD and VEGF. Results Bone volume fraction, tissue density and trabecular thickness were significantly decreased on the right side of the subchondral bone and mineralized cartilage (Botox was injected) when compared to the left side. There was no significant difference in the mandibular length and condylar head length; however, the condylar width was significantly decreased after Botox injection. Our histology showed decreased numbers of Col10a1 expressing cells, decreased cell proliferation and increased cell apoptosis in the subchondral bone and mandibular condylar cartilage, decreased TRAP activity and mineralization of Botox injected side cartilage and subchondral bone. Furthermore, we observed reduced proteoglycan and glycosaminoglycan distribution and decreased expression of pSMAD 1/5/8 and VEGF in the MCC of the Botox injected side in comparison to control side. Conclusion Injection of Botox in masseter muscle leads to decreased mineralization and matrix deposition, reduced chondrocyte proliferation and differentiation and increased cell apoptosis in the MCC and subchondral bone. PMID:27723812

Association of expression of the hedgehog signal with Merkel cell polyomavirus infection and prognosis of Merkel cell carcinoma.

PubMed

Kuromi, Teruyuki; Matsushita, Michiko; Iwasaki, Takeshi; Nonaka, Daisuke; Kuwamoto, Satoshi; Nagata, Keiko; Kato, Masako; Akizuki, Gen; Kitamura, Yukisato; Hayashi, Kazuhiko

2017-11-01

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer that mostly occurs in the elderly. Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of MCCs and is associated with carcinogenesis. Hedgehog signaling pathway plays a role in human embryogenesis and organogenesis. In addition, reactivation of this pathway later in life can cause tumors. Twenty-nineMCPyV-positive and 21 MCPyV-negative MCCs were immunohistochemically stained with primary antibodies for hedgehog signaling (SHH, IHH, PTCH1, SMO, GLI1, GLI2, and GLI3) and evaluated using H-score. Polymerase chain reaction and sequence analysis for SHH and GLI1 exons were also performed. Expression of SHH was higher in MCPyV-positive MCCs than in MCPyV-negative MCCs (P<.001). Higher expression of GLI1, MCPyV infection, male sex, and Japanese ethnicity were associated with better overall survival (P=.034, P=.001, P=.042, and P=.036, respectively). Higher expression of SHH and MCPyV infection were associated with improved MCC-specific survival (P=.037 and P=.002, respectively). The mutation analysis of prognosis-related GLI1 and SHH genes in our study revealed a low frequency of mutations in the 10 exons examined, except GLI1 exon 5 (18/22 cases), all having the same silent mutation of c.576G>A. Only 2 mutations with amino acid changes were detected in MCPyV-negative MCCs only: 1 missense mutation in GLI1 exon 4 and 1 nonsense mutation in SHH-3B. Expression of SHH and GLI1 may be useful prognostic markers of MCC because increased expression was associated with better prognosis. The high rate of c.576G>A silent mutation in GLI1 exon 5 was a feature of MCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Understanding the influence of patient demographics on disease severity, treatment strategy, and survival outcomes in merkel cell carcinoma: a surveillance, epidemiology, and end-results study.

PubMed

Ezaldein, Harib H; Ventura, Alessandra; DeRuyter, Nicolaas P; Yin, Emily S; Giunta, Alessandro

2017-07-01

To identify trends in patient presentation and outcomes data that may guide the development of clinical algorithms on Merkel Cell Carcinoma (MCC). We performed a retrospective cohort study searching in the National Cancer Institute's SEER registry for documented MCC cases from 1986-2013. No exclusion criteria were applied. We hereby identified 7,831 original MCC entries. Demographics, staging, and socioeconomic characteristics were identified and treatment modality likelihoods and survival data were calculated via logistic regression and Kaplan-Meier statistical modeling. Concerning tumor localization, 44.5% (n= 3,485) were located on the head and neck, and 47.8% were located on the trunk and extremities (n= 3,742). Male and younger patients are more likely to receive radiation than surgery with no differences seen among patient race. Caucasians and "Other" races both showed higher overall survival than African American patients. States with higher median household income levels demonstrated survival advantage. Income quartiles yielded no differences in surgical or radiotherapy interventions. Moreover, patients who forego radiotherapy had a poorer overall survival. Generalizability of SEER data, potential intrinsic coding inconsistencies, and limited information on patient comorbidities, sentinel lymph node and surgical margin status are major limitations. There is no information regarding medical intervention such as systemic chemotherapy or immunotherapy. Recoding efforts are inconclusive regarding variables such as tumor infiltrating lymphocytes, mutations, or immunosuppression status, which are well-documented for other cancers within the database. MCC lesions of the head and neck region, lower income quartiles, and African American race are associated with higher mortality. MCC patients have a median household income that is significantly higher than national values with no significant difference in subsequent treatment modalities (surgery or radiotherapy) based on socioeconomic markers. A lack of radiotherapy is associated with higher mortality.

The role of adjuvant therapy in the management of head and neck merkel cell carcinoma: an analysis of 4815 patients.

PubMed

Chen, Michelle M; Roman, Sanziana A; Sosa, Julie A; Judson, Benjamin L

2015-02-01

Merkel cell carcinoma (MCC) is a rare neuroendocrine malignant neoplasm that most commonly occurs in the head and neck and is rapidly increasing in incidence. The role of adjuvant chemoradiotherapy (CRT) in the management of head and neck MCC remains controversial. To evaluate the association between different adjuvant therapies and survival in head and neck MCC. Retrospective review of adult patients with head and neck MCC who had surgery recorded in the National Cancer Data Base from 1998 to 2011. Surgical excision, adjuvant radiation therapy (RT), or adjuvant CRT. Our main outcome was overall survival (OS). Statistical analysis included χ2, t tests, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. We identified 4815 patients; 92.0% underwent standard surgical excision, and 8.0% underwent Mohs surgery. On multivariate analysis, age at least 75 years (hazard ratio [HR], 2.83 [95% CI, 1.82-4.41]), larger tumor size, positive margins (HR, 1.52 [95% CI, 1.25-1.85]), and metastatic lymph nodes (HR, 2.29 [95% CI, 1.84-2.85]) were independently associated with decreased OS. Postoperative CRT (HR, 0.62 [95% CI, 0.47-0.81]) and RT (HR, 0.80 [95% CI, 0.70-0.92]) provided a survival benefit over surgery alone. Adjuvant CRT was associated with improved OS over adjuvant RT in patients with positive margins (HR, 0.48 [95% CI, 0.25-0.93]), tumor size at least 3 cm (HR, 0.52 [95% CI, 0.30-0.90]), and male sex (HR, 0.69 [95% CI, 0.50-0.94]). To our knowledge, this the first study examining the role of adjuvant CRT in head and neck MCC. Results suggest that adjuvant CRT may help improve survival in high-risk patients, such as males and those with positive margins and larger tumors.

Oxygen With Cold Bubble Humidification Is No Better Than Dry Oxygen in Preventing Mucus Dehydration, Decreased Mucociliary Clearance, and Decline in Pulmonary Function.

PubMed

Franchini, Michelle Lisidati; Athanazio, Rodrigo; Amato-Lourenço, Luis Fernando; Carreirão-Neto, Waldir; Saldiva, Paulo Hilario Nascimento; Lorenzi-Filho, Geraldo; Rubin, Bruce K; Nakagawa, Naomi Kondo

2016-08-01

Little is known about the effects of long-term nasal low-flow oxygen (NLFO) on mucus and symptoms and how this variable is affected by dry or cold humidified gas. The aim of this study was to investigate the effects of dry-NLFO and cold bubble humidified-NLFO on nasal mucociliary clearance (MCC), mucus properties, inflammation, and symptoms in subjects with chronic hypoxemia requiring long-term domiciliary oxygen therapy. Eighteen subjects (mean age, 68 years; 7 male; 66% with COPD) initiating NLFO were randomized to receive dry-NLFO (n = 10) or humidified-NLFO (n = 8). Subjects were assessed at baseline, 12 h, 7 days, 30 days, 12 months, and 24 months by measuring nasal MCC using the saccharin transit test, mucus contact angle (surface tension), inflammation (cells and cytokine concentration in nasal lavage), and symptoms according to the Sino-Nasal Outcome Test-20. Nasal MCC decreased significantly (40% longer saccharin transit times) and similarly in both groups over the study period. There was a significant association between impaired nasal MCC and decline in lung function. Nasal lavage revealed an increased proportion of macrophages, interleukin-8, and epidermal growth factor concentrations with decreased interleukin-10 during the study. No changes in the proportion of ciliated cells or contact angle were observed. Coughing and sleep symptoms decreased similarly in both groups. There were no outcome differences comparing dry vs cold bubble humidified NLFO. In subjects receiving chronic NLFO, cold bubble humidification does not adequately humidify inspired oxygen to prevent deterioration of MCC, mucus hydration, and pulmonary function. The unheated bubble humidification performed no better than no humidification. ClinicalTrials.gov; No.: NCT02515786; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

View of Mission Control Center during the Apollo 13 oxygen cell failure

NASA Technical Reports Server (NTRS)

1970-01-01

Several persons important to the Apollo 13 mission, at consoles in the Mission Operations Control Room of the Mission Control Center (MCC). Seated at consoles, from left to right, are Astronaut Donald K. Slayton, Director of Flight Crew Operations; Astronaut Jack R. Lousma, Shift 3 spacecraft communicator; and Astronaut John W. Young, commander of the Apollo 13 back-up crew. Standing, left to right, are Astronaut Tom K. Mattingly, who was replaced as Apollo 13 command module pilot after it was learned he may come down with measles, and Astronaut Vance D. Brand, Shift 2 spacecraft communicator. Several hours earlier crew members of the Apollo 13 mission reported to MCC that trouble had developed with an oxygen cell in their spacecraft.

Dielectric barrier discharge plasma pretreatment on hydrolysis of microcrystalline cellulose

NASA Astrophysics Data System (ADS)

Huang, Fangmin; Long, Zhouyang; Liu, Sa; Qin, Zhenglong

2017-04-01

Dielectric barrier discharge (DBD) plasma was used as a pretreatment method for downstream hydrolysis of microcrystalline cellulose (MCC). The degree of polymerization (DP) of MCC decreased after it was pretreated by DBD plasma under a carrier gas of air/argon. The effectiveness of depolymerization was found to be influenced by the crystallinity of MCC when under the pretreatment of DBD plasma. With the addition of tert-butyl alcohol in the treated MCC water suspension solution, depolymerization effectiveness of MCC was inhibited. When MCC was pretreated by DBD plasma for 30 min, the total reducing sugar concentration (TRSC) and liquefaction yield (LY) of pretreated-MCC (PMCC) increased by 82.98% and 34.18% respectively compared with those for raw MCC.

Preparation and Characterization of Cellulose Microcrystalline (MCC) from Fiber of Empty Fruit Bunch Palm Oil

NASA Astrophysics Data System (ADS)

Nasution, H.; Yurnaliza; Veronicha; Irmadani; Sitompul, S.

2017-03-01

Alpha cellulose which was isolated from cellulose of fiber empty fruit bunch palm oil was hidrolized with hydrochloric acid (2,5N) at 80°C to produce microcrystalline cellulose (MCC). Microcrystalline cellulose is an important additional ingredient in the pharmaceutical, food, cosmetics, and structural composites. In this study, MCC, alpha cellulose, and cellulose were characterized and thereafter were compared. Characterizations were made using some equipment such as x-ray diffraction (XRD), Fourier transform infrared (FTIR), scanning electron microscopy (SEM) and thermogravimetry analyzer (TGA). X-ray diffraction and infrared spectroscopy were studied to determine crystallinity and molecular structure of MCC, where scanning electron microscopy images were conducted for information about morfology of MCC. Meanwhile, thermal resistance of MCC was determined using thermogravimetry analyzer (TGA). From XRD and FTIR, the obtained results showed that the crystalline part was traced on MCC, where the -OH and C-O groups tended to reduced as alpha cellulose has changed to MCC. From SEM the image showed the reduction of particle size of MCC, while the thermal resistance of MCC was found lower as compared with cellulose and alpha cellulose as well, which was attributed to the lower molecular weight of MCC.

Isolation and characterization of microcrystalline cellulose from roselle fibers.

PubMed

Kian, Lau Kia; Jawaid, Mohammad; Ariffin, Hidayah; Alothman, Othman Y

2017-10-01

In this study, microcrystalline cellulose (MCC) was extracted from roselle fiber through acid hydrolysis treatment and its properties were compared with those of commercially available MCC. The physicochemical and morphological characteristics, elemental composition, size distribution, crystallinity and thermal properties of the obtained MCC were analyzed in this work. Fourier transform infrared spectroscopy (FTIR) analysis provided clear evidence that the characteristic peak of lignin was absent in the spectrum of the MCC prepared from roselle fiber. Rough surface and slight aggregation of MCC were observed by scanning electron microscopy (SEM). Energy dispersive X-ray (EDX) analysis showed that pure MCC with small quantities of residues and impurities was obtained, with a similar elemental composition to that of commercial MCC. A mean diameter of approximately 44.28μm was measured for MCC by using a particle size analyzer (PSA). X-ray diffraction (XRD) showed the crystallinity increased from 63% in roselle pulp to 78% in roselle MCC, the latter having a slightly higher crystallinity than that of commercial MCC (74%). TGA and DSC results indicated that the roselle MCC had better thermal stability than the roselle pulp, whereas it had poorer thermal stability in comparison with commercial MCC. Thus, the isolated MCC from roselle fibers will be going to use as reinforcing element in green composites and may be a precursor for future roselle derived nanocellulose, and thus a promising subject in nanocomposite research. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of total radiotherapy dose on survival for head and neck Merkel cell carcinoma after resection.

PubMed

Patel, Sagar A; Qureshi, Muhammad M; Mak, Kimberley S; Sahni, Debjani; Giacalone, Nicholas J; Ezzat, Waleed; Jalisi, Scharukh; Truong, Minh Tam

2017-07-01

Head and neck Merkel cell carcinoma (MCC) is commonly treated with surgery and adjuvant radiotherapy (RT) for high-risk features. The optimal radiation dose is unknown. One thousand six hundred twenty-five eligible patients with head and neck MCC were identified in the National Cancer Data Base (NCDB). Radiation dose was divided into 3 groups: 30 to <50 Gray (Gy), 50-55 Gy, and >55-70 Gy. Cox regression was used to compare overall survival (OS) between groups, accounting for age, sex, stage, surgery type, margin status, comorbidities, and use of chemotherapy. With a median follow-up of 33.5 months, 3-year OS was 48.9%, 70.3%, and 58.7% for 30 to <50 Gy, 50-55 Gy, and >55-70 Gy, respectively (P < .001). Compared to 50-55 Gy, doses between 30 to <50 Gy (adjusted hazard ratio [HR] 1.53; 95% confidence interval [CI] 1.17-1.99; P = .002) and >55-70 Gy (adjusted HR 1.21; 95% CI 1.0-1.46; P = .06) were associated with worse survival. Adjuvant radiation doses within 50-55 Gy may be optimal for head and neck MCC. © 2017 Wiley Periodicals, Inc.

Multicolor microRNA FISH effectively differentiates tumor types

PubMed Central

Renwick, Neil; Cekan, Pavol; Masry, Paul A.; McGeary, Sean E.; Miller, Jason B.; Hafner, Markus; Li, Zhen; Mihailovic, Aleksandra; Morozov, Pavel; Brown, Miguel; Gogakos, Tasos; Mobin, Mehrpouya B.; Snorrason, Einar L.; Feilotter, Harriet E.; Zhang, Xiao; Perlis, Clifford S.; Wu, Hong; Suárez-Fariñas, Mayte; Feng, Huichen; Shuda, Masahiro; Moore, Patrick S.; Tron, Victor A.; Chang, Yuan; Tuschl, Thomas

2013-01-01

MicroRNAs (miRNAs) are excellent tumor biomarkers because of their cell-type specificity and abundance. However, many miRNA detection methods, such as real-time PCR, obliterate valuable visuospatial information in tissue samples. To enable miRNA visualization in formalin-fixed paraffin-embedded (FFPE) tissues, we developed multicolor miRNA FISH. As a proof of concept, we used this method to differentiate two skin tumors, basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC), with overlapping histologic features but distinct cellular origins. Using sequencing-based miRNA profiling and discriminant analysis, we identified the tumor-specific miRNAs miR-205 and miR-375 in BCC and MCC, respectively. We addressed three major shortcomings in miRNA FISH, identifying optimal conditions for miRNA fixation and ribosomal RNA (rRNA) retention using model compounds and high-pressure liquid chromatography (HPLC) analyses, enhancing signal amplification and detection by increasing probe-hapten linker lengths, and improving probe specificity using shortened probes with minimal rRNA sequence complementarity. We validated our method on 4 BCC and 12 MCC tumors. Amplified miR-205 and miR-375 signals were normalized against directly detectable reference rRNA signals. Tumors were classified using predefined cutoff values, and all were correctly identified in blinded analysis. Our study establishes a reliable miRNA FISH technique for parallel visualization of differentially expressed miRNAs in FFPE tumor tissues. PMID:23728175

Merkel cell carcinoma in the community setting: a case report.

PubMed

Callaghan, Cameron M; Amornmarn, Rumpa

2018-04-12

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin initially believed to arise from the Merkel cells. In the community setting a general radiation oncologist may only encounter this pathology in a handful of cases over the course of their career. Due to the low incidence of this malignancy, few prospective randomized controlled trials have ever been conducted and therefore guidelines are based on relatively lower levels of evidence upon which the clinical recommendations are made. We discuss the case of a female in her 90s presenting with a classic MCC primary lesion, as well as satellite lesions proximal to both the primary and the draining regional lymph nodes with no evidence of nodal involvement. Here we discuss the presentation, management, treatment planning, underlying pathology, results and sequelae of treatment. We also review new treatment modalities, and the most current staging systems and guidelines.

Characteristics of the oceanic MCC, continental MCC, and coastal MCC over the Indonesian maritime continent

NASA Astrophysics Data System (ADS)

Trismidianto

2018-05-01

This study explains the comparison of mesoscale convective complexes (MCC) characteristics in the oceans, land and in the coast over Indonesian maritime continent (IMC). MCCs were identified and tracked during 15-years (2001-2015) over IMC by infrared satellite imagery using an algorithm that combines criteria of cloud coverage, eccentricity, and cloud lifetime. Infrared satellite imagery was obtained from Himawari generation satellite data. This study showed most of the continental MCC found near the mountains and the high elevation areas. The frequency of MCC occurrences was larger over the land than over the ocean. The oceanic MCCs, which lasted for more than 12 hours, were longer-lived than the continental MCCs. The MCCs with small size most frequently occurred in the continent, in contrast, the MCC with the medium and large size were most concentrated over the ocean. Generally, the continental and coastal MCC initiation occurs in the late afternoon and reach maximum size around midnight before decaying the next morning. In contrast, the oceanic MCC dominantly develops in midnight, and reach maximum size in the morning and then MCC decayed and dissipated from noon until afternoon. The evolution of MCC development in the ocean, land, and in the coast has almost the same stages and ways.

Midcingulate cortex: Structure, connections, homologies, functions and diseases.

PubMed

Vogt, Brent A

2016-07-01

Midcingulate cortex (MCC) has risen in prominence as human imaging identifies unique structural and functional activity therein and this is the first review of its structure, connections, functions and disease vulnerabilities. The MCC has two divisions (anterior, aMCC and posterior, pMCC) that represent functional units and the cytoarchitecture, connections and neurocytology of each is shown with immunohistochemistry and receptor binding. The MCC is not a division of anterior cingulate cortex (ACC) and the "dorsal ACC" designation is a misnomer as it incorrectly implies that MCC is a division of ACC. Interpretation of findings among species and developing models of human diseases requires detailed comparative studies which is shown here for five species with flat maps and immunohistochemistry (human, monkey, rabbit, rat, mouse). The largest neurons in human cingulate cortex are in layer Vb of area 24 d in pMCC which project to the spinal cord. This area is part of the caudal cingulate premotor area which is involved in multisensory orientation of the head and body in space and neuron responses are tuned for the force and direction of movement. In contrast, the rostral cingulate premotor area in aMCC is involved in action-reinforcement associations and selection based on the amount of reward or aversive properties of a potential movement. The aMCC is activated by nociceptive information from the midline, mediodorsal and intralaminar thalamic nuclei which evoke fear and mediates nocifensive behaviors. This subregion also has high dopaminergic afferents and high dopamine-1 receptor binding and is engaged in reward processes. Opposing pain/avoidance and reward/approach functions are selected by assessment of potential outcomes and error detection according to feedback-mediated, decision making. Parietal afferents differentially terminate in MCC and provide for multisensory control in an eye- and head-centric manner. Finally, MCC vulnerability in human disease confirms the unique organization of MCC and supports the predictive validity of the MCC dichotomy. Vulnerability of aMCC is shown in chronic pain, obsessive-compulsive disorder with checking symptoms and attention-deficit/hyperactivity disorder and methylphenidate and pain medications selectively impact aMCC. In contrast, pMCC vulnerabilities are for progressive supranuclear palsy, unipolar depression and posttraumatic stress disorder. Thus, there is an emerging picture of the organization, functions and diseases of MCC. Future work will take this type of modular analysis to individual areas of which there are at least 10 in MCC. Copyright © 2016 Elsevier B.V. All rights reserved.

The expression of Toll-like receptors 2, 4, 5, 7 and 9 in Merkel cell carcinoma.

PubMed

Jouhi, Lauri; Koljonen, Virve; Böhling, Tom; Haglund, Caj; Hagström, Jaana

2015-04-01

We sought to clarify whether the expression of toll-like receptors (TLR) in Merkel cell carcinoma (MCC) is linked to tumor and patient characteristics, especially the presence of Merkel cell polyoma virus (MCV). The study comprised of 128 patients with data on Merkel cell polyomavirus (MCV) status and clinical features were included in the study. Immunohistochemistry for TLR expression was performed on tissue microarray (TMA) slides. TLR 2, 4, 5, 7 and 9 expression was noted in most of the tumor specimens. Decreased expression of TLR 9 correlated strongly with MCV positivity. Cytoplasmic TLR 2 expression correlated with small tumor size, while nuclear TLR 2 and TLR 5 expressions with larger tumors. Increased nuclear TLR 4 expression and decreased TLR 7 expression were associated with older age. TLR 2, 4, 5, 7 and 9 appear to reflect certain clinicopathological variables and prognostic markers of MCC tumors. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation.

PubMed

Vladar, Eszter K; Nayak, Jayakar V; Milla, Carlos E; Axelrod, Jeffrey D

2016-08-18

Motile airway cilia that propel contaminants out of the lung are oriented in a common direction by planar cell polarity (PCP) signaling, which localizes PCP protein complexes to opposite cell sides throughout the epithelium to orient cytoskeletal remodeling. In airway epithelia, PCP is determined in a 2-phase process. First, cell-cell communication via PCP complexes polarizes all cells with respect to the proximal-distal tissue axis. Second, during ciliogenesis, multiciliated cells (MCCs) undergo cytoskeletal remodeling to orient their cilia in the proximal direction. The second phase not only directs cilium polarization, but also consolidates polarization across the epithelium. Here, we demonstrate that in airway epithelia, PCP depends on MCC differentiation. PCP mutant epithelia have misaligned cilia, and also display defective barrier function and regeneration, indicating that PCP regulates multiple aspects of airway epithelial homeostasis. In humans, MCCs are often sparse in chronic inflammatory diseases, and these airways exhibit PCP dysfunction. The presence of insufficient MCCs impairs mucociliary clearance in part by disrupting PCP-driven polarization of the epithelium. Consistent with defective PCP, barrier function and regeneration are also disrupted. Pharmacological stimulation of MCC differentiation restores PCP and reverses these defects, suggesting its potential for broad therapeutic benefit in chronic inflammatory disease.

Comparative study of antidiabetic activity of Cajanus cajan and Tamarindus indica in alloxan-induced diabetic mice with a reference to in vitro antioxidant activity

PubMed Central

Nahar, Laizuman; Nasrin, Fatema; Zahan, Ronok; Haque, Anamul; Haque, Ekramul; Mosaddik, Ashik

2014-01-01

Background: Oxidative stress not only develops complications in diabetic (type 1 and type 2) but also contributes to beta cell destruction in type 2 diabetes in insulin resistance hyperglycemia. Glucose control plays an important role in the pro-oxidant/antioxidant balance. Some antidiabetic agents may by themselves have antioxidant properties independently of their role on glucose control. Objective: The present investigation draws a comparison of the protective antioxidant activity, total phenol content and the antihyperglycemic activity of the methanolic extract of Cajanus cajan root (MCC) and Tamarindus indica seeds (MTI). Materials and Methods: Antidiabetic potentials of the plant extracts were evaluated in alloxan-induced diabetic Swiss albino mice. The plant extracts at the doses of 200 and 400 mg/kg body weight was orally administered for glucose tolerance test during 1-hour study and hypoglycemic effect during 5-day study period in comparison with reference drug Metformin HCl (50 mg/kg). In vitro antioxidant potential of MCC and MTI was investigated by using 1, 1- diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity at 517 nm. Total phenolic content, total antioxidant capacity and reducing power activity was also assayed. Results: There was a significant decrease in fasting serum glucose level (P < 0.001), reduction in blood glucose level (P < 0.001) in 5-days study, observed in the alloxan-induced diabetic mice. The reduction efficacy of blood glucose level of both the extracts is proportional to their dose but MCC is more potent than MTI. Antioxidant study and quantification of phenolic compound of both the extracts revealed that they have high antioxidant capacity. Conclusion: These studies showed that MCC and MTI have both hypoglycemic and antioxidant potential but MCC is more potent than MTI. The present study suggests that both MCC and MTI could be used in managing oxidative stress. PMID:24761124

Genotoxic and immunotoxic effects of cellulose nanocrystals in vitro.

PubMed

Catalán, Julia; Ilves, Marit; Järventaus, Hilkka; Hannukainen, Kati-Susanna; Kontturi, Eero; Vanhala, Esa; Alenius, Harri; Savolainen, Kai M; Norppa, Hannu

2015-03-01

Nanocellulosics are among the most promising innovations for a wide-variety of applications in materials science. Although nanocellulose is presently produced only on a small scale, its possible toxic effects should be investigated at this early stage. The aim of the present study was to examine the potential genotoxicity and immunotoxicity of two celluloses in vitro - cellulose nanocrystals (CNC; mean fibril length 135 nm, mean width 7.3 nm) and a commercially available microcrystalline (non-nanoscale) cellulose (MCC; particle size ∼50 µm). Both celluloses showed 55% cytotoxicity at approximately 100 µg/ml after 4-h, 24-h, and 48-h treatment of human bronchial epithelial BEAS 2B cells, as determined by luminometric detection of ATP and cell count (dead cells identified by propidium iodide). Neither of the materials was able to induce micronuclei (MN) in binucleate or mononucleate BEAS 2B cells after a 48-h treatment (2.5-100 µg/ml). In human monocyte-derived macrophages, MCC induced a release (measured by enzyme-linked immunosorbent assay; ELISA) of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and (after lipopolysaccharide-priming) interleukin 1β (IL-1β) after a 6-h exposure to a dose of 300 µg/ml, but CNC (30-300 µg/ml) did not. In conclusion, our results show that nanosized CNC is neither genotoxic nor immunotoxic under the conditions tested, whereas non-nanosized MCC is able to induce an inflammatory response. More studies are needed, especially in vivo, to further assess if CNC and other nanocelluloses induce secondary genotoxic effects mediated by inflammation. © 2014 Wiley Periodicals, Inc.

RhoA regulates actin network dynamics during apical surface emergence in multiciliated epithelial cells

PubMed Central

Sedzinski, Jakub; Hannezo, Edouard; Tu, Fan; Biro, Maté

2017-01-01

ABSTRACT Homeostatic replacement of epithelial cells from basal precursors is a multistep process involving progenitor cell specification, radial intercalation and, finally, apical surface emergence. Recent data demonstrate that actin-based pushing under the control of the formin protein Fmn1 drives apical emergence in nascent multiciliated epithelial cells (MCCs), but little else is known about this actin network or the control of Fmn1. Here, we explore the role of the small GTPase RhoA in MCC apical emergence. Disruption of RhoA function reduced the rate of apical surface expansion and decreased the final size of the apical domain. Analysis of cell shapes suggests that RhoA alters the balance of forces exerted on the MCC apical surface. Finally, quantitative time-lapse imaging and fluorescence recovery after photobleaching studies argue that RhoA works in concert with Fmn1 to control assembly of the specialized apical actin network in MCCs. These data provide new molecular insights into epithelial apical surface assembly and could also shed light on mechanisms of apical lumen formation. PMID:28089989

RhoA regulates actin network dynamics during apical surface emergence in multiciliated epithelial cells.

PubMed

Sedzinski, Jakub; Hannezo, Edouard; Tu, Fan; Biro, Maté; Wallingford, John B

2017-01-15

Homeostatic replacement of epithelial cells from basal precursors is a multistep process involving progenitor cell specification, radial intercalation and, finally, apical surface emergence. Recent data demonstrate that actin-based pushing under the control of the formin protein Fmn1 drives apical emergence in nascent multiciliated epithelial cells (MCCs), but little else is known about this actin network or the control of Fmn1. Here, we explore the role of the small GTPase RhoA in MCC apical emergence. Disruption of RhoA function reduced the rate of apical surface expansion and decreased the final size of the apical domain. Analysis of cell shapes suggests that RhoA alters the balance of forces exerted on the MCC apical surface. Finally, quantitative time-lapse imaging and fluorescence recovery after photobleaching studies argue that RhoA works in concert with Fmn1 to control assembly of the specialized apical actin network in MCCs. These data provide new molecular insights into epithelial apical surface assembly and could also shed light on mechanisms of apical lumen formation. © 2017. Published by The Company of Biologists Ltd.

Assays for the spindle assembly checkpoint in cell culture.

PubMed

Marcozzi, Chiara; Pines, Jonathon

2018-01-01

The spindle assembly checkpoint (SAC) is crucial to maintain genomic stability since it prevents premature separation of sister chromatids in mitosis and ensures the fidelity of chromosome segregation. The SAC arrests cells in mitosis and is not satisfied until all kinetochores are stably attached to the mitotic spindle. Improperly attached kinetochores activate the SAC and catalyze the formation of the mitotic checkpoint complex (MCC), containing Mad2, Cdc20, BubR1, and Bub3 proteins. The MCC binds and thereby inhibits the APC/C E3 ubiquitin ligase until the last kinetochore has attached to microtubules. Once the SAC is satisfied, the APC/C promptly activates and targets cyclin B1 and securin for degradation, thus allowing sister chromatids to separate and the cell to exit mitosis. Our understanding of SAC signaling has increased thanks to the development of new genetic, biochemical, molecular, and structural biology techniques. Here, we describe how live-cell imaging microscopy in combination with gene-targeting strategies and biochemical assays can be exploited to investigate the intrinsic properties of the SAC in mammalian cultured cells. © 2018 Elsevier Inc. All rights reserved.

A Minimal Anaphase Promoting Complex/Cyclosome (APC/C) in Trypanosoma brucei

PubMed Central

Bessat, Mohamed; Knudsen, Giselle; Burlingame, Alma L.; Wang, Ching C.

2013-01-01

The anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that initiates chromosome segregation and mitotic exit by targeting critical cell-cycle regulators for proteolytic destruction. Previously, seven APC/C subunit homologues were identified in the genome of Trypanosoma brucei. In the present study, we tested five of them in yeast complementation studies and found none of them capable of complementing the yeast mutants lacking the corresponding subunits, suggesting significant discrepancies between the two APC/C’s. Subunit homologues of mitotic checkpoint complex (MCC) have not yet been identified in T. brucei, raising the possibility that a MCC-APC/C complex equivalent may not exist in T. brucei. We performed tandem affinity purification of the protein complex containing a APC1 fusion protein expressed in the cells enriched in different phases of the cell cycle of procyclic form T. brucei, and compared their protein profiles using LC-MS/MS analyses. The seven putative APC/C subunits were identified in the protein complex throughout the cell cycle together with three additional proteins designated the associated proteins (AP) AP1, AP2 and AP3. Abundance of the 10 proteins remained relatively unchanged throughout the cell cycle, suggesting that they are the core subunits of APC/C. AP1 turned out to be a homologue of APC4. An RNAi knockdown of APC4 and AP3 showed no detectable cellular phenotype, whereas an AP2 knockdown enriched the cells in G2/M phase. The AP2-depleted cells showed stabilized mitotic cyclin B. An accumulation of poly-ubiquitinated cyclin B was indicated in the cells treated with the proteasome inhibitor MG132, demonstrating the involvement of proteasome in degrading poly-ubiquitinated cyclin B. In all, a 10-subunit APC/C machinery with a conserved function is identified in T. brucei without linking to a MCC-like complex, thus indicating a unique T. brucei APC/C. PMID:23533609

NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction

PubMed Central

Pavillard, Luís E.; Cañadas-Lozano, Diego; Alcocer-Gómez, Elísabet; Marín-Aguilar, Fabiola; Pereira, Sheila; Robertson, Avril A.B.; Muntané, Jordi; Ryffel, Bernhard; Cooper, Matthew A.; Quiles, José L.; Bullón, Pedro; Ruiz-Cabello, Jesús; Cordero, Mario D.

2017-01-01

The NLRP3-inflammasome complex has emerged as an important component of inflammatory processes in metabolic dysfunction induced by high-caloric diets. In this study, we investigate the molecular mechanisms by which NLRP3 inhibition may attenuate diet-induced cardiac injury. Here we show the cardiac damage induced by high sugar diet (HSD), high fat diet (HFD) or high sugar/fat diet (HSFD) over 15 weeks. Genetic ablation of NLRP3 protected against this damage by autophagy induction and apoptotic control. Furthermore, NLRP3 inhibition by the selective small molecule MCC950 resulted in similar autophagy induction and apoptotic control in hearts after diets. These data were reproduced in THP-1 cells treated with MCC950 and cultured in media supplemented with serum from mice dosed with MCC950 and fed with diets. NLRP3 inhibition exerted beneficial metabolic, and autophagic adaptations in hearts from obesogenic diets. The inhibition of NLRP3 activation may hold promise in the treatment of metabolic and cardiovascular diseases. PMID:29245937

NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction.

PubMed

Pavillard, Luís E; Cañadas-Lozano, Diego; Alcocer-Gómez, Elísabet; Marín-Aguilar, Fabiola; Pereira, Sheila; Robertson, Avril A B; Muntané, Jordi; Ryffel, Bernhard; Cooper, Matthew A; Quiles, José L; Bullón, Pedro; Ruiz-Cabello, Jesús; Cordero, Mario D

2017-11-21

The NLRP3-inflammasome complex has emerged as an important component of inflammatory processes in metabolic dysfunction induced by high-caloric diets. In this study, we investigate the molecular mechanisms by which NLRP3 inhibition may attenuate diet-induced cardiac injury. Here we show the cardiac damage induced by high sugar diet (HSD), high fat diet (HFD) or high sugar/fat diet (HSFD) over 15 weeks. Genetic ablation of NLRP3 protected against this damage by autophagy induction and apoptotic control. Furthermore, NLRP3 inhibition by the selective small molecule MCC950 resulted in similar autophagy induction and apoptotic control in hearts after diets. These data were reproduced in THP-1 cells treated with MCC950 and cultured in media supplemented with serum from mice dosed with MCC950 and fed with diets. NLRP3 inhibition exerted beneficial metabolic, and autophagic adaptations in hearts from obesogenic diets. The inhibition of NLRP3 activation may hold promise in the treatment of metabolic and cardiovascular diseases.

Effect of simulated microgravity and shear stress on microcin B17 production by Escherichia coli and on its excretion into the medium

NASA Technical Reports Server (NTRS)

Fang, A.; Pierson, D. L.; Koenig, D. W.; Mishra, S. K.; Demain, A. L.

1997-01-01

Production of the antibacterial polypeptide microcin B17 (MccB17) by Escherichia coli ZK650 was inhibited by simulated microgravity. The site of MccB17 accumulation was found to be different, depending on whether the organism was grown in shaking flasks or in rotating bioreactors designed to establish a simulated microgravity environment. In flasks, the accumulation was cellular, but in the reactors, virtually all the microcin was found in the medium. The change from a cellular site to an extracellular one was apparently not a function of gravity, since extracellular production occurred in these bioreactors, irrespective of whether they were operated in the simulated microgravity or normal gravity mode. More probably, excretion is due to the much lower degree of shear stress in the bioreactors. Addition of even a single glass bead to the 50-ml medium volume in the bioreactor created enough shear to change the site of MccB17 accumulation from the medium to the cells.

The Development of Multicultural Counselling Competencies (MCC) Training Module Based on MCC Matrix Model by Sue et al. (1992)

ERIC Educational Resources Information Center

Anuar, Azad Athahiri; Rozubi, Norsayyidatina Che; Abdullah, Haslee Sharil

2015-01-01

The aims of this study were to develop and validate a MCC training module for trainee counselor based on MCC matrix model by Sue et al. (1992). This module encompassed five sub modules and 11 activities developed along the concepts and components of the MCC matrix model developed by Sue, Arredondo dan McDavis (1992). The design method used in this…

James Webb Space Telescope Initial Mid-Course Correction Monte Carlo Implementation using Task Parallelism

NASA Technical Reports Server (NTRS)

Petersen, Jeremy; Tichy, Jason; Wawrzyniak, Geoffrey; Richon, Karen

2014-01-01

The James Webb Space Telescope will be launched into a highly elliptical orbit that does not possess sufficient energy to achieve a proper Sun-Earth L2 libration point orbit. Three mid-course correction (MCC) maneuvers are planned to rectify the energy deficit: MCC-1a, MCC-1b, and MCC-2. To validate the propellant budget and trajectory design methods, a set of Monte Carlo analyses that incorporate MCC maneuver modeling and execution are employed. The first analysis focuses on the effects of launch vehicle injection errors on the magnitude of MCC-1a. The second on the spread of potential V based on the performance of the propulsion system as applied to all three MCC maneuvers. The final highlights the slight, but notable, contribution of the attitude thrusters during each MCC maneuver. Given the possible variations in these three scenarios, the trajectory design methods are determined to be robust to errors in the modeling of the flight system.

James Webb Space Telescope Initial Mid-Course Correction Monte Carlo Implementation using Task Parallelism

NASA Technical Reports Server (NTRS)

Petersen, Jeremy; Tichy, Jason; Wawrzyniak, Geoffrey; Richon, Karen

2014-01-01

The James Webb Space Telescope will be launched into a highly elliptical orbit that does not possess sufficient energy to achieve a proper Sun-Earth/Moon L2 libration point orbit. Three mid-course correction (MCC) maneuvers are planned to rectify the energy deficit: MCC-1a, MCC-1b, and MCC-2. To validate the propellant budget and trajectory design methods, a set of Monte Carlo analyses that incorporate MCC maneuver modeling and execution are employed. The first analysis focuses on the effects of launch vehicle injection errors on the magnitude of MCC-1a. The second on the spread of potential V based on the performance of the propulsion system as applied to all three MCC maneuvers. The final highlights the slight, but notable, contribution of the attitude thrusters during each MCC maneuver. Given the possible variations in these three scenarios, the trajectory design methods are determined to be robust to errors in the modeling of the flight system.

View of Mission Control Center during the Apollo 13 oxygen cell failure

NASA Image and Video Library

1970-04-14

S70-34902 (14 April 1970) --- Several persons important to the Apollo 13 mission, at consoles in the Mission Operations Control Room (MOCR) of the Mission Control Center (MCC). Seated at consoles, from left to right, are astronauts Donald K. Slayton, director of flight crew operations; astronaut Jack R. Lousma, Shift 3 spacecraft communicator; and astronaut John W. Young, commander of the Apollo 13 backup crew. Standing, left to right, are astronaut Tom K. Mattingly II, who was replaced as Apollo 13 command module pilot after it was learned he may come down with measles, and astronaut Vance D. Brand, Shift 2 spacecraft communicator. Several hours earlier, in the late evening hours of April 13, crew members of the Apollo 13 mission reported to MCC that trouble had developed with an oxygen cell on their spacecraft.

A Mediterranean derecho: Catalonia (Spain), 17th August 2003

NASA Astrophysics Data System (ADS)

López, J. Manuel

2007-02-01

At approximately 6:10 UTC in the morning of 17th August 2003, a squall line developed over south Catalonia (the northeast region of Spain). During the next 9 h, the squall moved rapidly northeast and crossed Catalonia and the French regions of Languedoc-Roussillon and Province, damaging and uprooting hundreds of trees and blocking trains in the region. Wind gusts reached were recoded up to 52 m/s with evidence of F2 intensity damage. This case study shows the characteristics of a derecho (widespread convectively induced windstorm). Radar observations of the evolving squall line show signatures often correlated with damaging surface winds, including: Bow echoes, Rear inflow notches, Rear inflow jets, Medium altitude radial convergence, Narrow gradient of very marked reflectivity, Development of isolated cells ahead of the convective line, A band of convection off the northern end of the line known as a "warm advection wing". When examining the different surface observations, satellite, radar imagery and cloud-to-ground lightning data, this case shows many similarities to those investigated in the United States. The derecho is a hybrid case, but has many characteristics of warm season derechoes. This emanates from a mesoscale convective complex (MCC) moving along a quasi-stationary, low-level thermal boundary in an environment characterized by high potential instability and relatively strong mid-tropospheric winds.

[Merkel cell carcinoma of the vulva - case report and the literature review].

PubMed

Jońska-Gmyrek, Joanna; Bobkiewicz, Piotr; Gmyrek, Leszek; Zółciak-Siwińska, Agnieszka; Lindner, Bogusław; Staniaszek, Jagna

2013-05-01

Merkel cell carcinoma (MCC) is a rare malignant neoplasm, mostly affecting the skin (97% of cases). It is usually found in elderly people, in the sun-exposed areas of the skin. About 50-60% of MCC cases are located on the head and the neck, less often on the extremities and the torso, and extremely rarely in the genital area. Ultraviolet radiation may be the main factor responsible for the development of the tumors but viral etiology is also debated. Due to extremely rare incidence of MCC in the area of the vulva, proper management remains a challenging task. To present a case of an aggressive MCC of the vulva and a review of the literature. A previously healthy 72-year-old patient presented at the Oncology Center of the Maria Sklodowska-Curie Institute, Warsaw, in June 2010. Four months previously the patient noticed a painless lump in the vestibular region of the vagina. She received anti-inflammatory treatment at her local gynecological clinic, with no success. In February the patient underwent removal of the vulvar tumor Histopathological examination confirmed anaplastic carcinoma. Microscopic evaluation revealed the tumor diameter to be 15mm. Surgical margins were free of neoplastic infiltration. The patient did not receive adjuvant therapy due to the results from the histopathological protocol. The disease recurred after three months. Radical vulvectomy and bilateral inguinal femoral lymphadenectomy were performed in May 2010. Histopathological examination confirmed microcellular carcinoma with no metastases to the lymph nodes and complete resection of the tumor (RO). The disease recurred in the next two months: a 50-mm tumor was found in the right inguinal lymph nodes. The decision to verify all histopathological material obtained during all procedures performed so far was made. Immunohistochemical evaluation confirmed MCC. Adjuvant radiotherapy was recommended. The area of the vulva, pelvic and inguinal lymph nodes were irradiated. One month after therapy completion the patient complained of pain in the lumbar area. An ultrasound examination of the abdomen revealed a tumor (9 cm in diameter) in the para-aortic region but it was not histopathologically verified due to extremely poor overall condition of the patient. As the condition of the woman deteriorated systematically the patient was referred to a hospice facility where she died 9 months since the primary diagnosis. MCC of the vulva is a rare neoplasm with an aggressive course. Clinical and histopathological diagnostic difficulties and consequently lack of standardized management, result in low survival rates.

Merkel cell polyomavirus detection in Merkel cell cancer tumors in Northern Germany using PCR and protein expression.

PubMed

Leitz, Miriam; Stieler, Kristin; Grundhoff, Adam; Moll, Ingrid; Brandner, Johanna M; Fischer, Nicole

2014-10-01

Merkel cell carcinoma is a highly malignant skin cancer which predominantly occurs in elderly and immunocompromised persons. The identification of the Merkel cell polyomavirus (MCPyV) has inaugurated a new understanding of Merkel cell carcinoma pathogenesis. The frequent detection of the virus in Merkel cell carcinoma tissue (70-90%), its monoclonal integration in the tumor cells and the expression of viral oncogenes highly suggest that MCPyV is causally linked to the pathogenesis of the majority of Merkel cell cancer (MCC) cases. Using qualitative and quantitative PCR together with immunohistochemical staining this study aimed at characterizing the presence of MCPyV sequences and viral early gene expression in a cohort of MCC cases (n = 32) selected in Northern Germany. 40-57% of the cases were identified as MCPyV positive with 40.6% of the cases positive by immunohistochemical staining and 51.6-57.6% positive by PCR. Interestingly, in the majority (64%) of LT-Antigen positive tumors only 25-50% of tumor cells express LT-Antigen. These data are in accord with published studies describing heterogeneity in MCPyV viral loads and suggest that detection of MCPyV in Merkel cell carcinoma by PCR should be undertaken using multiple primer pairs. © 2013 Wiley Periodicals, Inc.

Non-contact weight measurement of flat-faced pharmaceutical tablets using terahertz transmission pulse delay measurements.

PubMed

Bawuah, Prince; Silfsten, Pertti; Ervasti, Tuomas; Ketolainen, Jarkko; Zeitler, J Axel; Peiponen, Kai-Erik

2014-12-10

By measuring the time delay of a terahertz pulse traversing a tablet, and hence its effective refractive index, it is possible to non-invasively and non-destructively detect the weight of tablets made of microcrystalline cellulose (MCC). Two sets of MCC tablets were used in the study: Set A (training set) consisted of 13 tablets with nominally constant height but varying porosities, whereas Set B (test set) comprised of 21 tablets with nominally constant porosity but different heights. A linear correlation between the estimated absolute weight based on the terahertz measurement and the measured weight of both sets of MCC tablets was found. In addition, it was possible to estimate the height of the tablets by utilizing the estimated absolute weight and calculating the relative change of height of each tablet with respect to an ideal tablet. A good agreement between the experimental and the calculated results was found highlighting the potential of this technique for in-line sensing of the weight, porosity and the relative change in height of the tablets compared to a reference/ideal tablet. In this context, we propose a quantitative quality control method to assess the deviations in porosity of tablets immediately after compaction. Copyright © 2014 Elsevier B.V. All rights reserved.

Three-dimensional printed polycaprolactone-microcrystalline cellulose scaffolds.

PubMed

Alemán-Domínguez, Maria Elena; Giusto, Elena; Ortega, Zaida; Tamaddon, Maryam; Benítez, Antonio Nizardo; Liu, Chaozong

2018-05-02

Microcrystalline cellulose (MCC) is proposed in this study as an additive in polycaprolactone (PCL) matrices to obtain three-dimensional (3D) printed scaffolds with improved mechanical and biological properties. Improving the mechanical behavior and the biological performance of polycaprolactone-based scaffolds allows to increase the potential of these structures for bone tissue engineering. Different groups of samples were evaluated in order to analyze the effect of the additive in the properties of the PCL matrix. The concentrations of MCC in the groups of samples were 0, 2, 5, and 10% (w/w). These combinations were subjected to a thermogravimetric analysis in order to evaluate the influence of the additive in the thermal properties of the composites. 3D printed scaffolds were manufactured with a commercial 3D printer based on fused deposition modelling. The operation conditions have been established in order to obtain scaffolds with a 0/90° pattern with pore sizes between 450 and 500 µm and porosity values between 50 and 60%. The mechanical properties of these structures were measured in the compression and flexural modes. The scaffolds containing 2 and 5% MCC have higher flexural and compression elastic modulus, although those containing 10% do not show this reinforcement effect. On the other hand, the proliferation of sheep bone marrow cells on the proposed scaffolds was evaluated over 8 days. The results show that the proliferation is significantly better (p < 0.05) on the group of samples containing 2% MCC. Therefore, these scaffolds (PCL:MCC 98:2) have suitable properties to be further evaluated for bone tissue engineering applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

WILLIAMS, CLIFTON C. ASTRONAUT - MISSION CONTROL CENTER (MCC) - GEMINI-TITAN (GT)-3 - MSC

NASA Image and Video Library

1965-03-23

S65-18063 (23 March 1965) --- Astronaut Clifton C. Williams is shown at console in the Mission Control Center (MCC) in Houston, Texas during the Gemini-Titan 3 flight. The GT-3 flight was monitored by the MCC in Houston, but was controlled by the MCC at Cape Kennedy.

Asporin stably expressed in the surface layer of mandibular condylar cartilage and augmented in the deeper layer with age.

PubMed

Miyamoto, Yutaka; Kanzaki, Hiroyuki; Wada, Satoshi; Tsuruoka, Sari; Itohiya, Kanako; Kumagai, Kenichi; Hamada, Yoshiki; Nakamura, Yoshiki

2017-12-01

Mandibular condylar cartilage (MCC) exhibits dual roles both articular cartilage and growth center. Of many growth factors, TGF-β has been implicated in the growth of articular cartilage including MCC. Recently, Asporin, decoy to TGF-β, was discovered and it blocks TGF-β signaling. Asporin is expressed in a variety of tissues including osteoarthritic articular cartilage, though there was no report of Asporin expression in MCC. In the present study, we investigated the temporal and spatial expression of Asporin in MCC. Gene expression profile of MCC and epiphyseal cartilage in tibia of 5 weeks old ICR mice were firstly compared with microarray analysis using the laser capture microdissected samples. Variance of gene expression was further confirmed by real-time RT-PCR and immunohistochemical staining at 1,3,10, and 20 weeks old. TGF-β and its signaling molecule, phosphorylated Smad-2/3 (p-Smad2/3), were also examined by immunohistochemical staining. Microarray analysis revealed that Asporin was highly expressed in MCC. Real-time RT-PCR analysis confirmed that the fibrous layer of MCC exhibited stable higher Asporin expression at any time points as compared to epiphyseal cartilage. This was also observed in immunohistochemical staining. Deeper layer in MCC augmented Asporin expression with age. Whereas, TGF-β was stably highly observed in the layer. The fibrous layer of MCC exhibited weak staining of p-Smad2/3, though the proliferating layer of MCC was strongly stained as compared to epiphyseal cartilage of tibia at early time point. Consistent with the increase of Asporin expression in the deeper layer of MCC, the intensity of p-Smad-2/3 staining was decreased with age. In conclusion, we discovered that Asporin was stably expressed at the fibrous layer of MCC, which makes it possible to manage both articular cartilage and growth center at the same time.

A mechanical chest compressor closed-loop controller with an effective trade-off between blood flow improvement and ribs fracture reduction.

PubMed

Zhang, Guang; Wu, Taihu; Song, Zhenxing; Wang, Haitao; Lu, Hengzhi; Wang, Yalin; Wang, Dan; Chen, Feng

2015-06-01

Chest compression (CC) is a significant emergency medical procedure for maintaining circulation during cardiac arrest. Although CC produces the necessary blood flow for patients with heart arrest, improperly deep CC will contribute significantly to the risk of chest injury. In this paper, an optimal CC closed-loop controller for a mechanical chest compressor (OCC-MCC) was developed to provide an effective trade-off between the benefit of improved blood perfusion and the risk of ribs fracture. The trade-off performance of the OCC-MCC during real automatic mechanical CCs was evaluated by comparing the OCC-MCC and the traditional mechanical CC method (TMCM) with a human circulation hardware model based on hardware simulations. A benefit factor (BF), risk factor (RF) and benefit versus risk index (BRI) were introduced in this paper for the comprehensive evaluation of risk and benefit. The OCC-MCC was developed using the LabVIEW control platform and the mechanical chest compressor (MCC) controller. PID control is also employed by MCC for effective compression depth regulation. In addition, the physiological parameters model for MCC was built based on a digital signal processor for hardware simulations. A comparison between the OCC-MCC and TMCM was then performed based on the simulation test platform which is composed of the MCC, LabVIEW control platform, physiological parameters model for MCC and the manikin. Compared with the TMCM, the OCC-MCC obtained a better trade-off and a higher BRI in seven out of a total of nine cases. With a higher mean value of cardiac output (1.35 L/min) and partial pressure of end-tidal CO2 (15.7 mmHg), the OCC-MCC obtained a larger blood flow and higher BF than TMCM (5.19 vs. 3.41) in six out of a total of nine cases. Although it is relatively difficult to maintain a stable CC depth when the chest is stiff, the OCC-MCC is still superior to the TMCM for performing safe and effective CC during CPR. The OCC-MCC is superior to the TMCM in performing safe and effective CC during CPR and can be incorporated into the current version of mechanical CC devices for high quality CPR, in both in-hospital and out-of-hospital CPR settings.

Comparison of Akt/mTOR/4E-BP1 pathway signal activation and mutations of PIK3CA in Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative carcinomas.

PubMed

Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Nagata, Keiko; Nakajima, Hideki; Sano, Shigetoshi; Hayashi, Kazuhiko

2015-02-01

Merkel cell polyomavirus (MCPyV) integrates monoclonally into the genomes of approximately 80% of Merkel cell carcinomas (MCCs), affecting their clinicopathological features. The molecular mechanisms underlying MCC development after MCPyV infection remain unclear. We investigated the association of MCPyV infection with activation of the Akt/mammalian target of rapamycin (mTOR)/4E-binding protein 1 (4E-BP1) signaling pathway in MCCs to elucidate the role of these signal transductions and to identify molecular targets for treatment. We analyzed the molecular and pathological characteristics of 41 MCPyV-positive and 27 MCPyV-negative MCCs. Expression of mTOR, TSC1, and TSC2 messenger RNA was significantly higher in MCPyV-negative MCCs, and Akt (T308) phosphorylation also was significantly higher (92% vs 66%; P = .019), whereas 4E-BP1 (S65 and T70) phosphorylation was common in both MCC types (92%-100%). The expression rates of most other tested signals were high (60%-100%) and not significantly correlated with MCPyV large T antigen expression. PIK3CA mutations were observed more frequently in MCPyV-positive MCCs (6/36 [17%] vs 2/20 [10%]). These results suggest that protein expression (activation) of most Akt/mTOR/4E-BP1 pathway signals was not significantly different in MCPyV-positive and MCPyV-negative MCCs, although these 2 types may differ in tumorigenesis, and MCPyV-negative MCCs showed significantly more frequent p-Akt (T308) activation. Therefore, certain Akt/mTOR/4E-BP1 pathway signals could be novel therapeutic targets for MCC regardless of MCPyV infection status. Copyright © 2015 Elsevier Inc. All rights reserved.

Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation

PubMed Central

Vladar, Eszter K.; Nayak, Jayakar V.; Milla, Carlos E.; Axelrod, Jeffrey D.

2016-01-01

Motile airway cilia that propel contaminants out of the lung are oriented in a common direction by planar cell polarity (PCP) signaling, which localizes PCP protein complexes to opposite cell sides throughout the epithelium to orient cytoskeletal remodeling. In airway epithelia, PCP is determined in a 2-phase process. First, cell-cell communication via PCP complexes polarizes all cells with respect to the proximal-distal tissue axis. Second, during ciliogenesis, multiciliated cells (MCCs) undergo cytoskeletal remodeling to orient their cilia in the proximal direction. The second phase not only directs cilium polarization, but also consolidates polarization across the epithelium. Here, we demonstrate that in airway epithelia, PCP depends on MCC differentiation. PCP mutant epithelia have misaligned cilia, and also display defective barrier function and regeneration, indicating that PCP regulates multiple aspects of airway epithelial homeostasis. In humans, MCCs are often sparse in chronic inflammatory diseases, and these airways exhibit PCP dysfunction. The presence of insufficient MCCs impairs mucociliary clearance in part by disrupting PCP-driven polarization of the epithelium. Consistent with defective PCP, barrier function and regeneration are also disrupted. Pharmacological stimulation of MCC differentiation restores PCP and reverses these defects, suggesting its potential for broad therapeutic benefit in chronic inflammatory disease. PMID:27570836

GEMC1 is a critical regulator of multiciliated cell differentiation.

PubMed

Terré, Berta; Piergiovanni, Gabriele; Segura-Bayona, Sandra; Gil-Gómez, Gabriel; Youssef, Sameh A; Attolini, Camille Stephan-Otto; Wilsch-Bräuninger, Michaela; Jung, Carole; Rojas, Ana M; Marjanović, Marko; Knobel, Philip A; Palenzuela, Lluís; López-Rovira, Teresa; Forrow, Stephen; Huttner, Wieland B; Valverde, Miguel A; de Bruin, Alain; Costanzo, Vincenzo; Stracker, Travis H

2016-05-02

The generation of multiciliated cells (MCCs) is required for the proper function of many tissues, including the respiratory tract, brain, and germline. Defects in MCC development have been demonstrated to cause a subclass of mucociliary clearance disorders termed reduced generation of multiple motile cilia (RGMC). To date, only two genes, Multicilin (MCIDAS) and cyclin O (CCNO) have been identified in this disorder in humans. Here, we describe mice lacking GEMC1 (GMNC), a protein with a similar domain organization as Multicilin that has been implicated in DNA replication control. We have found that GEMC1-deficient mice are growth impaired, develop hydrocephaly with a high penetrance, and are infertile, due to defects in the formation of MCCs in the brain, respiratory tract, and germline. Our data demonstrate that GEMC1 is a critical regulator of MCC differentiation and a candidate gene for human RGMC or related disorders. © 2016 The Authors.

Potential applicability of chymotrypsin-susceptible microcin J25 derivatives to food preservation.

PubMed

Pomares, María Fernanda; Salomón, Raúl A; Pavlova, Olga; Severinov, Konstantin; Farías, Ricardo; Vincent, Paula A

2009-09-01

Microcin J25 (MccJ25) is a 21-residue ribosomally synthesized lariat peptide antibiotic. MccJ25 is active against such food-borne disease-causing pathogens as Salmonella spp., Shigella spp., and Escherichia coli, including E. coli O157:H7 and non-O157 strains. MccJ25 is highly resistant to digestion by proteolytic enzymes present in the stomach and intestinal contents. MccJ25 would therefore remain active in the gastrointestinal tract, affecting normal intestinal microbiota, and this limits the potential use of MccJ25 as a food preservative. In the present paper, we describe a chymotrypsin-susceptible MccJ25 derivative with a mutation of Gly(12) to Tyr that retained almost full antibiotic activity and efficiently inhibited the growth of pathogenic Salmonella enterica serovar Newport and Escherichia coli O157:H7 in skim milk and egg yolk. However, unlike the wild-type MccJ25, the MccJ25(G12Y) variant was inactivated by digestive enzymes both in vitro and in vivo. To our knowledge, our results represent the first example of a rational modification of a microcin aimed at increasing its potential use in food preservation.

Physical and structural properties of polyaniline/microcrystalline cellulose nanocomposite

NASA Astrophysics Data System (ADS)

Abdi, Mahnaz M.; Liyana, Rawaida; Tahir, Paridah Md; Heng, Lee Yook; Sulaiman, Yusran; Waheeda, Nur Farhana; Hassan, Nabihah Abu

2017-12-01

A composite of Polyaniline/Microcrystalline Cellulose (PAni/MCC) was prepared via a chemical polymerization method in the presence of ammonium persulfate (NH4)2S2O8 as oxidant and cetyltrimethylammonium bromide (CTAB) as a cationic surfactant. The results of FESEM showed that the morphology of nanocomposite depends on the monomer concentration. Wire-like and porous nanostructure was observed for PAni/MCC/CTAB composite that could be suitable for enzyme immobilization and sensor applications. The electrochemical properties of the composites were studied using Cyclic Voltammetry (CV) and it was shown that PAni/MCC/CTAB composite generated a higher current response compared to the pure PAni. The synergy effect of MCC and CTAB on the physical and electrochemical properties of composite resulted in higher electron transferring in PAni/MCC/CTAB. The presence of significant peaks of PAni and MCC in FT-IR spectrum of nanocomposite indicating polymerization of aniline on the surface of MCC. Characteristic peaks of crystalline cellulose were observed at 22.8 and 14.7 2theta in XRD pattern.

Enteric coated spheres produced by extrusion/spheronization provide effective gastric protection and efficient release of live therapeutic bacteria.

PubMed

de Barros, João M S; Lechner, Tabea; Charalampopoulos, Dimitrios; Khutoryanskiy, Vitaliy V; Edwards, Alexander D

2015-09-30

We present a novel but simple enteric coated sphere formulation containing probiotic bacteria (Lactobacillus casei). Oral delivery of live bacterial cells (LBC) requires live cells to survive firstly manufacturing processes and secondly GI microbicidal defenses including gastric acid. We incorporated live L. casei directly in the granulation liquid, followed by granulation, extrusion, spheronization, drying and spray coating to produce dried live probiotic spheres. A blend of MCC, calcium-crosslinked alginate, and lactose was developed that gave improved live cell survival during manufacturing, and gave excellent protection from gastric acid plus rapid release in intestinal conditions. No significant loss of viability was observed in all steps except drying, which resulted in approximately 1 log loss of viable cells. Eudragit coating was used to protect dried live cells from acid, and microcrystalline cellulose (MCC) was combined with sodium alginate to achieve efficient sphere disintegration leading to rapid and complete bacterial cell release in intestinal conditions. Viability and release of L. casei was evaluated in vitro in simulated GI conditions. Uncoated spheres gave partial acid protection, but enteric coated spheres effectively protected dried probiotic LBC from acid for 2h, and subsequently released all viable cells within 1h of transfer into simulated intestinal fluid. Copyright © 2015 Elsevier B.V. All rights reserved.

Randomized Trial to Compare the Immunogenicity and Safety of a CRM or TT Conjugated Quadrivalent Meningococcal Vaccine in Teenagers who Received a CRM or TT Conjugated Serogroup C Vaccine at Preschool Age.

PubMed

Ishola, David A; Andrews, Nick; Waight, Pauline; Yung, Chee-Fu; Southern, Jo; Bai, Xilian; Findlow, Helen; Matheson, Mary; England, Anna; Hallis, Bassam; Findlow, Jamie; Borrow, Ray; Miller, Elizabeth

2015-08-01

Protection after meningococcal C (MenC) conjugate (MCC) vaccination in early childhood is short-lived. Boosting with a quadrivalent vaccine in teenage years, a high-risk period for MenC disease, should protect against additional serogroups but might compromise MenC response. The carrier protein in the primary MCC vaccine determines the response to MCC booster in toddlers, but the relationship between primary vaccine and booster given later is unclear. This study compared responses to a CRM-conjugated or tetanus toxoid (TT)-conjugated MenACWY vaccine in teenagers primed with different MCC vaccines at preschool age. Ninety-three teenagers (16-19 years), who were previously randomized at age 3-6 years to receive single-dose MCC-CRM or MCC-TT, were randomized to receive either MenACWY-CRM or MenACWY-TT booster. Serum bactericidal antibodies (SBA, protective titer ≥ 8) were measured before, 1 month and 6 or 9 months after boosting. Preboosting, MCC-TT-primed teenagers had significantly higher MenC SBA titers than those MCC-CRM-primed (P = 0.02). Postboosting, both MenACWY vaccines induced protective SBA titers to all 4 serogroups in most participants (≥ 98% at 1 month and ≥ 90% by 9 months postboost). The highest MenC SBA titers were seen in those MCC-TT-primed and MenACWY-TT-boosted [geometric mean titer (GMT) ~ 22,000] followed by those boosted with MenACWY-CRM irrespective of priming (GMT ~ 12,000) and then those MCC-CRM-primed and MenACWY-TT-boosted (GMT ~ 5500). The estimated postbooster MenC SBA decline beyond 1 month was ~40% as time since booster doubles. Both vaccines were well tolerated with no attributable serious adverse events. Both MenACWY vaccines safely induced protective sustained antibody responses against all targeted serogroups in MCC-primed teenagers.

When times get tough, what happens to TQM? Case study.

PubMed

Niven, D

1993-01-01

When Mueller Chemical Company's biggest customer, Ameriton, demanded that MCC install a total quality management system five years ago, the effort seemed worth it. Morale improved dramatically at the German company, as did quality and productivity. But now, in this fictional case study, Ameriton has gone bankrupt. As a result, MCC has had to cut its work force, and senior managers are meeting to decide whether TQM should be part of the downsized MCC. Horst Koblitz, director of TQM, and Division Manager Eva Stichen both vote yes. Stichen's division, which never supplied Ameriton, has turned its process-control system into the company's best thanks to TQM. The division is more cost-efficient, product defects are nearly nonexistent, and its safety record is spotless. As Koblitz notes, Ameriton's failure is no reason to abandon all that MCC has built. Furthermore, shareholders and customers would think that MCC was panicking. MCC just needs to tailor its TQM program to a smaller organization. But CFO Georg Becker doesn't think MCC has the time or resources for fine-tuning. And as he sees it, that might be just as well. The distractions that came with TQM took MCC away from its goal of becoming the chemicals market leader in Europe. While the company organized teams, developed measurement systems, and filled out quality reports, its competitors took away much of the market share MCC was after. TQM was a good long-term approach, but it didn't come with a plan for MCC's current situation. And CEO and Chairman Dieter Mueller won't compromise; TQM must either stay or go.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamics of Metamorphic Core Complexes Inferred From Modeling and Metamorphic Petrology

NASA Astrophysics Data System (ADS)

Whitney, D. L.; Rey, P.; Teyssier, C.

2008-12-01

Orogenic collapse involves extension and thinning of thick, hot, and in some cases partially molten, crust, leading to the formation of metamorphic core complexes (MCC) that are commonly cored by migmatite domes. 2D numerical modeling predicts that the geometry and P-T-t history of MCC varies as a function of the presence/absence of a partially molten layer in the deep crust; the nature of heterogeneities that localize the MCC (e.g. normal fault in upper crust vs. point-like anomaly in the deep crust); and extensional strain rate. The presence of melt in particular has a significant effect on the thermal and structural history of MCC because the presence of partially molten crust or magma bodies at depth enhances upward advection of material and heat. At high extension rate (cm/year in the region of the MCC), partially molten crust crystallizes as migmatite and cools along a high geothermal gradient (35-65 C/km); material remains partially molten during ascent, forming a migmatite dome when it crystallizes at shallower crustal levels (e.g. cordierite/sillimanite stability field). At low strain rate (mm/yr in the MCC region), the partially molten crust crystallizes at high pressure (e.g. kyanite zone); this material is subsequently deformed in the solid-state along a cooler geothermal gradient (20-35 C/km) during ascent. MCC that develop during extension of partially molten crust may therefore record distinct crystallization versus exhumation histories as a function of extensional strain rate. The mineral assemblages, metamorphic reaction histories, and structures of migmatite-cored (Mc) MCC can therefore be used to interpret the dynamics of MCC formation, e.g. "fast" McMCC in the northern N American Cordillera and Aegean regions.

Production of bioplastic from jackfruit seed starch (Artocarpus heterophyllus) reinforced with microcrystalline cellulose from cocoa pod husk (Theobroma cacao L.) using glycerol as plasticizer

NASA Astrophysics Data System (ADS)

Lubis, M.; Gana, A.; Maysarah, S.; Ginting, M. H. S.; Harahap, M. B.

2018-02-01

The production of bioplastic from jackfruit seed starch reinforced with microcrystalline cellulose (MCC) cocoa pod husk using glycerol as plasticizer was investigated to determine the most optimum mass and volume of MCC and glycerol in producing bioplastics. To produce MCC, Cocoa pod husk was subjected to alkali treatment, bleaching, and hydrochloric acid hydrolysis. The degree of crystallinity of MCC, were determined by XRD, functional group by FT-IR and morphologycal analysis by SEM. Analysis of bioplastic mechanical properties includes tensile strength and elongation at break based on ASTM D882 standard. Bioplastics were produced by casting method from jackfruit seed starch and reinforced with MCC from cocoa pod husk at starch mass to MCC ratio of 6:4, 7:3, 8:2, and 9:1, using glycerol as plasticizer at 20%, 25%, 30% (wt/v of glycerol to starch). From the result, the isolated MCC from cocoa pod husk were in a form of rod-like shape of length 5-10 µm with diameter 11.635 nm and 74% crystallinity. The highest tensile strength of bioplastics was obtained at starch to MCC mass ratio of 8:2, addition of 20% glycerol with measured tensile strength of 0.637 MPa and elongation at break of 7.04%. Transform infrared spectroscopy showed the functional groups of bioplastics, which the majority of O-H groups were found at the bioplastics with reinforcing filler MCC that represented substantial hydrogen bonds.

Production of Starch Based Bioplastic from Cassava Peel Reinforced with Microcrystalline Celllulose Avicel PH101 Using Sorbitol as Plasticizer

NASA Astrophysics Data System (ADS)

Maulida; Siagian, M.; Tarigan, P.

2016-04-01

The production of starch based bioplastics from cassava peel reeinforced with microcrystalline cellulose using sorbitol as plasticizer were investigated. Physical properties of bioplastics were determined by density, water uptake, tensile strength and Fourier Transform Infrared Spectroscopy. Bioplastics were prepared from cassava peel starch plasticized using sorbitol with variation of 20; 25; 30% (wt/v of sorbitol to starch) reinforced with microcrystalline celllulose (MCC) Avicel PH101 fillers with range of 0 to 6% (wt/wt of MCC to starch). The results showed improvement in tensile strength with higher MCC content up to 9, 12 mpa compared to non-reinforced bioplastics. This could be mainly attributed to the strong hydrogen bonds between MCC and starch. On the contrary, the addition of MCC decreased the elongation at break, density and water uptake. Fourier Transform Infrared Spectroscopy showed the functional groups of bioplastics, which the majority of O-H groups were found at the bioplastics with reinforcing filler MCC that represented substantial hydrogen bonds. The highest tensile strength value was obtained for bioplastic with MCC content 6% and sorbitol content 20%. With good adhesion between MCC and starch the production of bioplastics could be widely used as a substitute for conventional plastics with more benefits to the environment.

Intratumoral and peritumoral lymphovascular invasion detected by D2-40 immunohistochemistry correlates with metastasis in primary cutaneous Merkel cell carcinoma.

PubMed

Al-Rohil, Rami N; Milton, Denái R; Nagarajan, Priyadharsini; Curry, Jonathan L; Feldmeyer, Laurence; Torres-Cabala, Carlos A; Ivan, Doina; Prieto, Victor G; Tetzlaff, Michael T; Aung, Phyu P

2018-07-01

Primary cutaneous Merkel cell carcinoma (MCC) is an aggressive neuroendocrine malignancy in which lymphovascular invasion (LVI) correlates with more aggressive phenotype. The prognostic significance of LVI detected by D2-40 immunohistochemistry (IHC) in MCC remains controversial. We aimed to determine how LVI detected by D2-40 IHC compares with LVI detected by hematoxylin and eosin (H&E) staining in predicting MCC metastasis. Clinical and histopathologic features of MCCs diagnosed and treated in 2002 to 2015 were assembled and included 58 MCC tumors from 58 patients. H&E-stained tissue sections and D2-40 IHC studies were reviewed. When LVI was present, the location (peritumoral or intratumoral) and the size of the largest invaded vessel were recorded. LVI findings by H&E staining and D2-40 IHC were compared with each other and with histologic features and clinical outcomes. H&E staining showed LVI in 37 of 58 cases; D2-40 IHC confirmed LVI in 30 of these cases but failed to confirm LVI in 7. D2-40 IHC also detected 14 cases of LVI not identified on H&E staining. Histologically, D2-40-detected LVI was associated with infiltrative growth pattern and nonbrisk lymphoid infiltrate (P = .005 and P = .055, respectively). There was a statistically significant difference between the frequency of detection of peritumoral LVI by H&E in comparison to D2-40 IHC (P = .0009). MCCs in which D2-40 IHC-detected both intratumoral and peritumoral LVI were typically larger than MCCs without (mean, 24.5 mm versus 17.3 mm; P = .03) and more frequently metastasized (87% versus 51%; P = .03). D2-40 IHC detection of both intratumoral and peritumoral LVI is associated with metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Modeling OPC complexity for design for manufacturability

NASA Astrophysics Data System (ADS)

Gupta, Puneet; Kahng, Andrew B.; Muddu, Swamy; Nakagawa, Sam; Park, Chul-Hong

2005-11-01

Increasing design complexity in sub-90nm designs results in increased mask complexity and cost. Resolution enhancement techniques (RET) such as assist feature addition, phase shifting (attenuated PSM) and aggressive optical proximity correction (OPC) help in preserving feature fidelity in silicon but increase mask complexity and cost. Data volume increase with rise in mask complexity is becoming prohibitive for manufacturing. Mask cost is determined by mask write time and mask inspection time, which are directly related to the complexity of features printed on the mask. Aggressive RET increase complexity by adding assist features and by modifying existing features. Passing design intent to OPC has been identified as a solution for reducing mask complexity and cost in several recent works. The goal of design-aware OPC is to relax OPC tolerances of layout features to minimize mask cost, without sacrificing parametric yield. To convey optimal OPC tolerances for manufacturing, design optimization should drive OPC tolerance optimization using models of mask cost for devices and wires. Design optimization should be aware of impact of OPC correction levels on mask cost and performance of the design. This work introduces mask cost characterization (MCC) that quantifies OPC complexity, measured in terms of fracture count of the mask, for different OPC tolerances. MCC with different OPC tolerances is a critical step in linking design and manufacturing. In this paper, we present a MCC methodology that provides models of fracture count of standard cells and wire patterns for use in design optimization. MCC cannot be performed by designers as they do not have access to foundry OPC recipes and RET tools. To build a fracture count model, we perform OPC and fracturing on a limited set of standard cells and wire configurations with all tolerance combinations. Separately, we identify the characteristics of the layout that impact fracture count. Based on the fracture count (FC) data from OPC and mask data preparation runs, we build models of FC as function of OPC tolerances and layout parameters.

Chronic disease burden predicts food insecurity among older adults.

PubMed

Jih, Jane; Stijacic-Cenzer, Irena; Seligman, Hilary K; Boscardin, W John; Nguyen, Tung T; Ritchie, Christine S

2018-06-01

Increased out-of-pocket health-care expenditures may exert budget pressure on low-income households that leads to food insecurity. The objective of the present study was to examine whether older adults with higher chronic disease burden are at increased risk of food insecurity. Secondary analysis of the 2013 Health and Retirement Study (HRS) Health Care and Nutrition Study (HCNS) linked to the 2012 nationally representative HRS. USA. Respondents of the 2013 HRS HCNS with household incomes <300 % of the federal poverty line (n 3552). Chronic disease burden was categorized by number of concurrent chronic conditions (0-1, 2-4, ≥5 conditions), with multiple chronic conditions (MCC) defined as ≥2 conditions. The prevalence of food insecurity was 27·8 %. Compared with those having 0-1 conditions, respondents with MCC were significantly more likely to report food insecurity, with the adjusted odds ratio for those with 2-4 conditions being 2·12 (95 % CI 1·45, 3·09) and for those with ≥5 conditions being 3·64 (95 % CI 2·47, 5·37). A heavy chronic disease burden likely exerts substantial pressure on the household budgets of older adults, creating an increased risk for food insecurity. Given the high prevalence of food insecurity among older adults, screening those with MCC for food insecurity in the clinical setting may be warranted in order to refer to community food resources.

Strength-controllable graphene oxide amphiprotic aerogels as highly efficient carrier for anionic and cationic azo molecules

NASA Astrophysics Data System (ADS)

Xiong, Jiaqing; Jiao, Chenlu; Xu, Sijun; Tao, Jin; Zhang, Desuo; Lin, Hong; Chen, Yuyue

2015-06-01

Ice-bath self-assembly was employed to fabricate the GO/AP-MCC/CS aerogel based on natural materials. The components are amphiprotic microcrystalline cellulose (AP-MCC), chitosan (CS), and graphene oxide (GO), which act as the main framework, auxiliary framework and adhesive, respectively. The results of characterization determines the components form the GO/AP-MCC/CS aerogel according to chemical interactions. The mechanical properties depend largely on the mass ratio of AP-MCC/CS, which can be regulated by controlling the contents of AP-MCC and CS. The resultant GO/AP-MCC/CS aerogel was observed possessing three-dimensional (3D) interpenetrating porous networks with wrinkled structure on the inner wall, which provide a good encapsulation capacity for the guest molecules. As expected, owing to the amphiprotic properties and large specific surface area, GO/AP-MCC/CS aerogel exhibits high-efficiency load capacity for both anionic (CR) and cationic azo molecules (MB), which can reach up to about 132.2 mg/g for CR and 123.2 mg/g for MB, respectively.

Exploratory research for the development of a computer aided software design environment with the software technology program

NASA Technical Reports Server (NTRS)

Hardwick, Charles

1991-01-01

Field studies were conducted by MCC to determine areas of research of mutual interest to MCC and JSC. NASA personnel from the Information Systems Directorate and research faculty from UHCL/RICIS visited MCC in Austin, Texas to examine tools and applications under development in the MCC Software Technology Program. MCC personnel presented workshops in hypermedia, design knowledge capture, and design recovery on site at JSC for ISD personnel. The following programs were installed on workstations in the Software Technology Lab, NASA/JSC: (1) GERM (Graphic Entity Relations Modeler); (2) gIBIS (Graphic Issues Based Information System); and (3) DESIRE (Design Recovery tool). These applications were made available to NASA for inspection and evaluation. Programs developed in the MCC Software Technology Program run on the SUN workstation. The programs do not require special configuration, but they will require larger than usual amounts of disk space and RAM to operate properly.

Teamwork and team decision-making at multidisciplinary cancer conferences: barriers, facilitators, and opportunities for improvement.

PubMed

Lamb, Benjamin W; Sevdalis, Nick; Arora, Sonal; Pinto, Anna; Vincent, Charles; Green, James S A

2011-09-01

Anecdotally, multidisciplinary cancer conferences (MCCs) do not always function optimally. MCC members' experiences with and attitudes toward MCCs are explored, and barriers to and facilitators of effective team-working are identified. A total of 19 semistructured interviews were conducted with surgeons, oncologists, nurses, and administrators. Interviews explored participants' opinions on MCC attendance, information presentation, case discussion, leadership, team decision-making, and possible improvements to MCC meetings. Nonattendance was associated with not having protected time to attend the MCC. Contributions to MCC discussions were unequal among the participants, and patient-centered information was ignored. Good leadership was necessary to foster inclusive case discussion. Members were positive about MCCs, but protected time, improved case selection, and working in a more structured way were possible improvements. Results are consistent with previous research: Members of the MCC are positive about the benefits of MCCs, although improving the way MCCs work is a goal.

Prevalence of Multiple Chronic Conditions Among US Adults: Estimates From the National Health Interview Survey, 2010

PubMed Central

Schiller, Jeannine S.

2013-01-01

Preventing and ameliorating chronic conditions has long been a priority in the United States; however, the increasing recognition that people often have multiple chronic conditions (MCC) has added a layer of complexity with which to contend. The objective of this study was to present the prevalence of MCC and the most common MCC dyads/triads by selected demographic characteristics. We used respondent-reported data from the 2010 National Health Interview Survey (NHIS) to study the US adult civilian noninstitutionalized population aged 18 years or older (n = 27,157). We categorized adults as having 0 to 1, 2 to 3, or 4 or more of the following chronic conditions: hypertension, coronary heart disease, stroke, diabetes, cancer, arthritis, hepatitis, weak or failing kidneys, chronic obstructive pulmonary disease, or current asthma. We then generated descriptive estimates and tested for significant differences. Twenty-six percent of adults have MCC; the prevalence of MCC has increased from 21.8% in 2001 to 26.0% in 2010. The prevalence of MCC significantly increased with age, was significantly higher among women than men and among non-Hispanic white and non-Hispanic black adults than Hispanic adults. The most common dyad identified was arthritis and hypertension, and the combination of arthritis, hypertension, and diabetes was the most common triad. The findings of this study contribute information to the field of MCC research. The NHIS can be used to identify population subgroups most likely to have MCC and potentially lead to clinical guidelines for people with more common MCC combinations. PMID:23618545

Setup and Calibration of SLAC's Peripheral Monitoring Stations

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

Cooper, C.

2004-09-03

The goals of this project were to troubleshoot, repair, calibrate, and establish documentation regarding SLAC's (Stanford Linear Accelerator Center's) PMS (Peripheral Monitoring Station) system. The PMS system consists of seven PMSs that continuously monitor skyshine (neutron and photon) radiation levels in SLAC's environment. Each PMS consists of a boron trifluoride (BF{sub 3}) neutron detector (model RS-P1-0802-104 or NW-G-20-12) and a Geiger Moeller (GM) gamma ray detector (model TGM N107 or LND 719) together with their respective electronics. Electronics for each detector are housed in Nuclear Instrument Modules (NIMs) and are plugged into a NIM bin in the station. All communicationmore » lines from the stations to the Main Control Center (MCC) were tested prior to troubleshooting. To test communication with MCC, a pulse generator (Systron Donner model 100C) was connected to each channel in the PMS and data at MCC was checked for consistency. If MCC displayed no data, the communication cables to MCC or the CAMAC (Computer Automated Measurement and Control) crates were in need of repair. If MCC did display data, then it was known that the communication lines were intact. All electronics from each station were brought into the lab for troubleshooting. Troubleshooting usually consisted of connecting an oscilloscope or scaler (Ortec model 871 or 775) at different points in the circuit of each detector to record simulated pulses produced by a pulse generator; the input and output pulses were compared to establish the location of any problems in the circuit. Once any problems were isolated, repairs were done accordingly. The detectors and electronics were then calibrated in the field using radioactive sources. Calibration is a process that determines the response of the detector. Detector response is defined as the ratio of the number of counts per minute interpreted by the detector to the amount of dose equivalent rate (in mrem per hour, either calculated or measured). Detector response for both detectors is dependent upon the energy of the incident radiation; this trend had to be accounted for in the calibration of the BF{sub 3} detector. Energy dependence did not have to be taken into consideration when calibrating the GM detectors since GM detector response is only dependent on radiation energy below 100 keV; SLAC only produces a spectrum of gamma radiation above 100 keV. For the GM detector, calibration consisted of bringing a {sup 137}Cs source and a NIST-calibrated RADCAL Radiation Monitor Controller (model 9010) out to the field; the absolute dose rate was determined by the RADCAL device while simultaneously irradiating the GM detector to obtain a scaler reading corresponding to counts per minute. Detector response was then calculated. Calibration of the BF{sub 3} detector was done using NIST certified neutron sources of known emission rates and energies. Five neutron sources ({sup 238}PuBe, {sup 238}PuB, {sup 238}PuF4, {sup 238}PuLi and {sup 252}Cf) with different energies were used to account for the energy dependence of the response. The actual neutron dose rate was calculated by date-correcting NIST source data and considering the direct dose rate and scattered dose rate. Once the total dose rate (sum of the direct and scattered dose rates) was known, the response vs. energy curve was plotted. The first station calibrated (PMS6) was calibrated with these five neutron sources; all subsequent stations were calibrated with one neutron source and the energy dependence was assumed to be the same.« less

Roles of Chondrocytes in Endochondral Bone Formation and Fracture Repair

PubMed Central

Hinton, R.J.; Jing, Y.; Jing, J.; Feng, J.Q.

2016-01-01

The formation of the mandibular condylar cartilage (MCC) and its subchondral bone is an important but understudied topic in dental research. The current concept regarding endochondral bone formation postulates that most hypertrophic chondrocytes undergo programmed cell death prior to bone formation. Under this paradigm, the MCC and its underlying bone are thought to result from 2 closely linked but separate processes: chondrogenesis and osteogenesis. However, recent investigations using cell lineage tracing techniques have demonstrated that many, perhaps the majority, of bone cells are derived via direct transformation from chondrocytes. In this review, the authors will briefly discuss the history of this idea and describe recent studies that clearly demonstrate that the direct transformation of chondrocytes into bone cells is common in both long bone and mandibular condyle development and during bone fracture repair. The authors will also provide new evidence of a distinct difference in ossification orientation in the condylar ramus (1 ossification center) versus long bone ossification formation (2 ossification centers). Based on our recent findings and those of other laboratories, we propose a new model that contrasts the mode of bone formation in much of the mandibular ramus (chondrocyte-derived) with intramembranous bone formation of the mandibular body (non-chondrocyte-derived). PMID:27664203

Mesoscale Convective Complexes (MCCs) over the Indonesian Maritime Continent during the ENSO events

NASA Astrophysics Data System (ADS)

Trismidianto; Satyawardhana, H.

2018-05-01

This study analyzed the mesoscale convective complexes (MCCs) over the Indonesian Maritime Continent (IMC) during the El Niño/Southern Oscillation (ENSO) events for the the15-year period from 2001 to 2015. The MCCs identified by infrared satellite imagery that obtained from the Himawari generation satellite data. This study has reported that the frequencies of the MCC occurrences at the El Niño and La Niña were higher than that of neutral conditions during DJF. Peak of MCC occurrences during DJF at La Niña and neutral condition is in February, while El Niño is in January. ENSO strongly affects the occurrence of MCC during the DJF season. The existences of the MCC were also accompanied by increased rainfall intensity at the locations of the MCC occurrences for all ENSO events. During JJA seasons, the MCC occurrences are always found during neutral conditions, El Niño and La Niña in Indian Ocean. MCC occurring during the JJA season on El Niño and neutral conditions averaged much longer than during the DJF season. In contrast, MCCs occurring in La Niña conditions during the JJA season are more rapidly extinct than during the DJF. It indicates that the influence of MCC during La Niña during the DJF season is stronger than during the JJA season.

Mission Control Center (MCC) View - Apollo 13 Oxygen Cell Failure - MSC

NASA Image and Video Library

1970-04-15

S70-35014 (15 April 1970) --- A group of flight controllers gathers around the console of Glenn S. Lunney (seated, nearest camera), Shift 4 flight director, in the Mission Operations Control Room (MOCR) of Mission Control Center (MCC), located in Building 30 at the Manned Spacecraft Center (MSC). Their attention is drawn to a weather map of the proposed landing site in the South Pacific Ocean. Among those looking on is Dr. Christopher C. Kraft, deputy director, MSC, standing in black suit, on right. When this photograph was taken, the Apollo 13 lunar landing mission had been canceled, and the problem-plagued Apollo 13 crew members were in trans-Earth trajectory attempting to bring their crippled spacecraft back home.

Identification of Mesoscale Convective Complex (MCC) phenomenon with image of Himawari 8 Satellite and WRF ARW Model on Bangka Island (Case Study: 7-8 February 2016)

NASA Astrophysics Data System (ADS)

Rinaldy, Nanda; Saragih, Immanuel J. A.; Wandala Putra, Agie; Redha Nugraheni, Imma; Wijaya Yonas, Banu

2017-12-01

Based on monitoring on 7th and 8th February 2016 there has been a flood that occurred due to heavy rainfall in a long time in some areas of Bangka Island. Mesoscale Convective Complex (MCC) is one type of Mesoscale Convective System (MCS). Previous research on MCC mentions that MCC can cause heavy rain for a long time. This study aims to identify the phenomenon of MCC in Bangka Island both in the satellite imagery and the output of the model. In addition, this study was also conducted to determine the effect of MCC on the weather conditions in Bangka Island. The study area in this research is Bangka Island with Pangkalpinang Meteorological Station as the centre of research. The data used in this research are FNL (Final Analysis) data from http://rda.ucar.edu/, Satellite Image of Himawari-8 IR1 Channel from BMKG, and meteorological observation data (synoptic and radiosonde) from Pangkalpinang Meteorological Station. The FNL data is simulated using the WRF-ARW model, verified using observation data and then visualized using GrADS. The results of the analysis of Himawari-8 satellite image data showed that two MCCs occurred on 7th and 8th February 2016 on Bangka Island and the MCC was nocturnal, which appeared at night which then continued until extinction in the morning the next day. In a peak cloud temperature review with the coordinates of Pangkalpinang Meteorological Station (-2,163 N 106,137 E) when 1st MCC and 2nd MCC events ranged from -60°C to -80°C. The result of WRF-ARW model output analysis shows that MCC area has high humidity value and positive vertical velocity value which indicates the potential of heavy rain for a long time.

Identifying Meteorological Controls on Open and Closed Mesoscale Cellular Convection as Associated with Marine Cold Air Outbreaks

NASA Astrophysics Data System (ADS)

McCoy, Isabel; Wood, Robert; Fletcher, Jennifer

Marine low clouds are key influencers of the climate and contribute significantly to uncertainty in model climate sensitivity due to their small scale and complex processes. Many low clouds occur in large-scale cellular patterns, known as open and closed mesoscale cellular convection (MCC), which have significantly different radiative and microphysical properties. Investigating MCC development and meteorological controls will improve our understanding of their impacts on the climate. We conducted an examination of time-varying meteorological conditions associated with satellite-determined open and closed MCC. The spatial and temporal patterns of MCC clouds were compared with key meteorological control variables calculated from ERA-Interim Reanalysis to highlight dependencies and major differences. This illustrated the influence of environmental stability and surface forcing as well as the role of marine cold air outbreaks (MCAO, the movement of cold air from polar-regions across warmer waters) in MCC cloud formation. Such outbreaks are important to open MCC development and may also influence the transition from open to closed MCC. Our results may lead to improvements in the parameterization of cloudiness and advance the simulation of marine low clouds. National Science Foundation Graduate Research Fellowship Grant (DGE-1256082).

STS-26 simulation activities in JSC Mission Control Center (MCC)

NASA Technical Reports Server (NTRS)

1987-01-01

In JSC Mission Control Center (MCC) Bldg 30 Flight Control Room (FCR), flight controller Granvil A. Pennington, leaning on console, listens to communications during the STS-26 integrated simulations in progress between MCC and JSC Mission Simulation and Training Facility Bldg 5 fixed-base (FB) shuttle mission simulator (SMS). MCC FCR visual displays are seen in background. Five veteran astronauts were in the FB-SMS rehearsing their roles for the scheduled June 1988 flight aboard Discovery, Orbiter Vehicle (OV) 103.

Redox-active tyrosine residue in the microcin J25 molecule

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

Chalon, Miriam C.; Wilke, Natalia; Pedersen, Jens

2011-03-18

Research highlights: {yields} Cyclic voltammetry measurements showed irreversible oxidation of MccJ25 and MccJ25 (Y9F). {yields} Infrared spectroscopy studies showed that only Tyr9 could be deprotonated upon chemical oxidation. {yields} Formation of a long-lived tyrosyl radical in the native MccJ25 oxidized by H{sub 2}O{sub 2} was demonstrated. {yields} Tyr9 but not Tyr20 can be easily oxidized and form a tyrosyl radical. -- Abstract: Microcin J25 (MccJ25) is a 21 amino acid lasso-peptide antibiotic produced by Escherichia coli and composed of an 8-residues ring and a terminal 'tail' passing through the ring. We have previously reported two cellular targets for this antibiotic,more » bacterial RNA polymerase and the membrane respiratory chain, and shown that Tyr9 is essential for the effect on the membrane respiratory chain which leads to superoxide overproduction. In the present paper we investigated the redox behavior of MccJ25 and the mutant MccJ25 (Y9F). Cyclic voltammetry measurements showed irreversible oxidation of both Tyr9 and Tyr20 in MccJ25, but infrared spectroscopy studies demonstrated that only Tyr9 could be deprotonated upon chemical oxidation in solution. Formation of a long-lived tyrosyl radical in the native MccJ25 oxidized by H{sub 2}O{sub 2} was demonstrated by Electron Paramagnetic Resonance Spectroscopy; this radical was not detected when the reaction was carried out with the MccJ25 (Y9F) mutant. These results show that the essential Tyr9, but not Tyr20, can be easily oxidized and form a tyrosyl radical.« less

Role of positive ions on the surface production of negative ions in a fusion plasma reactor type negative ion source--Insights from a three dimensional particle-in-cell Monte Carlo collisions model

NASA Astrophysics Data System (ADS)

Fubiani, G.; Boeuf, J. P.

2013-11-01

Results from a 3D self-consistent Particle-In-Cell Monte Carlo Collisions (PIC MCC) model of a high power fusion-type negative ion source are presented for the first time. The model is used to calculate the plasma characteristics of the ITER prototype BATMAN ion source developed in Garching. Special emphasis is put on the production of negative ions on the plasma grid surface. The question of the relative roles of the impact of neutral hydrogen atoms and positive ions on the cesiated grid surface has attracted much attention recently and the 3D PIC MCC model is used to address this question. The results show that the production of negative ions by positive ion impact on the plasma grid is small with respect to the production by atomic hydrogen or deuterium bombardment (less than 10%).

STS-26 simulation activities in JSC Mission Control Center (MCC)

NASA Technical Reports Server (NTRS)

1987-01-01

Overall view of JSC Mission Control Center (MCC) Bldg 30 Flight Control Room (FCR) during Flight Day 1 of STS-26 integrated simulations in progress between MCC and JSC Mission Simulation and Training Facility Bldg 5 fixed-base (FB) shuttle mission simulator (SMS).

Burden of Multiple Chronic Conditions in Delaware, 2011–2014

PubMed Central

2016-01-01

The objective of this study was to use data from the Behavioral Risk Factor Surveillance System (BRFSS) to examine the prevalence of multiple chronic conditions (MCC) by select sociodemographic groups and determine the prevalence of most common MCC dyads and triads among Delaware adults. Combined data for 2011 through 2014 from BRFSS (n = 18,052) were analyzed to determine prevalence of MCC. Delaware adults were categorized as having 0, 1, 2, or 3 or more of the following diagnosed chronic conditions: angina, arthritis, asthma, cancer, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, high blood pressure, high cholesterol, myocardial infarction (heart attack), obesity, or stroke. More than 65% of Delaware adults had at least 1 of the 12 selected chronic conditions. Furthermore, 36.8% of Delaware adults had MCC. The arthritis/obesity dyad and the arthritis/high blood pressure/high cholesterol triad were the 2 most prevalent MCC combinations. The findings of this study contribute information to the field of MCC research. PMID:27880632

Methylmercury causes neuronal cell death through the suppression of the TrkA pathway: In vitro and in vivo effects of TrkA pathway activators

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

Fujimura, Masatake, E-mail: fujimura@nimd.go.jp; Usuki, Fusako

Methylmercury (MeHg) is an environmental toxin which induces cell death specific for the nervous systems. Here we show that MeHg causes neuronal cell death through the suppression of the tropomyosin receptor kinase A (TrkA) pathway, and that compounds activating the TrkA pathway prevent MeHg-induced nerve damage in vitro and in vivo. We first investigated the mechanism of MeHg-induced neurotoxicity in differentiating neurons using PC12 cells. Exposure to 100 nM MeHg for 1 day induced apoptosis in differentiating PC12 cells. Further, MeHg-induced apoptosis was preceded by inhibition of neurite extension, as determined by ELISA analyses of the neurite-specific protein neurofilament tripletmore » H protein (NF-H). To determine the mechanism of MeHg-induced apoptosis, we evaluated the effects of MeHg on the TrkA pathway, which is known to regulate neuronal differentiation and viability. Western blot analysis demonstrated that, like the TrkA phosphorylation inhibitor K252a, MeHg inhibited phosphorylation of TrkA and its downstream effectors. Furthermore, GM1 ganglioside and its analog MCC-257, which enhance TrkA phosphorylation, overcame the effect of MeHg in neurons, supporting the involvement of the TrkA pathway in MeHg-induced nerve damage. Finally, we demonstrated that MCC-257 rescued the clinical sign and pathological changes in MeHg-exposed rats. These findings indicate that MeHg-induced apoptosis in neuron is triggered by inhibition of the TrkA pathway, and that GM1 ganglioside and MCC-257 effectively prevent MeHg-induced nerve damage. - Highlights: • Exposure to 100 nM MeHg for 1 day induced apoptosis in differentiating PC12 cells. • Inhibition of neurite extension was involved in MeHg-induced apoptosis. • Like the TrkA phosphorylation inhibitor, MeHg inhibited phosphorylation of TrkA. • GM1 ganglioside and its analog effectively prevented MeHg-induced nerve damage.« less

Spatiotemporal multistage consensus clustering in molecular dynamics studies of large proteins.

PubMed

Kenn, Michael; Ribarics, Reiner; Ilieva, Nevena; Cibena, Michael; Karch, Rudolf; Schreiner, Wolfgang

2016-04-26

The aim of this work is to find semi-rigid domains within large proteins as reference structures for fitting molecular dynamics trajectories. We propose an algorithm, multistage consensus clustering, MCC, based on minimum variation of distances between pairs of Cα-atoms as target function. The whole dataset (trajectory) is split into sub-segments. For a given sub-segment, spatial clustering is repeatedly started from different random seeds, and we adopt the specific spatial clustering with minimum target function: the process described so far is stage 1 of MCC. Then, in stage 2, the results of spatial clustering are consolidated, to arrive at domains stable over the whole dataset. We found that MCC is robust regarding the choice of parameters and yields relevant information on functional domains of the major histocompatibility complex (MHC) studied in this paper: the α-helices and β-floor of the protein (MHC) proved to be most flexible and did not contribute to clusters of significant size. Three alleles of the MHC, each in complex with ABCD3 peptide and LC13 T-cell receptor (TCR), yielded different patterns of motion. Those alleles causing immunological allo-reactions showed distinct correlations of motion between parts of the peptide, the binding cleft and the complementary determining regions (CDR)-loops of the TCR. Multistage consensus clustering reflected functional differences between MHC alleles and yields a methodological basis to increase sensitivity of functional analyses of bio-molecules. Due to the generality of approach, MCC is prone to lend itself as a potent tool also for the analysis of other kinds of big data.

PD-1 and PD-L1 in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma.

PubMed

Mitteldorf, Christina; Berisha, Arbeneshe; Tronnier, Michael; Pfaltz, Monique C; Kempf, Werner

2017-09-01

Merkel cell carcinoma (MCC) is an aggressive neoplasm, which is often associated with Merkel cell polyomavirus (MCPyV). Programmed death-1 (PD-1) and its ligand PD-L1 are key players of the tumor microenvironment (TME). Fourteen paraffin-embedded tissue samples of MCC were stratified by their MCPyV detection. Apart from PD-L1 and PD-1, the TME was further characterized for the expression of CD33, FOXP3 and MxA. We observed PD-1 in 2 of 12 tumors. PD-L1 expression by tumor cells was found in 7 of 8 MCPyV(+) samples and was detected particularly in the periphery. The tumor cells were surrounded by a shield of PD-L1/CD33 immune cells. Expression of PD-L1 by the tumor cells was higher in areas with a denser immune infiltrate. CD33(+) cells without direct tumor contact were PD-L1 negative. Only a low number of FOXP3(+) regulatory T-cells was admixed. Tumor cells of MCPyV(-) samples were mostly PD-L1 negative. Our data demonstrate that PD-L1 expression occurs in tumor and immune cells, in areas in which they are close in contact. Interferon seems to play a role in this interaction. We postulate that PD-L1(+)/CD33(+) cells shield the tumor against attacking PD-1(+) immune cells. Therefore, next to anti-PD-1/PD-L1 antibodies, blockade of CD33 seems to be a promising therapeutic approach. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multiscale simulation of DC corona discharge and ozone generation from nanostructures

NASA Astrophysics Data System (ADS)

Wang, Pengxiang

Atmospheric direct current (dc) corona discharge from micro-sized objects has been widely used as an ion source in many devices, such as photocopiers, laser printers, and electronic air cleaners. Shrinking the size of the discharge electrode to the nanometer range (e.g., through the use of carbon nanotubes or CNTs) is expected to lead to a significant reduction in power consumption and detrimental ozone production in these devices. The objectives of this study are to unveil the fundamental physics of the nanoscale corona discharge and to evaluate its performance and ozone production through numerical models. The extremely small size of CNTs presents considerable complexity and challenges in modeling CNT corona discharges. A hybrid multiscale model, which combines a kinetic particle-in-cell plus Monte Carlo collision (PIC-MCC) model and a continuum model, is developed to simulate the corona discharge from nanostructures. The multiscale model is developed in several steps. First, a pure PIC-MCC model is developed and PIC-MCC simulations of corona plasma from micro-sized electrode with same boundary conditions as prior model are performed to validate the PIC-MCC scheme. The agreement between the PIC-MCC model and the prior continuum model indicates the validity of the PIC-MCC scheme. The validated PIC-MCC scheme is then coupled with a continuum model to simulate the corona discharge from a micro-sized electrode. Unlike the prior continuum model which only predicts the corona plasma region, the hybrid model successfully predicts the self-consistent discharge process in the entire corona discharge gap that includes both corona plasma region and unipolar ion region. The voltage-current density curves obtained by the hybrid model agree well with analytical prediction and experimental results. The hybrid modeling approach, which combines the accuracy of a kinetic model and the efficiency of a continuum model, is thus validated for modeling dc corona discharges. For simulation of corona discharges from nanostructures, a one-dimensional (1-D) multiscale model is used due to the prohibitive computational expense associated with two-dimensional (2-D) modeling. Near the nanoscale discharge electrode surface, a kinetic model based on PIC-MCC is used due to a relatively large Knudsen number in this region. Far away from the nanoscale discharge electrode, a continuum model is used since the Knudsen number is very small there. The multiscale modeling results are compared with experimental data. The quantitative agreement in positive discharges and qualitative agreement in negative discharges validate the modeling approach. The mechanism of sustaining the discharge process from nanostructures is revealed and is found to be different from that of discharge from micro- or macro-sized electrodes. Finally, the corona plasma model is combined with a plasma chemistry model and a transport model to predict the ozone production from the nanoscale corona. The dependence of ozone production on the applied potential and air velocity is studied. The electric field distribution in a 2-D multiscale domain (from nanoscale to microscale) is predicted by solving the Poisson's equation using a finite difference scheme. The discretized linear equations are solved using a multigrid method under the framework of PETSc on a paralleled supercomputer. Although the Poisson solver is able to resolve the multiscale field, the prohibitively long computation time limits the use of a 2-D solver in the current PIC-MCC scheme.

STS-26 long duration simulation in JSC Mission Control Center (MCC) Bldg 30

NASA Technical Reports Server (NTRS)

1988-01-01

STS-26 long duration simulation is conducted in JSC Mission Control Center (MCC) Bldg 30 Flight Control Room (FCR). CBS television camera personnel record MCC activities at Spacecraft Communicator (CAPCOM) and Flight Activities Officer (FAO) (foreground) consoles for '48 Hours' program to be broadcast at a later date. The integrated simulation involved communicating with crewmembers stationed in the fixed based (FB) shuttle mission simulator (SMS) located in JSC Mission Simulation and Training Facility Bldg 5. MCC FCR visual displays are seen in front of the rows of consoles.

Efficacy of mineral cationic carrier against sulphur mustard in skin decontamination.

PubMed

Vucemilović, Ante; Hadzija, Mirko; Jukić, Ivan

2008-12-01

The aim of this study was to evaluate decontamination (absorption) efficacy of a preparation called Mineral Cationic Carrier (MCC) against skin contamination with sulphur mustard in vivo. MCC is a synthetic preparation with known ion exchange, absorption efficiency, and bioactive potential. CBA mice were applied increasing doses of sulphur mustard on their skin and MCC was administered immediately after skin contamination. The results have confirmed the decontamination efficacy of MCC preparation, corresponding to 8.4 times the LD50 of percutaneous sulphur mustard, and call for further investigation.

Shuttle program. MCC Level C formulation requirements: Entry guidance and entry autopilot

NASA Technical Reports Server (NTRS)

Harpold, J. C.; Hill, O.

1980-01-01

A set of preliminary entry guidance and autopilot software formulations is presented for use in the Mission Control Center (MCC) entry processor. These software formulations meet all level B requirements. Revision 2 incorporates the modifications required to functionally simulate optimal TAEM targeting capability (OTT). Implementation of this logic in the MCC must be coordinated with flight software OTT implementation and MCC TAEM guidance OTT. The entry guidance logic is based on the Orbiter avionics entry guidance software. This MCC requirements document contains a definition of coordinate systems, a list of parameter definitions for the software formulations, a description of the entry guidance detailed formulation requirements, a description of the detailed autopilot formulation requirements, a description of the targeting routine, and a set of formulation flow charts.

Accelerating Multiple Compound Comparison Using LINGO-Based Load-Balancing Strategies on Multi-GPUs

PubMed Central

Lin, Chun-Yuan; Wang, Chung-Hung; Hung, Che-Lun; Lin, Yu-Shiang

2015-01-01

Compound comparison is an important task for the computational chemistry. By the comparison results, potential inhibitors can be found and then used for the pharmacy experiments. The time complexity of a pairwise compound comparison is O(n 2), where n is the maximal length of compounds. In general, the length of compounds is tens to hundreds, and the computation time is small. However, more and more compounds have been synthesized and extracted now, even more than tens of millions. Therefore, it still will be time-consuming when comparing with a large amount of compounds (seen as a multiple compound comparison problem, abbreviated to MCC). The intrinsic time complexity of MCC problem is O(k 2 n 2) with k compounds of maximal length n. In this paper, we propose a GPU-based algorithm for MCC problem, called CUDA-MCC, on single- and multi-GPUs. Four LINGO-based load-balancing strategies are considered in CUDA-MCC in order to accelerate the computation speed among thread blocks on GPUs. CUDA-MCC was implemented by C+OpenMP+CUDA. CUDA-MCC achieved 45 times and 391 times faster than its CPU version on a single NVIDIA Tesla K20m GPU card and a dual-NVIDIA Tesla K20m GPU card, respectively, under the experimental results. PMID:26491652

Accelerating Multiple Compound Comparison Using LINGO-Based Load-Balancing Strategies on Multi-GPUs.

PubMed

Lin, Chun-Yuan; Wang, Chung-Hung; Hung, Che-Lun; Lin, Yu-Shiang

2015-01-01

Compound comparison is an important task for the computational chemistry. By the comparison results, potential inhibitors can be found and then used for the pharmacy experiments. The time complexity of a pairwise compound comparison is O(n (2)), where n is the maximal length of compounds. In general, the length of compounds is tens to hundreds, and the computation time is small. However, more and more compounds have been synthesized and extracted now, even more than tens of millions. Therefore, it still will be time-consuming when comparing with a large amount of compounds (seen as a multiple compound comparison problem, abbreviated to MCC). The intrinsic time complexity of MCC problem is O(k (2) n (2)) with k compounds of maximal length n. In this paper, we propose a GPU-based algorithm for MCC problem, called CUDA-MCC, on single- and multi-GPUs. Four LINGO-based load-balancing strategies are considered in CUDA-MCC in order to accelerate the computation speed among thread blocks on GPUs. CUDA-MCC was implemented by C+OpenMP+CUDA. CUDA-MCC achieved 45 times and 391 times faster than its CPU version on a single NVIDIA Tesla K20m GPU card and a dual-NVIDIA Tesla K20m GPU card, respectively, under the experimental results.

Fragments of the Bacterial Toxin Microcin B17 as Gyrase Poisons

PubMed Central

Collin, Frédéric; Thompson, Robert E.; Jolliffe, Katrina A.; Payne, Richard J.; Maxwell, Anthony

2013-01-01

Fluoroquinolones are very important drugs in the clinical antibacterial arsenal; their success is principally due to their mode of action: the stabilisation of a gyrase-DNA intermediate (the cleavage complex), which triggers a chain of events leading to cell death. Microcin B17 (MccB17) is a modified peptide bacterial toxin that acts by a similar mode of action, but is unfortunately unsuitable as a therapeutic drug. However, its structure and mechanism could inspire the design of new antibacterial compounds that are needed to circumvent the rise in bacterial resistance to current antibiotics. Here we describe the investigation of the structural features responsible for MccB17 activity and the identification of fragments of the toxin that retain the ability to stabilise the cleavage complex. PMID:23593482

Fragments of the bacterial toxin microcin B17 as gyrase poisons.

PubMed

Collin, Frédéric; Thompson, Robert E; Jolliffe, Katrina A; Payne, Richard J; Maxwell, Anthony

2013-01-01

Fluoroquinolones are very important drugs in the clinical antibacterial arsenal; their success is principally due to their mode of action: the stabilisation of a gyrase-DNA intermediate (the cleavage complex), which triggers a chain of events leading to cell death. Microcin B17 (MccB17) is a modified peptide bacterial toxin that acts by a similar mode of action, but is unfortunately unsuitable as a therapeutic drug. However, its structure and mechanism could inspire the design of new antibacterial compounds that are needed to circumvent the rise in bacterial resistance to current antibiotics. Here we describe the investigation of the structural features responsible for MccB17 activity and the identification of fragments of the toxin that retain the ability to stabilise the cleavage complex.

Numerical validation of axial plasma momentum lost to a lateral wall induced by neutral depletion

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

Takao, Yoshinori, E-mail: takao@ynu.ac.jp; Takahashi, Kazunori

2015-11-15

Momentum imparted to a lateral wall of a compact inductively coupled plasma thruster is numerically investigated for argon and xenon gases by a particle-in-cell simulation with Monte Carlo collisions (PIC-MCC). Axial plasma momentum lost to a lateral wall is clearly shown when axial depletion of the neutrals is enhanced, which is in qualitative agreement with the result in a recent experiment using a helicon plasma source [Takahashi et al., Phys. Rev. Lett. 114, 195001 (2015)]. The PIC-MCC calculations demonstrate that the neutral depletion causes an axially asymmetric profile of the plasma density and potential, leading to axial ion acceleration andmore » the non-negligible net axial force exerted to the lateral wall in the opposite direction of the thrust.« less

The octahaem MccA is a haem c-copper sulfite reductase.

PubMed

Hermann, Bianca; Kern, Melanie; La Pietra, Luigi; Simon, Jörg; Einsle, Oliver

2015-04-30

The six-electron reduction of sulfite to sulfide is the pivot point of the biogeochemical cycle of the element sulfur. The octahaem cytochrome c MccA (also known as SirA) catalyses this reaction for dissimilatory sulfite utilization by various bacteria. It is distinct from known sulfite reductases because it has a substantially higher catalytic activity and a relatively low reactivity towards nitrite. The mechanistic reasons for the increased efficiency of MccA remain to be elucidated. Here we show that anoxically purified MccA exhibited a 2- to 5.5-fold higher specific sulfite reductase activity than the enzyme isolated under oxic conditions. We determined the three-dimensional structure of MccA to 2.2 Å resolution by single-wavelength anomalous dispersion. We find a homotrimer with an unprecedented fold and haem arrangement, as well as a haem bound to a CX15CH motif. The heterobimetallic active-site haem 2 has a Cu(I) ion juxtaposed to a haem c at a Fe-Cu distance of 4.4 Å. While the combination of metals is reminiscent of respiratory haem-copper oxidases, the oxidation-labile Cu(I) centre of MccA did not seem to undergo a redox transition during catalysis. Intact MccA tightly bound SO2 at haem 2, a dehydration product of the substrate sulfite that was partially turned over due to photoreduction by X-ray irradiation, yielding the reaction intermediate SO. Our data show the biometal copper in a new context and function and provide a chemical rationale for the comparatively high catalytic activity of MccA.

Solubilization of rehydrated frozen highly concentrated micellar casein for use in liquid food applications.

PubMed

Lu, Y; McMahon, D J; Metzger, L E; Kommineni, A; Vollmer, A H

2015-09-01

Highly concentrated micellar casein concentrate (HC-MCC), a potential ingredient of protein-fortified food, is a gel at cold temperature. It contains ~17 to 21% casein, with most serum proteins and lactose removed by microfiltration and diafiltration, and it is then further concentrated using vacuum evaporation. The HC-MCC can be stored frozen, and our objective was to determine the conditions needed to obtain complete solubility of thawed HC-MCC in water and to understand its gelation upon cooling. Dispersibility (ability to pass through a 250-µm mesh sieve), suspendability (percentage of protein not sedimented at 80 × g within 5min), and solubility (percentage of protein not sedimented at 20,000 × g within 5min) were measured at 4, 12, or 20°C after various mixing conditions. Gelation upon cooling from 50 to 5°C was monitored based on storage (G') and loss (G'') moduli. The gelled HC-MCC was also examined by transmission electron microscopy. Thawed HC-MCC was added to water to reach a protein concentration of 3% and mixed using high shear (7,500rpm) for 1min or low shear (800rpm) for 30min at 4, 12, 20, or 50°C and at pH 6.4 to 7.2. The HC-MCC completely dispersed at 50°C, or at ≤20°C followed by overnight storage at 4°C. Suspendability at 50°C was ~90% whereas mixing at ≤20°C followed by overnight storage resulted in only ~57% suspendability. Solubility followed a similar trend with ~83% at 50°C and only ~29% at ≤20°C. Mixing HC-MCC with 60mM trisodium citrate increased dispersibility to 99% and suspendability and solubility to 81% at 20°C. Cold-gelling temperature, defined as the temperature at which G'=G'' when cooling from 50 to 5°C, was positively correlated with protein level in HC-MCC. Gelation occurred at 38, 28, and 7°C with 23, 20, and 17% of protein, respectively. Gelation was reversible upon heating, although after a second cooling cycle the HC-MCC gel had lower G'. In micrographs of gelled HC-MCC, the casein micelles were observed to be within the normal size range but packed very closely together, with only ~20 to 50 nm of space between them. We proposed that cold-gelation of HC-MCC occurs when the kinetic energy of the casein micelles is sufficiently reduced to inhibit their mobility in relation to adjacent casein micelles. Understanding solubilization of rehydrated frozen HC-MCC and its rheological properties can help in designing process systems for using HC-MCC as a potential ingredient in liquid food. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

78 FR 65728 - Medley Capital Corporation, et al.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... privately-held middle market companies. MCC's board of directors (the ``MCC Board'') currently consists of... Act (the ``Independent Directors''). Each of Andrew Fentress, Brooke Taube, and Seth Taube (the ``Principals'') serves as a director on the MCC Board. \\1\\ Section 2(a)(48) defines a BDC to be any closed-end...

Racial/Ethnic Identity, Gender-Role Attitudes, and Multicultural Counseling Competence: The Role of Multicultural Counseling Training

ERIC Educational Resources Information Center

Chao, Ruth Chu-Lien

2012-01-01

Researchers and practitioners have been pursuing how to enhance counselors' multicultural counseling competencies (MCC). With a sample of 460 counselors, the author examined whether multicultural training changed the relationship between (a) racial/ethnic identity and MCC and (b) gender-role attitudes and MCC. The author found significant…

Finding a Good Fit: Using MCC in a "Third Space"

ERIC Educational Resources Information Center

Webster, Joan Parker; Wiles, Peter; Civil, Marta; Clark, Stacy

2005-01-01

Math in a Cultural Context (MCC) is based in traditional Yup'ik cultural values and ways of knowing and representing the world, which provide access to math concepts through hands-on exploration and active problem solving. This case illustrates how a novice and outsider teacher successfully implemented MCC in a classroom with predominantly…

A small molecule inhibitior of the NLRP3 inflammasome is a potential therapeutic for inflammatory diseases

PubMed Central

Coll, Rebecca C.; Robertson, Avril A. B.; Chae, Jae Jin; Higgins, Sarah C.; Muñoz-Planillo, Raúl; Inserra, Marco C.; Vetter, Irina; Dungan, Lara S.; Monks, Brian G.; Stutz, Andrea; Croker, Daniel E.; Butler, Mark S.; Haneklaus, Moritz; Sutton, Caroline E.; Núñez, Gabriel; Latz, Eicke; Kastner, Daniel L.; Mills, Kingston H. G.; Masters, Seth L.; Schroder, Kate; Cooper, Matthew A.; O’Neill, Luke A. J.

2015-01-01

The NLRP3 inflammasome is a component of the inflammatory process and its aberrant activation is pathogenic in inherited disorders such as the cryopyrin associated periodic syndromes (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes and atherosclerosis. We describe the development of MCC950, a potent, selective, small molecule inhibitor of NLRP3. MCC950 blocks canonical and non-canonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibits NLRP3 but not AIM2, NLRC4 or NLRP1 activation. MCC950 reduces Interleukin-1p (IL-1β) production in vivo and attenuates the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescues neonatal lethality in a mouse model of CAPS and is active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for the further study of the NLRP3 inflammasome in human health and disease. PMID:25686105

A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases.

PubMed

Coll, Rebecca C; Robertson, Avril A B; Chae, Jae Jin; Higgins, Sarah C; Muñoz-Planillo, Raúl; Inserra, Marco C; Vetter, Irina; Dungan, Lara S; Monks, Brian G; Stutz, Andrea; Croker, Daniel E; Butler, Mark S; Haneklaus, Moritz; Sutton, Caroline E; Núñez, Gabriel; Latz, Eicke; Kastner, Daniel L; Mills, Kingston H G; Masters, Seth L; Schroder, Kate; Cooper, Matthew A; O'Neill, Luke A J

2015-03-01

The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndrome (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and atherosclerosis. We describe the development of MCC950, a potent, selective, small-molecule inhibitor of NLRP3. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced interleukin-1β (IL-1β) production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for further study of the NLRP3 inflammasome in human health and disease.

Fabrication and characterization of regenerated cellulose films obtained from oil palm empty fruit bunch

NASA Astrophysics Data System (ADS)

Nor Amalini, A.; Melina Cheah, M. Y.; Wan Rosli, W. D.; Hayati, S.; Mohamad Haafiz, M. K.

2017-12-01

Development of regenerated cellulose (RC) derived from underutilized cellulosic biomass has recently gained attention as potential petroleum-based polymer replacers. The objective of this current work is to evaluate the properties of RC films obtained from oil palm empty fruit bunch microcrystalline cellulose (OPEFB-MCC) through environmental process. The RC films were fabricated by using different amounts of OPEFB-MCC (4, 6 and 8 %) and 1-butyl-3-methylimidazolium chloride (BMIMCl) was used as green OPEFB-MCC dissolving medium. The resultant RC films were then characterized by means of Fourier transform infrared (FTIR) spectroscopy, mechanical, thermal and morphological properties by using tensile test, differential scanning colorimetry (DSC), and scanning electron microscopy (SEM) respectively. Increase in OPEFB-MCC amounts from 4 to 8 % enhanced the tensile strength and elongation at break of RC by 101 and 78 %, respectively, indicating stronger and more flexible films were formed. It is interesting to note that the Tg (101-154 °C) and Tm(130-187 °C) were found shifted to higher temperature with higher proportions of OPEFB-MCC in RC films. Meanwhile, FTIR analysis showed no new peak presented in RC films, suggesting that BMIMCl is a non-derivatizing solvent to OPEFB-MCC. Conspicuous changes in the spectra of RC films compared to OPEFB-MCC at 3200-3600 cm-1, 1430 cm-1, 1162 cm-1, 1111 cm-1, 1020-1040 cm-1 and 896 cm-1 were associated with transformation of cellulose I to cellulose II structure or/and decrease in crystallinity occurred after regeneration process. SEM micrographs of the RC films revealed that higher OPEFB-MCC contents exhibited smoother and more homogeneous surfaces morphology. Overall, OPEFB-MCC exhibited good film forming ability for RC production and may offer potential application in various industries including food packaging, medical goods and electronic devices.

Merkel Cell Carcinoma: A Population Analysis on Survival.

PubMed

Sridharan, Vishwajith; Muralidhar, Vinayak; Margalit, Danielle N; Tishler, Roy B; DeCaprio, James A; Thakuria, Manisha; Rabinowits, Guilherme; Schoenfeld, Jonathan D

2016-10-01

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy. However, factors associated with disease presentation and outcomes remain uncertain, especially in light of recent changes in workup, such as sentinel lymph node biopsy. Therefore, this study used the SEER database to examine factors that could affect stage at presentation and treatment. We identified 4,543 patients and evaluated associations between sex, race, age, primary disease site, disease presentation, and treatment. We also used univariate and multivariate analyses to examine the effect of these factors on disease-specific survival (DSS) and overall survival (OS). We specifically conducted subgroup analyses on a more modern cohort of patients with MCC treated between 2006 and 2012. Male sex, older age, larger tumor size, and primary tumors of the scalp, neck, or trunk were associated with a higher burden of nodal disease. Multivariate predictors of worse DSS/OS in both the recent and overall cohort included age older than 75 years, number of lymph nodes involved, tumors greater than 5 cm, metastatic disease, or lack of radiation therapy. The number of involved nodes was the best predictor of DSS/OS. Associations with radiation therapy were most pronounced in patients with nodal disease and those not undergoing surgery. Sex, age, tumor size, and primary site of disease correlated with burden of nodal disease in MCC. Associations between disease presentation and treatment strategies such as radiation and DSS and OS have remained relatively constant in the modern era from 2006 to 2012 compared with findings from prior studies. Copyright © 2016 by the National Comprehensive Cancer Network.

Merkel Cell Carcinoma of Unknown Primary Origin

PubMed Central

Deneve, Jeremiah L.; Messina, Jane L.; Marzban, Suroosh S.; Gonzalez, Ricardo J.; Walls, Brooke M.; Fisher, Kate J.; Ann Chen, Y.; Wayne Cruse, C.; Sondak, Vernon K.; Zager, Jonathan S.

2015-01-01

Background Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. MCC from an unknown primary origin (MCCUP) can present a diagnostic and therapeutic challenge. We describe our single-institution experience with the diagnosis and management of MCCUP presenting as metastases to lymph nodes. Methods After institutional review board approval, our institutional database spanning the years 1998–2010 was queried for patients with MCCUP. Clinicopathologic variables and outcomes were assessed. Results From a database of 321 patients with MCC, 38 (12%) were identified as having nodal MCCUP. Median age was 67 years, and 79% were men. Nodal basins involved at presentation were cervical (58%), axillary/epitrochlear (21%), or inguinal/iliac (21%). CK20 staining was positive in 93% of tumors tested, and all were negative for thyroid transcription factor-1. Twenty-nine patients (76%) underwent complete regional lymph node dissection (LND): 3 had LND alone, ten had LND and adjuvant radiotherapy, and 16 underwent LND followed by chemoradiotherapy. Definitive chemoradiotherapy without surgery was provided to six patients (16%), while radiotherapy alone was provided to three (8%). Recurrence was observed in 34% of patients. Median recurrence-free survival was 35 months. Ten patients (26%) died, five of disease and five of other causes. The median overall survival was 104 months. Conclusions Nodal MCCUP is a rare disease affecting primarily elderly white men. Recurrence is observed in approximately one-third of patients, with a 104 month median overall survival after a multimodal treatment approach consisting of surgery along with adjuvant chemotherapy and radiotherapy in the majority of patients. PMID:22271206

STS-26 simulation activities in JSC Mission Control Center (MCC)

NASA Technical Reports Server (NTRS)

1987-01-01

In JSC Mission Control Center (MCC) Bldg 30 Flight Control Room (FCR), astronauts John O. Creighton (right) and L. Blaine Hammond review their notes while serving as spacecraft communicators (CAPCOMs) for STS-26 simulations in progress between MCC and JSC Mission Simulation and Training Facility Bldg 5 fixed-base (FB) shuttle mission simulator (SMS).

STS-26 simulation activities in JSC Mission Control Center (MCC)

NASA Technical Reports Server (NTRS)

1987-01-01

In JSC Mission Control Center (MCC) Bldg 30 Flight Control Room (FCR), flight directors (FDs) Lee Briscoe (left) and Charles W. Shaw, seated at FD console, view front visual display monitors during STS-26 simulations in progress between MCC and JSC Mission Simulation and Training Facility Bldg 5 fixed-base (FB) shuttle mission simulator (SMS).

135. VIEW OF MOTOR CONTROL CENTER 1 (MCC1) IN TRANSFORMER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

135. VIEW OF MOTOR CONTROL CENTER 1 (MCC1) IN TRANSFORMER ROOM (212), LSB (BLDG. 751), FACING NORTH. MCC1 MAKES UP A ROW OF CABINETS EAST OF AND PARALLEL TO THE TRANSFORMER CABINETS. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Evidence for the role of DNA strand passage in the mechanism of action of microcin B17 on DNA gyrase.

PubMed

Pierrat, Olivier A; Maxwell, Anthony

2005-03-22

Microcin B17 (MccB17) is a DNA gyrase poison; in previous work, this bacterial toxin was found to slowly and incompletely inhibit the reactions of supercoiling and relaxation of DNA by gyrase and to stabilize the cleavage complex, depending on the presence of ATP and the DNA topology. We now show that the action of MccB17 on the gyrase ATPase reaction and cleavage complex formation requires a linear DNA fragment of more than 150 base pairs. MccB17 is unable to stimulate the ATPase reaction by stabilizing the weak interactions between short linear DNA fragments (70 base pairs or less) and gyrase, in contrast with the quinolone ciprofloxacin. However, MccB17 can affect the ATP-dependent relaxation of DNA by gyrase lacking its DNA-wrapping or ATPase domains. From these findings, we propose a mode of action of MccB17 requiring a DNA molecule long enough to allow the transport of a segment through the DNA gate of the enzyme. Furthermore, we suggest that MccB17 may trap a transient intermediate state of the gyrase reaction present only during DNA strand passage and enzyme turnover. The proteolytic signature of MccB17 from trypsin treatment of the full enzyme requires DNA and ATP and shows a protection of the C-terminal 47-kDa domain of gyrase, indicating the involvement of this domain in the toxin mode of action and consistent with its proposed role in the mechanism of DNA strand passage. We suggest that the binding site of MccB17 is in the C-terminal domain of GyrB.

Effect of moderate electric fields in the properties of starch and chitosan films reinforced with microcrystalline cellulose.

PubMed

Coelho, Caroline C S; Cerqueira, Miguel A; Pereira, Ricardo N; Pastrana, Lorenzo M; Freitas-Silva, Otniel; Vicente, António A; Cabral, Lourdes M C; Teixeira, José A

2017-10-15

Microcrystalline cellulose (MCC) can provide improved properties when the aim is the development of biodegradable packaging materials. In this work the physicochemical properties of polysaccharide-based films (chitosan and starch) with the incorporation of MCC and the application of moderate electric field (MEF) and ultrasonic bath (UB) as treatments, were evaluated. For each treatment, the thickness, moisture content, solubility, water vapor permeability, contact angle, mechanical properties, along with its color and opacity were determined. The surface morphologies of the films were assessed by scanning electron microscopy (SEM). X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA) were also performed. It was observed that the addition of different concentrations of MCC as well as the application of MEF are responsible for changes in the properties of the films, being this effect dependent on the polysaccharide used. Chitosan-based films were slightly yellow, transparent and presented a more homogeneous structure. The use of MEF was efficient in decreasing the permeability to water vapor in chitosan based films without MCC, as well as in production of films with a more hydrophobic surface. The addition of MCC promoted more opaque, rigid, less flexible and less hydrophobic films. Starch-based films were whitish, with a more heterogeneous structure and the application of MEF generated more hydrophilic films with lower tensile strength and Young's modulus. The films with MCC were more opaque, less flexible and less hydrophilic than the films without MCC. The composites presented good thermal properties, which increases their applicability as packaging materials. Therefore, the incorporation of MCC into polysaccharide-based films as well as the application of MEF can be an approach to change the properties of films. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of diabatic heating on the ageostrophic circulation of an upper tropospheric jet streak

NASA Technical Reports Server (NTRS)

Keyser, D. A.; Johnson, D. R.

1982-01-01

Interaction between the mass circulation within a mesoscale convective complex (MCC) and a direct mass circulation in the entrance region of an upper tropospheric polar jet streak was examined within the isentropic structure to investigate mechanisms responsible for linking these two scales of motion. The results establish that latent heating in the MCC modifies the direct mass circulation in the jet streak entrance region through the diabatically induced components of ageostrophic motion analyzed within isentropic coordinates. Within the strong mesoscale mass circulation of each MCC, strong horizontal mass flux convergence into the MCC at low levels is balanced by strong horizontal mass flux divergence away from the convergence at upper levels. Locations of large diabatic heating rates correspond well to the MCC position for each case; diabatic heating forces the upward vertical branch for the mesoscale mass circulation.

Mate-choice copying: A fitness-enhancing behavior that evolves by indirect selection.

PubMed

Santos, Mauro; Sapage, Manuel; Matos, Margarida; Varela, Susana A M

2017-06-01

A spatially explicit, individual-based simulation model is used to study the spread of an allele for mate-choice copying (MCC) through horizontal cultural transmission when female innate preferences do or do not coevolve with a male viability-increasing trait. Evolution of MCC is unlikely when innate female preferences coevolve with the trait, as copier females cannot express a higher preference than noncopier females for high-fitness males. However, if a genetic polymorphism for innate preference persists in the population, MCC can evolve by indirect selection through hitchhiking: the copying allele hitchhikes on the male trait. MCC can be an adaptive behavior-that is, a behavior that increases a population's average fitness relative to populations without MCC-even though the copying allele itself may be neutral or mildly deleterious. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia

PubMed Central

Coote, K J; Paisley, D; Czarnecki, S; Tweed, M; Watson, H; Young, A; Sugar, R; Vyas, M; Smith, N J; Baettig, U; Groot-Kormelink, P J; Gosling, M; Lock, R; Ethell, B; Williams, G; Schumacher, A; Harris, J; Abraham, W M; Sabater, J; Poll, C T; Faller, T; Collingwood, S P; Danahay, H

2015-01-01

Background and Purpose Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia. Experimental Approach The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in primary human bronchial epithelial cells (HBECs) by short-circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC). Key Results In vitro, NVP-QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP-QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP-QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action. Conclusions and Implications NVP-QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds. PMID:25573195

NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia.

PubMed

Coote, K J; Paisley, D; Czarnecki, S; Tweed, M; Watson, H; Young, A; Sugar, R; Vyas, M; Smith, N J; Baettig, U; Groot-Kormelink, P J; Gosling, M; Lock, R; Ethell, B; Williams, G; Schumacher, A; Harris, J; Abraham, W M; Sabater, J; Poll, C T; Faller, T; Collingwood, S P; Danahay, H

2015-06-01

Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia. The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in primary human bronchial epithelial cells (HBECs) by short-circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC). In vitro, NVP-QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP-QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP-QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action. NVP-QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds. © 2015 The British Pharmacological Society.

Agile Development of Various Computational Power Adaptive Web-Based Mobile-Learning Software Using Mobile Cloud Computing

ERIC Educational Resources Information Center

Zadahmad, Manouchehr; Yousefzadehfard, Parisa

2016-01-01

Mobile Cloud Computing (MCC) aims to improve all mobile applications such as m-learning systems. This study presents an innovative method to use web technology and software engineering's best practices to provide m-learning functionalities hosted in a MCC-learning system as service. Components hosted by MCC are used to empower developers to create…

An Academic Development Plan for Post-Secondary Education on the Multi-Ethnic Island of Lana'i.

ERIC Educational Resources Information Center

Pezzoli, J. A.; McOmber, Phyllis

In 1980, Maui Community College (MCC) established the Lana'i Education Center (LEC) on the island of Lana'i to provide courses and services to island residents. Related to MCC's college-wide planning document, this Academic Development Plan outlines the planning strategies, long-range goals, and priorities specific to MCC's Lana'i efforts for…

An Academic Development Plan for the Island of Molokai in Hawaii, 1990-1996.

ERIC Educational Resources Information Center

Pezzoli, J. A.

Since 1970, Maui Community College (MCC) has offered credit courses on the island of Molokai, with the program expanding considerably in 1986 with the inception of the MCC-Molokai Center. Developed to project a more stable and comprehensive program for the residents of Molokai, this academic development plan outlines the priorities of MCC on the…

29 CFR 782.3 - Drivers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CFR parts 390-395; Ex parte No. MC-2, 3 M.C.C. 665; Ex parte No. MC-3, 23 M.C.C.1; Ex parte No. MC-4, 1 M.C.C. 1), is an individual who drives a motor vehicle in transporation which is, within the meaning of the Motor Carrier Act, in interstate or foreign commerce. (As to what is considered...

Influence of alkaline hydrogen peroxide pre-hydrolysis on the isolation of microcrystalline cellulose from oil palm fronds.

PubMed

Owolabi, Abdulwahab F; Haafiz, M K Mohamad; Hossain, Md Sohrab; Hussin, M Hazwan; Fazita, M R Nurul

2017-02-01

In the present study, microcrystalline cellulose (MCC) was isolated from oil palm fronds (OPF) using chemo-mechanical process. Wherein, alkaline hydrogen peroxide (AHP) was utilized to extract OPF fibre at different AHP concentrations. The OPF pulp fibre was then bleached with acidified sodium chlorite solution followed by the acid hydrolysis using hydrochloric acid. Several analytical methods were conducted to determine the influence of AHP concentration on thermal properties, morphological properties, microscopic and crystalline behaviour of isolated MCC. Results showed that the MCC extracted from OPF fibres had fibre diameters of 7.55-9.11nm. X-ray diffraction (XRD) analyses revealed that the obtained microcrystalline fibre had both celluloses I and cellulose II polymorphs structure, depending on the AHP concentrations. The Fourier transmission infrared (FTIR) analyses showed that the AHP pre-hydrolysis was successfully removed hemicelluloses and lignin from the OPF fibre. The crystallinity of the MCC was increased with the AHP concentrations. The degradation temperature of MCC was about 300°C. The finding of the present study showed that pre-treatment process potentially influenced the quality of the isolation of MCC from oil palm fronds. Copyright © 2016 Elsevier B.V. All rights reserved.

Consequences of broad auditory filters for identification of multichannel-compressed vowels

PubMed Central

Souza, Pamela; Wright, Richard; Bor, Stephanie

2012-01-01

Purpose In view of previous findings (Bor, Souza & Wright, 2008) that some listeners are more susceptible to spectral changes from multichannel compression (MCC) than others, this study addressed the extent to which differences in effects of MCC were related to differences in auditory filter width. Method Listeners were recruited in three groups: listeners with flat sensorineural loss, listeners with sloping sensorineural loss, and a control group of listeners with normal hearing. Individual auditory filter measurements were obtained at 500 and 2000 Hz. The filter widths were related to identification of vowels processed with 16-channel MCC and with a control (linear) condition. Results Listeners with flat loss had broader filters at 500 Hz but not at 2000 Hz, compared to listeners with sloping loss. Vowel identification was poorer for MCC compared to linear amplification. Listeners with flat loss made more errors than listeners with sloping loss, and there was a significant relationship between filter width and the effects of MCC. Conclusions Broadened auditory filters can reduce the ability to process amplitude-compressed vowel spectra. This suggests that individual frequency selectivity is one factor which influences benefit of MCC, when a high number of compression channels are used. PMID:22207696

Impact of carboxymethyl cellulose (CMC) and microcrystalline cellulose (MCC) on functional characteristics of emulsified sausages.

PubMed

Schuh, Valerie; Allard, Karin; Herrmann, Kurt; Gibis, Monika; Kohlus, Reinhard; Weiss, Jochen

2013-02-01

Inclusion of fibers, such as carboxymethyl cellulose (CMC) and microcrystalline cellulose (MCC), at the expense of fat or protein in meat batters could be used to produce healthier sausages while lowering production costs. To study the impact of CMC/MCC on structural/functional characteristics of emulsified sausages, standard-fat Lyoner-style sausages were formulated with CMC/MCC at concentrations of 0.3-2.0%. Methods of analysis included rheology, water binding capacity (WBC), texture measurements, and Confocal Laser Scanning Microscopy (CLSM). WBC, texture measurements, and rheology all indicated that addition of CMC (>0.7%) led to destabilization of the batter, which upon heating could no longer be converted into a coherent protein network, a fact that was also revealed in CLSM images. In contrast, MCC was highly compatible with the matrix and improved firmness (1405-1651N/100g) with increasing concentration compared to control (1381N/100g) while keeping WBC (4.6-5.9%) with <2% MCC at the level of the control (4.8%). Results were discussed in terms of molecular interactions of meat proteins with celluloses. Copyright © 2012 Elsevier Ltd. All rights reserved.

Particle model of a cylindrical inductively coupled ion source

NASA Astrophysics Data System (ADS)

Ippolito, N. D.; Taccogna, F.; Minelli, P.; Cavenago, M.; Veltri, P.

2017-08-01

In spite of the wide use of RF sources, a complete understanding of the mechanisms regulating the RF-coupling of the plasma is still lacking so self-consistent simulations of the involved physics are highly desirable. For this reason we are developing a 2.5D fully kinetic Particle-In-Cell Monte-Carlo-Collision (PIC-MCC) model of a cylindrical ICP-RF source, keeping the time step of the simulation small enough to resolve the plasma frequency scale. The grid cell dimension is now about seven times larger than the average Debye length, because of the large computational demand of the code. It will be scaled down in the next phase of the development of the code. The filling gas is Xenon, in order to minimize the time lost by the MCC collision module in the first stage of development of the code. The results presented here are preliminary, with the code already showing a good robustness. The final goal will be the modeling of the NIO1 (Negative Ion Optimization phase 1) source, operating in Padua at Consorzio RFX.

James Webb Space Telescope Orbit Determination Analysis

NASA Technical Reports Server (NTRS)

Yoon, Sungpil; Rosales, Jose; Richon, Karen

2014-01-01

The James Webb Space Telescope (JWST) is designed to study and answer fundamental astrophysical questions from an orbit about the Sun-Earth/Moon L2 libration point, 1.5 million km away from Earth. This paper describes the results of an orbit determination (OD) analysis of the JWST mission emphasizing the challenges specific to this mission in various mission phases. Three mid-course correction (MCC) maneuvers during launch and early orbit phase and transfer orbit phase are required for the spacecraft to reach L2. These three MCC maneuvers are MCC-1a at Launch+12 hours, MCC-1b at L+2.5 days and MCC-2 at L+30 days. Accurate OD solutions are needed to support MCC maneuver planning. A preliminary analysis shows that OD performance with the given assumptions is adequate to support MCC maneuver planning. During the nominal science operations phase, the mission requires better than 2 cm/sec velocity estimation performance to support stationkeeping maneuver planning. The major challenge to accurate JWST OD during the nominal science phase results from the unusually large solar radiation pressure force acting on the huge sunshield. Other challenges are stationkeeping maneuvers at 21-day intervals to keep JWST in orbit around L2, frequent attitude reorientations to align the JWST telescope with its targets and frequent maneuvers to unload momentum accumulated in the reaction wheels. Monte Carlo analysis shows that the proposed OD approach can produce solutions that meet the mission requirements.

Next-generation non-starch polysaccharide-degrading, multi-carbohydrase complex rich in xylanase and arabinofuranosidase to enhance broiler feed digestibility.

PubMed

Cozannet, Pierre; Kidd, Michael T; Montanhini Neto, Roberto; Geraert, Pierre-André

2017-08-01

This study was carried out to evaluate the effect of a multi-carbohydrase complex (MCC) rich in xylanase (Xyl) and arabinofuranosidase (Abf) on overall broiler feed digestibility in broilers. Energy utilization and digestibility of dry matter (DM), organic matter (OM), protein, starch, fat, and insoluble and soluble fibers were measured using the mass-balance method. The experiment was carried out on 120 broilers (3-week-old chickens). Broilers were distributed over 8 treatments to evaluate the effect of the dietary arabinoxylan content and nutrient density with and without MCC (Rovabio® Advance). The graded content of arabinoxylan (AX) was obtained using different raw materials (wheat, rye, barley, and dried distillers' wheat). Diet-energy density was modified with added fat. Measurements indicated that nutrient density and AX content had a significant effect on most digestibility parameters. Apparent metabolizable energy (AME) was significantly increased (265 kcal kg-1) by MCC. The addition of MCC also resulted in significant improvement in the digestibility of all evaluated nutrients, with average improvements of 3.0, 3.3, 3.2, 3.0, 6.2, 2.9, 5.8, and 3.8% units for DM, OM, protein, starch, fat, insoluble and soluble fibers, and energy utilization, respectively. The interaction between MCC and diet composition was significant for the digestibility of OM, fat, protein, and energy. Nutrient digestibility and diet AME were negatively correlated with AX content (P < 0.001). However, the addition of MCC resulted in a reduction of this negative effect (P < 0.001). The AME of diets with and without the addition of MCC were successfully predicted by the diet digestible nutrient (i.e., starch, protein, fat, insoluble and soluble fibers) content with and without MCC (R2 = 0.87; RSD = 78 kcal kg-1). This study confirms that the presence of AX in wheat-based diets and wheat-based diets with other cereals and cereal by-products reduces nutrient digestibility in broiler chickens. Furthermore, the dietary addition of MCC, which is rich in Xyn and Abf, reduced deleterious effect of fiber and improved overall nutrient digestibility in broiler diets. © 2017 Poultry Science Association Inc.

Mission Control Center (MCC) system specification for the shuttle Orbital Flight Test (OFT) timeframe

NASA Technical Reports Server (NTRS)

1978-01-01

The Mission Control Center Shuttle (MCC) Shuttle Orbital Flight Test (OFT) Data System (OFTDS) provides facilities for flight control and data systems personnel to monitor and control the Shuttle flights from launch (tower clear) to rollout (wheels stopped on runway). It also supports the preparation for flight (flight planning, flight controller and crew training, and integrated vehicle and network testing activities). The MCC Shuttle OFTDS is described in detail. Three major support systems of the OFTDS and the data types and sources of data entering or exiting the MCC were illustrated. These systems are the communication interface system, the data computation complex, and the display and control system.

A Comprehensive Review on Adaptability of Network Forensics Frameworks for Mobile Cloud Computing

PubMed Central

Abdul Wahab, Ainuddin Wahid; Han, Qi; Bin Abdul Rahman, Zulkanain

2014-01-01

Network forensics enables investigation and identification of network attacks through the retrieved digital content. The proliferation of smartphones and the cost-effective universal data access through cloud has made Mobile Cloud Computing (MCC) a congenital target for network attacks. However, confines in carrying out forensics in MCC is interrelated with the autonomous cloud hosting companies and their policies for restricted access to the digital content in the back-end cloud platforms. It implies that existing Network Forensic Frameworks (NFFs) have limited impact in the MCC paradigm. To this end, we qualitatively analyze the adaptability of existing NFFs when applied to the MCC. Explicitly, the fundamental mechanisms of NFFs are highlighted and then analyzed using the most relevant parameters. A classification is proposed to help understand the anatomy of existing NFFs. Subsequently, a comparison is given that explores the functional similarities and deviations among NFFs. The paper concludes by discussing research challenges for progressive network forensics in MCC. PMID:25097880

A comprehensive review on adaptability of network forensics frameworks for mobile cloud computing.

PubMed

Khan, Suleman; Shiraz, Muhammad; Wahab, Ainuddin Wahid Abdul; Gani, Abdullah; Han, Qi; Rahman, Zulkanain Bin Abdul

2014-01-01

Network forensics enables investigation and identification of network attacks through the retrieved digital content. The proliferation of smartphones and the cost-effective universal data access through cloud has made Mobile Cloud Computing (MCC) a congenital target for network attacks. However, confines in carrying out forensics in MCC is interrelated with the autonomous cloud hosting companies and their policies for restricted access to the digital content in the back-end cloud platforms. It implies that existing Network Forensic Frameworks (NFFs) have limited impact in the MCC paradigm. To this end, we qualitatively analyze the adaptability of existing NFFs when applied to the MCC. Explicitly, the fundamental mechanisms of NFFs are highlighted and then analyzed using the most relevant parameters. A classification is proposed to help understand the anatomy of existing NFFs. Subsequently, a comparison is given that explores the functional similarities and deviations among NFFs. The paper concludes by discussing research challenges for progressive network forensics in MCC.

Effect of Radiotherapy Dose and Volume on Relapse in Merkel Cell Cancer of the Skin

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

Foote, Matthew, E-mail: matthew_foote@health.qld.gov.a; Harvey, Jennifer; Porceddu, Sandro

Purpose: To assess the effect of radiotherapy (RT) dose and volume on relapse patterns in patients with Stage I-III Merkel cell carcinoma (MCC). Patients and Methods: This was a retrospective analysis of 112 patients diagnosed with MCC between January 2000 and December 2005 and treated with curative-intent RT. Results: Of the 112 evaluable patients, 88% had RT to the site of primary disease for gross (11%) or subclinical (78%) disease. Eighty-nine percent of patients had RT to the regional lymph nodes; in most cases (71%) this was for subclinical disease in the adjuvant or elective setting, whereas 21 patients (19%)more » were treated with RT to gross nodal disease. With a median follow-up of 3.7 years, the 2-year and 5-year overall survival rates were 72% and 53%, respectively, and the 2-year locoregional control rate was 75%. The in-field relapse rate was 3% for primary disease, and relapse was significantly lower for patients receiving {>=}50Gy (hazard ratio [HR] = 0.22; 95% confidence interval [CI], 0.06-0.86). Surgical margins did not affect the local relapse rate. The in-field relapse rate was 11% for RT to the nodes, with dose being significant for nodal gross disease (HR = 0.24; 95% CI, 0.07-0.87). Patients who did not receive elective nodal RT had a much higher rate of nodal relapse compared with those who did (HR = 6.03; 95% CI, 1.34-27.10). Conclusion: This study indicates a dose-response for subclinical and gross MCC. Doses of {>=}50Gy for subclinical disease and {>=}55Gy for gross disease should be considered. The draining nodal basin should be treated in all patients.« less

The Role of Radiotherapy Alone in Patients With Merkel Cell Carcinoma: Reporting the Australian Experience of 43 Patients

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

Veness, Michael, E-mail: michael.veness@swahs.health.nsw.gov.a; Foote, Matthew; Gebski, Val

2010-11-01

Purpose: To review the role of radiotherapy (RTx) alone in patients with Merkel cell carcinoma (MCC). Methods and Materials: The records of 43 patients with MCC treated with RTx alone between 1993 and 2007 at the Westmead and Royal Brisbane/Mater Hospitals, Australia, were reviewed. Multivariate analysis was performed by use of Cox regression analysis. Results: The median age was 79 years (range, 48-91 years) in 19 women (44%) and 24 men (56%). All patients were white, and 5 (12%) had immunosuppression. A majority (56%) underwent irradiation at initial diagnosis, with the remainder (44%) treated in the relapse setting. The medianmore » duration of follow-up was 39 months. The head and neck comprised the most frequently treated site (47%). The median maximum lesion size was 30 mm (range, 5-130 mm). Relapse developed in 60% of patients, with most being out-of-field relapses. The in-field control rate was 75%. Most out-of-field relapses were to visceral organs. Relapse developed outside the irradiated field in 53% of patients. On multivariate analysis, only nodal status (negative nodes vs. nodes present) was significantly associated with relapse-free survival, with p = 0.005 (hazard ratio, 0.25; 95% confidence interval, 0.96-0.663). Overall survival at 2 and 5 years was 58% and 37%, respectively. Conclusions: Patients with MCC treated with RTx have a high likelihood of obtaining in-field control. Doses of 50 to 55 Gy in 20 to 25 fractions are recommended. A minority of patients are cured, with many dying of systemic relapse. Lower dose fractionation schedules (e.g., 25 Gy in 5 fractions) may be considered in patients with a very poor performance status.« less

Millennium Challenge Account

DTIC Science & Technology

2008-10-08

resolution (H.R. 2638/P.L. 110-329), which provides foreign aid spending at the level in the FY2008 Consolidated Act ($1.54 billion). The resolution...raised by some Members of Congress concerns the level of funding to support MCC programs. Some fear that insufficient funds might force the MCC to...Members of Congress signed a letter addressed to House Appropriations Committee leadership supporting an FY2009 MCC funding level at least at the

Fisheye view from the back of the Flight control room of the MCC

NASA Image and Video Library

1984-10-06

Fisheye view from the back of the Flight Control Room (FCR) of the Mission Control Center (MCC). Visible are the Flight Directors console (left front), the CAPCOM console (right front) and the Payloads console. Some of the STS 41-G crew can be seen on a large screen at the front of the MCC along with a map tracking the progress of the orbiter.

29 CFR 782.2 - Requirements for exemption in general.

Code of Federal Regulations, 2014 CFR

2014-07-01

....C.A. 2); Hansen v. Salinas Valley Ice Co. (Cal. App.) 144 P. (2d) 896; Reynolds v. Rogers Cartage Co... Service of Motor Carrier Employees, 28 M.C.C. 125, 132), and (2) engage in activities of a character....S. 649; Ex parte No. MC-28, 13 M.C.C. 481; Ex parte Nos. MC-2 and MC-3, 28 M.C.C. 125; Walling v...

29 CFR 782.2 - Requirements for exemption in general.

Code of Federal Regulations, 2013 CFR

2013-07-01

....C.A. 2); Hansen v. Salinas Valley Ice Co. (Cal. App.) 144 P. (2d) 896; Reynolds v. Rogers Cartage Co... Service of Motor Carrier Employees, 28 M.C.C. 125, 132), and (2) engage in activities of a character....S. 649; Ex parte No. MC-28, 13 M.C.C. 481; Ex parte Nos. MC-2 and MC-3, 28 M.C.C. 125; Walling v...

29 CFR 782.2 - Requirements for exemption in general.

Code of Federal Regulations, 2012 CFR

2012-07-01

....C.A. 2); Hansen v. Salinas Valley Ice Co. (Cal. App.) 144 P. (2d) 896; Reynolds v. Rogers Cartage Co... Service of Motor Carrier Employees, 28 M.C.C. 125, 132), and (2) engage in activities of a character....S. 649; Ex parte No. MC-28, 13 M.C.C. 481; Ex parte Nos. MC-2 and MC-3, 28 M.C.C. 125; Walling v...

Functionality and nutritional aspects of microcrystalline cellulose in food.

PubMed

Nsor-Atindana, John; Chen, Maoshen; Goff, H Douglas; Zhong, Fang; Sharif, Hafiz Rizwan; Li, Yue

2017-09-15

Microcrystalline cellulose (MCC) is among the most commonly used cellulose derivatives in the food industry. In order assess the recent advances of MCC in food product development and its associated nutraceutical implications, google scholar and database of journals subscribed by Jiangnan university, China were used to source literature. Recently published research articles that reported physicochemical properties of MCC for food application or potential application in food and nutraceutical functions were reviewed and major findings outlined. The selected literature reviewed demonstrated that the material has been extensively explored as a functional ingredient in food including meat products, emulsions, beverages, dairy products, bakery, confectionary and filling. The carbohydrate polymer also has many promising applications in functional and nutraceutical food industries. Though widely used as control for many dietary fiber investigations, MCC has been shown to provide positive effects on gastrointestinal physiology, and hypolipidemic effects, influencing the expression of enzymes involved in lipid metabolism. These techno-functional and nutraceutical properties of MCC are influenced by the physicochemical of the material, which are defined by the raw material source and processing conditions. Apart from these functional properties, this review also highlighted limitations and gaps regarding the application of material in food and nutritional realms. Functional, Nutritional and health claims of MCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

The action of the bacterial toxin microcin B17. Insight into the cleavage-religation reaction of DNA gyrase.

PubMed

Pierrat, Olivier A; Maxwell, Anthony

2003-09-12

We have examined the effects of the bacterial toxin microcin B17 (MccB17) on the reactions of Escherichia coli DNA gyrase. MccB17 slows down but does not completely inhibit the DNA supercoiling and relaxation reactions of gyrase. A kinetic analysis of the cleavage-religation equilibrium of gyrase was performed to determine the effect of the toxin on the forward (cleavage) and reverse (religation) reactions. A simple mechanism of two consecutive reversible reactions with a nicked DNA intermediate was used to simulate the kinetics of cleavage and religation. The action of MccB17 on the kinetics of cleavage and religation was compared with that of the quinolones ciprofloxacin and oxolinic acid. With relaxed DNA as substrate, only a small amount of gyrase cleavage complex is observed with MccB17 in the absence of ATP, whereas the presence of the nucleotide significantly enhances the effect of the toxin on both the cleavage and religation reactions. In contrast, ciprofloxacin, oxolinic acid, and Ca2+ show lesser dependence on ATP to stabilize the cleavage complex. MccB17 enhances the overall rate of DNA cleavage by increasing the forward rate constant (k2) of the second equilibrium. In contrast, ciprofloxacin increases the amount of cleaved DNA by a combined effect on the forward and reverse rate constants of both equilibria. Based on these results and on the observations that MccB17 only slowly inhibits the supercoiling and relaxation reactions, we suggest a model of the interaction of MccB17 with gyrase.

Inhibition of the NLRP3-inflammasome as a potential approach for neuroprotection after stroke.

PubMed

Ismael, Saifudeen; Zhao, Liang; Nasoohi, Sanaz; Ishrat, Tauheed

2018-04-13

Activation of the NOD-like receptor protein (NLRP3)-inflammasome has been postulated to mediate inflammatory responses to brain damage during ischemic/reperfusion (I/R) injury. We therefore hypothesized that MCC950, a selective NLRP3-inflammasome inhibitor provides protection in mouse model of transient middle cerebral artery occlusion (tMCAO). Focal cerebral ischemia was induced by 60 min tMCAO followed by intraperitoneal administration of MCC950 (50 mg/kg) or saline at 1 h and 3 h post-occlusion. After 24 h of I/R, mice were tested for neurological outcome and were sacrificed for the analysis of infarct size and estimating NLRP3-inflammasome and apoptotic markers as well. Spectrophotometric method was used to determine hemoglobin (Hb) content as a marker of intracerebral hemorrhage. MCC950-treated mice showed a substantial reduction in infarction, edema and Hb content compared to saline controls in parallel with improved neurological deficits. MCC950 reduced expression of NLRP3-inflammasome cleavage products Caspase-1 and interlukin-1β (IL-1β) in penumbral region. These protective effects of MCC950 were associated with decreased TNF-α levels as well as poly (ADP-ribose) polymerase (PARP) and Caspase-3 cleavage and paralleled less phosphrylated NFκBp65 and IκBα levels. Taken together, these data indicate that inhibition of NLRP3-inflammasome with MCC950 has therapeutic potential in ischemic stroke models. Further investigations into the therapeutic efficacy and protocols are needed to confirm whether MCC950 treatment could be a promising candidate for clinical trials.

MCC950, the Selective Inhibitor of Nucleotide Oligomerization Domain-Like Receptor Protein-3 Inflammasome, Protects Mice against Traumatic Brain Injury.

PubMed

Ismael, Saifudeen; Nasoohi, Sanaz; Ishrat, Tauheed

2018-06-01

Nucleotide oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome may intimately contribute to sustaining damage after traumatic brain injury (TBI). This study aims to examine whether specific modulation of NLPR3 inflammasome by MCC950, a novel selective NLRP3 inhibitor, confers protection after experimental TBI. Unilateral cortical impact injury was induced in young adult C57BL/6 mice. MCC950 (50 mg/kg, intraperitoneally) or saline was administration at 1 and 3 h post-TBI. Animals were tested for neurological function and then sacrificed at 24 or 72 h post-TBI. Immunoblotting and histological analysis were performed to identify markers of NLRP3 inflammasome and proapoptotic activity in pericontusional areas of the brains at 24 or 72 h post-TBI. MCC950 treatment provided a significant improvement in neurological function and reduced cerebral edema in TBI animals. TBI upregulated NLRP3, apoptosis-associated speck-like adapter protein (ASC), cleaved caspase-1, and interlukein-1β (IL-1β) in the perilesional area. MCC950 efficiently repressed caspase-1 and IL-1β with a transient effect on ASC and NLRP3 post-TBI. MCC950 treatment also provided protection against proapoptotic activation of poly (ADP-ribose) polymerase and caspase-3 associated with TBI. A concurrent inhibition of inflammasome priming was also detectable at the nuclear factor kappa B/p65 and caspase-1 level. Our findings support the implication of NLRP3 inflammasome in the pathogenesis of TBI and further suggests the therapeutic potential of MCC950.

Multiple Chronic Conditions, Resilience, and Workforce Transitions in Later Life: A Socio-Ecological Model.

PubMed

Jason, Kendra J; Carr, Dawn C; Washington, Tiffany R; Hilliard, Tandrea S; Mingo, Chivon A

2017-04-01

Despite the growing prevalence of multiple chronic conditions (MCC), a problem that disproportionally affects older adults, few studies have examined the impact of MCC status on changes in workforce participation in later life. Recent research suggests that resilience, the ability to recover from adversity, may buffer the negative impact of chronic disease. Guided by an adapted socio-ecological risk and resilience conceptual model, this study examined the buffering effect of resilience on the relationship between individual and contextual risks, including MCC, and workforce transitions (i.e., leaving the workforce, working fewer hours, working the same hours, or working more hours). Using the Health and Retirement Study, this study pooled a sample of 4,861 older workers aged 51 and older with 2 consecutive biannual waves of data. Nonnested multinomial logistic regression analysis was applied. MCC are related to higher risk of transitioning out of the workforce. Resilience buffered the negative effects of MCC on workforce engagement and remained independently associated with increased probability of working the same or more hours compared with leaving work. MCC are associated with movement out of the paid workforce in later life. Despite the challenges MCC impose on older workers, having higher levels of resilience may provide the psychological resources needed to sustain work engagement in the face of new deficits. These findings suggest that identifying ways to bolster resilience may enhance the longevity of productive workforce engagement. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Implementing and Evaluating a Telephone-Based Centralized Maternity Care Coordination Program for Pregnant Veterans in the Department of Veterans Affairs.

PubMed

Mattocks, Kristin M; Kuzdeba, Judy; Baldor, Rebecca; Casares, Jose; Lombardini, Lisa; Gerber, Megan R

The purpose of this study was to develop and evaluate a comprehensive, telephonic maternity care coordination (MCC) program for all pregnant veterans enrolled for care at New England Department of Veterans Affairs (VA) facilities that comprise the Veterans Integrated Service Network 1. Telephone interviews were conducted with postpartum women veterans who had participated in the MCC program during their pregnancies. The program evaluation instrument assessed satisfaction and use of MCC services, prenatal education classes, and infant and maternal outcomes (e.g., newborn birthweight, insurance status, maternal depression) using both closed-ended and open-ended questions. A substantial majority (95%) of women enrolled in the MCC program expressed satisfaction with the services they received in the program. Women were most satisfied with help understanding VA maternity benefits and acquiring VA services and equipment, such as breast pumps and pregnancy-related medications. More than one-third of women noted their infants had experienced health problems since delivery, including neonatal intensive care unit hospitalizations. A majority of women planned to return to VA care in the future. Our findings suggest that MCC services play an important role for women veterans as they navigate both VA and non-VA care systems. MCC staff members coordinated maternity, medical, and mental health care services for women veterans. Additionally, by maintaining contact with the veteran during the postpartum period, MCC staff were able to assess the health of the mother and the infant, and refer women and their infants to medical and psychosocial services in the community as needed. Published by Elsevier Inc.

Corrupt practices negatively influenced food security and live expectancy in developing countries

PubMed Central

Uchendu, Florence Ngozi; Abolarin, Thaddeus Olatunbosun

2015-01-01

Malnutrition is a global public health problem more prevalent in developing countries than in developed countries. Indicators of malnutrition include household food security and life expectancy. Corruption might be one of socio-political problems fuelling malnutrition in developing countries. The aim of this paper is to compare influence of corruption on food security, live expectancy (LE) and population in developed and developing countries. Thirty two least corrupt countries (LCC) and most corrupt countries (MCC) representing developed and developing countries were systematically selected using Corruption Perceptions Index (CPI). Countries’ data on population, food security index (FSI) and LE scores were obtained from Global food security index (GFSI) and Population reference bureau. T-test, Multivariate (Wilks’ Lambda), Pearson product moment analysis were performed to determine relationship between CPI, FSI, LE, and population in LCC and MCC at p<.05. Data were presented in tables, means and percentages. Mean CPI, Population, FSI, and LE in LCC and MCC were 71.5% and 24.2%; 34.8 and 41.7million; 75.0% and 37.4%; and 78.4years and 62.4years. There was a significant difference between CPI, FSI and LE in LCC and MCC (p < 0.05). CPI had a significant positive relationship with FSI and LE in LCC not MCC. There was also a significant relationship between FSI and LE in MCC. Low CPI influenced high FSI and LE in LCC while Low LE was associated with low FSI in MCC. Policies discouraging corrupt practices and promoting good governance should be embraced to eradicate malnutrition in developing countries. PMID:26090058

Corrupt practices negatively influenced food security and live expectancy in developing countries.

PubMed

Uchendu, Florence Ngozi; Abolarin, Thaddeus Olatunbosun

2015-01-01

Malnutrition is a global public health problem more prevalent in developing countries than in developed countries. Indicators of malnutrition include household food security and life expectancy. Corruption might be one of socio-political problems fuelling malnutrition in developing countries. The aim of this paper is to compare influence of corruption on food security, live expectancy (LE) and population in developed and developing countries. Thirty two least corrupt countries (LCC) and most corrupt countries (MCC) representing developed and developing countries were systematically selected using Corruption Perceptions Index (CPI). Countries' data on population, food security index (FSI) and LE scores were obtained from Global food security index (GFSI) and Population reference bureau. T-test, Multivariate (Wilks' Lambda), Pearson product moment analysis were performed to determine relationship between CPI, FSI, LE, and population in LCC and MCC at p < .05. Data were presented in tables, means and percentages. Mean CPI, Population, FSI, and LE in LCC and MCC were 71.5% and 24.2%; 34.8 and 41.7 million; 75.0% and 37.4%; and 78.4 years and 62.4 years. There was a significant difference between CPI, FSI and LE in LCC and MCC (p < 0.05). CPI had a significant positive relationship with FSI and LE in LCC not MCC. There was also a significant relationship between FSI and LE in MCC. Low CPI influenced high FSI and LE in LCC while Low LE was associated with low FSI in MCC. Policies discouraging corrupt practices and promoting good governance should be embraced to eradicate malnutrition in developing countries.

Use of micellar casein concentrate for Greek-style yogurt manufacturing: effects on processing and product properties.

PubMed

Bong, D D; Moraru, C I

2014-03-01

The objective of this work was to develop and optimize an alternative make process for Greek-style yogurt (GSY), in which the desired level of protein was reached by fortification with micellar casein concentrate (MCC) obtained from milk by microfiltration. Two MCC preparations with 58 and 88% total protein (MCC-58 and MCC-88) were used to fortify yogurt milk to 9.80% (wt/wt) protein. Strained GSY of similar protein content was used as the control. Yogurt milk bases were inoculated with 0.02% (wt/wt) or 0.04% (wt/wt) direct vat set starter culture and fermented until pH 4.5. The acidification rate was faster for the MCC-fortified GSY than for the control, regardless of the inoculation level, which was attributed to the higher nonprotein nitrogen content in the MCC-fortified milk. Steady shear rate rheological analysis indicated a shear-thinning behavior for all GSY samples, which fitted well with the power law model. Dynamic rheological analysis at 5°C showed a weak frequency dependency of the elastic modulus (G') and viscous modulus (G") for all GSY samples, with G' > G", indicating a weak gel structure. Differences in the magnitude of viscoelastic parameters between the 2 types of GSY were found, with G' of MCC-fortified GSY < G' of control, indicating a different extent of protein interactionsin the 2 types of yogurt. Differences were also noticed in water-holding capacity, which was lower for the MCC-fortified GSY compared with the control, attributed to lower serum protein content in the former. Despite some differences in the physicochemical characteristics of the final product compared with GSY manufactured by straining, the alternative process developed here is a feasible alternative to the traditional GSY make process, with environmental and possibly financial benefits to the dairy industry. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Advantage of 3D volumetric dosemeter in delivery quality assurance of dynamic arc therapy: comparison of pencil beam and Monte Carlo calculations

PubMed Central

Shin, H-J; Song, J H; Jung, J-Y; Kwak, Y-K; Kay, C S; Kang, Y-N; Choi, B O; Jang, H S

2013-01-01

Objective: To evaluate the accuracy of pencil beam calculation (PBC) and Monte Carlo calculation (MCC) for dynamic arc therapy (DAT) in a cylindrically shaped homogenous phantom, by comparing the two plans with an ion chamber, a film and a three-dimensional (3D) volumetric dosemeter. Methods: For this study, an in-house phantom was constructed, and the PBC and MCC plans for DAT were performed using iPlan® RT (BrainLAB®, Heimstetten, Germany). The A16 micro ion chamber (Standard Imaging, Middleton, WI), Gafchromic® EBT2 film (International Specialty Products, Wayne, NJ) and ArcCHECK™ (Sun Nuclear, Melbourne, FL) were used for measurements. For comparison with each plan, two-dimensional (2D) and 3D gamma analyses were performed using 3%/3 mm and 2%/2 mm criteria. Results: The difference between the PBC and MCC plans using 2D and 3D gamma analyses was found to be 7.85% and 28.8%, respectively. The ion chamber and 2D dose distribution measurements did not exhibit this difference revealed by the comparison between the PBC and MCC plans. However, the 3D assessment showed a significant difference between the PBC and MCC (62.7% for PBC vs 93.4% for MCC, p = 0.034). Conclusion: Evaluation using a 3D volumetric dosemeter can be clinically useful for delivery quality assurance (QA), and the MCC should be used to achieve the most reliable dose calculation for DAT. Advances in knowledge: (1) The DAT plan calculated using the PBC has a limitation in the calculation methods, and a 3D volumetric dosemeter was found to be an adequate tool for delivery QA of DAT. (2) The MCC was superior to PBC in terms of the accuracy in dose calculation for DAT even in the homogenous condition. PMID:24234583

Specific inhibition of NLRP3 in chikungunya disease reveals a role for inflammasomes in alphavirus-induced inflammation.

PubMed

Chen, Weiqiang; Foo, Suan-Sin; Zaid, Ali; Teng, Terk-Shin; Herrero, Lara J; Wolf, Stefan; Tharmarajah, Kothila; Vu, Luan D; van Vreden, Caryn; Taylor, Adam; Freitas, Joseph R; Li, Rachel W; Woodruff, Trent M; Gordon, Richard; Ojcius, David M; Nakaya, Helder I; Kanneganti, Thirumala-Devi; O'Neill, Luke A J; Robertson, Avril A B; King, Nicholas J; Suhrbier, Andreas; Cooper, Matthew A; Ng, Lisa F P; Mahalingam, Suresh

2017-10-01

Mosquito-borne viruses can cause severe inflammatory diseases and there are limited therapeutic solutions targeted specifically at virus-induced inflammation. Chikungunya virus (CHIKV), a re-emerging alphavirus responsible for several outbreaks worldwide in the past decade, causes debilitating joint inflammation and severe pain. Here, we show that CHIKV infection activates the NLRP3 inflammasome in humans and mice. Peripheral blood mononuclear cells isolated from CHIKV-infected patients showed elevated NLRP3, caspase-1 and interleukin-18 messenger RNA expression and, using a mouse model of CHIKV infection, we found that high NLRP3 expression was associated with peak inflammatory symptoms. Inhibition of NLRP3 activation using the small-molecule inhibitor MCC950 resulted in reduced CHIKV-induced inflammation and abrogated osteoclastogenic bone loss and myositis, but did not affect in vivo viral replication. Mice treated with MCC950 displayed lower expression levels of the cytokines interleukin-6, chemokine ligand 2 and tumour necrosis factor in joint tissue. Interestingly, MCC950 treatment abrogated disease signs in mice infected with a related arthritogenic alphavirus, Ross River virus, but not in mice infected with West Nile virus-a flavivirus. Here, using mouse models of alphavirus-induced musculoskeletal disease, we demonstrate that NLRP3 inhibition in vivo can reduce inflammatory pathology and that further development of therapeutic solutions targeting inflammasome function could help treat arboviral diseases.

pH/Ultrasound Dual-Responsive Gas Generator for Ultrasound Imaging-Guided Therapeutic Inertial Cavitation and Sonodynamic Therapy.

PubMed

Feng, Qianhua; Zhang, Wanxia; Yang, Xuemei; Li, Yuzhen; Hao, Yongwei; Zhang, Hongling; Hou, Lin; Zhang, Zhenzhong

2018-03-01

Herein, a pH/ultrasound dual-responsive gas generator is reported, which is based on mesoporous calcium carbonate (MCC) nanoparticles by loading sonosensitizer (hematoporphyrin monomethyl ether (HMME)) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC-HA decomposes instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound (US) irradiation, concurrently accompanying with CO 2 generation and HMME release with spatial/temporal resolution. Afterward, the CO 2 bubbling and bursting effect under US stimulus results in cavitation-mediated irreversible cell necrosis, as well as the blood vessel destruction to further occlude the blood supply, providing a "bystander effect." Meanwhile, reactive oxygen species generated from HMME can target the apoptotic pathways for effective sonodynamic therapy. Thus, the combination of apoptosis/necrosis with multimechanisms consequently results in a remarkable antitumor therapeutic efficacy, simultaneously minimizing the side effects on major organs. Moreover, the echogenic property of CO 2 make the nanoplatform as a powerful ultrasound contrast agent to identify cancerous lesions. Based on the above findings, such all-in-one drug delivery platform of HMME/MCC-HA is utilized to provide the US imaging guidance for therapeutic inertial cavitation and sonodynamic therapy simultaneously, which highlights possibilities of advancing cancer theranostics in biomedical fields. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cost effectiveness of facility-based care, home-based care and mobile clinics for provision of antiretroviral therapy in Uganda.

PubMed

Babigumira, Joseph B; Sethi, Ajay K; Smyth, Kathleen A; Singer, Mendel E

2009-01-01

Stakeholders in HIV/AIDS care currently use different programmes for provision of antiretroviral therapy (ART) in Uganda. It is not known which of these represents the best value for money. To compare the cost effectiveness of home-based care (HBC), facility-based care (FBC) and mobile clinic care (MCC) for provision of ART in Uganda. Incremental cost-effectiveness analysis was performed using decision and Markov modeling of adult AIDS patients in WHO Clinical Stage 3 and 4 from the perspective of the Ugandan healthcare system. The main outcome measures were cost (year 2008 values), life expectancy in life-years (LY) and the incremental cost-effectiveness ratio (ICER) measured as cost per QALY or LY gained over 10 years. Ten-year mean undiscounted life expectancy was lowest for FBC (3.6 LY), followed by MCC (4.3 LY) and highest for HBC (5.3 LY), while the mean discounted QALYs were also lowest for FBC (2.3), followed by MCC (2.9) and highest for HBC (3.7). The 10-year mean costs per patient were lowest for FBC ($US3212), followed by MCC ($US4782) and highest for HBC ($US7033). The ICER was lower for MCC versus FBC ($US2241 per LY and $US2615 per QALY) than for HBC versus MCC ($US2251 per LY and $US2814 per QALY). FBC remained cost effective in univariate and probabilistic sensitivity analyses. FBC appears to be the most cost-effective programme for provision of ART in Uganda. This analysis supports the implementation of FBC for scale-up and sustainability of ART in Uganda. HBC and MCC would be competitive only if there is increased access, increased adherence or reduced cost.

Correlation-based discrimination between cardiac tissue and blood for segmentation of 3D echocardiographic images

NASA Astrophysics Data System (ADS)

Saris, Anne E. C. M.; Nillesen, Maartje M.; Lopata, Richard G. P.; de Korte, Chris L.

2013-03-01

Automated segmentation of 3D echocardiographic images in patients with congenital heart disease is challenging, because the boundary between blood and cardiac tissue is poorly defined in some regions. Cardiologists mentally incorporate movement of the heart, using temporal coherence of structures to resolve ambiguities. Therefore, we investigated the merit of temporal cross-correlation for automated segmentation over the entire cardiac cycle. Optimal settings for maximum cross-correlation (MCC) calculation, based on a 3D cross-correlation based displacement estimation algorithm, were determined to obtain the best contrast between blood and myocardial tissue over the entire cardiac cycle. Resulting envelope-based as well as RF-based MCC values were used as additional external force in a deformable model approach, to segment the left-ventricular cavity in entire systolic phase. MCC values were tested against, and combined with, adaptive filtered, demodulated RF-data. Segmentation results were compared with manually segmented volumes using a 3D Dice Similarity Index (3DSI). Results in 3D pediatric echocardiographic images sequences (n = 4) demonstrate that incorporation of temporal information improves segmentation. The use of MCC values, either alone or in combination with adaptive filtered, demodulated RF-data, resulted in an increase of the 3DSI in 75% of the cases (average 3DSI increase: 0.71 to 0.82). Results might be further improved by optimizing MCC-contrast locally, in regions with low blood-tissue contrast. Reducing underestimation of the endocardial volume due to MCC processing scheme (choice of window size) and consequential border-misalignment, could also lead to more accurate segmentations. Furthermore, increasing the frame rate will also increase MCC-contrast and thus improve segmentation.

Cost Effectiveness of Facility-Based Care, Home-Based Care and Mobile Clinics for Provision of Antiretroviral Therapy in Uganda

PubMed Central

Babigumira, Joseph B.; Sethi, Ajay K.; Smyth, Kathleen A.; Singer, Mendel E.

2012-01-01

Background Stakeholders in HIV/AIDS care currently use different programmes for provision of antiretroviral therapy (ART) in Uganda. It is not known which of these represents the best value for money. Objective To compare the cost effectiveness of home-based care (HBC), facility-based care (FBC) and mobile clinic care (MCC) for provision of ART in Uganda. Methods Incremental cost-effectiveness analysis was performed using decision and Markov modeling of adult AIDS patients in WHO Clinical Stage 3 and 4 from the perspective of the Ugandan healthcare system. The main outcome measures were cost (year 2008 values), life expectancy in life-years (LY) and the incremental cost-effectiveness ratio (ICER) measured as cost per QALY or LY gained over 10 years. Results Ten-year mean undiscounted life expectancy was lowest for FBC (3.6 LY), followed by MCC (4.3 LY) and highest for HBC (5.3 LY), while the mean discounted QALYs were also lowest for FBC (2.3), followed by MCC (2.9) and highest for HBC (3.7). The 10-year mean costs per patient were lowest for FBC ($US3212), followed by MCC ($US4782) and highest for HBC ($US7033). The ICER was lower for MCC versus FBC ($US2241 per LY and $US2615 per QALY) than for HBC versus MCC ($US2251 per LY and $US2814 per QALY). FBC remained cost effective in univariate and probabilistic sensitivity analyses. Conclusions FBC appears to be the most cost-effective programme for provision of ART in Uganda. This analysis supports the implementation of FBC for scale-up and sustainability of ART in Uganda. HBC and MCC would be competitive only if there is increased access, increased adherence or reduced cost. PMID:19888795

Synthesis of deuterium-labelled analogues of NLRP3 inflammasome inhibitor MCC950.

PubMed

Salla, Manohar; Butler, Mark S; Massey, Nicholas L; Reid, Janet C; Cooper, Matthew A; Robertson, Avril A B

2018-02-15

This study describes the syntheses of di, tetra and hexa deuterated analogues of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome inhibitor MCC950. In di and tetra deuterated analogues, deuteriums were incorporated into the 1,2,3,5,6,7-hexahydro-s-indacene moiety, whereas in the hexa deuterated MCC950 deuteriums were incorporated into the 2-(furan-3-yl)propan-2-ol moiety. The di deuterated MCC950 analogue was synthesised from 4-amino-3,5,6,7-tetrahydro-s-indacen-1(2H)-one 5. Tetra deuterated analogues were synthesised in 10 chemical steps starting with 5-bromo-2,3-dihydro-1H-inden-1-one 9, whereas the hexa deuterated analogue was synthesised in four chemical steps starting with ethyl-3-furoate 24. All of the compounds exhibited similar activity to MCC950 (IC 50  = 8 nM). These deuterated analogues are useful as internal standards in LC-MS analyses of biological samples from in vivo studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hospital Utilization, Costs, and Mortality for Adults With Multiple Chronic Conditions, Nationwide Inpatient Sample, 2009

PubMed Central

Friedman, Bernard

2013-01-01

Objective Our objective was to provide a national estimate across all payers of the distribution and cost of selected chronic conditions for hospitalized adults in 2009, stratified by demographic characteristics. Analysis We analyzed the Nationwide Inpatient Sample (NIS), the largest all-payer inpatient database in the United States. Use, cost, and mortality estimates across payer, age, sex, and race/ethnicity are produced for grouped or multiple chronic conditions (MCC). The 5 most common dyads and triads were determined. Results In 2009, there were approximately 28 million adult discharges from US hospitals other than those related to pregnancy and maternity; 39% had 2 to 3 MCC, and 33% had 4 or more. A higher number of MCC was associated with higher mortality, use of services, and average cost. The percentages of Medicaid, privately insured patients, and ethnic/racial groups with 4 or more MCC were highly sensitive to age. Summary This descriptive analysis of multipayer inpatient data provides a robust national view of the substantial use and costs among adults hospitalized with MCC. PMID:23618542

Mission Control Center (MCC) System Specification for the Shuttle Orbital Flight Test (OFT) Timeframe

NASA Technical Reports Server (NTRS)

1976-01-01

System specifications to be used by the mission control center (MCC) for the shuttle orbital flight test (OFT) time frame were described. The three support systems discussed are the communication interface system (CIS), the data computation complex (DCC), and the display and control system (DCS), all of which may interfere with, and share processing facilities with other applications processing supporting current MCC programs. The MCC shall provide centralized control of the space shuttle OFT from launch through orbital flight, entry, and landing until the Orbiter comes to a stop on the runway. This control shall include the functions of vehicle management in the area of hardware configuration (verification), flight planning, communication and instrumentation configuration management, trajectory, software and consumables, payloads management, flight safety, and verification of test conditions/environment.

Identification of a Polyomavirus microRNA Highly Expressed in Tumors

PubMed Central

Chen, Chun Jung; Cox, Jennifer E.; Azarm, Kristopher; Wylie, Karen N.; Woolard, Kevin D.; Pesavento, Patricia A.; Sullivan, Christopher S.

2014-01-01

Polyomaviruses (PyVs) are associated with tumors including Merkel cell carcinoma (MCC). Several PyVs encode microRNAs (miRNAs) but to date no abundant PyV miRNAs have been reported in tumors. To better understand the function of the Merkel cell PyV (MCPyV) miRNA, we examined phylogenetically-related viruses for miRNA expression. We show that two primate PyVs and the more distantly-related raccoon PyV (RacPyV) encode miRNAs that share genomic position and partial sequence identity with MCPyV miRNAs. Unlike MCPyV miRNA in MCC, RacPyV miRNA is highly abundant in raccoon tumors. RacPyV miRNA negatively regulates reporters of early viral (T antigen) transcripts, yet robust viral miRNA expression is tolerated in tumors. We also identify raccoon miRNAs expressed in RacPyV-associated neuroglial brain tumors, including several likely oncogenic miRNAs (oncomiRs). This work describes the first PyV miRNA abundantly expressed in tumors and is consistent with a possible role for both host and viral miRNAs in RacPyV-associated tumors. PMID:25514573

Factors Influencing Relapse-Free Survival in Merkel Cell Carcinoma of the Lower Limb-A Review of 60 Cases

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

Poulsen, Michael, E-mail: michael_poulsen@health.qld.gov.a; Round, Caroline; Keller, Jacqui

2010-02-01

Purpose: Factors affecting relapse-free survival (RFS) in patients with Merkel cell carcinoma (MCC) of the lower limb were reviewed. Methods and Materials: The records of 60 patients from 1986 to 2005 with a diagnosis of MCC of the lower limb or buttock were retrospectively reviewed. The patients were treated with curative intent with surgery, radiation, or chemotherapy. Results: The 5-year overall survival, disease-specific survival, and RFS were 53%, 61%, and 20%, respectively. Factors influencing RFS were analyzed using univariate analysis. It appeared that recurrent disease worsened RFS (p = 0.03) and the addition of any radiotherapy improved RFS (p <0.001),more » as did radiotherapy to the inguinal nodes (p = 0.01) or primary site and inguinal nodes (p = 0.003). Age, surgical margins, and stage were not statistically significant. On multivariate analysis, the only significant factor was the addition of radiotherapy (hazard ratio = 0.51 p = 0.03). Conclusion: The addition of radiotherapy improves RFS compared with surgery alone. Elective treatment should be given to the inguinal nodes to reduce the risk of relapse.« less

Glycosylation of DMP1 Is Essential for Chondrogenesis of Condylar Cartilage.

PubMed

Weng, Y; Liu, Y; Du, H; Li, L; Jing, B; Zhang, Q; Wang, X; Wang, Z; Sun, Y

2017-12-01

The mandibular condylar cartilage (MCC) shoulders force for the subchondral bone during mastication. The cartilage matrix contains various large molecules, such as type I, II, and X collagens and proteoglycans (PGs), which jointly play essential roles in maintaining cartilage characteristics. PGs play key roles in maintaining the elasticity of cartilage and providing a cushion against mastication forces. In addition to the well-known PGs, DMP1-PG, which is the PG form of dentin matrix protein 1 (DMP1), is a newly identified PG. DMP1 is proteolytically processed in vivo, and the N-terminus is glycosylated into its PG form-that is, DMP1-PG, which is highly expressed not only in tooth and bone but also in the matrix of the MCC. However, the specific functions of DMP1-PG in the MCC remain unclear. In human temporomandibular joint osteoarthritis and hyperocclusion model rat specimens, PGs are significantly downregulated, and DMP1-PG is the most prominently affected PG. To further investigate the role of DMP1-PG in condylar chondrogenesis, a glycosylation site mutant (S 89 -G 89 ) mouse model was established with knock-in methods. In the MCC of the S89G-DMP1 mice, the glycosylation level of DMP1 was significantly downregulated, and a series of abnormal developmental and pathologic changes could be observed. The morphologic changes included thinner cartilage layers, deformations of the MCC, and disordered arrangements of the chondrocytes, and an earlier onset of temporomandibular joint osteoarthritis-like changes was observed. In addition, markers of chondrogenesis were downregulated, and the matrix of the MCC displayed OA phenotypes in the S89G-DMP1 mice. Further investigations showed that the transforming growth factor β signaling molecules were affected in the MCC after the loss of DMP1-PG. In addition, the loss of DMP1-PG significantly accelerated the progression of cartilage injuries in the hyperocclusion models. Given these findings, we investigated the significant role of DMP1-PG in the chondrogenesis and maintenance of MCC.

Merkel cell polyomavirus infection and Merkel cell carcinoma.

PubMed

Liu, Wei; MacDonald, Margo; You, Jianxin

2016-10-01

Merkel cell polyomavirus is the only polyomavirus discovered to date that is associated with a human cancer. MCPyV infection is highly prevalent in the general population. Nearly all healthy adults asymptomatically shed MCPyV from their skin. However, in elderly and immunosuppressed individuals, the infection can lead to a lethal form of skin cancer, Merkel cell carcinoma. In the last few years, new findings have established links between MCPyV infection, host immune response, and Merkel cell carcinoma development. This review discusses these recent discoveries on how MCPyV interacts with host cells to achieve persistent infection and, in the immunocompromised population, contributes to MCC development. Copyright © 2016 Elsevier B.V. All rights reserved.

Extraction of microcrystalline cellulose from rice straw and its effect on polyvinyl alcohol biocomposites film

NASA Astrophysics Data System (ADS)

Chin, Kwok-Mern; Ting, Sam Sung; Lin, Ong Hui; Owi, Wei Tieng

2017-07-01

The poor management and underutilization of agricultural wastes had proliferated interest of researchers around the world to find alternatives to utilize them as potential value-added products. One of the green alternatives is by extracting cellulose from these waste materials and incorporating them in polymer as reinforcement fillers. The surging amount of plastic waste also posed major issues to the environment due to its recalcitrance to degrade. Microcrystalline cellulose (MCC-RS) was extracted from rice straw through cyclic alkaline and bleaching treatment to remove hemicellulose and lignin respectively. Polyvinyl alcohol (PVOH) was chosen as the matrix and different ratios of PVOH / MCC-RS films were prepared (2.5, 5.0, 7.5 and 10.0wt% of MCC) through solution casting method and its tensile, thermal and morphological properties were studied. X-ray powder diffraction (XRD) results showed increased crystallinity of MCC-RS after chemical treatment (from 44.5% to 60.8%) due to the successful removal of lignin and hemicellulose, which was then confirmed with Fourier transform infrared spectroscopy (FTIR) results. For the biocomposites, both tensile strength and Young's modulus of the films increased with increasing MCC-RS content up until 7.5wt%, supported with scanning electron microscopy (SEM) results which depicted improvement in the interfacial adhesion between MCC-RS and PVOH. From the overall results, the improvement in properties of biocomposite from cellulose-based microfiller had shown promising future in application of the water soluble plastic packaging industry.

Comparison of African American Children's Performances on a Minimal Competence Core for Morphosyntax and the Index of Productive Syntax.

PubMed

Stockman, Ida J; Newkirk-Turner, Brandi L; Swartzlander, Elaina; Morris, Lekeitha R

2016-02-01

This study is a response to the need for evidence-based measures of spontaneous oral language to assess African American children under the age of 4 years. We determined if pass/fail status on a minimal competence core for morphosyntax (MCC-MS) was more highly related to scores on the Index of Productive Syntax (IPSyn)-the measure of convergent criterion validity-than to scores on 3 measures of divergent validity: number of different words (Watkins, Kelly, Harbers, & Hollis, 1995), Percentage of Consonants Correct-Revised (Shriberg, Austin, Lewis, McSweeney, & Wilson, 1997), and the Leiter International Performance Scale-Revised (Roid & Miller, 1997). Archival language samples for 68 African American 3-year-olds were analyzed to determine MCC-MS pass/fail status and the scores on measures of convergent and divergent validity. Higher IPSyn scores were observed for 60 children who passed the MCC-MS than for 8 children who did not. A significant positive correlation, rpb = .73, between MCC-MS pass/fail status and IPSyn scores was observed. This coefficient was higher than MCC-MS correlations with measures of divergent validity: rpb = .13 (Leiter International Performance Scale-Revised), rpb = .42 (number of different words in 100 utterances), and rpb = .46 (Percentage of Consonants Correct-Revised). The MCC-MS has convergent criterion validity with the IPSyn. Although more research is warranted, both measures can be potentially used in oral language assessments of African American 3-year-olds.

Fluorimetric assay of the neurotensin-degrading metalloendopeptidase, endopeptidase 24.16.

PubMed

Dauch, P; Barelli, H; Vincent, J P; Checler, F

1991-12-01

Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp (Mcc = 3-carboxy-7-methoxycoumarin; Dnp = dinitrophenyl), a quenched fluorimetric substrate originally designed as a probe to measure Pz-peptidase (also called endopeptidase 24.15), was examined as a putative substrate of the neurotensin-degrading neutral metalloendopeptidase, endopeptidase 24.16. During the purification of endopeptidase 24.16 the neurotensin(1-10) and neurotensin(11-13) formation due to this enzyme was coeluted with Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp-hydrolysing activity. By both fluorimetric and h.p.l.c. analyses, we observed that the latter activity was dose-dependently and completely abolished by neurotensin with an IC50 value (2.6 microM) that closely corresponds to the affinity of purified endopeptidase 24.16 for neurotensin (Km = 2.5 microM). Furthermore, Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp hydrolysis was inhibited by a series of dipeptides with a rank of order of potencies that parallels that observed in competition experiments of tritiated neurotensin hydrolysis by brain and intestinal endopeptidase 24.16. Altogether, these data clearly demonstrate that, in addition to Pz-peptidase, Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp also behaves as a substrate of endopeptidase 24.16, with a Km of about 26 microM. In addition, we show that, even in crude membrane preparations, Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp behaves as a useful tool to monitor and accurately quantify endopeptidase 24.16.

Fluorimetric assay of the neurotensin-degrading metalloendopeptidase, endopeptidase 24.16.

PubMed Central

Dauch, P; Barelli, H; Vincent, J P; Checler, F

1991-01-01

Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp (Mcc = 3-carboxy-7-methoxycoumarin; Dnp = dinitrophenyl), a quenched fluorimetric substrate originally designed as a probe to measure Pz-peptidase (also called endopeptidase 24.15), was examined as a putative substrate of the neurotensin-degrading neutral metalloendopeptidase, endopeptidase 24.16. During the purification of endopeptidase 24.16 the neurotensin(1-10) and neurotensin(11-13) formation due to this enzyme was coeluted with Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp-hydrolysing activity. By both fluorimetric and h.p.l.c. analyses, we observed that the latter activity was dose-dependently and completely abolished by neurotensin with an IC50 value (2.6 microM) that closely corresponds to the affinity of purified endopeptidase 24.16 for neurotensin (Km = 2.5 microM). Furthermore, Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp hydrolysis was inhibited by a series of dipeptides with a rank of order of potencies that parallels that observed in competition experiments of tritiated neurotensin hydrolysis by brain and intestinal endopeptidase 24.16. Altogether, these data clearly demonstrate that, in addition to Pz-peptidase, Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp also behaves as a substrate of endopeptidase 24.16, with a Km of about 26 microM. In addition, we show that, even in crude membrane preparations, Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp behaves as a useful tool to monitor and accurately quantify endopeptidase 24.16. PMID:1747117

Pembrolizumab-associated Mucous Membrane Pemphigoid in a Merkel cell carcinoma patient.

PubMed

Haug, V; Behle, V; Benoit, S; Kneitz, H; Schilling, B; Goebeler, M; Gesierich, A

2018-05-14

the anti-programmed death-1 (PD-1) antibody pembrolizumab, routinely used for treatment of metastatic melanoma or non-small cell lung cancer, was recently shown to have clinical meaningful activity in metastatic Merkel cell carcinoma (MCC). Several cases of bullous pemphigoid (BP) induced by PD-1 antibodies in melanoma have been reported so far. Here we report a case of oral mucous membrane pemphigoid (MMP) - a previously unknown, severe immune-related adverse event (irAE) occurring during pembrolizumab therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Midline cervical cleft: a rare congenital anomaly.

PubMed

Renukaswamy, Gayathri Mandya; Soma, Marlene A; Hartley, Benjamin E J

2009-11-01

A midline cervical cleft (MCC) is a rare congenital anomaly due to failure of fusion of the first and second branchial arches during embryogenesis. It may present as a midline defect of the anterior neck skin with a skin projection or sinus, or as a subcutaneous fibrous cord. This report evaluates the clinical features and surgical management of an MCC. We analyzed a series of 4 patients with an MCC successfully treated at Great Ormond Street Hospital for Children in London. Three male patients and 1 female patient between 4 and 11 months of age were found to have an MCC. Each patient presented with an erythematous, fibrous band of tissue extending between the chin and the suprasternal notch. Treatment comprised surgical excision of the lesion and Z-plasty repair. We present the embryology, common clinical presentation, investigations, differential diagnosis, and histology, along with a literature review, of this uncommon malformation of the anterior neck. An MCC is a differential diagnosis to consider when assessing a child with a midline cervical lesion. Early surgical excision with Z-plasty repair of the soft tissue defect is the treatment of choice to prevent long-term complications.

Radiation response of nanotwinned Cu under multiple-collision cascades

NASA Astrophysics Data System (ADS)

Wu, Lianping; Yu, Wenshan; Hu, Shuling; Shen, Shengping

2018-07-01

In this paper, multiple collision cascades (MCC) of nanotwinned (nt) Cu with three different twin spacings are performed to model the response of nt Cu upon a radiation dose of 1 displacements per atom (dpa). Considering the defects developed with high randomness in the material during a MCC process, each MCC in a nt Cu is conducted for eight times. This enables us to analyze some average properties of defect clusters in the radiated nt Cu with different twin spacings at the different radiation doses. We also analyze the microstructural evolution in the nt Cu during the MCC. Smaller size of defect clusters and lower defect density are seen in the nt Cu with smaller twin spacing. In addition, a number of defect clusters could be removed via their frequent interactions with the coherent twin boundaries (CTBs) during the MCC. This induces either the migration of CTBs or the healing of CTBs. Moreover, the potential formation and elimination mechanisms of stacking fault are found to be due to the climb of Frank partial dislocation and glide of Shockley partial dislocations. This study provides further evidence on the irradiation tolerance of CTBs and the self-healing capability of CTBs in response to radiation.

Immunogenicity and immunologic memory of meningococcal C conjugate vaccine in premature infants.

PubMed

Collins, Clare L; Ruggeberg, Jens U; Balfour, Gail; Tighe, Helen; Archer, Marion; Bowen-Morris, Jane; Diggle, Linda; Borrow, Ray; Balmer, Paul; Buttery, Jim P; Moxon, E Richard; Pollard, Andrew J; Heath, Paul T

2005-11-01

Protein-polysaccharide conjugate vaccines against Neisseria meningitidis serogroup C were introduced into the U.K. routine immunization schedule in 1999. This study is the first to describe both persistence of antibody and evidence for induction of immune memory using meningococcal C conjugate (MCC) vaccine in preterm infants. Immunogenicity and induction of immunologic memory by as MCC vaccine was assessed in premature infants; 62 preterm and 60 term controls received MCC at the accelerated schedule (2, 3 and 4 months of age). A meningococcal C polysaccharide challenge was administered at 12 months of age. Both groups achieved similar protective titers after primary immunization that then waned significantly by 1 year of age. Postchallenge serum bactericidal activity was significantly lower in preterm infants (P = 0.03); 73% of preterm versus 88% of term controls achieved a 4-fold rise in serum bactericidal activity (P = 0.07). MCC vaccine is immunogenic and primes for immunologic memory in preterm infants. The decreased memory responses in these preterm infants in conjunction with waning clinical efficacy data for all U.K. infants suggest a role for a routine booster dose of vaccine in all infants receiving MCC, especially those born preterm.

A multiagent system enhancing home-care health services for chronic disease management.

PubMed

Koutkias, Vassilis G; Chouvarda, Ioanna; Maglaveras, Nicos

2005-12-01

In this paper, a multiagent system (MAS) is presented, aiming to enhance monitoring, surveillance, and educational services of a generic medical contact center (MCC) for chronic disease management. In such a home-care scenario, a persistent need arises for efficiently monitoring the patient contacts and the MCC's functionality, in order to effectively manage and interpret the large volume of medical data collected during the patient sessions with the system, and to assess the use of MCC resources. Software agents were adopted to provide the means to accomplish such real-time information-processing tasks, due to their autonomous, reactive and/or proactive nature, and their effectiveness in dynamic environments by incorporating coordination strategies. Specifically, the objective of the MAS is to monitor the MCC environment, detect important cases, and inform the healthcare and administrative personnel via alert messages, notifications, recommendations, and reports, prompting them for actions. The main aim of this paper is to present the overall design and implementation of a proposed MAS, emphasizing its functional model and architecture, as well as on the agent interactions and the knowledge-sharing mechanism incorporated, in the context of a generic MCC.

Safety and benefits of inhaled hypertonic saline following airway challenges with endotoxin and allergen in asthmatics.

PubMed

Alexis, Neil E; Bennett, William; Peden, David Blaine

2017-11-01

To determine whether induced sputum (IS) with hypertonic saline inhalation is safe to use in asthmatics within 24 hours of two commonly used airway challenges, namely endotoxin and dust mite allergen, and to assess whether IS can enhance mucociliary clearance (MCC) rates in asthmatics. IS (three 7-minute inhalation periods of 3%, 4%, and 5% hypertonic saline) was employed before (N = 29) and within 24 hours of inhaled challenges with endotoxin (N = 13) and dust mite allergen (N = 12) in a cohort of mild to moderate asthmatics. Safety was assessed by lung function (Forced Expiratory Volume in 1 second; FEV1) and MCC was measured using a radiolabeled gamma scintigraphy method (Tcm99 sulfur colloid). IS was performed pre and post MCC. No significant lung function decrement was observed before or after inhaled challenges with endotoxin or dust mite allergen. IS significantly enhanced MCC rates before and after inhaled endotoxin challenge. Based on a small cohort, IS is safe to use in mild to moderate asthmatics before and within 24 hours of inhaled challenges with endotoxin and dust mite allergen. Furthermore, IS has beneficial effects on host defense function in asthmatics by enhancing MCC rates.

Detection of Merkel Cell Polyomavirus DNA in Serum Samples of Healthy Blood Donors

PubMed Central

Mazzoni, Elisa; Rotondo, John C.; Marracino, Luisa; Selvatici, Rita; Bononi, Ilaria; Torreggiani, Elena; Touzé, Antoine; Martini, Fernanda; Tognon, Mauro G.

2017-01-01

Merkel cell polyomavirus (MCPyV) has been detected in 80% of Merkel cell carcinomas (MCC). In the host, the MCPyV reservoir remains elusive. MCPyV DNA sequences were revealed in blood donor buffy coats. In this study, MCPyV DNA sequences were investigated in the sera (n = 190) of healthy blood donors. Two MCPyV DNA sequences, coding for the viral oncoprotein large T antigen (LT), were investigated using polymerase chain reaction (PCR) methods and DNA sequencing. Circulating MCPyV sequences were detected in sera with a prevalence of 2.6% (5/190), at low-DNA viral load, which is in the range of 1–4 and 1–5 copies/μl by real-time PCR and droplet digital PCR, respectively. DNA sequencing carried out in the five MCPyV-positive samples indicated that the two MCPyV LT sequences which were analyzed belong to the MKL-1 strain. Circulating MCPyV LT sequences are present in blood donor sera. MCPyV-positive samples from blood donors could represent a potential vehicle for MCPyV infection in receivers, whereas an increase in viral load may occur with multiple blood transfusions. In certain patient conditions, such as immune-depression/suppression, additional disease or old age, transfusion of MCPyV-positive samples could be an additional risk factor for MCC onset. PMID:29238698

STS-26 long duration simulation in JSC Mission Control Center (MCC) Bldg 30

NASA Technical Reports Server (NTRS)

1988-01-01

STS-26 long duration simulation is conducted in JSC Mission Control Center (MCC) Bldg 30 Flight Control Room (FCR). Director of Mission Operations Directorate (MOD) Eugene F. Kranz (left) and Chief of the Flight Directors Office Tommy W. Holloway monitor activity during the simulation. The two are at their normal stations on the rear row of consoles. The integrated simulation involves MCC flight controllers communicating with crewmembers stationed in the fixed based (FB) shuttle mission simulator (SMS) located in JSC Mission Simulation and Training Facility Bldg 5.

Merkel cell polyomavirus in Merkel cell carcinogenesis: small T antigen-mediates c-Jun phosphorylation.

PubMed

Wu, Julie H; Simonette, Rebecca A; Nguyen, Harrison P; Rady, Peter L; Tyring, Stephen K

2016-06-01

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer associated with the Merkel cell polyomavirus (MCPyV). The MCPyV genome, which is clonally integrated in the majority of MCCs, encodes the regulatory small T (sT) antigen. Previously, reports have established MCPyV sT antigen as a potent oncogene capable of inducing cell transformation. In the current study, we demonstrate a distinct role for c-Jun hyperactivation in MCPyV sT antigen pathogenesis. As MCPyV sT antigen's association with aggressive cancer growth has been previously established, this finding may represent a potential therapeutic target for the treatment of MCCs.

Acute and chronic in vivo effects of exposure to nicotine and propylene glycol from an E-cigarette on mucociliary clearance in a murine model

PubMed Central

Laube, Beth L.; Afshar-Mohajer, Nima; Koehler, Kirsten; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.

2017-01-01

Objective To determine the effect of an acute (1 week) and chronic (3 weeks) exposure to E-cigarette (E-cig) emissions on mucociliary clearance (MCC) in murine lungs. Methods C57BL/6 male mice (age 10.5 ±2.4 weeks) were exposed for 20min/day to E-cigarette aerosol generated by a Joyetech 510-T® E-cig containing either 0% nicotine (N)/propylene glycol (PG) for 1 week (n = 6), or 3 weeks (n = 9), or 2.4% N/PG for one week (n = 6), or 3 weeks (n = 9), followed by measurement of MCC. Control mice (n = 15) were not exposed to PG alone, or N/PG. MCC was assessed by gamma camera following aspiration of 99mtechnetium aerosol and was expressed as the amount of radioactivity removed from both lungs over 6 hours (MCC6hrs). Venous blood was assayed for cotinine levels in control mice and in mice exposed for 3-weeks to PG alone and N/PG. Results MCC6hrs in control mice and in mice acutely exposed to PG alone and N/PG was similar, averaging (±1 standard deviation) 8.6±5.2%, 7.5±2.8% and 11.2±5.9%, respectively. In contrast, chronic exposure to PG alone stimulated MCC6hrs (17.2 ±8.0)% and this stimulation was significantly blunted following chronic exposure to N/PG (8.7 ±4.6)% (p < .05). Serum cotinine levels were <0.5ng/ml in control mice and in mice exposed to PG alone, whereas, N/PG exposed mice averaged 14.6 ± 12.0 ng/ml. Conclusions In this murine model, a chronic, daily, 20 min-exposure to N/PG, but not an acute exposure, slowed MCC, compared to exposure to PG alone and led to systemic absorption of nicotine. PMID:28651446

LC-MS/MS method for the simultaneous determination of Lys-MCC-DM1, MCC-DM1 and DM1 as potential intracellular catabolites of the antibody-drug conjugate trastuzumab emtansine (T-DM1).

PubMed

Liu, Yazhong; Zhou, Fang; Sang, Hua; Ye, Hui; Chen, Qianying; Yao, Lan; Ni, Ping; Wang, Guangji; Zhang, Jingwei

2017-04-15

Lysine-MCC-DM1, MCC-DM1 and DM1 are potential catabolites of trastuzumab emtansine (T-DM1). A convenient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to detect these catabolites simultaneously in in vitro investigations for the first time. Protein precipitation was utilized to prepare the samples. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100×2.1mm, 2.6μm) with mobile-phase gradient elution. The calibration curves of each analyte ranging from 1 to 100nM showed good linearity (r 2 >0.995). The method was validated successfully and applied to the intracellular catabolism and regulation of T-DM1. Copyright © 2017 Elsevier B.V. All rights reserved.

The action of the bacterial toxin, microcin B17, on DNA gyrase.

PubMed

Parks, William M; Bottrill, Andrew R; Pierrat, Olivier A; Durrant, Marcus C; Maxwell, Anthony

2007-04-01

Microcin B17 (MccB17) is a peptide-based bacterial toxin that targets DNA gyrase, the bacterial enzyme that introduces supercoils into DNA. The site and mode of action of MccB17 on gyrase are unclear. We review what is currently known about MccB17-gyrase interactions and summarise approaches to understanding its mode of action that involve modification of the toxin. We describe experiments in which treatment of the toxin at high pH leads to the deamidation of two asparagine residues to aspartates. The modified toxin was found to be inactive in vivo and in vitro, suggesting that the Asn residues are essential for activity. Following on from these studies we have used molecular modelling to suggest a 3D structure for microcin B17. We discuss the implications of this model for MccB17 action and investigate the possibility that it binds metal ions.

Detection of mesoscale convective complexes using multispectral RGB technique of Himawari-8 (Case Study: Jakarta, 20 February 2017)

NASA Astrophysics Data System (ADS)

Fatkhuroyan; Wati, T.

2018-05-01

Mesoscale Convective Complexes (MCC) is a well-organized convective cloud that has big size and long lifetime. The aim of the study is to detect and to monitor the development of MCC around Jakarta on 20th February 2017 using satellite Himawari-8. This study uses the analyzing method of the infrared channel and multispectral imagery RGB Technique to monitor the development of radiative, morphology and cloud position which describe the cloud top microphysics, structure and movement of the MCC. On 20th February 2017, the result from Himawari-8 shows that there are many dense-clouds with small ice particle and cloud top temperature could be < -50°C which can be seen as red and yellow dot colour by RGB Technique. The MCC caused a severe storm at Jakarta and its surrounding area.

Fluorescence in situ hybridization and qPCR to detect Merkel cell polyomavirus physical status and load in Merkel cell carcinomas.

PubMed

Haugg, Anke M; Rennspiess, Dorit; zur Hausen, Axel; Speel, Ernst-Jan M; Cathomas, Gieri; Becker, Jürgen C; Schrama, David

2014-12-15

The Merkel cell polyomavirus (MCPyV) is detected in 80% of Merkel cell carcinomas (MCC). Clonal integration and tumor-specific mutations in the large T antigen are strong arguments that MCPyV is a human tumor virus. However, the relationship between viral presence and cancer induction remains discussed controversially. Since almost all studies on virus prevalence are based on PCR techniques, we performed MCPyV fluorescence in situ hybridization (FISH) on MCC to gain information about the quality of the viral presence on the single cell level. MCPyV-FISH was performed on tissue microarrays containing 62 formalin-fixed and paraffin-embedded tissue samples including all tumor grades of 42 patients. The hybridization patterns were correlated to the qPCR data determined on corresponding whole tissue sections. Indeed, MCPyV-FISH and qPCR data were highly correlated, i.e. 83% for FISH-positive and 93% for FISH-negative cores. Accordingly, the mean of the qPCR values of all MCPyV-positive cores differed significantly from the mean of the negative cores (p = 0.0076). Importantly, two hybridization patterns were definable in the MCPyV-FISH: a punctate pattern (85%) indicating viral integration, which correlated with a moderate viral abundance and a combination of the punctate with a diffuse pattern (15%), suggesting a possible coexistence of integrated and episomal virus which was associated with very high viral load and VP1 expression. Thus, MCPyV-FISH adds important information on the single cell level within the histomorphological context and could therefore be an important tool to further elucidate MCPyV related carcinogenesis. © 2014 UICC.

Combining experimental design and orthogonal projections to latent structures to study the influence of microcrystalline cellulose properties on roll compaction.

PubMed

Dumarey, Melanie; Wikström, Håkan; Fransson, Magnus; Sparén, Anders; Tajarobi, Pirjo; Josefson, Mats; Trygg, Johan

2011-09-15

Roll compaction is gaining importance in pharmaceutical industry for the dry granulation of heat or moisture sensitive powder blends with poor flowing properties prior to tabletting. We studied the influence of microcrystalline cellulose (MCC) properties on the roll compaction process and the consecutive steps in tablet manufacturing. Four dissimilar MCC grades, selected by subjecting their physical characteristics to principal components analysis, and three speed ratios, i.e. the ratio of the feed screw speed and the roll speed of the roll compactor, were included in a full factorial design. Orthogonal projection to latent structures was then used to model the properties of the resulting roll compacted products (ribbons, granules and tablets) as a function of the physical MCC properties and the speed ratio. This modified version of partial least squares regression separates variation in the design correlated to the considered response from the variation orthogonal to that response. The contributions of the MCC properties and the speed ratio to the predictive and orthogonal components of the models were used to evaluate the effect of the design variation. The models indicated that several MCC properties, e.g. bulk density and compressibility, affected all granule and tablet properties, but only one studied ribbon property: porosity. After roll compaction, Ceolus KG 1000 resulted in tablets with obvious higher tensile strength and lower disintegration time compared to the other MCC grades. This study confirmed that the particle size increase caused by roll compaction is highly responsible for the tensile strength decrease of the tablets. Copyright © 2011 Elsevier B.V. All rights reserved.

Identification, Synthesis, and Biological Evaluation of the Major Human Metabolite of NLRP3 Inflammasome Inhibitor MCC950

PubMed Central

2016-01-01

MCC950 is an orally bioavailable small molecule inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that exhibits remarkable activity in multiple models of inflammatory disease. Incubation of MCC950 with human liver microsomes, and subsequent analysis by HPLC–MS/MS, revealed a major metabolite, where hydroxylation of MCC950 had occurred on the 1,2,3,5,6,7-hexahydro-s-indacene moiety. Three possible regioisomers were synthesized, and coelution using HPLC–MS/MS confirmed the structure of the metabolite. Further synthesis of individual enantiomers and coelution studies using a chiral column in HPLC–MS/MS showed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide (2a). Incubation of MCC950 with a panel of cytochrome P450 enzymes showed P450s 2A6, 2C9, 2C18, 2C19, 2J2, and 3A4 catalyze the formation of the major metabolite 2a, with a lower level of activity shown by P450s 1A2 and 2B6. All of the synthesized compounds were tested for inhibition of NLRP3-induced production of the pro-inflammatory cytokine IL-1β from human monocyte derived macrophages. The identified metabolite 2a was 170-fold less potent than MCC950, while one regioisomer had nanomolar inhibitory activity. These findings also give first insight into the SAR of the hexahydroindacene moiety. PMID:27994733

Identification, Synthesis, and Biological Evaluation of the Major Human Metabolite of NLRP3 Inflammasome Inhibitor MCC950.

PubMed

Salla, Manohar; Butler, Mark S; Pelingon, Ruby; Kaeslin, Geraldine; Croker, Daniel E; Reid, Janet C; Baek, Jong Min; Bernhardt, Paul V; Gillam, Elizabeth M J; Cooper, Matthew A; Robertson, Avril A B

2016-12-08

MCC950 is an orally bioavailable small molecule inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that exhibits remarkable activity in multiple models of inflammatory disease. Incubation of MCC950 with human liver microsomes, and subsequent analysis by HPLC-MS/MS, revealed a major metabolite, where hydroxylation of MCC950 had occurred on the 1,2,3,5,6,7-hexahydro- s -indacene moiety. Three possible regioisomers were synthesized, and coelution using HPLC-MS/MS confirmed the structure of the metabolite. Further synthesis of individual enantiomers and coelution studies using a chiral column in HPLC-MS/MS showed the metabolite was R -(+)- N -((1-hydroxy-1,2,3,5,6,7-hexahydro- s -indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide ( 2a ). Incubation of MCC950 with a panel of cytochrome P450 enzymes showed P450s 2A6, 2C9, 2C18, 2C19, 2J2, and 3A4 catalyze the formation of the major metabolite 2a , with a lower level of activity shown by P450s 1A2 and 2B6. All of the synthesized compounds were tested for inhibition of NLRP3-induced production of the pro-inflammatory cytokine IL-1β from human monocyte derived macrophages. The identified metabolite 2a was 170-fold less potent than MCC950, while one regioisomer had nanomolar inhibitory activity. These findings also give first insight into the SAR of the hexahydroindacene moiety.

An approach to a real-time distribution system

NASA Technical Reports Server (NTRS)

Kittle, Frank P., Jr.; Paddock, Eddie J.; Pocklington, Tony; Wang, Lui

1990-01-01

The requirements of a real-time data distribution system are to provide fast, reliable delivery of data from source to destination with little or no impact to the data source. In this particular case, the data sources are inside an operational environment, the Mission Control Center (MCC), and any workstation receiving data directly from the operational computer must conform to the software standards of the MCC. In order to supply data to development workstations outside of the MCC, it is necessary to use gateway computers that prevent unauthorized data transfer back to the operational computers. Many software programs produced on the development workstations are targeted for real-time operation. Therefore, these programs must migrate from the development workstation to the operational workstation. It is yet another requirement for the Data Distribution System to ensure smooth transition of the data interfaces for the application developers. A standard data interface model has already been set up for the operational environment, so the interface between the distribution system and the application software was developed to match that model as closely as possible. The system as a whole therefore allows the rapid development of real-time applications without impacting the data sources. In summary, this approach to a real-time data distribution system provides development users outside of the MCC with an interface to MCC real-time data sources. In addition, the data interface was developed with a flexible and portable software design. This design allows for the smooth transition of new real-time applications to the MCC operational environment.

A Multifeatures Fusion and Discrete Firefly Optimization Method for Prediction of Protein Tyrosine Sulfation Residues.

PubMed

Guo, Song; Liu, Chunhua; Zhou, Peng; Li, Yanling

2016-01-01

Tyrosine sulfation is one of the ubiquitous protein posttranslational modifications, where some sulfate groups are added to the tyrosine residues. It plays significant roles in various physiological processes in eukaryotic cells. To explore the molecular mechanism of tyrosine sulfation, one of the prerequisites is to correctly identify possible protein tyrosine sulfation residues. In this paper, a novel method was presented to predict protein tyrosine sulfation residues from primary sequences. By means of informative feature construction and elaborate feature selection and parameter optimization scheme, the proposed predictor achieved promising results and outperformed many other state-of-the-art predictors. Using the optimal features subset, the proposed method achieved mean MCC of 94.41% on the benchmark dataset, and a MCC of 90.09% on the independent dataset. The experimental performance indicated that our new proposed method could be effective in identifying the important protein posttranslational modifications and the feature selection scheme would be powerful in protein functional residues prediction research fields.

A Multifeatures Fusion and Discrete Firefly Optimization Method for Prediction of Protein Tyrosine Sulfation Residues

PubMed Central

Liu, Chunhua; Zhou, Peng; Li, Yanling

2016-01-01

Tyrosine sulfation is one of the ubiquitous protein posttranslational modifications, where some sulfate groups are added to the tyrosine residues. It plays significant roles in various physiological processes in eukaryotic cells. To explore the molecular mechanism of tyrosine sulfation, one of the prerequisites is to correctly identify possible protein tyrosine sulfation residues. In this paper, a novel method was presented to predict protein tyrosine sulfation residues from primary sequences. By means of informative feature construction and elaborate feature selection and parameter optimization scheme, the proposed predictor achieved promising results and outperformed many other state-of-the-art predictors. Using the optimal features subset, the proposed method achieved mean MCC of 94.41% on the benchmark dataset, and a MCC of 90.09% on the independent dataset. The experimental performance indicated that our new proposed method could be effective in identifying the important protein posttranslational modifications and the feature selection scheme would be powerful in protein functional residues prediction research fields. PMID:27034949

Building carbon–carbon bonds using a biocatalytic methanol condensation cycle

PubMed Central

Bogorad, Igor W.; Chen, Chang-Ting; Theisen, Matthew K.; Wu, Tung-Yun; Schlenz, Alicia R.; Lam, Albert T.; Liao, James C.

2014-01-01

Methanol is an important intermediate in the utilization of natural gas for synthesizing other feedstock chemicals. Typically, chemical approaches for building C–C bonds from methanol require high temperature and pressure. Biological conversion of methanol to longer carbon chain compounds is feasible; however, the natural biological pathways for methanol utilization involve carbon dioxide loss or ATP expenditure. Here we demonstrated a biocatalytic pathway, termed the methanol condensation cycle (MCC), by combining the nonoxidative glycolysis with the ribulose monophosphate pathway to convert methanol to higher-chain alcohols or other acetyl-CoA derivatives using enzymatic reactions in a carbon-conserved and ATP-independent system. We investigated the robustness of MCC and identified operational regions. We confirmed that the pathway forms a catalytic cycle through 13C-carbon labeling. With a cell-free system, we demonstrated the conversion of methanol to ethanol or n-butanol. The high carbon efficiency and low operating temperature are attractive for transforming natural gas-derived methanol to longer-chain liquid fuels and other chemical derivatives. PMID:25355907

Optimization of Nutrients and Culture Conditions for Alkaline Protease Production Using Two Endophytic Micrococci: Micrococcus aloeverae and Micrococcus yunnanensis.

PubMed

Prakash, Om; Nimonkar, Yogesh; Chavadar, Mahesh S; Bharti, Nidhi; Pawar, Shrikant; Sharma, Ashutosh; Shouche, Yogesh S

2017-06-01

An endophytic species of Micrococcus was isolated from Aloe vera leaf (syn. Aloe barbadensis ) and screened for protease production with five other species of Micrococcus . Data indicated that endophytic Micrococcus aloeverae AE-6 MCC 2184 T and Micrococcus yunnanensis DSM 21948 T showed efficient protease production potential and secreted active protease at high salt (10%), temperature (40 °C) and in wide range of pH 8-10. Unlike M . yunnanensis DSM 21948 T , protease production by M . aloeverae AE-6 MCC 2184 T was stringently controlled by pH. Protease induction study using different group of peptides, peptide carbohydrates and peptide macronutrient combinations showed variable response with both the organisms. Result indicated that the amount of protease was not directly related to cell biomass but it depends on nature of inducible peptides. In this study we also developed a modified agar-well assay for semi-quantitative data from large number of replicates.

MCC Coverage during STS-105

NASA Image and Video Library

2005-02-28

JSC2001-E-25411 (17 August 2001) --- Astronaut Joan E. Higginbotham, ISS spacecraft communicator (CAPCOM), inputs data into her computer at her console in the station flight control room (BFCR) in Houston's Mission Control Center (MCC) during the STS-105 mission.

Access to Electronic Personal Health Records Among Patients With Multiple Chronic Conditions: A Secondary Data Analysis

PubMed Central

Falisi, Angela L; Finney Rutten, Lila J; Chou, Wen-Ying Sylvia; Patel, Vaishali; Moser, Richard P; Hesse, Bradford W

2017-01-01

Background In the United States, national incentives for offering access to electronic personal health records (ePHRs) through electronic means are geared toward creating a culture of patient engagement. One group of patients who stand to benefit from online access to ePHRs is the growing population with multiple chronic conditions (MCC). However, little is known about the current availability and use of ePHRs and patient portals among those managing MCC. Objective The aim was to determine the associations between number of chronic conditions and sociodemographic characteristics and usage of ePHRs, and to assess how the public’s use of ePHRs varies across subpopulations, including those with MCC. Methods This study used data collected from the 2014 Health Information National Trends Survey (HINTS), and assessed differences in use of ePHRs between those with and without MCC (N=3497) using multiple logistic regression techniques. Variables associated with health care systems (insurance status, having a regular provider) and patient-reported self-efficacy were included in the statistical models. Results Those with MCC (n=1555) had significantly higher odds of accessing their records three or more times in the past year compared to those reporting no chronic conditions (n=1050; OR 2.46, 95% CI 1.37-4.45), but the overall percentage of those with MCC using ePHRs remained low (371 of 1529 item respondents, 25.63% weighted). No difference in odds of accessing their records was found between those reporting one chronic condition (n=892) and those reporting none (n=1050; OR 1.02, 95% CI 0.66-1.58). Significant differences in odds of accessing ePHRs were seen between income and age groups (P<.001 and P=.05, respectively), and by whether respondents had a regular provider (P=.03). Conclusions We conclude that ePHRs provide a unique opportunity to enhance MCC patient self-management, but additional effort is needed to ensure that these patients are able to access their ePHRs. An increase in availability of patient access to their ePHRs may provide an opportunity to increase patient engagement and support self-management for all patients and especially those with MCC. PMID:28576755

The Essential Role of Radiotherapy in the Treatment of Merkel Cell Carcinoma: A Study From the Rare Cancer Network

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

Ghadjar, Pirus, E-mail: pirus.ghadjar@insel.ch; Kaanders, Johannes H.; Poortmans, Philipp

2011-11-15

Purpose: To evaluate the role of postoperative radiotherapy (RT) in Merkel cell carcinoma (MCC). Methods and Materials: A retrospective multicenter study was performed in 180 patients with MCC treated between February 1988 and September 2009. Patients who had had surgery alone were compared with patients who received surgery and postoperative RT or radical RT. Local relapse-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) rates were assessed together with disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates. Results: Seventy-nine patients were male and 101 patients were female, and the median age was 73 yearsmore » old (range, 38-93 years). The majority of patients had localized disease (n = 146), and the remaining patients had regional lymph node metastasis (n = 34). Forty-nine patients underwent surgery for the primary tumor without postoperative RT to the primary site; the other 131 patients received surgery for the primary tumor, followed by postoperative RT (n = 118) or a biopsy of the primary tumor followed by radical RT (n = 13). Median follow-up was 5 years (range, 0.2-16.5 years). Patients in the RT group had improved LRFS (93% vs. 64%; p < 0.001), RRFS (76% vs. 27%; p < 0.001), DMFS (70% vs. 42%; p = 0.01), DFS (59% vs. 4%; p < 0.001), and CSS (65% vs. 49%; p = 0.03) rates compared to patients who underwent surgery for the primary tumor alone; LRFS, RRFS, DMFS, and DFS rates remained significant with multivariable Cox regression analysis. However OS was not significantly improved by postoperative RT (56% vs. 46%; p = 0.2). Conclusions: After multivariable analysis, postoperative RT was associated with improved outcome and seems to be an important component in the multimodality treatment of MCC.« less

A PIC-MCC code RFdinity1d for simulation of discharge initiation by ICRF antenna

NASA Astrophysics Data System (ADS)

Tripský, M.; Wauters, T.; Lyssoivan, A.; Bobkov, V.; Schneider, P. A.; Stepanov, I.; Douai, D.; Van Eester, D.; Noterdaeme, J.-M.; Van Schoor, M.; ASDEX Upgrade Team; EUROfusion MST1 Team

2017-12-01

Discharges produced and sustained by ion cyclotron range of frequency (ICRF) waves in absence of plasma current will be used on ITER for (ion cyclotron-) wall conditioning (ICWC, Te = 3{-}5 eV, ne < 1018 m-3 ). In this paper, we present the 1D particle-in-cell Monte Carlo collision (PIC-MCC) RFdinity1d for the study the breakdown phase of ICRF discharges, and its dependency on the RF discharge parameters (i) antenna input power P i , (ii) RF frequency f, (iii) shape of the electric field and (iv) the neutral gas pressure pH_2 . The code traces the motion of both electrons and ions in a narrow bundle of magnetic field lines close to the antenna straps. The charged particles are accelerated in the parallel direction with respect to the magnetic field B T by two electric fields: (i) the vacuum RF field of the ICRF antenna E_z^RF and (ii) the electrostatic field E_zP determined by the solution of Poisson’s equation. The electron density evolution in simulations follows exponential increase, {\\dot{n_e} ∼ ν_ion t } . The ionization rate varies with increasing electron density as different mechanisms become important. The charged particles are affected solely by the antenna RF field E_z^RF at low electron density ({ne < 1011} m-3 , {≤ft \\vert E_z^RF \\right \\vert \\gg ≤ft \\vert E_zP \\right \\vert } ). At higher densities, when the electrostatic field E_zP is comparable to the antenna RF field E_z^RF , the ionization frequency reaches the maximum. Plasma oscillations propagating toroidally away from the antenna are observed. The simulated energy distributions of ions and electrons at {ne ∼ 1015} m-3 correspond a power-law Kappa energy distribution. This energy distribution was also observed in NPA measurements at ASDEX Upgrade in ICWC experiments.

Skin decontamination with mineral cationic carrier against sarin determined in vivo.

PubMed

Vucemilović, Ante; Hadzija, Mirko; Jukić, Ivan

2009-06-01

Our Institute's nuclear, biological, and chemical defense research team continuously investigates and develops preparations for skin decontamination against nerve agents. In this in vivo study, we evaluated skin decontamination efficacy against sarin by a synthetic preparation called Mineral Cationic Carrier (MCC) with known ion exchange, absorption efficacy and bioactive potential. Mice were treated with increasing doses of sarin applied on their skin, and MCC was administered immediately after contamination. The results showed that decontamination with MCC could achieve therapeutic efficacy corresponding to 3 x LD(50) of percutaneous sarin and call for further research.

Multiple Chronic Conditions Among US Adults: A 2012 Update

PubMed Central

Schiller, Jeannine S.; Goodman, Richard A.

2014-01-01

The objective of this research was to update earlier estimates of prevalence rates of single chronic conditions and multiple (>2) chronic conditions (MCC) among the noninstitutionalized, civilian US adult population. Data from the 2012 National Health Interview Survey (NHIS) were used to generate estimates of MCC for US adults and by select demographic characteristics. Approximately half (117 million) of US adults have at least one of the 10 chronic conditions examined (ie, hypertension, coronary heart disease, stroke, diabetes, cancer, arthritis, hepatitis, weak or failing kidneys, current asthma, or chronic obstructive pulmonary disease [COPD]). Furthermore, 1 in 4 adults has MCC. PMID:24742395

Biosynthetic Tailoring of Microcin E492m: Post-Translational Modification Affords an Antibacterial Siderophore-Peptide Conjugate

PubMed Central

Nolan, Elizabeth M.; Fischbach, Michael A.; Koglin, Alexander; Walsh, Christopher T.

2008-01-01

The present work reveals that four proteins, MceCDIJ, encoded by the MccE492 gene cluster are responsible for the remarkable post-translational tailoring of Microcin E492 (MccE492), an 84-residue protein toxin secreted by Klebsiella pneumonaie RYC492 that targets neighboring gram-negative species. This modification results in attachment of a linearized and monoglycosylated derivative of enterobactin, a nonribosomal peptide and iron scavenger (siderophore), to the MccE492m C-terminus. MceC and MceD derivatize enterobactin by C-glycosylation at the C5 position of a N-(2,3-dihydroxybenzoyl) serine (DHB-Ser) moiety and regiospecific hydrolysis of an ester linkage in the trilactone scaffold, respectively. MceI and MceJ form a protein complex that attaches C-glycosylated enterobactins to the C-terminal serine residue of both aC10 model peptide and full-length MccE492. In the enzymatic product, the terminal serine residue is covalently attached to the C4′ oxygen of the glucose moiety. Non-enzymatic and base-catalyzed migration of the peptide to the C6′ position affords the C6′ glycosyl ester linkage observed in the mature toxin, MccE492m, isolated from bacterial cultures. PMID:17973380

Biosynthetic tailoring of microcin E492m: post-translational modification affords an antibacterial siderophore-peptide conjugate.

PubMed

Nolan, Elizabeth M; Fischbach, Michael A; Koglin, Alexander; Walsh, Christopher T

2007-11-21

The present work reveals that four proteins, MceCDIJ, encoded by the MccE492 gene cluster are responsible for the remarkable post-translational tailoring of microcin E492 (MccE492), an 84-residue protein toxin secreted by Klebsiella pneumonaie RYC492 that targets neighboring Gram-negative species. This modification results in attachment of a linearized and monoglycosylated derivative of enterobactin, a nonribosomal peptide and iron scavenger (siderophore), to the MccE492m C-terminus. MceC and MceD derivatize enterobactin by C-glycosylation at the C5 position of a N-(2,3-dihydroxybenzoyl)serine (DHB-Ser) moiety and regiospecific hydrolysis of an ester linkage in the trilactone scaffold, respectively. MceI and MceJ form a protein complex that attaches C-glycosylated enterobactins to the C-terminal serine residue of both a C10 model peptide and full-length MccE492. In the enzymatic product, the C-terminal serine residue is covalently attached to the C4' oxygen of the glucose moiety. Nonenzymatic and base-catalyzed migration of the peptide to the C6' position affords the C6' glycosyl ester linkage observed in the mature toxin, MccE492m, isolated from bacterial cultures.

Overcoming intratumoural heterogeneity for reproducible molecular risk stratification: a case study in advanced kidney cancer.

PubMed

Lubbock, Alexander L R; Stewart, Grant D; O'Mahony, Fiach C; Laird, Alexander; Mullen, Peter; O'Donnell, Marie; Powles, Thomas; Harrison, David J; Overton, Ian M

2017-06-26

Metastatic clear cell renal cell cancer (mccRCC) portends a poor prognosis and urgently requires better clinical tools for prognostication as well as for prediction of response to treatment. Considerable investment in molecular risk stratification has sought to overcome the performance ceiling encountered by methods restricted to traditional clinical parameters. However, replication of results has proven challenging, and intratumoural heterogeneity (ITH) may confound attempts at tissue-based stratification. We investigated the influence of confounding ITH on the performance of a novel molecular prognostic model, enabled by pathologist-guided multiregion sampling (n = 183) of geographically separated mccRCC cohorts from the SuMR trial (development, n = 22) and the SCOTRRCC study (validation, n = 22). Tumour protein levels quantified by reverse phase protein array (RPPA) were investigated alongside clinical variables. Regularised wrapper selection identified features for Cox multivariate analysis with overall survival as the primary endpoint. The optimal subset of variables in the final stratification model consisted of N-cadherin, EPCAM, Age, mTOR (NEAT). Risk groups from NEAT had a markedly different prognosis in the validation cohort (log-rank p = 7.62 × 10 -7 ; hazard ratio (HR) 37.9, 95% confidence interval 4.1-353.8) and 2-year survival rates (accuracy = 82%, Matthews correlation coefficient = 0.62). Comparisons with established clinico-pathological scores suggest favourable performance for NEAT (Net reclassification improvement 7.1% vs International Metastatic Database Consortium score, 25.4% vs Memorial Sloan Kettering Cancer Center score). Limitations include the relatively small cohorts and associated wide confidence intervals on predictive performance. Our multiregion sampling approach enabled investigation of NEAT validation when limiting the number of samples analysed per tumour, which significantly degraded performance. Indeed, sample selection could change risk group assignment for 64% of patients, and prognostication with one sample per patient performed only slightly better than random expectation (median logHR = 0.109). Low grade tissue was associated with 3.5-fold greater variation in predicted risk than high grade (p = 0.044). This case study in mccRCC quantitatively demonstrates the critical importance of tumour sampling for the success of molecular biomarker studies research where ITH is a factor. The NEAT model shows promise for mccRCC prognostication and warrants follow-up in larger cohorts. Our work evidences actionable parameters to guide sample collection (tumour coverage, size, grade) to inform the development of reproducible molecular risk stratification methods.

Sentinel Lymph Node Biopsy in Nonmelanoma Skin Cancer Patients

PubMed Central

Matthey-Giè, Marie-Laure; Boubaker, Ariane; Letovanec, Igor; Demartines, Nicolas; Matter, Maurice

2013-01-01

The management of lymph nodes in nonmelanoma skin cancer patients is currently still debated. Merkel cell carcinoma (MCC), squamous cell carcinoma (SCC), pigmented epithelioid melanocytoma (PEM), and other rare skin neoplasms have a well-known risk to spread to regional lymph nodes. The use of sentinel lymph node biopsy (SLNB) could be a promising procedure to assess this risk in clinically N0 patients. Metastatic SNs have been observed in 4.5–28% SCC (according to risk factors), in 9–42% MCC, and in 14–57% PEM. We observed overall 30.8% positive SNs in 13 consecutive patients operated for high-risk nonmelanoma skin cancer between 2002 and 2011 in our institution. These high rates support recommendation to implement SLNB for nonmelanoma skin cancer especially for SCC patients. Completion lymph node dissection following positive SNs is also a matter of discussion especially in PEM. It must be remembered that a definitive survival benefit of SLNB in melanoma patients has not been proven yet. However, because of its low morbidity when compared to empiric elective lymph node dissection or radiation therapy of lymphatic basins, SLNB has allowed sparing a lot of morbidity and could therefore be used in nonmelanoma skin cancer patients, even though a significant impact on survival has not been demonstrated. PMID:23476781

Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway.

PubMed

Wu, Dacheng; Wu, Keyan; Zhu, Qingtian; Xiao, Weiming; Shan, Qing; Yan, Zhigang; Wu, Jian; Deng, Bin; Xue, Yan; Gong, Weijuan; Lu, Guotao; Ding, Yanbing

2018-01-01

Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF- α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1 β ) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.

Magnetic versus manual catheter navigation for mapping and ablation of right ventricular outflow tract ventricular arrhythmias: a randomized controlled study.

PubMed

Zhang, Fengxiang; Yang, Bing; Chen, Hongwu; Ju, Weizhu; Kojodjojo, Pipin; Cao, Kejiang; Chen, Minglong

2013-08-01

No randomized controlled study has prospectively compared the performance and clinical outcomes of remote magnetic control (RMC) vs manual catheter control (MCC) during ablation of right ventricular outflow tract (RVOT) ventricular premature complexes (VPC) or ventricular tachycardia (VT). The purpose of this study was to prospectively evaluate the efficacy and safety of using either RMC vs MCC for mapping and ablation of RVOT VPC/VT. Thirty consecutive patients with idiopathic RVOT VPC/VT were referred for catheter ablation and randomized into either the RMC or MCC group. A noncontact mapping system was deployed in the RVOT to identify origins of VPC/VT. Conventional activation and pace-mapping was performed to guide ablation. If ablation performed using 1 mode of catheter control was acutely unsuccessful, the patient crossed over to the other group. The primary endpoints were patients' and physicians' fluoroscopic exposure and times. Mean procedural times were similar between RMC and MCC groups. The fluoroscopic exposure and times for both patients and physicians were much lower in the RMC group than in the MCC group. Ablation was acutely successful in 14 of 15 patients in the MCC group and 10 of 15 in the RMC group. Following crossover, acute success was achieved in all patients. No major complications occurred in either group. During 22 months of follow-up, RVOT VPC recurred in 2 RMC patients. RMC navigation significantly reduces patients' and physicians' fluoroscopic times by 50.5% and 68.6%, respectively, when used in conjunction with a noncontact mapping system to guide ablation of RVOT VPC/VT. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Signal presequences increase mitochondrial permeability and open the multiple conductance channel.

PubMed

Kushnareva, Y E; Campo, M L; Kinnally, K W; Sokolove, P M

1999-06-01

We have reported that the signal presequence of cytochrome oxidase subunit IV from Neurospora crassa increases the permeability of isolated rat liver mitochondria [P. M. Sokolove and K. W. Kinnally (1996) Arch. Biochem. Biophys. 336, 69] and regulates the behavior of the mutiple conductance channel (MCC) of yeast inner mitochondrial membrane [T. A. Lohret and K. W. Kinnally (1995) J. Biol. Chem. 270, 15950]. Here we examine in greater detail the action of a number of mitochondrial presequences from various sources and of several control peptides on the permeability of isolated rat liver mitochondria and on MCC activity monitored via patch-clamp techniques in both mammalian mitoplasts and a reconstituted yeast system. The data indicate that the ability to alter mitochondrial permeability is a property of most, but not all, signal peptides. Furthermore, it is clear that, although signal peptides are characterized by positive charge and the ability to form amphiphilic alpha helices, these two characteristics are not sufficient to guarantee mitochondrial effects. Finally, the results reveal a strong correlation between peptide effects on the permeability of isolated mitochondria and on MCC activity: peptides that induced swelling of mouse and rat mitochondria also activated the quiescent MCC of mouse mitoplasts and induced flickering of active MCC reconstituted from yeast mitochondrial membranes. Moreover, relative peptide efficacies were very similar for mitochondrial swelling and both types of patch-clamp experiments. We propose that patch-clamp recordings of MCC activity and the high-amplitude swelling induced by signal peptides reflect the opening of a single channel. Based on the selective responsiveness of that channel to signal peptides and the dependence of its opening in isolated mitochondria on membrane potential, we further suggest that the channel is involved in the mitochondrial protein import process. Copyright 1999 Academic Press.

Managing Cancer Care: a psycho-educational intervention to improve knowledge of care options and breast cancer self-management.

PubMed

Schulman-Green, Dena; Jeon, Sangchoon

2017-02-01

We tested the feasibility and acceptability of a psycho-educational self-management intervention, Managing Cancer Care: A Personal Guide (MCC), to improve knowledge of care options (curative, palliative, and hospice care) among a range of breast cancer self-management skills. We conducted a one-group, pre-post-test study among women with non-metastatic breast cancer (n = 105). We gave participants the printed, self-guided, seven-module intervention following enrollment. At baseline and 2  months, we measured knowledge of care options, desired and actual role in self-management, medical communication skills, experience and management of transitions, anxiety, depression, uncertainty, and self-efficacy. We conducted interviews to obtain module ratings and qualitative data on strengths and limitations of MCC. Knowledge of care options (δ = 0.40 (1.11), p = 0.0005) and desired role in self-management (δ = -0.28 (1.08), p = 0.0177) significantly improved. Less skilled medical communicators significantly improved their communication (δ = 3.47, standard deviation = 6.58, p = 0.0449). Multivariate modeling showed that changes in our primary outcomes of medical communication and management of transitions seemed to drive positive changes in our secondary outcomes of anxiety, depression, uncertainty, and self-efficacy. Participants highly rated MCC and reported the importance of understanding care options despite non-metastatic disease. MCC is a feasible and acceptable means of improving knowledge of care options and other aspects of breast cancer self-management. The combination of modules offered in MCC appears to have beneficial interactive effects. We are currently testing MCC more rigorously in a randomized controlled trial to explore mediating and moderating relationships. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Hadoop-MCC: Efficient Multiple Compound Comparison Algorithm Using Hadoop.

PubMed

Hua, Guan-Jie; Hung, Che-Lun; Tang, Chuan Yi

2018-01-01

In the past decade, the drug design technologies have been improved enormously. The computer-aided drug design (CADD) has played an important role in analysis and prediction in drug development, which makes the procedure more economical and efficient. However, computation with big data, such as ZINC containing more than 60 million compounds data and GDB-13 with more than 930 million small molecules, is a noticeable issue of time-consuming problem. Therefore, we propose a novel heterogeneous high performance computing method, named as Hadoop-MCC, integrating Hadoop and GPU, to copy with big chemical structure data efficiently. Hadoop-MCC gains the high availability and fault tolerance from Hadoop, as Hadoop is used to scatter input data to GPU devices and gather the results from GPU devices. Hadoop framework adopts mapper/reducer computation model. In the proposed method, mappers response for fetching SMILES data segments and perform LINGO method on GPU, then reducers collect all comparison results produced by mappers. Due to the high availability of Hadoop, all of LINGO computational jobs on mappers can be completed, even if some of the mappers encounter problems. A comparison of LINGO is performed on each the GPU device in parallel. According to the experimental results, the proposed method on multiple GPU devices can achieve better computational performance than the CUDA-MCC on a single GPU device. Hadoop-MCC is able to achieve scalability, high availability, and fault tolerance granted by Hadoop, and high performance as well by integrating computational power of both of Hadoop and GPU. It has been shown that using the heterogeneous architecture as Hadoop-MCC effectively can enhance better computational performance than on a single GPU device. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

MISSION CONTROL CENTER (MCC) - CELEBRATION - CONCLUSION - APOLLO 11 MISSION - MSC

NASA Image and Video Library

1969-07-25

S69-40023 (24 July 1969) --- Overall view of the Mission Operations Control Room (MOCR) in the Mission Control Center (MCC), Building 30, Manned Spacecraft Center (MSC), showing the flight controllers celebrating the successful conclusion of the Apollo 11 lunar landing mission.

Macomb Community College Recruitment Plan, 1987-1988.

ERIC Educational Resources Information Center

Macomb County Community Coll., Warren, MI.

Michigan's Macomb Community College's (MCC's) student recruitment plan outlines specific activities, timelines, and budgets to meet the institution's goals for college advancement and the instructional divisions' and service departments' goals and objectives for student recruitment. Section I offers a summary of MCC's market segmentation approach…

An Orientation & Leadership Training Handbook for International Students.

ERIC Educational Resources Information Center

Hansen, M. Eileen

This handbook provides guidance for implementing orientation activities for international students at Middlesex County College (MCC), in New Jersey. An introduction describes the development of MCC's orientation plan, indicating that, in response to problems faced by international students, the college developed an overnight orientation and…

The Relationship between Counselors' Multicultural Counseling Competence and Poverty Beliefs

ERIC Educational Resources Information Center

Clark, Madeline; Moe, Jeff; Hays, Danica G.

2017-01-01

The authors explored the relationship between counselors' multicultural counseling competence (MCC), poverty beliefs, and select demographic factors. Results of hierarchical linear regressions indicate that MCC is predictive of counselor individualistic and structural poverty beliefs. Implications for counselor multicultural training and immersion…

Preparation of nanocellulose from micro-crystalline cellulose: The effect on the performance and properties of agar-based composite films.

PubMed

Shankar, Shiv; Rhim, Jong-Whan

2016-01-01

A facile approach has been performed to prepare nanocellulose (NC) from micro-crystalline cellulose (MCC) and test their effect on the performance properties of agar-based composite films. The NC was characterized by STEM, XRD, FTIR, and TGA. The NC was well dispersed in distilled water after sonication and their size was in the range of 100-500nm. The XRD results revealed the crystallinity of NC. The crystallinity index of NC (0.71) was decreased compared to the MCC (0.81). The effect of NC or MCC content (1, 3, 5 and 10wt% based on agar) on the mechanical, water vapor permeability (WVP), and thermal properties of the composites were studied. The NC obtained from MCC can be used as a reinforcing agent for the preparation of biodegradable composites films for their potential use in the development of biodegradable food packaging materials. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acute and chronic in vivo effects of exposure to nicotine and propylene glycol from an E-cigarette on mucociliary clearance in a murine model.

PubMed

Laube, Beth L; Afshar-Mohajer, Nima; Koehler, Kirsten; Chen, Gang; Lazarus, Philip; Collaco, Joseph M; McGrath-Morrow, Sharon A

2017-04-01

To determine the effect of an acute (1 week) and chronic (3 weeks) exposure to E-cigarette (E-cig) emissions on mucociliary clearance (MCC) in murine lungs. C57BL/6 male mice (age 10.5 ± 2.4 weeks) were exposed for 20 min/day to E-cigarette aerosol generated by a Joyetech 510-T ® E-cig containing either 0% nicotine (N)/propylene glycol (PG) for 1 week (n = 6), or 3 weeks (n = 9), or 2.4% N/PG for one week (n = 6), or 3 weeks (n = 9), followed by measurement of MCC. Control mice (n = 15) were not exposed to PG alone, or N/PG. MCC was assessed by gamma camera following aspiration of 99m technetium aerosol and was expressed as the amount of radioactivity removed from both lungs over 6 hours (MCC6hrs). Venous blood was assayed for cotinine levels in control mice and in mice exposed for 3-weeks to PG alone and N/PG. MCC6hrs in control mice and in mice acutely exposed to PG alone and N/PG was similar, averaging (±1 standard deviation) 8.6 ± 5.2%, 7.5 ± 2.8% and 11.2 ± 5.9%, respectively. In contrast, chronic exposure to PG alone stimulated MCC6hrs (17.2 ± 8.0)% and this stimulation was significantly blunted following chronic exposure to N/PG (8.7 ± 4.6)% (p < .05). Serum cotinine levels were <0.5 ng/ml in control mice and in mice exposed to PG alone, whereas, N/PG exposed mice averaged 14.6 ± 12.0 ng/ml. In this murine model, a chronic, daily, 20 min-exposure to N/PG, but not an acute exposure, slowed MCC, compared to exposure to PG alone and led to systemic absorption of nicotine.

STS-102 Launch Activities inside the MCC.

NASA Image and Video Library

2001-03-08

JSC2001-E-06216 (8 March 2001) --- In Houston's Mission Control Center (MCC), the silhouette of astronaut Steven A. Hawley of the Flight Crew Operations Directorate appears just to the right of the monitor displaying the Space Shuttle Discovery's pre-launch activities several hundred miles away in Florida.

Multicultural Counseling Competencies, 2003: Association for Multicultural Counseling and Development.

ERIC Educational Resources Information Center

Roysircar, Gargi; Arredondo, Patricia; Fuertes, Jairo N.; Ponterotto, Joseph G.; Toporek, Rebecca L.

This book updates earlier Association for Multicultural Counseling and Development (AMCD) multicultural counseling competencies (MCC). Each chapter author particularizes definitions and/or conceptualizations of multicultural competencies to the topic of his or her chapter. The present document operationalizes the MCC into practice examples,…

Perceived Multicultural Counseling Competence of Malaysian Counselors: An Exploratory Study

ERIC Educational Resources Information Center

Aga Mohd Jaladin, Rafidah

2017-01-01

This study investigated the nature and extent of perceived multicultural counseling competence (MCC) of 508 professional counselors in Malaysia using a national survey approach. Differences in counselors' perceived MCC pertaining to gender, ethnicity, highest education, and multicultural training were examined. Results revealed 5 factors as…

Muskegon Community College Long-Range Plan.

ERIC Educational Resources Information Center

Turner, Peter M.; And Others

Long-range planning assumptions and goals are presented for Muskegon Community College (MCC) as they were submitted by a committee of area citizens. After introductory material summarizing the committee's mandate and activities, the report discusses the fiscal, demographic, curricular, and administrative changes likely to affect MCC during the…

Stress and brain functional changes in patients with Crohn's disease: A functional magnetic resonance imaging study.

PubMed

Agostini, A; Ballotta, D; Righi, S; Moretti, M; Bertani, A; Scarcelli, A; Sartini, A; Ercolani, M; Nichelli, P; Campieri, M; Benuzzi, F

2017-10-01

In Crohn's disease (CD) patients, stress is believed to influence symptoms generation. Stress may act via central nervous system pathways to affect visceral sensitivity and motility thus exacerbating gastrointestinal symptoms. The neural substrate underpinning these mechanisms needs to be investigated in CD. We conducted an explorative functional magnetic resonance imaging (fMRI) study in order to investigate potential differences in the brain stress response in CD patients compared to controls. 17 CD patients and 17 healthy controls underwent a fMRI scan while performing a stressful task consisting in a Stroop color-word interference task designed to induce mental stress in the fMRI environment. Compared to controls, in CD patients the stress task elicited greater blood oxygen level dependent (BOLD) signals in the midcingulate cortex (MCC). The MCC integrate "high" emotional processes with afferent sensory information ascending from the gut. In light of these integrative functions, the stress-evoked MCC hyperactivity in CD patients might represent a plausible neural substrate for the association between stress and symptomatic disease. The MCC dysfunction might be involved in mechanisms of central disinhibition of nociceptive inputs leading to amplify the visceral sensitivity. Finally, the stress-evoked MCC hyperactivity might affect the regulation of intestinal motility resulting in exacerbation of disease symptoms and the autonomic and neuroendocrine regulation of inflammation resulting in enhanced inflammatory activity. © 2017 John Wiley & Sons Ltd.

Designing a mixture experiment when the components are subject to a nonlinear multiple-component constraint

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

Piepel, Greg F.; Cooley, Scott K.; Vienna, John D.

This article presents a case study of developing an experimental design for a constrained mixture experiment when the experimental region is defined by single-component constraints (SCCs), linear multiple-component constraints (MCCs), and a nonlinear MCC. Traditional methods and software for designing constrained mixture experiments with SCCs and linear MCCs are not directly applicable because of the nonlinear MCC. A modification of existing methodology to account for the nonlinear MCC was developed and is described in this article. The case study involves a 15-component nuclear waste glass example in which SO3 is one of the components. SO3 has a solubility limit inmore » glass that depends on the composition of the balance of the glass. A goal was to design the experiment so that SO3 would not exceed its predicted solubility limit for any of the experimental glasses. The SO3 solubility limit had previously been modeled by a partial quadratic mixture (PQM) model expressed in the relative proportions of the 14 other components. The PQM model was used to construct a nonlinear MCC in terms of all 15 components. In addition, there were SCCs and linear MCCs. This article discusses the waste glass example and how a layered design was generated to (i) account for the SCCs, linear MCCs, and nonlinear MCC and (ii) meet the goals of the study.« less

A conceptual model of the role of complexity in the care of patients with multiple chronic conditions.

PubMed

Grembowski, David; Schaefer, Judith; Johnson, Karin E; Fischer, Henry; Moore, Susan L; Tai-Seale, Ming; Ricciardi, Richard; Fraser, James R; Miller, Donald; LeRoy, Lisa

2014-03-01

Effective healthcare for people with multiple chronic conditions (MCC) is a US priority, but the inherent complexity makes both research and delivery of care particularly challenging. As part of AHRQ Multiple Chronic Conditions Research Network (MCCRN) efforts, the Network developed a conceptual model to guide research in this area. To synthesize methodological and topical issues relevant to MCC patient care into a framework that can improve the delivery of care and advance future research about caring for patients with MCC. The Network synthesized essential constructs for MCC research identified from roundtable discussion, input from expert advisors, and previously published models. The AHRQ MCCRN conceptual model defines complexity as the gap between patient needs and healthcare services, taking into account both the multiple considerations that affect the needs of MCC patients, as well as the contextual factors that influence service delivery. The model reframes processes and outcomes to include not only clinical care quality and experience, but also patient health, well being, and quality of life. The single-condition paradigm for treating needs one-by-one falls apart and highlights the need for care systems to address dynamic patient needs. Defining complexity in terms of the misalignment between patient needs and services offers new insights in how to research and develop solutions to patient care needs.

Improvement of lipid content of Chlorella minutissima MCC 5 for biodiesel production.

PubMed

Chakraborty, Sourabh; Mohanty, Debabrata; Ghosh, Supratim; Das, Debabrata

2016-09-01

Lipids extracted from microalgae have been considered as a potential source for the production of biodiesel. Enhancement of lipid has the limitations of low biomass productivity. So, the main objective of the present study was to deduce suitable conditions for the improvement of biomass production followed by enhancement of lipid content. After optimization, a strategy for two stage cultivation was utilized where high lipid content was obtained with a high biomass concentration. Optimization of biomass production of Chlorella minutissima MCC 5 was carried out under different intensities of light, temperatures, concentrations of nitrate and phosphate using Taguchi model. A suitable synergy of the four parameters yielded maximum biomass (1.93 g L(-1)) in airlift reactor. Temperature was found to be relatively effective than other parameters for higher biomass production. Activation energy for the cell growth was determined (47.95 kJ mol(-1)). Among the various (photo, thermal, nitrate and phosphate) stress conditions studied, nitrate limitation (1 mM) was found to be suitable for the enhancement of lipid resulting highest yield (48.26% w/w). Two stage cultivation of the microalgae yielded a maximum lipid content of 46% w/w with a biomass concentration of 2.2 g L(-1). Additionally, FAME analysis exhibited significant increase of oleic acid in the biodiesel. So, C. minutissima MCC 5 cultivated under nitrate stress could be a possible feedstock for biodiesel production. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

View of Mission Control Center during the Apollo 13 oxygen cell failure

NASA Image and Video Library

1970-04-14

S70-34904 (14 April 1970) --- Astronaut Alan B. Shepard Jr., prime crew commander of the Apollo 14 mission, monitors communications between the Apollo 13 spacecraft and Mission Control Center. He is seated at a console in the Mission Operations Control Room of the MCC, Manned Spacecraft Center. The main concern of the moment was action taken by the three Apollo 13 crewmen - astronauts James A. Lovell Jr., John L. Swigert Jr. and Fred W. Haise Jr. - to make corrections inside the spacecraft following discovery of an oxygen cell failure several hours earlier.

22 CFR 1304.3 - Records available to the public.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the information requested is already available on its Web site, which contains information readily... writing, to advise the individual of the availability of the information on the public Web site. MCC... after November 1, 1996 shall be made available electronically via the Web site at http://www.mcc.gov. (2...

22 CFR 1304.3 - Records available to the public.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the information requested is already available on its Web site, which contains information readily... writing, to advise the individual of the availability of the information on the public Web site. MCC... after November 1, 1996 shall be made available electronically via the Web site at http://www.mcc.gov. (2...

AFRC2017-0076-1

NASA Image and Video Library

2017-04-04

NASA Armstrong’s Mission Control Center, or MCC, is where culmination of all data-gathering occurs. Engineers, flight controllers and researchers monitor flights and missions as they are carried out. Data and video run through the MCC and are recorded, displayed and archived. Data is then processed and prepared for post-flight analysis.

Environmental Scan: A Strategic Planning Document.

ERIC Educational Resources Information Center

Osborn, Frances

Information, perceptions, and predictions from a variety of sources are brought together in this document to help guide planning and decision making at Monroe Community College (MCC). The first section examines national events and trends with implications for the future of MCC, including employment projections; educational norms; data on community…

126. MOTOR CONTROL CENTER 1 (MCC1), FACING NORTH IN ROW ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

126. MOTOR CONTROL CENTER 1 (MCC-1), FACING NORTH IN ROW OF ELECTRICAL CABINETS JUST SOUTH OF TRANSFORMER SUBSTATION CABINETS IN TRANSFORMER ROOM (112), LSB (BLDG. 770) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Wide angle view of the Flight control room of Mission control center

NASA Image and Video Library

1984-10-06

Wide angle view of the flight control room (FCR) of the Mission Control Center (MCC). Some of the STS 41-G crew can be seen on a large screen at the front of the MCC along with a map tracking the progress of the orbiter.

Merkel Cell Polyomavirus Infection of Animal Dermal Fibroblasts.

PubMed

Liu, Wei; Krump, Nathan A; MacDonald, Margo; You, Jianxin

2018-02-15

Merkel cell polyomavirus (MCPyV) is the first polyomavirus to be associated with human cancer. Mechanistic studies attempting to fully elucidate MCPyV's oncogenic mechanisms have been hampered by the lack of animal models for MCPyV infection. In this study, we examined the ability of MCPyV-GFP pseudovirus (containing a green fluorescent protein [GFP] reporter construct), MCPyV recombinant virions, and several MCPyV chimeric viruses to infect dermal fibroblasts isolated from various model animals, including mouse ( Mus musculus ), rabbit ( Oryctolagus cuniculus ), rat ( Rattus norvegicus ), chimpanzee ( Pan troglodytes ), rhesus macaque ( Macaca mulatta ), patas monkey ( Erythrocebus patas ), common woolly monkey ( Lagothrix lagotricha ), red-chested mustached tamarin ( Saguinus labiatus ), and tree shrew ( Tupaia belangeri ). We found that MCPyV-GFP pseudovirus was able to enter the dermal fibroblasts of all species tested. Chimpanzee dermal fibroblasts were the only type that supported vigorous MCPyV gene expression and viral replication, and they did so to a level beyond that of human dermal fibroblasts. We further demonstrated that both human and chimpanzee dermal fibroblasts produce infectious MCPyV virions that can successfully infect new cells. In addition, rat dermal fibroblasts supported robust MCPyV large T antigen expression after infection with an MCPyV chimeric virus in which the entire enhancer region of the MCPyV early promoter has been replaced with the simian virus 40 (SV40) analog. Our results suggest that viral transcription and/or replication events represent the major hurdle for MCPyV cross-species transmission. The capacity of rat dermal fibroblasts to support MCPyV early gene expression suggests that the rat is a candidate model organism for studying viral oncogene function during Merkel cell carcinoma (MCC) oncogenic progression. IMPORTANCE MCPyV plays an important role in the development of a highly aggressive form of skin cancer, Merkel cell carcinoma (MCC). With the increasing number of MCC diagnoses, there is a need to better understand the virus and its oncogenic potential. However, studies attempting to fully elucidate MCPyV's oncogenic mechanisms have been hampered by the lack of animal models for MCPyV infection. To pinpoint the best candidate for developing an MCPyV infection animal model, we examined MCPyV's ability to infect dermal fibroblasts isolated from various established model animals. Of the animal cell types we tested, chimpanzee dermal fibroblasts were the only isolates that supported the full MCPyV infectious cycle. To overcome the infection blockade in the other model animals, we constructed chimeric viruses that achieved robust MCPyV entry and oncogene expression in rat fibroblasts. Our results suggest that the rat may serve as an in vivo model to study MCV oncogenesis. Copyright © 2018 American Society for Microbiology.

Development of a Convergent Spray Technologies(tm) Spray Process for a Solventless Sprayable Coating, MCC-1

NASA Technical Reports Server (NTRS)

Patel, Anil K.; Meeks, C.

1998-01-01

This paper discusses the application of Convergent Spray Technologies (TM) Spray Process to the development and successful implementation of Marshall Convergent Coating (MCC-1) as a primary Thermal Protection System (TPS) for the Space Shuttle Solid Rocket Boosters (SRBs). This paper discusses the environmental and process benefits of the MCC-1 technology, shows the systematic steps taken in developing the technology, including statistical sensitivity studies of about 35 variables. Based on the process and post-flight successes on the SRB, it will be seen that the technology is "field-proven". Application of this technology to other aerospace and commercial programs is summarized to illustrate the wide range of possibilities.

View - Mission Control Center (MCC) - Lunar Surface - Apollo XI Extravehicular Activity (EVA) - MSC

NASA Image and Video Library

1969-07-20

S69-39815 (20 July 1969) --- Interior view of the Mission Operations Control Room (MOCR) in the Mission Control Center (MCC) during the Apollo 11 lunar extravehicular activity (EVA). The television monitor shows astronauts Neil A. Armstrong and Edwin E. Aldrin Jr. on the surface of the moon.

S65-62938

NASA Image and Video Library

1965-12-16

S65-62938 (16 Dec. 1965) --- John D. Hodge (foreground), Christopher C. Kraft Jr. (center) and Eugene F. Kranz discuss recovery operations for the Gemini-6 spacecraft in the Mission Control Center (MCC) at the Manned Spacecraft Center (MSC) in Houston, Texas. The event was monitored via live television in MCC. Photo credit: NASA or National Aeronautics and Space Administration

Testimony. Subcommittee on Elementary, Secondary & Vocational Education.

ERIC Educational Resources Information Center

Lynch, Edward J.

The largest public community college in Michigan, Macomb Community College (MCC), is located in the county that is most closely tied to Michigan's automobile industry. Because of recent high unemployment in the automobile industry, MCC must now expand its occupational offerings to meet the needs of displaced workers who must either gain new skills…

77 FR 19360 - Report on Countries That Are Candidates for Millennium Challenge Account Eligibility in Fiscal...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-30

... report to Congress is provided in accordance with section 608(a) of the Millennium Challenge Act of 2003... report was initially published in September 2011. In December 2011, Congress enacted changes in MCC's FY... MILLENNIUM CHALLENGE CORPORATION [MCC 12-04] Report on Countries That Are Candidates for...

A pharmacodynamic comparison of piperidine and pyridine alkaloid actions at fetal muscle-type nicotinic acetylcholine receptors (nAChR)

USDA-ARS?s Scientific Manuscript database

Piperidine and pyridine alkaloids are found in many species of plants including Lobelia spp., Conium spp., Nicotiana spp., and Lupinus spp. Some of these alkaloids cause multiple congenital contracture deformities (MCC) and cleft palates in cattle, pigs, sheep, and goats. The mechanism behind MCC ...

Maui Community College Campus Safety and Security.

ERIC Educational Resources Information Center

Hawaii Univ., Kahului. Maui Community Coll.

This document discusses campus safety at Maui Community College (MCC) (Hawaii). MCC is situated on 75 acres of land; the campus population is approximately 2,700 day and night students, with a faculty and staff of approximately 175. The report presents information on campus security services, procedures for reporting crimes and emergencies,…

Is Middlesex County College Accomplishing Its Mission?

ERIC Educational Resources Information Center

Balabkins, Xenia P.

Over the past few years, New Jersey's Middlesex County College (MCC) has placed an inordinate amount of attention and effort on the issue of student transfer to four-year institutions. Although attention to traditional academic goals is important, MCC's stated mission also addresses other important segments of the college's market. The college has…

78 FR 57885 - Report on the Criteria and Methodology for Determining the Eligibility of Candidate Countries for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-20

...: Sources: Sources: Quarterly reporting Indicator tracking Quarterly tables reporting. Survey of MCC staff Quarterly reporting GAO Audits. Impact evaluations Survey of MCC staff. Similarly, the Board may consider a... reporting, documentation of changes in timing or scope of a threshold program in implementation, a survey of...

A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling.

PubMed

Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

2017-01-10

The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1-Bub3 and BubR1-Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1-Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/C Cdc20 ) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1-Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment.

3D PIC-MCC simulations of discharge inception around a sharp anode in nitrogen/oxygen mixtures

NASA Astrophysics Data System (ADS)

Teunissen, Jannis; Ebert, Ute

2016-08-01

We investigate how photoionization, electron avalanches and space charge affect the inception of nanosecond pulsed discharges. Simulations are performed with a 3D PIC-MCC (particle-in-cell, Monte Carlo collision) model with adaptive mesh refinement for the field solver. This model, whose source code is available online, is described in the first part of the paper. Then we present simulation results in a needle-to-plane geometry, using different nitrogen/oxygen mixtures at atmospheric pressure. In these mixtures non-local photoionization is important for the discharge growth. The typical length scale for this process depends on the oxygen concentration. With 0.2% oxygen the discharges grow quite irregularly, due to the limited supply of free electrons around them. With 2% or more oxygen the development is much smoother. An almost spherical ionized region can form around the electrode tip, which increases in size with the electrode voltage. Eventually this inception cloud destabilizes into streamer channels. In our simulations, discharge velocities are almost independent of the oxygen concentration. We discuss the physical mechanisms behind these phenomena and compare our simulations with experimental observations.

PIC-MCC analysis of electron multiplication in a cold-cathode Penning ion generator and its application to identify ignition voltage

NASA Astrophysics Data System (ADS)

Noori, H.; Ranjbar, A. H.; Mahjour-Shafiei, M.

2017-11-01

A cold-cathode Penning ion generator (PIG) has been developed in our laboratory to study the interaction of charged particles with matter. The ignition voltage was measured in the presence of the axial magnetic field in the range of 460-580 G. The performed measurements with stainless steel cathodes were in argon gas at pressure of 4 × 10-2 mbar. A PIC-MCC (particle-in-cell, Monte Carlo collision) technique has been used to calculate the electron multiplication coefficient M for various strength of axial magnetic field and applied voltage. An approach based on the coefficient M and the experimental values of the secondary electron emission coefficient γ, was proposed to determine the ignition voltages, theoretically. Applying the values of secondary coefficient γ leads to the average value of γM(V, B) to be = 1.05 ± 0.03 at the ignition of the PIG which satisfies the proposed ignition criterion. Thus, the ion-induced secondary electrons emitted from the cathode have dominant contribution to self-sustaining of the discharge process in a PIG.

Multiple Chronic Conditions and Disparities in 30-Day Hospital Readmissions Among Nonelderly Adults.

PubMed

Basu, Jayasree; Hanchate, Amresh; Koroukian, Siran

2018-05-15

This study examines the patterns of 30-day hospital readmissions by race/ethnicity and multiple chronic conditions (MCC) burden among nonelderly adult patients. We used hospital discharge data of patients in the 18- to 64-year age group in 5 US states, California, Florida, Missouri, New York, and Tennessee, for 2009 from the Healthcare Cost and Utilization Project State Inpatient Database (HCUP-SID) of the Agency for Healthcare Research and Quality, linked to contextual and provider data from the Health Resources and Services Administration. A multilevel logistic regression model was used for data pooled over 5 states, adjusting for patient, hospital, and community characteristics. Controlling for other covariates, the study found that a higher MCC burden was associated with a higher all-cause 30-day readmission risk. We found considerable heterogeneity in levels of readmission risk among racial/ethnic subgroups stratified by chronic conditions. Among patients with a lowest MCC burden, African Americans had the highest risk of readmission, but with a higher MCC burden, the risk of readmission increased most for Hispanics.

Steric exclusion and protein conformation determine the localization of plasma membrane transporters.

PubMed

Bianchi, Frans; Syga, Łukasz; Moiset, Gemma; Spakman, Dian; Schavemaker, Paul E; Punter, Christiaan M; Seinen, Anne-Bart; van Oijen, Antoine M; Robinson, Andrew; Poolman, Bert

2018-02-05

The plasma membrane (PM) of Saccharomyces cerevisiae contains membrane compartments, MCC/eisosomes and MCPs, named after the protein residents Can1 and Pma1, respectively. Using high-resolution fluorescence microscopy techniques we show that Can1 and the homologous transporter Lyp1 are able to diffuse into the MCC/eisosomes, where a limited number of proteins are conditionally trapped at the (outer) edge of the compartment. Upon addition of substrate, the immobilized proteins diffuse away from the MCC/eisosomes, presumably after taking a different conformation in the substrate-bound state. Our data indicate that the mobile fraction of all integral plasma membrane proteins tested shows extremely slow Brownian diffusion through most of the PM. We also show that proteins with large cytoplasmic domains, such as Pma1 and synthetic chimera of Can1 and Lyp1, are excluded from the MCC/eisosomes. We hypothesize that the distinct localization patterns found for these integral membrane proteins in S. cerevisiae arises from a combination of slow lateral diffusion, steric exclusion, and conditional trapping in membrane compartments.

Optimization of orodispersible and conventional tablets using simplex lattice design: Relationship among excipients and banana extract.

PubMed

Duangjit, Sureewan; Kraisit, Pakorn

2018-08-01

The objective of this study was focused on the optimization of the pharmaceutical excipients and banana extract in the preparation of orally disintegrating banana extract tablets (OD-BET) and conventional banana extract tablets (CO-BET) using a simplex lattice design. Various ratios of banana extract (BE), dibasic calcium phosphate (DCP) and microcrystalline cellulose (MCC) were used to prepare banana extract tablets (BET). The results indicated that the optimal OD-BET and CO-BET consisted of BE: DCP: MCC at 10.0, 88.8, 1.2, 10.0, 83.8: and 6.2, respectively. AFM demonstrated that the surface of BET with BE + MCC was smooth and compacted when compared to BET with BE + DCP + MCC and BE + DCP. FTIR and XRD showed a correlation in the results and indicated that no interaction of each ingredient occurred in the process of BET formulation. Therefore, the experimental design is potentially useful in formulated OD-BET and CO-BET by using only one design simultaneously. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bifunctional composite from spent "Cyprus coffee" for tetracycline removal and phenol degradation: Solar-Fenton process and artificial neural network.

PubMed

Oladipo, Akeem Adeyemi; Abureesh, Mosab Ali; Gazi, Mustafa

2016-09-01

Removals of tetracycline and photocatalytic degradation of phenol by Fe3O4/coffee residue (MCC) were investigated. Brunauer-Emmett-Teller (BET), vibrating sample magnetometer (VSM) and Boehm titration were employed to characterize MCC. Artificial neural network (ANN) model was developed to predict the tetracycline (TC) concentration in the column effluent. Maximum tetracycline adsorption capacity of 285.6mg/g was observed in a batch system. High removal efficiency (87%) was obtained at 3.3mL/min flow rate, 8.0cm bed height and 50mg/L influent TC concentration in a column system. Complete degradation of phenol by solar-Fenton was attained at 60min irradiation time. Total organic carbon (TOC) removal increased to 63.3% in the presence of 1.0g/L MCC, 1.2g/L H2O2 and solar irradiation. MCC showed remarkable potential to remove antibiotics from wastewater even in the presence of heavy metal (Ni(2+)) via magnetic separation. Copyright © 2015 Elsevier B.V. All rights reserved.

The Efficacy of Consensus Tree Methods for Summarizing Phylogenetic Relationships from a Posterior Sample of Trees Estimated from Morphological Data.

PubMed

O'Reilly, Joseph E; Donoghue, Philip C J

2018-03-01

Consensus trees are required to summarize trees obtained through MCMC sampling of a posterior distribution, providing an overview of the distribution of estimated parameters such as topology, branch lengths, and divergence times. Numerous consensus tree construction methods are available, each presenting a different interpretation of the tree sample. The rise of morphological clock and sampled-ancestor methods of divergence time estimation, in which times and topology are coestimated, has increased the popularity of the maximum clade credibility (MCC) consensus tree method. The MCC method assumes that the sampled, fully resolved topology with the highest clade credibility is an adequate summary of the most probable clades, with parameter estimates from compatible sampled trees used to obtain the marginal distributions of parameters such as clade ages and branch lengths. Using both simulated and empirical data, we demonstrate that MCC trees, and trees constructed using the similar maximum a posteriori (MAP) method, often include poorly supported and incorrect clades when summarizing diffuse posterior samples of trees. We demonstrate that the paucity of information in morphological data sets contributes to the inability of MCC and MAP trees to accurately summarise of the posterior distribution. Conversely, majority-rule consensus (MRC) trees represent a lower proportion of incorrect nodes when summarizing the same posterior samples of trees. Thus, we advocate the use of MRC trees, in place of MCC or MAP trees, in attempts to summarize the results of Bayesian phylogenetic analyses of morphological data.

The Efficacy of Consensus Tree Methods for Summarizing Phylogenetic Relationships from a Posterior Sample of Trees Estimated from Morphological Data

PubMed Central

O’Reilly, Joseph E; Donoghue, Philip C J

2018-01-01

Abstract Consensus trees are required to summarize trees obtained through MCMC sampling of a posterior distribution, providing an overview of the distribution of estimated parameters such as topology, branch lengths, and divergence times. Numerous consensus tree construction methods are available, each presenting a different interpretation of the tree sample. The rise of morphological clock and sampled-ancestor methods of divergence time estimation, in which times and topology are coestimated, has increased the popularity of the maximum clade credibility (MCC) consensus tree method. The MCC method assumes that the sampled, fully resolved topology with the highest clade credibility is an adequate summary of the most probable clades, with parameter estimates from compatible sampled trees used to obtain the marginal distributions of parameters such as clade ages and branch lengths. Using both simulated and empirical data, we demonstrate that MCC trees, and trees constructed using the similar maximum a posteriori (MAP) method, often include poorly supported and incorrect clades when summarizing diffuse posterior samples of trees. We demonstrate that the paucity of information in morphological data sets contributes to the inability of MCC and MAP trees to accurately summarise of the posterior distribution. Conversely, majority-rule consensus (MRC) trees represent a lower proportion of incorrect nodes when summarizing the same posterior samples of trees. Thus, we advocate the use of MRC trees, in place of MCC or MAP trees, in attempts to summarize the results of Bayesian phylogenetic analyses of morphological data. PMID:29106675

Current management of surgical oncologic emergencies.

PubMed

Bosscher, Marianne R F; van Leeuwen, Barbara L; Hoekstra, Harald J

2015-01-01

For some oncologic emergencies, surgical interventions are necessary for dissolution or temporary relieve. In the absence of guidelines, the most optimal method for decision making would be in a multidisciplinary cancer conference (MCC). In an acute setting, the opportunity for multidisciplinary discussion is often not available. In this study, the management and short term outcome of patients after surgical oncologic emergency consultation was analyzed. A prospective registration and follow up of adult patients with surgical oncologic emergencies between 01-11-2013 and 30-04-2014. The follow up period was 30 days. In total, 207 patients with surgical oncologic emergencies were included. Postoperative wound infections, malignant obstruction, and clinical deterioration due to progressive disease were the most frequent conditions for surgical oncologic emergency consultation. During the follow up period, 40% of patients underwent surgery. The median number of involved medical specialties was two. Only 30% of all patients were discussed in a MCC within 30 days after emergency consultation, and only 41% of the patients who underwent surgery were discussed in a MCC. For 79% of these patients, the surgical procedure was performed before the MCC. Mortality within 30 days was 13%. In most cases, surgery occurred without discussing the patient in a MCC, regardless of the fact that multiple medical specialties were involved in the treatment process. There is a need for prognostic aids and acute oncology pathways with structural multidisciplinary management. These will provide in faster institution of the most appropriate personalized cancer care, and prevent unnecessary investigations or invasive therapy.

Merkel Cell Polyomavirus: A Newly Discovered Human Virus with Oncogenic Potential

PubMed Central

Spurgeon, Megan E.; Lambert, Paul F.

2012-01-01

A marked escalation in the rate of discovery of new types of human polyomavirus has occurred over the last five years largely owing to recent technological advances in their detection. Among the newly discovered viruses, Merkel Cell Polyomavirus (MCPyV or MCV) has gained the most attention due to its link with a rare human cancer. Infection with MCPyV is common in the human population, and the virus is detected in several anatomical locations, but most frequently in skin. Study of MCPyV molecular virology has been complicated by the lack of straightforward cell culture models, but recent in vitro studies are making strides towards understanding the virus life cycle, its cellular tropism, and mode of transmission. While MCPyV shares several traditional traits with other human polyomaviruses, the burst of research since its discovery reveals insight into a virus with many unique genetic and mechanistic features. The evidence for a causal link between MCPyV and the rare neuroendocrine cancer, Merkel Cell Carcinoma (MCC), is compelling. A majority of MCCs contain clonally integrated viral DNA, express viral T antigen transcripts and protein, and exhibit an addiction to the viral large T and small t antigen oncoproteins. The MCPyV large T antigen contains MCC tumor-specific mutations that ablate its replication capacity but preserve its oncogenic functions, and the small t antigen promotes an environment favorable for cap-dependent translation. The mechanisms of MCPyV-induced transformation have not been fully elucidated, but the likely etiological role of this new polyomavirus in human cancer provides a strong opportunity to expand knowledge of virus-host interactions and viral oncology. PMID:23217622

Multimodal evidence of regional midcingulate gray matter volume underlying conflict monitoring.

PubMed

Parvaz, Muhammad A; Maloney, Thomas; Moeller, Scott J; Malaker, Pias; Konova, Anna B; Alia-Klein, Nelly; Goldstein, Rita Z

2014-01-01

Functional neuroimaging studies have long implicated the mid-cingulate cortex (MCC) in conflict monitoring, but it is not clear whether its structural integrity (i.e., the gray matter volume) influences its conflict monitoring function. In this multimodal study, we used T1-weighted MRI scans as well as event-related potentials (ERPs) to test whether the MCC gray matter volume is associated with the electrocortical marker (i.e., No-go N200 ERP component) of conflict monitoring in healthy individuals. The specificity of such a relationship in health was determined in two ways: by (A) acquiring the same data from individuals with cocaine use disorder (CUD), known to have deficits in executive function including behavioral monitoring; and (B) acquiring the P300 ERP component that is linked with attention allocation and not specifically with conflict monitoring. Twenty-five (39.1 ± 8.4 years; 8 females) healthy individuals and 25 (42.7 ± 5.9 years; 6 females) individuals with CUD underwent a rewarded Go/No-go task during which the ERP data was collected, and they also underwent a structural MRI scan. The whole brain regression analysis showed a significant correlation between MCC structural integrity and the well-known ERP measure of conflict monitoring (N200, but not the P300) in healthy individuals, which was absent in CUD who were characterized by reduced MCC gray matter volume, N200 abnormalities as well as reduced task accuracy. In individuals with CUD instead, the N200 amplitude was associated with drug addiction symptomatology. These results show that the integrity of MCC volume is directly associated with the electrocortical correlates of conflict monitoring in healthy individuals, and such an association breaks down in psychopathologies that impact these brain processes. Taken together, this MCC-N200 association may serve as a biomarker of improved behavioral monitoring processes in diseased populations.

Tart cherry concentrate does not enhance muscle protein synthesis response to exercise and protein in healthy older men.

PubMed

Jackman, Sarah R; Brook, Matthew S; Pulsford, Richard M; Cockcroft, Emma J; Campbell, Matthew I; Rankin, Debbie; Atherton, Philip; Smith, Kenneth; Bowtell, Joanna L

2018-06-08

Oxidative stress and inflammation may contribute to anabolic resistance in response to protein and exercise in older adults. We investigated whether consumption of montmorency cherry concentrate (MCC) increased anabolic sensitivity to protein ingestion and resistance exercise in healthy older men. Sixteen healthy older men were randomized to receive MCC (60 mL·d -1 ) or placebo (PLA) for two weeks, after baseline measures in week 1. During week 3, participants consumed 10 g whey protein·d -1 and completed three bouts of unilateral leg resistance exercise (4 × 8-10 repetitions at 80% 1RM). Participants consumed a bolus (150 mL) and weekly (50 mL) doses of deuterated water. Body water 2 H enrichment was measured in saliva and vastus lateralis biopsies were taken from the non-exercised leg after weeks 1, 2 and 3, and the exercised leg after week 3, to measure tracer incorporation at rest, in response to protein and protein + exercise. Myofibrillar protein synthesis increased in response to exercise + protein compared to rest (p < 0.05) in both groups, but there was no added effect of supplement (MCC: 1.79 ± 0.75 EX vs 1.15 ± 0.40 rest; PLA: 2.22 ± 0.54 vs 1.21 ± 0.18; all %·d -1 ). Muscle total NFĸB protein was decreased with exercise and protein in MCC (NFĸB: -20.7 ± 17.5%) but increased in PLA (NFĸB: 17.8 ± 31.3%, p = 0.073). Short-term MCC ingestion does not affect the anabolic response to protein and exercise in healthy, relatively active, older men, despite MCC ingestion attenuating expression of proteins involved in the muscle inflammatory response to exercise, which may influence the chronic training response. Copyright © 2018 Elsevier Inc. All rights reserved.

The 3D model: explaining densification and deformation mechanisms by using 3D parameter plots.

PubMed

Picker, Katharina M

2004-04-01

The aim of the study was to analyze very differently deforming materials using 3D parameter plots and consequently to gain deeper insights into the densification and deformation process described with the 3D model in order to define an ideal tableting excipient. The excipients used were dicalcium phosphate dihydrate (DCPD), sodium chloride (NaCl), microcrystalline cellulose (MCC), xylitol, mannitol, alpha-lactose monohydrate, maltose, hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC), cellulose acetate (CAC), maize starch, potato starch, pregelatinized starch, and maltodextrine. All of the materials were tableted to graded maximum relative densities (rhorel, max) using an eccentric tableting machine. The data which resulted, namely force, displacement, and time, were analyzed by the application of 3D modeling. Different particle size fractions of DCPD, CAC, and MCC were analyzed in addition. Brittle deforming materials such as DCPD exhibited a completely different 3D parameter plot, with low time plasticity, d, and low pressure plasticity, e, and a strong decrease in omega values when densification increased, in contrast to the plastically deforming MCC, which had much higher d, e, and omega values. e and omega values changed only slightly when densification increased for MCC. NaCl showed less of a decrease in omega values than DCPD did, and the d and e values were between those of MCC and DCPD. The sugar alcohols, xylitol and mannitol, behaved in a similar fashion to sodium chloride. This is also valid for the crystalline sugars, alpha-lactose monohydrate, and maltose. However, the sugars are more brittle than the sugar alcohols. The cellulose derivatives, HPMC, NaCMC, and CAC, are as plastic as MCC, however, their elasticity depends on substitution indicated by lower (more elastic) or higher (less elastic) omega values. The native starches, maize starch and potato starch, are very elastic, and pregelatinized starch and maltodextrine are less elastic and exhibited higher omega values. Deformation behavior as shown in 3D parameter plots depends on particle size for polymers such as CAC and MCC; however, it does not depend on particle size for brittle materials such as DCPD. An ideally deforming tableting excipient should exhibit high e, d, and omega values with a constant ratio of e and omega at increasing densification.

Operating and Managing a Backup Control Center

NASA Technical Reports Server (NTRS)

Marsh, Angela L.; Pirani, Joseph L.; Bornas, Nicholas

2010-01-01

Due to the criticality of continuous mission operations, some control centers must plan for alternate locations in the event an emergency shuts down the primary control center. Johnson Space Center (JSC) in Houston, Texas is the Mission Control Center (MCC) for the International Space Station (ISS). Due to Houston s proximity to the Gulf of Mexico, JSC is prone to threats from hurricanes which could cause flooding, wind damage, and electrical outages to the buildings supporting the MCC. Marshall Space Flight Center (MSFC) has the capability to be the Backup Control Center for the ISS if the situation is needed. While the MSFC Huntsville Operations Support Center (HOSC) does house the BCC, the prime customer and operator of the ISS is still the JSC flight operations team. To satisfy the customer and maintain continuous mission operations, the BCC has critical infrastructure that hosts ISS ground systems and flight operations equipment that mirrors the prime mission control facility. However, a complete duplicate of Mission Control Center in another remote location is very expensive to recreate. The HOSC has infrastructure and services that MCC utilized for its backup control center to reduce the costs of a somewhat redundant service. While labor talents are equivalent, experiences are not. Certain operations are maintained in a redundant mode, while others are simply maintained as single string with adequate sparing levels of equipment. Personnel at the BCC facility must be trained and certified to an adequate level on primary MCC systems. Negotiations with the customer were done to match requirements with existing capabilities, and to prioritize resources for appropriate level of service. Because some of these systems are shared, an activation of the backup control center will cause a suspension of scheduled HOSC activities that may share resources needed by the BCC. For example, the MCC is monitoring a hurricane in the Gulf of Mexico. As the threat to MCC increases, HOSC must begin a phased activation of the BCC, while working resource conflicts with normal HOSC activities. In a long duration outage to the MCC, this could cause serious impacts to the BCC host facility s primary mission support activities. This management of a BCC is worked based on customer expectations and negotiations done before emergencies occur. I.

Identifying the molecular functions of electron transport proteins using radial basis function networks and biochemical properties.

PubMed

Le, Nguyen-Quoc-Khanh; Nguyen, Trinh-Trung-Duong; Ou, Yu-Yen

2017-05-01

The electron transport proteins have an important role in storing and transferring electrons in cellular respiration, which is the most proficient process through which cells gather energy from consumed food. According to the molecular functions, the electron transport chain components could be formed with five complexes with several different electron carriers and functions. Therefore, identifying the molecular functions in the electron transport chain is vital for helping biologists understand the electron transport chain process and energy production in cells. This work includes two phases for discriminating electron transport proteins from transport proteins and classifying categories of five complexes in electron transport proteins. In the first phase, the performances from PSSM with AAIndex feature set were successful in identifying electron transport proteins in transport proteins with achieved sensitivity of 73.2%, specificity of 94.1%, and accuracy of 91.3%, with MCC of 0.64 for independent data set. With the second phase, our method can approach a precise model for identifying of five complexes with different molecular functions in electron transport proteins. The PSSM with AAIndex properties in five complexes achieved MCC of 0.51, 0.47, 0.42, 0.74, and 1.00 for independent data set, respectively. We suggest that our study could be a power model for determining new proteins that belongs into which molecular function of electron transport proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway

PubMed Central

Wu, Dacheng; Wu, Keyan; Zhu, Qingtian; Xiao, Weiming; Shan, Qing; Yan, Zhigang; Wu, Jian; Deng, Bin; Xue, Yan; Gong, Weijuan

2018-01-01

Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation. PMID:29507526

Metachronous colorectal cancer following segmental or extended colectomy in Lynch syndrome: a systematic review and meta-analysis.

PubMed

Malik, Salim S; Lythgoe, Mark P; McPhail, Mark; Monahan, Kevin J

2017-11-30

Around 5% of colorectal cancers are due to mutations within DNA mismatch repair genes, resulting in Lynch syndrome (LS). These mutations have a high penetrance with early onset of colorectal cancer at a mean age of 45 years. The mainstay of surgical management is either a segmental or extensive colectomy. Currently there is no unified agreement as to which management strategy is superior due to limited conclusive empirical evidence available. A systematic review and meta- analysis to evaluate the risk of metachronous colorectal cancer (MCC) and mortality in LS following segmental and extensive colectomy. A systematic review of the PubMed database was conducted. Studies were included/ excluded based on pre-specified criteria. To assess the risk of MCC and mortality attributed to segmental or extensive colectomies, relative risks (RR) were calculated and corresponding 95% confidence intervals (CI). Publication bias was investigated using funnel plots. Data about mortality, as well as patient ascertainment [Amsterdam criteria (AC), germline mutation (GM)] were also extracted. Statistical analysis was conducted using the R program (version 3.2.3). The literature search identified 85 studies. After further analysis ten studies were eligible for inclusion in data synthesis. Pooled data identified 1389 patients followed up for a mean of 100.7 months with a mean age of onset of 45.5 years of age. A total 1119 patients underwent segmental colectomies with an absolute risk of MCC in this group of 22.4% at the end of follow-up. The 270 patients who had extensive colectomies had a MCC absolute risk of 4.7% (0% in those with a panproctocolecomy). Segmental colectomy was significantly associated with an increased relative risk of MCC (RR = 5.12; 95% CI 2.88-9.11; Fig. 1), although no significant association with mortality was identified (RR = 1.65; 95% CI 0.90-3.02). There was no statistically significant difference in the risk of MCC between AC and GM cohorts (p = 0.5, Chi-squared test). In LS, segmental colectomy results in a significant increased risk of developing MCC. Despite the choice of segmental or extensive colectomies having no statistically significant impact on mortality, the choice of initial surgical management can impact a patient's requirement for further surgery. An extensive colectomy can result in decreased need for further surgery; reduced hospital stays and associated costs. The significant difference in the risk of MCC, following segmental or extensive colectomies should be discussed with patients when deciding appropriate management. An individualised approach should be utilised, taking into account the patient's age, co-morbidities and genotype. In order to determine likely germline-specific effects, or a difference in survival, larger and more comprehensive studies are required.

View of Mission Control Center (MCC) - Lunar Surface - Apollo XI - Extravehicular Activity (EVA) - MSC

NASA Image and Video Library

1969-07-20

S69-39817 (20 July 1969) --- Interior view of the Mission Operations Control Room (MOCR) in the Mission Control Center (MCC), Building 30, during the Apollo 11 lunar extravehicular activity (EVA). The television monitor shows astronauts Neil A. Armstrong and Edwin E. Aldrin Jr. on the surface of the moon.

How Community College Adjunct Faculty Members Teaching Communications Courses Understand Diversity as It Relates to Their Teaching

ERIC Educational Resources Information Center

Rediger, James N.

2013-01-01

The purpose of this study was to explore Midwestern Community College (MCC) communication adjunct faculty members' descriptions of techniques used to prepare for a diverse student population. This research was conducted in order to gain a better understanding of how adjunct faculty members teaching communications courses at MCC understood…

Financial Aid as a Service: A Review of Operations.

ERIC Educational Resources Information Center

Adams, Judith

A study was undertaken at Macomb Community College (MCC), in Michigan, to review the effectiveness of the college's financial aid department. Data were gathered from a search of the literature related to financial aid services and a review of comments and findings from MCC alumni and financial aid surveys. In addition, surveys were conducted of…

STS-49 Endeavour, Orbiter Vehicle (OV) 105, Planning Team in MCC Bldg 30 FCR

NASA Technical Reports Server (NTRS)

1992-01-01

STS-49 Endeavour, Orbiter Vehicle (OV) 105, Planning Team with Flight Director (FD) James M. Heflin, Jr (front right next to ship model) poses in JSC's Mission Control Center (MCC) Bldg 30 Flight Control Room (FCR). The group stands in front of visual displays projecting STS-49 data and ground track map.

Consequences of Broad Auditory Filters for Identification of Multichannel-Compressed Vowels

ERIC Educational Resources Information Center

Souza, Pamela; Wright, Richard; Bor, Stephanie

2012-01-01

Purpose: In view of previous findings (Bor, Souza, & Wright, 2008) that some listeners are more susceptible to spectral changes from multichannel compression (MCC) than others, this study addressed the extent to which differences in effects of MCC were related to differences in auditory filter width. Method: Listeners were recruited in 3 groups:…

What Senior Citizens Want from the Community College.

ERIC Educational Resources Information Center

Darden, Mary Landon; Cloud, Robert C.; Illich, Paul

This study for McLennan Community College (MCC), Texas, examines the issue of meeting the educational needs of the senior population of McLennan County. MCC aims to develop a Senior College. The Senior College would design classes specially for those age 55 and older, would make the classes affordable through use of expert volunteer instructors,…

Corporate Solicitation--SUNY Style: A Two-Year Urban Campus' Approach to Corporate Giving.

ERIC Educational Resources Information Center

Milligan, Frank G.

Monroe Community College (MCC) is located in a county with over one million residents, where over 40% of the workforce is employed in manufacturing and where a number of major corporations are engaged in high technology production. Strong links existing between MCC and local industry are illustrated by the degree programs offered in high…

MISSION CONTROL CENTER (MCC) - GEMINI-TITAN (GT)-6 - SCRUBBED - MSC

NASA Image and Video Library

1965-10-25

S65-44401 (1965) --- A group of National Aeronautics and Space Administration (NASA) and Manned Spacecraft Center (MSC) officials and personnel watch a Cape Kennedy press conference being telecast in the Mission Control Center (MCC) after the Gemini-6 mission was scrubbed due to the apparent failure of the Agena Target Vehicle to attain orbit.

Coverage of STS-104 Launch Coverage of Flight Controllers in MCC.

NASA Image and Video Library

2001-07-12

JSC2001-E-21333 (12 July 2001) --- From a familiar setting in the shuttle flight control room (WFCR)at Houston's Mission Control Center (MCC), Wayne Hale, ascent flight director for STS-104, pays close attention to new data related to the Space Shuttle Atlantis and its impending launch from the Kennedy Space Center (KSC) in Florida.

Coverage of STS-104 Launch Coverage of Flight Controllers in MCC.

NASA Image and Video Library

2001-07-12

JSC2001-E-21333 (12 July 2001) --- From a familiar setting in the shuttle flight control room (WFCR) at Houston's Mission Control Center (MCC), Wayne Hale, ascent flight director for STS-104, pays close attention to new data related to the Space Shuttle Atlantis and its impending launch from the Kennedy Space Center (KSC) in Florida.

Race/Ethnicity, Color-Blind Racial Attitudes, and Multicultural Counseling Competence: The Moderating Effects of Multicultural Counseling Training

ERIC Educational Resources Information Center

Chao, Ruth Chu-Lien; Wei, Meifen; Good, Glenn E.; Flores, Lisa Y.

2011-01-01

Increasing trainees' multicultural counseling competence (MCC) has been a hot topic in counseling. Scholars have identified predictors (e.g., race/ethnicity, color-blindness) of MCC, and educators provide multicultural training for trainees. Using a sample of 370 psychology trainees, this study examined whether multicultural training (a) moderated…

Community Needs Assessment for Office Administration and Technology Program: Health Unit Coordinator.

ERIC Educational Resources Information Center

Pezzoli, Jean A.; Johnson, Nancy; Lum, Kuuipo

In order to determine the potential employment demand and skills needed for health unit coordinators and other clerical workers in the medical field, Maui Community College (MCC) in Hawaii conducted a survey of 120 local health care providers in the spring semester of 1998. Forty respondents provided MCC with the following details: (1) 92 percent…

Pellet starters in layering technique using concentrated drug solution.

PubMed

Gryczová, Eva; Rabisková, Miloslava; Vetchý, David; Krejcová, Katerina

2008-12-01

Characteristics of inert starters in drug solution layering are important for successful active pellet formation. Four types of starters composed of sucrose or microcrystalline cellulose (MCC) or lactose and MCC were compared in our study. The active pellets were prepared using Wurster type apparatus. Yield and pellet quality parameters were determined. The highest yield (85.66-89.41%) was obtained for cores composed of MCC due to their insolubility in water (the drug solvent) and good mechanical properties. On the contrary, soluble and brittle sucrose cores dissolved partially during the process forming undesirable agglomerates and giving lower yield (76.2%). All pellet samples showed good flow properties and drug content from 82.4 to 94.5% of the theoretical drug amount.

Huntingtin interacting protein 1 as a histopathologic adjunct in the diagnosis of Merkel cell carcinoma.

PubMed

Marghalani, Siham; Feller, John Kyle; Mahalingam, Meera; Mirzabeigi, Marjan

2015-06-01

Huntington interacting protein 1 (HIP1), an antiapoptotic protein normally expressed in the brain, is highly expressed in Merkel cell carcinomas (MCCs). Given this, the aim of the current study was to ascertain the value of HIP1 as a histopathologic adjunct in the diagnosis of MCC. In this retrospective study, archival material from 26 cases with a diagnosis of MCC and/or neuroendocrine carcinoma were retrieved from the pathology files of the Skin Pathology Laboratory (Boston University School of Medicine, Boston, MA, USA). Histopathologic sections of all cases were re-reviewed and the diagnosis confirmed. All patient data were de-identified. Immunohistochemical studies were performed using antibodies to HIP1 and cytokeratins (CK) 20 and 7. A semiquantitative scoring system for immunohistochemical expression of HIP1 was utilized by deriving a cumulative score (based on percentage positivity of cells and intensity of expression). Using a cut-off total score of 3 or more as positive, the total number of positive cases was 22 for HIP1, 24 for CK20, and 11 for CK7. Comparing the results of HIP1 and CK20, there were four discordant pairs (three positive for CK20 but negative for HIP1 and one positive for HIP1 but negative for CK20). McNemar's test indicated that there was no statistical significance (P = 0.625), thereby implying a close agreement between the expression of HIP1 and CK20 in these neuroendocrine neoplasms. © 2014 The International Society of Dermatology.

The value of nodal information in predicting lung cancer relapse using 4DPET/4DCT

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

Li, Heyse, E-mail: heyse.li@mail.utoronto.ca; Becker, Nathan; Raman, Srinivas

2015-08-15

Purpose: There is evidence that computed tomography (CT) and positron emission tomography (PET) imaging metrics are prognostic and predictive in nonsmall cell lung cancer (NSCLC) treatment outcomes. However, few studies have explored the use of standardized uptake value (SUV)-based image features of nodal regions as predictive features. The authors investigated and compared the use of tumor and node image features extracted from the radiotherapy target volumes to predict relapse in a cohort of NSCLC patients undergoing chemoradiation treatment. Methods: A prospective cohort of 25 patients with locally advanced NSCLC underwent 4DPET/4DCT imaging for radiation planning. Thirty-seven image features were derivedmore » from the CT-defined volumes and SUVs of the PET image from both the tumor and nodal target regions. The machine learning methods of logistic regression and repeated stratified five-fold cross-validation (CV) were used to predict local and overall relapses in 2 yr. The authors used well-known feature selection methods (Spearman’s rank correlation, recursive feature elimination) within each fold of CV. Classifiers were ranked on their Matthew’s correlation coefficient (MCC) after CV. Area under the curve, sensitivity, and specificity values are also presented. Results: For predicting local relapse, the best classifier found had a mean MCC of 0.07 and was composed of eight tumor features. For predicting overall relapse, the best classifier found had a mean MCC of 0.29 and was composed of a single feature: the volume greater than 0.5 times the maximum SUV (N). Conclusions: The best classifier for predicting local relapse had only tumor features. In contrast, the best classifier for predicting overall relapse included a node feature. Overall, the methods showed that nodes add value in predicting overall relapse but not local relapse.« less

A lightweight distributed framework for computational offloading in mobile cloud computing.

PubMed

Shiraz, Muhammad; Gani, Abdullah; Ahmad, Raja Wasim; Adeel Ali Shah, Syed; Karim, Ahmad; Rahman, Zulkanain Abdul

2014-01-01

The latest developments in mobile computing technology have enabled intensive applications on the modern Smartphones. However, such applications are still constrained by limitations in processing potentials, storage capacity and battery lifetime of the Smart Mobile Devices (SMDs). Therefore, Mobile Cloud Computing (MCC) leverages the application processing services of computational clouds for mitigating resources limitations in SMDs. Currently, a number of computational offloading frameworks are proposed for MCC wherein the intensive components of the application are outsourced to computational clouds. Nevertheless, such frameworks focus on runtime partitioning of the application for computational offloading, which is time consuming and resources intensive. The resource constraint nature of SMDs require lightweight procedures for leveraging computational clouds. Therefore, this paper presents a lightweight framework which focuses on minimizing additional resources utilization in computational offloading for MCC. The framework employs features of centralized monitoring, high availability and on demand access services of computational clouds for computational offloading. As a result, the turnaround time and execution cost of the application are reduced. The framework is evaluated by testing prototype application in the real MCC environment. The lightweight nature of the proposed framework is validated by employing computational offloading for the proposed framework and the latest existing frameworks. Analysis shows that by employing the proposed framework for computational offloading, the size of data transmission is reduced by 91%, energy consumption cost is minimized by 81% and turnaround time of the application is decreased by 83.5% as compared to the existing offloading frameworks. Hence, the proposed framework minimizes additional resources utilization and therefore offers lightweight solution for computational offloading in MCC.

A Lightweight Distributed Framework for Computational Offloading in Mobile Cloud Computing

PubMed Central

Shiraz, Muhammad; Gani, Abdullah; Ahmad, Raja Wasim; Adeel Ali Shah, Syed; Karim, Ahmad; Rahman, Zulkanain Abdul

2014-01-01

The latest developments in mobile computing technology have enabled intensive applications on the modern Smartphones. However, such applications are still constrained by limitations in processing potentials, storage capacity and battery lifetime of the Smart Mobile Devices (SMDs). Therefore, Mobile Cloud Computing (MCC) leverages the application processing services of computational clouds for mitigating resources limitations in SMDs. Currently, a number of computational offloading frameworks are proposed for MCC wherein the intensive components of the application are outsourced to computational clouds. Nevertheless, such frameworks focus on runtime partitioning of the application for computational offloading, which is time consuming and resources intensive. The resource constraint nature of SMDs require lightweight procedures for leveraging computational clouds. Therefore, this paper presents a lightweight framework which focuses on minimizing additional resources utilization in computational offloading for MCC. The framework employs features of centralized monitoring, high availability and on demand access services of computational clouds for computational offloading. As a result, the turnaround time and execution cost of the application are reduced. The framework is evaluated by testing prototype application in the real MCC environment. The lightweight nature of the proposed framework is validated by employing computational offloading for the proposed framework and the latest existing frameworks. Analysis shows that by employing the proposed framework for computational offloading, the size of data transmission is reduced by 91%, energy consumption cost is minimized by 81% and turnaround time of the application is decreased by 83.5% as compared to the existing offloading frameworks. Hence, the proposed framework minimizes additional resources utilization and therefore offers lightweight solution for computational offloading in MCC. PMID:25127245

Conductivity percolation in loosely compacted microcrystalline cellulose: An in situ study by dielectric spectroscopy during densification.

PubMed

Nilsson, Martin; Frenning, Göran; Gråsjö, Johan; Alderborn, Göran; Strømme, Maria

2006-10-19

The present study aims at contributing to a complete understanding of the water-induced ionic charge transport in cellulose. The behavior of this transport in loosely compacted microcrystalline cellulose (MCC) powder was investigated as a function of density utilizing a new type of measurement setup, allowing for dielectric spectroscopy measurement in situ during compaction. The ionic conductivity in MCC was found to increase with increasing density until a leveling-out was observed for densities above approximately 0.7 g/cm3. Further, it was shown that the ionic conductivity vs density followed a percolation type behavior signifying the percolation of conductive paths in a 3D conducting network. The density percolation threshold was found to be between approximately 0.2 and 0.4 g/cm3, depending strongly on the cellulose moisture content. The observed percolation behavior was attributed to the forming of interparticulate bonds in the MCC and the percolation threshold dependence on moisture was linked to the moisture dependence of particle rearrangement and plastic deformation in MCC during compaction. The obtained results add to the understanding of the density-dependent water-induced ionic transport in cellulose showing that, at given moisture content, the two major parameters determining the magnitude of the conductivity are the connectedness of the interparticluate bonds and the connectedness of pores with a diameter in the 5-20 nm size range. At densities between approximately 0.7 and 1.2 g/cm3 both the bond and the pore networks have percolated, facilitating charge transport through the MCC compact.

Defining Multiple Chronic Conditions for Quality Measurement.

PubMed

Drye, Elizabeth E; Altaf, Faseeha K; Lipska, Kasia J; Spatz, Erica S; Montague, Julia A; Bao, Haikun; Parzynski, Craig S; Ross, Joseph S; Bernheim, Susannah M; Krumholz, Harlan M; Lin, Zhenqiu

2018-02-01

Patients with multiple chronic conditions (MCCs) are a critical but undefined group for quality measurement. We present a generally applicable systematic approach to defining an MCC cohort of Medicare fee-for-service beneficiaries that we developed for a national quality measure, risk-standardized rates of unplanned admissions for Accountable Care Organizations. To define the MCC cohort we: (1) identified potential chronic conditions; (2) set criteria for cohort conditions based on MCC framework and measure concept; (3) applied the criteria informed by empirical analysis, experts, and the public; (4) described "broader" and "narrower" cohorts; and (5) selected final cohort with stakeholder input. Subjects were patients with chronic conditions. Participants included 21.8 million Medicare fee-for-service beneficiaries in 2012 aged 65 years and above with ≥1 of 27 Medicare Chronic Condition Warehouse condition(s). In total, 10 chronic conditions were identified based on our criteria; 8 of these 10 were associated with notably increased admission risk when co-occurring. A broader cohort (2+ of the 8 conditions) included 4.9 million beneficiaries (23% of total cohort) with an admission rate of 70 per 100 person-years. It captured 53% of total admissions. The narrower cohort (3+ conditions) had 2.2 million beneficiaries (10%) with 100 admissions per 100 person-years and captured 32% of admissions. Most stakeholders viewed the broader cohort as best aligned with the measure concept. By systematically narrowing chronic conditions to those most relevant to the outcome and incorporating stakeholder input, we defined an MCC admission measure cohort supported by stakeholders. This approach can be used as a model for other MCC outcome measures.

Genetic Variation of pln Loci Among Probiotic Lactobacillus plantarum Group Strains with Antioxidant and Cholesterol-Lowering Ability.

PubMed

Devi, Sundru Manjulata; Halami, Prakash M

2017-10-13

In the present study, 14 different plantaricin-encoding genes of pln loci were studied and compared to available sequences from public domain database of probiotic Lactobacillus plantarum strains. Based upon the presence and absence of selected genes, pln locus was grouped into eight clusters. Further, quantitative real-time PCR (qRT-PCR) analysis for seven genes has discriminated the complex pln locus into five types which includes WCFS1 (in Lactobacillus plantarum subsp. plantarum MCC 2976 and MCC 2974 and Lactobacillus paraplantarum MCC 2978), closely related to J51 (in Lb. paraplantarum MCC 2973 and MCC 2977), J23 (in Lb. plantarum MTCC 5422), NC8 (in Lb. paraplantarum MTCC 9483), and a new E1 type (in Lb. plantarum subsp. plantarum E1). It was observed that the plnA, EF, NC8βα, NC81F, NC8HK, and G were expressed in E1 strain. Further, southern hybridization confirmed the chromosome-encoded plantaricin in Lb. plantarum group (LPG) strains. Several PCR assays and DNA sequence analysis of the regions amplified in pln loci of E1 isolate suggested a hybrid variant of NC8 and J51 plantaritypes. This indicates the wide distribution of plantaricin with remarkable variation, diversity, and plasticity among the LPG strains of vegetable origin. Further, the selected strains were able to reduce the growth of Kocuria rhizophila ATCC 9341 by 40-54% within 6 h of co-incubation under in vitro pathogen exclusion assay. These isolates also possessed cholesterol-lowering and antioxidant activity suggesting their application in the development of functional foods.

Current Management of Surgical Oncologic Emergencies

PubMed Central

Bosscher, Marianne R. F.; van Leeuwen, Barbara L.; Hoekstra, Harald J.

2015-01-01

Objectives For some oncologic emergencies, surgical interventions are necessary for dissolution or temporary relieve. In the absence of guidelines, the most optimal method for decision making would be in a multidisciplinary cancer conference (MCC). In an acute setting, the opportunity for multidisciplinary discussion is often not available. In this study, the management and short term outcome of patients after surgical oncologic emergency consultation was analyzed. Method A prospective registration and follow up of adult patients with surgical oncologic emergencies between 01-11-2013 and 30-04-2014. The follow up period was 30 days. Results In total, 207 patients with surgical oncologic emergencies were included. Postoperative wound infections, malignant obstruction, and clinical deterioration due to progressive disease were the most frequent conditions for surgical oncologic emergency consultation. During the follow up period, 40% of patients underwent surgery. The median number of involved medical specialties was two. Only 30% of all patients were discussed in a MCC within 30 days after emergency consultation, and only 41% of the patients who underwent surgery were discussed in a MCC. For 79% of these patients, the surgical procedure was performed before the MCC. Mortality within 30 days was 13%. Conclusion In most cases, surgery occurred without discussing the patient in a MCC, regardless of the fact that multiple medical specialties were involved in the treatment process. There is a need for prognostic aids and acute oncology pathways with structural multidisciplinary management. These will provide in faster institution of the most appropriate personalized cancer care, and prevent unnecessary investigations or invasive therapy. PMID:25933135

Evidence-Based Nanoscopic and Molecular Framework for Excipient Functionality in Compressed Orally Disintegrating Tablets

PubMed Central

Al-khattawi, Ali; Alyami, Hamad; Townsend, Bill; Ma, Xianghong; Mohammed, Afzal R.

2014-01-01

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2–10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. PMID:25025427

Multiple Chronic Conditions and Hospitalizations Among Recipients of Long-Term Services and Supports

PubMed Central

Van Cleave, Janet H.; Egleston, Brian L.; Abbott, Katherine M.; Hirschman, Karen B.; Rao, Aditi; Naylor, Mary D.

2016-01-01

Background Among older adults receiving long term-services and supports (LTSS), debilitating hospitalizations is a pervasive clinical and research problem. Multiple chronic conditions (MCC) are prevalent in LTSS recipients. However, the combination of MCC and diseases associated with hospitalizations of LTSS recipients is unclear. Objective The purpose of this analysis was to determine the association between classes of MCC in newly enrolled LTSS recipients and the number of hospitalizations over a one-year period following enrollment. Methods This report is based on secondary analysis of extant data from a longitudinal cohort study of 470 new recipients of LTSS, ages 60 years and older, receiving services in assisted living facilities, nursing homes, or through home- and community-based services. Using baseline chronic conditions reported in medical records, latent class analysis (LCA) was used to identify classes of MCC and posterior probabilities of membership in each class. Poisson regressions were used to estimate the relative ratio between posterior probabilities of class membership and number of hospitalizations during the 3 month period prior to the start of LTSS (baseline) and then every three months forward through 12 months. Results Three latent MCC-based classes named Cardiopulmonary, Cerebrovascular/Paralysis, and All Other Conditions were identified. The Cardiopulmonary class was associated with elevated numbers of hospitalization compared to the All Other Conditions class (relative ratio [RR] = 1.88, 95% CI [1.33, 2.65], p < .001). Conclusion Older LTSS recipients with a combination of MCCs that includes cardiopulmonary conditions have increased risk for hospitalization. PMID:27801713

Effect of environmental conditions on the mechanical properties and fungal degradation of polycaprolactone/microcrystalline cellulose/wood flour composites

Treesearch

Ronald Sabo; Liwei Jin; Nicole Stark; Rebecca E. Ibach

2013-01-01

Polycaprolactone (PCL) filled with microcrystalline cellulose (MCC), wood flour (WF), or both were characterized before and after exposure to various environmental conditions for 60 days. PCL/WF composites had the greatest tensile strength and modulus compared to neat PCL or PCL composites containing MCC. Electron microscopy indicated better adhesion between WF...

78 FR 67335 - Solid Urea From the Russian Federation: Final Results of Antidumping Duty Administrative Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

... (Russia). For the final results, we continue to find that MCC EuroChem has not sold subject merchandise at... of the antidumping duty order on solid urea from Russia.\\1\\ We invited interested parties to comment... conducted a verification of the sales information reported by MCC EuroChem in Russia.\\2\\ \\2\\ See Memorandum...

View from the back of the Flight control room of Mission control center

NASA Image and Video Library

1984-10-06

View from the back of the Mission Control Center (MCC). Visible are the Flight Directors console (left front), the CAPCOM console (right front) and the Payloads console. Some of the STS 41-G crew can be seen on a large screen at the front of the MCC along with a map tracking the progress of the orbiter.

Early Communication System (ECOMM) for ISS

NASA Technical Reports Server (NTRS)

Gaylor, Kent; Tu, Kwei

1999-01-01

The International Space Station (ISS) Early Communications System (ECOMM) was a Johnson Space Center (JSC) Avionic Systems Division (ASD) in-house developed communication system to provide early communications between the ISS and the Mission Control Center-Houston (MCC-H). This system allows for low rate commands (link rate of 6 kbps) to be transmitted through the Tracking and Data Relay Satellite System (TDRSS) from MCC-H to the ISS using TDRSS's S-band Single Access Forward (SSA/) link service. This system also allows for low rate telemetry (link rate of 20.48 kbps) to be transmitted from ISS to MCC-H through the TDRSS using TDRSS's S-band Single Access Return (SSAR) link service. In addition this system supports a JSC developed Onboard Communications Adapter (OCA) that allows for a two-way data exchange of 128 kbps between MCC-H and the ISS through TDRSS. This OCA data can be digital video/audio (two-way videoconference), and/or file transfers, and/or "white board". The key components of the system, the data formats used by the system to insure compatibility with the future ISS S-Band System, as well as how other vehicles may be able to use this system for their needs are discussed in this paper.

Airway Hydration and COPD

PubMed Central

Ghosh, Arunava; Boucher, R.C.; Tarran, Robert

2015-01-01

Chronic obstructive pulmonary disease (COPD) is one of the prevalent causes of worldwide mortality and encompasses two major clinical phenotypes, i.e., chronic bronchitis (CB) and emphysema. The most common cause of COPD is chronic tobacco inhalation. Research focused on the chronic bronchitic phenotype of COPD has identified several pathological processes that drive disease initiation and progression. For example, the lung’s mucociliary clearance (MCC) system performs the critical task of clearing inhaled pathogens and toxic materials from the lung. MCC efficiency is dependent on: (i) the ability of apical plasma membrane ion channels such as the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na+ channel (ENaC) to maintain airway hydration; (ii) ciliary beating; and, (iii) appropriate rates of mucin secretion. Each of these components is impaired in CB and likely contributes to the mucus stasis/accumulation seen in CB patients. This review highlights the cellular components responsible for maintaining MCC and how this process is disrupted following tobacco exposure and with CB. We shall also discuss existing therapeutic strategies for the treatment of chronic bronchitis and how components of the MCC can be used as biomarkers for the evaluation of tobacco or tobacco-like-product exposure. PMID:26068443

The voice of conscience: neural bases of interpersonal guilt and compensation

PubMed Central

Yu, Hongbo; Hu, Jie; Hu, Li

2014-01-01

People feel bad for inflicting harms upon others; this emotional state is termed interpersonal guilt. In this study, the participant played multiple rounds of a dot-estimation task with anonymous partners while undergoing fMRI. The partner would receive pain stimulation if the partner or the participant or both responded incorrectly; the participant was then given the option to intervene and bear a proportion of pain for the partner. The level of pain voluntarily taken and the activations in anterior middle cingulate cortex (aMCC) and bilateral anterior insula (AI) were higher when the participant was solely responsible for the stimulation (Self_Incorrect) than when both committed an error (Both_Incorrect). Moreover, the gray matter volume in the aMCC predicted the individual’s compensation behavior, measured as the difference between the level of pain taken in the Self_Incorrect and Both_Incorrect conditions. Furthermore, a mediation pathway analysis revealed that activation in a midbrain region mediated the relationship between aMCC activation and the individual’s tendency to compensate. These results demonstrate that the aMCC and the midbrain nucleus not only play an important role in experiencing interpersonal guilt, but also contribute to compensation behavior. PMID:23893848

A study of a co-processed dry binder composed of microcrystalline cellulose and glycerol monostearate.

PubMed

Mužíková, Jitka; Muchová, Sandra

2012-10-01

The paper studies the co-processed dry binder LubriToseTM MCC from the viewpoint of energy evaluation of the compression process, strength and disintegration time of tablets. The results were compared with the identical evaluation of physical mixtures of microcrystalline cellulose with several types of lubricants. LubriTose MCC showed the lowest value of energy for friction, the highest value of energy accumulated by the tablet, and the highest plasticity of all tableting materials under study. There were no marked differences in the values of the energy of decompression. The tensile strength of tablets from LubriTose MCC was lower than in those from the mixture of Vivapur® 12 and glycerol monostearate, in the compression forces of 4 and 5 kN it was comparable with the tensile strength of tablets from Vivapur 12 with Poloxamer 407. Disintegration time of tablets from LubriTose MCC was shorter than that of those from Vivapur 12 with glycerol monostearate at the compression force of 3 kN, in the case of the compression forces of 4 and 5 kN no statistically significant difference was found between the values of these tableting materials.

Multi-Capillary Column-Ion Mobility Spectrometry of Volatile Metabolites Emitted by Saccharomyces Cerevisiae

PubMed Central

Halbfeld, Christoph; Ebert, Birgitta E.; Blank, Lars M.

2014-01-01

Volatile organic compounds (VOCs) produced during microbial fermentations determine the flavor of fermented food and are of interest for the production of fragrances or food additives. However, the microbial synthesis of these compounds from simple carbon sources has not been well investigated so far. Here, we analyzed the headspace over glucose minimal salt medium cultures of Saccharomyces cerevisiae using multi-capillary column-ion mobility spectrometry (MCC-IMS). The high sensitivity and fast data acquisition of the MCC-IMS enabled online analysis of the fermentation off-gas and 19 specific signals were determined. To four of these volatile compounds, we could assign the metabolites ethanol, 2-pentanone, isobutyric acid, and 2,3-hexanedione by MCC-IMS measurements of pure standards and cross validation with thermal desorption–gas chromatography-mass spectrometry measurements. Despite the huge biochemical knowledge of the biochemistry of the model organism S. cerevisiae, only the biosynthetic pathways for ethanol and isobutyric acid are fully understood, demonstrating the considerable lack of research of volatile metabolites. As monitoring of VOCs produced during microbial fermentations can give valuable insight into the metabolic state of the organism, fast and non-invasive MCC-IMS analyses provide valuable data for process control. PMID:25197771

Measuring the structure factor of simple fluids under extreme conditions

NASA Astrophysics Data System (ADS)

Weck, Gunnar

2013-06-01

The structure and dynamics of fluids, although a long standing matter of investigations, is still far from being well established. In particular, with the existence of a first order liquid-liquid phase transition (LLT) discovered in liquid phosphorus at 0.9 GPa and 1300 K it is now recognized that the fluid state could present complex structural changes. At present, very few examples of LLTs have been clearly evidenced, which may mean that a larger range of densities must be probed. First order transitions between a molecular and a polymeric liquid have been recently predicted by first principles calculations in liquid nitrogen at 88 GPa and 2000 K and in liquid CO2 at 45 GPa and 1850 K. The only device capable of reaching these extreme conditions is the diamond anvil cell (DAC), in which, the sample is sandwiched between two diamond anvils of thickness 100 times larger. Consequently, the diffracted signal from the sample is very weak compared to the Compton signal of the anvils, and becomes hardly measurable for pressures above ~20 GPa. A similar problem has been faced by the high pressure community using large volume press so as to drastically reduce the x-ray background from the sample environment. In the angle-dispersive diffraction configuration, it was proposed to use a multichannel collimator (MCC). This solution has been implemented to fit the constraints of the Paris-Edimburg (PE) large volume press and it is now routinely used on beamline ID27 of the European Synchrotron Radiation Facility. In this contribution, we present our adaptation of the MCC device accessible at ID27 for the DAC experiment. Because of the small sample volume a careful alignment procedure between the MCC slits and the DAC had to be implemented. The data analysis procedure initially developed by Eggert et al. has also been completed in order to take into account the complex contribution of the MCC slits. A large reduction of the Compton diffusion from the diamond anvils is obtained enabling quantitative structure factor measurement, even for the weakest x-ray scatterer liquid. Experimental results on fluid hydrogen will be presented to test the limits of this new setup. In collaboration with Gaston Garbarino, ESRF, France; Frederic Datchi, Sandra Ninet, Université Pierre et Marie Curie-Paris VI, France; Dylan Spaulding, Paul Loubeyre, CEA, DAM, DIF, France; and Mohamed Mezouar, ESRF, France.

Naringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 Inflammasome.

PubMed

Chen, Fenqin; Wei, Guozhu; Xu, Jiao; Ma, Xiaoyu; Wang, Qiuyue

2018-06-22

The Nucleotide binding and oligomerization domain-like receptorfamily pyrin domain-containing 3 (NLRP3)-inflammasome plays an important role in various diseases, including a variety of kidney diseases. Naringin exhibits anti-inflammatory and anti-oxidation effects among others, but its specific mechanisms are not clear. We investigated the expression of the NLRP3-inflammasome under high-glucose conditions, assessed the effects of naringin on that process, and further elucidated the role of naringin in the pathogenesis of diabetic kidney disease(DKD). To assess the therapeutic potential of naringin and the mechanisms involved, we cultured rat glomerular mesangial cells and grouped them according to different glucose concentrations, different action times, different concentrations of MCC950, and different concentrations of naringin.The cell proliferation was measured by MTT assay. The expression of Interleukin-1β(IL-1β) and Interleukin18 (IL-18) in the cell supernatant were detected by ELISA. The expression and activity of NLPR3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and Caspase-1 were detected by Western Blot. The expressions of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in rat glomerular mesangial cells were significantly higher in the high glucose (HG) group than in the control normal glucose (NG) group and exhibited time-dependence activity. The expression levels of NLRP3, caspase-1, IL-1β, and IL-18 in different treatment groups were significantly lower compared with the HG group after 48 h of MCC950 pre-treatment (p < 0.05). Pre-treatment with naringin produced the same results. Naringin also inhibited the proliferation of cells. The NLRP3-inflammasome potentially plays a role in the process of activation and inflammation of glomerular mesangial cells as induced by high-glucose conditions. Naringin inhibited the proliferation of cells that were induced by high glucose. Further, it reduced the expression of inflammatory factors that are mediated by NLRP3 through the NLRP3-caspase-1-IL-1β/IL-18 signaling pathway, which makes naringin a potentially novel treatment for DKD disease.

s95-16439

NASA Image and Video Library

2014-08-14

S95-16439 (13-22 July 1995) --- An overall view from the rear shows activity in the new Mission Control Center (MCC), opened for operation and dedicated during the STS-70 mission. The new MCC, developed at a cost of about 50 million, replaces the main-frame based, NASA-unique design of the old Mission Control with a standard workstation-based, local area network system commonly in use today.

29 CFR 782.5 - Loaders.

Code of Federal Regulations, 2012 CFR

2012-07-01

... parte Nos. MC-2 and MC-3, 28 M.C.C. 125, 133, 134, 139), is an employee of a carrier subject to section... U.S. 649; Pyramid Motor Freight Corp. v. Ispass, 330 U.S. 695; Walling v. Gordon's Transport (W.D...; Walling v. Huber & Huber Motor Express, 67 F. Supp. 855; Ex parte Nos. MC-2 and MC-3, 28 M.C.C. 125, 133...

29 CFR 782.5 - Loaders.

Code of Federal Regulations, 2013 CFR

2013-07-01

... parte Nos. MC-2 and MC-3, 28 M.C.C. 125, 133, 134, 139), is an employee of a carrier subject to section... U.S. 649; Pyramid Motor Freight Corp. v. Ispass, 330 U.S. 695; Walling v. Gordon's Transport (W.D...; Walling v. Huber & Huber Motor Express, 67 F. Supp. 855; Ex parte Nos. MC-2 and MC-3, 28 M.C.C. 125, 133...

29 CFR 782.5 - Loaders.

Code of Federal Regulations, 2014 CFR

2014-07-01

... parte Nos. MC-2 and MC-3, 28 M.C.C. 125, 133, 134, 139), is an employee of a carrier subject to section... U.S. 649; Pyramid Motor Freight Corp. v. Ispass, 330 U.S. 695; Walling v. Gordon's Transport (W.D...; Walling v. Huber & Huber Motor Express, 67 F. Supp. 855; Ex parte Nos. MC-2 and MC-3, 28 M.C.C. 125, 133...

STS-56 CAPCOMs Chilton and Brown monitor mission from a console at JSC MCC

NASA Image and Video Library

1993-04-17

STS056-S-080 (13 April 1993) --- Astronauts Kevin P. Chilton (left) and Curtis L. Brown Jr. are seen at the spacecraft communicator (CAPCOM) console in the flight control room of Houston's Mission Control Center (MCC). The two are part of the CAPCOM team who communicated with the five crewmembers aboard Discovery for the STS-56 mission in Earth orbit.

Effect of a single 1200 Mg dose of Mucinex® on mucociliary and cough clearance during an acute respiratory tract infection.

PubMed

Bennett, W D; Kala, A; Duckworth, H; Zeman, K L; Wu, J; Henderson, A; Yopp, M; Rubin, B K

2015-11-01

Observational studies suggest that orally administered guaifenesin (GGE) may thin lower respiratory tract secretions but none have examined its effects on mucociliary and cough clearance (MCC/CC) during a respiratory tract infection (RTI). The current study was a randomized, parallel-group, double-blind, placebo-controlled study in non-smoking adults who suffered from an acute upper RTI. We assessed the effects of a single dose of Mucinex(®) 1200 mg (2 × 600 mg extended release tablets) (ER GGE) on 1) MCC/CC by assessing the rate of removal from the lung of inhaled radioactive tracer particles (Tc99m-sulfur colloid), 2) sputum dynamic rheology by stress/strain creep transformation over the linear part of the curve, 3) sessile drop interfacial tension by the deNouy ring technique, and 4) subjective symptom measures. MCC was measured during the morning (period 1) and compared to that in the afternoon 4 h later (period 2) immediately following either drug (n = 19) or placebo (n = 19). For both period 1 and 2 subjects performed 60 voluntary coughs from 60 to 90 min after inhalation of radio-labeled aerosol for a measure of CC. Sputum properties were measured from subjects who expectorated sputum during the cough period post treatment (n = 8-12 for each cohort). We found no effect of ER GGE on MCC or CC compared to placebo. MCC through 60 min for period 1 vs. 2 = 8.3 vs. 11.8% (placebo) and = 9.7 vs. 11.1% (drug) (NS) and CC for period 1 vs. 2 was 9.9 vs. 9.1% (placebo) and 10.8 vs. 5.6% (drug) (NS). There was no significant difference in sputum biophysical properties after administration of drug or placebo. There was no significant effect of a single dose of ER GGE on MCC/CC or on sputum biophysical properties compared to placebo in this population of adult patients with an acute RTI. ClinicalTrials.gov Identifier: NCT01114581. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Deviated Nasal Septum Type on Nasal Mucociliary Clearance, Olfactory Function, Quality of Life, and Efficiency of Nasal Surgery.

PubMed

Berkiten, Güler; Kumral, Tolgar Lütfi; Saltürk, Ziya; Atar, Yavuz; Yildirim, Güven; Uyar, Yavuz; Aydoğdu, Imran; Arslanoğlu, Ahmet

2016-07-01

The aim of this study was to analyze the influence of deviated nasal septum (DNS) type on nasal mucociliary clearance, quality of life (QoL), olfactory function, and efficiency of nasal surgery (septoplasty with or without inferior turbinate reduction and partial middle turbinectomy). Fifty patients (20 females and 30 males) with septal deviation were included in the study and were divided into 6 groups according to deviation type after examination by nasal endoscopy and paranasal computed tomography. The saccharin clearance test to evaluate the nasal mucociliary clearance time, Connecticut Chemosensory Clinical Research Center smell test for olfactory function, and sinonasal outcome test-22 (SNOT-22) for patient satisfaction were applied preoperatively and postoperatively at the sixth week after surgery. Nasal mucociliary clearance, smell, and SNOT-22 scores were measured before surgery and at the sixth week following surgery. No significant difference was found in olfactory and SNOT-22 scores for any of the DNS types (both convex and concave sides) (P > 0.05). In addition, there was no difference in the saccharin clearance time (SCT) of the concave and convex sides (P > 0.05). According to the DNS type, the mean SCT of the convex sides showed no difference, but that of the concave sides showed a difference in types 3, 4, 5, and 6. These types had a prolonged SCT (P < 0.05). Olfactory scores revealed no difference postoperatively in types 5 and 6 but were decreased significantly in types 1 to 4 (P < 0.05). There was no significant difference in the healing of both the mucociliary clearance (MCC) and olfactory functions. SNOT-22 results showed a significant decrease in type 3. All DNS types disturb the QoL regarding nasal MCC and olfaction functions. MCC values, olfactory function, and QoL scores are similar among the DNS types. Both sides of the DNS types affect the MCC scores symmetrically. Septal surgery improves olfaction function and QoL at the sixth week following surgery but disturbs nasal MCC; thus, the sixth week is too early to assess nasal MCC.

Subliminal enhancement of predictive effects during syntactic processing in the left inferior frontal gyrus: an MEG study

PubMed Central

Iijima, Kazuki; Sakai, Kuniyoshi L.

2014-01-01

Predictive syntactic processing plays an essential role in language comprehension. In our previous study using Japanese object-verb (OV) sentences, we showed that the left inferior frontal gyrus (IFG) responses to a verb increased at 120–140 ms after the verb onset, indicating predictive effects caused by a preceding object. To further elucidate the automaticity of the predictive effects in the present magnetoencephalography study, we examined whether a subliminally presented verb (“subliminal verb”) enhanced the predictive effects on the sentence-final verb (“target verb”) unconsciously, i.e., without awareness. By presenting a subliminal verb after the object, enhanced predictive effects on the target verb would be detected in the OV sentences when the transitivity of the target verb matched with that of the subliminal verb (“congruent condition”), because the subliminal verb just after the object could determine the grammaticality of the sentence. For the OV sentences under the congruent condition, we observed significantly increased left IFG responses at 140–160 ms after the target verb onset. In contrast, responses in the precuneus and midcingulate cortex (MCC) were significantly reduced for the OV sentences under the congruent condition at 110–140 and 280–300 ms, respectively. By using partial Granger causality analyses for the OV sentences under the congruent condition, we revealed a bidirectional interaction between the left IFG and MCC at 60–160 ms, as well as a significant influence from the MCC to the precuneus. These results indicate that a top-down influence from the left IFG to the MCC, and then to the precuneus, is critical in syntactic decisions, whereas the MCC shares its task-set information with the left IFG to achieve automatic and predictive processes of syntax. PMID:25404899

Subliminal enhancement of predictive effects during syntactic processing in the left inferior frontal gyrus: an MEG study.

PubMed

Iijima, Kazuki; Sakai, Kuniyoshi L

2014-01-01

Predictive syntactic processing plays an essential role in language comprehension. In our previous study using Japanese object-verb (OV) sentences, we showed that the left inferior frontal gyrus (IFG) responses to a verb increased at 120-140 ms after the verb onset, indicating predictive effects caused by a preceding object. To further elucidate the automaticity of the predictive effects in the present magnetoencephalography study, we examined whether a subliminally presented verb ("subliminal verb") enhanced the predictive effects on the sentence-final verb ("target verb") unconsciously, i.e., without awareness. By presenting a subliminal verb after the object, enhanced predictive effects on the target verb would be detected in the OV sentences when the transitivity of the target verb matched with that of the subliminal verb ("congruent condition"), because the subliminal verb just after the object could determine the grammaticality of the sentence. For the OV sentences under the congruent condition, we observed significantly increased left IFG responses at 140-160 ms after the target verb onset. In contrast, responses in the precuneus and midcingulate cortex (MCC) were significantly reduced for the OV sentences under the congruent condition at 110-140 and 280-300 ms, respectively. By using partial Granger causality analyses for the OV sentences under the congruent condition, we revealed a bidirectional interaction between the left IFG and MCC at 60-160 ms, as well as a significant influence from the MCC to the precuneus. These results indicate that a top-down influence from the left IFG to the MCC, and then to the precuneus, is critical in syntactic decisions, whereas the MCC shares its task-set information with the left IFG to achieve automatic and predictive processes of syntax.

First report on the molecular prevalence of Mycoplasma capricolum subspecies capripneumoniae (Mccp) in goats the cause of contagious caprine pleuropneumonia (CCPP) in Balochistan province of Pakistan.

PubMed

Awan, Mohammad Arif; Abbas, Ferhat; Yasinzai, Masoom; Nicholas, Robin A J; Babar, Shakeel; Ayling, Roger D; Attique, Mohammad Adnan; Ahmed, Zafar; Wadood, Abdul; Khan, Faisal Ameer

2010-10-01

Contagious caprine pleuropneumonia (CCPP) caused by Mycoplasma capricolum subspecies capripneumoniae (Mccp) is a disease of goats which causes high morbidity and mortality and is reported in many countries of the world. There are probably no reports on the molecular prevalence of Mccp, Mycoplasma capricolum subsp. capricolum (Mcc) and Mycoplasma putrefaciens (Mp) in Balochistan and any other part of Pakistan. Thirty goats (n = 30) with marked respiratory symptoms were selected and procured from forty goat flocks in Pishin district of Balochistan in 2008. The genomic deoxyribonucleic acid (DNA) from the lung samples (n = 30) of the slaughtered goats was purified and subjected to polymerase chain reaction (PCR) assays for the presence of Mycoplasma mycoides cluster members and Mp. The PCR-RFLP (restriction fragment length polymorphism) was also used to further confirm the Mccp. Of the thirty lung samples 17 (56.67%) were positive for the molecular prevalence of Mcc, Mccp and Mp. In total the molecular prevalence was observed as 17.65% for Mccp (n = 3), 70.59% for Mcc (n = 12) and 11.76% for Mp (n = 2). The RFLP profile has also validated the PCR results of Mccp by yielding two bands of 190 and 126 bp. The results of PCR-RFLP coupled with the presence of fibrinous pleuropneumonia and pleurisy during postmortem of goats (n = 3) strongly indicated the prevalence of CCPP in this part of world. Moreover the prevalence of Mcc and Mp is also alarming in the study area. We report for the very first time the molecular prevalence of Mcc, Mccp, and Mp in the lung tissues of goats in the Pishin district of Balochistan, Pakistan.

Imaging demonstration of a flexible micro-OCT endobronchial probe (Conference Presentation)

NASA Astrophysics Data System (ADS)

Cui, Dongyao; Chu, Kengyeh K.; Ford, Timothy N.; Hyun, Daryl Chulho; Leung, Hui Min; Yin, Biwei; Birket, Susan E.; Solomon, George M.; Rowe, Steven M.; Tearney, Guillermo J.

2017-04-01

The human respiratory system is protected by a defense mechanism termed mucociliary clearance (MCC). Deficiency in MCC leads to respiratory obstruction and pulmonary infection, which often are the main causes of morbidity and mortality in diseases such as cystic fibrosis and chronic obstructive pulmonary disease (COPD). Studying key parameters that govern MCC, including ciliary beat frequency, velocity and volume of airway mucus transport, as well as periciliary liquid layer thickness are therefore of great importance in understanding human respiratory health. However, direct, in vivo visualization of ciliary function and MCC has been challenging, hindering the diagnosis of disease pathogenesis and mechanistic evaluation of novel therapeutics. Our laboratory has previously developed a 1-µm resolution optical coherence tomography method, termed Micro-OCT, which is a unique tool for visualizing the spatiotemporal features of ciliary function and MCC. We have previously described the design of a flexible 2.5 mm Micro-OCT probe that is compatible with standard flexible bronchoscopes. This device utilizes a common-path interferometer and annular sample arm apodization to attain a sharply focused spot over an extended depth of focus. Here, we present the most recent iteration of this probe and demonstrate its imaging performance in a mouse trachea tissue culture model. In addition, we have developed an ergonomic assembly for attaching the probe to a standard bronchoscope. The ergonomic assembly fixes the Micro-OCT probe's within the bronchoscope and contains a means transducing linear motion through the sheath so that the Micro-OCT beam can be scanned along the trachea. We have tested the performance of these devices for Micro-OCT imaging in an anatomically correct model of the human airway. Future studies are planned to use this technology to conduct Micro-OCT in human trachea and bronchi in vivo.

Muc5b is required for airway defence

NASA Astrophysics Data System (ADS)

Roy, Michelle G.; Livraghi-Butrico, Alessandra; Fletcher, Ashley A.; McElwee, Melissa M.; Evans, Scott E.; Boerner, Ryan M.; Alexander, Samantha N.; Bellinghausen, Lindsey K.; Song, Alfred S.; Petrova, Youlia M.; Tuvim, Michael J.; Adachi, Roberto; Romo, Irlanda; Bordt, Andrea S.; Bowden, M. Gabriela; Sisson, Joseph H.; Woodruff, Prescott G.; Thornton, David J.; Rousseau, Karine; de La Garza, Maria M.; Moghaddam, Seyed J.; Karmouty-Quintana, Harry; Blackburn, Michael R.; Drouin, Scott M.; Davis, C. William; Terrell, Kristy A.; Grubb, Barbara R.; O'Neal, Wanda K.; Flores, Sonia C.; Cota-Gomez, Adela; Lozupone, Catherine A.; Donnelly, Jody M.; Watson, Alan M.; Hennessy, Corinne E.; Keith, Rebecca C.; Yang, Ivana V.; Barthel, Lea; Henson, Peter M.; Janssen, William J.; Schwartz, David A.; Boucher, Richard C.; Dickey, Burton F.; Evans, Christopher M.

2014-01-01

Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b-/- mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.

A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling

PubMed Central

Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

2017-01-01

The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1–Bub3 and BubR1–Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1–Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/CCdc20) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1–Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment. DOI: http://dx.doi.org/10.7554/eLife.22513.001 PMID:28072388

Unknown primary Merkel cell carcinoma: 23 new cases and a review.

PubMed

Tarantola, Tina I; Vallow, Laura A; Halyard, Michele Y; Weenig, Roger H; Warschaw, Karen E; Weaver, Amy L; Roenigk, Randall K; Brewer, Jerry D; Otley, Clark C

2013-03-01

Knowledge is limited regarding unknown primary Merkel cell carcinoma (UPMCC). We sought to document the characteristics and behavior of UPMCC, and determine the most appropriate treatment. A multicenter, retrospective, consecutive study reviewing patients given a diagnosis of UPMCC between 1981 and 2008 was completed. In addition, a literature review of cases of UPMCC was performed. In all, 23 patients with UPMCC are described and 34 cases from previous reports are compiled. Among the 23 new cases of UPMCC, the average age at diagnosis was 66.0 years; the majority of patients were male (87%) and Caucasian (100% of those reported). One patient was immunosuppressed, and 39% had a history of other cancer. After the initial biopsy, 16 patients had further evaluation of the involved lymph node basin. Half of these had additional positive nodes (8 of 16). The majority of patients had lymph node basin involvement only (78%), whereas 22% had lymph node basin and distant metastasis. The most common lymph node basin involved was inguinal. The median size of the involved lymph node at diagnosis was 5.0 cm. At 2 years, the overall survival of stage IIIB UPMCC was significantly improved versus stage IIIB known primary Merkel cell carcinoma (MCC): 76.9% to 36.4%. Limited number of cases and retrospective review are limitations. Our data demonstrate improved overall survival in patients with stage IIIB UPMCC versus those with stage IIIB known primary MCC. Because of the unpredictable natural history of UPMCC, we recommend individualization of care based on the details of each patient's clinical presentation. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

JSC MCC Bldg 30 personnel monitor STS-26 post landing activities

NASA Image and Video Library

1988-10-03

JSC Mission Control Center (MCC) Bldg 30 flight control room (FCR) personnel monitor STS-26 post landing activities and ceremonies at Edwards Air Force Base (EAFB) via their monitors. Displayed on front screens are approach and landing diagrams, data, the space shuttle program insignia, the STS-26 mission insignia, the Mission Operations Directorate insignia, and the STS-26 crew standing in front of Discovery, Orbiter Vehicle (OV) 103.

Software Design Document MCC CSCI (1). Volume 1 Sections 1.0-2.18

DTIC Science & Technology

1991-06-01

AssociationUserProtocol /simnet/common!include/prot ____________________ ____________________ ocol/p assoc.h Primitive long Standard C type...Information. 2.2.1.4.2 ProcessMessage ProcessMessage processes a message from another process. type describes the message as either one-way, a synchronous or...Macintosh Consoles. This is sometimes necessary due to normal clock skew so that operations among the MCC components will remain synchronized . This

Coverage of STS-104 Launch Coverage of Flight Controllers in MCC.

NASA Image and Video Library

2001-07-12

JSC2001-E-21337 (12 July 2001) --- Rob Navias (right), at the Public Affairs Officer (PAO) console in Houston's Mission Control Center (MCC), awaits to do his commentary as he views the firing of Space Shuttle Atlantis' main engines on his monitor just seconds before launch and the beginning of the STS-104 mission. Daniel K. Carpenter, director of the Public Affairs Office, looks on.

Display formats manual

NASA Technical Reports Server (NTRS)

Runnels, R. L.

1973-01-01

The standards and procedures for the generation of operational display formats to be used in the Mission Control Center (MCC) display control system are presented. The required effort, forms, and fundamentals for the design, specifications, and production of display formats are identified. The principles of display design and system constraints controlling the creation of optimum operational displays for mission control are explained. The basic two types of MCC display systems for presenting information are described.

STS-49 Endeavour, Orbiter Vehicle (OV) 105, Planning Team in MCC Bldg 30 FCR

NASA Image and Video Library

1992-05-15

S92-36606 (20 May 1992) --- STS-49 Endeavour, Orbiter Vehicle (OV) 105, Planning Team with Flight Director (FD) James M. Heflin, Jr. (front right next to ship model) poses in Johnson Space Center?s (JSC) Mission Control Center (MCC) Bldg 30 Flight Control Room (FCR). The group stands in front of visual displays projecting STS-49 data and ground track map.

STS-100 MCC Launch Activities

NASA Image and Video Library

2001-04-19

JSC2001-E-12125 (19 April 2001) --- Astronauts Mark L. Polansky, from the left, Christopher J. (Gus) Loria, and Scott D. Altman discuss the approaching STS-100 launch at their positions at the Spacecraft Communicator console in Houston's Mission Control Center (MCC). Loria's position addresses weather issues, of which there were few on this particular launch. He will also be assigned to weather matters for the entry phase of the flight.

Constant Perimeter, Varying Area: A Case Study of Teaching and Learning Mathematics to Design a Fish Rack

ERIC Educational Resources Information Center

Rickard, Anthony

2005-01-01

This case study examines a sixth-grade teacher and her students in an urban school district in Alaska, engaging in an activity from a module that is part of the Math in a Cultural Context (MCC) series. By analyzing the module, the teacher's practice, classroom discourse, and students' work, the case shows that the teacher and the MCC module…

Race/ethnicity, color-blind racial attitudes, and multicultural counseling competence: the moderating effects of multicultural counseling training.

PubMed

Chao, Ruth Chu-Lien; Wei, Meifen; Good, Glenn E; Flores, Lisa Y

2011-01-01

Increasing trainees' multicultural counseling competence (MCC) has been a hot topic in counseling. Scholars have identified predictors (e.g., race/ethnicity, color-blindness) of MCC, and educators provide multicultural training for trainees. Using a sample of 370 psychology trainees, this study examined whether multicultural training (a) moderated racial/ethnic differences on MCC and (b) changed the relationship between color-blindness and MCC. Results indicated a significant interaction effect of race/ethnicity (i.e., White vs. ethnic minority) and multicultural training on multicultural awareness, but not on multicultural knowledge. Specifically, at lower levels of training, racial/ethnic minority trainees had significantly higher multicultural awareness than their White counterparts; at higher levels of training, no significant difference was found. Described differently, more training significantly enhanced Whites' multicultural awareness, but did not enhance racial/ethnic minority trainees' awareness. Additionally, there was a significant interaction effect of color-blindness and multicultural training on multicultural knowledge, but not on multicultural awareness. The association between color-blindness and multicultural knowledge was stronger at higher levels of multicultural training than at lower levels of training. Alternatively, the effect of training on enhancing knowledge was stronger for those with lower color-blindness than for those with higher color-blindness.

An experimental investigation of temperature rise during compaction of pharmaceutical powders.

PubMed

Krok, Alexander; Mirtic, Andreja; Reynolds, Gavin K; Schiano, Serena; Roberts, Ron; Wu, Chuan-Yu

2016-11-20

During pharmaceutical powder compaction, temperature rise in the compressed powder can affect physiochemical properties of the powder, such as thermal degradation and change in crystallinity. Thus, it is of practical importance to understand the effect of process conditions and material properties on the thermal response of pharmaceutical formulations during compaction. The aim of this study was to examine the temperature rise of pharmaceutical powders during tableting, in particular, to explore how the temperature rise depends on material properties, compression speed and tablet shape. Three grades of microcrystalline cellulose (MCC) were considered: MCC Avicel pH 101, MCC Avicel pH 102 and MCC DG. These powders were compressed using a compaction simulator at various compaction speeds (10-500mm/s). Flat faced, shallow convex and normal convex tablets were produced and temperature distributions on the surface of theses tablets upon ejection were examined using an infrared thermoviewer. It was found that an increase in the compaction speed led to an increase in the average surface temperature. A higher surface temperature was induced when the powder was compressed into a tablet with larger surface curvature. This was primarily due to the increasing degree of powder deformation (i.e. the volume reduction) and the effect of interparticule/wall friction. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural analysis and deformation characteristics of the Yingba metamorphic core complex, northwestern margin of the North China craton, NE Asia

NASA Astrophysics Data System (ADS)

Yin, Congyuan; Zhang, Bo; Han, Bao-Fu; Zhang, Jinjiang; Wang, Yang; Ai, Sheng

2017-01-01

The presence of the Yingba (Yinggete-Bagemaode) metamorphic core complex (MCC) is confirmed near the Sino-Mongolian border in China. We report its structural evolution and the rheological features of ductile shear zones within this complex. Three deformations (Ds, Dm, and Db) since the Late Jurassic are identified. Ds is characterized by ductile structures that resulted from early NW-oriented, low-angle, extensional ductile shearing. Dm is associated with partial melting and magmatic diapirism, which accelerated the formation of the dome-like geometry of the Yingba MCC. Synchronously with or slightly subsequently to Ds and Dm, the Yingba MCC was subjected to brittle, extensional faulting (Db), which was accompanied by the exhumation of the lower crust and the formation of supracrustal basins. The ductile shearing (Ds) developed under greenschist-to amphibolite-facies metamorphic conditions (400-650 °C), as indicated by microstructures in quartz and feldspar, quartz [c] axis fabrics, and two-feldspar geothermometry. The mean kinematic vorticity estimates of 48-62% show a pure shear-preferred flow during Ds. The Yingba MCC provides an excellent sample that recorded an intermediate to high temperature shearing, which also implies the widely extensional regime in northeastern Asia at that time.

Surface currents in the Bohai Sea derived from the Korean Geostationary Ocean Color Imager (GOCI)

NASA Astrophysics Data System (ADS)

Jiang, L.; Wang, M.

2016-02-01

The first geostationary ocean color satellite sensor, the Geostationary Ocean Color Imager (GOCI) onboard the Korean Communication, Ocean, and Meteorological Satellite can monitor and measure ocean phenomena over an area of 2500 × 2500 km2 around the western Pacific region centered at 36°N and 130°E. Hourly measurements during the day around 9:00 to 16:00 local time are a unique capability of GOCI to monitor ocean features of higher temporal variability. In this presentation, we show some recent results of GOCI-derived ocean surface currents in the Bohai Sea using the Maximum Cross-Correlation (MCC) feature tracking method and compare the results with altimetry-inversed tidal current observations produced from Oregon State University (OSU) Tidal Inversion Software (OTIS). The performance of the GOCI-based MCC method is assessed and the discrepancies between the GOCI- and OTIS-derived currents are evaluated. A series of sensitivity studies are conducted with images from various satellite products and of various time differences, MCC adjustable parameters, and influence from other forcings such as wind, to find the best setups for optimal MCC performance. Our results demonstrate that GOCI can effectively provide real-time monitoring of not only water optical, biological, and biogeochemical variability, but also the physical dynamics in the region.

The AGING Initiative experience: a call for sustained support for team science networks.

PubMed

Garg, Tullika; Anzuoni, Kathryn; Landyn, Valentina; Hajduk, Alexandra; Waring, Stephen; Hanson, Leah R; Whitson, Heather E

2018-05-18

Team science, defined as collaborative research efforts that leverage the expertise of diverse disciplines, is recognised as a critical means to address complex healthcare challenges, but the practical implementation of team science can be difficult. Our objective is to describe the barriers, solutions and lessons learned from our team science experience as applied to the complex and growing challenge of multiple chronic conditions (MCC). MCC is the presence of two or more chronic conditions that have a collective adverse effect on health status, function or quality of life, and that require complex healthcare management, decision-making or coordination. Due to the increasing impact on the United States society, MCC research has been identified as a high priority research area by multiple federal agencies. In response to this need, two national research entities, the Healthcare Systems Research Network (HCSRN) and the Claude D. Pepper Older Americans Independence Centers (OAIC), formed the Advancing Geriatrics Infrastructure and Network Growth (AGING) Initiative to build nationwide capacity for MCC team science. This article describes the structure, lessons learned and initial outcomes of the AGING Initiative. We call for funding mechanisms to sustain infrastructures that have demonstrated success in fostering team science and innovation in translating findings to policy change necessary to solve complex problems in healthcare.

Flight directors at JSC MCC Bldg 30 monitor STS-30 prelaunch activities

NASA Image and Video Library

1989-05-04

Only moments away from ignition, Atlantis, Orbiter Vehicle (OV) 104, and its five member crew are the subjects of concern drawing serious countenance in this scene in the Flight Control Room (FCR) of JSC's Mission Control Center (MCC) Bldg 30. Ascent Flight Director Alan L. Briscoe, monitors the Kennedy Space Center pre-launch activity from the flight director (FD) console, along with Ronald D. Dittemore (center) and N. Wayne Hale, Jr.

JSC officials in MCC Bldg 30 monitor STS-26 Discovery, OV-103, activity

NASA Image and Video Library

1988-10-03

JSC officials, laughing, listen to crewmembers' commentary onboard Discovery, Orbiter Vehicle (OV) 103, during STS-26. In the Flight Control Room (FCR) of JSC's Mission Control Center (MCC) Bldg 30 and seated at the Mission Operations Directorate (MOD) console, MOD Director Eugene F. Kranz (foreground), wearing red, white and blue vest, smiles along with JSC Director Aaron Cohen and Flight Crew Operations Deputy Director Henry W. Hartsfield, Jr. (far right).

JSC Officials in MCC Bldg 30 monitor STS-26 Discovery, OV-103, activity

NASA Technical Reports Server (NTRS)

1988-01-01

JSC Officials, laughing, listen to crewmembers' commentary onboard Discovery, Orbiter Vehicle (OV) 103, during STS-26. In the Flight Control Room (FCR) of JSC's Mission Control Center (MCC) Bldg 30 and seated at the Mission Operations Directorate (MOD) console, MOD Director Eugene F. Kranz (foreground), wearing red, white and blue vest, smiles along with JSC Director Aaron Cohen and Flight Crew Operations Deputy Director Henry W. Hartsfield, Jr. (far right).

Coverage of STS-104 Launch Coverage of Flight Controllers in MCC.

NASA Image and Video Library

2001-07-12

JSC2001-E-21341 (12 July 2001) --- From a familiar setting near the rear of shuttle flight control room (WFCR) at Houston's Mission Control Center (MCC), Wayne Hale (second left), ascent flight director for STS-104, pays close attention to new data related to the Space Shuttle Atlantis and its impending launch from the Kennedy Space Center (KSC) in Florida. Several other flight controllers are visible in the wide shot.

Computational fluid dynamics analysis of SSME phase 2 and phase 2+ preburner injector element hydrogen flow paths

NASA Technical Reports Server (NTRS)

Ruf, Joseph H.

1992-01-01

Phase 2+ Space Shuttle Main Engine powerheads, E0209 and E0215 degraded their main combustion chamber (MCC) liners at a faster rate than is normal for phase 2 powerheads. One possible cause of the accelerated degradation was a reduction of coolant flow through the MCC. Hardware changes were made to the preburner fuel leg which may have reduced the resistance and, therefore, pulled some of the hydrogen from the MCC coolant leg. A computational fluid dynamics (CFD) analysis was performed to determine hydrogen flow path resistances of the phase 2+ fuel preburner injector elements relative to the phase 2 element. FDNS was implemented on axisymmetric grids with the hydrogen assumed to be incompressible. The analysis was performed in two steps: the first isolated the effect of the different inlet areas and the second modeled the entire injector element hydrogen flow path.

The Solubility of Microcrystalline Cellulose in Sodium Hydroxide Solution Is Inconsistent with International Specifications.

PubMed

Kodama, Hanayo; Tamura, Yoshinaga; Kamei, Ichiro; Sato, Kyoko; Akiyama, Hiroshi

2017-01-01

Microcrystalline cellulose (MCC) is used globally as an inactive ingredient in food and nutraceutical products and is commonly used as a food additive. To confirm the conformity of MCC to the solubility requirements stipulated in international specifications, the solubilities of commercially available MCC products were tested in sodium hydroxide (NaOH) solution. All of the samples were insoluble in NaOH solution, which is inconsistent with the descriptions provided in international specifications. We also prepared celluloses with different degree of polymerization (DP) values by acid hydrolysis. Celluloses with lower DP were prepared using a three-step process, and their solubilities were tested in NaOH solution. These celluloses were found to be insoluble, which is inconsistent with the descriptions provided in international specifications. The present study suggests that the descriptions of the solubility of the celluloses in NaOH solution found in the current international specifications should be revised.

Increasing conclusiveness of clinical breath analysis by improved baseline correction of multi capillary column - ion mobility spectrometry (MCC-IMS) data.

PubMed

Szymańska, Ewa; Tinnevelt, Gerjen H; Brodrick, Emma; Williams, Mark; Davies, Antony N; van Manen, Henk-Jan; Buydens, Lutgarde M C

2016-08-05

Current challenges of clinical breath analysis include large data size and non-clinically relevant variations observed in exhaled breath measurements, which should be urgently addressed with competent scientific data tools. In this study, three different baseline correction methods are evaluated within a previously developed data size reduction strategy for multi capillary column - ion mobility spectrometry (MCC-IMS) datasets. Introduced for the first time in breath data analysis, the Top-hat method is presented as the optimum baseline correction method. A refined data size reduction strategy is employed in the analysis of a large breathomic dataset on a healthy and respiratory disease population. New insights into MCC-IMS spectra differences associated with respiratory diseases are provided, demonstrating the additional value of the refined data analysis strategy in clinical breath analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Creating Conditions for Patients’ Values to Emerge in Clinical Conversations: Perspectives of Health Care Team Members

PubMed Central

Berry, Andrew B.L.; Lim, Catherine; Hartzler, Andrea L.; Hirsch, Tad; Ludman, Evette; Wagner, Edward H.; Ralston, James D.

2017-01-01

Eliciting, understanding, and honoring patients’ values— the things most important to them in daily life—is a cornerstone of patient-centered care. However, this rarely occurs explicitly as a routine part of clinical practice. This is particularly problematic for individuals with multiple chronic conditions (MCC) because they face difficult choices about how to balance competing demands for self-care in accordance with their values. In this study, we sought to inform the design of interventions to support conversations about patient values between patients with MCC and their health care providers. We conducted a field study that included observations of 21 clinic visits for patients who have MCC, and interviews with 16 care team members involved in those visits. This paper contributes a practice-based account of ways in which providers engage with patient values, and discusses how future work in interactive systems design might extend and enrich these engagements. PMID:28890950

Midcingulate Motor Map and Feedback Detection: Converging Data from Humans and Monkeys

PubMed Central

Procyk, Emmanuel; Wilson, Charles R. E.; Stoll, Frederic M.; Faraut, Maïlys C. M.; Petrides, Michael; Amiez, Céline

2016-01-01

The functional and anatomical organization of the cingulate cortex across primate species is the subject of considerable and often confusing debate. The functions attributed to the midcingulate cortex (MCC) embrace, among others, feedback processing, pain, salience, action-reward association, premotor functions, and conflict monitoring. This multiplicity of functional concepts suggests either unresolved separation of functional contributions or integration and convergence. We here provide evidence from recent experiments in humans and from a meta-analysis of monkey data that MCC feedback-related activity is generated in the rostral cingulate premotor area by specific body maps directly related to the modality of feedback. As such, we argue for an embodied mechanism for adaptation and exploration in MCC. We propose arguments and precise tools to resolve the origins of performance monitoring signals in the medial frontal cortex, and to progress on issues regarding homology between human and nonhuman primate cingulate cortex. PMID:25217467

Mrs. Haise in viewing room overlooking FCR

NASA Image and Video Library

1970-04-14

S70-34900 (14 April 1970) --- Mrs. Mary Haise receives an explanation of the revised flight plan of the Apollo 13 mission from astronaut Gerald P. Carr in the viewing room of the Mission Control Center (MCC), Building 30, at the Manned Spacecraft Center (MSC). Her husband, astronaut Fred W. Haise Jr., lunar module pilot for the Apollo 13 mission, was joining fellow crew members, astronauts James A. Lovell Jr., and John L. Swigert Jr. in making correction in their spacecraft following discovery of an oxygen cell failure several hours earlier.

Evaluation of tableting and tablet properties of Kollidon SR: the influence of moisture and mixtures with theophylline monohydrate.

PubMed

Hauschild, Karsten; Picker-Freyer, Katharina M

2006-02-01

The aim of the study was firstly to investigate the influence of moisture on the tableting and tablet properties of Kollidon SR and secondly to investigate the influence of theophylline monohydrate on the tableting behavior and tablet properties produced from binary mixtures with Kollidon SR. In comparison to Kollidon SR, microcrystalline cellulose (MCC) was used. The glass transition temperature (Tg) of the powder over the whole range of RH (0-90%), and in addition, the Tg of tablets of Kollidon SR were measured. Densities and flowability of the powders were analyzed. The tablets were produced at five different maximum relative densities (rho(rel), max) on an instrumented eccentric tableting machine. They were produced at three different relative humidities (RH), 30%, 45%, and 60% RH for the pure substances and binary mixtures with different ratios of drug and excipient were tableted at 45% RH. The tableting properties were analyzed by 3D modeling, force-displacement profiles, and compactibility plots. First, the Tg of the powder decreased with increasing RH and the Tg of the tablet was 4-8 K lower than the powder. The predominant deformation of Kollidon SR is plastic deformation and Kollidon SR showed a higher compactibility than MCC. The parameters of the 3D model showed an extreme change between 45 and 60% RH, and at higher RH more and more particles deformed elastically. This was confirmed by analysis of force-displacement profiles. At 60% RH, the radial tensile strength of the Kollidon SR tablets was half of the radial tensile strength at 45% RH. The reason is a higher relative energy of plastic deformation than for MCC. This results in a better utilization of the energy to deform the powder into a tablet and the exceeding of the glass transition temperature at higher RH. In conclusion, at 60% RH at the same rho(rel, max), tableting and tablet properties of Kollidon SR are extremely changed since plasticity is significantly higher. In the second part of the study, the insufficient flowability of theophylline monohydrate can be compensated by using Kollidon SR in a mixture with up to 20% theophylline. Further, pressure plasticity e of MCC and Kollidon SR was lowered in the mixture with theophylline monohydrate. The same is valid for the compactibility. The influence of theophylline monohydrate on the pressure plasticity e of the mixtures was better compensated in the mixture with MCC than in a mixture with Kollidon SR. This compensation was also visible by analyzing the force-displacement-profiles. However, hardly any influence on the radial tensile strength could be detected. Kollidon SR and Kollidon SR mixtures exhibited a higher compactibility than MCC and MCC mixtures. The differences became smaller with increasing theophylline content.

Design And Construction Of A Miniaturized Motor Controller For Interplanetary Rover

NASA Astrophysics Data System (ADS)

Lofgren, Henrik; Lijemark, Tomas; Lamoureux, Enrique; Bruhn, Fredrik; Hagstrom, Maria; Hall, Karin; Ljunggren, Anders; Habinc, Sandi; Gruener, Gabriel; Rusconi, Andrea; Boyes, Ben; Wagenbach, Susanne; Poulakis, Pantelis; Kohler, Johan

2011-10-01

ÅAC Microtec AB is leading an international consortium developing a Motion Control Chip (MCC) for the European Space Agency (ESA) under a TRP contract. The team consists of the prime ÅAC (Sweden), Aeroflex Gaisler (Sweden), Centre Suisse d'Electroniqueet de Microtechnique (CSEM, Switzerland), Selex Galileo Italy), Astrium (UK) and DLR Institute of Space Systems (Germany). In order to improve performance of rovers and robotic arms, one solution is to place the controller physically as close as possible to the motors. This reduces the harness and hence saves weight, decreases thermal leakage from the main system body and simplifies the final assembly. Nevertheless, with this approach the constraints on the electronics become more stringent: the assembly has to survive a very wide temperature range as well as vibrations and possibly dust, and at the same time it should be as small and light as possible. To cope with these design constraints, the Motion Control Chip (MCC) is based on stacked ceramic substrate technology in a Multi Chip Module (MCM), on which active components are assembled as bare dies. This approach was chosen in favor of special large ASIC development to reduce cost and make the design more flexible. By choosing a MCM solution, the design will allow both FPGA and ASICs to be used. FPGAs are used initially to lower the prototyping cost and later be replaced with ASICs as the packaging technology is qualified for the extreme environments of ISS, Mars and Moon. The manufacturing of the first iteration of miniaturized MCC modules is ongoing and initial functional tests have been executed. The results are currently being evaluated and when this is finalized the full test campaign including environmental tests will planned in detail. The tests are assumed to be finalized during the spring of 2011. Aeroflex Gaisler is the official ESA maintainer of the RTEMS port for the LEON3 processor and has been providing support to several developments. CSEM is providing the software for the MCC, which includes PID position, velocity, and torque control for brushed and brushless DC motors, as well as telecommand, telemetry and housekeeping through SpaceWire and CAN bus. Astrium UK is in charge of the definition of requirements for rover locomotion applications of the MCC. Astrium UK has experience from the Beagle project and is responsible for the Exomars rover development. Selex Galileo is in charge of the definition of requirements for three major applications of the MCC: robotic arms, complex motorized payloads (as drills and sample distribution systems) and exoskeletons. DLR Institute of Space Systems contributes to the definition of requirements related to rover locomotion drives and is furthermore in charge of environmental testing of the MCC prototype.

Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy.

PubMed

Goh, Gerald; Walradt, Trent; Markarov, Vladimir; Blom, Astrid; Riaz, Nadeem; Doumani, Ryan; Stafstrom, Krista; Moshiri, Ata; Yelistratova, Lola; Levinsohn, Jonathan; Chan, Timothy A; Nghiem, Paul; Lifton, Richard P; Choi, Jaehyuk

2016-01-19

Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous neuroendocrine carcinoma, associated with the Merkel cell polyomavirus (MCPyV) in 80% of cases. To define the genetic basis of MCCs, we performed exome sequencing of 49 MCCs. We show that MCPyV-negative MCCs have a high mutation burden (median of 1121 somatic single nucleotide variants (SSNVs) per-exome with frequent mutations in RB1 and TP53 and additional damaging mutations in genes in the chromatin modification (ASXL1, MLL2, and MLL3), JNK (MAP3K1 and TRAF7), and DNA-damage pathways (ATM, MSH2, and BRCA1). In contrast, MCPyV-positive MCCs harbor few SSNVs (median of 12.5 SSNVs/tumor) with none in the genes listed above. In both subgroups, there are rare cancer-promoting mutations predicted to activate the PI3K pathway (HRAS, KRAS, PIK3CA, PTEN, and TSC1) and to inactivate the Notch pathway (Notch1 and Notch2). TP53 mutations appear to be clinically relevant in virus-negative MCCs as 37% of these tumors harbor potentially targetable gain-of-function mutations in TP53 at p.R248 and p.P278. Moreover, TP53 mutational status predicts death in early stage MCC (5-year survival in TP53 mutant vs wild-type stage I and II MCCs is 20% vs. 92%, respectively; P = 0.0036). Lastly, we identified the tumor neoantigens in MCPyV-negative and MCPyV-positive MCCs. We found that virus-negative MCCs harbor more tumor neoantigens than melanomas or non-small cell lung cancers (median of 173, 65, and 111 neoantigens/sample, respectively), two cancers for which immune checkpoint blockade can produce durable clinical responses. Collectively, these data support the use of immunotherapies for virus-negative MCCs.

Sea surface velocities from visible and infrared multispectral atmospheric mapping sensor imagery

NASA Technical Reports Server (NTRS)

Pope, P. A.; Emery, W. J.; Radebaugh, M.

1992-01-01

High resolution (100 m), sequential Multispectral Atmospheric Mapping Sensor (MAMS) images were used in a study to calculate advective surface velocities using the Maximum Cross Correlation (MCC) technique. Radiance and brightness temperature gradient magnitude images were formed from visible (0.48 microns) and infrared (11.12 microns) image pairs, respectively, of Chandeleur Sound, which is a shallow body of water northeast of the Mississippi delta, at 145546 GMT and 170701 GMT on 30 Mar. 1989. The gradient magnitude images enhanced the surface water feature boundaries, and a lower cutoff on the gradient magnitudes calculated allowed the undesirable sunglare and backscatter gradients in the visible images, and the water vapor absorption gradients in the infrared images, to be reduced in strength. Requiring high (greater than 0.4) maximum cross correlation coefficients and spatial coherence of the vector field aided in the selection of an optimal template size of 10 x 10 pixels (first image) and search limit of 20 pixels (second image) to use in the MCC technique. Use of these optimum input parameters to the MCC algorithm, and high correlation and spatial coherence filtering of the resulting velocity field from the MCC calculation yielded a clustered velocity distribution over the visible and infrared gradient images. The velocity field calculated from the visible gradient image pair agreed well with a subjective analysis of the motion, but the velocity field from the infrared gradient image pair did not. This was attributed to the changing shapes of the gradient features, their nonuniqueness, and large displacements relative to the mean distance between them. These problems implied a lower repeat time for the imagery was needed in order to improve the velocity field derived from gradient imagery. Suggestions are given for optimizing the repeat time of sequential imagery when using the MCC method for motion studies. Applying the MCC method to the infrared brightness temperature imagery yielded a velocity field which did agree with the subjective analysis of the motion and that derived from the visible gradient imagery. Differences between the visible and infrared derived velocities were 14.9 cm/s in speed and 56.7 degrees in direction. Both of these velocity fields also agreed well with the motion expected from considerations of the ocean bottom topography and wind and tidal forcing in the study area during the 2.175 hour time interval.

Granite intrusion in a metamorphic core complex: the example of the Mykonos laccolith (Cyclades, Greece)

NASA Astrophysics Data System (ADS)

Denèle, Yoann; Lecomte, Emmanuel; Jolivet, Laurent; Huet, Benjamin; Labrousse, Loïc.; Le Pourhiet, Laetitia; Lacombe, Olivier

2010-05-01

Numerical and analogical modelling underlined the importance of a pre-existing anomaly of viscosity-density such as a granite or migmatitic body below the brittle-ductile transition as a primary cause of metamorphic core complex (MCC) developpement. While field studies of MCC show a spatial and temporal link between MCC formation and plutonic activity, thermochronological studies show that there is no link between the intrusion of granites and the velocity of slip on the detachement plane. The Aegean domain is a good natural laboratory for studying the formation of MCC and syn-tectonic granites. In the northern Cyclades, the Mykonos-Delos-Rhenia MCC is characterised by the intrusion of a plurikilometric Late Miocene pluton of I-type granite within a migmatitic gneiss dome. AMS (Anisotropy of magnetic susceptibility) and microstructural studies in the Mykonos granites combined with recent cooling rate data allow us to use the granites as strain marker. The Mykonos granitoïds form a plurikilometric laccolith slightly deeping to the east and presenting an elliptical shape with a N170°E long axis. The laccolith is strongly asymmetrical with an outlying root zone in the SW cropping out on Delos and Rhenia islands and a major body mainly developed to the NE and cropping out on Mykonos Island. The laccolith consists of various petrographic facies presenting straight contacts that demonstrate emplacement by successive pulses of more or less differentiated magmas. The laccolith was developed at the interface between the Cycladic Basement and the Blueschists Unit and within the Blueschist Unit. Two events of deformation have been recorded in the granites. The first event is characterized by submagmatic and high to middle temperature protomylonite microstructures developped during or just after the intrusion. The second event of deformation characterized by low temperature mylonites and cataclasites close to the major detachment fault corresponds to the localization of deformation at the top of the laccolith after cooling due to heat exchange with country rocks and exhumation of the Mykonos MCC. The study of fabric evolution in the laccolith suggests that the laccolith structuration results from the interaction between regional deformation and lateral extension of magmas. Fabrics are indeed strongly planar close to the detachment, show an evolution toward plano-linear close to the bottom of the laccolith and are strongly linear in the root zone. Structural data suggest an evolution of the Mykonos MCC in three stages as follows: (i) a first stage characterized by the formation of a migmatitic "a-type dome" with a major axis parallel to the lineation such as Naxos dome by competition between regional N20 extension and EW shortening; (ii) a second stage marked by the emplacement of the Mykonos laccolith at 13 Ma at the top of the migmatitic paragneiss in the Blueschist Unit (iii) a progressive localisation of the deformation occured at the top of the laccolith in semi-ductile conditions on a thickness at about 500 m and thus in brittle conditions in the major detachment plane. Our study shows that intensity of submagmatic to high temperature deformation observed in the laccolith remains low compared to the deformation observed in country-rocks. This suggests that intrusion of a laccolith in the roof of a MCC in partially molten rocks does not localize the deformation. By contrast the geometry of the intrusion shows that the magmas are sucked into the direction of regional extension and that the intrusion of magmas will inevitably cause a local acceleration of the MCC development. Finally, during its cooling the laccolith will localize the brittle ductile transition in its roof and caused the formation of a strong deformation zone first ductile and then brittle.

Mission Control Center (MCC) - Celebration - Conclusion - Apollo XI Mission - MSC

NASA Image and Video Library

1969-07-24

S69-40301 (24 July 1969) --- Overall view of the Mission Operations Control Room (MOCR) in the Mission Control Center (MCC), Building 30, Manned Spacecraft Center (MSC), at the conclusion of the Apollo 11 lunar landing mission. The television monitor shows President Richard M. Nixon greeting the Apollo 11 astronauts aboard the USS Hornet in the Pacific recovery area. Astronauts Neil A. Armstrong, Michael Collins, and Edwin E. Aldrin Jr. are inside the Mobile Quarantine Facility (MQF).

A Test-Bed of Secure Mobile Cloud Computing for Military Applications

DTIC Science & Technology

2016-09-13

searching databases. This kind of applications is a typical example of mobile cloud computing (MCC). MCC has lots of applications in the military...Release; Distribution Unlimited UU UU UU UU 13-09-2016 1-Aug-2014 31-Jul-2016 Final Report: A Test-bed of Secure Mobile Cloud Computing for Military...Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 Test-bed, Mobile Cloud Computing , Security, Military Applications REPORT

STS-49 Endeavour, Orbiter Vehicle (OV) 105, Orbit Team O1 in MCC Bldg 30 FCR

NASA Technical Reports Server (NTRS)

1992-01-01

STS-49 Endeavour, Orbiter Vehicle (OV) 105, Orbit Team 1 (O1) poses in front of large display screens in JSC's Mission Control Center (MCC) Bldg 30 Flight Control Room (FCR) for group portrait. Lead Flight Director (FD) Granvil A. Pennington stands next to a model of the James Cook's ship, the Endeavour (left). Astronaut and Spacecraft Communicator (CAPCOM) John H. Casper stands at the right of the model.

Navigation/Prop Software Suite

NASA Technical Reports Server (NTRS)

Bruchmiller, Tomas; Tran, Sanh; Lee, Mathew; Bucker, Scott; Bupane, Catherine; Bennett, Charles; Cantu, Sergio; Kwong, Ping; Propst, Carolyn

2012-01-01

Navigation (Nav)/Prop software is used to support shuttle mission analysis, production, and some operations tasks. The Nav/Prop suite containing configuration items (CIs) resides on IPS/Linux workstations. It features lifecycle documents, and data files used for shuttle navigation and propellant analysis for all flight segments. This suite also includes trajectory server, archive server, and RAT software residing on MCC/Linux workstations. Navigation/Prop represents tool versions established during or after IPS Equipment Rehost-3 or after the MCC Rehost.

Potentiated processing of negative feedback in depression is attenuated by anhedonia

PubMed Central

Mueller, E. M.; Pechtel, P.; Cohen, A.L.; Douglas, S.R.; Pizzagalli, D.A.

2014-01-01

Background Although cognitive theories of depression have postulated enhanced processing of negatively valenced information, previous EEG studies have shown both increased and reduced sensitivity for negative performance feedback in MDD. To reconcile these paradoxical findings, it has been speculated that sensitivity for negative feedback is potentiated in moderate MDD but reduced in highly anhedonic subjects. The goal of this study was to test this hypothesis by analyzing the feedback-related negativity (FRN), frontomedial theta power (FMT), and source-localized anterior midcingulate cortex (aMCC) activity after negative feedback. Methods Fourteen unmedicated participants with MDD and 15 control participants performed a reinforcement learning task while 128-channel EEG was recorded. FRN, FMT and LORETA source-localized aMCC activity after negative and positive feedback were compared between groups. Results The MDD group showed higher FRN amplitudes and aMCC activation to negative feedback than controls. Moreover, aMCC activation to negative feedback was inversely related to self-reported anhedonia. In contrast, self-reported anxiety correlated with feedback-evoked frontomedial theta (FMT) within the depression group. Conclusions The present findings suggest that, among depressed and anxious individuals, enhanced processing of negative feedback occurs relatively early in the information processing stream. These results extend prior work and indicate that although moderate depression is associated with elevated sensitivity for negative feedback, high levels of anhedonia may attenuate this effect. PMID:25620272

Tablet mechanics depend on nano and micro scale adhesion, lubrication and structure.

PubMed

Badal Tejedor, Maria; Nordgren, Niklas; Schuleit, Michael; Rutland, Mark W; Millqvist-Fureby, Anna

2015-01-01

Tablets are the most convenient form for drug administration. However, despite the ease of manufacturing problems such as powder adhesion occur during the production process. This study presents surface and structural characterization of tablets formulated with commonly used excipients (microcrystalline cellulose (MCC), lactose, mannitol, magnesium (Mg) stearate) pressed under different compaction conditions. Tablet surface analyses were performed with scanning electron microscopy (SEM), profilometry and atomic force microscopy (AFM). The mechanical properties of the tablets were evaluated with a tablet hardness test. Local adhesion detected by AFM decreased when Mg stearate was present in the formulation. Moreover, the tablet strength of plastically deformable excipients such as MCC was significantly decreased after addition of Mg stearate. Combined these facts indicate that Mg stearate affects the particle-particle bonding and thus elastic recovery. The MCC excipient also displayed the highest hardness which is characteristic for a highly cohesive material. This is discussed in the view of the relatively high adhesion found between MCC and a hydrophilic probe at the nanoscale using AFM. In contrast, the tablet strength of brittle materials like lactose and mannitol is unaffected by Mg stearate. Thus fracture occurs within the excipient particles and not at particle boundaries, creating new surfaces not previously exposed to Mg stearate. Such uncoated surfaces may well promote adhesive interactions with tools during manufacture. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of realistic heavy particle induced secondary electron emission coefficients on the electron power absorption dynamics in single- and dual-frequency capacitively coupled plasmas

NASA Astrophysics Data System (ADS)

Daksha, M.; Derzsi, A.; Wilczek, S.; Trieschmann, J.; Mussenbrock, T.; Awakowicz, P.; Donkó, Z.; Schulze, J.

2017-08-01

In particle-in-cell/Monte Carlo collisions (PIC/MCC) simulations of capacitively coupled plasmas (CCPs), the plasma-surface interaction is generally described by a simple model in which a constant secondary electron emission coefficient (SEEC) is assumed for ions bombarding the electrodes. In most PIC/MCC studies of CCPs, this coefficient is set to γ = 0.1, independent of the energy of the incident particle, the electrode material, and the surface conditions. Here, the effects of implementing energy-dependent secondary electron yields for ions, fast neutrals, and taking surface conditions into account in PIC/MCC simulations is investigated. Simulations are performed using self-consistently calculated effective SEECs, {γ }* , for ‘clean’ (e.g., heavily sputtered) and ‘dirty’ (e.g., oxidized) metal surfaces in single- and dual-frequency discharges in argon and the results are compared to those obtained by assuming a constant secondary electron yield of γ =0.1 for ions. In single-frequency (13.56 MHz) discharges operated under conditions of low heavy particle energies at the electrodes, the pressure and voltage at which the transition between the α- and γ-mode electron power absorption occurs are found to strongly depend on the surface conditions. For ‘dirty’ surfaces, the discharge operates in α-mode for all conditions investigated due to a low effective SEEC. In classical dual-frequency (1.937 MHz + 27.12 MHz) discharges {γ }* significantly increases with increasing low-frequency voltage amplitude, {V}{LF}, for dirty surfaces. This is due to the effect of {V}{LF} on the heavy particle energies at the electrodes, which negatively influences the quality of the separate control of ion properties at the electrodes. The new results on the separate control of ion properties in such discharges indicate significant differences compared to previous results obtained with different constant values of γ.

Site Specific Discrete PEGylation of 124I-Labeled mCC49 Fab′ Fragments Improves Tumor MicroPET/CT Imaging in Mice

PubMed Central

Ding, Haiming; Carlton, Michelle M.; Povoski, Stephen P.; Milum, Keisha; Kumar, Krishan; Kothandaraman, Shankaran; Hinkle, George H.; Colcher, David; Brody, Rich; Davis, Paul D.; Pokora, Alex; Phelps, Mitchell; Martin, Edward W.; Tweedle, Michael F.

2014-01-01

The tumor-associated glycoprotein-72 (TAG-72) antigen is highly overexpressed in various human adenocarcinomas and anti-TAG-72 monoclonal antibodies, and fragments are therefore useful as pharmaceutical targeting vectors. In this study, we investigated the effects of site-specific PEGylation with MW 2–4 kDa discrete, branched PEGylation reagents on mCC49 Fab′ (MW 50 kDa) via in vitro TAG72 binding, and in vivo blood clearance kinetics, biodistribution, and mouse tumor microPET/CT imaging. mCC49Fab′ (Fab′-NEM) was conjugated at a hinge region cysteine with maleimide-dPEG12-(dPEG24COOH)3 acid (Mal-dPEG-A), maleimide-dPEG12-(dPEG12COOH)3 acid (Mal-dPEG-B), or maleimide-dPEG12-(m-dPEG24)3 (Mal-dPEG-C), and then radiolabeled with iodine-124 (124I) in vitro radioligand binding assays and in vivo studies used TAG-72 expressing LS174T human colon carcinoma cells and xenograft mouse tumors. Conjugation of mCC49Fab′ with Mal-dPEG-A (Fab′-A) reduced the binding affinity of the non PEGylated Fab′ by 30%; however, in vivo, Fab′-A significantly lengthened the blood retention vs Fab′-NEM (47.5 vs 28.1%/ID at 1 h, 25.1 vs 8.4%/ID at 5 h, p < 0.01), showed excellent tumor to background, better microPET/CT images due to higher tumor accumulation, and increased tumor concentration in excised tissues at 72 h by 130% (5.09 ± 0.83 vs 3.83 ± 1.50%ID/g, p < 0.05). Despite the strong similarity of the three PEGylation reagents, PEGylation with Mal-dPEG-B or -C reduced the in vitro binding affinity of Fab′-NEM by 70%, blood retention, microPET/CT imaging tumor signal intensity, and residual 72 h tumor concentration by 49% (3.83 ± 1.50 vs 1.97 ± 0.29%ID/g, p < 0.05) and 63% (3.83 ± 1.50 vs 1.42 ± 0.35%ID/g, p < 0.05), respectively. We conclude that remarkably subtle changes in the structure of the PEGylation reagent can create significantly altered biologic behavior. Further study is warranted of conjugates of the triple branched, negatively charged Mal-dPEG-A. PMID:24175669

The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.

PubMed

Abdul-Sada, Hussein; Müller, Marietta; Mehta, Rajni; Toth, Rachel; Arthur, J Simon C; Whitehouse, Adrian; Macdonald, Andrew

2017-04-11

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-kB activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.

Multimodal evidence of regional midcingulate gray matter volume underlying conflict monitoring

PubMed Central

Parvaz, Muhammad A.; Maloney, Thomas; Moeller, Scott J.; Malaker, Pias; Konova, Anna B.; Alia-Klein, Nelly; Goldstein, Rita Z.

2014-01-01

Functional neuroimaging studies have long implicated the mid-cingulate cortex (MCC) in conflict monitoring, but it is not clear whether its structural integrity (i.e., the gray matter volume) influences its conflict monitoring function. In this multimodal study, we used T1-weighted MRI scans as well as event-related potentials (ERPs) to test whether the MCC gray matter volume is associated with the electrocortical marker (i.e., No-go N200 ERP component) of conflict monitoring in healthy individuals. The specificity of such a relationship in health was determined in two ways: by (A) acquiring the same data from individuals with cocaine use disorder (CUD), known to have deficits in executive function including behavioral monitoring; and (B) acquiring the P300 ERP component that is linked with attention allocation and not specifically with conflict monitoring. Twenty-five (39.1 ± 8.4 years; 8 females) healthy individuals and 25 (42.7 ± 5.9 years; 6 females) individuals with CUD underwent a rewarded Go/No-go task during which the ERP data was collected, and they also underwent a structural MRI scan. The whole brain regression analysis showed a significant correlation between MCC structural integrity and the well-known ERP measure of conflict monitoring (N200, but not the P300) in healthy individuals, which was absent in CUD who were characterized by reduced MCC gray matter volume, N200 abnormalities as well as reduced task accuracy. In individuals with CUD instead, the N200 amplitude was associated with drug addiction symptomatology. These results show that the integrity of MCC volume is directly associated with the electrocortical correlates of conflict monitoring in healthy individuals, and such an association breaks down in psychopathologies that impact these brain processes. Taken together, this MCC–N200 association may serve as a biomarker of improved behavioral monitoring processes in diseased populations. PMID:24918068

Neural Mechanisms of the Transformation from Objective Value to Subjective Utility: Converting from Count to Worth.

PubMed

Kurnianingsih, Yoanna A; Mullette-Gillman, O'Dhaniel A

2016-01-01

When deciding, we aim to choose the "best" possible outcome. This is not just selection of the option that is the most numerous or physically largest, as options are translated from objective value (count) to subjective value (worth or utility). We localized the neural instantiation of the value-to-utility transformation to the dorsal anterior midcingulate cortex (daMCC), with independent replication. The daMCC encodes the context-specific information necessary to convert from count to worth. This encoding is not simply a representation of utility or preference, but the interaction of the two. Specifically, the relationship of brain activation to value is dependent on individual preference, with both positive and negative slopes across the population depending on whether each individual's preference results in enhancement or diminishment of the valuation. For a given value, across participants, enhanced daMCC activation corresponds to diminished subjective valuation, deactivation to enhanced subjective valuation, and non-modulated activation with non-modulated subjective valuation. Further, functional connectivity analyses identified brain regions (positive connectivity with the inferior frontal gyrus and negative connectivity with the nucleus accumbens) through which contextual information may be integrated into the daMCC and allow for outputs to modulate valuation signals. All analyses were replicated through an independent within-study replication, with initial testing in the gains domain and replication in the intermixed and mirrored losses trials. We also present and discuss an ancillary finding: we were unable to identify parametric value signals for losses through whole-brain analyses, and ROI analyses of the vmPFC presented non-modulation across loss value levels. These results identify the neural locus of the value-to-utility transformation, and provide a specific computational function for the daMCC in the production of subjective valuation through the integration of value, context, and preferences.

The impacts of selective logging and clear-cutting on woody plant diversity after 40years of natural recovery in a tropical montane rain forest, south China.

PubMed

Ding, Yi; Zang, Runguo; Lu, Xinghui; Huang, Jihong

2017-02-01

Historically, clear-cutting and selective logging have been the commercial logging practices. However, the effect of these pervasive timber extraction methods on biodiversity in tropical forests is still poorly understood. In this study, we compared abiotic factors, species diversity, community composition, and structure between ca. 40-year-old clear-cut (MCC); ca. 40-year-old selectively logged (MSL); and tropical old growth montane rain forests (MOG) on Hainan Island, China. Results showed that there were a large number of trees with a diameter at breast height (DBH) <30cm in the two logged forests. Additionally, the two logged forests only had 40% of the basal area of the large trees (DBH≥30cm) found in the old growth forest. The species richness and Shannon-Wiener diversity indices generally showed no difference among the three forest types. MCC had 70% of the species richness of the large trees in the MOG, whereas MSL and MOG had similar species richness. High value timber species had similar species richness among the three forest types, but a lower abundance and basal area of large trees in MCC. The species composition was distinct between the three forests. Large trees belonging to the family Fagaceae dominated in the logged forests and played a more important role in the old growth forest. Huge trees (DBH≥70cm) were rare in MCC, but were frequently found in MSL. Most abiotic factors varied inconsistently among the three forest types and few variables related to species diversity, community structure and composition. Our study indicated that MSL had a relatively faster recovery rate than MCC in a tropical montane rain forest after 40years, but both logged forests had a high recovery potential over a long-term. Copyright © 2016 Elsevier B.V. All rights reserved.

Quality-by-design (QbD): effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powder measured by the ASTM D 6940-04 segregation tester.

PubMed

Xie, Lin; Wu, Huiquan; Shen, Meiyu; Augsburger, Larry L; Lyon, Robbe C; Khan, Mansoor A; Hussain, Ajaz S; Hoag, Stephen W

2008-10-01

The objective of this study was to examine the effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powders measured by the ASTM D 6940-04 segregation tester using design of experiments (DOE) approaches. The test blends consisted of 4% aspirin (ASP) and 96% microcrystalline cellulose (MCC) with and without magnesium stearate (MgS). The segregation tendency of a blend was determined by measuring the last/first (L/F) ratio, the ratio of aspirin concentrations between the first and last samples discharged from the tester. A 2(2) factorial design was used to determine the effects of measurement parameters [amount of material loaded (W), number of segregation cycles] with number of replicates 6. ANOVA showed that W was a critical parameter for segregation testing. The L/F value deviated further from 1 (greater segregation tendency) with increasing W. A 2(3) full factorial design was used to assess the effects of formulation variables: grade of ASP (unmilled, milled), grade of MCC, and amount of lubricant, MgS. MLR and ANOVA showed that the grade of ASP was the main effect contributing to segregation tendency. Principal Component Regression Analysis established a correlation between L/F and the physical properties of the blend related to ASP and MCC, the ASP/MCC particle size ratio (PSR) and powder cohesion. The physical properties of the blend related to density and flow were not influenced by the grade of ASP and were not related to the segregation tendency of the blend. The direct relationship between L/F and PSR was determined by univariate analysis. Segregation tendency increased as the ASP to MCC particle size increased. This study highlighted critical test parameters for segregation testing and identified critical physical properties of the blends that influence segregation tendency. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

Neural Mechanisms of the Transformation from Objective Value to Subjective Utility: Converting from Count to Worth

PubMed Central

Kurnianingsih, Yoanna A.; Mullette-Gillman, O'Dhaniel A.

2016-01-01

When deciding, we aim to choose the “best” possible outcome. This is not just selection of the option that is the most numerous or physically largest, as options are translated from objective value (count) to subjective value (worth or utility). We localized the neural instantiation of the value-to-utility transformation to the dorsal anterior midcingulate cortex (daMCC), with independent replication. The daMCC encodes the context-specific information necessary to convert from count to worth. This encoding is not simply a representation of utility or preference, but the interaction of the two. Specifically, the relationship of brain activation to value is dependent on individual preference, with both positive and negative slopes across the population depending on whether each individual's preference results in enhancement or diminishment of the valuation. For a given value, across participants, enhanced daMCC activation corresponds to diminished subjective valuation, deactivation to enhanced subjective valuation, and non-modulated activation with non-modulated subjective valuation. Further, functional connectivity analyses identified brain regions (positive connectivity with the inferior frontal gyrus and negative connectivity with the nucleus accumbens) through which contextual information may be integrated into the daMCC and allow for outputs to modulate valuation signals. All analyses were replicated through an independent within-study replication, with initial testing in the gains domain and replication in the intermixed and mirrored losses trials. We also present and discuss an ancillary finding: we were unable to identify parametric value signals for losses through whole-brain analyses, and ROI analyses of the vmPFC presented non-modulation across loss value levels. These results identify the neural locus of the value-to-utility transformation, and provide a specific computational function for the daMCC in the production of subjective valuation through the integration of value, context, and preferences. PMID:27881949

Effects of intensive cognitive-behavioral therapy on cingulate neurochemistry in obsessive–compulsive disorder

PubMed Central

O'Neill, Joseph; Gorbis, Eda; Feusner, Jamie D.; Yip, Jenny C.; Chang, Susanna; Maidment, Karron M.; Levitt, Jennifer G.; Salamon, Noriko; Ringman, John M.; Saxena, Sanjaya

2013-01-01

The neurophysiological bases of cognitive-behavioral therapy (CBT) for obsessive–compulsive disorder (OCD) are incompletely understood. Previous studies, though sparse, implicate metabolic changes in pregenual anterior cingulate cortex (pACC) and anterior middle cingulate cortex (aMCC) as neural correlates of response to CBT. The goal of this pilot study was to determine the relationship between levels of the neurochemically interlinked metabolites glutamate + glutamine (Glx) and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (tNAA) in pACC and aMCC to pretreatment OCD diagnostic status and OCD response to CBT. Proton magnetic resonance spectroscopic imaging (1H MRSI) was acquired from pACC and aMCC in 10 OCD patients at baseline, 8 of whom had a repeat scan after 4 weeks of intensive CBT. pACC was also scanned (baseline only) in 8 age-matched healthy controls. OCD symptoms improved markedly in 8/8 patients after CBT. In right pACC, tNAA was significantly lower in OCD patients than controls at baseline and then increased significantly after CBT. Baseline tNAA also correlated with post-CBT change in OCD symptom severity. In left aMCC, Glx decreased significantly after intensive CBT. These findings add to evidence implicating the pACC and aMCC as loci of the metabolic effects of CBT in OCD, particularly effects on glutamatergic and N-acetyl compounds. Moreover, these metabolic responses occurred after just 4 weeks of intensive CBT, compared to 3 months for standard weekly CBT. Baseline levels of tNAA in the pACC may be associated with response to CBT for OCD. Lateralization of metabolite effects of CBT, previously observed in subcortical nuclei and white matter, may also occur in cingulate cortex. Tentative mechanisms for these effects are discussed. Comorbid depressive symptoms in OCD patients may have contributed to metabolite effects, although baseline and post-CBT change in depression ratings varied with choline-compounds and myo-inositol rather than Glx or tNAA. PMID:23290560

Understanding the Context of Health for Persons With Multiple Chronic Conditions: Moving From What Is the Matter to What Matters

PubMed Central

Bayliss, Elizabeth A.; Bonds, Denise E.; Boyd, Cynthia M.; Davis, Melinda M.; Finke, Bruce; Fox, Michael H.; Glasgow, Russell E.; Goodman, Richard A.; Heurtin-Roberts, Suzanne; Lachenmayr, Sue; Lind, Cristin; Madigan, Elizabeth A.; Meyers, David S.; Mintz, Suzanne; Nilsen, Wendy J.; Okun, Sally; Ruiz, Sarah; Salive, Marcel E.; Stange, Kurt C.

2014-01-01

PURPOSE An isolated focus on 1 disease at a time is insufficient to generate the scientific evidence needed to improve the health of persons living with more than 1 chronic condition. This article explores how to bring context into research efforts to improve the health of persons living with multiple chronic conditions (MCC). METHODS Forty-five experts, including persons with MCC, family and friend caregivers, researchers, policy makers, funders, and clinicians met to critically consider 4 aspects of incorporating context into research on MCC: key contextual factors, needed research, essential research methods for understanding important contextual factors, and necessary partnerships for catalyzing collaborative action in conducting and applying research. RESULTS Key contextual factors involve complementary perspectives across multiple levels: public policy, community, health care systems, family, and person, as well as the cellular and molecular levels where most research currently is focused. Needed research involves moving from a disease focus toward a person-driven, goal-directed research agenda. Relevant research methods are participatory, flexible, multilevel, quantitative and qualitative, conducive to longitudinal dynamic measurement from diverse data sources, sufficiently detailed to consider what works for whom in which situation, and generative of ongoing communities of learning, living and practice. Important partnerships for collaborative action include cooperation among members of the research enterprise, health care providers, community-based support, persons with MCC and their family and friend caregivers, policy makers, and payers, including government, public health, philanthropic organizations, and the business community. CONCLUSION Consistent attention to contextual factors is needed to enhance health research for persons with MCC. Rigorous, integrated, participatory, multimethod approaches to generate new knowledge and diverse partnerships can be used to increase the relevance of research to make health care more sustainable, safe, equitable and effective, to reduce suffering, and to improve quality of life. PMID:24821898

Identifying and understanding the health and social care needs of older adults with multiple chronic conditions and their caregivers: a protocol for a scoping review

PubMed Central

Commisso, Elana; McGilton, Katherine S; Ayala, Ana Patricia; Andrew, Melissa, K; Bergman, Howard; Beaudet, Line; Dubé, Veronique; Gray, Mikaela; Hale, Lori; Keatings, Margaret; Marshall, Emily Gard; McElhaney, Janet; Morgan, Debra; Parrott, Edna; Ploeg, Jenny; Sampalli, Tara; Stephens, Douglas; Vedel, Isabelle; Walker, Jennifer; Puts, Martine T E

2017-01-01

Introduction People are living longer; however, they are not necessarily experiencing good health and well-being as they age. Many older adults live with multiple chronic conditions (MCC), and complex health issues, which adversely affect their day-to-day functioning and overall quality of life. As a result, they frequently rely on the support of friend and/or family caregivers. Caregivers of older adults with MCC often face challenges to their own well-being and also require support. Currently, not enough is known about the health and social care needs of older adults with MCC and the needs of their caregivers or how best to identify and meet these needs. This study will examine and synthesise the literature on the needs of older adults with MCC and those of their caregivers, and identify gaps in evidence and directions for further research. Methods and analysis We will conduct a scoping review of the peer-reviewed and grey literature using the updated Arksey and O’Malley framework. The literature will be identified using a multidatabase and grey literature search strategy developed by a health sciences librarian. Papers, reports and other materials addressing the health and social care needs of older adults and their friend/family caregivers will be included. Search results will be screened, independently, by two reviewers, and data will be abstracted from included literature and charted in duplicate. Ethics and dissemination This scoping review does not require ethics approval. We anticipate that study findings will inform novel strategies for identifying and ascertaining the health and social care needs of older adults living with MCC and those of their caregivers. Working with knowledge-user members of our team, we will prepare materials and presentations to disseminate findings to relevant stakeholder and end-user groups at local, national and international levels. We will also publish our findings in a peer-reviewed journal. PMID:29288180

INFLIGHT (MISSION CONTROL CENTER [MCC]) - STS-1 - ELLINGTON AFB (EAFB), TX

NASA Image and Video Library

1981-04-13

S81-32876 (13 April 1981) --- Brig. Gen. William T. Twinting studies the monitor at the Department of Defense (DOD) console in the mission operations control room (MOCR) at the Johnson Space Center?s Mission Control Center (MCC). He is deputy DOD manager for Space Shuttle Support Operations. Gen. Twinting and the other flight controllers seen in the background listen as astronaut John W. Young, STS-1 commander, describes the scenery of a downlink TV transmission. Photo credit: NASA

JSC MCC Bldg 30 Instrumentation and Communications Officer (INCO) RTDS

NASA Image and Video Library

1988-06-02

Instrumentation and Communications Officer (INCO) John F. Muratore monitors conventional workstation displays during an STS-26 simulation in JSC Mission Control Center (MCC) Bldg 30 Flight Control Room (FCR). Next to Muratore an operator views the real time data system (RTDS), an expert system. During the STS-29 mission two conventional monochrome console display units will be removed and replaced with RTDS displays. View is for the STS-29 press kit from Office of Aeronautics and Space Technology (OAST) RTDS.

Mesoscale Convective Complex versus Non-Mesoscale Convective Complex Thunderstorms: A Comparison of Selected Meteorological Variables.

DTIC Science & Technology

1986-08-01

mean square errors for selected variables . . 34 8. Variable range and mean value for MCC and non-MCC cases . . 36 9. Alpha ( a ) levels at which the...Table 9. For each variable, the a level is listed at which the two mean values are determined to be significantly 38 Table 9. Alpha ( a ) levels at...vorticity advection None 700 mb vertical velocity forecast .20 different. These a levels express the probability of erroneously con- cluding that the

STS-26 Mission Control Center (MCC) activity at JSC

NASA Technical Reports Server (NTRS)

1988-01-01

Flight controllers in JSC's Mission Control Center (MCC) Bldg 30 flight control room (FCR) listen to a presentation by STS-26 crewmembers on the fourth day of Discovery's, Orbiter Vehicle (OV) 103's, orbital mission. Instrumentation and Communications Officers (INCOs) Harold Black (left foreground) and John F. Muratore and other controllers view a television (TV) transmission of the crew on a screen in front of the FCR as each member relates some inner feelings while paying tribute to the 51L Challenger crew.

STS-26 Mission Control Center (MCC) activity at JSC

NASA Image and Video Library

1988-10-02

Flight controllers in JSC's Mission Control Center (MCC) Bldg 30 flight control room (FCR) listen to a presentation by STS-26 crewmembers on the fourth day of Discovery's, Orbiter Vehicle (OV) 103's, orbital mission. Instrumentation and Communications Officers (INCOs) Harold Black (left foreground) and John F. Muratore and other controllers view a television (TV) transmission of the crew on a screen in front of the FCR as each member relates some inner feelings while paying tribute to the 51L Challenger crew.

SEI Report on Graduate Software Engineering Education for 1991

DTIC Science & Technology

1991-04-01

12, 12 (Dec. 1979), 85-94. Andrews83 Andrews, Gregory R . and Schneider, Fred B. “Concepts and Notations for Concurrent Programming.” ACM Computing...Barringer87 Barringer , H. “Up and Down the Temporal Way.” Computer J. 30, 2 (Apr. 1987), 134-148. Bjørner78 The Vienna Development Method: The Meta-Language...Lecture Notes in Computer Science. Bruns86 Bruns, Glenn R . Technology Assessment: PAISLEY. Tech. Rep. MCC TR STP-296-86, MCC, Austin, Texas, Sept

Active and passive transport of cargo in a corrugated channel: A lattice model study

NASA Astrophysics Data System (ADS)

Dey, Supravat; Ching, Kevin; Das, Moumita

2018-04-01

Inside cells, cargos such as vesicles and organelles are transported by molecular motors to their correct locations via active motion on cytoskeletal tracks and passive, Brownian diffusion. During the transportation of cargos, motor-cargo complexes (MCCs) navigate the confining and crowded environment of the cytoskeletal network and other macromolecules. Motivated by this, we study a minimal two-state model of motor-driven cargo transport in confinement and predict transport properties that can be tested in experiments. We assume that the motion of the MCC is directly affected by the entropic barrier due to confinement if it is in the passive, unbound state but not in the active, bound state where it moves with a constant bound velocity. We construct a lattice model based on a Fokker Planck description of the two-state system, study it using a kinetic Monte Carlo method and compare our numerical results with analytical expressions for a mean field limit. We find that the effect of confinement strongly depends on the bound velocity and the binding kinetics of the MCC. Confinement effectively reduces the effective diffusivity and average velocity, except when it results in an enhanced average binding rate and thereby leads to a larger average velocity than when unconfined.

Effects of neutral distribution and external magnetic field on plasma momentum in electrodeless plasma thrusters

NASA Astrophysics Data System (ADS)

Takase, Kazuki; Takahashi, Kazunori; Takao, Yoshinori

2018-02-01

The effects of neutral distribution and an external magnetic field on plasma distribution and thruster performance are numerically investigated using a particle-in-cell simulation with Monte Carlo collisions (PIC-MCC) and the direct simulation Monte Carlo (DSMC) method. The modeled thruster consists of a quartz tube 1 cm in diameter and 3 cm in length, where a double-turn rf loop antenna is wound at the center of the tube and a solenoid is placed between the loop antenna and the downstream tube exit. A xenon propellant is introduced from both the upstream and downstream sides of the thruster, and the flow rates are varied while maintaining the total gas flow rate of 30 μg/s. The PIC-MCC calculations have been conducted using the neutral distribution obtained from the DSMC calculations, which were applied with different strengths of the magnetic field. The numerical results show that both the downstream gas injection and the external magnetic field with a maximum strength near the thruster exit lead to a shift of the plasma density peak from the upstream to the downstream side. Consequently, a larger total thrust is obtained when increasing the downstream gas injection and the magnetic field strength, which qualitatively agrees with a previous experiment using a helicon plasma source.

Managing Risk in Safety Critical Operations - Lessons Learned from Space Operations

NASA Technical Reports Server (NTRS)

Gonzalez, Steven A.

2002-01-01

The Mission Control Center (MCC) at Johnson Space Center (JSC) has a rich legacy of supporting Human Space Flight operations throughout the Apollo, Shuttle and International Space Station eras. Through the evolution of ground operations and the Mission Control Center facility, NASA has gained a wealth of experience of what it takes to manage the risk in Safety Critical Operations, especially when human life is at risk. The focus of the presentation will be on the processes (training, operational rigor, team dynamics) that enable the JSC/MCC team to be so successful. The presentation will also share the evolution of the Mission Control Center architecture and how the evolution was introduced while managing the risk to the programs supported by the team. The details of the MCC architecture (e.g., the specific software, hardware or tools used in the facility) will not be shared at the conference since it would not give any additional insight as to how risk is managed in Space Operations.

Effect of structural changes of lignocelluloses material upon pre-treatment using green solvents

NASA Astrophysics Data System (ADS)

Gunny, Ahmad Anas Nagoor; Arbain, Dachyar; Jamal, Parveen

2017-04-01

The Malaysia Biomass strategy 2020 stated that the key step of biofuel production from biomass lies on the pretreatment process. Conventional `pre-treatment' methods are `non-green" and costly. The recent green and cost-effective biomass pretreatment is using new generation of Ionic Liquids also known as Deep Eutectic Solvents (DESs). DESs are made of renewable components are cheaper, greener and the process synthesis are easier. Thus, the present paper concerns with the preparation of various combination of DES and to study the effect of DESs pretreatment process on microcrystalline cellulose (MCC), a model substrate. The crystalline structural changes were studied using using X-ray Diffraction Methods, Fourier Transformed Infrared Spectroscopy (FTIR) and surface area and pore size analysis. Results showed reduction of crystalline structure of MCC treated with the DESs and increment of surface area and pore size of MCC after pre-treatment process. These results indicated the DES has successfully converted the lignocelluloses material in the form suitable for hydrolysis and conversion to simple sugar.

An Interactive Platform to Visualize Data-Driven Clinical Pathways for the Management of Multiple Chronic Conditions.

PubMed

Zhang, Yiye; Padman, Rema

2017-01-01

Patients with multiple chronic conditions (MCC) pose an increasingly complex health management challenge worldwide, particularly due to the significant gap in our understanding of how to provide coordinated care. Drawing on our prior research on learning data-driven clinical pathways from actual practice data, this paper describes a prototype, interactive platform for visualizing the pathways of MCC to support shared decision making. Created using Python web framework, JavaScript library and our clinical pathway learning algorithm, the visualization platform allows clinicians and patients to learn the dominant patterns of co-progression of multiple clinical events from their own data, and interactively explore and interpret the pathways. We demonstrate functionalities of the platform using a cluster of 36 patients, identified from a dataset of 1,084 patients, who are diagnosed with at least chronic kidney disease, hypertension, and diabetes. Future evaluation studies will explore the use of this platform to better understand and manage MCC.

Mussel-inspired fabrication of konjac glucomannan/microcrystalline cellulose intelligent hydrogel with pH-responsive sustained release behavior.

PubMed

Wang, Lin; Du, Yu; Yuan, Yi; Mu, Ruo-Jun; Gong, Jingni; Ni, Yongsheng; Pang, Jie; Wu, Chunhua

2018-07-01

Intelligent hydrogels are attractive biomaterials for various applications, however, fabricating a hydrogel with both adequate self-healing ability and mechanical properties remains a challenge. Herein, a series of novel intelligent konjac glucomannan (KGM)/microcrystalline cellulose (MCC) hydrogels were prepared vis the mussel-inspired chemistry. MCC was firstly functionalized by the oxidative polymerization of dopamine, and the intelligent hydrogels were obtained by mixing aqueous solutions of KGM and functionalized MCC (PDMCC). By introducing PDMCC, a more compact interconnected porous structure formed for the resulting hydrogels. The self-healing ability and mechanical properties of intelligent hydrogels were dependence on the PDMCC content. Compared with KGM hydrogels, KGM/PDMCC hydrogels exhibited a more distinct pH sensitivity and a lower initial burst release, which was attributed to the compact structure and strong intermolecular hydrogen bond interaction between PDMCC and KGM. These results suggest that the KGM/PDMCC intelligent hydrogels may be promising carriers for controlled drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Midcingulate Motor Map and Feedback Detection: Converging Data from Humans and Monkeys.

PubMed

Procyk, Emmanuel; Wilson, Charles R E; Stoll, Frederic M; Faraut, Maïlys C M; Petrides, Michael; Amiez, Céline

2016-02-01

The functional and anatomical organization of the cingulate cortex across primate species is the subject of considerable and often confusing debate. The functions attributed to the midcingulate cortex (MCC) embrace, among others, feedback processing, pain, salience, action-reward association, premotor functions, and conflict monitoring. This multiplicity of functional concepts suggests either unresolved separation of functional contributions or integration and convergence. We here provide evidence from recent experiments in humans and from a meta-analysis of monkey data that MCC feedback-related activity is generated in the rostral cingulate premotor area by specific body maps directly related to the modality of feedback. As such, we argue for an embodied mechanism for adaptation and exploration in MCC. We propose arguments and precise tools to resolve the origins of performance monitoring signals in the medial frontal cortex, and to progress on issues regarding homology between human and nonhuman primate cingulate cortex. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

SSME Main Combustion Chamber (MCC) hot oil dewaxing

NASA Technical Reports Server (NTRS)

Akpati, Anthony U.

1995-01-01

In an attempt to comply with the changing environmental regulations, a process was developed for the replacement of perchloroethylene in the dewaxing of the Space Shuttle Main Engine (SSME) Main Combustion Chamber (MCC) and other associated hardware filled with the Rigidax (R) casting compound. Rigidax (R) is a hard blue-dyed, calcium carbonate filled thermoplastic casting compound (melting point 77 C) that is melted and poured into hardware cavities to prevent contamination during material removal processes, i.e. machining, grinding, drilling, and deburring. Additionally, it serves as a maskant for designated areas during electroforming processes. Laboratory testing was conducted to evaluate seven alternate fluids for the replacement of perchloroethylene in the dewaxing process. Based upon successful laboratory results, a mineral oil was selected for testing on actual hardware. The final process developed involves simultaneous immersion and flushing of the MCC channels using a distinct eight stage process. A nonvolatile hydrocarbon analysis of a solvent flush sample is performed to determine the hardware cleanliness for comparison to the previous perchloroethylene dewaxing process.

Switching the JLab Accelerator Operations Environment from an HP-UX Unix-based to a PC/Linux-based environment

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

Mcguckin, Theodore

2008-10-01

The Jefferson Lab Accelerator Controls Environment (ACE) was predominantly based on the HP-UX Unix platform from 1987 through the summer of 2004. During this period the Accelerator Machine Control Center (MCC) underwent a major renovation which included introducing Redhat Enterprise Linux machines, first as specialized process servers and then gradually as general login servers. As computer programs and scripts required to run the accelerator were modified, and inherent problems with the HP-UX platform compounded, more development tools became available for use with Linux and the MCC began to be converted over. In May 2008 the last HP-UX Unix login machinemore » was removed from the MCC, leaving only a few Unix-based remote-login servers still available. This presentation will explore the process of converting an operational Control Room environment from the HP-UX to Linux platform as well as the many hurdles that had to be overcome throughout the transition period (including a discussion of« less

Frontal Midline Theta Reflects Anxiety and Cognitive Control: Meta-Analytic Evidence

PubMed Central

Cavanagh, James F.; Shackman, Alexander J.

2014-01-01

Evidence from imaging and anatomical studies suggests that the midcingulate cortex (MCC) is a dynamic hub lying at the interface of affect and cognition. In particular, this neural system appears to integrate information about conflict and punishment in order to optimize behavior in the face of action-outcome uncertainty. In a series of meta-analyses, we show how recent human electrophysiological research provides compelling evidence that frontal-midline theta signals reflecting MCC activity are moderated by anxiety and predict adaptive behavioral adjustments. These findings underscore the importance of frontal theta activity to a broad spectrum of control operations. We argue that frontal-midline theta provides a neurophysiologically plausible mechanism for optimally adjusting behavior to uncertainty, a hallmark of situations that elicit anxiety and demand cognitive control. These observations compel a new perspective on the mechanisms guiding motivated learning and behavior and provide a framework for understanding the role of the MCC in temperament and psychopathology. PMID:24787485

SSME Main Combustion Chamber (MCC) 'Hot Oil' Dewaxing

NASA Technical Reports Server (NTRS)

Akpati, Anthony U.

1994-01-01

In an attempt to comply with the changing environmental regulations, a process was developed for the replacement of perchloroethylene in the dewaxing of the Space Shuttle Main Engine (SSME) Main Combustion Chamber (MCC) and other associated hardware filled with the Rigidax(registered mark) casting compound. Rigidax(registered mark) is a hard blue-dyed, calcium carbonate filled thermoplastic casting compound (melting point 77 C) that is melted and poured into hardware cavities to prevent contamination during material removal processes, i.e. machining, grinding, drilling, and deburring. Additionally, it serves as a maskant for designated areas during electroforming processes. Laboratory testing was conducted to evaluate seven alternate fluids for the replacement of perchloroethylene in the dewaxing process. Based upon successful laboratory results, a mineral oil was selected for testing on actual hardware. The final process developed involves simultaneous immersion and flushing of the MCC channels using a distinct eight stage process. A nonvolatile hydrocarbon analysis of a solvent flush sample is performed to determine the hardware cleanliness for comparison to the previous perchloroethylene dewaxing process.

Implementation of Joint Multi-Segment Training

NASA Technical Reports Server (NTRS)

Reagan, Marc; Smith, Wyatt; Bugrova, Skella; Silkov, Sergei

2000-01-01

The highest level of training for ISS flight is Joint Multi-Segment Training (JMST) simulations. These simulations allow two or more partners to conduct multi-segment training for their respective Mission Control Centers (MCC), include actual crew members, and usually include training facilities in each of the participating International Partner (IP) locations. It is the dress rehearsal for those events that exercise the interface between different IP modules and/or the decision making process between the different MCCs involved. This presentation will describe the challenge of successfully implementing JMST. It will start with a brief overview of who is involved, where they are located, and when JMSTs are required. Finally, it will illustrate many of the complications involved in just running a JMST between MCC-M and MCC-H. The viewer will leave with a much better appreciation for the complexities involved in successfully conducting a JMST of this nature, as well as an idea of how the picture will change as the other partners and payloads become involved.

The Regulatory Review Process in South Africa: Challenges and Opportunities for a New Improved System.

PubMed

Keyter, Andrea; Gouws, Joey; Salek, Sam; Walker, Stuart

2018-01-01

The aims of this study were to assess the regulatory review process in South Africa from 2015 to 2017, identify the key milestones and timelines; evaluate the effectiveness of measures to ensure consistency, transparency, timeliness, and predictability in the review process; and to provide recommendations for enhanced regulatory practices. A questionnaire was completed by the Medicines Control Council (MCC) to describe the organization of the authority, record key milestones and timelines in the review process and to identify good review practices (GRevPs). Currently, the MCC conducts a full assessment of quality, efficacy, and safety data in the review of all applications. The overall regulatory median approval time decreased by 14% in 2017 (1411 calendar days) compared with that of 2016, despite the 27% increase in the number of applications. However, the MCC has no target for overall approval time of new active substance applications and no targets for key review milestones. Guidelines, standard operating procedures, and review templates are in place, while the formal implementation of GRevPs and the application of an electronic document management system are planned for the near future. As the MCC transitions to the newly established South Africa Health Products Regulatory Authority, it would be crucial for the authority to recognize the opportunities for an enhanced regulatory review and should consider models such as abridged assessment, which encompass elements of risk stratification and reliance. It is hoped that resource constraints may then be alleviated and capacity developed to meet target timelines.

Policy at play: The implementation of Healthy Eating and Active Living Guidelines in municipal child care settings.

PubMed

McKay, Kelly; Nigro, Sherry

2017-03-01

In 2012, Ottawa Public Health (OPH) partnered with the City of Ottawa Municipal Child Care (MCC) Services to develop Healthy Eating and Active Living (HEAL) Guidelines. The Guidelines aim to promote consistent standards of practice in child care settings related to healthy environments and food, physical activity, physical literacy, decreased sedentary behaviours, and positive role modeling by staff. The Guidelines targeted 498 children aged 18 months to 5 years, attending MCC centres. Resources and training were provided to 10 supervisors, 63 child care educators and 9 cooks. Components of the Guidelines were piloted in 5 MCC sites prior to being launched in 10 MCC sites across Ottawa, Ontario. Two project Advisory Groups supported the development of the Guidelines. Staff training, resources, recipes and menus were provided. An evaluation was conducted and has informed the Guidelines' subsequent community implementation. In 2015, accompanying web-based resources and e-modules were developed. The evaluation demonstrated environmental and programming changes. Parent satisfaction was high and preliminary findings showed no real changes in food costs. Following implementation, the cooks reported high compliance to the 6-week menu plans provided, and the number of sites offering 120 minutes or more of daily physical activity increased. Through novel intersectoral partnerships, OPH was able to implement and evaluate HEAL Guidelines in tandem. The interdisciplinary project Advisory Groups, training of cooks, and engagement of the Ontario Coaches Association were all innovative elements of this project and may influence future public health activity in this area.

Impact of novel polymorphisms related to cytotoxicity of cytarabine in the induction treatment of acute myeloid leukemia.

PubMed

Megías-Vericat, Juan E; Montesinos, Pau; Herrero, María J; Moscardó, Federico; Bosó, Virginia; Martínez-Cuadrón, David; Poveda, José L; Sanz, Miguel Á; Aliño, Salvador F

2017-07-01

Several novel single nucleotide polymorphisms (SNPs) involved in cytarabine cytotoxicity and related to clinical outcomes have been reported recently in a series of 232 pediatric patients with acute myeloid leukemia (AML). We report the first adult AML cohort in which the influence of these SNPs in cytarabine efficacy and toxicity was analyzed. Six of polymorphisms with clinical significance in the previous study [rs12036333, rs10758713, rs9883101, rs6550826, IRX2: rs2897047, mutated in colorectal cancers (MCC): rs7729269] were analyzed in a cohort of 225 adult patients at initial diagnosis of AML treated with an induction scheme of idarubicin plus cytarabine. The variant alleles of rs12036333 and rs10758713 confirmed the previous associations with lower survival rates. The minor alleles of rs9883101 and rs6550826 were also related to lower survival, in concordance with higher cytarabine-induced cytotoxicity observed in pediatric patients. However, discordant findings between AML adult and pediatric population were observed with IRX2 rs2897047, showing higher survival in heterozygous genotype carriers. The heterozygous genotype of MCC rs7729269 was associated with higher cytarabine-induced toxicities (renal, hepatic, lung, skin toxicities), whereas lower time to thrombocytopenia recovery was associated with the MCC rs7729269 minor allele. This study confirms the influence in survival rates of these polymorphisms in an adult AML population. Novel associations between MCC SNPs and cytarabine toxicities were reported and should be validated in prospective studies involving larger groups of patients.

Monopolar spindle 1 (MPS1) kinase promotes production of closed MAD2 (C-MAD2) conformer and assembly of the mitotic checkpoint complex.

PubMed

Tipton, Aaron R; Ji, Wenbin; Sturt-Gillespie, Brianne; Bekier, Michael E; Wang, Kexi; Taylor, William R; Liu, Song-Tao

2013-12-06

MPS1 kinase is an essential component of the spindle assembly checkpoint (SAC), but its functioning mechanisms are not fully understood. We have shown recently that direct interaction between BUBR1 and MAD2 is critical for assembly and function of the human mitotic checkpoint complex (MCC), the SAC effector. Here we report that inhibition of MPS1 kinase activity by reversine disrupts BUBR1-MAD2 as well as CDC20-MAD2 interactions, causing premature activation of the anaphase-promoting complex/cyclosome. The effect of MPS1 inhibition is likely due to reduction of closed MAD2 (C-MAD2), as expressing a MAD2 mutant (MAD2(L13A)) that is locked in the C conformation rescued the checkpoint defects. In the presence of reversine, exogenous C-MAD2 does not localize to unattached kinetochores but is still incorporated into the MCC. Contrary to a previous report, we found that sustained MPS1 activity is required for maintaining both the MAD1·C-MAD2 complex and open MAD2 (O-MAD2) at unattached kinetochores to facilitate C-MAD2 production. Additionally, mitotic phosphorylation of BUBR1 is also affected by MPS1 inhibition but seems dispensable for MCC assembly. Our results support the notion that MPS1 kinase promotes C-MAD2 production and subsequent MCC assembly to activate the SAC.

Ancestry Dependent DNA Methylation and Influence of Maternal Nutrition

PubMed Central

Mozhui, Khyobeni; Smith, Alicia K.; Tylavsky, Frances A.

2015-01-01

There is extensive variation in DNA methylation between individuals and ethnic groups. These differences arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we compare genome-wide DNA methylation in neonatal cord blood from African American (AA; N = 112) and European American (EA; N = 91) participants of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood). Our goal is to determine if there are replicable ancestry-specific methylation patterns that may implicate risk factors for diseases that have differential prevalence between populations. To identify the most robust ancestry-specific CpG sites, we replicate our results in lymphoblastoid cell lines from Yoruba African and CEPH European panels of HapMap. We also evaluate the influence of maternal nutrition—specifically, plasma levels of vitamin D and folate during pregnancy—on methylation in newborns. We define stable ancestry-dependent methylation of genes that include tumor suppressors and cell cycle regulators (e.g., APC, BRCA1, MCC). Overall, there is lower global methylation in African ancestral groups. Plasma levels of 25-hydroxy vitamin D are also considerably lower among AA mothers and about 60% of AA and 40% of EA mothers have concentrations below 20 ng/ml. Using a weighted correlation analysis, we define a network of CpG sites that is jointly modulated by ancestry and maternal vitamin D. Our results show that differences in DNA methylation patterns are remarkably stable and maternal micronutrients can exert an influence on the child epigenome. PMID:25742137

S70-34903

NASA Image and Video Library

1970-04-14

S70-34903 (14 April 1970) --- Dr. Thomas O. Paine, Administrator, National Aeronautics and Space Administration (NASA), talks on the telephone to President Richard M. Nixon. Dr. Paine is seated at his console in the Mission Operations Control Room (MOCR) at the Mission Control Center (MCC), Manned Spacecraft Center (MSC). Also pictured are Dr. Rocco Petrone, Apollo program director, Office Manned Spaceflight, NASA Headquarters (facing camera); and Chester M. Lee, Apollo mission director, Office of Manned Spaceflight, NASA Headquarters (HQ). Dr. Paine and the President were discussing the revised Apollo 13 flight plan following discovery of an oxygen cell failure in the Apollo 13 spacecraft several hours earlier.

Surface structure, crystallographic and ice-nucleating properties of cellulose

NASA Astrophysics Data System (ADS)

Hiranuma, Naruki; Möhler, Ottmar; Kiselev, Alexei; Saathoff, Harald; Weidler, Peter; Shutthanandan, Shuttha; Kulkarni, Gourihar; Jantsch, Evelyn; Koop, Thomas

2015-04-01

Increasing evidence of the high diversity and efficient freezing ability of biological ice-nucleating particles is driving a reevaluation of their impact upon climate. Despite their potential importance, little is known about their atmospheric abundance and ice nucleation efficiency, especially non-proteinaceous ones, in comparison to non-biological materials (e.g., mineral dust). Recently, microcrystalline cellulose (MCC; non-proteinaceous plant structural polymer) has been identified as a potential biological ice-nucleating particle. However, it is still uncertain if the ice-nucleating activity is specific to the MCC structure or generally relevant to all cellulose materials, such that the results of MCC can be representatively scaled up to the total cellulose content in the atmosphere to address its role in clouds and the climate system. Here we use the helium ion microscopy (HIM) imaging and the X-ray diffraction (XRD) technique to characterize the nanoscale surface structure and crystalline properties of the two different types of cellulose (MCC and fibrous cellulose extracted from natural wood pulp) as model proxies for atmospheric cellulose particles and to assess their potential accessibility for water molecules. To complement these structural characterizations, we also present the results of immersion freezing experiments using the cold stage-based droplet freezing BINARY (Bielefeld Ice Nucleation ARaY) technique. The HIM results suggest that both cellulose types have a complex porous morphology with capillary spaces between the nanoscale fibrils over the microfiber surface. These surface structures may make cellulose accessible to water. The XRD results suggest that the structural properties of both cellulose materials are in agreement (i.e., P21 space group; a=7.96 Å, b=8.35 Å, c=10.28 Å) and comparable to the crystallographic properties of general monoclinic cellulose (i.e., Cellulose Iβ). The results obtained from the BINARY measurements suggest that there is no significant difference of the immersion ice nucleation activity of MCC and fibrous cellulose in supercooled water. Overall, our findings support the view that MCC may be a good proxy for inferring water uptake, wettability and ice nucleating properties of various cellulose materials. In addition, we discuss the ice-nucleating efficiencies of both cellulose samples and plant debris from the AIDA (Aerosol Interaction and Dynamics in the Atmosphere) chamber experiments in comparison to the BINARY results. The influence of the acid processing of cellulose on its ice nucleation propensity may also be discussed to further demonstrate their atmospheric relevancy. Acknowledgement: We acknowledge support by German Research Society (DFG) and Ice Nuclei research UnIT (FOR 1525 INUIT).

Serum 25-hydroxyvitamin D and breast cancer risk by pathological subtype (MCC-Spain).

PubMed

Lope, Virginia; Castelló, Adela; Mena-Bravo, Antonio; Amiano, Pilar; Aragonés, Nuria; Fernández-Villa, Tania; Guevara, Marcela; Dierssen-Sotos, Trinidad; Fernandez-Tardón, Guillermo; Castaño-Vinyals, Gemma; Marcos-Gragera, Rafael; Moreno, Víctor; Salas-Trejo, Dolores; Diaz-Santos, Marian; Oribe, Madalen; Romieu, Isabel; Kogevinas, Manolis; Priego-Capote, Feliciano; Pérez-Gómez, Beatriz; Pollán, Marina

2018-04-19

Epidemiologic evidence on the association between vitamin D and breast cancer is still inconclusive. This study analyzes the association between serum 25-hydroxyvitamin D (25(OH)D) and breast cancer risk by pathologic subtype, stage at diagnosis and specific breast cancer risk factors. We conducted a population-based multicase-control study where 546 histologically-confirmed breast cancer cases and 558 population controls, frequently matched by geographic area, age and body mass index, were recruited in 12 Spanish provinces (MCC-Spain). Information was collected by a questionnaire and plasma 25(OH)D was measured by solid-phase extraction on-line coupled to liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS). Odds ratios and 95% confidence intervals were calculated using logistic and multinomial mixed regression models. We found a clear protective effect between 25(OH)D levels and breast cancer risk, with a significant dose-response trend (OR per 10 nmol/L = 0.88; 95%CI = 0.82-0.94). While no differences were observed between pre and postmenopausal women, stage at diagnosis, or across strata of the main breast cancer risk factors, the protection was more pronounced for triple negative tumors (OR per 10 nmol/L = 0.64; p-heterogeneity = 0.038). Similar results were observed when only cases sampled in the first month after diagnosis were considered. The protective effect of vitamin D on breast cancer risk may be subtype specific, being stronger for more aggressive tumors, which provides a new approach to prevent this disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

STS-26 long duration simulation in JSC Mission Control Center (MCC) Bldg 30

NASA Technical Reports Server (NTRS)

1988-01-01

STS-26 long duration simulation is conducted in JSC Mission Control Center (MCC) Bldg 30 Flight Control Room (FCR). Front row of consoles with Propulsion Engineer (PROP) and Guidance, Navigation, and Control Systems Engineer (GNC) are visible in the foreground. CBS television camera personnel record front visual displays (orbital chart and data) for '48 Hours' program to be broadcast at a later date. The integrated simulation involved communicating with crewmembers stationed in the fixed based (FB) shuttle mission simulator (SMS) located in JSC Mission Simulation and Training Facility Bldg 5.

Development of a quarterly referral productivity report.

PubMed

Wu, Cai; Sandoval, Alex; Hicks, Katrina N; Edwards, Tim J; Green, Lyle D

2007-10-11

The Office of Physician Relations at The University of Texas M. D. Anderson Cancer Center (MDACC) has developed a dynamic referral productivity reporting tool for its Multidisciplinary Care Centers (MCC). The tool leverages information within the institution's Enterprise Information Warehouse (EIW) using business intelligent software Hyperion Intelligent Explorer Suite 8.3. the referral productivity reports are intended to provide each MCC with detailed referral and registration data outlining how, and from where, patients arrive here for treatment. The reports supports operational and strategic initiatives aimed at improving referral processes and market related program development.

s95-16445

NASA Image and Video Library

2014-08-07

S95-16445 (13-22 July 1995) --- A wide angle view from the rear shows activity in the new Mission Control Center (MCC), opened for operation and dedicated during the STS-70 mission. The Space Shuttle Discovery was just passing over Florida at the time this photo was taken (note mercator map and TV scene on screens). The new MCC, developed at a cost of about 50 million, replaces the main-frame based, NASA-unique design of the old Mission Control with a standard workstation-based, local area network system commonly in use today.

Mission Control Center (MCC) - Apollo 13 - Fourth (4th) Television Signal - MSC

NASA Image and Video Library

1970-04-13

S70-35139 (13 April 1970) --- Overall view of the Mission Operations Control Room (MOCR) in the Mission Control Center (MCC) at Manned Spacecraft Center (MSC), during the fourth television transmission from the Apollo 13 mission in space. Eugene F. Kranz (foreground, back to camera), one of four Apollo 13 flight directors, views the large screen at front of MOCR, astronaut Fred W. Haise Jr., lunar module pilot, is seen on the screen. The fourth TV transmission from the Apollo 13 mission was on the evening of April 13, 1970.

[Study on preparation of phenols gastric floating tablet].

PubMed

Zhai, Xiao-Ling; Ni, Jian; Gu, Yu-Long

2008-01-01

To study the preparation of phenols gastric floating tablet. The tablets which were prepared using Eudragit IV, HPMC(K4M), MCC101 and Octadecanol as excipients were evaluated by vitro floatation and releasing performance. The pressure of preparationg was also study to select the optimal preparation. The tablets were successfully prepared in which the drug, Eudragit IV, Octadecanol were 31% respectively,and MCC101 was 7%. And 3-4 kg was found to be the eligible pressure. The study was found to be effective in the process of phenols gastric floating tablet.

New rodent models for studies of chemopreventive agents.

PubMed

Lipkin, M

1997-01-01

Some recent studies of the effects of chemopreventive agents have begun to use new rodent models to improve the analysis of stages of colonic preneoplasia, and how chemopreventive agents modify progressive abnormal cell development. In one of the models of inherited predisposition to colon cancer, mice carrying a truncated Apc allele with a nonsense mutation in exon 15 have been generated by gene targeting and embryonic stem cell technology (Apc1638 mice). These mice develop multiple gastrointestinal lesions, including adenomas and carcinomas, focal areas of high-grade dysplasia (FAD), and polypoid hyperplasias with FADS. The incidence of inherited colonic neoplasms has now been modulated by a chemopreventive regimen. Colonic lesions significantly increased in Apc1638 mice on a Western-style diet, which has higher fat content and lower calcium and vitamin D compared to the same mice on AIN-76A diet. In another rodent model, Min mice were treated with sulindac, which markedly reduced the incidence of intestinal tumors. A third new rodent model containing a targeted mutation in the gene Mcc (mutated in colorectal cancer) recently became available for chemoprevention studies. These mice develop multiple types of neoplasms including adenocarcinomas, focal areas of gastrointestinal dysplasia, papillomas of the forestomach, and tumors in other organs including lung, liver, and lymphoid tissue. Feeding a Western-style diet to the Mcc mutant mice also resulted in significantly increased gastrointestinal lesions. These nutrient modifications also have been given to normal mice, demonstrating without any chemical carcinogen that a Western-style diet induced colonic tumorigenesis. Western-style diets also have now induced modulation of cell proliferation in other organs including mammary gland, pancreas, and prostate. These findings help develop new preclinical rodent models to aid the analysis of genetic and environmental factors leading to neoplasia, as well as new methods for evaluating the chemopreventive efficacy of specific nutrients and pharmacological agents.

Digital Multicasting of Multiple Audio Streams

NASA Technical Reports Server (NTRS)

Macha, Mitchell; Bullock, John

2007-01-01

The Mission Control Center Voice Over Internet Protocol (MCC VOIP) system (see figure) comprises hardware and software that effect simultaneous, nearly real-time transmission of as many as 14 different audio streams to authorized listeners via the MCC intranet and/or the Internet. The original version of the MCC VOIP system was conceived to enable flight-support personnel located in offices outside a spacecraft mission control center to monitor audio loops within the mission control center. Different versions of the MCC VOIP system could be used for a variety of public and commercial purposes - for example, to enable members of the general public to monitor one or more NASA audio streams through their home computers, to enable air-traffic supervisors to monitor communication between airline pilots and air-traffic controllers in training, and to monitor conferences among brokers in a stock exchange. At the transmitting end, the audio-distribution process begins with feeding the audio signals to analog-to-digital converters. The resulting digital streams are sent through the MCC intranet, using a user datagram protocol (UDP), to a server that converts them to encrypted data packets. The encrypted data packets are then routed to the personal computers of authorized users by use of multicasting techniques. The total data-processing load on the portion of the system upstream of and including the encryption server is the total load imposed by all of the audio streams being encoded, regardless of the number of the listeners or the number of streams being monitored concurrently by the listeners. The personal computer of a user authorized to listen is equipped with special- purpose MCC audio-player software. When the user launches the program, the user is prompted to provide identification and a password. In one of two access- control provisions, the program is hard-coded to validate the user s identity and password against a list maintained on a domain-controller computer at the MCC. In the other access-control provision, the program verifies that the user is authorized to have access to the audio streams. Once both access-control checks are completed, the audio software presents a graphical display that includes audiostream-selection buttons and volume-control sliders. The user can select all or any subset of the available audio streams and can adjust the volume of each stream independently of that of the other streams. The audio-player program spawns a "read" process for the selected stream(s). The spawned process sends, to the router(s), a "multicast-join" request for the selected streams. The router(s) responds to the request by sending the encrypted multicast packets to the spawned process. The spawned process receives the encrypted multicast packets and sends a decryption packet to audio-driver software. As the volume or muting features are changed by the user, interrupts are sent to the spawned process to change the corresponding attributes sent to the audio-driver software. The total latency of this system - that is, the total time from the origination of the audio signals to generation of sound at a listener s computer - lies between four and six seconds.

The PP2AB56 phosphatase promotes the association of Cdc20 with APC/C in mitosis.

PubMed

Lee, Sun Joo; Rodriguez-Bravo, Veronica; Kim, Hyunjung; Datta, Sutirtha; Foley, Emily A

2017-05-15

PP2A comprising B56 regulatory subunit isoforms (PP2A B56 ) is a serine/threonine phosphatase essential for mitosis. At the kinetochore, PP2A B56 both stabilizes microtubule binding and promotes silencing of the spindle assembly checkpoint (SAC) through its association with the SAC protein BubR1. Cells depleted of the B56 regulatory subunits of PP2A are delayed in activation of Cdc20-containing APC/C (APC/C Cdc20 ), which is an essential step for mitotic exit. It has been hypothesized that this delay arises from increased production of the mitotic checkpoint complex (MCC), an APC/C Cdc20 inhibitor formed at unattached kinetochores through SAC signaling. In contrast to this prediction, we show that depletion of B56 subunits does not increase the amount or stability of the MCC. Rather, delays in APC/C Cdc20 activation in B56-depleted cells correlate with impaired Cdc20 binding to APC/C. Stimulation of APC/C Cdc20 assembly does not require binding between PP2A B56 and BubR1, and thus this contribution of PP2A B56 towards mitotic exit is distinct from its functions at kinetochores. PP2A B56 associates with APC/C constitutively in a BubR1-independent manner. A mitotic phosphorylation site on Cdc20, known to be a substrate of PP2A B56 , modulates APC/C Cdc20 assembly. These results elucidate the contributions of PP2A B56 towards completion of mitosis. © 2017. Published by The Company of Biologists Ltd.

A modular computational framework for automated peak extraction from ion mobility spectra

PubMed Central

2014-01-01

Background An ion mobility (IM) spectrometer coupled with a multi-capillary column (MCC) measures volatile organic compounds (VOCs) in the air or in exhaled breath. This technique is utilized in several biotechnological and medical applications. Each peak in an MCC/IM measurement represents a certain compound, which may be known or unknown. For clustering and classification of measurements, the raw data matrix must be reduced to a set of peaks. Each peak is described by its coordinates (retention time in the MCC and reduced inverse ion mobility) and shape (signal intensity, further shape parameters). This fundamental step is referred to as peak extraction. It is the basis for identifying discriminating peaks, and hence putative biomarkers, between two classes of measurements, such as a healthy control group and a group of patients with a confirmed disease. Current state-of-the-art peak extraction methods require human interaction, such as hand-picking approximate peak locations, assisted by a visualization of the data matrix. In a high-throughput context, however, it is preferable to have robust methods for fully automated peak extraction. Results We introduce PEAX, a modular framework for automated peak extraction. The framework consists of several steps in a pipeline architecture. Each step performs a specific sub-task and can be instantiated by different methods implemented as modules. We provide open-source software for the framework and several modules for each step. Additionally, an interface that allows easy extension by a new module is provided. Combining the modules in all reasonable ways leads to a large number of peak extraction methods. We evaluate all combinations using intrinsic error measures and by comparing the resulting peak sets with an expert-picked one. Conclusions Our software PEAX is able to automatically extract peaks from MCC/IM measurements within a few seconds. The automatically obtained results keep up with the results provided by current state-of-the-art peak extraction methods. This opens a high-throughput context for the MCC/IM application field. Our software is available at http://www.rahmannlab.de/research/ims. PMID:24450533

A modular computational framework for automated peak extraction from ion mobility spectra.

PubMed

D'Addario, Marianna; Kopczynski, Dominik; Baumbach, Jörg Ingo; Rahmann, Sven

2014-01-22

An ion mobility (IM) spectrometer coupled with a multi-capillary column (MCC) measures volatile organic compounds (VOCs) in the air or in exhaled breath. This technique is utilized in several biotechnological and medical applications. Each peak in an MCC/IM measurement represents a certain compound, which may be known or unknown. For clustering and classification of measurements, the raw data matrix must be reduced to a set of peaks. Each peak is described by its coordinates (retention time in the MCC and reduced inverse ion mobility) and shape (signal intensity, further shape parameters). This fundamental step is referred to as peak extraction. It is the basis for identifying discriminating peaks, and hence putative biomarkers, between two classes of measurements, such as a healthy control group and a group of patients with a confirmed disease. Current state-of-the-art peak extraction methods require human interaction, such as hand-picking approximate peak locations, assisted by a visualization of the data matrix. In a high-throughput context, however, it is preferable to have robust methods for fully automated peak extraction. We introduce PEAX, a modular framework for automated peak extraction. The framework consists of several steps in a pipeline architecture. Each step performs a specific sub-task and can be instantiated by different methods implemented as modules. We provide open-source software for the framework and several modules for each step. Additionally, an interface that allows easy extension by a new module is provided. Combining the modules in all reasonable ways leads to a large number of peak extraction methods. We evaluate all combinations using intrinsic error measures and by comparing the resulting peak sets with an expert-picked one. Our software PEAX is able to automatically extract peaks from MCC/IM measurements within a few seconds. The automatically obtained results keep up with the results provided by current state-of-the-art peak extraction methods. This opens a high-throughput context for the MCC/IM application field. Our software is available at http://www.rahmannlab.de/research/ims.

Experimental Design for Hanford Low-Activity Waste Glasses with High Waste Loading

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

Piepel, Gregory F.; Cooley, Scott K.; Vienna, John D.

This report discusses the development of an experimental design for the initial phase of the Hanford low-activity waste (LAW) enhanced glass study. This report is based on a manuscript written for an applied statistics journal. Appendices A, B, and E include additional information relevant to the LAW enhanced glass experimental design that is not included in the journal manuscript. The glass composition experimental region is defined by single-component constraints (SCCs), linear multiple-component constraints (MCCs), and a nonlinear MCC involving 15 LAW glass components. Traditional methods and software for designing constrained mixture experiments with SCCs and linear MCCs are not directlymore » applicable because of the nonlinear MCC. A modification of existing methodology to account for the nonlinear MCC was developed and is described in this report. One of the glass components, SO 3, has a solubility limit in glass that depends on the composition of the balance of the glass. A goal was to design the experiment so that SO 3 would not exceed its predicted solubility limit for any of the experimental glasses. The SO 3 solubility limit had previously been modeled by a partial quadratic mixture model expressed in the relative proportions of the 14 other components. The partial quadratic mixture model was used to construct a nonlinear MCC in terms of all 15 components. In addition, there were SCCs and linear MCCs. This report describes how a layered design was generated to (i) account for the SCCs, linear MCCs, and nonlinear MCC and (ii) meet the goals of the study. A layered design consists of points on an outer layer, and inner layer, and a center point. There were 18 outer-layer glasses chosen using optimal experimental design software to augment 147 existing glass compositions that were within the LAW glass composition experimental region. Then 13 inner-layer glasses were chosen with the software to augment the existing and outer-layer glasses. The experimental design was completed by a center-point glass, a Vitreous State Laboratory glass, and replicates of the center point and Vitreous State Laboratory glasses.« less

In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse transsulphuration, regulates motility through modulation of flagellar gene transcription

PubMed Central

2010-01-01

Background LuxS may function as a metabolic enzyme or as the synthase of a quorum sensing signalling molecule, auto-inducer-2 (AI-2); hence, the mechanism underlying phenotypic changes upon luxS inactivation is not always clear. In Helicobacter pylori, we have recently shown that, rather than functioning in recycling methionine as in most bacteria, LuxS (along with newly-characterised MccA and MccB), synthesises cysteine via reverse transsulphuration. In this study, we investigated whether and how LuxS controls motility of H. pylori, specifically if it has its effects via luxS-required cysteine metabolism or via AI-2 synthesis only. Results We report that disruption of luxS renders H. pylori non-motile in soft agar and by microscopy, whereas disruption of mccAHp or mccBHp (other genes in the cysteine provision pathway) does not, implying that the lost phenotype is not due to disrupted cysteine provision. The motility defect of the ΔluxSHp mutant was complemented genetically by luxSHp and also by addition of in vitro synthesised AI-2 or 4, 5-dihydroxy-2, 3-pentanedione (DPD, the precursor of AI-2). In contrast, exogenously added cysteine could not restore motility to the ΔluxSHp mutant, confirming that AI-2 synthesis, but not the metabolic effect of LuxS was important. Microscopy showed reduced number and length of flagella in the ΔluxSHp mutant. Immunoblotting identified decreased levels of FlaA and FlgE but not FlaB in the ΔluxSHp mutant, and RT-PCR showed that the expression of flaA, flgE, motA, motB, flhA and fliI but not flaB was reduced. Addition of DPD but not cysteine to the ΔluxSHp mutant restored flagellar gene transcription, and the number and length of flagella. Conclusions Our data show that as well as being a metabolic enzyme, H. pylori LuxS has an alternative role in regulation of motility by modulating flagellar transcripts and flagellar biosynthesis through production of the signalling molecule AI-2. PMID:20691071

Material and Compression Properties of Cedrela odorata Gum Co-Processed with Plantain Starch and Microcrystalline Cellulose.

PubMed

Adetunji, Oladapo Adewale; Odeniyi, Michael Ayodele

2016-01-01

Many excipients used in tableting exhibit some undesirable properties such as poor flow, cohesion and lubricating characteristics, thus necessitating some modification to achieve the desired product. The objective of this study was to enhance the material, flow and compressional properties of Cedrela odorata gum (COG) (Family: Meliaceae) by co-processing with plantain starch (PS) and microcrystalline cellulose (MCC). The COG was co-processed with PS (or MCC) by physical co-grinding at ratio 1 : 1, 1 : 2 and 1 : 4, and characterized using morphological analysis, swelling index viscosity measurements, particle size analysis and FTIR spectra. The material, flow and compressional properties of the co-processed excipients were also evaluated. Results were analyzed using mean and standard deviation of data. There was a decrease in the degree of agglomeration of COG and a reduction in the size of the powdered gum. The co-processed excipients were more spherical than the native excipients. The COG had the highest viscosity, while MCC and COG : PS (1 : 2) showed the highest and lowest degrees of swelling at 27.0 ± 0.05°C respectively. Water absorption capacity of the component excipients improved with co-processing COG : MCC increasing from 171.8 ± 1.54 (1 : 1) to 214.8 ± 1.07 (1 : 2), while COG : PS increased from 95.2 ± 0.08 (1 : 1) to 206.2 ± 0.13. There was a decrease in the percentage solubility of the co-processed excipients with the highest and lowest solubility observed in COG (54.1 ± 0.07%) and PS (3.7 ± 0.16%), respectively. The FTIR spectra indicate no significant interaction between the excipients. The poor flow of the component excipients did not improve with co-processing; however, there was a significant increase in compressibility. Generally, COG co-processed with MCC showed better compression properties when compared with COG co-processed with PS. Co-processing of COD with MC or PS enhanced the characters of the component excipients, thus making the co-processed excipients suitable for direct compression of tablets without altering the chemical nature of the component excipients.