Membrane adaptive optics

NASA Astrophysics Data System (ADS)

Marker, Dan K.; Wilkes, James M.; Ruggiero, Eric J.; Inman, Daniel J.

2005-08-01

An innovative adaptive optic is discussed that provides a range of capabilities unavailable with either existing, or newly reported, research devices. It is believed that this device will be inexpensive and uncomplicated to construct and operate, with a large correction range that should dramatically relax the static and dynamic structural tolerances of a telescope. As the areal density of a telescope primary is reduced, the optimal optical figure and the structural stiffness are inherently compromised and this phenomenon will require a responsive, range-enhanced wavefront corrector. In addition to correcting for the aberrations in such innovative primary mirrors, sufficient throw remains to provide non-mechanical steering to dramatically improve the Field of regard. Time dependent changes such as thermal disturbances can also be accommodated. The proposed adaptive optic will overcome some of the issues facing conventional deformable mirrors, as well as current and proposed MEMS-based deformable mirrors and liquid crystal based adaptive optics. Such a device is scalable to meter diameter apertures, eliminates high actuation voltages with minimal power consumption, provides long throw optical path correction, provides polychromatic dispersion free operation, dramatically reduces the effects of adjacent actuator influence, and provides a nearly 100% useful aperture. This article will reveal top-level details of the proposed construction and include portions of a static, dynamic, and residual aberration analysis. This device will enable certain designs previously conceived by visionaries in the optical community.

Distinct Mechanisms of the ORANGE Protein in Controlling Carotenoid Flux1[OPEN

PubMed Central

Ohali, Shachar; Meir, Ayala; Sa’ar, Uzi; Mazourek, Michael; Lewinsohn, Efraim; Schaffer, Arthur A.; Burger, Joseph

2017-01-01

β-Carotene adds nutritious value and determines the color of many fruits, including melon (Cucumis melo). In melon mesocarp, β-carotene accumulation is governed by the Orange gene (CmOr) golden single-nucleotide polymorphism (SNP) through a yet to be discovered mechanism. In Arabidopsis (Arabidopsis thaliana), OR increases carotenoid levels by posttranscriptionally regulating phytoene synthase (PSY). Here, we identified a CmOr nonsense mutation (Cmor-lowβ) that lowered fruit β-carotene levels with impaired chromoplast biogenesis. Cmor-lowβ exerted a minimal effect on PSY transcripts but dramatically decreased PSY protein levels and enzymatic activity, leading to reduced carotenoid metabolic flux and accumulation. However, the golden SNP was discovered to not affect PSY protein levels and carotenoid metabolic flux in melon fruit, as shown by carotenoid and immunoblot analyses of selected melon genotypes and by using chemical pathway inhibitors. The high β-carotene accumulation in golden SNP melons was found to be due to a reduced further metabolism of β-carotene. This was revealed by genetic studies with double mutants including carotenoid isomerase (yofi), a carotenoid-isomerase nonsense mutant, which arrests the turnover of prolycopene. The yofi F2 segregants accumulated prolycopene independently of the golden SNP. Moreover, Cmor-lowβ was found to inhibit chromoplast formation and chloroplast disintegration in fruits from 30 d after anthesis until ripening, suggesting that CmOr regulates the chloroplast-to-chromoplast transition. Taken together, our results demonstrate that CmOr is required to achieve PSY protein levels to maintain carotenoid biosynthesis metabolic flux but that the mechanism of the CmOr golden SNP involves an inhibited metabolism downstream of β-carotene to dramatically affect both carotenoid content and plastid fate. PMID:27837090

Antioxidative effects of cinnamomi cortex: A potential role of iNOS and COX-II

PubMed Central

Chung, Jin-Won; Kim, Jeong-Jun; Kim, Sung-Jin

2011-01-01

Background: Cinnamomi cortex has wide varieties of pharmacological actions such as anti-inflammatory action, anti-platelet aggregation, and improving blood circulation. In this study, we tested to determine whether the Cinnamomi cortex extract has antioxidant activities. Materials and Methods: Antioxidative actions were explored by measuring free radical scavenging activity, NO levels, and reducing power. The mechanism of antioxidative action of Cinnamomi cortex was determined by measuring iNOS and COX-II expression in lipopolysaccharide (LPS) stimulated Raw cells. Results: Seventy percent methanolic extract of Cinnamomi cortex exerted significant 1,1-diphenyl--2--picrylhydrazyl (DPPH) free radicals and NO scavenging activities in a dose-dependent manner. More strikingly, the Cinnamomi cortex extract exerted dramatic reducing power activity (13-fold over control). Production of iNOS induced by LPS was significantly inhibited by the Cinnamomi cortex extract, suggesting that it inhibits NO production by suppressing iNOS expression. Additionally, COX-2 induced by LPS was dramatically inhibited by the Cinnamomi cortex extract. Conclusion: These results suggest that 70% methanolic extract of Cinnamomi cortex exerts significant antioxidant activity via inhibiting iNOS and COX-II induction. PMID:22262934

Tobacco and the Escalating Global Cancer Burden

PubMed Central

Oppeltz, Richard F.; Jatoi, Ismail

2011-01-01

The global burden of cancer is escalating as a result of dramatic increases in the use of tobacco in the developing world. The use of tobacco is linked to the development of a broad variety of cancers, mainly lung cancer, the single most common cancer in the world. Tobacco smoking-attributable deaths extends beyond cancer and include stroke, heart attack and COPD. Widening disparities in cancer-related mortality have shifted towards a more dramatic burden in the developing world. Appropriate interventions must be implemented to reduce tobacco use and prevent global mortality that has escalated to epidemic levels. Tobacco control policies, including public health advertisement campaigns, warning labels, adoption of smoke-free laws, comprehensive bans and tax policies are highly effective measures to control tobacco use. Clinicians and academic institutions have to be actively committed to support tobacco control initiatives. The reduction in cancer related morbidity and mortality should be viewed as a global crisis and definitive results will depend on a multilevel effort to effectively reduce the burden of cancer, particularly in underprivileged regions of the world. PMID:21869888

Siloxane Modifiers for Epoxy Resins.

DTIC Science & Technology

1983-12-01

similarly prepared ATBN- and CTBN -modified epoxies. Wear rate was quite dramatically reduced with some of the modifiers. Wear results are discussed in...similarly prepared ATBN- and CTBN -modified epoxies. Wear rate was quite dramatically reduced with some of the modifiers. Wear results are discussed...acrylonitrile copolymers having both carboxyl ( CTBN ) and amine (ATBN) end groups have been widely used as epoxy modifiers (4-11). During the curing process, the

Anabolic androgenic steroid nandrolone decanoate reduces hypothalamic proopiomelanocortin mRNA levels.

PubMed

Lindblom, Jonas; Kindlundh, Anna M S; Nyberg, Fred; Bergström, Lena; Wikberg, Jarl E S

2003-10-03

Supratherapeutical doses of anabolic androgenic steroids (AASs) have dramatic effects on metabolism in humans, and also inhibit feeding and reduce the rate of body weight gain in rats. In order to test the hypothesis that the AAS metabolic syndrome is accompanied by alterations in the central melanocortin system, we evaluated body weight, food intake and hypothalamic agouti-related protein (AgRP) and proopiomelanocortin (POMC) mRNA levels following administration of different doses of the anabolic androgenic steroid nandrolone decanoate. In order to distinguish changes induced by the steroid treatment per se from those resulting from the reduced food intake and growth rate, we also compared the effect of nandrolone decanoate on AgRP and POMC mRNA expression with both normally fed, and food restricted control groups. We here report that administration of nandrolone specifically reduces arcuate nucleus POMC mRNA levels while not affecting the expression level of AgRP. The effect on POMC expression was not observed in the food restricted controls, excluding the possibility that the observed effect was a mere response to the reduced food intake and body weight. These results raise the possibility that some of the metabolic and behavioural consequences of AAS abuse may be the result of alterations in the melanocortin system.

Further LDL cholesterol lowering through targeting PCSK9 for coronary artery disease.

PubMed

Cao, Guoqing; Qian, Yue-Wei; Kowala, Mark C; Konrad, Robert J

2008-12-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that belongs to the proprotein convertase family. PCSK9 is synthesized as a zymogen and its prodomain is cleaved by its own catalytic activity. The cleaved prodomain forms a protein complex with the rest of the PCSK9 carboxyl terminus within the endoplasmic reticulum and is secreted. Secreted PCSK9 has been shown to be able to reduce low-density lipoprotein receptor (LDLR) levels in vitro and in vivo. Thus PCSK9 has emerged as an important player modulating LDLR levels and plasma LDL cholesterol. Furthermore, PCSK9 deficiency leads to significantly lowered LDL cholesterol levels in humans and provides dramatic protection against coronary heart disease. We review here the current understanding of PCSK9 and its potential as a therapeutic target through which to reduce LDL cholesterol for prevention and treatment of coronary heart disease.

[Paradoxical effect of methylphenidate in the treatment of a patient with severe traumatic brain injury].

PubMed

Grønborg, Pia; Liljegren, Jeanette; Jansen, Jette

2009-06-22

Methylphenidate is a central nervous system (CNS)-stimulating agent. During recent years methylphenidate has been shown to increase arousal in patients with traumatic brain injury. We describe a patient with a severe traumatic injury in whom arousal was increased when methylphenidate was given, and the level of arousal decreased when the amount was diminished after some months. Due to possible side effects, methylphenidate treatment was reduced over several weeks 2 years after the trauma. Surprisingly, the cognitive level was then dramatically improved. To our knowledge, such paradoxical effect of methylphenidate has not previously been described.

Dietary mung bean protein reduces high-fat diet-induced weight gain by modulating host bile acid metabolism in a gut microbiota-dependent manner.

PubMed

Nakatani, Akiho; Li, Xuan; Miyamoto, Junki; Igarashi, Miki; Watanabe, Hitoshi; Sutou, Asuka; Watanabe, Keita; Motoyama, Takayasu; Tachibana, Nobuhiko; Kohno, Mitsutaka; Inoue, Hiroshi; Kimura, Ikuo

2018-07-02

The 8-globulin-rich mung bean protein (MPI) suppresses hepatic lipogenesis in rodent models and reduces fasting plasma glucose and insulin levels in obese adults. However, its effects on mitigating high fat diet (HFD)-induced obesity and the mechanism underlying these effects remain to be elucidated. Herein, we examined the metabolic phenotype, intestinal bile acid (BA) pool, and gut microbiota of conventionally raised (CONV-R) male C57BL/6 mice and germ-free (GF) mice that were randomized to receive either regular HFD or HFD containing mung bean protein isolate (MPI) instead of the dairy protein present in regular HFD. MPI intake significantly reduced HFD-induced weight gain and adipose tissue accumulation, and attenuated hepatic steatosis. Enhancement in the secretion of intestinal glucagon-like peptide-1 (GLP-1) and an enlarged cecal and fecal BA pool of dramatically elevated secondary/primary BA ratio were observed in mice that had consumed MPI. These effects were abolished in GF mice, indicating that the effects were dependent upon the presence of the microbiota. As revealed by 16S rRNA gene sequence analysis, MPI intake also elicited dramatic changes in the gut microbiome, such as an expansion of taxa belonging to the phylum Bacteroidetes along with a reduced abundance of the Firmicutes. Copyright © 2018 Elsevier Inc. All rights reserved.

The impact of a forced reduction in traffic volumes on urban air pollution

NASA Astrophysics Data System (ADS)

Yuval; Flicstein, Bernanda; Broday, David M.

The Middle East military conflict of summer 2006 resulted in a few weeks in which the city of Haifa, Israel, and its environs experienced very profound variations in the commercial and personal activities. Large industrial plants continued almost normal operations but activities of small scale industry, shopping, and personal commuting were drastically reduced, leading to a dramatic decrease in the commercial and personal traffic volumes. This period of reduced activity serves as a real life experiment for assessment and demonstration of the impact that human activity, and mainly road traffic, may have on the air pollution levels in a bustling middle-sized city. The analysis is made especially sharp and reliable due to the abruptness of the beginning and the end of the reduced activity period, its length, and the stable summer meteorological conditions in the eastern Mediterranean region. The reduced traffic volumes resulted in lowered levels of NO 2, hydrocarbons and particulate matter. The decrease in these pollutants' mean concentration was significantly larger than the reduction in the mean traffic volume. Slightly higher mean O 3 concentrations were observed during the reduced traffic period.

Differential Changes in Expression of Stress- and Metabolic-Related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal

PubMed Central

Núnez, Cristina; Zelei, Edina; Polyák, Ágnes; Milanés, M. Victoria

2013-01-01

Chronic morphine treatment and naloxone precipitated morphine withdrawal activates stress-related brain circuit and results in significant changes in food intake, body weight gain and energy metabolism. The present study aimed to reveal hypothalamic mechanisms underlying these effects. Adult male rats were made dependent on morphine by subcutaneous implantation of constant release drug pellets. Pair feeding revealed significantly smaller weight loss of morphine treated rats compared to placebo implanted animals whose food consumption was limited to that eaten by morphine implanted pairs. These results suggest reduced energy expenditure of morphine-treated animals. Chronic morphine exposure or pair feeding did not significantly affect hypothalamic expression of selected stress- and metabolic related neuropeptides - corticotropin-releasing hormone (CRH), urocortin 2 (UCN2) and proopiomelanocortin (POMC) compared to placebo implanted and pair fed animals. Naloxone precipitated morphine withdrawal resulted in a dramatic weight loss starting as early as 15–30 min after naloxone injection and increased adrenocorticotrophic hormone, prolactin and corticosterone plasma levels in morphine dependent rats. Using real-time quantitative PCR to monitor the time course of relative expression of neuropeptide mRNAs in the hypothalamus we found elevated CRH and UCN2 mRNA and dramatically reduced POMC expression. Neuropeptide Y (NPY) and arginine vasopressin (AVP) mRNA levels were transiently increased during opiate withdrawal. These data highlight that morphine withdrawal differentially affects expression of stress- and metabolic-related neuropeptides in the rat hypothalamus, while relative mRNA levels of these neuropeptides remain unchanged either in rats chronically treated with morphine or in their pair-fed controls. PMID:23805290

Restoration of metabolic health by decreased consumption of branched-chain amino acids.

PubMed

Cummings, Nicole E; Williams, Elizabeth M; Kasza, Ildiko; Konon, Elizabeth N; Schaid, Michael D; Schmidt, Brian A; Poudel, Chetan; Sherman, Dawn S; Yu, Deyang; Arriola Apelo, Sebastian I; Cottrell, Sara E; Geiger, Gabriella; Barnes, Macy E; Wisinski, Jaclyn A; Fenske, Rachel J; Matkowskyj, Kristina A; Kimple, Michelle E; Alexander, Caroline M; Merrins, Matthew J; Lamming, Dudley W

2018-02-15

We recently found that feeding healthy mice a diet with reduced levels of branched-chain amino acids (BCAAs), which are associated with insulin resistance in both humans and rodents, modestly improves glucose tolerance and slows fat mass gain. In the present study, we show that a reduced BCAA diet promotes rapid fat mass loss without calorie restriction in obese mice. Selective reduction of dietary BCAAs also restores glucose tolerance and insulin sensitivity to obese mice, even as they continue to consume a high-fat, high-sugar diet. A low BCAA diet transiently induces FGF21 (fibroblast growth factor 21) and increases energy expenditure. We suggest that dietary protein quality (i.e. the precise macronutrient composition of dietary protein) may impact the effectiveness of weight loss diets. Obesity and diabetes are increasing problems around the world, and although even moderate weight loss can improve metabolic health, reduced calorie diets are notoriously difficult to sustain. Branched-chain amino acids (BCAAs; leucine, isoleucine and valine) are elevated in the blood of obese, insulin-resistant humans and rodents. We recently demonstrated that specifically reducing dietary levels of BCAAs has beneficial effects on the metabolic health of young, growing mice, improving glucose tolerance and modestly slowing fat mass gain. In the present study, we examine the hypothesis that reducing dietary BCAAs will promote weight loss, reduce adiposity, and improve blood glucose control in diet-induced obese mice with pre-existing metabolic syndrome. We find that specifically reducing dietary BCAAs rapidly reverses diet-induced obesity and improves glucoregulatory control in diet-induced obese mice. Most dramatically, mice eating an otherwise unhealthy high-calorie, high-sugar Western diet with reduced levels of BCAAs lost weight and fat mass rapidly until regaining a normal weight. Importantly, this normalization of weight was mediated not by caloric restriction or increased activity, but by increased energy expenditure, and was accompanied by a transient induction of the energy balance regulating hormone FGF21 (fibroblast growth factor 21). Consumption of a Western diet reduced in BCAAs was also accompanied by a dramatic improvement in glucose tolerance and insulin resistance. Our results link dietary BCAAs with the regulation of metabolic health and energy balance in obese animals, and suggest that specifically reducing dietary BCAAs may represent a highly translatable option for the treatment of obesity and insulin resistance. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Development of Chemically Amplified Optical Sensors for Continuous Blood Glucose Monitoring Final Report CRADA No. TSB-1162-95

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

Lane, Stephen M.; Mastrototaro, John J.

Diabetes is a chronic disease that affects 14 million people in the U.S. and more than 110 million people worldwide. Each year in this country 27,000 diabetic patients become blind, 15,000 have kidney failure, and over 54,000 have peripheral limb amputations. In 1992, total healthcare costs in the U.S. for diabetes were more than $105 billion, approximately 15% of our healthcare budget. Conventional therapy for the most severe form of diabetes, insulin-dependent diabetes mellitus (IDDM) or Type I diabetes, is to administer one or two injections per day of various forms of insulin while monitoring blood glucose levels twice ormore » three times daily with commercial glucometers that require blood samples. Near normal blood sugar levels (glycemic control) is difficult to achieve with conventional therapy. In the fall of 1993, the results of the 10-year $165 million Diabetes Control and Complications Trial (DCCT) were published which showed that intensive insulin management would lead to dramatically fewer cases of retinopathy (which leads to blindness), nephropathy (which leads to kidney failure), and neuropathy (which can lead to limb amputations) [New England Journal of Medicine, Vo1239, No.14 977-986 (1993)]. If existing commercial insulin pumps could be combined with a continuous glucose sensor, a more physiological and fine-tuned therapy could be provided - in effect, an artificial biomechanical pancreas would be available. Existing research suggested that such a development would dramatically improve glucose control, thus greatly reducing morbidity and mortality from this disease. MiniMed Technologies in Sylmar, CA, identified a number of optically based sensor strategies as well as candidate chemical reactions that could be used to implement a minimally invasive opto-chemical glucose sensor. LLNL evaluated these sensor strategies and chemical reactions. These evaluations were the first steps leading to development of a sensor of considerable importance that could maintain near normal physiological glycemic levels, thus dramatically reducing the risk of the microvascular complications mentioned above.« less

Surgical and healing changes to ocular aberrations following refractive surgery

NASA Astrophysics Data System (ADS)

Straub, Jochen; Schwiegerling, Jim

2003-07-01

Purpose: To measure ocular aberrations before and at several time periods after LASIK surgery to determine the change to the aberration structure of the eye. Methods: A Shack-Hartmann wavefront sensor was used to measure 88 LASIK patients pre-operatively and at 1 week and 12 months following surgery. Reconstructed wavefront errors are compared to look at induced differences. Manifest refraction was measured at 1 week, 1 month, 3 months, 6 months and 12 months following surgery. Sphere, cylinder, spherical aberration, and pupil diameter are analyzed. Results: A dramatic elevation in spherical aberration is seen following surgery. This elevation appears almost immediately and remains for the duration of the study. A temporary increase in pupil size is seen following surgery. Conclusions: LASIK surgery dramatically reduces defocus and astigmatism in the eye, but simultaneously increases spherical aberration levels. This increase occurs at the time of surgery and is not an effect of the healing response.

The all electric airplane-benefits and challenges

NASA Technical Reports Server (NTRS)

Spitzer, C. R.; Hood, R. V.

1982-01-01

The all electric aircraft considered in the present investigation is an aircraft which has digital flight crucial controls, electromechanical actuators, and electrical secondary power. There are no hydraulic or pneumatic systems. The characteristics of an all electric aircraft are related to reduced acquisition cost, reduced weight, reduced fuel consumption, increased reliability, reduced support equipment, simpler maintenance, an expanded flight envelope, and improved survivability. An additional benefit is the dramatically increased design flexibility and mission adaptability. However, the implementation of the all electric aircraft concept requires the resolution of a number of major technology issues. Issues in the digital flight controls area are related to achieving the required levels of safety and reliability in a cost effective manner. Other challenges which have to be met are concerned with electromechanical actuators, environmental control and ice protection systems, and engine technology.

Creative Dramatics Handbook.

ERIC Educational Resources Information Center

Philadelphia School District, PA. Office of Early Childhood Programs.

This handbook on creative dramatics at the elementary school level is primarily intended to assist the teacher who already has some training in creative dramatics. The handbook contains sections on (1) the philosophy and objectives of the program, including a discussion of an affective curriculum; (2) definitions of key concepts, including general…

Advances in lipid-lowering therapy through gene-silencing technologies.

PubMed

Nordestgaard, Børge G; Nicholls, Stephen J; Langsted, Anne; Ray, Kausik K; Tybjærg-Hansen, Anne

2018-05-01

New treatment opportunities are emerging in the field of lipid-lowering therapy through gene-silencing approaches. Both antisense oligonucleotide inhibition and small interfering RNA technology aim to degrade gene mRNA transcripts to reduce protein production and plasma lipoprotein levels. Elevated levels of LDL, remnant lipoproteins, and lipoprotein(a) all cause cardiovascular disease, whereas elevated levels of triglyceride-rich lipoproteins in some patients can cause acute pancreatitis. The levels of each of these lipoproteins can be reduced using gene-silencing therapies by targeting proteins that have an important role in lipoprotein production or removal (for example, the protein products of ANGPTL3, APOB, APOC3, LPA, and PCSK9). Using this technology, plasma levels of these lipoproteins can be reduced by 50-90% with 2-12 injections per year; such dramatic reductions are likely to reduce the incidence of cardiovascular disease or acute pancreatitis in at-risk patients. The reported adverse effects of these new therapies include injection-site reactions, flu-like symptoms, and low blood platelet counts. However, newer-generation drugs are more efficiently delivered to liver cells, requiring lower drug doses, which leads to fewer adverse effects. Although these findings are promising, robust evidence of cardiovascular disease reduction and long-term safety is needed before these gene-silencing technologies can have widespread implementation. Before the availability of such evidence, these drugs might have roles in patients with unmet medical needs through orphan indications.

Educational and intervention programmes for gestational diabetes mellitus (GDM) management: An integrative review.

PubMed

Carolan-OIah, Mary C

2016-01-01

Gestational diabetes mellitus (GDM) is a serious pregnancy disorder, which is linked to stillbirth, birth damage and later development of type 2 diabetes. Rates of GDM have increased dramatically in the past 20 years, related to obesity, sedentary lifestyles and ethnicity. The aim of this integrative review was to identify and to critically review existing self-management programmes for GDM. A search for studies published between 2000 and 2013 was conducted on: PubMed, CINAHL, Medline, OvidSP, ProQuest, SCOPUS and Wiley online library. GDM search terms included gestational diabetes mellitus; GDM, pregnancy diabetes. Search terms for self-management programmes, included educational programmes; lifestyle intervention; exercise, diet, weight management in pregnancy; life-style interventions. Fifty papers were located in the search, and 12 were included in the review. Interventions fell into three main groups: (1) dietary and exercise interventions; (2) self-monitoring of blood glucose levels; and (3) counselling/behavioural interventions. This review found that although interventions varied in approach, most were successful in reducing insulin requirements; in reducing rates of macrosomia and hypertensive disorders, and in improving levels of knowledge and pregnancy outcomes. Only one study found that the intervention did not contribute some positive outcome. Interventions that include adopting a low glycemic index diet and increasing levels of activity appear to be successful at reducing maternal blood glucose levels and reducing insulin requirements during pregnancy. Reducing maternal blood glucose levels, in turn, is associated with a reduction of macrosomia and maternal weight gain.

Transgenic upregulation of the condensed tannin pathway in poplar leads to a dramatic shift in leaf palatability for two tree-feeding Lepidoptera.

PubMed

Boeckler, G Andreas; Towns, Megan; Unsicker, Sybille B; Mellway, Robin D; Yip, Lynn; Hilke, Ines; Gershenzon, Jonathan; Constabel, C Peter

2014-02-01

Transgenic hybrid aspen (Populus tremula x tremuloides) overexpressing the MYB134 tannin regulatory gene show dramatically enhanced condensed tannin (proanthocyanidin) levels, as well as shifts in other phenolic metabolites. A series of insect bioassays with forest tent caterpillars (Malacosoma disstria) and gypsy moth (Lymantria dispar) caterpillars was carried out to determine how this metabolic shift affects food preference and performance of generalist tree-feeding lepidopterans. Both species showed a distinct preference for the high-tannin MYB134 overexpressor plants, and L. dispar performance was enhanced relative to controls. L. dispar reached greater pupal weight and showed reduced time to pupation when reared on the MYB134 overexpressing poplar. These results were unexpected since enhanced condensed tannin levels were predicted to act as feeding deterrents. However, the data may be explained by the observed decrease in the salicinoids (phenolic glycosides) salicortin and tremulacin that accompanied the upregulation of the condensed tannins in the transgenics. We conclude that for these two lepidopteran species, condensed tannin levels are unlikely to be a major determinant of caterpillar food preference or performance. However, our experiments show that overexpression of a single regulatory gene in transgenic aspen can have a significant impact on herbivorous insects.

Regulated Breathing Effect of Silicon Negative Electrode for Dramatically Enhanced Performance of Li-Ion Battery

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

Xiao, Xingcheng; Zhou, Weidong; Kim, Youngnam

Si is an attractive negative electrode material for lithium ion batteries due to its high specifi c capacity (≈3600 mAh g –1 ). However, the huge volume swelling and shrinking during cycling, which mimics a breathing effect at the material/electrode/cell level, leads to several coupled issues including fracture of Si particles, unstable solid electrolyte interphase, and low Coulombic effi ciency. In this work, the regulation of the breathing effect is reported by using Si–C yolk–shell nanocomposite which has been well-developed by other researchers. The focus is on understanding how the nanoscaled materials design impacts the mechanical and electrochemical response atmore » electrode level. For the fi rst time, it is possible to observe one order of magnitude of reduction on breathing effect at the electrode level during cycling: the electrode thickness variation reduced down to 10%, comparing with 100% in the electrode with Si nanoparticles as active materials. The Si–C yolk–shell nanocomposite electrode exhibits excellent capacity retention and high cycle effi ciency. In situ transmission electron microscopy and fi nite element simulations consistently reveals that the dramatically enhanced performance is associated with the regulated breathing of the Si in the new composite, therefore the suppression of the overall electrode expansion.« less

On-chip phase-change photonic memory and computing

NASA Astrophysics Data System (ADS)

Cheng, Zengguang; Ríos, Carlos; Youngblood, Nathan; Wright, C. David; Pernice, Wolfram H. P.; Bhaskaran, Harish

2017-08-01

The use of photonics in computing is a hot topic of interest, driven by the need for ever-increasing speed along with reduced power consumption. In existing computing architectures, photonic data storage would dramatically improve the performance by reducing latencies associated with electrical memories. At the same time, the rise of `big data' and `deep learning' is driving the quest for non-von Neumann and brain-inspired computing paradigms. To succeed in both aspects, we have demonstrated non-volatile multi-level photonic memory avoiding the von Neumann bottleneck in the existing computing paradigm and a photonic synapse resembling the biological synapses for brain-inspired computing using phase-change materials (Ge2Sb2Te5).

Payment Reduction and Medicare Private Fee-for-Service Plans

PubMed Central

Frakt, Austin B.; Pizer, Steven D.; Feldman, Roger

2009-01-01

Medicare private fee-for-service (PFFS) plans are paid like other Medicare Advantage (MA) plans but are exempt from many MA requirements. Recently, Congress set average payments well above the costs of traditional fee-for-service (FFS) Medicare, inducing dramatic increases in PFFS plan enrollment. This has significant implications for Medicare's budget, provoking calls for policy change. We predict the effect of proposals to cut PFFS payments on PFFS plan participation and enrollment. We find that small reductions in payment rates would reduce PFFS participation and enrollment; if Congress reduces payments to traditional FFS levels it would cause the vast majority (85 percent) of PFFS plans to exit the market. PMID:19544932

σ2-Adaptin Facilitates Basal Synaptic Transmission and Is Required for Regenerating Endo-Exo Cycling Pool Under High-Frequency Nerve Stimulation in Drosophila.

PubMed

Choudhury, Saumitra Dey; Mushtaq, Zeeshan; Reddy-Alla, Suneel; Balakrishnan, Sruthi S; Thakur, Rajan S; Krishnan, Kozhalmannom S; Raghu, Padinjat; Ramaswami, Mani; Kumar, Vimlesh

2016-05-01

The functional requirement of adapter protein 2 (AP2) complex in synaptic membrane retrieval by clathrin-mediated endocytosis is not fully understood. Here we isolated and functionally characterized a mutation that dramatically altered synaptic development. Based on the aberrant neuromuscular junction (NMJ) synapse, we named this mutation angur (a Hindi word meaning "grapes"). Loss-of-function alleles of angur show more than twofold overgrowth in bouton numbers and a dramatic decrease in bouton size. We mapped the angur mutation to σ2-adaptin, the smallest subunit of the AP2 complex. Reducing the neuronal level of any of the subunits of the AP2 complex or disrupting AP2 complex assembly in neurons phenocopied the σ2-adaptin mutation. Genetic perturbation of σ2-adaptin in neurons leads to a reversible temperature-sensitive paralysis at 38°. Electrophysiological analysis of the mutants revealed reduced evoked junction potentials and quantal content. Interestingly, high-frequency nerve stimulation caused prolonged synaptic fatigue at the NMJs. The synaptic levels of subunits of the AP2 complex and clathrin, but not other endocytic proteins, were reduced in the mutants. Moreover, bone morphogenetic protein (BMP)/transforming growth factor β (TGFβ) signaling was altered in these mutants and was restored by normalizing σ2-adaptin in neurons. Thus, our data suggest that (1) while σ2-adaptin facilitates synaptic vesicle (SV) recycling for basal synaptic transmission, its activity is also required for regenerating SVs during high-frequency nerve stimulation, and (2) σ2-adaptin regulates NMJ morphology by attenuating TGFβ signaling. Copyright © 2016 by the Genetics Society of America.

Apoplastic peroxidases are required for salicylic acid-mediated defense against Pseudomonas syringae.

PubMed

Mammarella, Nicole D; Cheng, Zhenyu; Fu, Zheng Qing; Daudi, Arsalan; Bolwell, G Paul; Dong, Xinnian; Ausubel, Frederick M

2015-04-01

Reactive oxygen species (ROS) generated by NADPH oxidases or apoplastic peroxidases play an important role in the plant defense response. Diminished expression of at least two Arabidopsis thaliana peroxidase encoding genes, PRX33 (At3g49110) and PRX34 (At3g49120), as a consequence of anti-sense expression of a heterologous French bean peroxidase gene (asFBP1.1), were previously shown to result in reduced levels of ROS following pathogen attack, enhanced susceptibility to a variety of bacterial and fungal pathogens, and reduced levels of callose production and defense-related gene expression in response to the microbe associated molecular pattern (MAMP) molecules flg22 and elf26. These data demonstrated that the peroxidase-dependent oxidative burst plays an important role in the elicitation of pattern-triggered immunity (PTI). Further work reported in this paper, however, shows that asFBP1.1 antisense plants are not impaired in all PTI-associated responses. For example, some but not all flg22-elicited genes are induced to lower levels by flg22 in asFPB1.1, and callose deposition in asFPB1.1 is similar to wild-type following infiltration with a Pseudomonas syringae hrcC mutant or with non-host P. syringae pathovars. Moreover, asFPB1.1 plants did not exhibit any apparent defect in their ability to mount a hypersensitive response (HR). On the other hand, salicylic acid (SA)-mediated activation of PR1 was dramatically impaired in asFPB1.1 plants. In addition, P. syringae-elicited expression of many genes known to be SA-dependent was significantly reduced in asFBP1.1 plants. Consistent with this latter result, in asFBP1.1 plants the key regulator of SA-mediated responses, NPR1, showed both dramatically decreased total protein abundance and a failure to monomerize, which is required for its translocation into the nucleus. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Bio-ecological control of chronic liver disease and encephalopathy].

PubMed

Bengmark, S; Di Cocco, P; Clemente, K; Corona, L; Angelico, R; Manzia, T; Famulari, A; Pisani, F; Orlando, G

2011-08-01

Minimal encephalopathy was originally associated with chronic liver disease but is increasingly associated with most other chronic diseases and particularly with diabetes and also chronic disorders in other organs: kidneys, lungs, thyroid and with obesity. It is increasingly with dramatically increased and more or less permanent increase in systemic inflammation, most likely a result of Western lifestyle. Frequent physical exercise and intake of foods rich in vitamins, antioxidants, fibres, lactic acid bacteria etc in combination with reduction in intake of refined and processed foods is known to reduce systemic inflammation and prevent chronic diseases. Some lactic acid bacteria, especially Lb paracasei, lb plantarum and pediococcus pentosaceus have proven effective to reduce inflammation and eliminate encephalopathy. Significant reduction in blood ammonia levels and endotoxin levels were reported in parallel to improvement of liver disease. Subsequent studies with other lactic acid bacteria seem to demonstrate suppression of inflammation and one study also provides evidence of clinical improvement.

Algorithms and analyses for stochastic optimization for turbofan noise reduction using parallel reduced-order modeling

NASA Astrophysics Data System (ADS)

Yang, Huanhuan; Gunzburger, Max

2017-06-01

Simulation-based optimization of acoustic liner design in a turbofan engine nacelle for noise reduction purposes can dramatically reduce the cost and time needed for experimental designs. Because uncertainties are inevitable in the design process, a stochastic optimization algorithm is posed based on the conditional value-at-risk measure so that an ideal acoustic liner impedance is determined that is robust in the presence of uncertainties. A parallel reduced-order modeling framework is developed that dramatically improves the computational efficiency of the stochastic optimization solver for a realistic nacelle geometry. The reduced stochastic optimization solver takes less than 500 seconds to execute. In addition, well-posedness and finite element error analyses of the state system and optimization problem are provided.

Alkaline phosphatase in osteoblasts is down-regulated by pulsatile fluid flow

NASA Technical Reports Server (NTRS)

Hillsley, M. V.; Frangos, J. A.

1997-01-01

It is our hypothesis that interstitial fluid flow plays a role in the bone remodeling response to mechanical loading. The fluid flow-induced expression of three proteins (collagen, osteopontin, and alkaline phosphatase) involved in bone remodeling was investigated. Rat calvarial osteoblasts subjected to pulsatile fluid flow at an average shear stress of 5 dyne/cm2 showed decreased alkaline phosphatase (AP) mRNA expression after only 1 hour of flow. After 3 hours of flow, AP mRNA levels had decreased to 30% of stationary control levels and remained at this level for an additional 5 hours of flow. Steady flow (4 dyne/cm2 fluid shear stress), in contrast, resulted in a delayed and less dramatic decrease in AP mRNA expression to 63% of control levels after 8 hours of flow. The reduced AP mRNA expression under pulsatile flow conditions was followed by reduced AP enzyme activity after 24 hours. No changes in collagen or osteopontin mRNA expression were detected over 8 hours of pulsatile flow. This is the first time fluid flow has been shown to affect gene expression in osteoblasts.

The impact of heavy metals from environmental tobacco smoke on indoor air quality as determined by Compton suppression neutron activation analysis.

PubMed

Landsberger, S; Wu, D

1995-12-01

The method of instrumental neutron activation analysis (NAA) has been improved for air filter samples in the determination of low level heavy metals in indoor air. By using the techniques of epithermal neutron irradiation in conjunction with Compton suppression, the detection limits of cadmium, arsenic and antimony measurements have been dramatically reduced to 2 ng for Cd, 0.2 ng for As, and 0.03 ng for Sb. The determination of these heavy metals in particulate material generated from cigarette smoking in indoor environments has been conducted. Other elements, Br, Cl, Na, K, Zn were also found at elevated levels.

Ultra-Compact Transputer-Based Controller for High-Level, Multi-Axis Coordination

NASA Technical Reports Server (NTRS)

Zenowich, Brian; Crowell, Adam; Townsend, William T.

2013-01-01

The design of machines that rely on arrays of servomotors such as robotic arms, orbital platforms, and combinations of both, imposes a heavy computational burden to coordinate their actions to perform coherent tasks. For example, the robotic equivalent of a person tracing a straight line in space requires enormously complex kinematics calculations, and complexity increases with the number of servo nodes. A new high-level architecture for coordinated servo-machine control enables a practical, distributed transputer alternative to conventional central processor electronics. The solution is inherently scalable, dramatically reduces bulkiness and number of conductor runs throughout the machine, requires only a fraction of the power, and is designed for cooling in a vacuum.

Fat and fibre interfere with the dramatic effect that nanoemulsified d-limonene has on the heat resistance of Listeria monocytogenes.

PubMed

Maté, Javier; Periago, Paula M; Ros-Chumillas, María; Grullón, Coralin; Huertas, Juan Pablo; Palop, Alfredo

2017-04-01

The application of d-limonene in form of nanoemulsion has been proved to reduce dramatically the thermal resistance of Listeria monocytogenes in culture media. The present research shows very promising results on the application in food products. The thermal resistance of L. monocytogenes was reduced 90 times when 0.5 mM nanoemulsified d-limonene was added to apple juice. This is the biggest reduction in the heat resistance of a microorganism caused by an antimicrobial described ever. However, no effect was found in carrot juice. A carrot juice system was prepared in an attempt to unravel which juice constituents were responsible for the lack of effect. When fat and fibre were not included in the carrot juice system formulation, the thermal resistance of L. monocytogenes was, again, dramatically reduced in presence of nanoemulsified d-limonene, so these components were shown to interfere with the effect. Once this interaction with food constituents becomes solved, the addition of nanoemulsified antimicrobials would allow to reduce greatly the intensity of the thermal treatments currently applied in the food processing industry. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Thermo-mechanical stress analysis of cryopreservation in cryobags and the potential benefit of nanowarming.

PubMed

Solanki, Prem K; Bischof, John C; Rabin, Yoed

2017-06-01

Cryopreservation by vitrification is the only promising solution for long-term organ preservation which can save tens of thousands of lives across the world every year. One of the challenges in cryopreservation of large-size tissues and organs is to prevent fracture formation due to the tendency of the material to contract with temperature. The current study focuses on a pillow-like shape of a cryobag, while exploring various strategies to reduce thermo-mechanical stress during the rewarming phase of the cryopreservation protocol, where maximum stresses are typically found. It is demonstrated in this study that while the level of stress may generally increase with the increasing amount of CPA filled in the cryobag, the ratio between width and length of the cryobag play a significant role. Counterintuitively, the overall maximum stress is not found when the bag is filled to its maximum capacity (when the filled cryobag resembles a sphere). Parametric investigation suggests that reducing the initial rewarming rate between the storage temperature and the glass transition temperature may dramatically decrease the thermo-mechanical stress. Adding a temperature hold during rewarming at the glass transition temperature may reduce the thermo-mechanical stress in some cases, but may have an adverse effect in other cases. Finally, it is demonstrated that careful incorporation of volumetric heating by means on nanoparticles in an alternating magnetic field, or nanowarming, can dramatically reduce the resulting thermo-mechanical stress. These observations display the potential benefit of a thermo-mechanical design of the cryopreservation protocols in order to prevent structural damage. Copyright © 2017 Elsevier Inc. All rights reserved.

Drinking Water Research Division's research activities in support of EPA's regulatory agenda

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

Clark, R.M.; Feige, W.A.

1991-01-01

The Safe Drinking Water Act and its Amendments will have a dramatic impact on the way in which one views the treatment and distribution of water in the U.S. The paper discusses the regulatory agenda, including proposed and promulgated regulations for volatile and synthetic organic contaminants, pesticides, lead, copper, inorganic contaminants, and radionuclides. In addition, the Surface Water Treatment and Coliform Rules are discussed in some detail. Tables are presented that list the Maximum Contaminant Levels (MCLs) and Maximum Contaminant Level Goals (MCLGs), as well as Best Available Technology (BAT) for reducing many of these contaminants to acceptable levels. Finally,more » a discussion of expected disinfection requirements and the regulation of disinfection by-products (DBP) is made. Treatment techniques for controlling DBPs are briefly described.« less

Increased kinin levels and decreased responsiveness to kinins during aging.

PubMed

Pérez, Viviana; Velarde, Victoria; Acuña-Castillo, Claudio; Gómez, Christian; Nishimura, Sumiyo; Sabaj, Valeria; Walter, Robin; Sierra, Felipe

2005-08-01

Kinins are vasoactive peptides released from precursors called kininogens, and serum levels of both T- and K-kininogens increase dramatically as rats age. Kinin release is tightly regulated, and here we show that serum kinin levels also increase with age, from 63 +/- 16 nmol/L in young Fisher 344 rats to 398 +/- 102 nmol/L in old animals. Both K- and T-kininogens contribute sequentially to this increase, with the increase in middle-aged animals being driven primarily by K-kininogen, whereas the further augmentation in older rats occurs by increasing T-kininogen. By measuring ERK activation, we show that aorta endothelial cells from old animals are hyporesponsive to exogenous bradykinin. However, if serum kinin levels are experimentally decreased by lipopolysaccharide treatment, then the endothelial response to bradykinin is re-established. These results indicate that serum levels of kinins increase with age, whereas the responsiveness of target cells to kinins is reduced in these same animals.

Waveguide-coupled resonator filters on AlN on silicon

NASA Technical Reports Server (NTRS)

Liaw, H. M.; Cameron, T. P.; Hunt, W. D.; Hickernell, F. S.

1994-01-01

In the effort to continually reduce the size and cost of wireless communications products the level of integration has improved dramatically in recent years. In order to reduce future generations of wireless systems to single chip form, there is a need for on-chip filtering capabilities. In this paper, the first report of an experimental waveguide-coupled resonator filter for cellular radio applications is presented. Measured results indicate a typical insertion loss of 26 dB at a center frequency of 132 MHz using a 2 um AlN film on (001) less than 110 greater than Si. In addition, a laser probe analysis has been conducted and a theoretical analysis of the first order reflection coefficients is presented.

A Nuclear Renaissance: The Role of Nuclear Power in Mitigating Climate Change

NASA Astrophysics Data System (ADS)

Winslow, Anne

2011-06-01

The U. N. Framework Convention on Climate Change calls for the stabilization of greenhouse gas (GHG) emissions at double the preindustrial atmospheric carbon dioxide concentration to avoid dangerous anthropogenic interference with the climate system. To achieve this goal, carbon emissions in 2050 must not exceed their current level, despite predictions of a dramatic increase in global electricity demand. The need to reduce GHG emissions and simultaneously provide for additional electricity demand has led to a renewed interest in the expansion of alternatives to fossil fuels—particularly renewable energy and nuclear power. As renewable energy sources are often constrained by the intermittency of natural energy forms, scale-ability concerns, cost and environmental barriers, many governments and even prominent environmentalist turn to nuclear energy as a source of clean, reliable base-load electricity. Described by some as a "nuclear renaissance", this trend of embracing nuclear power as a tool to mitigate climate change will dramatically influence the feasibility of emerging nuclear programs around the world.

A Nuclear Renaissance: The Role of Nuclear Power in Mitigating Climate Change

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

Winslow, Anne

2011-06-28

The U. N. Framework Convention on Climate Change calls for the stabilization of greenhouse gas (GHG) emissions at double the preindustrial atmospheric carbon dioxide concentration to avoid dangerous anthropogenic interference with the climate system. To achieve this goal, carbon emissions in 2050 must not exceed their current level, despite predictions of a dramatic increase in global electricity demand. The need to reduce GHG emissions and simultaneously provide for additional electricity demand has led to a renewed interest in the expansion of alternatives to fossil fuels--particularly renewable energy and nuclear power. As renewable energy sources are often constrained by the intermittencymore » of natural energy forms, scale-ability concerns, cost and environmental barriers, many governments and even prominent environmentalist turn to nuclear energy as a source of clean, reliable base-load electricity. Described by some as a ''nuclear renaissance'', this trend of embracing nuclear power as a tool to mitigate climate change will dramatically influence the feasibility of emerging nuclear programs around the world.« less

Toyota's tips drive dramatic ED improvements.

PubMed

2002-11-01

The Toyota Motor Corp.'s key concepts of allowing workers to make changes, putting the customer first, and reducing waste can have a dramatic impact when implemented in emergency departments. Staff should be empowered to make changes to improve quality. A chain of events should be set in motion for each customer request. Identify and eliminate roadblocks that cause delays.

Taraxacum official (dandelion) leaf extract alleviates high-fat diet-induced nonalcoholic fatty liver.

PubMed

Davaatseren, Munkhtugs; Hur, Haeng Jeon; Yang, Hye Jeong; Hwang, Jin-Taek; Park, Jae Ho; Kim, Hyun-Jin; Kim, Min Jung; Kwon, Dae Young; Sung, Mi Jeong

2013-08-01

The purpose of this study is to determine the protective effect of Taraxacum official (dandelion) leaf extract (DLE) on high-fat-diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. To determine the hepatoprotective effect of DLE, we fed C57BL/6 mice with normal chow diet (NCD), high-fat diet (HFD), HFD supplemented with 2g/kg DLE DLE (DL), and HFD supplemented with 5 g/kg DLE (DH). We found that the HFD supplemented by DLE dramatically reduced hepatic lipid accumulation compared to HFD alone. Body and liver weights of the DL and DH groups were significantly lesser than those of the HFD group, and DLE supplementation dramatically suppressed triglyceride (TG), total cholesterol (TC), insulin, fasting glucose level in serum, and Homeostatic Model Assessment Insulin Resistance (HOMA-IR) induced by HFD. In addition, DLE treatment significantly increased activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) in liver and muscle protein. DLE significantly suppressed lipid accumulation in the liver, reduced insulin resistance, and lipid in HFD-fed C57BL/6 mice via the AMPK pathway. These results indicate that the DLE may represent a promising approach for the prevention and treatment of obesity-related nonalcoholic fatty liver disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Targeted Disruption of NF1 in Osteocytes Increases FGF23 and Osteoid With Osteomalacia-like Bone Phenotype.

PubMed

Kamiya, Nobuhiro; Yamaguchi, Ryosuke; Aruwajoye, Olumide; Kim, Audrey J; Kuroyanagi, Gen; Phipps, Matthew; Adapala, Naga Suresh; Feng, Jian Q; Kim, Harry Kw

2017-08-01

Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations, exhibits multi-system abnormalities, including skeletal deformities in humans. Osteocytes play critical roles in controlling bone modeling and remodeling. However, the role of neurofibromin, the protein product of the NF1 gene, in osteocytes is largely unknown. This study investigated the role of neurofibromin in osteocytes by disrupting Nf1 under the Dmp1-promoter. The conditional knockout (Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an osteomalacia-like bone phenotype. Serum FGF23 levels were 4 times increased in cKO mice compared with age-matched controls. In addition, calcium-phosphorus metabolism was significantly altered (calcium reduced; phosphorus reduced; parathyroid hormone [PTH] increased; 1,25(OH) 2 D decreased). Bone histomorphometry showed dramatically increased osteoid parameters, including osteoid volume, surface, and thickness. Dynamic bone histomorphometry revealed reduced bone formation rate and mineral apposition rate in the cKO mice. TRAP staining showed a reduced osteoclast number. Micro-CT demonstrated thinner and porous cortical bones in the cKO mice, in which osteocyte dendrites were disorganized as assessed by electron microscopy. Interestingly, the cKO mice exhibited spontaneous fractures in long bones, as found in NF1 patients. Mechanical testing of femora revealed significantly reduced maximum force and stiffness. Immunohistochemistry showed significantly increased FGF23 protein in the cKO bones. Moreover, primary osteocytes from cKO femora showed about eightfold increase in FGF23 mRNA levels compared with control cells. The upregulation of FGF23 was specifically and significantly inhibited by PI3K inhibitor Ly294002, indicating upregulation of FGF23 through PI3K in Nf1-deficient osteocytes. Taken together, these results indicate that Nf1 deficiency in osteocytes dramatically increases FGF23 production and causes a mineralization defect (ie, hyperosteoidosis) via the alteration of calcium-phosphorus metabolism. This study demonstrates critical roles of neurofibromin in osteocytes for osteoid mineralization. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

The impact of deficit reduction on the nursing labour market in Canada: unintended consequences of fiscal reform.

PubMed

Vujicic, Marko; Evans, Robert G

2005-01-01

Beginning in 1992, governments throughout Canada began reducing expenditures in an effort to eliminate fiscal deficits and reduce their alarmingly high debt burden. As part of this deficit-fighting era, governments reduced hospital expenditure levels quite dramatically. Some of the current problems in the Canadian healthcare system - the recent unrest in the nursing labour market in particular - are often attributed to this hospital downsizing era. This article examines trends in the labour market for registered nurses in Canada during the hospital downsizing period. Of particular interest is the effect of hospital spending reforms on nurse employment levels in hospitals and on the age structure of the nursing workforce. After identifying the trends, the main factors driving the trends are discussed. Results indicate that a decrease in the demand for nursing labour resulted in large staff layoffs during the restructuring period, particularly among the youngest age groups. The evidence does not support the claim that deteriorating wages and working conditions in hospitals led nurses to quit their jobs during the hospital downsizing period.

Reduced levels of NADH-dependent glutamate dehydrogenase decrease the glutamate content of ripe tomato fruit but have no effect on green fruit or leaves.

PubMed

Ferraro, Gisela; D'Angelo, Matilde; Sulpice, Ronan; Stitt, Mark; Valle, Estela M

2015-06-01

Glutamate (Glu) is a taste enhancer that contributes to the characteristic flavour of foods. In fruit of tomato (Solanum lycopersicum L.), the Glu content increases dramatically during the ripening process, becoming the most abundant free amino acid when the fruit become red. There is also a concomitant increase in NADH-dependent glutamate dehydrogenase (GDH) activity during the ripening transition. This enzyme is located in the mitochondria and catalyses the reversible amination of 2-oxoglutarate to Glu. To investigate the potential effect of GDH on Glu metabolism, the abundance of GDH was altered by artificial microRNA technology. Efficient silencing of all the endogenous SlGDH genes was achieved, leading to a dramatic decrease in total GDH activity. This decrease in GDH activity did not lead to any clear morphological or metabolic phenotype in leaves or green fruit. However, red fruit on the transgenic plants showed markedly reduced levels of Glu and a large increase in aspartate, glucose and fructose content in comparison to wild-type fruit. These results suggest that GDH is involved in the synthesis of Glu in tomato fruit during the ripening processes. This contrasts with the biological role ascribed to GDH in many other tissues and species. Overall, these findings suggest that GDH has a major effect on the control of metabolic composition during tomato fruit ripening, but not at other stages of development. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Glutamine Acts as a Neuroprotectant against DNA Damage, Beta-Amyloid and H2O2-Induced Stress

PubMed Central

Chen, Jianmin; Herrup, Karl

2012-01-01

Glutamine is the most abundant free amino acid in the human blood stream and is ‘conditionally essential’ to cells. Its intracellular levels are regulated both by the uptake of extracellular glutamine via specific transport systems and by its intracellular synthesis by glutamine synthetase (GS). Adding to the regulatory complexity, when extracellular glutamine is reduced GS protein levels rise. Unfortunately, this excess GS can be maladaptive. GS overexpression is neurotoxic especially if the cells are in a low-glutamine medium. Similarly, in low glutamine, the levels of multiple stress response proteins are reduced rendering cells hypersensitive to H2O2, zinc salts and DNA damage. These altered responses may have particular relevance to neurodegenerative diseases of aging. GS activity and glutamine levels are lower in the Alzheimer's disease (AD) brain, and a fraction of AD hippocampal neurons have dramatically increased GS levels compared with control subjects. We validated the importance of these observations by showing that raising glutamine levels in the medium protects cultured neuronal cells against the amyloid peptide, Aβ. Further, a 10-day course of dietary glutamine supplementation reduced inflammation-induced neuronal cell cycle activation, tau phosphorylation and ATM-activation in two different mouse models of familial AD while raising the levels of two synaptic proteins, VAMP2 and synaptophysin. Together, our observations suggest that healthy neuronal cells require both intracellular and extracellular glutamine, and that the neuroprotective effects of glutamine supplementation may prove beneficial in the treatment of AD. PMID:22413000

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

Rudd, A.

This document covers a description of the need and applied solutions for supplemental dehumidification in warm-humid climates, especially for energy efficient homes where the sensible cooling load has been dramatically reduced. In older homes in warm-humid climates, cooling loads are typically high and cooling equipment runs a lot to cool the air. The cooling process also removes indoor moisture, reducing indoor relative humidity. However, at current residential code levels, and especially for above-code programs, sensible cooling loads have been so dramatically reduced that the cooling system does not run a lot to cool the air, resulting in much less moisturemore » being removed. In these new homes, cooling equipment is off for much longer periods of time especially during spring/fall seasons, summer shoulder months, rainy periods, some summer nights, and some winter days. In warm-humid climates, those long off periods allow indoor humidity to become elevated due to internally generated moisture and ventilation air change. Elevated indoor relative humidity impacts comfort, indoor air quality, and building material durability. Industry is responding with supplemental dehumidification options, but that effort is really in its infancy regarding year-round humidity control in low-energy homes. Available supplemental humidity control options are discussed. Some options are less expensive but may not control indoor humidity as well as more expensive and comprehensive options. The best performing option is one that avoids overcooling and avoids adding unnecessary heat to the space by using waste heat from the cooling system to reheat the cooled and dehumidified air to room-neutral temperature.« less

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

Rudd, Armin

This document covers a description of the need and applied solutions for supplemental dehumidification in warm-humid climates, especially for energy efficient homes where the sensible cooling load has been dramatically reduced. Cooling loads are typically high and cooling equipment runs a lot to cool the air in older homes in warm-humid climates. The cooling process also removes indoor moisture, reducing indoor relative humidity. However, at current residential code levels, and especially for above-code programs, sensible cooling loads have been so dramatically reduced that the cooling system does not run a lot to cool the air, resulting in much less moisturemore » being removed. In these new homes, cooling equipment is off for much longer periods of time especially during spring/fall seasons, summer shoulder months, rainy periods, some summer nights, and winter days. In warm-humid climates, those long-off periods allow indoor humidity to become elevated due to internally generated moisture and ventilation air change. Elevated indoor relative humidity impacts comfort, indoor air quality, and building material durability. Industry is responding with supplemental dehumidification options, but that effort is really in its infancy regarding year-round humidity control in low-energy homes. Available supplemental humidity control options are discussed. Some options are less expensive but may not control indoor humidity as well as more expensive and comprehensive options. The best performing option is one that avoids overcooling and adding unnecessary heat to the space by using waste heat from the cooling system to reheat the cooled and dehumidified air to room-neutral temperature.« less

An Ongoing Shift in Pacific Ocean Sea Level

NASA Astrophysics Data System (ADS)

Cheon, S. H.; Hamlington, B.; Thompson, P. R.; Merrifield, M. A.; Nerem, R. S.; Leben, R. R.; Kim, K. Y.

2016-12-01

According to the satellite altimeter data, local sea level trends have shown considerable diversity spatially as well as temporally. In particular, dramatic changes in sea level in the Pacific have been observed throughout the altimeter record, with high trends in the western tropical Pacific (WTP) and comparatively lower trends in the eastern Pacific. In recent years, however, a shift appears to be occurring, with falling trends in the (WTP) and rising trends in the eastern tropical and northeastern Pacific (ETP and NEP). From a planning perspective, it is important to figure out whether these sharp changes are part of a short-term shift or the beginning of a longer-term change in sea level. In this study, we distinguish the origins of the recent shift in Pacific Ocean sea level. Cyclostationary empirical orthogonal function (CSEOF) analysis is applied to separate the properties of the recent sea level change in the Pacific Ocean. From the CSEOF analysis results, we point out two dominant modes of sea level shift in the Pacific Ocean. The first mode is related to the biennial oscillation associated with El Nino-Southern Oscillation (ENSO) and the other is related to lower-frequency variability with a strong signal in the northern Pacific. Considering a relatively high correlation between recent sea level change and the low-frequency mode, we suggest that the low-frequency mode has played a dominant role in the sea level shift in the Pacific Ocean. Using a reconstructed sea level dataset, we examine the variability of this low-frequency mode in the past, and find similar periods of dramatic sea level change in the Pacific. Based on the sea level record of the last five years and according to the analysis, we conclude that in the coming decades, higher sea level trends off the U.S. West Coast should be expected, while reduced trends in the WTP will likely be observed.

Radically Reducing Radiation Exposure during Routine Medical Imaging

Cancer.gov

Exposure to radiation from medical imaging in the United States has increased dramatically. NCI and several partner organizations sponsored a 2011 summit to promote efforts to reduce radiation exposure from medical imaging.

A dramatic, objective antiandrogen withdrawal response: case report and review of the literature.

PubMed

Lau, Yiu-Keung; Chadha, Manpreet K; Litwin, Alan; Trump, Donald L

2008-11-05

Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation.

Green tea extract inhibits proliferation of uterine leiomyoma cells in vitro and in nude mice

PubMed Central

ZHANG, Dong; AL-HENDY, Mohamed; RICHARD-DAVIS, Gloria; MONTGOMERY-RICE, Valerie; SHARAN, Chakradhari; RAJARATNAM, Veera; KHURANA, Anjali; AL-HENDY, Ayman

2010-01-01

Objective Investigate the effect of epigallocatechin gallate (EGCG), on rat leiomyoma (ELT3) cells in vitro and in nude mice model. Study Design ELT3 cells were treated with various concentrations of EGCG. Cell proliferation, PCNA and Cdk4 protein levels were evaluated. ELT3 cells were inoculated subcutaneously in female athymic nude mice. Animals were fed 1.25mg EGCG (in drinking water)/mouse/day. Tumors were collected and evaluated at 4 and 8 weeks post-treatment. Results Inhibitory effect of EGCG (200 μM) on ELT3 cells was observed after 24 h treatment (p<0.05). At ≥50μM, EGCG significantly decreased PCNA and Cdk4 protein levels (p<0.05). In vivo, EGCG treatment dramatically reduced the volume and weight of tumors at 4 and 8 weeks post-treatment (p<0.05). The PCNA and Cdk4 protein levels were significantly reduced in EGCG treated group (p<0.05). Conclusion EGCG effectively inhibits the proliferation and induce apoptosis in rat ELT3 uterine leiomyoma cells in vitro and in vivo. PMID:20074693

Caveolins/caveolae protect adipocytes from fatty acid-mediated lipotoxicity.

PubMed

Meshulam, Tova; Breen, Michael R; Liu, Libin; Parton, Robert G; Pilch, Paul F

2011-08-01

Mice and humans lacking functional caveolae are dyslipidemic and have reduced fat stores and smaller fat cells. To test the role of caveolins/caveolae in maintaining lipid stores and adipocyte integrity, we compared lipolysis in caveolin-1 (Cav1)-null fat cells to that in cells reconstituted for caveolae by caveolin-1 re-expression. We find that the Cav1-null cells have a modestly enhanced rate of lipolysis and reduced cellular integrity compared with reconstituted cells as determined by the release of lipid metabolites and lactic dehydrogenase, respectively, into the media. There are no apparent differences in the levels of lipolytic enzymes or hormonally stimulated phosphorylation events in the two cell lines. In addition, acute fasting, which dramatically raises circulating fatty acid levels in vivo, causes a significant upregulation of caveolar protein constituents. These results are consistent with the hypothesis that caveolae protect fat cells from the lipotoxic effects of elevated levels fatty acids, which are weak detergents at physiological pH, by virtue of the property of caveolae to form detergent-resistant membrane domains.

Caveolins/caveolae protect adipocytes from fatty acid-mediated lipotoxicity

PubMed Central

Meshulam, Tova; Breen, Michael R.; Liu, Libin; Parton, Robert G.; Pilch, Paul F.

2011-01-01

Mice and humans lacking functional caveolae are dyslipidemic and have reduced fat stores and smaller fat cells. To test the role of caveolins/caveolae in maintaining lipid stores and adipocyte integrity, we compared lipolysis in caveolin-1 (Cav1)-null fat cells to that in cells reconstituted for caveolae by caveolin-1 re-expression. We find that the Cav1-null cells have a modestly enhanced rate of lipolysis and reduced cellular integrity compared with reconstituted cells as determined by the release of lipid metabolites and lactic dehydrogenase, respectively, into the media. There are no apparent differences in the levels of lipolytic enzymes or hormonally stimulated phosphorylation events in the two cell lines. In addition, acute fasting, which dramatically raises circulating fatty acid levels in vivo, causes a significant upregulation of caveolar protein constituents. These results are consistent with the hypothesis that caveolae protect fat cells from the lipotoxic effects of elevated levels fatty acids, which are weak detergents at physiological pH, by virtue of the property of caveolae to form detergent-resistant membrane domains. PMID:21652731

Exposure to extremely low frequency electromagnetic fields alters the behaviour, physiology and stress protein levels of desert locusts

PubMed Central

Wyszkowska, Joanna; Shepherd, Sebastian; Sharkh, Suleiman; Jackson, Christopher W.; Newland, Philip L.

2016-01-01

Electromagnetic fields (EMFs) are present throughout the modern world and are derived from many man-made sources including overhead transmission lines. The risks of extremely-low frequency (ELF) electromagnetic fields are particularly poorly understood especially at high field strengths as they are rarely encountered at ground level. Flying insects, however, can approach close to high field strength transmission lines prompting the question as to how these high levels of exposure affect behaviour and physiology. Here we utilise the accessible nervous system of the locust to ask how exposure to high levels of ELF EMF impact at multiple levels. We show that exposure to ELF EMFs above 4 mT leads to reduced walking. Moreover, intracellular recordings from an identified motor neuron, the fast extensor tibiae motor neuron, show increased spike latency and a broadening of its spike in exposed animals. In addition, hind leg kick force, produced by stimulating the extensor tibiae muscle, was reduced following exposure, while stress-protein levels (Hsp70) increased. Together these results suggest that ELF EMF exposure has the capacity to cause dramatic effects from behaviour to physiology and protein expression, and this study lays the foundation to explore the ecological significance of these effects in other flying insects. PMID:27808167

Impact of sea level rise on tide gate function.

PubMed

Walsh, Sean; Miskewitz, Robert

2013-01-01

Sea level rise resulting from climate change and land subsidence is expected to severely impact the duration and associated damage resulting from flooding events in tidal communities. These communities must continuously invest resources for the maintenance of existing structures and installation of new flood prevention infrastructure. Tide gates are a common flood prevention structure for low-lying communities in the tidal zone. Tide gates close during incoming tides to prevent inundation from downstream water propagating inland and open during outgoing tides to drain upland areas. Higher downstream mean sea level elevations reduce the effectiveness of tide gates by impacting the hydraulics of the system. This project developed a HEC-RAS and HEC-HMS model of an existing tide gate structure and its upland drainage area in the New Jersey Meadowlands to simulate the impact of rising mean sea level elevations on the tide gate's ability to prevent upstream flooding. Model predictions indicate that sea level rise will reduce the tide gate effectiveness resulting in longer lasting and deeper flood events. The results indicate that there is a critical point in the sea level elevation for this local area, beyond which flooding scenarios become dramatically worse and would have a significantly negative impact on the standard of living and ability to do business in one of the most densely populated areas of America.

Are methamphetamine precursor control laws effective tools to fight the methamphetamine epidemic?

PubMed

Nonnemaker, James; Engelen, Mark; Shive, Daniel

2011-05-01

One of the most notable trends in illegal substance use among Americans over the past decade is the dramatic growth and spread of methamphetamine use. In response to the dramatic rise in methamphetamine use and its associated burden, a broad range of legislations has been passed to combat the problem. In this paper, we assess the impact of retail-level laws intended to restrict chemicals used to manufacture methamphetamine (methamphetamine precursor laws) in reducing indicators of domestic production, methamphetamine availability, and the consequences of methamphetamine use. Specifically, we examine trends in these indicators of methamphetamine supply and use over a period spanning the implementation of the federal Methamphetamine Anti-Proliferation Act (MAPA) (October 2000) and a more stringent state-level restriction enacted in California (January 2000). The results are mixed in terms of the effectiveness of legislative efforts to control methamphetamine production and use, depending on the strength of the legislation (California Uniform Controlled Substances Act versus federal MAPA), the specification of the comparison group, and the particular outcome of interest. Some evidence suggests that domestic production was impacted by these legislative efforts, but there is also evidence that prices fell, purities rose, and treatment episodes increased. Copyright © 2010 John Wiley & Sons, Ltd.

A new system to reduce formaldehyde levels improves safety conditions during gross veterinary anatomy learning.

PubMed

Nacher, Víctor; Llombart, Cristina; Carretero, Ana; Navarro, Marc; Ysern, Pere; Calero, Sebastián; Fígols, Enric; Ruberte, Jesús

2007-01-01

Dissection is a very useful method of learning veterinary anatomy. However, formaldehyde, which is widely used to preserve cadavers, is an irritant, and it has recently been classified as a carcinogen. In 1997, the Instituto Nacional de Seguridad e Higiene en el Trabajo [National Institute of Workplace Security and Hygiene] found that the levels of formaldehyde in our dissection room were above the threshold limit values. Unfortunately, no optimal substitute for formaldehyde is currently available. Therefore, we designed a new ventilation system that combines slow propulsion of fresh air from above the dissection table and rapid aspiration of polluted air from the perimeter. Formaldehyde measurements performed in 2004, after the introduction of this new system into our dissection laboratory, showed a dramatic reduction (about tenfold, or 0.03 ppm). A suitable propelling/aspirating air system successfully reduces the concentration of formaldehyde in the dissection room, significantly improving safety conditions for students, instructors, and technical staff during gross anatomy learning.

Automatic external defibrillators for public access defibrillation: recommendations for specifying and reporting arrhythmia analysis algorithm performance, incorporating new waveforms, and enhancing safety. A statement for health professionals from the American Heart Association Task Force on Automatic External Defibrillation, Subcommittee on AED and Efficacy.

PubMed

1997-01-01

These recommendations are presented to enhance the safety and efficacy of AEDs intended for public access. The task force recommends that manufacturers present developmental and validation data on their own devices, emphasizing high sensitivity for shockable rhythms and high specificity for nonshockable rhythms. Alternative defibrillation waveforms may reduce energy requirements, reducing the size and weight of the device. The highest levels of safety for public access defibrillation are needed. Safe and effective use of AEDs that are widely available and easily handled by non-medical personnel has the potential to dramatically increase survival from cardiac arrest.

The receiving simplification partnership: a win-win approach to better service and higher profitability.

PubMed

Beech, W D; Berg, R C

1999-02-01

To achieve competitive advantage, customers and suppliers are increasingly forming logistics partnerships to improve supply chain performance and reduce costs. The partnerships are typically motivated by the need to solve a particular problem, but with attention and open communication, new program ideas can develop, sometimes even breakthrough concepts. During the course of their partnership, Avery Dennison and United Stationers created a program that dramatically simplifies and speeds receiving and put-away of shipments with the aim of reducing workloads, improving service, and increasing profitability. The program involves optimizing order quantity increments to full-pallet, layer, and case volumes based on demand and warehouse configurations. Within six weeks, the results included a 50 percent reduction in shipment line items and 92 percent fewer put-away pieces, despite unchanged inventory levels.

Differential Modulation of Spontaneous and Evoked Thalamocortical Network Activity by Acetylcholine Level In Vitro

PubMed Central

Wester, Jason C.

2013-01-01

Different levels of cholinergic neuromodulatory tone have been hypothesized to set the state of cortical circuits either to one dominated by local cortical recurrent activity (low ACh) or to one dependent on thalamic input (high ACh). High ACh levels depress intracortical but facilitate thalamocortical synapses, whereas low levels potentiate intracortical synapses. Furthermore, recent work has implicated the thalamus in controlling cortical network state during waking and attention, when ACh levels are highest. To test this hypothesis, we used rat thalamocortical slices maintained in medium to generate spontaneous up- and down-states and applied different ACh concentrations to slices in which thalamocortical connections were either maintained or severed. The effects on spontaneous and evoked up-states were measured using voltage-sensitive dye imaging, intracellular recordings, local field potentials, and single/multiunit activity. We found that high ACh can increase the frequency of spontaneous up-states, but reduces their duration in slices with intact thalamocortical connections. Strikingly, when thalamic connections are severed, high ACh instead greatly reduces or abolishes spontaneous up-states. Furthermore, high ACh reduces the spatial propagation, velocity, and depolarization amplitude of evoked up-states. In contrast, low ACh dramatically increases up-state frequency regardless of the presence or absence of intact thalamocortical connections and does not reduce the duration, spatial propagation, or velocity of evoked up-states. Therefore, our data support the hypothesis that strong cholinergic modulation increases the influence, and thus the signal-to-noise ratio, of afferent input over local cortical activity and that lower cholinergic tone enhances recurrent cortical activity regardless of thalamic input. PMID:24198382

Nanomanufacturing and sustainability: opportunities and challenges

NASA Astrophysics Data System (ADS)

Busnaina, Ahmed A.; Mead, Joey; Isaacs, Jacqueline; Somu, Sivasubramanian

2013-10-01

New nanomanufacturing technologies, although still in research labs, present a great opportunity to drastically reduce the cost of making nanostructures on a large scale and at high-rates. Such new bottom-up directed assembly-based approaches involve adding materials selectively thereby both reducing waste and the number of required processes. Directed assembly-based processes are conducted at room pressure and temperatures which significantly reduces the cost of nanomanufacturing equipment and tools, ensuring long-term sustainability by reducing energy, consumables, and waste costs. This paradigm shift in nanomanufacturing will unleash not only a wave of creativity in sustainable nanomanufacturing but lessons learnt along the way can be used in various other sectors. Along with the exquisite technological promise that nanotechnology holds, nano-enabled products are heralded as a means for energy and resource reduction, resulting in potential manufacturing cost reductions and further, for potential improvements to environmental remediation. Sustainable nanomanufacturing will, by dramatically lowering current nanomanufacturing barriers, spur innovation, and the creation of entirely new industries by leveling the playing and ultimately leading to the democratization of nanomanufacturing.

A dramatic, objective antiandrogen withdrawal response: case report and review of the literature

PubMed Central

Lau, Yiu-Keung; Chadha, Manpreet K; Litwin, Alan; Trump, Donald L

2008-01-01

Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation. PMID:18986533

An evaluation of retrofit engineering control interventions to reduce perchloroethylene exposures in commercial dry-cleaning shops.

PubMed

Earnest, G Scott; Ewers, Lynda M; Ruder, Avima M; Petersen, Martin R; Kovein, Ronald J

2002-02-01

Real-time monitoring was used to evaluate the ability of engineering control devices retrofitted on two existing dry-cleaning machines to reduce worker exposures to perchloroethylene. In one dry-cleaning shop, a refrigerated condenser was installed on a machine that had a water-cooled condenser to reduce the air temperature, improve vapor recovery, and lower exposures. In a second shop, a carbon adsorber was retrofitted on a machine to adsorb residual perchloroethylene not collected by the existing refrigerated condenser to improve vapor recovery and reduce exposures. Both controls were successful at reducing the perchloroethylene exposures of the dry-cleaning machine operator. Real-time monitoring was performed to evaluate how the engineering controls affected exposures during loading and unloading the dry-cleaning machine, a task generally considered to account for the highest exposures. The real-time monitoring showed that dramatic reductions occurred in exposures during loading and unloading of the dry-cleaning machine due to the engineering controls. Peak operator exposures during loading and unloading were reduced by 60 percent in the shop that had a refrigerated condenser installed on the dry-cleaning machine and 92 percent in the shop that had a carbon adsorber installed. Although loading and unloading exposures were dramatically reduced, drops in full-shift time-weighted average (TWA) exposures were less dramatic. TWA exposures to perchloroethylene, as measured by conventional air sampling, showed smaller reductions in operator exposures of 28 percent or less. Differences between exposure results from real-time and conventional air sampling very likely resulted from other uncontrolled sources of exposure, differences in shop general ventilation before and after the control was installed, relatively small sample sizes, and experimental variability inherent in field research. Although there were some difficulties and complications with installation and maintenance of the engineering controls, this study showed that retrofitting engineering controls may be a feasible option for some dry-cleaning shop owners to reduce worker exposures to perchloroethylene. By installing retrofit controls, a dry-cleaning facility can reduce exposures, in some cases dramatically, and bring operators into compliance with the Occupational Safety and Health Administration (OSHA) peak exposure limit of 300 ppm. Retrofit engineering controls are also likely to enable many dry-cleaning workers to lower their overall personal TWA exposures to perchloroethylene.

Lessons from the war on dietary fat.

PubMed

Walker, Thomas B; Parker, Mary Jo

2014-01-01

Conventional dietary guidelines put forth by health care institutions and providers for the past 40 years have stressed the importance of reducing the amount of dietary fat consumed. Such a diet is purported to mitigate metabolic risk factors and optimize the ability to achieve or maintain a healthy body weight. However, over the past 35 years obesity rates in the United States have risen dramatically though the level of dietary fat consumed by U.S. adults has fallen. This review examines the potential reasons for this paradox. Various meta-analyses, controlled trials, and cohort studies have demonstrated that reducing dietary fat intake provides for very little weight loss unless accompanied by equal or greater reductions in total energy intake. Due to both psychological (e.g., the tendency for people to eat more of what they consider low fat) and physiological (e.g., the low satiety that accompanies carbohydrate intake) factors, reducing total caloric intake while simultaneously reducing fat intake is a difficult challenge. Further, reductions in total carbohydrate intake, increases in protein intake, and adoption of a Mediterranean diet seem to be more effective in inducing weight loss than reductions in fat intake. Traditional claims that simply reducing dietary fat will improve metabolic risk factors are also not borne out by research. There is some evidence that replacing dietary saturated fat with unsaturated fat may improve metabolic risk factors, but that research is not conclusive. • Over the past 40 years, Americans have decreased the percentage of calories they get from dietary fat while rates of overweight and obesity have risen dramatically. • It appears that a decrease in total dietary fat in ad libitum diets may induce a very small decrease in body weight. • Evidence suggests that reductions in total dietary fat intake often occur in conjunction with an increase in total caloric intake. • It seems reasonable to conclude that guiding the public to simply reduce dietary fat intake is an ineffective method to mitigate the rise in obesity and improve public health.

Cytokinin signaling regulates cambial development in poplar

PubMed Central

Nieminen, Kaisa; Immanen, Juha; Laxell, Marjukka; Kauppinen, Leila; Tarkowski, Petr; Dolezal, Karel; Tähtiharju, Sari; Elo, Annakaisa; Decourteix, Mélanie; Ljung, Karin; Bhalerao, Rishikesh; Keinonen, Kaija; Albert, Victor A.; Helariutta, Ykä

2008-01-01

Although a substantial proportion of plant biomass originates from the activity of vascular cambium, the molecular basis of radial plant growth is still largely unknown. To address whether cytokinins are required for cambial activity, we studied cytokinin signaling across the cambial zones of 2 tree species, poplar (Populus trichocarpa) and birch (Betula pendula). We observed an expression peak for genes encoding cytokinin receptors in the dividing cambial cells. We reduced cytokinin levels endogenously by engineering transgenic poplar trees (P. tremula × tremuloides) to express a cytokinin catabolic gene, Arabidopsis CYTOKININ OXIDASE 2, under the promoter of a birch CYTOKININ RECEPTOR 1 gene. Transgenic trees showed reduced concentration of a biologically active cytokinin, correlating with impaired cytokinin responsiveness. In these trees, both apical and radial growth was compromised. However, radial growth was more affected, as illustrated by a thinner stem diameter than in WT at same height. To dissect radial from apical growth inhibition, we performed a reciprocal grafting experiment. WT scion outgrew the diameter of transgenic stock, implicating cytokinin activity as a direct determinant of radial growth. The reduced radial growth correlated with a reduced number of cambial cell layers. Moreover, expression of a cytokinin primary response gene was dramatically reduced in the thin-stemmed transgenic trees. Thus, a reduced level of cytokinin signaling is the primary basis for the impaired cambial growth observed. Together, our results show that cytokinins are major hormonal regulators required for cambial development. PMID:19064928

Extrinsic factors regulate partial agonist efficacy of strychnine-sensitive glycine receptors

PubMed Central

Farroni, Jeffrey S; McCool, Brian A

2004-01-01

Background Strychnine-sensitive glycine receptors in many adult forebrain regions consist of alpha2 + beta heteromeric channels. This subunit composition is distinct from the alpha1 + beta channels found throughout the adult spinal cord. Unfortunately, the pharmacology of forebrain alpha2beta receptors are poorly defined compared to 'neonatal' alpha2 homomeric channels or 'spinal' alpha1beta heteromers. In addition, the pharmacologic properties of native alpha2beta glycine receptors have been generally distinct from receptors produced by heterologous expression. To identify subtype-specific pharmacologic tools for the forebrain alpha2beta receptors, it is important to identify a heterologous expression system that closely resembles these native glycine-gated chloride channels. Results While exploring pharmacological properties of alpha2beta glycine receptors compared to alpha2-homomers, we found that distinct heterologous expression systems appeared to differentially influence partial agonist pharmacology. The β-amino acid taurine possessed 30–50% efficacy for alpha2-containing receptor isoforms when expressed in HEK 293 cells. However, taurine efficacy was dramatically reduced in L-cell fibroblasts. Similar results were obtained for β-alanine. The efficacy of these partial agonists was also strongly reduced by the beta subunit. There were no significant differences in apparent strychnine affinity values calculated from concentration-response data between expression systems or subunit combinations. Nor did relative levels of expression correlate with partial agonist efficacy when compared within or between several different expression systems. Finally, disruption of the tubulin cytoskeleton reduced the efficacy of partial agonists in a subunit-dependent, but system-independent, fashion. Conclusions Our results suggest that different heterologous expression systems can dramatically influence the agonist pharmacology of strychnine-sensitive glycine receptors. In the systems examine here, these effects are independent of both absolute expression level and any system-related alterations in the agonist binding site. We conclude that complex interactions between receptor composition and extrinsic factors may play a significant role in determining strychnine-sensitive glycine receptor partial agonist pharmacology. PMID:15301692

Extrinsic factors regulate partial agonist efficacy of strychnine-sensitive glycine receptors.

PubMed

Farroni, Jeffrey S; McCool, Brian A

2004-08-09

Strychnine-sensitive glycine receptors in many adult forebrain regions consist of alpha2 + beta heteromeric channels. This subunit composition is distinct from the alpha1 + beta channels found throughout the adult spinal cord. Unfortunately, the pharmacology of forebrain alpha2beta receptors are poorly defined compared to 'neonatal' alpha2 homomeric channels or 'spinal' alpha1beta heteromers. In addition, the pharmacologic properties of native alpha2beta glycine receptors have been generally distinct from receptors produced by heterologous expression. To identify subtype-specific pharmacologic tools for the forebrain alpha2beta receptors, it is important to identify a heterologous expression system that closely resembles these native glycine-gated chloride channels. While exploring pharmacological properties of alpha2beta glycine receptors compared to alpha2-homomers, we found that distinct heterologous expression systems appeared to differentially influence partial agonist pharmacology. The beta-amino acid taurine possessed 30-50% efficacy for alpha2-containing receptor isoforms when expressed in HEK 293 cells. However, taurine efficacy was dramatically reduced in L-cell fibroblasts. Similar results were obtained for beta-alanine. The efficacy of these partial agonists was also strongly reduced by the beta subunit. There were no significant differences in apparent strychnine affinity values calculated from concentration-response data between expression systems or subunit combinations. Nor did relative levels of expression correlate with partial agonist efficacy when compared within or between several different expression systems. Finally, disruption of the tubulin cytoskeleton reduced the efficacy of partial agonists in a subunit-dependent, but system-independent, fashion. Our results suggest that different heterologous expression systems can dramatically influence the agonist pharmacology of strychnine-sensitive glycine receptors. In the systems examine here, these effects are independent of both absolute expression level and any system-related alterations in the agonist binding site. We conclude that complex interactions between receptor composition and extrinsic factors may play a significant role in determining strychnine-sensitive glycine receptor partial agonist pharmacology.

Impacts of land use and climate change on carbon dynamics in south-central Senegal

USGS Publications Warehouse

Liu, Shu-Guang; Kaire, M.; Wood, Eric C.; Diallo, O.; Tieszen, Larry L.

2004-01-01

Total carbon stock in vegetation and soils was reduced 37% in south-central Senegal from 1900 to 2000. The decreasing trend will continue during the 21st century unless forest clearing is stopped, selective logging dramatically reduced, and climate change, if any, relatively small. Developing a sustainable fuelwood and charcoal production system could be the most feasible and significant carbon sequestration project in the region. If future climate changes dramatically as some models have predicted, cropland productivity will drop more than 65% around 2100, posing a serious threat to food security and the efficiency of carbon sequestration projects.

Exercise recommendations for individuals with spinal cord injury.

PubMed

Jacobs, Patrick L; Nash, Mark S

2004-01-01

Persons with spinal cord injury (SCI) exhibit deficits in volitional motor control and sensation that limit not only the performance of daily tasks but also the overall activity level of these persons. This population has been characterised as extremely sedentary with an increased incidence of secondary complications including diabetes mellitus, hypertension and atherogenic lipid profiles. As the daily lifestyle of the average person with SCI is without adequate stress for conditioning purposes, structured exercise activities must be added to the regular schedule if the individual is to reduce the likelihood of secondary complications and/or to enhance their physical capacity. The acute exercise responses and the capacity for exercise conditioning are directly related to the level and completeness of the spinal lesion. Appropriate exercise testing and training of persons with SCI should be based on the individual's exercise capacity as determined by accurate assessment of the spinal lesion. The standard means of classification of SCI is by application of the International Standards for Classification of Spinal Cord Injury, written by the Neurological Standards Committee of the American Spinal Injury Association. Individuals with complete spinal injuries at or above the fourth thoracic level generally exhibit dramatically diminished cardiac acceleration with maximal heart rates less than 130 beats/min. The work capacity of these persons will be limited by reductions in cardiac output and circulation to the exercising musculature. Persons with complete spinal lesions below the T(10) level will generally display injuries to the lower motor neurons within the lower extremities and, therefore, will not retain the capacity for neuromuscular activation by means of electrical stimulation. Persons with paraplegia also exhibit reduced exercise capacity and increased heart rate responses (compared with the non-disabled), which have been associated with circulatory limitations within the paralysed tissues. The recommendations for endurance and strength training in persons with SCI do not vary dramatically from the advice offered to the general population. Systems of functional electrical stimulation activate muscular contractions within the paralysed muscles of some persons with SCI. Coordinated patterns of stimulation allows purposeful exercise movements including recumbent cycling, rowing and upright ambulation. Exercise activity in persons with SCI is not without risks, with increased risks related to systemic dysfunction following the spinal injury. These individuals may exhibit an autonomic dysreflexia, significantly reduced bone density below the spinal lesion, joint contractures and/or thermal dysregulation. Persons with SCI can benefit greatly by participation in exercise activities, but those benefits can be enhanced and the relative risks may be reduced with accurate classification of the spinal injury.

Fasting, but Not Aging, Dramatically Alters the Redox Status of Cysteine Residues on Proteins in Drosophila melanogaster

PubMed Central

Menger, Katja E.; James, Andrew M.; Cochemé, Helena M.; Harbour, Michael E.; Chouchani, Edward T.; Ding, Shujing; Fearnley, Ian M.; Partridge, Linda; Murphy, Michael P.

2015-01-01

Summary Altering the redox state of cysteine residues on protein surfaces is an important response to environmental challenges. Although aging and fasting alter many redox processes, the role of cysteine residues is uncertain. To address this, we used a redox proteomic technique, oxidative isotope-coded affinity tags (OxICAT), to assess cysteine-residue redox changes in Drosophila melanogaster during aging and fasting. This approach enabled us to simultaneously identify and quantify the redox state of several hundred cysteine residues in vivo. Cysteine residues within young flies had a bimodal distribution with peaks at ∼10% and ∼85% reversibly oxidized. Surprisingly, these cysteine residues did not become more oxidized with age. In contrast, 24 hr of fasting dramatically oxidized cysteine residues that were reduced under fed conditions while also reducing cysteine residues that were initially oxidized. We conclude that fasting, but not aging, dramatically alters cysteine-residue redox status in D. melanogaster. PMID:26095360

Antiapoptotic Effect of Recombinant HMGB1 A-box Protein via Regulation of microRNA-21 in Myocardial Ischemia-Reperfusion Injury Model in Rats.

PubMed

Han, Qiang; Zhang, Hua-Yong; Zhong, Bei-Long; Zhang, Bing; Chen, Hua

2016-04-01

The ~80 amino acid A box DNA-binding domain of high mobility group box 1 (HMGB1) protein antagonizes proinflammatory responses during myocardial ischemia reperfusion (I/R) injury. The exact role of microRNA-21 (miR-21) is unknown, but its altered levels are evident in I/R injury. This study examined the roles of HMGB1 A-box and miR-21 in rat myocardial I/R injury model. Sixty Sprague-Dawley rats were randomly divided into six equal groups: (1) Sham; (2) I/R; (3) Ischemic postconditioning (IPost); (4) AntagomiR-21 post-treatment; (5) Recombinant HMGB1 A-box pretreatment; and (6) Recombinant HMGB1 A-box + antagomiR-21 post-treatment. Hemodynamic indexes, arrhythmia scores, ischemic area and infarct size, myocardial injury, and related parameters were studied. Expression of miR-21 was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to quantify apoptosis. Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of pressure rise (+dp/dtmax), and decline (-dp/dtmax) showed clear reduction upon treatment with recombinant HMGB1 A-box. Arrhythmia was relieved and infarct area decreased in the group pretreated with recombinant HMGB1 A-box, compared with other groups. Circulating lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels increased in response to irreversible cellular injury, while creatine kinase MB isoenzymes (CK-MB) and superoxide dismutase (SOD) activities were reduced in the I/R group, which was reversed following recombinant HMGB1 A-box treatment. Interestingly, pretreatment with recombinant HMGB1 A-box showed the most dramatic reductions in miR-21 levels, compared with other groups. Significantly reduced apoptotic index (AI) was seen in recombinant HMGB1 A-box pretreatment group and recombinant HMGB1 A-box + antagomiR-21 post-treatment group, with the former showing a more dramatic lowering in AI than the latter. Bax, caspase-8, and CHOP showed reduced expression, and Bcl-2 and p-AKT levels were upregulated in recombinant HMGB1 A-box pretreatment group. Thus, recombinant HMGB1 A-box treatment protects against I/R injury and the mechanisms may involve inhibition of miR-21 expression.

Growth Hormone Receptor Antagonist Transgenic Mice Are Protected From Hyperinsulinemia and Glucose Intolerance Despite Obesity When Placed on a HF Diet

PubMed Central

Yang, Tianxu; Householder, Lara A.; Lubbers, Ellen R.; List, Edward O.; Troike, Katie; Vesel, Clare; Duran-Ortiz, Silvana; Kopchick, John J.

2015-01-01

Reduced GH levels have been associated with improved glucose metabolism and increased longevity despite obesity in multiple mouse lines. However, one mouse line, the GH receptor antagonist (GHA) transgenic mouse, defies this trend because it has reduced GH action and increased adiposity, but glucose metabolism and life span are similar to controls. Slight differences in glucose metabolism and adiposity profiles can become exaggerated on a high-fat (HF) diet. Thus, in this study, male and female GHA and wild-type (WT) mice in a C57BL/6 background were placed on HF and low-fat (LF) diets for 11 weeks, starting at 10 weeks of age, to assess how GHA mice respond to additional metabolic stress of HF feeding. On a HF diet, all mice showed significant weight gain, although GHA gained weight more dramatically than WT mice, with males gaining more than females. Most of this weight gain was due to an increase in fat mass with WT mice increasing primarily in the white adipose tissue perigonadal depots, whereas GHA mice gained in both the sc and perigonadal white adipose tissue regions. Notably, GHA mice were somewhat protected from detrimental glucose metabolism changes on a HF diet because they had only modest increases in serum glucose levels, remained glucose tolerant, and did not develop hyperinsulinemia. Sex differences were observed in many measures with males reacting more dramatically to both a reduction in GH action and HF diet. In conclusion, our findings show that GHA mice, which are already obese, are susceptible to further adipose tissue expansion with HF feeding while remaining resilient to alterations in glucose homeostasis. PMID:25406017

miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-{beta}

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

Song, Libing, E-mail: lb.song1@gmail.com; Huang, Quan; Chen, Kun

2010-11-05

Research highlights: {yields} miR-218 is markedly downregulated in glioma cell lines and in primary glioma tissues. {yields} Upregulation of miR-218 dramatically reduces the invasive ability of glioma cells. {yields} Ectopic expression of miR-218 inactivates IKK-{beta}/NF-{kappa}B signaling pathway. {yields} miR-218 directly targets the 3'-untranslated region (3'-UTR) of IKK-{beta}. -- Abstract: Aberrant activation of nuclear factor-kappa B (NF-{kappa}B) pathway has been proven to play important roles in the development and progression of cancers. Activation of NF-{kappa}B via the classical pathway is modulated by I{kappa}Bs kinase (IKK-{beta}). However, the mechanism underlying the epigenetic regulation of IKK-{beta}/NF-{kappa}B pathway remains largely unknown. In this study,more » we found that the expression level of miR-218 was markedly downregulated in glioma cell lines and in human primary glioma tissues. Upregulation of miR-218 dramatically reduced the migratory speed and invasive ability of glioma cells. Furthermore, we showed that ectopically expressing miR-218 in glioma cells resulted in downregulation of matrix metalloproteinase-9 (MMP-9) and reduction in NF-{kappa}B transactivity at a transcriptional level, but inhibition of miR-218 enhanced the expression of MMP-9 and transcriptional activity of NF-{kappa}B. Moreover, we showed that miR-218 inactivated the NF-{kappa}B pathway through downregulating IKK-{beta} expression by directly targeting the 3'-untranslated region (3'-UTR) of IKK-{beta}. Taken together, our results suggest that miR-218 plays an important role in preventing the invasiveness of glioma cells, and our results present a novel mechanism of miRNA-mediated direct suppression of IKK-{beta}/NF-{kappa}B pathway in gliomas.« less

Expression levels of DNA replication and repair genes predict regional somatic repeat instability in the brain but are not altered by polyglutamine disease protein expression or age.

PubMed

Mason, Amanda G; Tomé, Stephanie; Simard, Jodie P; Libby, Randell T; Bammler, Theodor K; Beyer, Richard P; Morton, A Jennifer; Pearson, Christopher E; La Spada, Albert R

2014-03-15

Expansion of CAG/CTG trinucleotide repeats causes numerous inherited neurological disorders, including Huntington's disease (HD), several spinocerebellar ataxias and myotonic dystrophy type 1. Expanded repeats are genetically unstable with a propensity to further expand when transmitted from parents to offspring. For many alleles with expanded repeats, extensive somatic mosaicism has been documented. For CAG repeat diseases, dramatic instability has been documented in the striatum, with larger expansions noted with advancing age. In contrast, only modest instability occurs in the cerebellum. Using microarray expression analysis, we sought to identify the genetic basis of these regional instability differences by comparing gene expression in the striatum and cerebellum of aged wild-type C57BL/6J mice. We identified eight candidate genes enriched in cerebellum, and validated four--Pcna, Rpa1, Msh6 and Fen1--along with a highly associated interactor, Lig1. We also explored whether expression levels of mismatch repair (MMR) proteins are altered in a line of HD transgenic mice, R6/2, that is known to show pronounced regional repeat instability. Compared with wild-type littermates, MMR expression levels were not significantly altered in R6/2 mice regardless of age. Interestingly, expression levels of these candidates were significantly increased in the cerebellum of control and HD human samples in comparison to striatum. Together, our data suggest that elevated expression levels of DNA replication and repair proteins in cerebellum may act as a safeguard against repeat instability, and may account for the dramatically reduced somatic instability present in this brain region, compared with the marked instability observed in the striatum.

Generalized Reich-Moore R-matrix approximation

NASA Astrophysics Data System (ADS)

Arbanas, Goran; Sobes, Vladimir; Holcomb, Andrew; Ducru, Pablo; Pigni, Marco; Wiarda, Dorothea

2017-09-01

A conventional Reich-Moore approximation (RMA) of R-matrix is generalized into a manifestly unitary form by introducing a set of resonant capture channels treated explicitly in a generalized, reduced R-matrix. A dramatic reduction of channel space witnessed in conventional RMA, from Nc × Nc full R-matrix to Np × Np reduced R-matrix, where Nc = Np + Nγ, Np and Nγ denoting the number of particle and γ-ray channels, respectively, is due to Np < Nγ. A corresponding reduction of channel space in generalized RMA (GRMA) is from Nc × Nc full R-matrix to N × N, where N = Np + N, and where N is the number of capture channels defined in GRMA. We show that N = Nλ where Nλ is the number of R-matrix levels. This reduction in channel space, although not as dramatic as in the conventional RMA, could be significant for medium and heavy nuclides where N < Nγ. The resonant capture channels defined by GRMA accommodate level-level interference (via capture channels) neglected in conventional RMA. The expression for total capture cross section in GRMA is formally equal to that of the full Nc × NcR-matrix. This suggests that GRMA could yield improved nuclear data evaluations in the resolved resonance range at a cost of introducing N(N - 1)/2 resonant capture width parameters relative to conventional RMA. Manifest unitarity of GRMA justifies a method advocated by Fröhner and implemented in the SAMMY nuclear data evaluation code for enforcing unitarity of conventional RMA. Capture widths of GRMA are exactly convertible into alternative R-matrix parameters via Brune tranform. Application of idealized statistical methods to GRMA shows that variance among conventional RMA capture widths in extant RMA evaluations could be used to estimate variance among off-diagonal elements neglected by conventional RMA. Significant departure of capture widths from an idealized distribution may indicate the presence of underlying doorway states.

LLMapReduce: Multi-Lingual Map-Reduce for Supercomputing Environments

DTIC Science & Technology

2015-11-20

1990s. Popularized by Google [36] and Apache Hadoop [37], map-reduce has become a staple technology of the ever- growing big data community...Lexington, MA, U.S.A Abstract— The map-reduce parallel programming model has become extremely popular in the big data community. Many big data ...to big data users running on a supercomputer. LLMapReduce dramatically simplifies map-reduce programming by providing simple parallel programming

Easy-to-Make Cryophoruses

ERIC Educational Resources Information Center

Battino, Rubin; Letcher, Trevor M.

2008-01-01

The cryophorus dramatically demonstrates the cooling effect of evaporation. This article describes some simple and easy-to-make cryophoruses, ideal for demonstrating evaporative cooling to students at all levels. The most dramatic effects occurred with cyclohexane and benzene, with water generally freezing more slowly. (Contains 4 notes, 2 tables,…

Macrophage Sortilin Promotes LDL Uptake, Foam Cell Formation, and Atherosclerosis

PubMed Central

Patel, Kevin M.; Strong, Alanna; Tohyama, Junichiro; Jin, Xueting; Morales, Carlos R.; Billheimer, Jeffery; Millar, John; Kruth, Howard; Rader, Daniel J.

2015-01-01

Rationale Non-coding gene variants at the SORT1 locus are strongly associated with LDL-C levels as well as with coronary artery disease (CAD). SORT1 encodes a protein called sortilin, and hepatic sortilin modulates LDL metabolism by targeting apoB-containing lipoproteins to the lysosome. Sortilin is also expressed in macrophages, but its role in macrophage uptake of LDL and in atherosclerosis independent of plasma LDL-C levels is unknown. Objective To determine the effect of macrophage sortilin expression on LDL uptake, foam cell formation, and atherosclerosis. Methods and Results We crossed Sort1−/− mice onto a ‘humanized’ Apobec1−/−; hAPOB Tg background and determined that Sort1 deficiency on this background had no effect on plasma LDL-C levels but dramatically reduced atherosclerosis in the aorta and aortic root. In order to test whether this effect was a result of macrophage sortilin deficiency, we transplanted Sort1−/−;LDLR−/− or Sort1+/+;LDLR−/− bone marrow into Ldlr−/− mice and observed a similar reduction in atherosclerosis in mice lacking hematopoetic sortilin without an effect on plasma LDL-C levels. In an effort to determine the mechanism by which hematopoetic sortilin deficiency reduced atherosclerosis, we found no effect of sortilin deficiency on macrophage recruitment or LPS-induced cytokine release in vivo. In contrast, sortilin deficient macrophages had significantly reduced uptake of native LDL ex vivo and reduced foam cell formation in vivo, whereas sortilin overexpression in macrophages resulted in increased LDL uptake and foam cell formation. Conclusions Macrophage sortilin deficiency protects against atherosclerosis by reducing macrophage uptake of LDL. Sortilin-mediated uptake of native LDL into macrophages may be an important mechanism of foam cell formation and contributor to atherosclerosis development. PMID:25593281

Geldanamycin Reduces Acute Respiratory Distress Syndrome and Promotes the Survival of Mice Infected with the Highly Virulent H5N1 Influenza Virus.

PubMed

Wang, Chengmin; Liu, Pengpeng; Luo, Jing; Ding, Hua; Gao, Yan; Sun, Lei; Luo, Fubing; Liu, Xiaodong; He, Hongxuan

2017-01-01

Infections with lethal influenza viruses lead to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), which may be related to the activation of the host's immune system. Here, in our study, male C57BL/6 mice were infected with 10 LD 50 of the H5N1 influenza virus and treated with geldanamycin or oseltamivir 2 h after infection. Lung injury was assessed by histopathology on days 4 and 7. The viral load was quantified by measuring the NP gene expression level on days 2, 4, and 7. Levels of cytokines and chemokines in bronchoalveolar lavage fluids and inflammatory cells were analyzed at different time points. Geldanamycin administration prolonged survival in mice and dramatically reduced lung injury and pulmonary inflammatory compared with other mice. Viral loads in geldanamycin-treated mice also significantly reduced compared with non-treated mice, but not to the extent as the oseltamivir-treated mice. Furthermore, the geldanamycin treatment markedly reduced the production of major proinflammatory cytokines and chemokines and attenuated the infiltration and activation of immune cells, but it did not alter the generation of virus-neutralizing antibodies. In conclusion, geldanamycin plays an important role in attenuating virus infection-induced ALI/ARDS by reducing the host's inflammatory responses and may provide an important reference for clinical treatments.

Electronic Dimmable Ballasts for High-Intensity Discharge Sodium Vapor and Metal Halide Lamps

NASA Technical Reports Server (NTRS)

Boulanger, Richard

2002-01-01

Two types of high-intensity discharge lamps were tested using dimmable ballasts. The main purpose for evaluating this lighting system was to determine its efficacy for saving power. Whereas previous variable level lighting systems for HID lamps in Advanced Life Support applications were adjustable in two or three steps using capacitive switching, this system allows for continuously adjustable lamp output. This type of lighting system when used as part of an Advanced Life Support biomass production system would provide only the amount of light energy a crop needed at any particular point in its growth cycle. Since most of the equivalent system mass in an ALS system is from the light energy required to grow the crops, controlling that light energy dynamically over a continuous range of operation would dramatically reduce the power consumption and reduce system mass.

Heterogenised Molecular Catalysts for the Reduction of CO₂ to Fuels.

PubMed

Windle, Christopher D; Reisner, Erwin

2015-08-19

CO2 conversion provides a possible solution to curtail the growing CO2 levels in our atmosphere and reduce dependence on fossil fuels. To this end, it is essential to develop efficient catalysts for the reduction of CO2. The structure and activity of molecular CO2 reduction catalysts can be tuned and they offer good selectivity with reasonable stability. Heterogenisation of these molecules reduces solvent restrictions, facilitates recyclability and can dramatically improve activity by preventing catalyst inactivation and perturbing the kinetics of intermediates. The nature and morphology of the solid-state material upon which the catalyst is immobilised can significantly influence the activity of the hybrid assembly. Although work in this area began forty years ago, it has only drawn substantial attention in recent years. This review article gives an overview of the historical development of the field.

Heterogenised Molecular Catalysts for the Reduction of CO2 to Fuels.

PubMed

Windle, Christopher D; Reisner, Erwin

2015-01-01

CO(2) conversion provides a possible solution to curtail the growing CO(2) levels in our atmosphere and reduce dependence on fossil fuels. To this end, it is essential to develop efficient catalysts for the reduction of CO(2). The structure and activity of molecular CO(2) reduction catalysts can be tuned and they offer good selectivity with reasonable stability. Heterogenisation of these molecules reduces solvent restrictions, facilitates recyclability and can dramatically improve activity by preventing catalyst inactivation and perturbing the kinetics of intermediates. The nature and morphology of the solid-state material upon which the catalyst is immobilised can significantly influence the activity of the hybrid assembly. Although work in this area began forty years ago, it has only drawn substantial attention in recent years. This review article gives an overview of the historical development of the field.

Microstructural changes in Beta-silicon nitride grains upon crystallizing the grain-boundary glass

NASA Technical Reports Server (NTRS)

Lee, William E.; Hilmas, Gregory E.; Lange, F. F. (Editor)

1991-01-01

Crystallizing the grain boundary glass of a liquid phase sintered Si3N4 ceramic for 2 h or less at 1500 C led to formation of gamma Y2Si2O7. After 5 h at 1500 C, the gamma Y2Si2O7 had transformed to beta Y2Si2O7 with a concurrent dramatic increase in dislocation density within beta Si3N4 grains. Reasons for the increased dislocation density is discussed. Annealing for 20 h at 1500 C reduced dislocation densities to the levels found in as-sintered materials.

Wigner functions for nonparaxial, arbitrarily polarized electromagnetic wave fields in free space.

PubMed

Alonso, Miguel A

2004-11-01

New representations are defined for describing electromagnetic wave fields in free space exactly in terms of rays for any wavelength, level of coherence or polarization, and numerical aperture, as long as there are no evanescent components. These representations correspond to tensors assigned to each ray such that the electric and magnetic energy densities, the Poynting vector, and the polarization properties of the field correspond to simple integrals involving these tensors for the rays that go through the specified point. For partially coherent fields, the ray-based approach provided by the new representations can reduce dramatically the computation times for the physical properties mentioned earlier.

Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency.

PubMed

Di Giovanni, S; Mirabella, M; Spinazzola, A; Crociani, P; Silvestri, G; Broccolini, A; Tonali, P; Di Mauro, S; Servidei, S

2001-08-14

Two brothers with myopathic coenzyme Q10 (CoQ10) deficiency responded dramatically to CoQ10 supplementation. Muscle biopsies before therapy showed ragged-red fibers, lipid storage, and complex I + III and II + III deficiency. Approximately 30% of myofibers had multiple features of apoptosis. After 8 months of treatment, excessive lipid storage resolved, CoQ10 level normalized, mitochondrial enzymes increased, and proportion of fibers with TUNEL-positive nuclei decreased to 10%. The authors conclude that muscle CoQ10 deficiency can be corrected by supplementation of CoQ10, which appears to stimulate mitochondrial proliferation and to prevent apoptosis.

The controlling effect of viscous dissipation on magma flow in silicic conduits

USGS Publications Warehouse

Mastin, L.G.

2005-01-01

Nearly all volcanic conduit models assume that flow is Newtonian and isothermal. Such models predict that, during high-flux silicic eruptions, gradients in pressure with depth increase upward as magma accelerates and becomes more viscous, leading to extremely low pressure and fragmentation at a depth of kilometers below the surface. In this paper I show that shear heating, also known as viscous dissipation, dramatically reduces the pressure gradient required for flow and concentrates shear in narrow zones along the conduit margin. The reduction in friction may eliminate the zone of low pressure predicted by isothermal models and move the fragmentation level up to the surface.

Ocean acidification affects prey detection by a predatory reef fish.

PubMed

Cripps, Ingrid L; Munday, Philip L; McCormick, Mark I

2011-01-01

Changes in olfactory-mediated behaviour caused by elevated CO(2) levels in the ocean could affect recruitment to reef fish populations because larval fish become more vulnerable to predation. However, it is currently unclear how elevated CO(2) will impact the other key part of the predator-prey interaction--the predators. We investigated the effects of elevated CO(2) and reduced pH on olfactory preferences, activity levels and feeding behaviour of a common coral reef meso-predator, the brown dottyback (Pseudochromis fuscus). Predators were exposed to either current-day CO(2) levels or one of two elevated CO(2) levels (∼600 µatm or ∼950 µatm) that may occur by 2100 according to climate change predictions. Exposure to elevated CO(2) and reduced pH caused a shift from preference to avoidance of the smell of injured prey, with CO(2) treated predators spending approximately 20% less time in a water stream containing prey odour compared with controls. Furthermore, activity levels of fish was higher in the high CO(2) treatment and feeding activity was lower for fish in the mid CO(2) treatment; indicating that future conditions may potentially reduce the ability of the fish to respond rapidly to fluctuations in food availability. Elevated activity levels of predators in the high CO(2) treatment, however, may compensate for reduced olfactory ability, as greater movement facilitated visual detection of food. Our findings show that, at least for the species tested to date, both parties in the predator-prey relationship may be affected by ocean acidification. Although impairment of olfactory-mediated behaviour of predators might reduce the risk of predation for larval fishes, the magnitude of the observed effects of elevated CO(2) acidification appear to be more dramatic for prey compared to predators. Thus, it is unlikely that the altered behaviour of predators is sufficient to fully compensate for the effects of ocean acidification on prey mortality.

Altered regulation of Fc gamma RII on aged follicular dendritic cells correlates with immunoreceptor tyrosine-based inhibition motif signaling in B cells and reduced germinal center formation.

PubMed

Aydar, Yüksel; Balogh, Péter; Tew, John G; Szakal, Andras K

2003-12-01

Aging is associated with reduced trapping of Ag in the form of in immune complexes (ICs) by follicular dendritic cells (FDCs). We postulated that this defect was due to altered regulation of IC trapping receptors. The level of FDC-M1, complement receptors 1 and 2, FcgammaRII, and FDC-M2 on FDCs was immunohistochemically quantitated in draining lymph nodes of actively immunized mice for 10 days after Ag challenge. Initially, FDC FcgammaRII levels were similar but by day 3 a drastic reduction in FDC-FcgammaRII expression was apparent in old mice. FDC-M2 labeling, reflecting IC trapping, was also reduced and correlated with a dramatic reduction in germinal center (GC) B cells as indicated by reduced GC size and number. Nevertheless, labeling of FDC reticula with FDC-M1 and anti-complement receptors 1 and 2 was preserved, indicating that FDCs were present. FDCs in active GCs normally express high levels of FcRs that are thought to bind Fc portions of Abs in ICs and minimize their binding to FcRs on B cells. Thus, cross-linking of B cell receptor and FcR via IC is minimized, thereby reducing signaling via the immunoreceptor tyrosine-based inhibition motif. Old FDCs taken at day 3, when they lack FcgammaRII, were incapable of preventing immunoreceptor tyrosine-based inhibition motif signaling in wild-type B cells but old FDCs stimulated B cells from FcgammaRIIB(-/-) mice to produce near normal levels of specific Ab. The present data support the concept that FcR are regulated abnormally on old FDCs. This abnormality correlates with a reduced IC retention and with a reduced capacity of FDCs to present ICs in a way that will activate GC B cells.

Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery

PubMed Central

Crooks, Daniel R.; Ghosh, Manik C.; Haller, Ronald G.; Tong, Wing-Hang

2010-01-01

Mammalian ferrochelatase, the terminal enzyme in the heme biosynthetic pathway, possesses an iron-sulfur [2Fe-2S] cluster that does not participate in catalysis. We investigated ferrochelatase expression in iron-deficient erythropoietic tissues of mice lacking iron regulatory protein 2, in iron-deficient murine erythroleukemia cells, and in human patients with ISCU myopathy. Ferrochelatase activity and protein levels were dramatically decreased in Irp2−/− spleens, whereas ferrochelatase mRNA levels were increased, demonstrating posttranscriptional regulation of ferrochelatase in vivo. Translation of ferrochelatase mRNA was unchanged in iron-depleted murine erythroleukemia cells, and the stability of mature ferrochelatase protein was also unaffected. However, the stability of newly formed ferrochelatase protein was dramatically decreased during iron deficiency. Ferrochelatase was also severely depleted in muscle biopsies and cultured myoblasts from patients with ISCU myopathy, a disease caused by deficiency of a scaffold protein required for Fe-S cluster assembly. Together, these data suggest that decreased Fe-S cluster availability because of cellular iron depletion or impaired Fe-S cluster assembly causes reduced maturation and stabilization of apo-ferrochelatase, providing a direct link between Fe-S biogenesis and completion of heme biosynthesis. We propose that decreased heme biosynthesis resulting from impaired Fe-S cluster assembly can contribute to the pathogenesis of diseases caused by defective Fe-S cluster biogenesis. PMID:19965627

Joint denoising, demosaicing, and chromatic aberration correction for UHD video

NASA Astrophysics Data System (ADS)

Jovanov, Ljubomir; Philips, Wilfried; Damstra, Klaas Jan; Ellenbroek, Frank

2017-09-01

High-resolution video capture is crucial for numerous applications such as surveillance, security, industrial inspection, medical imaging and digital entertainment. In the last two decades, we are witnessing a dramatic increase of the spatial resolution and the maximal frame rate of video capturing devices. In order to achieve further resolution increase, numerous challenges will be facing us. Due to the reduced size of the pixel, the amount of light also reduces, leading to the increased noise level. Moreover, the reduced pixel size makes the lens imprecisions more pronounced, which especially applies to chromatic aberrations. Even in the case when high quality lenses are used some chromatic aberration artefacts will remain. Next, noise level additionally increases due to the higher frame rates. To reduce the complexity and the price of the camera, one sensor captures all three colors, by relying on Color Filter Arrays. In order to obtain full resolution color image, missing color components have to be interpolated, i.e. demosaicked, which is more challenging than in the case of lower resolution, due to the increased noise and aberrations. In this paper, we propose a new method, which jointly performs chromatic aberration correction, denoising and demosaicking. By jointly performing the reduction of all artefacts, we are reducing the overall complexity of the system and the introduction of new artefacts. In order to reduce possible flicker we also perform temporal video enhancement. We evaluate the proposed method on a number of publicly available UHD sequences and on sequences recorded in our studio.

Case for Deploying Complex Systems Utilizing Commodity Components

NASA Technical Reports Server (NTRS)

Bryant, Barry S.; Pitts, R. Lee

2003-01-01

When the International Space Station (ISS) finally reached an operational state, many of the Payload Operations and Integration Facility (POIF) hardware components were reaching end of life, COTS product costs were soaring, and the ISS budget was becoming severely constrained. However, most requirement development was complete. In addition, the ISS program is a fully functioning program with at least fifteen years of operational life remaining. Therefore it is critical that any upgrades, refurbishments, or enhancements be accomplished in realtime with minimal disruptions to service. For these and other reasons, it was necessary to ensure the viability of the POIF. Due to the to the breadth of capability of the POIF (a NASA ground station), it is believed that the lessons to be learned by other complex systems are applicable and any solutions garnered by the POIF are applicable to other complex systems as well. With that in mind, a number of new approaches have been investigated to increase the portability of the POIF and reduce the cost of refurbishment, operations, and maintenance. These new approaches were directed at the Total Cost of Ownership (TCO); not only the refurbishment but also current operational difficulties, licensing, and anticipation of the next refurbishment. Our basic premise is that technology had evolved dramatically since the concept of the POIF ground system and we should leverage our experience on this new technological landscape. Fortunately, Moore's law and market forces have changed the landscape considerably. These changes are manifest in five (5) ways that are particularly relevant to POIF: 1. Complex Instruction Set Computing (CISC) processors have advanced to unprecedented levels of compute capacity with a dramatic cost break, 2. Linux has become a major operating system supported by most vendors on a broad range of platforms, 3. Windows(TradeMark) based desktops are pervasive in the office environment, 4. Stable and affordable WindowsTM development environments and tools are available and offer a rich set of capabilities, 5. The WindowsTM 2000 provides a stable client platform, Therefore, five studies were proposed, developed, and are in the current process of deployment which dramatically reduces the cost of operations, maintenance, refurbishment, and deployment of a ground system. Restating and refining the basic premise stated earlier, it is possible to enhance operations through the replacement of hardware and software components with commodity based items wherever applicable. This will dramatically reduce the overall lifecycle cost of the project. The first study leveraged the POIF S secure, three-tier, web architecture to replace the client workstations with lower cost PC platforms. A second study initiated a review of COTS products to examine the level of added value of each product. This study included replacement of some COTS products with custom code, deletions, substitutions, and consolidation of COTS products. Studies three and four reviewed the server architectures of the data distribution systems and Enhanced HOSC System (EHS) command and telemetry system to propose migration to new platforms, both software and hardware. The final study reviewed current IP communication technologies, developed an operational model for flight operations, and demonstrated that voice over IP was practical and could be integrated into operations.

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

Sun, Xingshu; Silverman, Timothy J.; Zhou, Zhiguang

For commercial one-sun solar modules, up to 80% of the incoming sunlight may be dissipated as heat, potentially raising the temperature 20-30 °C higher than the ambient. In the long term, extreme self-heating erodes efficiency and shortens lifetime, thereby dramatically reducing the total energy output. Therefore, it is critically important to develop effective and practical (and preferably passive) cooling methods to reduce operating temperature of photovoltaic (PV) modules. In this paper, we explore two fundamental (but often overlooked) origins of PV self-heating, namely, sub-bandgap absorption and imperfect thermal radiation. The analysis suggests that we redesign the optical properties of themore » solar module to eliminate parasitic absorption (selective-spectral cooling) and enhance thermal emission (radiative cooling). Comprehensive opto-electro-thermal simulation shows that the proposed techniques would cool one-sun terrestrial solar modules up to 10 °C. As a result, this self-cooling would substantially extend the lifetime for solar modules, with corresponding increase in energy yields and reduced levelized cost of electricity.« less

Overcoming the Adoption Barrier to Electric Flight

NASA Technical Reports Server (NTRS)

Borer, Nicholas K.; Nickol, Craig L.; Jones, Frank P.; Yasky, Richard J.; Woodham, Kurt; Fell, Jared S.; Litherland, Brandon L.; Loyselle, Patricia L.; Provenza, Andrew J.; Kohlman, Lee W.;

A comparison of two methods of infiltration in breast reduction surgery.

PubMed

Armour, A D; Rotenberg, B W; Brown, M H

2001-08-01

The superwet technique has been shown in previous studies to dramatically reduce blood loss in breast reduction surgery, compared with standard infiltration. A retrospective chart review of 303 consecutive patients undergoing bilateral breast reduction surgery was undertaken to demonstrate additional differences in complication rate, operative time, or sponge use in the operating room. In this series, 132 consecutive patients received standard infiltration along incision lines (25 cc per breast of 1:100,000 epinephrine), and 171 patients received superwet infiltration with 240 cc per breast of 1:1,000,000 epinephrine. The average operative time was significantly reduced in the superwet group, from 78.5 minutes to 70.7 minutes (p < 0.01 level). The average number of sponges used intraoperatively was also decreased significantly (p < 0.01), from 26 to 20 sponges. Complication rates were equally low in both groups, demonstrating the safety of the superwet technique. In addition to limiting blood loss, the superwet infiltration effectively reduces operative time and sponge use without increasing complications in breast reduction surgery.

Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels.

PubMed

Peng, Xian-E; Wu, Yun-Li; Zhu, Yi-Bing; Huang, Rong-Dong; Lu, Qing-Qing; Lin, Xu

2015-01-01

Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD) and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = -0.320, P = 0.003), while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014). Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans.

Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels

PubMed Central

Zhu, Yi-bing; Huang, Rong-dong; Lu, Qing-Qing; Lin, Xu

2015-01-01

Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD) and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = —0.320, P = 0.003), while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014). Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans. PMID:26439934

Fulcrum of Change: Leveraging 50 States to Turn around 5000 Schools

ERIC Educational Resources Information Center

Rhim, Lauren Morando; Redding, Sam

2011-01-01

In 2010, unprecedented levels of resources began to flow through state education agencies (SEAs) to support dramatic change in persistently low-performing schools under the expanded federal School Improvement Grant (SIG) program. The challenge for states is to leverage the federal investment to drive dramatic and sustainable change efforts in…

Modified formulation of CPDA for storage of whole blood, and of SAGM for storage of red blood cells, to maintain the concentration of 2,3-diphosphoglycerate.

PubMed

Kurup, P A; Arun, P; Gayathri, N S; Dhanya, C R; Indu, A R

2003-11-01

A dramatic decrease in the level of 2,3-diphosphoglycerate (2,3-DPG) takes place during the storage of whole blood (WB) in CPDA (citrate-phosphate-dextrose-adenine) and a similar decrease occurs during the storage of red blood cells (RBCs) in SAGM (saline-adenine-glucose-mannitol). The aim of the present study was to prevent this decrease by modifying CPDA and SAGM. The pH of WB anticoagulant or RBC preservative solution was maintained at 7.6 by autoclaving the dextrose solution separately, by incorporating ascorbic acid and nicotinic acid into both CPDA and SAGM (to produce modified CPDA and SAGM solutions), and by reducing the concentration of adenine and adding citrate to the modified SAGM solution. The concentration of 2,3-DPG in WB after 28 days of storage in modified CPDA, and in RBCs stored in modified SAGM, was compared with that in WB or RBCs stored in unmodified solutions. The initial 2,3-DPG levels were maintained after 28 days in the modified formulations [10.63 +/- 2.58 microM/g of haemoglobin (Hb) in the case of modified CPDA and 12.07 +/- 1.47 microM/g of Hb in the case of modified SAGM], whereas in standard CPDA and SAGM solutions, the concentration of 2,3-DPG decreased to very low levels (0.86 +/- 0.97 microM/g Hb for CPDA and 0.12 +/- 0.008 for SAGM). Our modification in the formulation of CPDA or SAGM is effective in arresting the dramatic decrease in the level of 2,3-DPG that occurs during storage of WB and RBCs in unmodified solutions.

Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice

PubMed Central

Farook, Justin M.; Krazem, Ali; Littleton, John M.; Barron, Susan

2008-01-01

In the present study, we examined the effects of acamprosate for its ability to reduce handling induced convulsions (HICs) during alcohol withdrawal. Diazepam was used as a positive control. Swiss Webster male mice received three daily IP injections of alcohol (2.5 g/kg) or alcohol (2.5 g/kg) + methylpyrazole (4-MP) (9 mg/kg). (4-MP, being an alcohol dehydrogenase inhibitor slows down the breakdown of alcohol. 4-MP in combination with alcohol exhibits a dramatic increase in blood alcohol level compared to alcohol alone). Ten hours following the last alcohol injection, the mice were picked up by the tail and examined for their seizure susceptibility (HICs). Diazepam, a benzodiazepine known to reduce seizures during alcohol withdrawal, significantly reduced these HICs at doses of 0.25, 0.5 and 1mg/kg (p’s < 0.001). Acamprosate, an anti-relapse compound used clinically in newly abstinent alcoholics, also reduced these HICs at doses of 100, 200 and 300mg/kg (p’s < 0.05). This study supports the use of acamprosate during periods of alcohol withdrawal as well as during abstinence. PMID:18577392

Polar flagella rotation in Vibrio parahaemolyticus confers resistance to bacteriophage infection

PubMed Central

Zhang, Hui; Li, Lu; Zhao, Zhe; Peng, Daxin; Zhou, Xiaohui

2016-01-01

Bacteriophage has been recognized as a novel approach to treat bacterial infectious diseases. However, phage resistance may reduce the efficacy of phage therapy. Here, we described a mechanism of bacterial resistance to phage infections. In Gram-negative enteric pathogen Vibrio parahaemolyticus, we found that polar flagella can reduce the phage infectivity. Deletion of polar flagella, but not the lateral flagella, can dramatically promote the adsorption of phage to the bacteria and enhances the phage infectivity to V. parahaemolyticus, indicating that polar flagella play an inhibitory role in the phage infection. Notably, it is the rotation, not the physical presence, of polar flagella that inhibits the phage infection of V. parahaemolyticus. Strikingly, phage dramatically reduces the virulence of V. parahaemolyticus only when polar flagella were absent both in vitro and in vivo. These results indicated that polar flagella rotation is a previously unidentified mechanism that confers bacteriophage resistance. PMID:27189325

The effect of shallow vs. deep level doping on the performance of thermoelectric materials

NASA Astrophysics Data System (ADS)

Song, Qichen; Zhou, Jiawei; Meroueh, Laureen; Broido, David; Ren, Zhifeng; Chen, Gang

2016-12-01

It is well known that the efficiency of a good thermoelectric material should be optimized with respect to doping concentration. However, much less attention has been paid to the optimization of the dopant's energy level. Thermoelectric materials doped with shallow levels may experience a dramatic reduction in their figures of merit at high temperatures due to the excitation of minority carriers that reduces the Seebeck coefficient and increases bipolar heat conduction. Doping with deep level impurities can delay the excitation of minority carriers as it requires a higher temperature to ionize all dopants. We find through modeling that, depending on the material type and temperature range of operation, different impurity levels (shallow or deep) will be desired to optimize the efficiency of a thermoelectric material. For different materials, we further clarify where the most preferable position of the impurity level within the bandgap falls. Our research provides insight on why different dopants often affect thermoelectric transport properties differently and directions in searching for the most appropriate dopants for a thermoelectric material in order to maximize the device efficiency.

Pertussis leukocytosis: mechanisms, clinical relevance and treatment

PubMed Central

Carbonetti, Nicholas H.

2016-01-01

The significant and sometimes dramatic rise in the number of circulating white blood cells (leukocytosis) in infants suffering from pertussis (whooping cough) has been recognized for over a century. Although pertussis is a disease that afflicts people of all ages, it can be particularly severe in young infants, and these are the individuals in whom leukocytosis is most pronounced. Very high levels of leukocytosis are associated with poor outcome in infants hospitalized with pertussis and modern treatments are often aimed at reducing the number of leukocytes. Pertussis leukocytosis is caused by pertussis toxin, a soluble protein toxin released by Bordetella pertussis during infection, but the exact mechanisms by which this occurs are still unclear. In this minireview, I discuss the history of clinical and experimental findings on pertussis leukocytosis, possible contributing mechanisms causing this condition and treatments aimed at reducing leukocytosis in hospitalized infants. Since recent studies have detailed significant associations between specific levels of pertussis leukocytosis and fatal outcome, this is a timely review that may stimulate new thinking on how to understand and combat this problem. PMID:27609461

Silencing Onion Lachrymatory Factor Synthase Causes a Significant Change in the Sulfur Secondary Metabolite Profile1[W][OA

PubMed Central

Eady, Colin C.; Kamoi, Takahiro; Kato, Masahiro; Porter, Noel G.; Davis, Sheree; Shaw, Martin; Kamoi, Akiko; Imai, Shinsuke

2008-01-01

Through a single genetic transformation in onion (Allium cepa), a crop recalcitrant to genetic transformation, we suppressed the lachrymatory factor synthase gene using RNA interference silencing in six plants. This reduced lachrymatory synthase activity by up to 1,544-fold, so that when wounded the onions produced significantly reduced levels of tear-inducing lachrymatory factor. We then confirmed, through a novel colorimetric assay, that this silencing had shifted the trans-S-1-propenyl-l-cysteine sulfoxide breakdown pathway so that more 1-propenyl sulfenic acid was converted into di-1-propenyl thiosulfinate. A consequence of this raised thiosulfinate level was a marked increase in the downstream production of a nonenzymatically produced zwiebelane isomer and other volatile sulfur compounds, di-1-propenyl disulfide and 2-mercapto-3,4-dimethyl-2,3-dihydrothiophene, which had previously been reported in trace amounts or had not been detected in onion. The consequences of this dramatic simultaneous down- and up-regulation of secondary sulfur products on the health and flavor attributes of the onion are discussed. PMID:18583530

Fitness trade-offs of group formation and movement by Thomson's gazelles in the Serengeti ecosystem.

PubMed

Fryxell, John M; Berdahl, Andrew M

2018-05-19

Collective behaviours contributing to patterns of group formation and coordinated movement are common across many ecosystems and taxa. Their ubiquity is presumably due to altering interactions between individuals and their predators, resources and physical environment in ways that enhance individual fitness. On the other hand, fitness costs are also often associated with group formation. Modifications to these interactions have the potential to dramatically impact population-level processes, such as trophic interactions or patterns of space use in relation to abiotic environmental variation. In a wide variety of empirical systems and models, collective behaviour has been shown to enhance access to ephemeral patches of resources, reduce the risk of predation and reduce vulnerability to environmental fluctuation. Evolution of collective behaviour should accordingly depend on the advantages of collective behaviour weighed against the costs experienced at the individual level. As an illustrative case study, we consider the potential trade-offs on Malthusian fitness associated with patterns of group formation and movement by migratory Thomson's gazelles in the Serengeti ecosystem.This article is part of the theme issue 'Collective movement ecology'. © 2018 The Authors.

Silencing onion lachrymatory factor synthase causes a significant change in the sulfur secondary metabolite profile.

PubMed

Eady, Colin C; Kamoi, Takahiro; Kato, Masahiro; Porter, Noel G; Davis, Sheree; Shaw, Martin; Kamoi, Akiko; Imai, Shinsuke

2008-08-01

Through a single genetic transformation in onion (Allium cepa), a crop recalcitrant to genetic transformation, we suppressed the lachrymatory factor synthase gene using RNA interference silencing in six plants. This reduced lachrymatory synthase activity by up to 1,544-fold, so that when wounded the onions produced significantly reduced levels of tear-inducing lachrymatory factor. We then confirmed, through a novel colorimetric assay, that this silencing had shifted the trans-S-1-propenyl-l-cysteine sulfoxide breakdown pathway so that more 1-propenyl sulfenic acid was converted into di-1-propenyl thiosulfinate. A consequence of this raised thiosulfinate level was a marked increase in the downstream production of a nonenzymatically produced zwiebelane isomer and other volatile sulfur compounds, di-1-propenyl disulfide and 2-mercapto-3,4-dimethyl-2,3-dihydrothiophene, which had previously been reported in trace amounts or had not been detected in onion. The consequences of this dramatic simultaneous down- and up-regulation of secondary sulfur products on the health and flavor attributes of the onion are discussed.

Warming increases the sensitivity of seedling growth capacity to rainfall in six temperate deciduous tree species

PubMed Central

Smith, Nicholas G; Hoeppner, Susanne S; Dukes, Jeffrey S

2018-01-01

Abstract Predicting the effects of climate change on tree species and communities is critical for understanding the future state of our forested ecosystems. We used a fully factorial precipitation (three levels; ambient, −50 % ambient, +50 % ambient) by warming (four levels; up to +4 °C) experiment in an old-field ecosystem in the northeastern USA to study the climatic sensitivity of seedlings of six native tree species. We measured whole plant-level responses: survival, total leaf area (TLA), seedling insect herbivory damage, as well as leaf-level responses: specific leaf area (SLA), leaf-level water content (LWC), foliar nitrogen (N) concentration, foliar carbon (C) concentration and C:N ratio of each of these deciduous species in each treatment across a single growing season. We found that canopy warming dramatically increased the sensitivity of plant growth (measured as TLA) to rainfall across all species. Warm, dry conditions consistently reduced TLA and also reduced leaf C:N in four species (Acer rubrum, Betula lenta, Prunus serotina, Ulmus americana), primarily as a result of reduced foliar C, not increased foliar N. Interestingly, these conditions also harmed the other two species in different ways, increasing either mortality (Populus grandidentata) or herbivory (Quercus rubra). Specific leaf area and LWC varied across species, but did not show strong treatment responses. Our results indicate that, in the northeastern USA, dry years in a future warmer environment could have damaging effects on the growth capacity of these early secondary successional forests, through species-specific effects on leaf production (total leaves and leaf C), herbivory and mortality. PMID:29484151

Biomimetic optimization research on wind noise reduction of an asymmetric cross-section bar.

PubMed

Zhang, Yingchao; Meng, Weijiang; Fan, Bing; Tang, Wenhui

2016-01-01

In this paper, we used the principle of biomimetics to design two-dimensional and three-dimensional bar sections, and used computational fluid dynamics software to numerically simulate and analyse the aerodynamic noise, to reduce drag and noise. We used the principle of biomimetics to design the cross-section of a bar. An owl wing shape was used for the initial design of the section geometry; then the feathered form of an owl wing, the v-shaped micro-grooves of a shark's skin, the tubercles of a humpback whale's flipper, and the stripy surface of a scallop's shell were used to inspire surface features, added to the initial section and three-dimensional shape. Through computational aeroacoustic simulations, we obtained the aerodynamic characteristics and the noise levels of the models. These biomimetic models dramatically decreased noise levels.

Stochastic coupled cluster theory: Efficient sampling of the coupled cluster expansion

NASA Astrophysics Data System (ADS)

Scott, Charles J. C.; Thom, Alex J. W.

2017-09-01

We consider the sampling of the coupled cluster expansion within stochastic coupled cluster theory. Observing the limitations of previous approaches due to the inherently non-linear behavior of a coupled cluster wavefunction representation, we propose new approaches based on an intuitive, well-defined condition for sampling weights and on sampling the expansion in cluster operators of different excitation levels. We term these modifications even and truncated selections, respectively. Utilising both approaches demonstrates dramatically improved calculation stability as well as reduced computational and memory costs. These modifications are particularly effective at higher truncation levels owing to the large number of terms within the cluster expansion that can be neglected, as demonstrated by the reduction of the number of terms to be sampled when truncating at triple excitations by 77% and hextuple excitations by 98%.

Caloric Restriction Dramatically Stalls Lesion Growth in Mice With Induced Endometriosis.

PubMed

Yin, Bo; Liu, Xishi; Guo, Sun-Wei

2018-01-01

Caloric restriction (CR) has been demonstrated to have many health-beneficial effects in many species, but whether CR can impede the development of endometriosis is unknown. To test the hypothesis that CR can impede the growth of endometriotic lesions and fibrogenesis, we conducted 2 experiments. In experiment 1, 20 female Balb/C mice were randomly assigned to either ad libitum (AL) group that was fed AL or to CR group that was fed 30% less calories than that of AL mice. Two weeks after the implementation of the dietary intervention, endometriosis was induced by intraperitoneal injection of endometrial fragments. Two weeks after the induction, all mice were sacrificed and their lesion samples were evaluated. In experiment 2, another 20 mice were used and CR was implemented 2 weeks after induction of endometriosis and lasted for 4 weeks. Caloric restriction instituted before the induction of endometriosis reduced the lesion weight by 88.5%, whereas CR implemented well after lesions were established reduced the lesion weight by 93.0%. In both cases, CR significantly increased staining levels of markers of autophagy but reduced proliferation, angiogenesis, steroidogenesis, and fibrosis in lesions as compared with the AL group. Consequently, CR, instituted either before or after the induction of endometriosis, dramatically curbs the growth of endometriotic lesions and fibrogenesis through multiple mechanisms. Caloric restriction and CR mimetics, a family of compounds mimicking the beneficial effect of CR, even when instituted well after lesions are established, may stall the development of endometriosis. Given the scarcity in research on how lifestyle can impact on the development of endometriosis, our study should hopefully stimulate more research in this area.

Design considerations for legalizing cannabis: lessons inspired by analysis of California's Proposition 19.

PubMed

Caulkins, Jonathan P; Kilmer, Beau; MacCoun, Robert J; Pacula, Rosalie Liccardo; Reuter, Peter

2012-05-01

No modern jurisdiction has ever legalized commercial production, distribution and possession of cannabis for recreational purposes. This paper presents insights about the effect of legalization on production costs and consumption and highlights important design choices. Insights were uncovered through our analysis of recent legalization proposals in California. The effect on the cost of producing cannabis is largely based on existing estimates of current wholesale prices, current costs of producing cannabis and other legal agricultural goods, and the type(s) of production that will be permitted. The effect on consumption is based on production costs, regulatory regime, tax rate, price elasticity of demand, shape of the demand curve and non-price effects (e.g. change in stigma). Removing prohibitions on producing and distributing cannabis will dramatically reduce wholesale prices. The effect on consumption and tax revenues will depend on many design choices, including: the tax level, whether there is an incentive for a continued black market, whether to tax and/or regulate cannabinoid levels, whether there are allowances for home cultivation, whether advertising is restricted, and how the regulatory system is designed and adjusted. The legal production costs of cannabis will be dramatically below current wholesale prices, enough so that taxes and regulation will be insufficient to raise retail price to prohibition levels. We expect legalization will increase consumption substantially, but the size of the increase is uncertain since it depends on design choices and the unknown shape of the cannabis demand curve. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Terrestrial Microgravity Model and Threshold Gravity Simulation sing Magnetic Levitation

NASA Technical Reports Server (NTRS)

Ramachandran, N.

2005-01-01

What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for such a gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successiblly simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars.

Control-oriented reduced order modeling of dipteran flapping flight

NASA Astrophysics Data System (ADS)

Faruque, Imraan

Flying insects achieve flight stabilization and control in a manner that requires only small, specialized neural structures to perform the essential components of sensing and feedback, achieving unparalleled levels of robust aerobatic flight on limited computational resources. An engineering mechanism to replicate these control strategies could provide a dramatic increase in the mobility of small scale aerial robotics, but a formal investigation has not yet yielded tools that both quantitatively and intuitively explain flapping wing flight as an "input-output" relationship. This work uses experimental and simulated measurements of insect flight to create reduced order flight dynamics models. The framework presented here creates models that are relevant for the study of control properties. The work begins with automated measurement of insect wing motions in free flight, which are then used to calculate flight forces via an empirically-derived aerodynamics model. When paired with rigid body dynamics and experimentally measured state feedback, both the bare airframe and closed loop systems may be analyzed using frequency domain system identification. Flight dynamics models describing maneuvering about hover and cruise conditions are presented for example fruit flies (Drosophila melanogaster) and blowflies (Calliphorids). The results show that biologically measured feedback paths are appropriate for flight stabilization and sexual dimorphism is only a minor factor in flight dynamics. A method of ranking kinematic control inputs to maximize maneuverability is also presented, showing that the volume of reachable configurations in state space can be dramatically increased due to appropriate choice of kinematic inputs.

Alteration of the Alkaloid Profile in Genetically Modified Tobacco Reveals a Role of Methylenetetrahydrofolate Reductase in Nicotine N-Demethylation1[C][W][OA

PubMed Central

Hung, Chiu-Yueh; Fan, Longjiang; Kittur, Farooqahmed S.; Sun, Kehan; Qiu, Jie; Tang, She; Holliday, Bronwyn M.; Xiao, Bingguang; Burkey, Kent O.; Bush, Lowell P.; Conkling, Mark A.; Roje, Sanja; Xie, Jiahua

2013-01-01

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of the tetrahydrofolate (THF)-mediated one-carbon (C1) metabolic network. This enzyme catalyzes the reduction of 5,10-methylene-THF to 5-methyl-THF. The latter donates its methyl group to homocysteine, forming methionine, which is then used for the synthesis of S-adenosyl-methionine, a universal methyl donor for numerous methylation reactions, to produce primary and secondary metabolites. Here, we demonstrate that manipulating tobacco (Nicotiana tabacum) MTHFR gene (NtMTHFR1) expression dramatically alters the alkaloid profile in transgenic tobacco plants by negatively regulating the expression of a secondary metabolic pathway nicotine N-demethylase gene, CYP82E4. Quantitative real-time polymerase chain reaction and alkaloid analyses revealed that reducing NtMTHFR expression by RNA interference dramatically induced CYP82E4 expression, resulting in higher nicotine-to-nornicotine conversion rates. Conversely, overexpressing NtMTHFR1 suppressed CYP82E4 expression, leading to lower nicotine-to-nornicotine conversion rates. However, the reduced expression of NtMTHFR did not affect the methionine and S-adenosyl-methionine levels in the knockdown lines. Our finding reveals a new regulatory role of NtMTHFR1 in nicotine N-demethylation and suggests that the negative regulation of CYP82E4 expression may serve to recruit methyl groups from nicotine into the C1 pool under C1-deficient conditions. PMID:23221678

Dyslipidemia and Auditory Function

PubMed Central

Evans, M. Bradley; Tonini, Ross; Shope, Cynthia Do; Oghalai, John S.; Jerger, James F.; Insull, William; Brownell, William E.

2013-01-01

The relationship between dyslipidemia and hearing is unclear. This study was conducted to investigate whether elevated serum lipid levels impact auditory function in humans and in guinea pigs. In the human study, a cross-sectional study of 40 volunteers with dyslipidemia was conducted. Pure tone thresholds, distortion product otoacoustic emissions, and lipid profiles were analyzed. When controlled for patient age and sex, we found that elevated triglycerides were associated with reduced hearing. In the guinea pig study, a prospective study of animals fed a high-fat diet for 14 weeks was conducted. Although the high-fat diet led to a dramatic elevation in the average weight and total cholesterol in all animals (from 61 to 589 mg/dl), there were no meaningful changes in distortion product otoacoustic emission magnitudes. These results suggest that whereas chronic dyslipidemia associated with elevated triglycerides may reduce auditory function, short-term dietary changes may not. PMID:16868509

Fertility Regulation in an Economic Crisis

PubMed Central

McKelvey, Christopher; Thomas, Duncan; Frankenberg, Elizabeth

2015-01-01

Substantial international aid is spent reducing the cost of contraception in developing countries, as part of a larger effort to reduce global fertility and increase investment per child worldwide. The importance for fertility behaviors of keeping contraceptive prices low, however, remains unclear. Targeting of subsidies and insufficient price variation have hindered prior attempts to estimate the effect of monetary and non-monetary contraceptive costs on fertility behavior. Using longitudinal survey data from the Indonesia Family Life Survey, we exploit dramatic variation in prices and incomes that was induced by the economic crisis in the late 1990s to pin down the effect of contraceptive availability and costs as well as household resources on contraceptive use and method choice. The results are unambiguous: monetary costs of contraceptives and levels of family economic resources have a very small (and well-determined) impact on contraceptive use and choice of method. PMID:25843969

Assessment of Adaptive Guidance for Responsive Launch Vehicles and Spacecraft

DTIC Science & Technology

2009-04-29

Figures 1 Earth centered inertial and launch plumbline coordinate systems . . . . . . . 7 2 Geodetic and geocentric latitude...Dramatically reduced reoccurring costs related to guidance. The same features of the closed-loop ascent guidance that provide operational flexibility...also result in greatly reduced need for human intervention. Thus the operational costs related to ascent guidance could be reduced to minimum

α-Lipoic acid suppresses the development of DNFB-induced atopic dermatitis-like symptoms in NC/Nga mice.

PubMed

Kim, Gun-Dong; Kim, Tae-Ho; Jang, An-Hee; Ahn, Hyun-Jong; Park, Yong Seek; Park, Cheung-Seog

2011-02-01

Atopic dermatitis (AD) is a common skin disease that has complex pathogenic mechanisms. Under specific pathogen-free conditions, repeated epicutaneous treatment of 2-4-dinitrofluorobenzene (DNFB) evokes AD-like clinical symptoms in NC/Nga mice. α-Lipoic acid (α-LA; 1, 2-dithiolane-3-pentanoic acid) is a dietary component that is synthesized in bacteria, yeast, plants, and mammals. α-LA and its reduced form, dihydrolipoic acid, are powerful antioxidants that have many physiological functions, including free radical scavenging of reactive oxygen species, generation of cellular antioxidants, chelation of metal ions, and inflammatory suppression. In this study, we investigated whether α-LA suppresses AD-like skin lesions induced by repeated DNFB application in NC/Nga mice. α-LA significantly suppressed production of interferon (IFN)-γ and interleukin (IL)-4 by activated CD4(+) T cells. We found that the oral administration of α-LA reduced AD-like clinical symptoms and inhibited increases of epidermal thickness in DNFB-induced AD-like skin lesions of NC/Nga mice. Furthermore, total serum IgE levels were dramatically reduced by topical α-LA treatment. Our findings suggest that oral administration of α-LA suppresses the development of AD in DNFB-treated NC/Nga mice and reduces IFN-γ and IL-4 production from activated CD4(+) T cells as well as total serum IgE levels. © 2011 John Wiley & Sons A/S.

The neuroprotective properties of the superoxide dismutase mimetic tempol correlate with its ability to reduce pathological glutamate release in a rodent model of stroke

PubMed Central

Dohare, Preeti; Hyzinski-García, María C.; Vipani, Aarshi; Bowens, Nicole H.; Nalwalk, Julia W.; Feustel, Paul J.; Keller, Richard W.; Jourd’heuil, David; Mongin, Alexander A.

2014-01-01

The contribution of oxidative stress to ischemic brain damage is well established. Nevertheless, for unknown reasons, several clinically tested antioxidant therapies failed to show benefits in human stroke. Based on our previous in vitro work, we hypothesized that the neuroprotective potency of antioxidants is related to their ability to limit release of the excitotoxic amino acids, glutamate and aspartate. We explored the effects of two antioxidants, tempol and edaravone, on amino acid release in the brain cortex, in a rat model of transient occlusion of the middle cerebral artery (MCAo). Amino acid levels were quantified using a microdialysis approach, with the probe positioned in the ischemic penumbra as verified by a laser Doppler technique. Two-hour MCAo triggered a dramatic increase in the levels of glutamate, aspartate, taurine and alanine. Microdialysate delivery of 10 mM tempol reduced the amino acid release by 60–80%, while matching levels of edaravone had no effect. In line with these latter data, an intracerebroventri-cular injection of tempol but not edaravone (500 nmols each, 15 minutes prior to MCAo) reduced infarction volumes by ~50% and improved neurobehavioral outcomes. In vitro assays showed that tempol was superior in removing superoxide anion, whereas edaravone was more potent in scavenging hydrogen peroxide, hydroxyl radical, and peroxynitrite. Overall, our data suggests that the neuroprotective properties of tempol are likely related to its ability to reduce tissue levels of the superoxide anion and pathological glutamate release, and, in such a way, limit progression of brain infarction within ischemic penumbra. These new findings may be instrumental in developing new antioxidant therapies for treatment of stroke. PMID:25224033

NFI-Ski interactions mediate transforming growth factor beta modulation of human papillomavirus type 16 early gene expression.

PubMed

Baldwin, Amy; Pirisi, Lucia; Creek, Kim E

2004-04-01

Human papillomaviruses (HPVs) are present in virtually all cervical cancers. An important step in the development of malignant disease, including cervical cancer, involves a loss of sensitivity to transforming growth factor beta (TGF-beta). HPV type 16 (HPV16) early gene expression, including that of the E6 and E7 oncoprotein genes, is under the control of the upstream regulatory region (URR), and E6 and E7 expression in HPV16-immortalized human epithelial cells is inhibited at the transcriptional level by TGF-beta. While the URR contains a myriad of transcription factor binding sites, including seven binding sites for nuclear factor I (NFI), the specific sequences within the URR or the transcription factors responsible for TGF-beta modulation of the URR remain unknown. To identify potential transcription factors and binding sites involved in TGF-beta modulation of the URR, we performed DNase I footprint analysis on the HPV16 URR using nuclear extracts from TGF-beta-sensitive HPV16-immortalized human keratinocytes (HKc/HPV16) treated with and without TGF-beta. Differentially protected regions were found to be located around NFI binding sites. Electrophoretic mobility shift assays, using the NFI binding sites as probes, showed decreased binding upon TGF-beta treatment. This decrease in binding was not due to reduced NFI protein or NFI mRNA levels. Mutational analysis of individual and multiple NFI binding sites in the URR defined their role in TGF-beta sensitivity of the promoter. Overexpression of the NFI family members in HKc/HPV16 decreased the ability of TGF-beta to inhibit the URR. Since the oncoprotein Ski has been shown to interact with and increase the transcriptional activity of NFI and since cellular Ski levels are decreased by TGF-beta treatment, we explored the possibility that Ski may provide a link between TGF-beta signaling and NFI activity. Anti-NFI antibodies coimmunoprecipitated endogenous Ski in nuclear extracts from HKc/HPV16, confirming that NFI and Ski interact in these cells. Ski levels dramatically decreased upon TGF-beta treatment of HKc/HPV16, and overexpression of Ski eliminated the ability of TGF-beta to inhibit the URR. Based on these studies, we propose that TGF-beta inhibition of HPV16 early gene expression is mediated by a decrease in Ski levels, which in turn dramatically reduces NFI activity.

Phospho-eIF2α level is important for determining abilities of BACE1 reduction to rescue cholinergic neurodegeneration and memory defects in 5XFAD mice.

PubMed

Devi, Latha; Ohno, Masuo

2010-09-23

β-Site APP-cleaving enzyme 1 (BACE1) initiates amyloid-β (Aβ) generation and thus represents a prime therapeutic target in treating Alzheimer's disease (AD). Notably, increasing evidence indicates that BACE1 levels become elevated in AD brains as disease progresses; however, it remains unclear how the BACE1 upregulation may affect efficacies of therapeutic interventions including BACE1-inhibiting approaches. Here, we crossed heterozygous BACE1 knockout mice with AD transgenic mice (5XFAD model) and compared the abilities of partial BACE1 reduction to rescue AD-like phenotypes at earlier (6-month-old) and advanced (15-18-month-old) stages of disease, which expressed normal (∼100%) and elevated (∼200%) levels of BACE1, respectively. BACE1(+/-) deletion rescued memory deficits as tested by the spontaneous alternation Y-maze task in 5XFAD mice at the earlier stage and prevented their septohippocampal cholinergic deficits associated with significant neuronal loss. Importantly, BACE1(+/-) deletion was no longer able to rescue memory deficits or cholinergic neurodegeneration in 5XFAD mice at the advanced stage. Moreover, BACE1(+/-) deletion significantly reduced levels of Aβ42 and the β-secretase-cleaved C-terminal fragment (C99) in 6-month-old 5XFAD mouse brains, while these neurotoxic β-cleavage products dramatically elevated with age and were not affected by BACE1(+/-) deletion in 15-18-month-old 5XFAD brains. Interestingly, although BACE1(+/-) deletion lowered BACE1 expression by ∼50% in 5XFAD mice irrespective of age in concordance with the reduction in gene copy number, BACE1 equivalent to wild-type controls remained in BACE1(+/-)·5XFAD mice at the advanced age. In accord, phosphorylation of the translation initiation factor eIF2α, an important mediator of BACE1 elevation, was dramatically increased (∼9-fold) in 15-18-month-old 5XFAD mice and remained highly upregulated (∼6-fold) in age-matched BACE1(+/-)·5XFAD mice. Together, our results indicate that partial reduction of BACE1 is not sufficient to block the phospho-eIF2α-dependent BACE1 elevation during the progression of AD, thus limiting its abilities to reduce cerebral Aβ/C99 levels and rescue memory deficits and cholinergic neurodegeneration.

Mutant LRRK2 Toxicity in Neurons Depends on LRRK2 Levels and Synuclein But Not Kinase Activity or Inclusion Bodies

PubMed Central

Skibinski, Gaia; Nakamura, Ken; Cookson, Mark R.

2014-01-01

By combining experimental neuron models and mathematical tools, we developed a “systems” approach to deconvolve cellular mechanisms of neurodegeneration underlying the most common known cause of Parkinson's disease (PD), mutations in leucine-rich repeat kinase 2 (LRRK2). Neurons ectopically expressing mutant LRRK2 formed inclusion bodies (IBs), retracted neurites, accumulated synuclein, and died prematurely, recapitulating key features of PD. Degeneration was predicted from the levels of diffuse mutant LRRK2 that each neuron contained, but IB formation was neither necessary nor sufficient for death. Genetic or pharmacological blockade of its kinase activity destabilized LRRK2 and lowered its levels enough to account for the moderate reduction in LRRK2 toxicity that ensued. By contrast, targeting synuclein, including neurons made from PD patient-derived induced pluripotent cells, dramatically reduced LRRK2-dependent neurodegeneration and LRRK2 levels. These findings suggest that LRRK2 levels are more important than kinase activity per se in predicting toxicity and implicate synuclein as a major mediator of LRRK2-induced neurodegeneration. PMID:24403142

Bisphenol A disrupts gene expression in human placental trophoblast cells.

PubMed

Rajakumar, Chandrew; Guan, Haiyan; Langlois, David; Cernea, Maria; Yang, Kaiping

2015-06-01

This study examined the effect of bisphenol A (BPA) on human placental gene expression using primary trophoblast cells as an in vitro model system. Trophoblast cells were isolated from human placentas at term, cultured and then exposed to environmentally relevant concentrations of BPA (0.1-2 μg/ml) for up to 24h, after which levels of 11β-HSD2 mRNA, protein and activity were determined by standard radiometric conversion assay, western blotting, and qRT-PCR, respectively. The mRNA levels of several other prominent placental hormones/factors were also assessed by qRT-PCR. BPA dramatically increased levels of 11β-HSD2 activity, protein and mRNA in a time- and concentration-dependent manner (> 4-fold). BPA also augmented aromatase, glucose transporter-1, CRH, and hCG mRNA levels while reducing the level of leptin mRNA. These findings demonstrate that BPA severely disrupts human placental gene expression in vitro, which suggests that exposure to BPA may contribute to altered placental function and consequent pregnancy complications. Copyright © 2015 Elsevier Inc. All rights reserved.

Reducing early childhood caries in a Medicaid population: a systems model analysis.

PubMed

Edelstein, Burton L; Hirsch, Gary; Frosh, Marcy; Kumar, Jayanth

2015-04-01

Despite early childhood caries (ECC) being largely preventable, its repair accounts for a disproportionate share of Medicaid expenditures. In this study, the authors model disease reductions and cost savings from ECC management alternatives. The authors apply system dynamics modeling to the New York State Medicaid population of young children to compare potential outcomes of 9 preventive interventions (water fluoridation, fluoride varnish, fluoride toothpaste, medical screening and fluoride varnish application, bacterial transmission reduction, motivational interviewing, dental prevention visits, secondary prevention, and combinations) and the effect of defluoridating New York City. Model simulations help project 10-year disease reductions and net savings from water fluoridation, motivational interviewing, and fluoride toothpaste. Interventions requiring health professionals cost more than they save. Interventions that target children at high risk, begin early, and combine multiple strategies hold greatest potential. Defluoridating New York City would increase disease and costs dramatically. The variety of population-level and individual-level interventions available to control ECC differ substantially in their capacity to improve children's oral health and reduce state Medicaid expenditures. Using Medicaid and health department dollars to deliver ECC preventive and management interventions holds strong promise to improve children's oral health while reducing state dental expenditures in Medicaid. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

Compact system with handheld microfabricated optoelectronic probe for needle-based tissue sensing applications

NASA Astrophysics Data System (ADS)

Lee, Seung Yup; Na, Kyounghwan; Pakela, Julia M.; Scheiman, James M.; Yoon, Euisik; Mycek, Mary-Ann

2017-02-01

We present the design, development, and bench-top verification of an innovative compact clinical system including a miniaturized handheld optoelectronic sensor. The integrated sensor was microfabricated with die-level light-emitting diodes and photodiodes and fits into a 19G hollow needle (internal diameter: 0.75 mm) for optical sensing applications in solid tissues. Bench-top studies on tissue-simulating phantoms have verified system performance relative to a fiberoptic based tissue spectroscopy system. With dramatically reduced system size and cost, the technology affords spatially configurable designs for optoelectronic light sources and detectors, thereby enabling customized sensing configurations that would be impossible to achieve with needle-based fiber-optic probes.

A novel copper-hydrogen peroxide formulation for prion decontamination.

PubMed

Solassol, Jerome; Pastore, Manuela; Crozet, Carole; Perrier, Veronique; Lehmann, Sylvain

2006-09-15

With the appearance of variant Creutzfeldt-Jakob disease (CJD) and the detection of infectious prions in the peripheral organs of persons with sporadic CJD, the development of decontamination methods that are compatible with medical equipment has become a major issue. Here, we show that a formulation of copper metal ions in combination with hydrogen peroxide dramatically reduces the level of prion protein (PrP)(Sc) (the scrapie isoform of PrP) present in homogenates of samples from prion-infected brains, including brain samples from humans with CJD. An animal bioassay confirmed the reduction in prion infectivity, indicating that this novel Cu(2+)-H(2)O(2) formulation has great potential for prion decontamination.

Plasma levels of endothelial and B-cell-derived microparticles are restored by fingolimod treatment in multiple sclerosis patients.

PubMed

Zinger, Anna; Latham, Sharissa L; Combes, Valery; Byrne, Scott; Barnett, Michael H; Hawke, Simon; Grau, Georges E

2016-12-01

No molecular marker can monitor disease progression and treatment efficacy in multiple sclerosis (MS). Circulating microparticles represent a potential snapshot of disease activity at the blood brain barrier. To profile plasma microparticles by flow cytometry in MS and determine how fingolimod could impact endothelial microparticles production. In non-treated MS patients compared to healthy and fingolimod-treated patients, endothelial microparticles were higher, while B-cell-microparticle numbers were lower. Fingolimod dramatically reduced tumour necrosis factor (TNF)-induced endothelial microparticle release in vitro. Fingolimod restored dysregulated endothelial and B-cell-microparticle numbers, which could serve as a biomarker in MS. © The Author(s), 2016.

Cell Adhesion Modification of Streptococcus viridians in the Presence of Xylitol

NASA Astrophysics Data System (ADS)

Esmacher, Jason; Vidakovich, Blair; Giangrande, Michael; Hoffmann, Peter

2012-10-01

There is scientific documentation that those who chew gum sweetened by the sugar alcohol xylitol report a dramatically lower incident of both dental caries and otitis media compared to those who chew conventional gum sweetened by sucrose. An explanation contends that xylitol interferes with the ability of Streptococcus viridian (SV) to form biofilms which is a necessary precursor to the bacteria's ability to damage human tissues. We have used atomic force microscopy to study the cell wall/fimbria properties at the nanonewton level in both the presence and absence of xylitol. The first set of measurements used varying concentrations of xylitol incorporated within the incubation medium. The second used non-xylitol grown bacteria, the xylitol was added externally at various concentrations. Our study suggests that growing SV with xylitol reduces their ability to adhere together. Additionally, externally added xylitol showed grouping of cell adhesion to a relatively narrow nanonewton spread that is concentration dependent. Measurement of the adhesion properties of the bacterial cell wall have found that there is a dramatic increase in the cell wall's firmness which simultaneously accompanied a decrease in its ability to support adhesion, even at very low concentrations of xylitol.

School Fire Protection: Contents Count

ERIC Educational Resources Information Center

American School and University, 1976

1976-01-01

The heart of a fire protection system is the sprinkler system. National Fire Protection Association (NFPA) statistics show that automatic sprinklers dramatically reduce fire damage and loss of life. (Author)

Mantle of the Expert: Integrating Dramatic Inquiry and Visual Arts in Social Studies

ERIC Educational Resources Information Center

Johnson, Edric C.; Liu, Katrina; Goble, Kristin

2015-01-01

This article introduces the social studies field to Dorothy Heatchote's Mantle of Expert (MOE). MOE is a dramatic inquiry approach used in several subject areas and can work at all levels in the social studies curriculum. The authors go into the development of using this approach in an elementary and middle teacher education program. After sharing…

3D Rainbow Particle Tracking Velocimetry

NASA Astrophysics Data System (ADS)

Aguirre-Pablo, Andres A.; Xiong, Jinhui; Idoughi, Ramzi; Aljedaani, Abdulrahman B.; Dun, Xiong; Fu, Qiang; Thoroddsen, Sigurdur T.; Heidrich, Wolfgang

2017-11-01

A single color camera is used to reconstruct a 3D-3C velocity flow field. The camera is used to record the 2D (X,Y) position and colored scattered light intensity (Z) from white polyethylene tracer particles in a flow. The main advantage of using a color camera is the capability of combining different intensity levels for each color channel to obtain more depth levels. The illumination system consists of an LCD projector placed perpendicularly to the camera. Different intensity colored level gradients are projected onto the particles to encode the depth position (Z) information of each particle, benefiting from the possibility of varying the color profiles and projected frequencies up to 60 Hz. Chromatic aberrations and distortions are estimated and corrected using a 3D laser engraved calibration target. The camera-projector system characterization is presented considering size and depth position of the particles. The use of these components reduces dramatically the cost and complexity of traditional 3D-PTV systems.

Manganese peroxidase from the white-rot fungus Phanerochaete chrysosporium is enzymatically active and accumulates to high levels in transgenic maize seed.

PubMed

Clough, Richard C; Pappu, Kameshwari; Thompson, Kevin; Beifuss, Katherine; Lane, Jeff; Delaney, Donna E; Harkey, Robin; Drees, Carol; Howard, John A; Hood, Elizabeth E

2006-01-01

Manganese peroxidase (MnP) has been implicated in lignin degradation and thus has potential applications in pulp and paper bleaching, enzymatic remediation and the textile industry. Transgenic plants are an emerging protein expression platform that offer many advantages over traditional systems, in particular their potential for large-scale industrial enzyme production. Several plant expression vectors were created to evaluate the accumulation of MnP from the wood-rot fungus Phanerochaete chrysosporium in maize seed. We showed that cell wall targeting yielded full-length MnP, whereas cytoplasmic localization resulted in multiple truncated peroxidase polypeptides as detected by immunoblot analysis. In addition, the use of a seed-preferred promoter dramatically increased the expression levels and reduced the negative effects on plant health. Multiple independent transgenic lines were backcrossed with elite inbred corn lines for several generations with the maintenance of high-level expression, indicating genetic stability of the transgene.

HO2 rovibrational eigenvalue studies for nonzero angular momentum

NASA Astrophysics Data System (ADS)

Wu, Xudong T.; Hayes, Edward F.

1997-08-01

An efficient parallel algorithm is reported for determining all bound rovibrational energy levels for the HO2 molecule for nonzero angular momentum values, J=1, 2, and 3. Performance tests on the CRAY T3D indicate that the algorithm scales almost linearly when up to 128 processors are used. Sustained performance levels of up to 3.8 Gflops have been achieved using 128 processors for J=3. The algorithm uses a direct product discrete variable representation (DVR) basis and the implicitly restarted Lanczos method (IRLM) of Sorensen to compute the eigenvalues of the polyatomic Hamiltonian. Since the IRLM is an iterative method, it does not require storage of the full Hamiltonian matrix—it only requires the multiplication of the Hamiltonian matrix by a vector. When the IRLM is combined with a formulation such as DVR, which produces a very sparse matrix, both memory and computation times can be reduced dramatically. This algorithm has the potential to achieve even higher performance levels for larger values of the total angular momentum.

Regulation of Synaptic Structure by the Ubiquitin C-terminal Hydrolase UCH-L1

PubMed Central

Cartier, Anna E.; Djakovic, Stevan N.; Salehi, Afshin; Wilson, Scott M.; Masliah, Eliezer; Patrick, Gentry N.

2009-01-01

UCH-L1 is a de-ubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We have found that UCH-L1 activity is rapidly up-regulated by NMDA receptor activation which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of pre and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1 inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner. PMID:19535597

Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1.

PubMed

Cartier, Anna E; Djakovic, Stevan N; Salehi, Afshin; Wilson, Scott M; Masliah, Eliezer; Patrick, Gentry N

2009-06-17

Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We found that UCH-L1 activity is rapidly upregulated by NMDA receptor activation, which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of presynaptic and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1-inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner.

Echo planar imaging at 4 Tesla with minimum acoustic noise.

PubMed

Tomasi, Dardo G; Ernst, Thomas

2003-07-01

To minimize the acoustic sound pressure levels of single-shot echo planar imaging (EPI) acquisitions on high magnetic field MRI scanners. The resonance frequencies of gradient coil vibrations, which depend on the coil length and the elastic properties of the materials in the coil assembly, were measured using piezoelectric transducers. The frequency of the EPI-readout train was adjusted to avoid the frequency ranges of mechanical resonances. Our MRI system exhibited two sharp mechanical resonances (at 720 and 1220 Hz) that can increase vibrational amplitudes up to six-fold. A small adjustment of the EPI-readout frequency made it possible to reduce the sound pressure level of EPI-based perfusion and functional MRI scans by 12 dB. Normal vibrational modes of MRI gradient coils can dramatically increase the sound pressure levels during echo planar imaging (EPI) scans. To minimize acoustic noise, the frequency of EPI-readout trains and the resonance frequencies of gradient coil vibrations need to be different. Copyright 2003 Wiley-Liss, Inc.

Reducing DNA context dependence in bacterial promoters

PubMed Central

Carr, Swati B.; Densmore, Douglas M.

2017-01-01

Variation in the DNA sequence upstream of bacterial promoters is known to affect the expression levels of the products they regulate, sometimes dramatically. While neutral synthetic insulator sequences have been found to buffer promoters from upstream DNA context, there are no established methods for designing effective insulator sequences with predictable effects on expression levels. We address this problem with Degenerate Insulation Screening (DIS), a novel method based on a randomized 36-nucleotide insulator library and a simple, high-throughput, flow-cytometry-based screen that randomly samples from a library of 436 potential insulated promoters. The results of this screen can then be compared against a reference uninsulated device to select a set of insulated promoters providing a precise level of expression. We verify this method by insulating the constitutive, inducible, and repressible promotors of a four transcriptional-unit inverter (NOT-gate) circuit, finding both that order dependence is largely eliminated by insulation and that circuit performance is also significantly improved, with a 5.8-fold mean improvement in on/off ratio. PMID:28422998

Lean, Mean and Green: An Affordable Net Zero School

ERIC Educational Resources Information Center

Stanfield, Kenneth

2010-01-01

From its conception, Richardsville Elementary was designed to be an affordable net zero facility. The design team explored numerous energy saving strategies to dramatically reduce energy consumption. By reducing energy use to 19.31 kBtus annually, the net zero goal could be realized through the implementation of a solar array capable of producing…

A Strategic Plan for the Crusader Howitzer

DTIC Science & Technology

2001-12-01

of the system was its “volume under armor ,” which describes the actual size of the vehicle and hence its weight (DoD, December 2000, pg. 13). By...reducing the Crusader’s volume under armor , the designers would be able to dramatically reduce the system’s overall weight. This became one of the

Analyzing phorbol ester effects on gap junctional communication: a dramatic inhibition of assembly

PubMed Central

1994-01-01

The effect of 12-O-tetradeconylphorbol-13-acetate (TPA) on gap junction assembly between Novikoff hepatoma cells was examined. Cells were dissociated with EDTA to single cells and then reaggregated to form new junctions. When TPA (25 nM) was added to the cells at the onset of the 60-min reaggregation, dye transfer was detected at only 0.6% of the cell-cell interfaces compared to 72% for the untreated control and 74% for 4-alpha TPA, an inactive isomer of TPA. Freeze-fracture electron microscopy of reaggregated control cells showed interfaces containing an average of more than 600 aggregated intramembranous gap junction particles, while TPA-treated cells had no gap junctions. However, Lucifer yellow dye transfer between nondissociated cells via gap junctions was unaffected by 60 min of TPA treatment. Therefore, TPA dramatically inhibited gap junction assembly but did not alter channel gating nor enhance disassembly of preexisting gap junction structures. Short term TPA treatment (< 30 min) increased phosphorylation of the gap junction protein molecular weight of 43,000 (Cx43), but did not change the cellular level of Cx43. Cell surface biotinylation experiments suggested that TPA did not substantially reduce the plasma membrane concentration of Cx43. Therefore, the simple presence of Cx43 in the plasma membrane is not sufficient for gap junction assembly, and protein kinase C probably exerts an effect on assembly of gap junctions at the plasma membrane level. PMID:7806568

Development of an online SPE-UHPLC-MS/MS method for the multiresidue analysis of the 17 compounds from the EU "Watch list".

PubMed

Gusmaroli, Lucia; Insa, Sara; Petrovic, Mira

2018-04-24

During the last decades, the quality of aquatic ecosystems has been threatened by increasing levels of pollutions, caused by the discharge of man-made chemicals, both via accidental release of pollutants as well as a consequence of the constant outflow of inadequately treated wastewater effluents. For this reason, the European Union is updating its legislations with the aim of limiting the release of emerging contaminants. The Commission Implementing Decision (EU) 2015/495 published in March 2015 drafts a "Watch list" of compounds to be monitored Europe-wide. In this study, a methodology based on online solid-phase extraction (SPE) ultra-high-performance liquid chromatography coupled to a triple-quadrupole mass spectrometer (UHPLC-MS/MS) was developed for the simultaneous determination of the 17 compounds listed therein. The proposed method offers advantages over already available methods, such as versatility (all 17 compounds can be analyzed simultaneously), shorter time required for analysis, robustness, and sensitivity. The employment of online sample preparation minimized sample manipulation and reduced dramatically the sample volume needed and time required, dramatically the sample volume needed and time required, thus making the analysis fast and reliable. The method was successfully validated in surface water and influent and effluent wastewater. Limits of detection ranged from sub- to low-nanogram per liter levels, in compliance with the EU limits, with the only exception of EE2. Graphical abstract Schematic of the workflow for the analysis of the Watch list compounds.

Effect of a marathon run on serum lipoproteins, creatine kinase, and lactate dehydrogenase in recreational runners.

PubMed

Kobayashi, Yoshio; Takeuchi, Toshiko; Hosoi, Teruo; Yoshizaki, Hidekiyo; Loeppky, Jack A

2005-12-01

The objective of this study was to determine the effect of a marathon run on serum lipid and lipoprotein concentrations and serum muscle enzyme activities and follow their recovery after the run. These blood concentrations were measured before, immediately after, and serially after a marathon run in 15 male recreational runners. The triglyceride level was significantly elevated postrace, then fell 30% below baseline 1 day after the run, and returned to baseline after 1 week. Total cholesterol responded less dramatically but with a similar pattern. High-density lipoprotein cholesterol remained significantly elevated and low-density lipoprotein cholesterol was transiently reduced for 3 days after the run. The total cholesterol/high-density cholesterol ratio was significantly lowered for 3 days. Serum lactate dehydrogenase activity significantly doubled postrace and then declined but remained elevated for 2 weeks. Serum creatine kinase activity peaked 24 hr after the run, with a 15-fold rise, and returned to baseline after 1 week. The rise of these enzymes reflects mechanically damaged muscle cells leaking contents into the interstitial fluid. It is concluded that a prolonged strenuous exercise bout in recreational runners, such as a marathon, produces beneficial changes in lipid blood profiles that are significant for only 3 days. However, muscle damage is also evident for 1 week or more from the dramatic and long-lasting effect on enzyme levels. Laboratory values for these runners were outside normal ranges for some days after the race.

Comparison of ovariectomy and retinyl acetate on the growth of established 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat

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

Gandlihon, P.; Melancon, R.; Djiane, J.

1982-08-01

Prolonged exposure to retinyl acetate (RA) in the diet inhibits the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary cancers in rats. The effectiveness of RA was examined when given 6 months after the administration of DMBA. Non-inbred female Sprague-Dawley rats with DMBA-induced mammary tumors were divided into 3 groups and treated for 4 weeks as follows: Group 1 served as controls, group 2 was ovariectomized, and group 3 received 328 mg RA/kg diet. Ovariectomy (OVX) markedly reduced both the number and size of the tumors. RA administration failed to induce any significant regression in tumor number but significantly retarded tumor growth whenmore » compared to tumor growth in group 1 controls. The levels of estradiol, progestin, and prolactin (PRL) receptors were significantly reduced after OVX, whereas only the levels of PRL receptors declined significantly after RA administration. Circulating progesterone concentrations were not affected in the RA-treated group but the plasma PRL level was significantly increased. The present studies show that if treatment with RA is delayed until 6 months after carcinogen administration, the protective effect of RA can still be observed although its effectiveness is less dramatic than when it is administered earlier.« less

Herbivores and nutrients control grassland plant diversity via light limitation

USGS Publications Warehouse

Borer, Elizabeth T.; Seabloom, Eric W.; Gruner, Daniel S.; Harpole, W. Stanley; Hillebrand, Helmut; Lind, Eric M.; Alder, Peter B.; Alberti, Juan; Anderson, T. Michael; Bakker, Jonathan D.; Biederman, Lori; Blumenthal, Dana; Brown, Cynthia S.; Brudvig, Lars A.; Buckley, Yvonne M.; Cadotte, Marc; Chu, Cheng-Jin; Cleland, Elsa E.; Crawley, Michael J.; Daleo, Pedro; Damschen, Ellen Ingman; Davies, Kendi F.; DeCrappeo, Nicole M.; Du, Guozhen; Firn, Jennifer; Hautier, Yann; Heckman, Robert W.; Hector, Andy; HilleRisLambers, Janneke; Iribarne, Oscar; Klein, Julia A.; Knops, Johannes M.H.; La Pierre, Kimberly J.; Leakey, Andrew D.B.; Li, Wei; MacDougall, Andrew S.; McCulley, Rebecca L.; Melbourne, Brett A.; Mitchell, Charles E.; Moore, Joslin L.; Mortensen, Brent; O'Halloran, Lydia R.; Orrock, John L.; Pascual, Jesús; Prober, Suzanne M.; Pyke, David A.; Risch, Anita C.; Schuetz, Martin; Smith, Melinda D.; Stevens, Carly J.; Sullivan, Lauren L.; Williams, Ryan J.; Wragg, Peter D.; Wright, Justin P.; Yang, Louie H.

2014-01-01

Human alterations to nutrient cycles and herbivore communities are affecting global biodiversity dramatically. Ecological theory predicts these changes should be strongly counteractive: nutrient addition drives plant species loss through intensified competition for light, whereas herbivores prevent competitive exclusion by increasing ground-level light, particularly in productive systems. Here we use experimental data spanning a globally relevant range of conditions to test the hypothesis that herbaceous plant species losses caused by eutrophication may be offset by increased light availability due to herbivory. This experiment, replicated in 40 grasslands on 6 continents, demonstrates that nutrients and herbivores can serve as counteracting forces to control local plant diversity through light limitation, independent of site productivity, soil nitrogen, herbivore type and climate. Nutrient addition consistently reduced local diversity through light limitation, and herbivory rescued diversity at sites where it alleviated light limitation. Thus, species loss from anthropogenic eutrophication can be ameliorated in grasslands where herbivory increases ground-level light.

Optimization of conditions for thermal treatment of rice bran using an accelerator including an organo-iron compound.

PubMed

Kanno, Hikari; Tachibana, Naoya; Fukushima, Masami

2011-02-01

A method for thermal conversion of raw organic waste (ROW) to a compost-like material (CLM) with higher levels of unsaturated carbohydrates, nitrogen- and oxygen-containing compounds was developed, in which rice bran and an organo-iron compound were employed as a model ROW and the accelerator, respectively. To evaluate the qualities of CLMs, organic substances of an acid insoluble fraction of alkaline extracts (AIAEs) from a CLM were structurally characterized by elemental analysis, pyrolysis-gas chromatography/mass spectrometry and FT-IR. The levels of unsaturated carbohydrates, and nitrogen- and oxygen-containing compounds in the CLM samples were increased by long-term treatment (60°C for 5 days, 170°C for 3 days). In particular, the high lipid content of the AIAEs, which was indicative of inadequate digestion of CLM components, was dramatically reduced in the presence of the accelerator. Copyright © 2010 Elsevier Ltd. All rights reserved.

Image quality enhancement in low-light-level ghost imaging using modified compressive sensing method

NASA Astrophysics Data System (ADS)

Shi, Xiaohui; Huang, Xianwei; Nan, Suqin; Li, Hengxing; Bai, Yanfeng; Fu, Xiquan

2018-04-01

Detector noise has a significantly negative impact on ghost imaging at low light levels, especially for existing recovery algorithm. Based on the characteristics of the additive detector noise, a method named modified compressive sensing ghost imaging is proposed to reduce the background imposed by the randomly distributed detector noise at signal path. Experimental results show that, with an appropriate choice of threshold value, modified compressive sensing ghost imaging algorithm can dramatically enhance the contrast-to-noise ratio of the object reconstruction significantly compared with traditional ghost imaging and compressive sensing ghost imaging methods. The relationship between the contrast-to-noise ratio of the reconstruction image and the intensity ratio (namely, the average signal intensity to average noise intensity ratio) for the three reconstruction algorithms are also discussed. This noise suppression imaging technique will have great applications in remote-sensing and security areas.

Stability amidst turmoil: Grit buffers the effects of negative life events on suicidal ideation.

PubMed

Blalock, Dan V; Young, Kevin C; Kleiman, Evan M

2015-08-30

The goal of the current study is to examine the role of grit as a resilience factor that reduces the risk for suicidal ideation conferred by negative life events. Participants (N=209) completed measures of negative life events and grit at baseline and a measure of suicidal ideation at follow-up four weeks later. Poisson regression analyses found that higher levels of grit buffered the relationship between negative life events and suicidal ideation such that negative life events only predicted suicidal ideation if grit was low. These results suggest that high grit can abate the increased suicidal ideation associated with negative life events. Aside from absolute levels of suicidal ideation, being able to predict or buffer dramatic shifts in suicidal ideation can be a useful diagnostic tool during interventions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Herbivores and nutrients control grassland plant diversity via light limitation.

PubMed

Borer, Elizabeth T; Seabloom, Eric W; Gruner, Daniel S; Harpole, W Stanley; Hillebrand, Helmut; Lind, Eric M; Adler, Peter B; Alberti, Juan; Anderson, T Michael; Bakker, Jonathan D; Biederman, Lori; Blumenthal, Dana; Brown, Cynthia S; Brudvig, Lars A; Buckley, Yvonne M; Cadotte, Marc; Chu, Chengjin; Cleland, Elsa E; Crawley, Michael J; Daleo, Pedro; Damschen, Ellen I; Davies, Kendi F; DeCrappeo, Nicole M; Du, Guozhen; Firn, Jennifer; Hautier, Yann; Heckman, Robert W; Hector, Andy; HilleRisLambers, Janneke; Iribarne, Oscar; Klein, Julia A; Knops, Johannes M H; La Pierre, Kimberly J; Leakey, Andrew D B; Li, Wei; MacDougall, Andrew S; McCulley, Rebecca L; Melbourne, Brett A; Mitchell, Charles E; Moore, Joslin L; Mortensen, Brent; O'Halloran, Lydia R; Orrock, John L; Pascual, Jesús; Prober, Suzanne M; Pyke, David A; Risch, Anita C; Schuetz, Martin; Smith, Melinda D; Stevens, Carly J; Sullivan, Lauren L; Williams, Ryan J; Wragg, Peter D; Wright, Justin P; Yang, Louie H

2014-04-24

Human alterations to nutrient cycles and herbivore communities are affecting global biodiversity dramatically. Ecological theory predicts these changes should be strongly counteractive: nutrient addition drives plant species loss through intensified competition for light, whereas herbivores prevent competitive exclusion by increasing ground-level light, particularly in productive systems. Here we use experimental data spanning a globally relevant range of conditions to test the hypothesis that herbaceous plant species losses caused by eutrophication may be offset by increased light availability due to herbivory. This experiment, replicated in 40 grasslands on 6 continents, demonstrates that nutrients and herbivores can serve as counteracting forces to control local plant diversity through light limitation, independent of site productivity, soil nitrogen, herbivore type and climate. Nutrient addition consistently reduced local diversity through light limitation, and herbivory rescued diversity at sites where it alleviated light limitation. Thus, species loss from anthropogenic eutrophication can be ameliorated in grasslands where herbivory increases ground-level light.

Unexpected patterns of fisheries collapse in the world's oceans.

PubMed

Pinsky, Malin L; Jensen, Olaf P; Ricard, Daniel; Palumbi, Stephen R

2011-05-17

Understanding which species are most vulnerable to human impacts is a prerequisite for designing effective conservation strategies. Surveys of terrestrial species have suggested that large-bodied species and top predators are the most at risk, and it is commonly assumed that such patterns also apply in the ocean. However, there has been no global test of this hypothesis in the sea. We analyzed two fisheries datasets (stock assessments and landings) to determine the life-history traits of species that have suffered dramatic population collapses. Contrary to expectations, our data suggest that up to twice as many fisheries for small, low trophic-level species have collapsed compared with those for large predators. These patterns contrast with those on land, suggesting fundamental differences in the ways that industrial fisheries and land conversion affect natural communities. Even temporary collapses of small, low trophic-level fishes can have ecosystem-wide impacts by reducing food supply to larger fish, seabirds, and marine mammals.

Nutritional modulation of cataract

PubMed Central

Weikel, Karen A; Garber, Caren; Baburins, Alyssa; Taylor, Allen

2014-01-01

Lens opacification or cataract reduces vision in over 80 million people worldwide and blinds 18 million. These numbers will increase dramatically as both the size of the elderly demographic and the number of those with carbohydrate metabolism-related problems increase. Preventative measures for cataract are critical because the availability of cataract surgery in much of the world is insuficient. Epidemiologic literature suggests that the risk of cataract can be diminished by diets that are optimized for vitamin C, lutein/zeaxanthin, B vitamins, omega-3 fatty acids, multivitamins, and carbohydrates: recommended levels of micronutrients are salutary. The limited data from intervention trials provide some support for observational studies with regard to nuclear – but not other types of – cataracts. Presented here are the beneficial levels of nutrients in diets or blood and the total number of participants surveyed in epidemiologic studies since a previous review in 2007. PMID:24279748

Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression.

PubMed

Chen, Xia; Sun, Chang-Kai; Han, Guo-Zhu; Peng, Jin-Yong; Li, Ying; Liu, Yan-Xia; Lv, Yuan-Yuan; Liu, Ke-Xin; Zhou, Qin; Sun, Hui-Jun

2009-04-21

To investigate the hepatoprotective activity of tea polyphenols (TP) and its relation with cytochrome P450 (CYP450) expression in mice. Hepatic CYP450 and CYPb(5) levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP (25, 50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100, 200 and 400 mg/kg per day) for six days before paracetamol (1000 mg/kg) was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP (100, 200, and 400 mg/kg per day) for five days before paracetamol (500 mg/kg) was given. Hepatic CYP2E1 and CYP1A2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction. The hepatic CYP450 and CYPb(5) levels in mice of TP-treated groups (100, 200 and 400 mg/kg per day) were decreased in a dose-dependent manner compared with those in the negative control mice. TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner. TP possess potential hepatoprotective properties and can suppress CYP450 expression.

Update on control of Staphylococcus aureus and Streptococcus agalactiae for management of mastitis.

PubMed

Keefe, Greg

2012-07-01

The primary method of spread for S agalactiae and S aureus is from cow to cow, so prevention focuses on within and between herd biosecurity to reduce or eliminate the reservoir of infection. S agalactiae is an obligate pathogen of the mammary gland, whereas S aureus is more widespread on other cow body sites and in the environment. Both organisms cause persistent infections, with S agalactiae typically causing higher SCC and bacteria counts in milk. Conventional methods of detection through culture perform well at the cow level. In bulk tanks, augmented procedures should be considered. PCR methods show promise of high sensitivity and specificity, at both the cow and bulk tank level. In developed dairy industries, prevalence of infection has decreased dramatically over the past 30 years for S agalactiae. For S aureus, the herd level of infection remains very high, although with rigorous, consistent application of control measures, within-herd prevalence has decreased. Because the milking time is the primary period for new IMI, it is the focal point of most prevention activities. Premilking and postmilking teat disinfection and proper stimulation and milk-out with adequately functioning equipment are key factors. There is growing evidence that the use of milking gloves is an integral part of contagious mastitis control and the production of high-quality milk. Treatment success is dramatically different between the 2 pathogens. For S agalactiae, eradication can be completed rapidly through a culture and treatment program with minimal culling. For S aureus, treatment success, particularly during lactation, is often disappointing and depends on cow, pathogen, and treatment factors. These factors should be reviewed prior to initiating any treatment to determine the potential for cure. Blanket dry cow therapy and strategic culling are important control procedures for contagious mastitis pathogens. Maintaining a closed herd or, at minimum, adhering to clearly defined biosecurity protocols is critical to reduce risk of reintroduction of S agalactiae or the addition of new, potentially more virulent strains of S aureus to endemic herds.

Fluoride exposure changed the structure and the expressions of Y chromosome related genes in testes of mice.

PubMed

Cao, Jinling; Chen, Yan; Chen, Jianjie; Yan, Hanghang; Li, Meiyan; Wang, Jundong

2016-10-01

It is known that during spermatogenesis, pluripotent germ cells differentiate to become efficient delivery vehicles to the oocyte of paternal DNA, and the process is easily damaged by external poison. In this study, the effects of fluoride on the body weight, fluoride content in femur, testosterone levels in serum and testis, sperm quality, and the expressions of Y chromosome microdeletion genes and protein levels were examined in testes of Kunming male mice treated with different concentrations of 0, 25, 50, 100 mg/L of NaF in drinking water for 11 weeks, respectively. The results showed that compared with the control group, fluoride contents in three treatment groups were significantly increased and the structure of testes was seriously injured. The testosterone contents and the sperm count were decreased. Sperm malformation ratio was distinctly elevated. The expressions of Sly and HSF2 mRNA were markedly reduced in 100 mg/L NaF group and Ssty2 mRNA expression was dramatically decreased in 50 and 100 mg/L NaF groups. Meanwhile, the protein levels of Ssty2 and Sly were significantly reduced in 50 and 100 mg/L NaF groups and HSF2 protein levels were significantly decreased in 100 mg/L NaF group. These studies indicated that fluoride had toxic effects on male reproductive system by reducing the testosterone and sperm count, and increasing the sperm malformation ratio, supported by the damage of testicular structure, as a consequence of depressed HSF2 level, which resulted in the down-regulation of Ssty2 and Sly mRNA and protein. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alcohol and liver disease in Europe--Simple measures have the potential to prevent tens of thousands of premature deaths.

PubMed

Sheron, Nick

2016-04-01

In the World Health Organisation European Region, more than 2,370,000 years of life are lost from liver disease before the age of 50; more than lung cancer, trachea, bronchus, oesophageal, stomach, colon, rectum and pancreatic cancer combined. Between 60-80% of these deaths are alcohol related, a disease for which no pharmaceutical therapy has yet been shown to improve long-term survival. The toxicity of alcohol is dose related at an individual level, and is dose related at a population level; overall liver mortality is largely determined by population alcohol consumption. Trends in alcohol consumption correlate closely with trends in overall liver mortality, with 3-5-fold decreases or increases in liver mortality in different European countries over the last few decades. The evidence base for alcohol control measures aimed at reducing population alcohol consumption has been subjected to rigorous evaluation; most recently by the Organisation for Economic Co-Operation and Development (OECD). Effective alcohol policy measures reduce alcohol mortality, including mortality from liver disease. The most effective and cost effective measures have been summarised by the OECD and the World Health Organisation: regular incremental above inflation tax increases, a minimum price for alcohol, effective protection of children from alcohol marketing and low level interventions from clinicians. Simple, cheap and effective changes to alcohol policy by European Institutions and member states have the potential to dramatically reduce liver mortality in Europe. Copyright © 2016. Published by Elsevier B.V.

Lipopolysaccharide inhibits the self-renewal of spermatogonial stem cells in vitro via downregulation of GDNF expression in Sertoli cells.

PubMed

Zhang, Xiaoli; Shi, Kun; Li, Yi; Zhang, Haiyu; Hao, Jing

2014-06-01

Lipopolysaccharide (LPS) can reduce sperm count and sperm quality. The molecular mechanisms underlying this process are not fully understood. In this report, we investigated the effects of LPS-treated Sertoli cells on self-renewal and differentiation of spermatogoinial stem cells (SSCs). Sertoli cell cultures were established and incubated with LPS (10μg/ml) for 1, 2 or 3 days, respectively. The culture media were collected and used as conditioned media (CM) to culture SSCs. The expression of glial cell-derived neurotrophic factor (GDNF), stem cell factor (SCF) and bone morphogenetic protein 4 (BMP4) in Sertoli cells treated with LPS was analyzed by RT-PCR and Western blotting. The results showed that the expression of SSC differentiation markers, c-kit and Sohlh2, was increased, while the expression of SSC self-renewal markers, plzf, oct4, and PCNA, was repressed when cultured in CM from LPS-treated Sertoli cells. GDNF levels in Sertoli cells and CM reduced dramatically after LPS treatments, while SCF and BMP4 levels did not show any significant changes. Moreover, correlated with the GDNF levels in CM, GDNF target genes, Bcl6b and Etv5, were reduced markedly in SSCs. Our results suggest that LPS inhibits the expression of GDNF in Sertoli cells, and might prevent the SSC self-renewal via down-regulation of GDNF target genes. Copyright © 2014 Elsevier Inc. All rights reserved.

Differential depuration of poliovirus, Escherichia coli, and a coliphage by the common mussel, Mytilus edulis

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

Power, U.F.; Collins, J.K.

1989-06-01

The elimination of sewage effluent-associated poliovirus, Escherichia coli, and a 22-nm icosahedral coliphage by the common mussel, Mytilus edulis, was studied. Both laboratory-and commercial-scale recirculating, UV depuration systems were used in this study. In the laboratory system, the logarithms of the poliovirus, E. coli, and coliphage levels were reduced by 1.86, 2.9, and 2.16, respectively, within 52 h of depuration. The relative patterns and rates of elimination of the three organisms suggest that they are eliminated from mussels by different mechanisms during depuration under suitable conditions. Poliovirus was not included in experiments undertaken in the commercial-scale depuration system. The differencesmore » in the relative rates and patterns of elimination were maintained for E. coli and coliphage in this system, with the logarithm of the E. coli levels being reduced by 3.18 and the logarithm of the coliphage levels being reduced by 0.87. The results from both depuration systems suggest that E. coli is an inappropriate indicator of the efficiency of virus elimination during depuration. The coliphage used appears to be a more representative indicator. Depuration under stressful conditions appeared to have a negligible affect on poliovirus and coliphage elimination rates from mussels. However, the rate and pattern of E. coli elimination were dramatically affected by these conditions. Therefore, monitoring E. coli counts might prove useful in ensuring that mussels are functioning well during depuration.« less

Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood.

PubMed

Duggal, Niharika Arora; Pollock, Ross D; Lazarus, Norman R; Harridge, Stephen; Lord, Janet M

2018-04-01

It is widely accepted that aging is accompanied by remodelling of the immune system including thymic atrophy and increased frequency of senescent T cells, leading to immune compromise. However, physical activity, which influences immunity but declines dramatically with age, is not considered in this literature. We assessed immune profiles in 125 adults (55-79 years) who had maintained a high level of physical activity (cycling) for much of their adult lives, 75 age-matched older adults and 55 young adults not involved in regular exercise. The frequency of naïve T cells and recent thymic emigrants (RTE) were both higher in cyclists compared with inactive elders, and RTE frequency in cyclists was no different to young adults. Compared with their less active counterparts, the cyclists had significantly higher serum levels of the thymoprotective cytokine IL-7 and lower IL-6, which promotes thymic atrophy. Cyclists also showed additional evidence of reduced immunesenescence, namely lower Th17 polarization and higher B regulatory cell frequency than inactive elders. Physical activity did not protect against all aspects of immunesenescence: CD28 -ve CD57 +ve senescent CD8 T-cell frequency did not differ between cyclists and inactive elders. We conclude that many features of immunesenescence may be driven by reduced physical activity with age. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Engaging in Dramatic Activities in English as a Foreign Language Classes at the University Level

ERIC Educational Resources Information Center

Algarra Carrasco, Victoria

2012-01-01

In this article, we discuss how, through dramatic activities, fiction and reality can work together to help the English as a Foreign language learner communicate in a more personal and meaningful way. The kind of activities proposed are designed to help engender a space where students can personally engage with each other in an atmosphere that is…

Into the Curriculum. Dramatics/Reading/Language Arts: Jellyfish Jiggle and More; Reading/Language Arts: Birthstone Folklore; Science: Jellyfish FAQ; Science: Minerals in Caves; Social Studies: Mapping the Oceans.

ERIC Educational Resources Information Center

School Library Media Activities Monthly, 2003

2003-01-01

Provides five fully developed library media activities that are designed for use with specific curriculum units in dramatics, reading, language arts, science, and social studies. Library media skills, curriculum objectives, grade levels, resources, instructional roles, activities and procedures, evaluation, and follow-up are describes for each…

Adolescent smokers' response to reducing the nicotine content of cigarettes: Acute effects on withdrawal symptoms and subjective evaluations.

PubMed

Cassidy, Rachel N; Colby, Suzanne M; Tidey, Jennifer W; Jackson, Kristina M; Cioe, Patricia A; Krishnan-Sarin, Suchitra; Hatsukami, Dorothy

2018-05-15

Mandating a reduction in the nicotine content of cigarettes to a minimally addictive level could dramatically reduce smoking rates in the US. However, little is known about the effects of reduced nicotine content cigarettes in adolescents. Following overnight abstinence, adolescent daily smokers (ages 15-19, n = 50) reported on their craving, withdrawal, and positive and negative affect pre- and post- ad lib smoking of one cigarette containing varying nicotine content (15.8, 5.2, 1.3 and 0.4 mg/g of tobacco) in the laboratory and reported their subjective evaluations of each cigarette. Carbon monoxide (CO) boost from pre- to post-cigarette was calculated to determine if lower-nicotine cigarettes led to differential acute changes in toxicant exposure. All four nicotine cigarette types significantly reduced abstinence-induced craving, withdrawal, and negative affect (all p's < .05). Mixed models evaluating the effect of nicotine content, with nicotine dependence level and gender included as covariates, revealed a significant effect of nicotine content on craving and subjective evaluations: higher nicotine content resulted in greater reductions in craving and increases in both positive and negative subjective evaluations. There were no significant effects of nicotine dose on withdrawal symptoms, negative affect, or CO boost. These results suggest that lower nicotine cigarettes might result in reduced abuse liability compared to higher nicotine content cigarettes due to reduced positive subjective effects, while still reducing withdrawal, in adolescents. These results highlight the potential feasibility of this policy approach and support continued research on how a nicotine reduction policy may affect adolescent smoking patterns. Copyright © 2018 Elsevier B.V. All rights reserved.

Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration

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

Arulanandam, Rozanne; Geletu, Mulu; Feracci, Helene

2010-03-10

Rac1 (Rac) is a member of the Rho family of small GTPases which controls cell migration by regulating the organization of actin filaments. Previous results suggested that mutationally activated forms of the Rho GTPases can activate the Signal Transducer and Activator of Transcription-3 (Stat3), but the exact mechanism is a matter of controversy. We recently demonstrated that Stat3 activity of cultured cells increases dramatically following E-cadherin engagement. To better understand this pathway, we now compared Stat3 activity levels in mouse HC11 cells before and after expression of the mutationally activated Rac1 (Rac{sup V12}), at different cell densities. The results revealedmore » for the first time a dramatic increase in protein levels and activity of both the endogenous Rac and Rac{sup V12} with cell density, which was due to inhibition of proteasomal degradation. In addition, Rac{sup V12}-expressing cells had higher Stat3, tyrosine-705 phosphorylation and activity levels at all densities, indicating that Rac{sup V12} is able to activate Stat3. Further examination of the mechanism of Stat3 activation showed that Rac{sup V12} expression caused a surge in mRNA of Interleukin-6 (IL6) family cytokines, known potent Stat3 activators. Knockdown of gp130, the common subunit of this family reduced Stat3 activity, indicating that these cytokines may be responsible for the Stat3 activation by Rac{sup V12}. The upregulation of IL6 family cytokines was required for cell migration and proliferation induced by Rac{sup V12}, as shown by gp130 knockdown experiments, thus demonstrating that the gp130/Stat3 axis represents an essential effector of activated Rac for the regulation of key cellular functions.« less

Terrestrial Microgravity Model and Threshold Gravity Simulation using Magnetic Levitation

NASA Technical Reports Server (NTRS)

Ramachandran, N.

2005-01-01

What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for such a gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successfully simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars. The paper will discuss experiments md modeling work to date in support of this project.

Threshold Gravity Determination and Artificial Gravity Studies Using Magnetic Levitation

NASA Technical Reports Server (NTRS)

Ramachandran, N.; Leslie, F.

2005-01-01

What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required (magnitude and duration)? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for a variable gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successfully simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars.

Reducing Air Pollution from International Transportation

EPA Pesticide Factsheets

Because of their reliance on petroleum-based fuels and their dramatic growth rates in recent decades, air and sea transport are responsible for significant emissions of both traditional air pollutants and greenhouse gases.

Core Noise Reduction

NASA Technical Reports Server (NTRS)

Hultgren, Lennart S.

2011-01-01

This presentation is a technical summary of and outlook for NASA-internal and NASA-sponsored external research on core (combustor and turbine) noise funded by the Fundamental Aeronautics Program Subsonic Fixed Wing (SFW) Project. Sections of the presentation cover: the SFW system-level noise metrics for the 2015, 2020, and 2025 timeframes; turbofan design trends and their aeroacoustic implications; the emerging importance of core noise and its relevance to the SFW Reduce-Perceived-Noise Technical Challenge; and the current research activities in the core noise area. Recent work1 on the turbine-transmission loss of combustor noise is briefly described, two2,3 new NRA efforts in the core-noise area are outlined, and an effort to develop CMC-based acoustic liners for broadband noise reduction suitable for turbofan-core application is delineated. The NASA Fundamental Aeronautics Program has the principal objective of overcoming today's national challenges in air transportation. The reduction of aircraft noise is critical to enabling the anticipated large increase in future air traffic. The Subsonic Fixed Wing Project's Reduce-Perceived-Noise Technical Challenge aims to develop concepts and technologies to dramatically reduce the perceived aircraft noise outside of airport boundaries.

Optics-based approach to thermal management of photovoltaics: Selective-spectral and radiative cooling

DOE PAGES

Sun, Xingshu; Silverman, Timothy J.; Zhou, Zhiguang; ...

2017-01-20

For commercial one-sun solar modules, up to 80% of the incoming sunlight may be dissipated as heat, potentially raising the temperature 20-30 °C higher than the ambient. In the long term, extreme self-heating erodes efficiency and shortens lifetime, thereby dramatically reducing the total energy output. Therefore, it is critically important to develop effective and practical (and preferably passive) cooling methods to reduce operating temperature of photovoltaic (PV) modules. In this paper, we explore two fundamental (but often overlooked) origins of PV self-heating, namely, sub-bandgap absorption and imperfect thermal radiation. The analysis suggests that we redesign the optical properties of themore » solar module to eliminate parasitic absorption (selective-spectral cooling) and enhance thermal emission (radiative cooling). Comprehensive opto-electro-thermal simulation shows that the proposed techniques would cool one-sun terrestrial solar modules up to 10 °C. As a result, this self-cooling would substantially extend the lifetime for solar modules, with corresponding increase in energy yields and reduced levelized cost of electricity.« less

Non-wetting surface-driven high-aspect-ratio crystalline grain growth for efficient hybrid perovskite solar cells

DOE PAGES

Bi, Cheng; Wang, Qi; Shao, Yuchuan; ...

2015-07-20

Large-aspect-ratio grains are needed in polycrystalline thin-film solar cells for reduced charge recombination at grain boundaries; however, the grain size in organolead trihalide perovskite (OTP) films is generally limited by the film thickness. Here we report the growth of OTP grains with high average aspect ratio of 2.3–7.9 on a wide range of non-wetting hole transport layers (HTLs), which increase nucleus spacing by suppressing heterogeneous nucleation and facilitate grain boundary migration in grain growth by imposing less drag force. The reduced grain boundary area and improved crystallinity dramatically reduce the charge recombination in OTP thin films to the level inmore » OTP single crystals. Combining the high work function of several HTLs, a high stabilized device efficiency of 18.3% in low-temperature-processed planar-heterojunction OTP devices under 1 sun illumination is achieved. As a result, this simple method in enhancing OTP morphology paves the way for its application in other optoelectronic devices for enhanced performance.« less

An Equation-Free Reduced-Order Modeling Approach to Tropical Pacific Simulation

NASA Astrophysics Data System (ADS)

Wang, Ruiwen; Zhu, Jiang; Luo, Zhendong; Navon, I. M.

2009-03-01

The “equation-free” (EF) method is often used in complex, multi-scale problems. In such cases it is necessary to know the closed form of the required evolution equations about oscopic variables within some applied fields. Conceptually such equations exist, however, they are not available in closed form. The EF method can bypass this difficulty. This method can obtain oscopic information by implementing models at a microscopic level. Given an initial oscopic variable, through lifting we can obtain the associated microscopic variable, which may be evolved using Direct Numerical Simulations (DNS) and by restriction, we can obtain the necessary oscopic information and the projective integration to obtain the desired quantities. In this paper we apply the EF POD-assisted method to the reduced modeling of a large-scale upper ocean circulation in the tropical Pacific domain. The computation cost is reduced dramatically. Compared with the POD method, the method provided more accurate results and it did not require the availability of any explicit equations or the right-hand side (RHS) of the evolution equation.

Polyploidization of murine mesenchymal cells is associated with suppression of the long noncoding RNA H19 and reduced tumorigenicity.

PubMed

Shoshani, Ofer; Massalha, Hassan; Shani, Nir; Kagan, Sivan; Ravid, Orly; Madar, Shalom; Trakhtenbrot, Luba; Leshkowitz, Dena; Rechavi, Gideon; Zipori, Dov

2012-12-15

Mesenchymal stromal cells (MSC) are used extensively in clinical trials; however, the possibility that MSCs have a potential for malignant transformation was raised. We examined the genomic stability versus the tumor-forming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less stable and more prone to malignant transformation than their human counterparts. A large series of independently isolated MSC populations exhibited low tumorigenic potential under syngeneic conditions, which increased in immunocompromised animals. Unexpectedly, higher ploidy correlated with reduced tumor-forming capacity. Furthermore, in both cultured MSCs and primary hepatocytes, polyploidization was associated with a dramatic decrease in the expression of the long noncoding RNA H19. Direct knockdown of H19 expression in diploid cells resulted in acquisition of polyploid cell traits. Moreover, artificial tetraploidization of diploid cancer cells led to a reduction of H19 levels, as well as to an attenuation of the tumorigenic potential. Polyploidy might therefore serve as a protective mechanism aimed at reducing malignant transformation through the involvement of the H19 regulatory long noncoding RNA.

Strategies to maintain health in the Third World.

PubMed

Korte, R; Rehle, T; Merkle, A

1991-12-01

International cooperation with Third World countries aims at reducing the high morbidity and mortality of the population to a tolerable level. The main health problems are caused by poverty. Thus, the range of diseases in tropical countries can be explained more readily by the socio-economic situation than solely by the climate. Health services, in Africa in particular, have had to reduce drastically their budgets in the last ten years and now have only approximately 1/1000th of the funds usually available in industrialised countries. High population growth reduces the resources available per head, increases infection potential and worsens living conditions. Control strategies must take account of these circumstances in order to achieve the required sustained effect within the framework of primary health care. The example of the control of several infectious diseases, such as schistosomiasis, pneumonia, malaria and AIDS, is used to show that control programmes can be effective but, in the current conditions, can hardly be maintained without outside support. In the future, diseases caused by environmental problems and new life styles as a result of industrialization, urbanization and slum growth will move dramatically into the foreground.

Method and apparatus for reducing sample dispersion in turns and junctions of microchannel systems

DOEpatents

Griffiths, Stewart K.; Nilson, Robert H.

2001-01-01

The performance of microchannel devices is improved by providing turns, wyes, tees, and other junctions that produce little dispersions of a sample as it traverses the turn or junction. The reduced dispersion results from contraction and expansion regions that reduce the cross-sectional area over some portion of the turn or junction. By carefully designing the geometries of these regions, sample dispersion in turns and junctions is reduced to levels comparable to the effects of ordinary diffusion. A numerical algorithm was employed to evolve low-dispersion geometries by computing the electric or pressure field within candidate configurations, sample transport through the turn or junction, and the overall effective dispersion. These devices should greatly increase flexibility in the design of microchannel devices by permitting the use of turns and junctions that do not induce large sample dispersion. In particular, the ability to fold electrophoretic and electrochrornatographic separation columns will allow dramatic improvements in the miniaturization of these devices. The low-lispersion devices are particularly suited to electrochromatographic and electrophoretic separations, as well as pressure-driven chromatographic separation. They are further applicable to microfluidic systems employing either electroosrnotic or pressure-driven flows for sample transport, reaction, mixing, dilution or synthesis.

Voluntary medical male circumcision: an HIV prevention priority for PEPFAR.

PubMed

Reed, Jason Bailey; Njeuhmeli, Emmanuel; Thomas, Anne Goldzier; Bacon, Melanie C; Bailey, Robert; Cherutich, Peter; Curran, Kelly; Dickson, Kim; Farley, Tim; Hankins, Catherine; Hatzold, Karin; Justman, Jessica; Mwandi, Zebedee; Nkinsi, Luke; Ridzon, Renee; Ryan, Caroline; Bock, Naomi

2012-08-15

As the science demonstrating strong evidence for voluntary medical male circumcision (VMMC) for HIV prevention has evolved, the President's Emergency Plan for AIDS Relief (PEPFAR) has collaborated with international agencies, donors, and partner country governments supporting VMMC programming. Mathematical models forecast that quickly reaching a large number of uncircumcised men with VMMC in strategically chosen populations may dramatically reduce community-level HIV incidence and save billions of dollars in HIV care and treatment costs. Because VMMC is a 1-time procedure that confers life-long partial protection against HIV, programs for adult men are vital short-term investments with long-term benefits. VMMC also provides a unique opportunity to reach boys and men with HIV testing and counseling services and referrals for other HIV services, including treatment. After formal recommendations by WHO in 2007, priority countries have pursued expansion of VMMC. More than 1 million males have received VMMC thus far, with the most notable successes coming from Kenya's Nyanza Province. However, a myriad of necessary cultural, political, and ethical considerations have moderated the pace of overall success. Because many millions more uncircumcised men would benefit from VMMC services now, US President Barack Obama committed PEPFAR to provide 4.7 million males with VMMC by 2014. Innovative circumcision methods-such as medical devices that remove the foreskin without injected anesthesia and/or sutures-are being rigorously evaluated. Incorporation of safe innovations into surgical VMMC programs may provide the opportunity to reach more men more quickly with services and dramatically reduce HIV incidence for all.

Red Sky with Red Mesa

ScienceCinema

None

2018-01-16

The Red Sky/Red Mesa supercomputing platform dramatically reduces the time required to simulate complex fuel models, from 4-6 months to just 4 weeks, allowing researchers to accelerate the pace at which they can address these complex problems. Its speed also reduces the need for laboratory and field testing, allowing for energy reduction far beyond data center walls.

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

None

This factsheet describes a project that developed and demonstrated a new manufacturing-informed design framework that utilizes advanced multi-scale, physics-based process modeling to dramatically improve manufacturing productivity and quality in machining operations while reducing the cost of machined components.

An adaptive cryptographic accelerator for network storage security on dynamically reconfigurable platform

NASA Astrophysics Data System (ADS)

Tang, Li; Liu, Jing-Ning; Feng, Dan; Tong, Wei

2008-12-01

Existing security solutions in network storage environment perform poorly because cryptographic operations (encryption and decryption) implemented in software can dramatically reduce system performance. In this paper we propose a cryptographic hardware accelerator on dynamically reconfigurable platform for the security of high performance network storage system. We employ a dynamic reconfigurable platform based on a FPGA to implement a PowerPCbased embedded system, which executes cryptographic algorithms. To reduce the reconfiguration latency, we apply prefetch scheduling. Moreover, the processing elements could be dynamically configured to support different cryptographic algorithms according to the request received by the accelerator. In the experiment, we have implemented AES (Rijndael) and 3DES cryptographic algorithms in the reconfigurable accelerator. Our proposed reconfigurable cryptographic accelerator could dramatically increase the performance comparing with the traditional software-based network storage systems.

Alpha-Glucan, Water Dikinase 1 Affects Starch Metabolism and Storage Root Growth in Cassava (Manihot esculenta Crantz).

PubMed

Zhou, Wenzhi; He, Shutao; Naconsie, Maliwan; Ma, Qiuxiang; Zeeman, Samuel C; Gruissem, Wilhelm; Zhang, Peng

2017-08-29

Regulation of storage root development by source strength remains largely unknown. The cassava storage root delay (srd) T-DNA mutant postpones storage root development but manifests normal foliage growth as wild-type plants. The SRD gene was identified as an orthologue of α-glucan, water dikinase 1 (GWD1), whose expression is regulated under conditions of light/dark cycles in leaves and is associated with storage root development. The GWD1-RNAi cassava plants showed both retarded plant and storage root growth, as a result of starch excess phenotypes with reduced photosynthetic capacity and decreased levels of soluble saccharides in their leaves. These leaves contained starch granules having greatly increased amylose content and type C semi-crystalline structures with increased short chains that suggested storage starch. In storage roots of GWD1-RNAi lines, maltose content was dramatically decreased and starches with much lower phosphorylation levels showed a drastically reduced β-amylolytic rate. These results suggested that GWD1 regulates transient starch morphogenesis and storage root growth by decreasing photo-assimilation partitioning from the source to the sink and by starch mobilization in root crops.

Mutations in the Cholesterol Transporter Gene ABCA5 Are Associated with Excessive Hair Overgrowth

PubMed Central

DeStefano, Gina M.; Kurban, Mazen; Anyane-Yeboa, Kwame; Dall'Armi, Claudia; Di Paolo, Gilbert; Feenstra, Heather; Silverberg, Nanette; Rohena, Luis; López-Cepeda, Larissa D.; Jobanputra, Vaidehi; Fantauzzo, Katherine A.; Kiuru, Maija; Tadin-Strapps, Marija; Sobrino, Antonio; Vitebsky, Anna; Warburton, Dorothy; Levy, Brynn; Salas-Alanis, Julio C.; Christiano, Angela M.

2014-01-01

Inherited hypertrichoses are rare syndromes characterized by excessive hair growth that does not result from androgen stimulation, and are often associated with additional congenital abnormalities. In this study, we investigated the genetic defect in a case of autosomal recessive congenital generalized hypertrichosis terminalis (CGHT) (OMIM135400) using whole-exome sequencing. We identified a single base pair substitution in the 5′ donor splice site of intron 32 in the ABC lipid transporter gene ABCA5 that leads to aberrant splicing of the transcript and a decrease in protein levels throughout patient hair follicles. The homozygous recessive disruption of ABCA5 leads to reduced lysosome function, which results in an accumulation of autophagosomes, autophagosomal cargos as well as increased endolysosomal cholesterol in CGHT keratinocytes. In an unrelated sporadic case of CGHT, we identified a 1.3 Mb cryptic deletion of chr17q24.2-q24.3 encompassing ABCA5 and found that ABCA5 levels are dramatically reduced throughout patient hair follicles. Collectively, our findings support ABCA5 as a gene underlying the CGHT phenotype and suggest a novel, previously unrecognized role for this gene in regulating hair growth. PMID:24831815

The CNS glycoprotein Shadoo has PrPC-like protective properties and displays reduced levels in prion infections

PubMed Central

Watts, Joel C; Drisaldi, Bettina; Ng, Vivian; Yang, Jing; Strome, Bob; Horne, Patrick; Sy, Man-Sun; Yoong, Larry; Young, Rebecca; Mastrangelo, Peter; Bergeron, Catherine; Fraser, Paul E; Carlson, George A; Mount, Howard T J; Schmitt-Ulms, Gerold; Westaway, David

2007-01-01

The cellular prion protein, PrPC, is neuroprotective in a number of settings and in particular prevents cerebellar degeneration mediated by CNS-expressed Doppel or internally deleted PrP (‘ΔPrP'). This paradigm has facilitated mapping of activity determinants in PrPC and implicated a cryptic PrPC-like protein, ‘π'. Shadoo (Sho) is a hypothetical GPI-anchored protein encoded by the Sprn gene, exhibiting homology and domain organization similar to the N-terminus of PrP. Here we demonstrate Sprn expression and Sho protein in the adult CNS. Sho expression overlaps PrPC, but is low in cerebellar granular neurons (CGNs) containing PrPC and high in PrPC-deficient dendritic processes. In Prnp0/0 CGNs, Sho transgenes were PrPC-like in their ability to counteract neurotoxic effects of either Doppel or ΔPrP. Additionally, prion-infected mice exhibit a dramatic reduction in endogenous Sho protein. Sho is a candidate for π, and since it engenders a PrPC-like neuroprotective activity, compromised neuroprotective activity resulting from reduced levels may exacerbate damage in prion infections. Sho may prove useful in deciphering several unresolved facets of prion biology. PMID:17703189

Large drought-induced variations in oak leaf volatile organic compound emissions during PINOT NOIR 2012

DOE PAGES

Geron, Chris; Gu, Lianhong; Daly, Ryan; ...

2015-12-17

Here, leaf-level isoprene and monoterpene emissions were collected and analyzed from five of the most abundant oak (Quercus) species in Central Missouri's Ozarks Region in 2012 during PINOT NOIR (Particle Investigations at a Northern Ozarks Tower – NOx, Oxidants, Isoprene Research). June measurements, prior to the onset of severe drought, showed isoprene emission rates and leaf temperature responses similar to those previously reported in the literature and used in Biogenic Volatile Organic Compound (BVOC) emission models. During the peak of the drought in August, isoprene emission rates were substantially reduced, and response to temperature was dramatically altered, especially for themore » species in the red oak subgenus (Erythrobalanus).« less

Integration of Photo-Patternable Low-κ Material into Advanced Cu Back-End-Of-The-Line

NASA Astrophysics Data System (ADS)

Lin, Qinghuang; Nelson, Alshakim; Chen, Shyng-Tsong; Brock, Philip; Cohen, Stephan A.; Davis, Blake; Kaplan, Richard; Kwong, Ranee; Liniger, Eric; Neumayer, Debra; Patel, Jyotica; Shobha, Hosadurga; Sooriyakumaran, Ratnam; Purushothaman, Sampath; Miller, Robert; Spooner, Terry; Wisnieff, Robert

2010-05-01

We report herein the demonstration of a simple, low-cost Cu back-end-of-the-line (BEOL) dual-damascene integration using a novel photo-patternable low-κ dielectric material concept that dramatically reduces Cu BEOL integration complexity. This κ=2.7 photo-patternable low-κ material is based on the SiCOH-based material platform and has sub-200 nm resolution capability with 248 nm optical lithography. Cu/photo-patternable low-κ dual-damascene integration at 45 nm node BEOL fatwire levels has been demonstrated with very high electrical yields using the current manufacturing infrastructure. The photo-patternable low-κ concept is, therefore, a promising technology for highly efficient semiconductor Cu BEOL manufacturing.

An extended Kalman filter approach to non-stationary Bayesian estimation of reduced-order vocal fold model parameters.

PubMed

Hadwin, Paul J; Peterson, Sean D

2017-04-01

The Bayesian framework for parameter inference provides a basis from which subject-specific reduced-order vocal fold models can be generated. Previously, it has been shown that a particle filter technique is capable of producing estimates and associated credibility intervals of time-varying reduced-order vocal fold model parameters. However, the particle filter approach is difficult to implement and has a high computational cost, which can be barriers to clinical adoption. This work presents an alternative estimation strategy based upon Kalman filtering aimed at reducing the computational cost of subject-specific model development. The robustness of this approach to Gaussian and non-Gaussian noise is discussed. The extended Kalman filter (EKF) approach is found to perform very well in comparison with the particle filter technique at dramatically lower computational cost. Based upon the test cases explored, the EKF is comparable in terms of accuracy to the particle filter technique when greater than 6000 particles are employed; if less particles are employed, the EKF actually performs better. For comparable levels of accuracy, the solution time is reduced by 2 orders of magnitude when employing the EKF. By virtue of the approximations used in the EKF, however, the credibility intervals tend to be slightly underpredicted.

How Energy Efficiency is Adding Jobs in St. Paul, Minnesota

ScienceCinema

Hannigan, Jim; Coleman, Chris; Oliver, LeAnn; Jambois, Louis

2018-02-07

Saint Paul, Minnesota is using an energy efficiency grant to provide commercial retrofits that will allow a local produce distribution company to dramatically reduce its energy costs and add dozens of new workers.

Proactive approach to transportation resource allocation under severe winter weather emergencies.

DOT National Transportation Integrated Search

2012-01-01

Severe winter weather dramatically reduces road transportation infrastructure : serviceability and decreases safety throughout Oklahoma. Although it has relatively mild winters : when compared with northern regions of the United States, Oklahoma has ...

Microwave-assisted synthesis of organics and nanomaterials

EPA Science Inventory

Microwave-assisted chemistry techniques and greener reaction media are dramatically reducing chemical waste and reaction times in several organic transformations and material synthesis. This presentation summarizes author’s own experience in developing MW-assisted chemical proces...

How Energy Efficiency is Adding Jobs in St. Paul, Minnesota

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

Hannigan, Jim; Coleman, Chris; Oliver, LeAnn

2011-01-01

Saint Paul, Minnesota is using an energy efficiency grant to provide commercial retrofits that will allow a local produce distribution company to dramatically reduce its energy costs and add dozens of new workers.

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

Wang, Yan; Wu, Jian-Feng; Tang, Yan-Yan

Highlights: • U II reduces cholesterol efflux in THP-1 macrophages. • U II decreases the expression of ABCA1. • Inhibition of the ERK/NF-κB pathway reduces U II effects on ABCA1 expression and cholesterol efflux. - Abstract: Objective: Foam cell formation in the arterial wall plays a key role in the development of atherosclerosis. Recent studies showed that Urotensin II (U II) is involved in the pathogenesis of atherosclerosis. Here we examined the effects of human U II on ATP-binding cassette transporter A1 (ABCA1) expression and the underlying mechanism in THP-1 macrophages. Methods and results: Cultured THP-1 macrophages were treated withmore » U II, followed by measuring the intracellular lipid contents, cholesterol efflux and ABCA1 levels. The results showed that U II dramatically decreased ABCA1 levels and impaired cholesterol efflux. However, the effects of U II on ABCA1 protein expression and cellular cholesterol efflux were partially reversed by inhibition of extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa B (NF-κB) activity, suggesting the potential roles of ERK1/2 and NF-κB in ABCA1 expression, respectively. Conclusion: Our current data indicate that U II may have promoting effects on the progression of atherosclerosis, likely through suppressing ABCA1 expression via activation of the ERK/NF-κB pathway and reducing cholesterol efflux to promote macrophage foam cell formation.« less

Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus.

PubMed

Yang, J; Li, Q; Yang, X; Li, M

2016-04-01

Prolactin (PRL) is known to aid effector B cells and augment autoimmunity, but the role of PRL in systemic lupus erythematosus (SLE) is not fully elucidated. The aim of this study was to determine the correlation between the serum levels of PRL and autoantibody production in SLE. Blood levels of PRL, anti-double-stranded DNA (ds-DNA) antibody, immunoglobulin M (IgM) and immunoglobulin G (IgG) were determined in samples from 30 adult patients with SLE and 25 healthy controls. The relationships between the serum level of PRL and SLE disease activity, as well as the titres of the ds-DNA antibody, IgM and IgG were determined. The serum level of PRL was higher in the SLE patients than in the healthy controls. PRL concentration increased during SLE flares-ups and decreased following disease remission. There was a positive correlation between the PRL concentration and serum levels of IgM, IgG and ds-DNA antibody titre. These data suggest that the serum level of PRL was closely related to the antibody production and disease activity of SLE patients. PRL concentration was dramatically reduced upon the remission of disease activity, indicating that PRL levels might be a promising predictor of SLE disease severity. © The Author(s) 2015.

Disease and community structure: white-nose syndrome alters spatial and temporal niche partitioning in sympatric bat species

USGS Publications Warehouse

Jachowski, David S.; Dobony, Christopher A.; Coleman, Laci S.; Ford, W. Mark; Britzke, Eric R.; Rodrigue, Jane L.

2014-01-01

AimEmerging infectious diseases present a major perturbation with apparent direct effects such as reduced population density, extirpation and/or extinction. Comparatively less is known about the potential indirect effects of disease that likely alter community structure and larger ecosystem function. Since 2006, white-nose syndrome (WNS) has resulted in the loss of over 6 million hibernating bats in eastern North America. Considerable evidence exists concerning niche partitioning in sympatric bat species in this region, and the unprecedented, rapid decline in multiple species following WNS may provide an opportunity to observe a dramatic restructuring of the bat community.LocationWe conducted our study at Fort Drum Army Installation in Jefferson and Lewis counties, New York, USA, where WNS first impacted extant bat species in winter 2007–2008.MethodsAcoustical monitoring during 2003–2011 allowed us to test the hypothesis that spatial and temporal niche partitioning by bats was relaxed post-WNS.ResultsWe detected nine bat species pre- and post-WNS. Activity for most bat species declined post-WNS. Dramatic post-WNS declines in activity of little brown bat (Myotis lucifugus, MYLU), formerly the most abundant bat species in the region, were associated with complex, often species-specific responses by other species that generally favoured increased spatial and temporal overlap with MYLU.Main conclusionsIn addition to the obvious direct effects of disease on bat populations and activity levels, our results provide evidence that disease can have cascading indirect effects on community structure. Recent occurrence of WNS in North America, combined with multiple existing stressors, is resulting in dramatic shifts in temporal and spatial niche partitioning within bat communities. These changes might influence long-term population viability of some bat species as well as broader scale ecosystem structure and function.

Necrotic cell death by hydrogen peroxide in immortal DF-1 chicken embryo fibroblast cells expressing deregulated MnSOD and catalase.

PubMed

Kim, H; You, S; Kong, B W; Foster, L K; Farris, J; Foster, D N

2001-08-22

The reactive oxygen species are known as endogenous toxic oxidant damaging factors in a variety of cell types, and in response, the antioxidant genes have been implicated in cell proliferation, senescence, immortalization, and tumorigenesis. The expression of manganese superoxide dismutase mRNA was shown to increase in most of the immortal chicken embryo fibroblast (CEF) cells tested, while expression of catalase mRNA appeared to be dramatically decreased in all immortal CEF cells compared to their primary counterparts. The expression of copper-zinc superoxide dismutase mRNA was shown to increase slightly in some immortal CEF cells. The glutathione peroxidase expressed relatively similar levels in both primary and immortal CEF cells. As primary and immortal DF-1 CEF cells were treated with 10-100 microM of hydrogen peroxide (concentrations known to be sublethal in human diploid fibroblasts), immortal DF-1 CEF cells were shown to be more sensitive to hydrogen peroxide, and total cell numbers were dramatically reduced when compared with primary cell counterparts. This increased sensitivity to hydrogen peroxide in immortal DF-1 cells occurred without evident changes in either antioxidant gene expression, mitochondrial membrane potential, cell cycle distribution or chromatin condensation. However, the total number of dead cells without chromatin condensation was dramatically elevated in immortal DF-1 CEFs treated with hydrogen peroxide, indicating that the inhibition of immortal DF-1 cell growth by low concentrations of hydrogen peroxide is due to increased necrotic cell death, but not apoptosis. Taken together, our observation suggests that the balanced antioxidant function might be important for cell proliferation in response to toxic oxidative damage by hydrogen peroxide.

Manufacturers and distributors in the U.S. hardwood lumber supply chain: Perceptions of industry trends

Treesearch

Omar Espinoza; Urs Buehlmann; Matthew Bumgardner; Bob Smith

2011-01-01

Global competition, a slowing housing market, and shifts in the customer base have contributed to reduced demand for hardwood lumber and have increased the need for specialized services by suppliers of hardwood lumber such as sawmills or distributors. Customers of hardwood lumber suppliers also have started initiatives to reduce internal costs dramatically, frequently...

'Leaner' lighting's dramatic impact.

PubMed

Kearney, Steve

2012-04-01

Steve Kearney, business manager for Newey & Eyre - Energy Saving 24/7, a team of 'energy experts' established early last year within one of the UK's leading distributors of electrical supplies, discusses the technologies and simple measures now available to reduce emissions and cut wastage generated by lighting in healthcare facilities, at a time when the NHS, especially, is under increasing pressure to reduce its carbon footprint.

The effect of peroxiredoxin 4 on fly physiology is a complex interplay of antioxidant and signaling functions

PubMed Central

Radyuk, Svetlana N.; Klichko, Vladimir I.; Michalak, Katarzyna; Orr, William C.

2013-01-01

Peroxiredoxin 4 (Prx4) has been implicated in a wide variety of biological processes, including development, progression of cancer, inflammation, and antioxidant function. The purpose of this study was to provide further insight into its multiple roles at the whole-animal level, using Drosophila. Reduced expression of dPrx4 (up to 90%) resulted in greater sensitivity to oxidative stress, an elevated H2O2 flux, and increases in lipid peroxidation, but no effect on longevity. Overexpression at low levels (<2-fold) gave reduced levels of oxidative damage and tended to show an increase in longevity. Flies expressing dPrx4 globally at high levels (>5-fold) had a dramatically reduced life span (by 20–80%) and increased apoptosis. Analysis of these overexpressors revealed an aberrant redistribution of the dPrx4 protein from the endoplasmic reticulum (ER) to cytosol and hemolymph. In addition to the known proapoptotic effects of the cytosolic form of dPrx4, dPrx4 overexpression triggered an NF-κB-mediated proinflammatory response, similar to that observed in cells under ER stress or when microbially challenged. Finally, we provide the first evidence that dPrx4, on secretion into the hemolymph, elicits a JAK/STAT-mediated response. The effects on fly survival and homeostasis appear to represent a combination of differential effects dictated in large part by dPrx4 subcellular and tissue-specific localization.—Radyuk, S. N., Klichko, V. I., Michalak, K., Orr, W. C. The effect of peroxiredoxin 4 on fly physiology is a complex interplay of antioxidant and signaling functions. PMID:23271054

Dramatically reduced surface expression of NK cell receptor KIR2DS3 is attributed to multiple residues throughout the molecule.

PubMed

VandenBussche, C J; Mulrooney, T J; Frazier, W R; Dakshanamurthy, S; Hurley, C K

2009-03-01

Using flow cytometry, fluorescent microscopy and examination of receptor glycosylation status, we demonstrate that an entire killer cell immunoglobulin-like receptor (KIR) locus (KIR2DS3)--assumed earlier to be surface expressed--appears to have little appreciable surface expression in transfected cells. This phenotype was noted for receptors encoded by three allelic variants including the common KIR2DS3*001 allele. Comparing the surface expression of KIR2DS3 with that of the better-studied KIR2DS1 molecule in two different cell lines, mutational analysis identified multiple polymorphic amino-acid residues that significantly alter the proportion of molecules present on the cell surface. A simultaneous substitution of five residues localized to the leader peptide (residues -18 and -7), second domain (residues 123 and 150) and transmembrane region (residue 234) was required to restore KIR2DS3 to the expression level of KIR2DS1. Corresponding simultaneous substitutions of KIR2DS1 to the KIR2DS3 residues resulted in a dramatically decreased surface expression. Molecular modeling was used to predict how these substitutions contribute to this phenotype. Alterations in receptor surface expression are likely to affect the balance of immune cell signaling impacting the characteristics of the response to pathogens or malignancy.

Recent increases in the large glacial-relict calanoid Limnocalanus macrurus in Lake Michigan

USGS Publications Warehouse

Barbiero, R.P.; Bunnell, D.B.; Rockwell, D.C.; Tuchman, M.L.

2009-01-01

Since 2004, population density of the large hypolimnetic calanoid Limnocalanus macrurus Sars. has increased dramatically in Lake Michigan. The average summer biomass of this species between 2004 and 2006 was roughly three times that of the period 1984–2003, and at levels unprecedented in our 22-year dataset, making L. macrurus the dominant zooplankter in the lake in terms of biomass. These increases have been accentuated by coincident population declines of the main daphnid, Daphnia mendotae, in the lake with the result that in 2006, L. macrurus accounted for 75% and 50% of the large (> 0.9 mm) crustacean biomass in the northern and southern basins of Lake Michigan, respectively. The increases in L. macrurus populations have closely coincided with equally dramatic increases in summer water clarity. Recent extinction coefficients are among the lowest recorded for the lake, and deepening light penetration has permitted increases in the size of the deep chlorophyll layer. In addition, planktivorous fish populations have declined coincidently with the increases in L. macrurus. It seems likely that an increase in sub-epilimnetic production has resulted in increased food resources for the deep-living L. macrurus, while low planktivore abundances have reduced predation loss, permitting L. macrurus to respond to these increases in sub-epilimnetic production.

Quieting Weinberg 5C: a case study in hospital noise control.

PubMed

MacLeod, Mark; Dunn, Jeffrey; Busch-Vishniac, Ilene J; West, James E; Reedy, Anita

2007-06-01

Weinberg 5C of Johns Hopkins Hospital is a very noisy hematological cancer unit in a relatively new building of a large medical campus. Because of the requirements for dealing with immuno-suppressed patients, options for introducing sound absorbing materials are limited. In this article, a case study of noise control in a hospital, the sound environment in the unit before treatment is described, the chosen noise control approach of adding custom-made sound absorbing panels is presented, and the impact of the noise control installation is discussed. The treatment of Weinberg 5C involved creating sound absorbing panels of 2-in.-thick fiberglass wrapped in an anti-bacterial fabric. Wallpaper paste was used to hold the fabric to the backing of the fiberglass. Installation of these panels on the ceiling and high on corridor walls had a dramatic effect. The noise on the unit (as measured by the equivalent sound pressure level) was immediately reduced by 5 dB(A) and the reverberation time dropped by a factor of over 2. Further, this drop in background noise and reverberation time understates the dramatic impact of the change. Surveys of staff and patients before and after the treatment indicated a change from viewing the unit as very noisy to a view of the unit as relatively quiet.

Table-driven configuration and formatting of telemetry data in the Deep Space Network

NASA Technical Reports Server (NTRS)

Manning, Evan

1994-01-01

With a restructured software architecture for telemetry system control and data processing, the NASA/Deep Space Network (DSN) has substantially improved its ability to accommodate a wide variety of spacecraft in an era of 'better, faster, cheaper'. In the new architecture, the permanent software implements all capabilities needed by any system user, and text tables specify how these capabilities are to be used for each spacecraft. Most changes can now be made rapidly, outside of the traditional software development cycle. The system can be updated to support a new spacecraft through table changes rather than software changes, reducing the implementation, test, and delivery cycle for such a change from three months to three weeks. The mechanical separation of the text table files from the program software, with tables only loaded into memory when that mission is being supported, dramatically reduces the level of regression testing required. The format of each table is a different compromise between ease of human interpretation, efficiency of computer interpretation, and flexibility.

A Connective Tissue Disorder Caused by Mutations of the Lysyl Hydroxylase 3 Gene

PubMed Central

Salo, Antti M.; Cox, Helen; Farndon, Peter; Moss, Celia; Grindulis, Helen; Risteli, Maija; Robins, Simon P.; Myllylä, Raili

2008-01-01

Lysyl hydroxylase 3 (LH3, encoded by PLOD3) is a multifunctional enzyme capable of catalyzing hydroxylation of lysyl residues and O-glycosylation of hydroxylysyl residues producing either monosaccharide (Gal) or disaccharide (Glc-Gal) derivatives, reactions that form part of the many posttranslational modifications required during collagen biosynthesis. Animal studies have confirmed the importance of LH3, particularly in biosynthesis of the highly glycosylated type IV and VI collagens, but to date, the functional significance in vivo of this enzyme in man is predominantly unknown. We report here a human disorder of LH3 presenting as a compound heterozygote with recessive inheritance. One mutation dramatically reduced the sugar-transfer activity of LH3, whereas another abrogated lysyl hydroxylase activity; these changes were accompanied by reduced LH3 protein levels in cells. The disorder has a unique phenotype causing severe morbidity as a result of features that overlap with a number of known collagen disorders. PMID:18834968

Oxidative DNA damage is instrumental in hyperreplication stress-induced inviability of Escherichia coli

PubMed Central

Charbon, Godefroid; Bjørn, Louise; Mendoza-Chamizo, Belén; Frimodt-Møller, Jakob; Løbner-Olesen, Anders

2014-01-01

In Escherichia coli, an increase in the ATP bound form of the DnaA initiator protein results in hyperinitiation and inviability. Here, we show that such replication stress is tolerated during anaerobic growth. In hyperinitiating cells, a shift from anaerobic to aerobic growth resulted in appearance of fragmented chromosomes and a decrease in terminus concentration, leading to a dramatic increase in ori/ter ratio and cessation of cell growth. Aerobic viability was restored by reducing the level of reactive oxygen species (ROS) or by deleting mutM (Fpg glycosylase). The double-strand breaks observed in hyperinitiating cells therefore results from replication forks encountering single-stranded DNA lesions generated while removing oxidized bases, primarily 8-oxoG, from the DNA. We conclude that there is a delicate balance between chromosome replication and ROS inflicted DNA damage so the number of replication forks can only increase when ROS formation is reduced or when the pertinent repair is compromised. PMID:25389264

VGLUT2-dependent sensory neurons in the TRPV1 population regulate pain and itch.

PubMed

Lagerström, Malin C; Rogoz, Katarzyna; Abrahamsen, Bjarke; Persson, Emma; Reinius, Björn; Nordenankar, Karin; Olund, Caroline; Smith, Casey; Mendez, José Alfredo; Chen, Zhou-Feng; Wood, John N; Wallén-Mackenzie, Asa; Kullander, Klas

2010-11-04

The natural response to itch sensation is to scratch, which relieves the itch through an unknown mechanism. Interaction between pain and itch has been frequently demonstrated, and the selectivity hypothesis of itch, based on data from electrophysiological and behavioral experiments, postulates the existence of primary pain afferents capable of repressing itch. Here, we demonstrate that deletion of vesicular glutamate transporter (VGLUT) 2 in a subpopulation of neurons partly overlapping with the vanilloid receptor (TRPV1) primary afferents resulted in a dramatic increase in itch behavior accompanied by a reduced responsiveness to thermal pain. The increased itch behavior was reduced by administration of antihistaminergic drugs and by genetic deletion of the gastrin-releasing peptide receptor, demonstrating a dependence on VGLUT2 to maintain normal levels of both histaminergic and nonhistaminergic itch. This study establishes that VGLUT2 is a major player in TRPV1 thermal nociception and also serves to regulate a normal itch response. Copyright © 2010 Elsevier Inc. All rights reserved.

Phospho-eIF2α Level Is Important for Determining Abilities of BACE1 Reduction to Rescue Cholinergic Neurodegeneration and Memory Defects in 5XFAD Mice

PubMed Central

Devi, Latha; Ohno, Masuo

2010-01-01

β-Site APP-cleaving enzyme 1 (BACE1) initiates amyloid-β (Aβ) generation and thus represents a prime therapeutic target in treating Alzheimer's disease (AD). Notably, increasing evidence indicates that BACE1 levels become elevated in AD brains as disease progresses; however, it remains unclear how the BACE1 upregulation may affect efficacies of therapeutic interventions including BACE1-inhibiting approaches. Here, we crossed heterozygous BACE1 knockout mice with AD transgenic mice (5XFAD model) and compared the abilities of partial BACE1 reduction to rescue AD-like phenotypes at earlier (6-month-old) and advanced (15–18-month-old) stages of disease, which expressed normal (∼100%) and elevated (∼200%) levels of BACE1, respectively. BACE1+/− deletion rescued memory deficits as tested by the spontaneous alternation Y-maze task in 5XFAD mice at the earlier stage and prevented their septohippocampal cholinergic deficits associated with significant neuronal loss. Importantly, BACE1+/− deletion was no longer able to rescue memory deficits or cholinergic neurodegeneration in 5XFAD mice at the advanced stage. Moreover, BACE1+/− deletion significantly reduced levels of Aβ42 and the β-secretase-cleaved C-terminal fragment (C99) in 6-month-old 5XFAD mouse brains, while these neurotoxic β-cleavage products dramatically elevated with age and were not affected by BACE1+/− deletion in 15–18-month-old 5XFAD brains. Interestingly, although BACE1+/− deletion lowered BACE1 expression by ∼50% in 5XFAD mice irrespective of age in concordance with the reduction in gene copy number, BACE1 equivalent to wild-type controls remained in BACE1+/−·5XFAD mice at the advanced age. In accord, phosphorylation of the translation initiation factor eIF2α, an important mediator of BACE1 elevation, was dramatically increased (∼9-fold) in 15–18-month-old 5XFAD mice and remained highly upregulated (∼6-fold) in age-matched BACE1+/−·5XFAD mice. Together, our results indicate that partial reduction of BACE1 is not sufficient to block the phospho-eIF2α-dependent BACE1 elevation during the progression of AD, thus limiting its abilities to reduce cerebral Aβ/C99 levels and rescue memory deficits and cholinergic neurodegeneration. PMID:20886088

Microwave-assisted 'greener' synthesis of organics and nanomaterials

EPA Science Inventory

Microwave selective heating techniques in conjunction with greener reaction media are dramatically reducing chemical waste and reaction times in several organic transformations and material synthesis. This presentation summarizes author’s own experience in developing MW-assisted ...

3 CFR 8940 - Proclamation 8940 of March 15, 2013. National Poison Prevention Week, 2013

Code of Federal Regulations, 2014 CFR

2014-01-01

... have dramatically reduced childhood death rates from accidental poisoning—but work remains. To keep our...-800-222-1222. Today, the majority of unintentional poisoning deaths are caused by overdoses involving...

Dramatic Increases in Maternal Opioid Use and Neonatal Abstinence Syndrome

MedlinePlus

... estimated 21,732 infants were born with NAS —equivalent to one baby suffering from opiate withdrawal born ... for back pain shows missed opportunities to prescribe non-opioid medications ( June 2018 ) Methadone and buprenorphine reduce ...

A Petunia Homeodomain-Leucine Zipper Protein, PhHD-Zip, Plays an Important Role in Flower Senescence

PubMed Central

Chang, Xiaoxiao; Donnelly, Linda; Sun, Daoyang; Rao, Jingping; Reid, Michael S.; Jiang, Cai-Zhong

2014-01-01

Flower senescence is initiated by developmental and environmental signals, and regulated by gene transcription. A homeodomain-leucine zipper transcription factor, PhHD-Zip, is up-regulated during petunia flower senescence. Virus-induced gene silencing of PhHD-Zip extended flower life by 20% both in unpollinated and pollinated flowers. Silencing PhHD-Zip also dramatically reduced ethylene production and the abundance of transcripts of genes involved in ethylene (ACS, ACO), and ABA (NCED) biosynthesis. Abundance of transcripts of senescence-related genes (SAG12, SAG29) was also dramatically reduced in the silenced flowers. Over-expression of PhHD-Zip accelerated petunia flower senescence. Furthermore, PhHD-Zip transcript abundance in petunia flowers was increased by application of hormones (ethylene, ABA) and abiotic stresses (dehydration, NaCl and cold). Our results suggest that PhHD-Zip plays an important role in regulating petunia flower senescence. PMID:24551088

A Petunia homeodomain-leucine zipper protein, PhHD-Zip, plays an important role in flower senescence.

PubMed

Chang, Xiaoxiao; Donnelly, Linda; Sun, Daoyang; Rao, Jingping; Reid, Michael S; Jiang, Cai-Zhong

2014-01-01

Flower senescence is initiated by developmental and environmental signals, and regulated by gene transcription. A homeodomain-leucine zipper transcription factor, PhHD-Zip, is up-regulated during petunia flower senescence. Virus-induced gene silencing of PhHD-Zip extended flower life by 20% both in unpollinated and pollinated flowers. Silencing PhHD-Zip also dramatically reduced ethylene production and the abundance of transcripts of genes involved in ethylene (ACS, ACO), and ABA (NCED) biosynthesis. Abundance of transcripts of senescence-related genes (SAG12, SAG29) was also dramatically reduced in the silenced flowers. Over-expression of PhHD-Zip accelerated petunia flower senescence. Furthermore, PhHD-Zip transcript abundance in petunia flowers was increased by application of hormones (ethylene, ABA) and abiotic stresses (dehydration, NaCl and cold). Our results suggest that PhHD-Zip plays an important role in regulating petunia flower senescence.

Electrical properties of zinc-oxide-based thin-film transistors using strontium-oxide-doped semiconductors

NASA Astrophysics Data System (ADS)

Wu, Shao-Hang; Zhang, Nan; Hu, Yong-Sheng; Chen, Hong; Jiang, Da-Peng; Liu, Xing-Yuan

2015-10-01

Strontium-zinc-oxide (SrZnO) films forming the semiconductor layers of thin-film transistors (TFTs) are deposited by using ion-assisted electron beam evaporation. Using strontium-oxide-doped semiconductors, the off-state current can be dramatically reduced by three orders of magnitude. This dramatic improvement is attributed to the incorporation of strontium, which suppresses carrier generation, thereby improving the TFT. Additionally, the presence of strontium inhibits the formation of zinc oxide (ZnO) with the hexagonal wurtzite phase and permits the formation of an unusual phase of ZnO, thus significantly changing the surface morphology of ZnO and effectively reducing the trap density of the channel. Project supported by the National Natural Science Foundation of China (Grant No. 6140031454) and the Innovation Program of Chinese Academy of Sciences and State Key Laboratory of Luminescence and Applications.

Polymers And Riblets Reduce Hydrodynamic Skin Friction

NASA Technical Reports Server (NTRS)

Bushnell, Dennis M.; Reed, Jason C.

1991-01-01

Polymers injected into riblet grooves dramatically reduce polymer flow rate required for drag reduction. Polymer solution injected into valleys of grooves through array of holes or slots angled downstream to keep injected streams within grooves. Injection repeated some distance downstream because volumes of grooves finite and polymer becomes depleted as slowly pulled from groove by turbulence. Potentially useful for oil tankers as means of markedly reducing cost of fuel and used extensively on submarines, other ships, and other marine vehicles.

Sources of atmospheric aerosols in Ankara (Turkey) atmosphere

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

Tuncel, S.G.; Yatin, M.; Aras, N.K.

1996-12-31

Ankara was heavily polluted owing to combustion of coal and fuel oil for space heating. Air quality over the city improved after 1993 due to use of low sulfur coal and natural gas for residential heating. These regulatory actions resulted in a dramatic decrease in SO{sub 2} concentrations measured in the air quality network, after 1990. Although concentration of particulate matter also decreased in the same period, the decrease was not as dramatic as that observed in SO{sub 2} concentrations, suggesting that sources other than space heating also contribute on observed aerosol concentrations. Currently, the concentrations of suspended particles aremore » slightly below the air quality standards effective in Turkey. A better source receptor relation must be established to reduce atmospheric levels of particulate matter. In this study, sources contributing to the observed levels of particles was determined through a receptor modeling approach. Factors controlling the observed concentrations of elements and ions were determined by relating their concentrations, to source strengths and determined by relating their concentrations, to source strengths and meteorological parameters. Residential heating was found out to be the main source of anthropogenic elements in Ankara. In the second part of the study, sources contributing on observed concentrations of elements were determined by a principal component analysis and relative contribution of each source were determined by Chemical Mass Balance study. The results indicated that, the airborne soil is the most important source of aerosol in the Ankara atmosphere during summer season, but emissions from coal combustion dominates aerosol mass during winter months.« less

A systems biology approach uncovers cellular strategies used by Methylobacterium extorquens AM1 during the switch from multi- to single-carbon growth.

PubMed

Skovran, Elizabeth; Crowther, Gregory J; Guo, Xiaofeng; Yang, Song; Lidstrom, Mary E

2010-11-24

When organisms experience environmental change, how does their metabolic network reset and adapt to the new condition? Methylobacterium extorquens is a bacterium capable of growth on both multi- and single-carbon compounds. These different modes of growth utilize dramatically different central metabolic pathways with limited pathway overlap. This study focused on the mechanisms of metabolic adaptation occurring during the transition from succinate growth (predicted to be energy-limited) to methanol growth (predicted to be reducing-power-limited), analyzing changes in carbon flux, gene expression, metabolites and enzymatic activities over time. Initially, cells experienced metabolic imbalance with excretion of metabolites, changes in nucleotide levels and cessation of cell growth. Though assimilatory pathways were induced rapidly, a transient block in carbon flow to biomass synthesis occurred, and enzymatic assays suggested methylene tetrahydrofolate dehydrogenase as one control point. This "downstream priming" mechanism ensures that significant carbon flux through these pathways does not occur until they are fully induced, precluding the buildup of toxic intermediates. Most metabolites that are required for growth on both carbon sources did not change significantly, even though transcripts and enzymatic activities required for their production changed radically, underscoring the concept of metabolic setpoints. This multi-level approach has resulted in new insights into the metabolic strategies carried out to effect this shift between two dramatically different modes of growth and identified a number of potential flux control and regulatory check points as a further step toward understanding metabolic adaptation and the cellular strategies employed to maintain metabolic setpoints.

Response of common murres to the Exxon Valdez Oil Spill and long-term changes in the Gulf of Alaska marine ecosystem

USGS Publications Warehouse

Piatt, John F.; Anderson, Paul; Rice, S.D.; Spies, R.B.; Wolfe, D.A.; Wright, B.A.

1996-01-01

Short-term effects of the 1989 TV Exxon Valdez oil spill on seabirds were dramatic and well documented. Seabird populations at sea in the spill zone were immediately depressed, and more than 30,000 dead, oiled seabirds were recovered from beaches within months of the spill. It is estimated that 250,000 seabirds were killed by oil, of which 74% were murres. Based on comparisons of prespill (1970s) and postspill (1989-1994) data, long-term effects on murres attributed to oil pollution included population declines, reduced breeding success, and delayed breeding phenology. Populations remained depressed, but breeding success phenology gradually returned to normal levels by 1993. An alternative hypothesis to explain these long-term effects is that murres were responding to natural events in their marine environment. Flow of the Alaska Coastal Current (ACC) was at an all-time low in 1989, and this may have reduced and delayed biological productivity in the ACC. On a broader time scale, marked changes in marine fish communities have occurred during the past 20 years. Coincident with cyclical fluctuations in seawater temperatures, the abundance of small forage species (e.g., humpy shrimp, capelin, and Pacific sandfish) declined precipitously in the late 1970s while populations of large predatory fish (e.g., walleye pollock, Pacific cod, and flatfish) increased dramatically. Correspondingly, seabird diets shifted from mostly capelin in the 1970s to mostly Pacific sand land and juvenile pollock in the late 1980s. Furthermore, a variety of seabirds and marine mammals both inside and outside of the oil spill zone exhibited signs of food stress (population declines, reduced productivity, die-offs) throughout the 1980s and early 1990s. We conclude that available data are inadequate to distinguish between long-term effects of the Exxon Valdez oil spill on murres and a natural response of murres to long-term changes in their marine environment.

Bacterial persistence by RNA endonucleases

PubMed Central

Maisonneuve, Etienne; Shakespeare, Lana J.; Jørgensen, Mikkel Girke; Gerdes, Kenn

2011-01-01

Bacteria form persisters, individual cells that are highly tolerant to different types of antibiotics. Persister cells are genetically identical to nontolerant kin but have entered a dormant state in which they are recalcitrant to the killing activity of the antibiotics. The molecular mechanisms underlying bacterial persistence are unknown. Here, we show that the ubiquitous Lon (Long Form Filament) protease and mRNA endonucleases (mRNases) encoded by toxin-antitoxin (TA) loci are required for persistence in Escherichia coli. Successive deletion of the 10 mRNase-encoding TA loci of E. coli progressively reduced the level of persisters, showing that persistence is a phenotype common to TA loci. In all cases tested, the antitoxins, which control the activities of the mRNases, are Lon substrates. Consistently, cells lacking lon generated a highly reduced level of persisters. Moreover, Lon overproduction dramatically increased the levels of persisters in wild-type cells but not in cells lacking the 10 mRNases. These results support a simple model according to which mRNases encoded by TA loci are activated in a small fraction of growing cells by Lon-mediated degradation of the antitoxins. Activation of the mRNases, in turn, inhibits global cellular translation, and thereby induces dormancy and persistence. Many pathogenic bacteria known to enter dormant states have a plethora of TA genes. Therefore, in the future, the discoveries described here may lead to a mechanistic understanding of the persistence phenomenon in pathogenic bacteria. PMID:21788497

Identification of a peroxisomal-targeted aldolase involved in chlorophyll biosynthesis and sugar metabolism in rice.

PubMed

Zhang, Fei; Zhang, Pan; Zhang, Yu; Wang, Shouchuang; Qu, Lianghuan; Liu, Xianqing; Luo, Jie

2016-09-01

Chlorophyll plays remarkable and critical roles in photosynthetic light-harvesting, energy transduction and plant development. In this study, we identified a rice Chl-deficient mutant, ygdl-1 (yellow green and droopy leaf-1), which showed yellow-green leaves throughout plant development with decreased content of Chls and carotene and an increased Chl a/b ratio. The ygdl-1 mutant also exhibited severe defects in chloroplast development, including disorganized grana stacks. Sequence analysis revealed that the mutant contained a T-DNA insertion within the promoter of a fructose-1,6-bisphosphate aldolase (OsAld-Y), which dramatically reduced the OsAld-Y mRNA level, and its identity was verified by transgenic complementation. Real-time PCR analysis showed that the expression levels of genes associated with chlorophyll biosynthesis and chloroplast development were concurrently altered in the ygdl-1 mutant. The expression of OsAld-Y-GFP fusion protein in tobacco epidermal cells showed that OsAld-Y was localized to the peroxisome. In addition, the analysis of primary carbon metabolites revealed the significantly reduced levels of sucrose and fructose in the mutant leaves, while the glucose content was similar to wild-type plants. Our results suggest that the OsAld-Y participates in Chl accumulation, chloroplast development and plant growth by influencing the photosynthetic rate of leaves and the sugar metabolism of rice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Sla1 adaptor-clathrin interaction regulates coat formation and progression of endocytosis.

PubMed

Tolsma, Thomas O; Cuevas, Lena M; Di Pietro, Santiago M

2018-06-01

Clathrin-mediated endocytosis is a fundamental transport pathway that depends on numerous protein-protein interactions. Testing the importance of the adaptor protein-clathrin interaction for coat formation and progression of endocytosis in vivo has been difficult due to experimental constrains. Here, we addressed this question using the yeast clathrin adaptor Sla1, which is unique in showing a cargo endocytosis defect upon substitution of 3 amino acids in its clathrin-binding motif (sla1 AAA ) that disrupt clathrin binding. Live-cell imaging showed an impaired Sla1-clathrin interaction causes reduced clathrin levels but increased Sla1 levels at endocytic sites. Moreover, the rate of Sla1 recruitment was reduced indicating proper dynamics of both clathrin and Sla1 depend on their interaction. sla1 AAA cells showed a delay in progression through the various stages of endocytosis. The Arp2/3-dependent actin polymerization machinery was present for significantly longer time before actin polymerization ensued, revealing a link between coat formation and activation of actin polymerization. Ultimately, in sla1 AAA cells a larger than normal actin network was formed, dramatically higher levels of various machinery proteins other than clathrin were recruited, and the membrane profile of endocytic invaginations was longer. Thus, the Sla1-clathrin interaction is important for coat formation, regulation of endocytic progression and membrane bending. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Simulated warming shifts the flowering phenology and sexual reproduction of Cardamine hirsuta under different Planting densities

PubMed Central

Cao, YuSong; Xiao, Yian; Huang, Haiqun; Xu, Jiancheng; Hu, Wenhai; Wang, Ning

2016-01-01

Climate warming can shift the reproductive phenology of plant, and hence dramatically reduced the reproductive capacity both of density-dependent and -independent plant species. But it is still unclear how climate warming affects flowering phenology and reproductive allocation of plant under different planting densities. Here, we assessed the impact of simulated warming on flowering phenology and sexual reproduction in the ephemeral herb Cardamine hirsuta under four densities. We found that simulated warming delayed the onset of flowering averagely for 3.6 days but preceded the end of flowering for about 1 day, which indicated climate warming shortened the duration of the flowering. And the flowering amplitude in the peak flowering day also dramatically increased in the simulated warming treatment, which caused a mass-flowering pattern. Climate warming significantly increased the weights of the fruits, seeds and seed, but reduced fruit length and sexual reproductive allocation under all the four densities. The duration of flowering was shortened and the weights of the fruits, seeds and seed, and sexual reproductive allocation were reduced under The highest density. PMID:27296893

Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion: Progesterone receptor levels may play an important role

PubMed Central

Allen, Rachael S.; Sayeed, Iqbal; Oumarbaeva, Yuliya; Morrison, Katherine C.; Choi, Paul H.; Pardue, Machelle T.; Stein, Donald G.

2018-01-01

Background/Objective To determine whether inflammation increases in retina as it does in brain following middle cerebral artery occlusion (MCAO), and whether the neurosteroid progesterone, shown to have protective effects in both retina and brain after MCAO, reduces inflammation in retina as well as brain. Methods MCAO rats treated systemically with progesterone or vehicle were compared with shams. Protein levels of cytosolic NF-κB, nuclear NF-κB, phosphorylated NF-κB, IL-6, TNF-α, CD11b, progesterone receptor A and B, and pregnane × receptor were assessed in retinas and brains at 24 and 48 h using western blots. Results Following MCAO, significant increases were observed in the following inflammatory markers: pNF-κB and CD11b at 24 h in both brain and retina, nuclear NF-κB at 24 h in brain and 48 h in retina, and TNF-α at 24 h in brain. Progesterone treatment in MCAO animals significantly attenuated levels of the following markers in brain: pNF-κB, nuclear NF-κB, IL-6, TNF-α, and CD11b, with significantly increased levels of cytosolic NF-κB. Retinas from progesterone-treated animals showed significantly reduced levels of nuclear NF-κB and IL-6 and increased levels of cytosolic NF-κB, with a trend for reduction in other markers. Post-MCAO, progesterone receptors A and B were upregulated in brain and downregulated in retina. Conclusion Inflammatory markers increased in both brain and retina after MCAO, with greater increases observed in brain. Progesterone treatment reduced inflammation, with more dramatic reductions observed in brain than retina. This differential effect may be due to differences in the response of progesterone receptors in brain and retina after injury. PMID:27802245

Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion: Progesterone receptor levels may play an important role.

PubMed

Allen, Rachael S; Sayeed, Iqbal; Oumarbaeva, Yuliya; Morrison, Katherine C; Choi, Paul H; Pardue, Machelle T; Stein, Donald G

2016-11-22

To determine whether inflammation increases in retina as it does in brain following middle cerebral artery occlusion (MCAO), and whether the neurosteroid progesterone, shown to have protective effects in both retina and brain after MCAO, reduces inflammation in retina as well as brain. MCAO rats treated systemically with progesterone or vehicle were compared with shams. Protein levels of cytosolic NF-κB, nuclear NF-κB, phosphorylated NF-κB, IL-6, TNF-α, CD11b, progesterone receptor A and B, and pregnane X receptor were assessed in retinas and brains at 24 and 48 h using western blots. Following MCAO, significant increases were observed in the following inflammatory markers: pNF-κB and CD11b at 24 h in both brain and retina, nuclear NF-κB at 24 h in brain and 48 h in retina, and TNF-α at 24 h in brain.Progesterone treatment in MCAO animals significantly attenuated levels of the following markers in brain: pNF-κB, nuclear NF-κB, IL-6, TNF-α, and CD11b, with significantly increased levels of cytosolic NF-κB. Retinas from progesterone-treated animals showed significantly reduced levels of nuclear NF-κB and IL-6 and increased levels of cytosolic NF-κB, with a trend for reduction in other markers. Post-MCAO, progesterone receptors A and B were upregulated in brain and downregulated in retina. Inflammatory markers increased in both brain and retina after MCAO, with greater increases observed in brain. Progesterone treatment reduced inflammation, with more dramatic reductions observed in brain than retina. This differential effect may be due to differences in the response of progesterone receptors in brain and retina after injury.

Melatonin mediated antidepressant-like effect in the hippocampus of chronic stress-induced depression rats: Regulating vesicular monoamine transporter 2 and monoamine oxidase A levels.

PubMed

Stefanovic, Bojana; Spasojevic, Natasa; Jovanovic, Predrag; Jasnic, Nebojsa; Djordjevic, Jelena; Dronjak, Sladjana

2016-10-01

The hippocampus is sensitive to stress which activates norepinephrine terminals deriving from the locus coeruleus. Melatonin exerts positive effects on the hippocampal neurogenic process and on depressive-like behaviour. Thus, in the present study, an examination was made of the effect of chronic melatonin treatment on norepinephrine content, synthesis, uptake, vesicular transport and degradation in the hippocampus of rats exposed to CUMS. This entailed quantifying the norephinephrine, mRNA and protein levels of DBH, NET, VMAT 2, MAO-A and COMT. The results show that CUMS evoked prolonged immobility. Melatonin treatment decreased immobility in comparison with the placebo group, reflecting an antidepressant-like effect. Compared with the placebo group, a dramatic decrease in norepinephrine content, decreased VMAT2 mRNA and protein and increased MAO-A protein levels in the hippocampus of the CUMS rats were observed. However, no significant differences in the levels of DBH, NET, COMT mRNA and protein and MAO-A mRNA levels between the placebo and the stressed groups were found. The results showed the restorative effects of melatonin on the stress-induced decline in the norepinephrine content of the hippocampus. It was observed that melatonin treatment in the CUMS rats prevented the stress-induced decrease in VMAT2 mRNA and protein levels, whereas it reduced the increase of the mRNA of COMT and protein levels of MAO-A. Chronic treatment with melatonin failed to alter the gene expression of DBH or NET in the hippocampus of the CUMS rats. Additionally, the results show that melatonin enhances VMAT2 expression and norepinephrine storage, whilst it reduces norepinephrine degrading enzymes. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Nutritional modulation of cataract

USDA-ARS?s Scientific Manuscript database

Cataract, or lens opacification, remains a major cause of blindness worldwide. Cataracts reduce vision in over eighty million people, causing blindness in eighteen million people. The number afflicted by cataract will increase dramatically as the proportion of the elderly global population increase...

Profiling 1366 Technologies: One Year Later

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

Van Mierlo, Frank; Sachs, Ely

2011-01-01

Last January, we took a look at how ARPA-E performer, 1366 Technologies is working to dramatically reduce the cost of solar energy. A year later, we revisited their headquarters in Lexington, MA to see the progress they've made.

Chemical activation by mechanochemical mixing, microwave, and ultrasonic irradiation

EPA Science Inventory

The use of emerging MW-assisted chemistry techniques in conjunction with benign reaction media is dramatically reducing chemical waste ad reaction times in several organic syntheses and chemical transformations. This editorial comments on the recent developments in mechanochemica...

Profiling 1366 Technologies: One Year Later

ScienceCinema

Van Mierlo, Frank; Sachs, Ely

2018-05-30

Last January, we took a look at how ARPA-E performer, 1366 Technologies is working to dramatically reduce the cost of solar energy. A year later, we revisited their headquarters in Lexington, MA to see the progress they've made.

Grape seed extract reduces oxidative stress and fibrosis in experimental biliary obstruction.

PubMed

Dulundu, Ender; Ozel, Yahya; Topaloglu, Umit; Toklu, Hale; Ercan, Feriha; Gedik, Nursal; Sener, Goksel

2007-06-01

The aim of this study was to assess the protective effect of grape seed extract (GSE) against oxidative liver injury and fibrosis induced by biliary obstruction in rats. Wistar albino rats were divided into four groups; control (C), GSE-treated, bile duct ligated (BDL), and BDL and GSE-treated (BDL + GSE) groups. GSE was administered at a dose of 50 mg/kg a day orally for 28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Tumor necrosis factor-alpha (TNF-alpha) and antioxidant capacity (AOC) were assayed in plasma samples. Liver tissues were taken for determination of the hepatic malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence (CL) assay. Serum AST, ALT, LDH and plasma TNF-alpha were elevated in the BDL group as compared to the control group and were significantly decreased with GSE treatment. Plasma AOC and hepatic GSH level, depressed by BDL, was elevated back to the control level in the GSE-treated BDL group. Increases in tissue MDA level, MPO activity and collagen content due to BDL were also attenuated by GSE treatment. Furthermore, luminol and lucigenin CL values in the BDL group increased dramatically compared to the control and were reduced by GSE treatment. These results suggest that GSE protects the liver from oxidative damage following bile duct ligation in rats. This effect possibly involves the inhibition of neutrophil infiltration and lipid peroxidation; thus, restoration of oxidant and antioxidant status in the tissue.

Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection.

PubMed

Berger, Christoph T; Greiff, Victor; Mehling, Matthias; Fritz, Stefanie; Meier, Marc A; Hoenger, Gideon; Conen, Anna; Recher, Mike; Battegay, Manuel; Reddy, Sai T; Hess, Christoph

2015-01-01

Vaccines dramatically reduce infection-related morbidity and mortality. Determining factors that modulate the host response is key to rational vaccine design and demands unsupervised analysis. To longitudinally resolve influenza-specific humoral immune response dynamics we constructed vaccine response profiles of influenza A- and B-specific IgM and IgG levels from 42 healthy and 31 HIV infected influenza-vaccinated individuals. Pre-vaccination antibody levels and levels at 3 predefined time points after vaccination were included in each profile. We performed hierarchical clustering on these profiles to study the extent to which HIV infection associated immune dysfunction, adaptive immune factors (pre-existing influenza-specific antibodies, T cell responses), an innate immune factor (Mannose Binding Lectin, MBL), demographic characteristics (gender, age), or the vaccine preparation (split vs. virosomal) impacted the immune response to influenza vaccination. Hierarchical clustering associated vaccine preparation and pre-existing IgG levels with the profiles of healthy individuals. In contrast to previous in vitro and animal data, MBL levels had no impact on the adaptive vaccine response. Importantly, while HIV infected subjects with low CD4 T cell counts showed a reduced magnitude of their vaccine response, their response profiles were indistinguishable from those of healthy controls, suggesting quantitative but not qualitative deficits. Unsupervised profile-based analysis ranks factors impacting the vaccine-response by relative importance, with substantial implications for comparing, designing and improving vaccine preparations and strategies. Profile similarity between HIV infected and HIV negative individuals suggests merely quantitative differences in the vaccine response in these individuals, offering a rationale for boosting strategies in the HIV infected population.

Roles of leptin, adiponectin and resistin in the transcriptional regulation of steroidogenic genes contributing to decreased Leydig cells function in obesity.

PubMed

Roumaud, Pauline; Martin, Luc J

2015-10-01

The increase in obesity rate is a major public health issue associated with increased pathological conditions such as type 2 diabetes or cardiovascular diseases. Obesity also contributes to decreased testosterone levels in men. Indeed, the adipose tissue is an endocrine organ which produces hormones such as leptin, adiponectin and resistin. Obesity results in pathological accumulations of leptin and resistin, whereas adiponectin plasma levels are markedly reduced, all having a negative impact on testosterone synthesis. This review focuses on current knowledge related to transcriptional regulation of Leydig cells' steroidogenesis by leptin, adiponectin and resistin. We show that there are crosstalks between the regulatory mechanisms of these hormones and androgen production which may result in a dramatic negative influence on testosterone plasma levels. Indeed leptin, adiponectin and resistin can impact expression of different steroidogenic genes such as Star, Cyp11a1 or Sf1. Further investigations will be required to better define the implications of adipose derived hormones on regulation of steroidogenic genes expression within Leydig cells under physiological as well as pathological conditions.

In the carotid body, galanin is a signal for neurogenesis in young, and for neurodegeneration in the old and in drug-addicted subjects

PubMed Central

Mazzatenta, Andrea; Marconi, Guya D.; Zara, Susi; Cataldi, Amelia; Porzionato, Andrea; Di Giulio, Camillo

2014-01-01

The carotid body is a highly specialized chemoreceptive structure for the detection of and reaction to hypoxia, through induction of an increase in hypoxia inducible factor. As tissue hypoxia increases with aging and can have dramatic effects in respiratory depression induced by drug addiction, we investigated the carotid body in young and old healthy subjects in comparison with drug-addicted subjects, including the expression of the neurotransmitter galanin. Galanin expression was recently reported for neuronal-like cells of the human carotid body, and it is implicated in several functions in neurons. In particular, this includes the regulation of differentiation of neural stem cells, and participation in the development and plasticity of the nervous system. Using immunohistochemistry detection, we demonstrate that galanin expression in the human carotid body in healthy older subjects and drug-addicted subjects is significantly reduced in comparison with healthy young subjects. This demonstrates not only the effects of normal aging and senescence, but also in the drug-addicted subjects, this appears to be due to a disorganization of the chemo-sensory region. With both aging and drug addiction, this results in a physiological reduction in neuronal-like cells, coupled with interlobular and intralobular increases in connective tissue fibers. Consequently, in both aging and drug addiction, this reduction of neuronal-like cells and the regeneration suggest that the carotid body is losing its sensory capabilities, with the transmission of chemoreceptive signals dramatically and vitally reduced. The level of galanin expression would thus provide a signal for neurogenesis in young subjects, and for neurodegeneration in older and drug-addicted subjects. PMID:25400591

Functional Characterization of Dihydroflavonol-4-Reductase in Anthocyanin Biosynthesis of Purple Sweet Potato Underlies the Direct Evidence of Anthocyanins Function against Abiotic Stresses

PubMed Central

Wang, Hongxia; Fan, Weijuan; Li, Hong; Yang, Jun; Huang, Jirong; Zhang, Peng

2013-01-01

Dihydroflavonol-4-reductase (DFR) is a key enzyme in the catalysis of the stereospecific reduction of dihydroflavonols to leucoanthocyanidins in anthocyanin biosynthesis. In the purple sweet potato (Ipomoea batatas Lam.) cv. Ayamurasaki, expression of the IbDFR gene was strongly associated with anthocyanin accumulation in leaves, stems and roots. Overexpression of the IbDFR in Arabidopsis tt3 mutants fully complemented the pigmentation phenotype of the seed coat, cotyledon and hypocotyl. Downregulation of IbDFR expression in transgenic sweet potato (DFRi) using an RNAi approach dramatically reduced anthocyanin accumulation in young leaves, stems and storage roots. In contrast, the increase of flavonols quercetin-3-O-hexose-hexoside and quercetin-3-O-glucoside in the leaves and roots of DFRi plants is significant. Therefore, the metabolic pathway channeled greater flavonol influx in the DFRi plants when their anthocyanin and proanthocyanidin accumulation were decreased. These plants also displayed reduced antioxidant capacity compared to the wild type. After 24 h of cold treatment and 2 h recovery, the wild-type plants were almost fully restored to the initial phenotype compared to the slower recovery of DFRi plants, in which the levels of electrolyte leakage and hydrogen peroxide accumulation were dramatically increased. These results provide direct evidence of anthocyanins function in the protection against oxidative stress in the sweet potato. The molecular characterization of the IbDFR gene in the sweet potato not only confirms its important roles in flavonoid metabolism but also supports the protective function of anthocyanins of enhanced scavenging of reactive oxygen radicals in plants under stressful conditions. PMID:24223813

Fairing Well: Aerodynamic Truck Research at NASA Dryden Flight Research Center. From Shoebox to Bat Truck and Beyond

NASA Technical Reports Server (NTRS)

Gelzer, Christian

2011-01-01

In 1973 engineers at Dryden began investigating ways to reduce aerodynamic drag on land vehicles. They began with a delivery van whose shape they changed dramatically, finally reducing its aerodynamic drag by more than 5 percent. They then turned their attention to tracator-trailers, modifying a cab-over and reducing its aerodynamic drag by nearly 25 percent. Further research identified additional areas worth attention, but in the intervening decades few of those changes have appeared.

Development of desiccant based air conditioning for hotels and motels. Final report, phase 1

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

Banks, N.J.

1994-10-01

This report contains final reports from two phases of field tests: Phase I at the Marriott Courtyard in West Palm Beach, completed in October 1991, and Phase II at the Walt Disney World Swan Hotel in Orlando, completed in August 1993. The goal was to measure the performance and reliability of the desiccant units. The successfull program proved the value of the gas-fired desiccant technology to the hospitality industry. The desiccant units reduced moisture by 15 to 20% relative humidity. Measurements of temperature, humidity, and wallboard moisture content showed a dramatic reduction in the humidity levels experienced prior to installationmore » of the units and in the control areas without desiccants. Moisture damage was kept in check and remodelling due to it was eliminated.« less

Nonlinear pulse propagation in one-dimensional metal-dielectric multilayer stacks: ultrawide bandwidth optical limiting.

PubMed

Scalora, Michael; Mattiucci, Nadia; D'Aguanno, Giuseppe; Larciprete, MariaCristina; Bloemer, Mark J

2006-01-01

We numerically study the nonlinear optical properties of metal-dielectric photonic band gap structures in the pulsed regime. We exploit the high chi3 of copper metal to induce nonlinear effects such as broadband optical limiting, self-phase modulation, and unusual spectral narrowing of high intensity pulses. We show that in a single pass through a typical, chirped multilayer stack nonlinear transmittance and peak powers can be reduced by nearly two orders of magnitude compared to low light intensity levels across the entire visible range. Chirping dielectric layer thickness dramatically improves the linear transmittance through the stack and achieves large fields inside the copper to access the large nonlinearity. At the same time, the linear properties of the stack block most of the remaining electromagnetic spectrum.

Novel Electrochemical Raman Spectroscopy Enabled by Water Immersion Objective.

PubMed

Zeng, Zhi-Cong; Hu, Shu; Huang, Sheng-Chao; Zhang, Yue-Jiao; Zhao, Wei-Xing; Li, Jian-Feng; Jiang, Chaoyang; Ren, Bin

2016-10-04

Electrochemical Raman spectroscopy is a powerful molecular level diagnostic technique for in situ investigation of adsorption and reactions on various material surfaces. However, there is still a big room to improve the optical path to meet the increasing request of higher detection sensitivity and spatial resolution. Herein, we proposed a novel electrochemical Raman setup based on a water immersion objective. It dramatically reduces mismatch of the refractive index in the light path. Consequently, significant improvement in detection sensitivity and spatial resolution has been achieved from both Zemax simulation and the experimental results. Furthermore, the thickness of electrolyte layer could be expanded to 2 mm without any influence on the signal collection. Such a thick electrolyte layer allows a much normal electrochemical response during the spectroelectrochemical investigations of the methanol oxidation.

Biosynthesis of the Halogenated Auxin, 4-Chloroindole-3-Acetic Acid1[W][OA

PubMed Central

Tivendale, Nathan D.; Davidson, Sandra E.; Davies, Noel W.; Smith, Jason A.; Dalmais, Marion; Bendahmane, Abdelhafid I.; Quittenden, Laura J.; Sutton, Lily; Bala, Raj K.; Le Signor, Christine; Thompson, Richard; Horne, James; Reid, James B.; Ross, John J.

2012-01-01

Seeds of several agriculturally important legumes are rich sources of the only halogenated plant hormone, 4-chloroindole-3-acetic acid. However, the biosynthesis of this auxin is poorly understood. Here, we show that in pea (Pisum sativum) seeds, 4-chloroindole-3-acetic acid is synthesized via the novel intermediate 4-chloroindole-3-pyruvic acid, which is produced from 4-chlorotryptophan by two aminotransferases, TRYPTOPHAN AMINOTRANSFERASE RELATED1 and TRYPTOPHAN AMINOTRANSFERASE RELATED2. We characterize a tar2 mutant, obtained by Targeting Induced Local Lesions in Genomes, the seeds of which contain dramatically reduced 4-chloroindole-3-acetic acid levels as they mature. We also show that the widespread auxin, indole-3-acetic acid, is synthesized by a parallel pathway in pea. PMID:22573801

Molecular biology of myocardial recovery.

PubMed

Zhang, Jianyi; Narula, Jagat

2004-02-01

The use of LVADs that leads to a dramatic mechanical and hemodynamic unloading of the failing left ventricle offers a unique opportunity to investigate the mechanisms of remodeling and reverse remodeling. Although it is being increasingly realized that the LVAD unloading results in regression of hypertrophy and improvement of myocyte function and LV geometry, the cellular and molecular mechanisms responsible for these beneficial effects remain undefined. The favorable alterations in geometry that occur in parallel fashion at the organ, cellular, and molecular levels are most likely caused by the reduced LV wall stress/stretch as a consequence of the mechanical support provided by LVAD. If it is confirmed that LVAD unloading can contribute significantly to reverse remodeling, the role of LVADs may graduate from bridge-to-transplantation or destination therapy to bridge-to-recovery.

FAST TRACK COMMUNICATION: High pressure study of BaFe2As2—the role of hydrostaticity and uniaxial stress

NASA Astrophysics Data System (ADS)

Duncan, W. J.; Welzel, O. P.; Harrison, C.; Wang, X. F.; Chen, X. H.; Grosche, F. M.; Niklowitz, P. G.

2010-02-01

We investigate the evolution of the electrical resistivity of BaFe2As2 single crystals with pressure. The samples used were from the same batch, grown using a self-flux method, and showed properties that were highly reproducible. Samples were pressurized using three different pressure media: pentane-isopentane (in a piston-cylinder cell), Daphne oil (in an alumina anvil cell) and steatite (in a Bridgman cell). Each pressure medium has its own intrinsic level of hydrostaticity, which dramatically affects the phase diagram. An increasing uniaxial pressure component in this system quickly reduces the spin density wave order and favours the appearance of superconductivity, which is similar to what is seen in SrFe2As2.

Chlorination and safe storage of household drinking water in developing countries to reduce waterborne disease.

PubMed

Sobsey, M D; Handzel, T; Venczel, L

2003-01-01

Simple, effective and affordable methods are needed to treat and safely store non-piped, gathered household water. This study evaluated point-of-use chlorination and storage in special plastic containers of gathered household water for improving microbial quality and reducing diarrhoeal illness of consumers living under conditions of poor sanitation and hygiene. Community families were recruited and randomly divided into intervention (household water chlorination and storage in a special container) and control (no intervention) households. Microbes in stored household water were extensively inactivated by 1-5-mg/L doses of hypochlorite. Escherichia coli levels in stored household waters were < 1/100 mL in most intervention households but readily detectable at high levels in control households. Stored water of intervention households was also lower in Clostridium perfringens and heterotrophic plate count bacteria than in control households. The intervention reduced household diarrhoeal illness. In Bolivia, monthly episodes of household diarrhoeal illness were 1.25 and 2.2 in intervention and control families, respectively (P = < 0.002) indicating that 43% of community diarrhoea was preventable by using the intervention. In Bangladesh, mean episodes of child diarrhoea/1,000 d were 19.6 and 24.8 in intervention and control groups respectively (P = < 0.03) indicating that about 24% of observed diarrhoea was preventable by using the intervention. Chlorine disinfection and storage in an appropriate container significantly improved the microbiological quality of non-piped household drinking water and reduced community diarrhoeal disease. Widespread use of this simple treatment and storage system for non-piped domestic water has the potential to dramatically reduce the global burden of waterborne diarrhoeal disease.

T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells.

PubMed

Leiva-Salcedo, Elias; Perez, Viviana; Acuña-Castillo, Claudio; Walter, Robin; Sierra, Felipe

2002-01-01

Serum levels of T-kininogen increase dramatically as rats approach the end of their lifespan. Stable expression of the protein in Balb/c 3T3 fibroblasts leads to a dramatic inhibition of cell proliferation, as well as inhibition of the ERK signaling pathway. T-kininogen is a potent inhibitor of cysteine proteinases, and we have described that the inhibition of ERK activity occurs, at least in part, via stabilization of the MAP kinase phosphatase, MKP-1. Since fibroblasts are not a physiological target of T-kininogen, we have now purified the protein from rat serum, and used it to assess the effect of T-kininogen on endothelial cells. Adding purified T-kininogen to EAhy 926 hybridoma cells resulted in inhibition of basal ERK activity levels, as estimated using appropriate anti-phospho ERK antibodies. Furthermore, exogenously added T-kininogen inhibited the activation of the ERK pathway induced by either bradykinin or T-kinin. We conclude that the age-related increase in hepatic T-kininogen gene expression and serum levels of the protein could have dramatic consequences on endothelial cell physiology, both under steady state conditions, and after activation by cell-specific stimuli. Our results are consistent with T-kininogen being an important modulator of the senescent phenotype in vivo.

Effects of Persistent Atrial Fibrillation-Induced Electrical Remodeling on Atrial Electro-Mechanics - Insights from a 3D Model of the Human Atria.

PubMed

Adeniran, Ismail; MacIver, David H; Garratt, Clifford J; Ye, Jianqiao; Hancox, Jules C; Zhang, Henggui

2015-01-01

Atrial stunning, a loss of atrial mechanical contraction, can occur following a successful cardioversion. It is hypothesized that persistent atrial fibrillation-induced electrical remodeling (AFER) on atrial electrophysiology may be responsible for such impaired atrial mechanics. This simulation study aimed to investigate the effects of AFER on atrial electro-mechanics. A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4 states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2-3 months after cardioversion (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodeled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+ content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+ transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished. This study provides novel insights into understanding atrial electro-mechanics illustrating that AFER impairs atrial contraction due to reduced intracellular Ca2+ transients.

Effective Dust Control Systems on Concrete Dowel Drilling Machinery

PubMed Central

Echt, Alan S.; Sanderson, Wayne T.; Mead, Kenneth R.; Feng, H. Amy; Farwick, Daniel R.; Farwick, Dawn Ramsey

2016-01-01

Rotary-type percussion dowel drilling machines, which drill horizontal holes in concrete pavement, have been documented to produce respirable crystalline silica concentrations above recommended exposure criteria. This places operators at potential risk for developing health effects from exposure. United States manufacturers of these machines offer optional dust control systems. The effectiveness of the dust control systems to reduce respirable dust concentrations on two types of drilling machines was evaluated under controlled conditions with the machines operating inside large tent structures in an effort to eliminate secondary exposure sources not related to the dowel-drilling operation. Area air samples were collected at breathing zone height at three locations around each machine. Through equal numbers of sampling rounds with the control systems randomly selected to be on or off, the control systems were found to significantly reduce respirable dust concentrations from a geometric mean of 54 mg per cubic meter to 3.0 mg per cubic meter on one machine and 57 mg per cubic meter to 5.3 mg per cubic meter on the other machine. This research shows that the dust control systems can dramatically reduce respirable dust concentrations by over 90% under controlled conditions. However, these systems need to be evaluated under actual work conditions to determine their effectiveness in reducing worker exposures to crystalline silica below hazardous levels. PMID:27074062

Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model

PubMed Central

Labrie, Viviane; Fukumura, Ryutaro; Rastogi, Anjali; Fick, Laura J.; Wang, Wei; Boutros, Paul C.; Kennedy, James L.; Semeralul, Mawahib O.; Lee, Frankie H.; Baker, Glen B.; Belsham, Denise D.; Barger, Steven W.; Gondo, Yoichi; Wong, Albert H.C.; Roder, John C.

2009-01-01

Abnormal N-methyl-d-aspartate receptor (NMDAR) function has been implicated in the pathophysiology of schizophrenia. d-serine is an important NMDAR modulator, and to elucidate the role of the d-serine synthesis enzyme serine racemase (Srr) in schizophrenia, we identified and characterized mice with an ENU-induced mutation that results in a complete loss of Srr activity and dramatically reduced d-serine levels. Mutant mice displayed behaviors relevant to schizophrenia, including impairments in prepulse inhibition, sociability and spatial discrimination. Behavioral deficits were exacerbated by an NMDAR antagonist and ameliorated by d-serine or the atypical antipsychotic clozapine. Expression profiling revealed that the Srr mutation influenced several genes that have been linked to schizophrenia and cognitive ability. Transcript levels altered by the Srr mutation were also normalized by d-serine or clozapine treatment. Furthermore, analysis of SRR genetic variants in humans identified a robust association with schizophrenia. This study demonstrates that aberrant Srr function and diminished d-serine may contribute to schizophrenia pathogenesis. PMID:19483194

Warming and Resource Availability Shift Food Web Structure and Metabolism

PubMed Central

O'Connor, Mary I.; Piehler, Michael F.; Leech, Dina M.; Anton, Andrea; Bruno, John F.

2009-01-01

Climate change disrupts ecological systems in many ways. Many documented responses depend on species' life histories, contributing to the view that climate change effects are important but difficult to characterize generally. However, systematic variation in metabolic effects of temperature across trophic levels suggests that warming may lead to predictable shifts in food web structure and productivity. We experimentally tested the effects of warming on food web structure and productivity under two resource supply scenarios. Consistent with predictions based on universal metabolic responses to temperature, we found that warming strengthened consumer control of primary production when resources were augmented. Warming shifted food web structure and reduced total biomass despite increases in primary productivity in a marine food web. In contrast, at lower resource levels, food web production was constrained at all temperatures. These results demonstrate that small temperature changes could dramatically shift food web dynamics and provide a general, species-independent mechanism for ecological response to environmental temperature change. PMID:19707271

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

Borer, Elizabeth T.; et al, et al

Human alterations to nutrient cycles1,2 and herbivore communities3–7 are affecting global biodiversity dramatically2. Ecological theory predicts these changes should be strongly counteractive: nutrient addition drives plant species loss through intensified competition for light, whereas herbivores prevent competitive exclusion by increasing ground-level light, particularly in productive systems8,9. Here we use experimental data spanning a globally relevant range of conditions to test the hypothesis that herbaceous plant species losses caused by eutrophication may be offset by increased light availability due to herbivory. This experiment, replicated in 40 grasslands on 6 continents, demonstrates that nutrients and herbivores can serve as counteracting forces tomore » control local plant diversity through light limitation, independent of site productivity, soil nitrogen, herbivore type and climate. Nutrient addition consistently reduced local diversity through light limitation, and herbivory rescued diversity at sites where it alleviated light limitation. Thus, species loss from anthropogenic eutrophication can be ameliorated in grasslands where herbivory increases ground-level light.« less

The nature of outsourced preclinical research--the example of chemical synthesis.

PubMed

Festel, Gunter W

2013-09-01

The possibility to buy standardized external services or even new and innovative methods within drug discovery has increased dramatically during the last decades. Service providers are able to provide timely and efficient solutions to any given problem within preclinical research. The outsourcing behavior depends on the specific company type. Generally, the outsourcing level of emerging pharmaceutical and biotechnology companies is much higher than established companies due to low or missing internal resources. Whereas the "make-or-buy" decisions of large and fully integrated pharmaceutical companies are mainly competency driven, those of mid-size and small pharmaceutical, as well as biotech companies show a specific combination of cost/capacity and competency. The three different cooperation models "price competition", "project selection," and "strategic partnership" were identified. For all types of companies, the cooperation model of "strategic partnership" offers access to high-level expertise while reducing fixed costs and complexity. This was shown using chemical synthesis as an example but is also true for other areas of preclinical research.

Electrochemical Evaluation of trans-Resveratrol Levels in Red Wine Based on the Interaction between Resveratrol and Graphene.

PubMed

Liu, Lantao; Zhou, Yanli; Kang, Yiyu; Huang, Haihong; Li, Congming; Xu, Maotian; Ye, Baoxian

2017-01-01

trans -Resveratrol is often considered as one of the quality standards of red wine, and the development of a sensitive and reliable method for monitoring the trans -resveratrol levels in red wine is an urgent requirement for the quality control. Here, a novel voltammetric approach was described for probing trans -resveratrol using a graphene-modified glassy carbon (GC) electrode. The proposed electrode was prepared by one-step electrodeposition of reduced graphene oxide (ERGO) at a GC electrode. Compared with the bare GC electrode, the introduced graphene film on the electrode surface dramatically improved the sensitivity of the sensor response due to the π - π interaction between the graphene and trans -resveratrol. The developed sensor exhibited low detection limit of 0.2  μ M with wide linear range of 0.8-32  μ M and high stability. For the analysis of trans -resveratrol in red wine, the high anti-interference ability and the good recoveries indicated the great potential for practical applications.

Electrochemical Evaluation of trans-Resveratrol Levels in Red Wine Based on the Interaction between Resveratrol and Graphene

PubMed Central

Liu, Lantao; Kang, Yiyu; Huang, Haihong; Li, Congming; Ye, Baoxian

2017-01-01

trans-Resveratrol is often considered as one of the quality standards of red wine, and the development of a sensitive and reliable method for monitoring the trans-resveratrol levels in red wine is an urgent requirement for the quality control. Here, a novel voltammetric approach was described for probing trans-resveratrol using a graphene-modified glassy carbon (GC) electrode. The proposed electrode was prepared by one-step electrodeposition of reduced graphene oxide (ERGO) at a GC electrode. Compared with the bare GC electrode, the introduced graphene film on the electrode surface dramatically improved the sensitivity of the sensor response due to the π-π interaction between the graphene and trans-resveratrol. The developed sensor exhibited low detection limit of 0.2 μM with wide linear range of 0.8–32 μM and high stability. For the analysis of trans-resveratrol in red wine, the high anti-interference ability and the good recoveries indicated the great potential for practical applications. PMID:28819581

AUTOMATION OF EXPERIMENTS WITH A HAND-HELD PROGRAMMABLE CALCULATOR

EPA Science Inventory

Technological developments have dramatically reduced the cost of data collection, experimental control and computation. Products are now available which allow automation of experiments both in the laboratory and in the field at substantially lower cost and with less technical exp...

Connected vehicle applications for adaptive overhead lighting (on-demand lighting) : final research report.

DOT National Transportation Integrated Search

2016-07-01

The Virginia Tech Transportation Institute (VTTI) has developed an on-demand roadway lighting : system and has tested the systems effect on driver visual performance. On-demand roadway : lighting can dramatically reduce energy usage while maintain...

Microwave-assisted transformations and synthesis of polymer nanocomposites and nanomaterials

EPA Science Inventory

The use of emerging MW-assisted chemistry techniques in conjunction with greener reaction media is dramatically reducing chemical waste and reaction times in several organic transformations and material synthesis. This account summarizes our own experience in developing MW-assist...

Air-Microfluidics: Creating Small, Low-cost, Portable Air Quality Sensors

EPA Science Inventory

Air-microfluidics shows great promise in dramatically reducing the size, cost, and power requirements of future air quality sensors without compromising their accuracy. Microfabrication provides a suite of relatively new tools for the development of micro electro mechanical syste...

The synthesis and applications of a micro-pine-structured nanocatalyst

EPA Science Inventory

The use of emerging MW-assisted chemistry techniques in conjunction with benign reaction media is dramatically reducing chemical waste and reaction times in several organic syntheses and chemical transformations. This editorial comments on the recent developments in mechanochemic...

Underwater sound from vessel traffic reduces the effective communication range in Atlantic cod and haddock.

PubMed

Stanley, Jenni A; Van Parijs, Sofie M; Hatch, Leila T

2017-11-07

Stellwagen Bank National Marine Sanctuary is located in Massachusetts Bay off the densely populated northeast coast of the United States; subsequently, the marine inhabitants of the area are exposed to elevated levels of anthropogenic underwater sound, particularly due to commercial shipping. The current study investigated the alteration of estimated effective communication spaces at three spawning locations for populations of the commercially and ecologically important fishes, Atlantic cod (Gadus morhua) and haddock (Melanogrammus aeglefinus). Both the ambient sound pressure levels and the estimated effective vocalization radii, estimated through spherical spreading models, fluctuated dramatically during the three-month recording periods. Increases in sound pressure level appeared to be largely driven by large vessel activity, and accordingly exhibited a significant positive correlation with the number of Automatic Identification System tracked vessels at the two of the three sites. The near constant high levels of low frequency sound and consequential reduction in the communication space observed at these recording sites during times of high vocalization activity raises significant concerns that communication between conspecifics may be compromised during critical biological periods. This study takes the first steps in evaluating these animals' communication spaces and alteration of these spaces due to anthropogenic underwater sound.

Collective efficacy, family attachment, and urban adolescent suicide attempts.

PubMed

Maimon, David; Browning, Christopher R; Brooks-Gunn, Jeanne

2010-09-01

The suicide rate among American adolescents between the ages of 14-25 has dramatically increased during the last 50 years, and this fact has been the focus of extensive social-scientific investigation. To date, however, research focusing on the joint effects of mental health, family, and contextual-level predictors on adolescents' suicidal behaviors is scarce. Drawing on Durkheim's classic macro-level approach to suicide and collective efficacy theory, we use data from the Project on Human Development in Chicago Neighborhoods (PHDCN) to examine the effect of informal social controls on adolescents' suicide attempts. Analyzing reports from 990 youth, we examine the hypothesis that neighborhood-level collective efficacy and family-level integration and social control independently affect suicide attempts. We also examine the extent to which they interact in their effects on suicidal behavior. Overall, results from multilevel logit models support the Durkheimian expectation that family attachment reduces the probability that adolescents will attempt suicide. The effect of collective efficacy is interactive in nature. Specifically, we find that collective efficacy significantly enhances the protective effect of family attachment and support on adolescent suicidal behaviors. We discuss findings within the context of social control theory.

Collective Efficacy, Family Attachment, and Urban Adolescent Suicide Attempts

PubMed Central

Maimon, David; Browning, Christopher R.; Brooks-Gunn, Jeanne

2011-01-01

The suicide rate among American adolescents between the ages of 14–25 has dramatically increased during the last 50 years, and this fact has been the focus of extensive social-scientific investigation. To date, however, research focusing on the joint effects of mental health, family, and contextual-level predictors on adolescents’ suicidal behaviors is scarce. Drawing on Durkheim’s classic macro-level approach to suicide and collective efficacy theory, we use data from the Project on Human Development in Chicago Neighborhoods (PHDCN) to examine the effect of informal social controls on adolescents’ suicide attempts. Analyzing reports from 990 youth, we examine the hypothesis that neighborhood-level collective efficacy and family-level integration and social control independently affect suicide attempts. We also examine the extent to which they interact in their effects on suicidal behavior. Overall, results from multilevel logit models support the Durkheimian expectation that family attachment reduces the probability that adolescents will attempt suicide. The effect of collective efficacy is interactive in nature. Specifically, we find that collective efficacy significantly enhances the protective effect of family attachment and support on adolescent suicidal behaviors. We discuss findings within the context of social control theory. PMID:20943592

CatB is Critical for Total Catalase Activity and Reduces Bactericidal Effects of Phenazine-1-Carboxylic Acid on Xanthomonas oryzae pv. oryzae and X. oryzae pv. oryzicola.

PubMed

Pan, Xiayan; Wu, Jian; Xu, Shu; Duan, Yabing; Zhou, Mingguo

2017-02-01

Rice bacterial leaf blight, caused by Xanthomonas oryzae pv. oryzae, and rice bacterial leaf streak, caused by X. oryzae pv. oryzicola, are major diseases of rice. Phenazine-1-carboxylic acid (PCA) is a natural product that is isolated from Pseudomonas spp. and is used to control many important rice diseases in China. We previously reported that PCA disturbs the redox balance, which results in the accumulation of reactive oxygen species in X. oryzae pv. oryzae. In this study, we found that PCA significantly upregulated the transcript levels of catB and katE, which encode catalases, and that PCA sensitivity was reduced when X. oryzae pvs. oryzae and oryzicola were cultured with exogenous catalase. Furthermore, catB deletion mutants of X. oryzae pvs. oryzae and oryzicola showed dramatically decreased total catalase activity, increased sensitivity to PCA, and reduced virulence in rice. In contrast, deletion mutants of srpA and katG, which also encode catalases, exhibited little change in PCA sensitivity. The results indicate that catB in both X. oryzae pvs. oryzae and oryzicola encodes a catalase that helps protect the bacteria against PCA-induced stress.

Erosion-corrosion resistance properties of 316L austenitic stainless steels after low-temperature liquid nitriding

NASA Astrophysics Data System (ADS)

Zhang, Xiangfeng; Wang, Jun; Fan, Hongyuan; Pan, Dong

2018-05-01

The low-temperature liquid nitriding of stainless steels can result in the formation of a surface zone of so-called expanded austenite (S-phase) by the dissolution of large amounts of nitrogen in the solid solution and formation of a precipitate-free layer supersaturated with high hardness. Erosion-corrosion measurements were performed on low-temperature nitrided and non-nitrided 316L stainless steels. The total erosion-corrosion, erosion-only, and corrosion-only wastages were measured directly. As expected, it was shown that low-temperature nitriding dramatically reduces the degree of erosion-corrosion in stainless steels, caused by the impingement of particles in a corrosive medium. The nitrided 316L stainless steels exhibited an improvement of almost 84% in the erosion-corrosion resistance compared to their non-nitrided counterparts. The erosion-only rates and synergistic levels showed a general decline after low-temperature nitriding. Low-temperature liquid nitriding can not only reduce the weight loss due to erosion but also significantly reduce the weight loss rate of interactions, so that the total loss of material decreased evidently. Therefore, 316L stainless steels displayed excellent erosion-corrosion behaviors as a consequence of their highly favorable corrosion resistances and superior wear properties.

Diagnostic accuracy at several reduced radiation dose levels for CT imaging in the diagnosis of appendicitis

NASA Astrophysics Data System (ADS)

Zhang, Di; Khatonabadi, Maryam; Kim, Hyun; Jude, Matilda; Zaragoza, Edward; Lee, Margaret; Patel, Maitraya; Poon, Cheryce; Douek, Michael; Andrews-Tang, Denise; Doepke, Laura; McNitt-Gray, Shawn; Cagnon, Chris; DeMarco, John; McNitt-Gray, Michael

2012-03-01

Purpose: While several studies have investigated the tradeoffs between radiation dose and image quality (noise) in CT imaging, the purpose of this study was to take this analysis a step further by investigating the tradeoffs between patient radiation dose (including organ dose) and diagnostic accuracy in diagnosis of appendicitis using CT. Methods: This study was IRB approved and utilized data from 20 patients who underwent clinical CT exams for indications of appendicitis. Medical record review established true diagnosis of appendicitis, with 10 positives and 10 negatives. A validated software tool used raw projection data from each scan to create simulated images at lower dose levels (70%, 50%, 30%, 20% of original). An observer study was performed with 6 radiologists reviewing each case at each dose level in random order over several sessions. Readers assessed image quality and provided confidence in their diagnosis of appendicitis, each on a 5 point scale. Liver doses at each case and each dose level were estimated using Monte Carlo simulation based methods. Results: Overall diagnostic accuracy varies across dose levels: 92%, 93%, 91%, 90% and 90% across the 100%, 70%, 50%, 30% and 20% dose levels respectively. And it is 93%, 95%, 88%, 90% and 90% across the 13.5-22mGy, 9.6-13.5mGy, 6.4-9.6mGy, 4-6.4mGy, and 2-4mGy liver dose ranges respectively. Only 4 out of 600 observations were rated "unacceptable" for image quality. Conclusion: The results from this pilot study indicate that the diagnostic accuracy does not change dramatically even at significantly reduced radiation dose.

Antibiotic prophylaxis in the era of multidrug-resistant bacteria.

PubMed

Wittekamp, Bastiaan H J; Bonten, Marc J M

2012-06-01

The prophylactic use of antibiotics can only be justified when clinical benefits on relevant patient outcomes, such as morbidity or mortality, cost-effectiveness, and absence of immediate emergence of antibiotic resistance have been unequivocally demonstrated. In some intensive care unit (ICU) patients, antibiotic prophylaxis is used as part of selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD). Recent trials in ICUs with low levels of antibiotic resistance strongly suggest that both regimens reduce the incidence of ICU-acquired infections and improve patient survival. Naturally, the unique microbial ecology of such settings reduce generalizability of results. Therefore, the routine use of SOD and SDD remains highly controversial, especially in ICUs with higher levels of antibiotic resistance. Moreover, convincing evidence is still missing on several important aspects related to efficacy and safety. Despite numerous trials, effects of SDD and SOD on antibiotic resistance during and after decolonization treatment have still been insufficiently investigated, and existing results are contradicting. Furthermore, the effects of both regimens on the non-culturable part of the intestinal flora remain unknown. Finally, cost-effectiveness has not been thoroughly investigated, and prices of the antimicrobial agents that have been used have increased dramatically in recent years. In this review, important knowledge gaps that so far prevent the widespread use of SDD and SOD will be addressed.

α-Syntrophin stabilizes catalase to reduce endogenous reactive oxygen species levels during myoblast differentiation.

PubMed

Moon, Jae Yun; Choi, Su Jin; Heo, Cheol Ho; Kim, Hwan Myung; Kim, Hye Sun

2017-07-01

α-Syntrophin is a component of the dystrophin-glycoprotein complex that interacts with various intracellular signaling proteins in muscle cells. The α-syntrophin knock-down C2 cell line (SNKD), established by infecting lentivirus particles with α-syntrophin shRNA, is characterized by a defect in terminal differentiation and increase in cell death. Since myoblast differentiation is accompanied by intensive mitochondrial biogenesis, the generation of intracellular reactive oxygen species (ROS) is also increased during myogenesis. Two-photon microscopy imaging showed that excessive intracellular ROS accumulated during the differentiation of SNKD cells as compared with control cells. The formation of 4-hydroxynonenal adduct, a byproduct of lipid peroxidation during oxidative stress, significantly increased in differentiated SNKD myotubes and was dramatically reduced by epigallocatechin-3-gallate, a well-known ROS scavenger. Among antioxidant enzymes, catalase was significantly decreased during differentiation of SNKD cells without changes at the mRNA level. Of interest was the finding that the degradation of catalase was rescued by MG132, a proteasome inhibitor, in the SNKD cells. This study demonstrates a novel function of α-syntrophin. This protein plays an important role in the regulation of oxidative stress from endogenously generated ROS during myoblast differentiation by modulating the protein stability of catalase. © 2017 Federation of European Biochemical Societies.

Tensile stress-dependent fracture behavior and its influences on photovoltaic characteristics in flexible PbS/CdS thin-film solar cells.

PubMed

Lee, Seung Min; Yeon, Deuk Ho; Mohanty, Bhaskar Chandra; Cho, Yong Soo

2015-03-04

Tensile stress-dependent fracture behavior of flexible PbS/CdS heterojunction thin-film solar cells on indium tin oxide-coated polyethylene terephthalate (PET) substrates is investigated in terms of the variations of fracture parameters with applied strains and their influences on photovoltaic properties. The PbS absorber layer that exhibits only mechanical cracks within the applied strain range from ∼0.67 to 1.33% is prepared by chemical bath deposition at different temperatures of 50, 70, and 90 °C. The PbS thin films prepared at 50 °C demonstrate better mechanical resistance against the applied bending strain with the highest crack initiating bending strain of ∼1.14% and the lowest saturated crack density of 0.036 μm(-1). Photovoltaic properties of the cells depend on the deposition temperature and the level of applied tensile stress. The values of short-circuit current density and fill factor are dramatically reduced above a certain level of applied strain, while open-circuit voltage is nearly maintained. The dependency of photovoltaic properties on the progress of fractures is understood as related to the reduced fracture energy and toughness, which is limitedly controllable by microstructural features of the absorber layer.

Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice.

PubMed

Jung, Dae Young; Ko, Hwi Jin; Lichtman, Eben I; Lee, Eunjung; Lawton, Elizabeth; Ong, Helena; Yu, Kristine; Azuma, Yoshihiro; Friedline, Randall H; Lee, Ki Won; Kim, Jason K

2013-05-01

Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.

Catalase (KatA) Plays a Role in Protection against Anaerobic Nitric Oxide in Pseudomonas aeruginosa

PubMed Central

Su, Shengchang; Panmanee, Warunya; Wilson, Jeffrey J.; Mahtani, Harry K.; Li, Qian; VanderWielen, Bradley D.; Makris, Thomas M.; Rogers, Melanie; McDaniel, Cameron; Lipscomb, John D.; Irvin, Randall T.; Schurr, Michael J.; Lancaster, Jack R.; Kovall, Rhett A.; Hassett, Daniel J.

2014-01-01

Pseudomonas aeruginosa (PA) is a common bacterial pathogen, responsible for a high incidence of nosocomial and respiratory infections. KatA is the major catalase of PA that detoxifies hydrogen peroxide (H2O2), a reactive oxygen intermediate generated during aerobic respiration. Paradoxically, PA displays elevated KatA activity under anaerobic growth conditions where the substrate of KatA, H2O2, is not produced. The aim of the present study is to elucidate the mechanism underlying this phenomenon and define the role of KatA in PA during anaerobiosis using genetic, biochemical and biophysical approaches. We demonstrated that anaerobic wild-type PAO1 cells yielded higher levels of katA transcription and expression than aerobic cells, whereas a nitrite reductase mutant ΔnirS produced ∼50% the KatA activity of PAO1, suggesting that a basal NO level was required for the increased KatA activity. We also found that transcription of the katA gene was controlled, in part, by the master anaerobic regulator, ANR. A ΔkatA mutant and a mucoid mucA22 ΔkatA bacteria demonstrated increased sensitivity to acidified nitrite (an NO generator) in anaerobic planktonic and biofilm cultures. EPR spectra of anaerobic bacteria showed that levels of dinitrosyl iron complexes (DNIC), indicators of NO stress, were increased significantly in the ΔkatA mutant, and dramatically in a ΔnorCB mutant compared to basal levels of DNIC in PAO1 and ΔnirS mutant. Expression of KatA dramatically reduced the DNIC levels in ΔnorCB mutant. We further revealed direct NO-KatA interactions in vitro using EPR, optical spectroscopy and X-ray crystallography. KatA has a 5-coordinate high spin ferric heme that binds NO without prior reduction of the heme iron (K d ∼6 μM). Collectively, we conclude that KatA is expressed to protect PA against NO generated during anaerobic respiration. We proposed that such protective effects of KatA may involve buffering of free NO when potentially toxic concentrations of NO are approached. PMID:24663218

Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.

PubMed

Warren, Emily Booth; Aicher, Aidan Edward; Fessel, Joshua Patrick; Konradi, Christine

2017-01-01

Mitochondrial DNA (mtDNA), the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD) patients who had developed L-DOPA Induced Dyskinesia (LID), compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr) treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.

Increasing Marriage Will Dramatically Reduce Child Poverty. A Report of the Heritage Center for Data Analysis.

ERIC Educational Resources Information Center

Rector, Robert E.; Johnson, Kirk A.; Fagan, Patrick F.; Noyes, Lauren R.

This report uses data from the Fragile Families and Child Well-Being Study (a nationwide survey that collects data on married and non-married parents at the time of the child's birth) to determine how much marriage could reduce poverty among couples who are not married at the time of birth. To determine the impact of marriage on children's and…

Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice.

PubMed

Villarroya, Joan; Dorado, Beatriz; Vilà, Maya R; Garcia-Arumí, Elena; Domingo, Pere; Giralt, Marta; Hirano, Michio; Villarroya, Francesc

2011-01-01

Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues. © 2011 Villarroya et al.

Thymidine Kinase 2 Deficiency-Induced Mitochondrial DNA Depletion Causes Abnormal Development of Adipose Tissues and Adipokine Levels in Mice

PubMed Central

Villarroya, Joan; Dorado, Beatriz; Vilà, Maya R.; Garcia-Arumí, Elena; Domingo, Pere; Giralt, Marta; Hirano, Michio; Villarroya, Francesc

2011-01-01

Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues. PMID:22216345

NREL in the News | Transportation Research | NREL

Science.gov Websites

Promises Power Electronics Innovation Wide bandgap (WBG) technology promises to dramatically increase performance, reduce cost, and improve reliability of electronics packaging in electric-drive vehicles and Department's new Manufacturing Innovation Institute for Next Generation Power Electronics to accelerate

Greener and Expeditious Synthesis of Bioactive Heterocycles using Microwave Irradiation

EPA Science Inventory

The utilization of green chemistry techniques is dramatically reducing chemical waste and reaction times as has recently been proven in several organic syntheses and chemical transformations. To illustrate these advantages in the synthesis of bio-active heterocycles, we have stud...

Microwave-Assisted Organic Synthesis and Transformations using Benign Reaction Media

EPA Science Inventory

The nonclassical heating technique using microwaves, termed as 'Bunsen burner of the 21st century, is rapidly becoming popular and is dramatically reducing the reaction times. The significant outcomes of microwave (MW)-assisted green chemistry endeavors are summarized that have r...

Oncologists partner with Watson on genomics.

PubMed

2015-08-01

A new collaboration between IBM Watson Health and more than a dozen cancer centers uses the power of cognitive computing to dramatically reduce the time it takes to analyze data from patients' DNA and identify targeted treatment options. ©2015 American Association for Cancer Research.

NREL’s Advanced Analytics Research for Buildings – Social Media Version

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

None

Forty percent of the total energy consumption in the United States comes from buildings. Working together, we can dramatically shrink that number. NREL’s advanced analytics research has already proven to reduce energy use, save money, and stabilize the grid.

Suppressor of cytokine signaling 1 modulates invasion and metastatic potential of colorectal cancer cells.

PubMed

David, Muriel; Naudin, Cécile; Letourneur, Martine; Polrot, Mélanie; Renoir, Jack-Michel; Lazar, Vladimir; Dessen, Philippe; Roche, Serge; Bertoglio, Jacques; Pierre, Josiane

2014-07-01

Suppressor of cytokine signaling (SOCS) 1 is an inducible negative regulator of cytokine signaling but its role in human cancer is not completely established. Here we report that, while SOCS1 is expressed in normal colonic epithelium and colon adenocarcinomas, its level decreases during progression of colon adenocarcinomas, the lowest level being found in the most aggressive stage and least differentiated carcinomas. Forced expression of SOCS1 in metastatic colorectal SW620 cells reverses many characteristics of Epithelial-Mesenchymal Transition (EMT), as highlighted by the disappearance of the transcription factor ZEB1 and the mesenchymal form of p120ctn and the re-expression of E-cadherin. Furthermore, miRNA profiling indicated that SOCS1 also up-regulates the expression of the mir-200 family of miRNAs, which can promote the mesenchymal-epithelial transition and reduce tumor cell migration. Accordingly, overexpression of SOCS1 induced cell morphology changes and dramatically reduced tumor cell invasion in vitro. When injected in nude mice, SOCS1-expressing SW620 cells induced metastases in a smaller number of animals than parental SW620 cells, and did not generate any adrenal gland or bone metastasis. Overall, our results suggest that SOCS1 controls metastatic progression of colorectal tumors by preventing the mesenchymal-epithelial transition (MET), including E-cadherin expression. This pathway may be associated with survival to colorectal cancer by reducing the capacity of generating metastases. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Ro52-mediated Monoubiquitination of IKKβ Down-regulates NF-κB Signalling

PubMed Central

Wada, Keiji; Niida, Motoko; Tanaka, Makoto; Kamitani, Tetsu

2009-01-01

Upon activation, NF-κB translocates into the nucleus and initiates biological events. This NF-κB signalling is mainly regulated by the protein kinase IKKβ. Early in this signalling pathway, IKKβ is phosphorylated for activation by several factors, such as pro-inflammatory cytokines and the Tax oncoprotein of HTLV-1. In cells infected by HTLV-1, IKKβ is persistently phosphorylated and conjugated with monoubiquitin due to Tax expression. Although this Tax-induced monoubiquitination appears to be an important regulation system for IKKβ, how the monoubiquitination occurs is unknown and its role in NF-κB signalling is still unclear. Here, we show that an E3-ubiquitin ligase Ro52 interacts weakly with wild-type IKKβ but strongly with a phosphomimetic mutant IKKβ to conjugate monoubiquitin in cooperation with an E2-ubiquitin-conjugating enzyme UbcH5B. These results suggest that the Tax-induced phosphorylation of IKKβ causes an interaction with Ro52 for the subsequent monoubiquitination. NF-κB reporter assays have shown that the IKKβ activity is suppressed by wild-type Ro52, but not by its inactive mutant. In addition, monoubiquitin fusion of IKKβ reduced its activity for NF-κB signalling. We also found that Ro52 dramatically reduces the level of Tax. These results suggest that Ro52 down-regulates Tax-induced NF-κB signalling by monoubiquitinating IKKβ and by reducing the level of Tax. PMID:19675099

Green revolution trees: semidwarfism transgenes modify gibberellins, promote root growth, enhance morphological diversity, and reduce competitiveness in hybrid poplar.

PubMed

Elias, Ani A; Busov, Victor B; Kosola, Kevin R; Ma, Cathleen; Etherington, Elizabeth; Shevchenko, Olga; Gandhi, Harish; Pearce, David W; Rood, Stewart B; Strauss, Steven H

2012-10-01

Semidwarfism has been used extensively in row crops and horticulture to promote yield, reduce lodging, and improve harvest index, and it might have similar benefits for trees for short-rotation forestry or energy plantations, reclamation, phytoremediation, or other applications. We studied the effects of the dominant semidwarfism transgenes GA Insensitive (GAI) and Repressor of GAI-Like, which affect gibberellin (GA) action, and the GA catabolic gene, GA 2-oxidase, in nursery beds and in 2-year-old high-density stands of hybrid poplar (Populus tremula × Populus alba). Twenty-nine traits were analyzed, including measures of growth, morphology, and physiology. Endogenous GA levels were modified in most transgenic events; GA(20) and GA(8), in particular, had strong inverse associations with tree height. Nearly all measured traits varied significantly among genotypes, and several traits interacted with planting density, including aboveground biomass, root-shoot ratio, root fraction, branch angle, and crown depth. Semidwarfism promoted biomass allocation to roots over shoots and substantially increased rooting efficiency with most genes tested. The increased root proportion and increased leaf chlorophyll levels were associated with changes in leaf carbon isotope discrimination, indicating altered water use efficiency. Semidwarf trees had dramatically reduced growth when in direct competition with wild-type trees, supporting the hypothesis that semidwarfism genes could be effective tools to mitigate the spread of exotic, hybrid, and transgenic plants in wild and feral populations.

Green Revolution Trees: Semidwarfism Transgenes Modify Gibberellins, Promote Root Growth, Enhance Morphological Diversity, and Reduce Competitiveness in Hybrid Poplar1[C][W][OA

PubMed Central

Elias, Ani A.; Busov, Victor B.; Kosola, Kevin R.; Ma, Cathleen; Etherington, Elizabeth; Shevchenko, Olga; Gandhi, Harish; Pearce, David W.; Rood, Stewart B.; Strauss, Steven H.

2012-01-01

Semidwarfism has been used extensively in row crops and horticulture to promote yield, reduce lodging, and improve harvest index, and it might have similar benefits for trees for short-rotation forestry or energy plantations, reclamation, phytoremediation, or other applications. We studied the effects of the dominant semidwarfism transgenes GA Insensitive (GAI) and Repressor of GAI-Like, which affect gibberellin (GA) action, and the GA catabolic gene, GA 2-oxidase, in nursery beds and in 2-year-old high-density stands of hybrid poplar (Populus tremula × Populus alba). Twenty-nine traits were analyzed, including measures of growth, morphology, and physiology. Endogenous GA levels were modified in most transgenic events; GA20 and GA8, in particular, had strong inverse associations with tree height. Nearly all measured traits varied significantly among genotypes, and several traits interacted with planting density, including aboveground biomass, root-shoot ratio, root fraction, branch angle, and crown depth. Semidwarfism promoted biomass allocation to roots over shoots and substantially increased rooting efficiency with most genes tested. The increased root proportion and increased leaf chlorophyll levels were associated with changes in leaf carbon isotope discrimination, indicating altered water use efficiency. Semidwarf trees had dramatically reduced growth when in direct competition with wild-type trees, supporting the hypothesis that semidwarfism genes could be effective tools to mitigate the spread of exotic, hybrid, and transgenic plants in wild and feral populations. PMID:22904164

BTBR T+tf/J MICE: AUTISM-RELEVANT BEHAVIORS AND REDUCED FRACTONE-ASSOCIATED HEPARAN SULFATE

PubMed Central

Blanchard, D. Caroline; Defensor, Erwin B.; Meyza, Ksenia Z.; Pobbe, Roger L.H.; Pearson, Brandon L.; Bolivar, Valerie J.; Blanchard, Robert J.

2011-01-01

BTBR T+tf/J (BTBR) mice have emerged as strong candidates to serve as models of a range of autism-relevant behaviors, showing deficiencies in social behaviors; reduced or unusual ultrasonic vocalizations in conspecific situations; and enhanced, repetitive self grooming. Recent studies have described their behaviors in a seminatural Visible Burrow System (VBS); a social proximity test in which avoidance of a conspecific is impossible; and in an object approach and investigation test evaluating attention to specific objects and potential stereotypies in the order of approaching/investigating objects. VBS results confirmed strong BTBR avoidance of conspecifics and in the social proximity test, BTBR showed dramatic differences in several close-in behaviors, including specific avoidance of a nose-to-nose contact that may potentially be related to gaze-avoidance. Diazepam normalized social avoidance by BTBRs in a three-chamber test, and some additional behaviors –but not nose to nose avoidance- in the social proximity test. BTBR also showed higher levels of preference for particular objects, and higher levels of sequences investigating 3- or 4- objects in the same order. Heparan sulfate (HS) associated with fractal structures in the subventricular zone of the lateral ventricles was severely reduced in BTBR. HS may modulate the functions of a range of growth and guidance factors during development, and HS abnormalities are associated with relevant brain (callosal agenesis) and behavioral (reductions in sociality) changes; suggesting the value of examination of the dynamics of the HS system in the context of autism. PMID:21741402

α-1 Antitrypsin Enhances Islet Engraftment by Suppression of Instant Blood-Mediated Inflammatory Reaction.

PubMed

Wang, Jingjing; Sun, Zhen; Gou, Wenyu; Adams, David B; Cui, Wanxing; Morgan, Katherine A; Strange, Charlie; Wang, Hongjun

2017-04-01

Islet cell transplantation has limited effectiveness because of an instant blood-mediated inflammatory reaction (IBMIR) that occurs immediately after cell infusion and leads to dramatic β-cell death. In intraportal islet transplantation models using mouse and human islets, we demonstrated that α-1 antitrypsin (AAT; Prolastin-C), a serine protease inhibitor used for the treatment of AAT deficiency, inhibits IBMIR and cytokine-induced inflammation in islets. In mice, more diabetic recipients reached normoglycemia after intraportal islet transplantation when they were treated with AAT compared with mice treated with saline. AAT suppressed blood-mediated coagulation pathways by diminishing tissue factor production, reducing plasma thrombin-antithrombin complex levels and fibrinogen deposition on islet grafts, which correlated with less graft damage and apoptosis. AAT-treated mice showed reduced serum tumor necrosis factor-α levels, decreased lymphocytic infiltration, and decreased nuclear factor (NF)-κB activation compared with controls. The potent anti-inflammatory effect of AAT is possibly mediated by suppression of c-Jun N-terminal kinase (JNK) phosphorylation. Blocking JNK activation failed to further reduce cytokine-induced apoptosis in β-cells. Taken together, AAT significantly improves islet graft survival after intraportal islet transplantation by mitigation of coagulation in IBMIR and suppression of cytokine-induced JNK and NF-κB activation. AAT-based therapy has the potential to improve graft survival in human islet transplantation and other cellular therapies on the horizon. © 2017 by the American Diabetes Association.

Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium.

PubMed Central

Dalton, T; Fu, K; Enders, G C; Palmiter, R D; Andrews, G K

1996-01-01

Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. Transgenic and control males were injected with cadmium, and the histology of the testes was examined. An injection of 7.5 mumol Cd/kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 mumol Cd/kg caused rapid changes in the histology of the testes and resulted in pronounced testicular necrosis in both control and transgenic mice. Female transgenic and control mice were mated and then injected with cadmium (30-45 mumol Cd/kg) on the day of blastocyst implantation (day 4). In both of these groups, injection of cadmium reduced pregnancy rate, and no dramatic protection was afforded by maternal and/or embryonic overexpression of MT. Thus, overexpression of MT-I does not significantly protect against either of these cadmium-induced effects on fertility. Images Figure 1. A Figure 1. B Figure 2. A Figure 2. B Figure 2. C Figure 3. Figure 4. A Figure 4. A Figure 4. B Figure 4. B Figure 4. B Figure 4. B Figure 4. D4 Figure 4. D4 Figure 4. D6 Figure 4. D6 Figure 4. D8 Figure 5. A Figure 5. B Figure 5. C Figure 5. D Figure 5. E Figure 6. A Figure 6. B Figure 6. C Figure 6. D Figure 6. E Figure 6. F PMID:8834864

Policing the drunk driver: measuring law enforcement involvement in reducing alcohol-impaired driving.

PubMed

Dula, Chris S; Dwyer, William O; LeVerne, Gilbert

2007-01-01

With many thousands of deaths still annually attributable to driving under the influence (DUI), it remains imperative that we continually address the problem of producing and sustaining effective countermeasures, and that we subject these efforts to empirical scrutiny. This article presents relevant findings from state-wide datasets. A formula generating a potentially useful metric for assessing aspects of the DUI prosecutorial chain is presented, focusing on the rate of proactive DUI arrests. While in need of cautious interpretation due to issues of inherent inaccuracies in large databases, small numbers of crashes and/or arrests in multiple jurisdictions, and the lack of replication in other states, the analyses show no relationship between the level of DUI arrest activity and DUI-related crashes. This finding brings into question the efficacy of the many millions of dollars devoted each year to targeted DUI enforcement, as it is currently being implemented. Results are discussed in terms of developing adequate disincentives to DUI so as to raise general deterrence via dramatic increases in proactive DUI enforcement and then engaging in pervasive and persistent social marketing of such efforts to maximize the perception that arrest and punishment for DUI is always imminent, that penalties will be swift, certain, and severe. It is echoed that accurate data need to be collected at all levels of the DUI arrest and prosecution process in every jurisdiction within a state, so as to facilitate the empirical assessment of countermeasure efficacy in reducing alcohol-related crashes. Given that this work needs to be replicated, the impact on the traffic safety industry is potentially huge. The present data indicate that law enforcement efforts to further abate DUI-related crashes are apparently ineffective, though likely necessary to maintain reductions achieved in the 80s and early 90s. Thus, to attain additional systematic reductions, a dramatic increase in enforcement will be necessary as will a diversification of abatement efforts, including an increase in aggressive social marketing tactics to positively impact our traffic safety culture by making DUI universally unacceptable (for a discussion of this latter issue and on the use of positive reinforcement to change driver behavior, see Dula & Geller, 2007).

Identification of a Novel EF-Loop in the N-terminus of TRPM2 Channel Involved in Calcium Sensitivity

PubMed Central

Luo, Yuhuan; Yu, Xiafei; Ma, Cheng; Luo, Jianhong; Yang, Wei

2018-01-01

As an oxidative stress sensor, transient receptor potential melastatin 2 (TRPM2) channel is involved in many physiological and pathological processes including warmth sensing, ischemia injury, inflammatory diseases and diabetes. Intracellular calcium is critical for TRPM2 channel activation and the IQ-like motif in the N-terminus has been shown to be important by mediating calmodulin binding. Sequence analysis predicted two potential EF-loops in the N-terminus of TRPM2. Site-directed mutagenesis combining with functional assay showed that substitution with alanine of several residues, most of which are conserved in the typical EF-loop, including D267, D278, D288, and E298 dramatically reduced TRPM2 channel currents. By further changing the charges or side chain length of these conserved residues, our results indicate that the negative charge of D267 and the side chain length of D278 are critical for calcium-induced TRPM2 channel activation. G272I mutation also dramatically reduced the channel currents, suggesting that this site is critical for calcium-induced TRPM2 channel activation. Furthermore, D267A mutant dramatically reduced the currents induced by calcium alone compared with that by ADPR, indicating that D267 residue in D267–D278 motif is the most important site for calcium sensitivity of TRPM2. In addition, inside-out recordings showed that mutations at D267, G272, D278, and E298 had no effect on single-channel conductance. Taken together, our data indicate that D267–D278 motif in the N-terminus as a novel EF-loop is critical for calcium-induced TRPM2 channel activation.

Charging effects in single InP/GaInP baby dots

NASA Astrophysics Data System (ADS)

Persson, Jonas

2001-03-01

It has recently been demonstrated that the matrix material plays a major role for the physical behavior of self-assembled InP/GaInP quantum dots. As the "intrinsically" n-type GaInP matrix fills the quantum dot with electrons the spectral behavior of the dot dramatically changes. For the larger, fully developed dots, the charging gives rise to several broad lines. With an external bias it is possible to reduce the electron population of the dot. For smaller dots, baby dots, we show the possibility of dramatically changing the appearance of the dot spectrum by a precise tuning of the size of the quantum dot. When the dot is small enough it is uncharged and the spectrum is very similar to other material systems, whereas a slightly larger dot is charged and the number of lines is dramatically increased. We present high spectral resolution photoluminescence measurements of individual InP/GaInP baby-dots and k\\cdotp calculations including direct and exchange interactions.

A Systems Biology Approach Uncovers Cellular Strategies Used by Methylobacterium extorquens AM1 During the Switch from Multi- to Single-Carbon Growth

PubMed Central

Skovran, Elizabeth; Crowther, Gregory J.; Guo, Xiaofeng; Yang, Song; Lidstrom, Mary E.

2010-01-01

Background When organisms experience environmental change, how does their metabolic network reset and adapt to the new condition? Methylobacterium extorquens is a bacterium capable of growth on both multi- and single-carbon compounds. These different modes of growth utilize dramatically different central metabolic pathways with limited pathway overlap. Methodology/Principal Findings This study focused on the mechanisms of metabolic adaptation occurring during the transition from succinate growth (predicted to be energy-limited) to methanol growth (predicted to be reducing-power-limited), analyzing changes in carbon flux, gene expression, metabolites and enzymatic activities over time. Initially, cells experienced metabolic imbalance with excretion of metabolites, changes in nucleotide levels and cessation of cell growth. Though assimilatory pathways were induced rapidly, a transient block in carbon flow to biomass synthesis occurred, and enzymatic assays suggested methylene tetrahydrofolate dehydrogenase as one control point. This “downstream priming” mechanism ensures that significant carbon flux through these pathways does not occur until they are fully induced, precluding the buildup of toxic intermediates. Most metabolites that are required for growth on both carbon sources did not change significantly, even though transcripts and enzymatic activities required for their production changed radically, underscoring the concept of metabolic setpoints. Conclusions/Significance This multi-level approach has resulted in new insights into the metabolic strategies carried out to effect this shift between two dramatically different modes of growth and identified a number of potential flux control and regulatory check points as a further step toward understanding metabolic adaptation and the cellular strategies employed to maintain metabolic setpoints. PMID:21124828

Effects of Oxidation on Oxidation-Resistant Graphite

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

Windes, William; Smith, Rebecca; Carroll, Mark

2015-05-01

The Advanced Reactor Technology (ART) Graphite Research and Development Program is investigating doped nuclear graphite grades that exhibit oxidation resistance through the formation of protective oxides on the surface of the graphite material. In the unlikely event of an oxygen ingress accident, graphite components within the VHTR core region are anticipated to oxidize so long as the oxygen continues to enter the hot core region and the core temperatures remain above 400°C. For the most serious air-ingress accident which persists over several hours or days the continued oxidation can result in significant structural damage to the core. Reducing the oxidationmore » rate of the graphite core material during any air-ingress accident would mitigate the structural effects and keep the core intact. Previous air oxidation testing of nuclear-grade graphite doped with varying levels of boron-carbide (B4C) at a nominal 739°C was conducted for a limited number of doped specimens demonstrating a dramatic reduction in oxidation rate for the boronated graphite grade. This report summarizes the conclusions from this small scoping study by determining the effects of oxidation on the mechanical strength resulting from oxidation of boronated and unboronated graphite to a 10% mass loss level. While the B4C additive did reduce mechanical strength loss during oxidation, adding B4C dopants to a level of 3.5% or more reduced the as-fabricated compressive strength nearly 50%. This effectively minimized any benefits realized from the protective film formed on the boronated grades. Future work to infuse different graphite grades with silicon- and boron-doped material as a post-machining conditioning step for nuclear components is discussed as a potential solution for these challenges in this report.« less

Tenebrio molitor Gram-negative-binding protein 3 (TmGNBP3) is essential for inducing downstream antifungal Tenecin 1 gene expression against infection with Beauveria bassiana JEF-007.

PubMed

Yang, Yi-Ting; Lee, Mi Rong; Lee, Se Jin; Kim, Sihyeon; Nai, Yu-Shin; Kim, Jae Su

2017-05-23

The Toll signaling pathway is responsible for defense against both Gram-positive bacteria and fungi. Gram-negative binding protein 3 (GNBP3) has a strong affinity for the fungal cell wall component, β-1,3-glucan, which can activate the prophenoloxidase (proPO) cascade and induce the Toll signaling pathway. Myeloid differentiation factor 88 (MyD88) is an intracellular adaptor protein involved in the Toll signaling pathway. In this study, we monitored the response of 5 key genes (TmGNBP3, TmMyD88, and Tenecin 1, 2, and 3) in the Toll pathway of the mealworm Tenebrio molitor immune system against the fungus Beauveria bassiana JEF-007 using RT-PCR. TmGNBP3, Tenecin 1, and Tenecin 2 were significantly upregulated after fungal infection. To better understand the roles of the Toll signaling pathway in the mealworm immune system, TmGNBP3 and TmMyD88 were knocked down by RNAi silencing. Target gene expression levels decreased at 2 d postknockdown and were dramatically reduced at 6 d post-dsRNA injection. Therefore, mealworms were compromised by B. bassiana JEF-007 at 6 d post-dsRNA injection. Silencing of TmMyD88 and TmGNBP3 resulted in reduced resistance of the host to fungal infection. Particularly, reducing TmGNBP3 levels obviously downregulated Tenecin 1 and Tenecin 2 expression levels, whereas silencing TmMyD88 expression resulted in decreased Tenecin 2 expression. These results indicate that TmGNBP3 is essential to induce downstream antifungal peptide Tenecin 1 expression against B. bassiana JEF-007. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Effects of a short-course MDMA binge on dopamine transporter binding and on levels of dopamine and its metabolites in adult male rats

PubMed Central

Biezonski, Dominik K.; Piper, Brian J.; Shinday, Nina M.; Kim, Peter J.; Ali, Syed F.; Meyer, Jerrold S.

2013-01-01

Although the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is often described as a selective serotonergic neurotoxin, some research has challenged this view. The objective of this study was to determine the influence of MDMA on subsequent levels of two different markers of dopaminergic function, the dopamine transporter (DAT) as well as dopamine and its major metabolites. In experiment I, adult male Sprague–Dawley rats were administered either a low or moderate dose MDMA binge (2.5 or 5.0 mg/kg × 4 with an inter-dose interval of 1 h) or saline, and were killed 1 week later. The moderate dose dramatically reduced [3H]WIN 35,428 binding to striatal DAT by 73.7% (P ≤ 0.001). In experiment II, animals were binged with a higher dose of MDMA (10 mg/kg × 4) to determine the drug’s effects on concentrations of serotonin (5-HT), dopamine, and their respective major metabolites 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum and frontal cortex 1 week later. As expected, MDMA significantly reduced 5-HT and 5-HIAA (≥ 50%) in these structures, while only a marginal decrease in dopamine was noted in the striatum. In contrast, levels of DOPAC (34.3%, P < 0.01) and HVA (33.5%, P < 0.001) were reduced by MDMA treatment, suggesting a decrease in dopamine turnover. Overall, these findings indicate that while serotonergic markers are particularly vulnerable to MDMA-induced depletion, significant dopaminergic deficits may also occur under some conditions. Importantly, DAT expression may be more vulnerable to perturbation by MDMA than dopamine itself. PMID:23276666

A preliminary study on the role of the complement regulatory protein, cluster of differentiation 55, in mice with diabetic neuropathic pain.

PubMed

Nie, Fachuan; Su, Dong; Shi, Ying; Chen, Jinmei; Wang, Haihui; Qin, Wanxiang; Chen, Yaohua; Wang, Suxia; Li, Lei

2015-03-01

The aim of this study was to investigate the role of the complement regulatory protein cluster of differentiation 55 (CD55) in the pathogenesis of diabetic neuropathic pain (DNP). Healthy adult male C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ) in order to induce DNP. Peripheral blood glucose and protein, and the mRNA expression levels of C3 and CD55 in the spinal cord were determined. In addition, the behaviors of these mice were observed. The results showed that STZ‑treated mice displayed the clinical manifestations of diabetes mellitus, and that their peripheral blood glucose was markedly increased. On the 21st and 28th days following the STZ injection, the mechanical pain threshold and thermal pain threshold of the mice were dramatically reduced (P<0.05). |Additionally, 14 days post‑STZ injection, the mRNA expression of C3 in the spinal cord was significantly increased, which continued for 28 days. On the 21st and 28th days, the number of C3 positive cells in the spinal cord was markedly increased. Seven days after the STZ injection, the number of cells positive for CD55 was markedly reduced in the spinal dorsal horn and subsequently remained at a low level. The mRNA expression of CD55 also was significantly reduced (P<0.05) and remained so for 28 days. The reduction in the expression levels of CD55 occurred earlier than the changes in the expression of C3, suggesting that the downregulation of CD55 expression precedes, and has an important role regarding, the activation of C3 in the occurrence and development of DNP.

Disease ecology and the global emergence of zoonotic pathogens.

PubMed

Wilcox, Bruce A; Gubler, Duane J

2005-09-01

The incidence and frequency of epidemic transmission of zoonotic diseases, both known and newly recognized, has increased dramatically in the past 30 years. It is thought that this dramatic disease emergence is primarily the result of the social, demographic, and environmental transformation that has occurred globally since World War II. However, the causal linkages have not been elucidated. Investigating emerging zoonotic pathogens as an ecological phenomenon can provide significant insights as to why some of these pathogens have jumped species and caused major epidemics in humans. A review of concepts and theory from biological ecology and of causal factors in disease emergence previously described suggests a general model of global zoonotic disease emergence. The model links demographic and societal factors to land use and land cover change whose associated ecological factors help explain disease emergence. The scale and magnitude of these changes are more significant than those associated with climate change, the effects of which are largely not yet understood. Unfortunately, the complex character and non-linear behavior of the human-natural systems in which host-pathogen systems are embedded makes specific incidences of disease emergence or epidemics inherently difficult to predict. Employing a complex systems analytical approach, however, may show how a few key ecological variables and system properties, including the adaptive capacity of institutions, explains the emergence of infectious diseases and how an integrated, multi-level approach to zoonotic disease control can reduce risk.

Quantum dynamics of tunneling dominated reactions at low temperatures

NASA Astrophysics Data System (ADS)

Hazra, Jisha; Balakrishnan, N.

2015-05-01

We report a quantum dynamics study of the Li + HF → LiF + H reaction at low temperatures of interest to cooling and trapping experiments. Contributions from non-zero partial waves are analyzed and results show narrow resonances in the energy dependence of the cross section that survive partial wave summation. The computations are performed using the ABC code and a simple modification of the ABC code that enables separate energy cutoffs for the reactant and product rovibrational energy levels is found to dramatically reduce the basis set size and computational expense. Results obtained using two ab initio electronic potential energy surfaces for the LiHF system show strong sensitivity to the choice of the potential. In particular, small differences in the barrier heights of the two potential surfaces are found to dramatically influence the reaction cross sections at low energies. Comparison with recent measurements of the reaction cross section (Bobbenkamp et al 2011 J. Chem. Phys. 135 204306) shows similar energy dependence in the threshold regime and an overall good agreement with experimental data compared to previous theoretical results. Also, usefulness of a recently introduced method for ultracold reactions that employ the quantum close-coupling method at short-range and the multichannel quantum defect theory at long-range, is demonstrated in accurately evaluating product state-resolved cross sections for D + H2 and H + D2 reactions.

Development and Pilot Randomized Control Trial of a Drama Program to Enhance Well-being Among Older Adults

PubMed Central

Moore, Raeanne C.; Straus, Elizabeth; Dev, Sheena I.; Parish, Steven M.; Sueko, Seema; Eyler, Lisa T.

2016-01-01

Objective Develop a novel theatre-based program and test its feasibility, tolerability, and preliminary efficacy for improving empathy/compassion and well-being among older adults. Method Thirteen older adults were randomized to a 6-week Drama Workshop (DW) program or time-equivalent Backstage Pass (BP) control condition. Pre- and post-treatment measures included empathy, compassion, and mood scales. Additional post-treatment measures included self-rated change in empathy/compassion, confidence, and affect. Participants also rated their mood/affect after each session. Results The program was successfully completed and well-liked. No pre-to-post-treatment changes in empathy/compassion or mood symptoms were found in either group. Compared to BP, DW weekly ratings indicated higher levels of anxiety and lower happiness; however, the DW program had higher self-ratings of positive change in self-esteem, confidence, and happiness post-treatment. Discussion While the DW may not promote empathy/compassion and was personally challenging during the program, engagement in dramatic exercises and rehearsing and performing a dramatic piece was seen by participants as a positive growth experience, as indicated by the post-treatment ratings of enhanced self-esteem, confidence and happiness. Thus, such a program might be useful for counteracting some of the potential negative aspects of aging, including reduced self-efficacy due to physical limitations and negative affect due to losses. PMID:28503015

Severe Alterations in Lipid Composition of Frontal Cortex Lipid Rafts from Parkinson’s Disease and Incidental Parkinson’s Disease

PubMed Central

Fabelo, Noemí; Martín, Virginia; Santpere, Gabriel; Marín, Raquel; Torrent, Laia; Ferrer, Isidre; Díaz, Mario

2011-01-01

Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein–lipid and protein–protein interactions. We purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson’s disease (PD) and incidental Parkinson’s disease (iPD) subjects and analyzed their lipid composition. We observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paralleling these findings, unsaturation and peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint a dramatic increase in lipid raft order due to the aberrant biochemical structure in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal cortex occur at early stages of PD pathology. The findings correlate with abnormal lipid raft signaling and cognitive decline observed during the development of these neurodegenerative disorders. PMID:21717034

Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4

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

Song, Jun; Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX; Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX

2010-02-26

Objective: The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Strategies to reduce lipid accumulation in macrophages may have therapeutic potential for preventing and treating atherosclerosis and cardiovascular complications. The antidiabetic drug metformin has been reported to reduce lipid accumulation in adipocytes. In this study, we examined the effects of metformin on lipid accumulation in macrophages and investigated the mechanisms involved. Methods and results: We observed that metformin significantly reduced palmitic acid (PA)-induced intracellular lipid accumulation in macrophages. Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4)more » which was involved in PA-induced lipid accumulation. Quantitative real-time PCR showed that metformin regulates FABP4 expression at the transcriptional level. We identified forkhead transcription factor FOXO1 as a positive regulator of FABP4 expression. Inhibiting FOXO1 expression with FOXO1 siRNA significantly reduced basal and PA-induced FABP4 expression. Overexpression of wild-type FOXO1 and constitutively active FOXO1 significantly increased FABP4 expression, whereas dominant negative FOXO1 dramatically decreased FABP4 expression. Metformin reduced FABP4 expression by promoting FOXO1 nuclear exclusion and subsequently inhibiting its activity. Conclusions: Taken together, these results suggest that metformin reduces lipid accumulation in macrophages by repressing FOXO1-mediated FABP4 transcription. Thus, metformin may have a protective effect against lipid accumulation in macrophages and may serve as a therapeutic agent for preventing and treating atherosclerosis in metabolic syndrome.« less

Organo- and nano-catalyst in greener reaction medium: Microwave-assisted expedient synthesis of fine chemicals

EPA Science Inventory

The use of emerging microwave (MW) -assisted chemistry techniques is dramatically reducing chemical waste and reaction times in several organic syntheses and chemical transformations. A brief account of our experiences in developing MW-assisted organic transformations, which invo...

Internal curing as a new tool for infrastructural renewal : reducing repair congestion, increasing service life, and improving sustainability.

DOT National Transportation Integrated Search

2014-04-01

Internal curing has recently been developed as a new concrete technology that has the potential to : dramatically extend the service life of concrete infrastructure elements like bridge decks. Internal curing : uses prewetted lightweight aggregate in...

Microwave-Assisted Chemistry: A Rapid and Sustainable Route to Synthesis of Organics and Nanomaterials

EPA Science Inventory

The use of emerging MW-assisted chemistry techniques in conjunction with benign reaction media is dramatically reducing chemical waste and reaction times in several organic syntheses and chemical transformations. This review summarizes recent developments in MW-assisted synthesis...

Postnatal Ablation of POMC Neurons Induces an Obese Phenotype Characterized by Decreased Food Intake and Enhanced Anxiety-Like Behavior

PubMed Central

Greenman, Yona; Drori, Yonat; Asa, Sylvia L.; Navon, Inbal; Forkosh, Oren; Gil, Shosh; Stern, Naftali

2013-01-01

Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus are central components of systems regulating appetite and energy homeostasis. Here we report on the establishment of a mouse model in which the ribonuclease III ribonuclease Dicer-1 has been specifically deleted from POMC-expressing neurons (POMCΔDCR), leading to postnatal cell death. Mice are born phenotypically normal, at the expected genetic ratio and with normal hypothalamic POMC-mRNA levels. At 6 weeks of age, no POMC neurons/cells could be detected either in the arcuate nucleus or in the pituitary of POMCΔDCR mice. POMCΔDCR develop progressive obesity secondary to decreased energy expenditure but unrelated to food intake, which was surprisingly lower than in control mice. Reduced expression of AgRP and ghrelin receptor in the hypothalamus and reduced uncoupling protein 1 expression in brown adipose tissue can potentially explain the decreased food intake and decreased heat production, respectively, in these mice. Fasting glucose levels were dramatically elevated in POMCΔDCR mice and the glucose tolerance test revealed marked glucose intolerance in these mice. Secondary to corticotrope ablation, basal and stress-induced corticosterone levels were undetectable in POMCΔDCR mice. Despite this lack of activation of the neuroendocrine stress response, POMCΔDCR mice exhibited an anxiogenic phenotype, which was accompanied with elevated levels of hypothalamic corticotropin-releasing factor and arginine-vasopressin transcripts. In conclusion, postnatal ablation of POMC neurons leads to enhanced anxiety and the development of obesity despite decreased food intake and glucocorticoid deficiency. PMID:23676213

Innovation in Building Design

NASA Technical Reports Server (NTRS)

1983-01-01

Thomas & Betts Corporation's Flat Conductor Cables, or FCC, were developed of necessity as aircraft and spacecraft became increasingly complex. In order to reduce size and weight of components, the use of thin flat wire instead of relatively thick and protrusive round cable, provided a dramatic reduction of the space occupied by the many miles of power distribution lines in an aerospace vehicle. Commercially, FCC offers cost savings in simplified building construction, reduced installation time and ease of alteration.

Phytotoxic properties of nordihydroguaiaretic acid, a lignan fromLarrea tridentata (Creosote bush).

PubMed

Elakovich, S D; Stevens, K L

1985-01-01

The phytotoxic properties of nordihydroguaiaretic acid (NDGA) isolated from creosote bush,Larrea tridentata (Zygophyllaceae), were examined. NDGA dramatically reduces the seedling root growth of barnyard grass, green foxtail, perennial ryegrass, annual ryegrass, red millet, lambsquarter, lettuce, and alfalfa, and reduces the hypocotyl growth of lettuce and green foxtail. It has no effect on the germination of lettuce seeds. NDGA almost certainly contributes to the observed allelopathic nature of creosote bush.

Birdsong and anthropogenic noise: implications and applications for conservation.

PubMed

Slabbekoorn, Hans; Ripmeester, Erwin A P

2008-01-01

The dramatic increase in human activities all over the world has caused, on an evolutionary time scale, a sudden rise in especially low-pitched noise levels. Ambient noise may be detrimental to birds through direct stress, masking of predator arrival or associated alarm calls, and by interference of acoustic signals in general. Two of the most important functions of avian acoustic signals are territory defence and mate attraction. Both of these functions are hampered when signal efficiency is reduced through rising noise levels, resulting in direct negative fitness consequences. Many bird species are less abundant near highways and studies are becoming available on reduced reproductive success in noisy territories. Urbanization typically leads to homogenization of bird communities over large geographical ranges. We review current evidence for whether and how anthropogenic noise plays a role in these patterns of decline in diversity and density. We also provide details of a case study on great tits (Parus major), a successful urban species. Great tits show features that other species may lack and make them unsuitable for city life. We hypothesize that behavioural plasticity in singing behaviour may allow species more time to adapt to human-altered environments and we address the potential for microevolutionary changes and urban speciation in European blackbirds (Turdus merula). We conclude by providing an overview of mitigating measures available to abate noise levels that are degrading bird breeding areas. Bird conservationists probably gain most by realizing that birds and humans often benefit from the same or only slightly modified measures.

CHARACTERIZATION OF AN ACTIVELY COOLED METAL FOIL THERMAL RADIATION SHIELD

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

Feller, J. R.; Salerno, L. J.; Kashani, A.

2010-04-09

Zero boil-off (ZBO) or reduced boil-off (RBO) systems that involve active cooling of large cryogenic propellant tanks will most likely be required for future space exploration missions. For liquid oxygen or methane, such systems could be implemented using existing high technology readiness level (TRL) cryocoolers. However, for liquid hydrogen temperatures (approx20 K) no such coolers exist. In order to partially circumvent this technology gap, the concept of broad area cooling (BAC) has been developed, whereby a low mass thermal radiation shield could be maintained at temperatures around 100 K by steady circulation of cold pressurized gas through a network ofmore » narrow tubes. By this method it is possible to dramatically reduce the radiative heat leak to the 20 K tank. A series of experiments, designed to investigate the heat transfer capabilities of BAC systems, have been conducted at NASA Ames Research Center (ARC). Results of the final experiment in this series, investigating heat transfer from a metal foil film to a distributed cooling line, are presented here.« less

Conformational co-dependence between Plasmodium berghei LCCL proteins promotes complex formation and stability.

PubMed

Saeed, Sadia; Tremp, Annie Z; Dessens, Johannes T

2012-10-01

Malaria parasites express a conserved family of LCCL-lectin adhesive-like domain proteins (LAPs) that have essential functions in sporozoite transmission. In Plasmodium falciparum all six family members are expressed in gametocytes and form a multi-protein complex. Intriguingly, knockout of P. falciparum LCCL proteins adversely affects expression of other family members at protein, but not at mRNA level, a phenomenon termed co-dependent expression. Here, we investigate this in Plasmodium berghei by crossing a PbLAP1 null mutant parasite with a parasite line expressing GFP-tagged PbLAP3 that displays strong fluorescence in gametocytes. Selected and validated double mutants show normal synthesis and subcellular localization of PbLAP3::GFP. However, GFP-based fluorescence is dramatically reduced without PbLAP1 present, indicating that PbLAP1 and PbLAP3 interact. Moreover, absence of PbLAP1 markedly reduces the half-life of PbLAP3, consistent with a scenario of misfolding. These findings unveil a potential mechanism of conformational interdependence that facilitates assembly and stability of the functional LCCL protein complex. Copyright © 2012 Elsevier B.V. All rights reserved.

Turbulence characteristics of swirling flowfields. Ph.D. Thesis. Final Report

NASA Technical Reports Server (NTRS)

Jackson, T. W.; Lilley, D. G.

1985-01-01

The time mean and turbulence properties of a confined swirling jet using the six orientation, single hot wire technique were obtained. The effect of swirl on a confined, expanding jet is to reduce the size of the corner recirculation zone and generate a central recirculation zone followed by a precessing vortex core. The effect of introducing a contraction nozzle of area ratio four, located two test section diameters downstream of the inlet, is to dramatically reduce the size and shape of the central recirculation zone for the swirling flows considered. The shear stresses are found to increase by an order of magnitude in the region of the contraction nozzle because of large radial gradients of axial velocity. Reduction of the expansion ratio to D/o = 1 causes the time mean flow field to be homogeneous throughout the entire test section with the tangential velocity dominating in the swirling cases. No recirculation zones were observed for these particular flows. Turbulence levels and dissipation rates were found to be low except in the entrance regions and in areas of acceleration in the swirling flow cases.

Enhanced degradation of p53 protein in HPV-6 and BPV-1 E6-immortalized human mammary epithelial cells.

PubMed Central

Band, V; Dalal, S; Delmolino, L; Androphy, E J

1993-01-01

Normal mammary epithelial cells are efficiently immortalized by the E6 gene of human papillomavirus (HPV)-16, a virus commonly associated with cervical cancers. Surprisingly, introduction of the E6 gene from HPV-6, which is rarely found in cervical cancer, or bovine papillomavirus (BPV)-1, into normal mammary cells resulted in the generation of immortal cell lines. The establishment of HPV-6 and BPV-1 E6-immortalized cells was less efficient and required a longer period in comparison to HPV-16 E6. These HPV-6- and BPV-1 E6-immortalized cells demonstrated dramatically reduced levels of p53 protein by immunoprecipitation. While the half-life of p53 protein in normal mammary epithelial cells was approximately 3 h, it was reduced to approximately 15 min in all the E6-immortalized cells. These results demonstrate that the E6 genes of both high-risk and low-risk papilloma viruses immortalize human mammary epithelial cells and induce a marked degradation of p53 protein in vivo. Images PMID:8387914

[Social programs and reducing obesity in Peru: reflections from the research].

PubMed

Diez-Canseco, Francisco; Saavedra-Garcia, Lorena

2017-01-01

In recent decades, overweight or obesity have increased dramatically in middle- and low-income countries; a situation which consolidates chronic non-communicable diseases (NCD) as one of the leading causes of mortality and disability worldwide. Currently, half the people in Peru over the age of 15 years are overweight, and one fifth suffer from obesity. The situation is worsening and increasingly affects people in poverty, who frequently benefit from food supplement programs designed to combat food insecurity and malnutrition. There is an urgent worldwide need to find policies and programs that help fight the problem of obesity at the population level, a task that is still pending. In this article, we review the current epidemic of overweight and obesity in Peru and the world and its most significant consequences and causes, with an emphasis on access to and availability of foods. We describe the largest food supplement programs and synthesize the research on interventions in order to reflect on how their findings might help social programs work as a platform to reduce obesity and prevent NCD in Peru.

A comprehensive fluvial geomorphology study of riverbank erosion on the Red River in Winnipeg, Manitoba, Canada

NASA Astrophysics Data System (ADS)

Kimiaghalam, Navid; Goharrokhi, Masoud; Clark, Shawn P.; Ahmari, Habib

2015-10-01

Riverbank erosion on the Red River in Winnipeg, Manitoba has raised concerns over the last 20 years and more. Although several recent studies have shown that fluvial erosion can reduce riverbank stability and promote geotechnical slope failure, there are too few that have focused on this phenomenon. The present study includes field measurements, experimental testing, and numerical modelling to quantify fluvial erosion through a 10 km reach of the Red River. Results have shown that seasonal freeze-thaw processes can dramatically reduce the critical shear stress and increase erodibility of the riverbanks. Moreover, a simple method has been employed using hydrodynamic numerical models to define the applied shear stresses on the river banks based on the river water level, which will be useful for further research and design purposes. The TEMP/W numerical model was used to define seasonal frost depth to estimate freeze-thaw effects. Finally all field measurements, experimental and numerical models results were used to predict annual fluvial erosion through this reach of the river.

The jellification of north temperate lakes

PubMed Central

Jeziorski, Adam; Tanentzap, Andrew J.; Yan, Norman D.; Paterson, Andrew M.; Palmer, Michelle E.; Korosi, Jennifer B.; Rusak, James A.; Arts, Michael T.; Keller, Wendel (Bill); Ingram, Ron; Cairns, Allegra; Smol, John P.

2015-01-01

Calcium (Ca) concentrations are decreasing in softwater lakes across eastern North America and western Europe. Using long-term contemporary and palaeo-environmental field data, we show that this is precipitating a dramatic change in Canadian lakes: the replacement of previously dominant pelagic herbivores (Ca-rich Daphnia species) by Holopedium glacialis, a jelly-clad, Ca-poor competitor. In some lakes, this transformation is being facilitated by increases in macro-invertebrate predation, both from native (Chaoborus spp.) and introduced (Bythotrephes longimanus) zooplanktivores, to which Holopedium, with its jelly coat, is relatively invulnerable. Greater representation by Holopedium within cladoceran zooplankton communities will reduce nutrient transfer through food webs, given their lower phosphorus content relative to daphniids, and greater absolute abundances may pose long-term problems to water users. The dominance of jelly-clad zooplankton will likely persist while lakewater Ca levels remain low. PMID:25411451

Identification of Stevioside Using Tissue Culture-Derived Stevia (Stevia rebaudiana) Leaves

PubMed Central

Karim, Md. Ziaul; Uesugi, Daisuke; Nakayama, Noriyuki; Hossain, M. Monzur; Ishihara, Kohji; Hamada, Hiroki

2015-01-01

Stevioside is a natural sweetener from Stevia leaf, which is 300 times sweeter than sugar. It helps to reduce blood sugar levels dramatically and thus can be of benefit to diabetic people. Tissue culture is a very potential modern technology that can be used in large-scale disease-free stevia production throughout the year. We successfully produced stevia plant through in vitro culture for identification of stevioside in this experiment. The present study describes a potential method for identification of stevioside from tissue culture-derived stevia leaf. Stevioside in the sample was identified using HPLC by measuring the retention time. The percentage of stevioside content in the leaf samples was found to be 9.6%. This identification method can be used for commercial production and industrialization of stevia through in vitro culture across the world. PMID:28008268

The role of Medicare reimbursement in contemporary hospital finance.

PubMed

Golub, S

1986-01-01

A hospital, while performing its major function of providing health care, is also viewed as a business. It needs capital from a wide variety of sources, many of which are government regulated. Over the past few years, federal expenditures for Medicare have increased dramatically, as has regulation of hospital revenue sources. Congress enacted the Medicare Prospective Payment System (PPS) to curb hospital cost inflation. This Note examines historical trends in health care financing and analyzes the Medicare reimbursement system, with emphasis on PPS and its impact on hospital revenues. The Note suggests that hospitals, due to the effects of PPS, will be forced to reduce their levels of financial leverage and will have to look for corporate financial alternatives. PPS may signal a new era in hospital finance. Survival mandates an increased focus on efficient corporate, financial and managerial policies.

Phenotypic behavior of C2C12 myoblasts upon expression of the dystrophy-related caveolin-3 P104L and TFT mutants.

PubMed

Fanzani, Alessandro; Stoppani, Elena; Gualandi, Laura; Giuliani, Roberta; Galbiati, Ferruccio; Rossi, Stefania; Fra, Anna; Preti, Augusto; Marchesini, Sergio

2007-10-30

Caveolin-3 (Cav-3) is the main scaffolding protein present in myofiber caveolae. We transfected C2C12 myoblasts with dominant negative forms of Cav-3, P104L or DeltaTFT, respectively, which cause the limb-girdle muscular dystrophy 1-C. Both these forms triggered Cav-3 loss during C2C12 cell differentiation. The P104L mutation reduced myofiber formation by impaired AKT signalling, accompanied by dramatic expression of the E3 ubiquitin ligase Atrogin. On the other hand, the DeltaTFT mutation triggered hypertrophic myotubes sustained by prolonged AKT activation, but independent of increased levels of follistatin and interleukin 4 expression. These data suggest that separated mutations within the same dystrophy-related gene may cause muscle degeneration through different mechanisms.

Conflict resolution in insect societies.

PubMed

Ratnieks, Francis L W; Foster, Kevin R; Wenseleers, Tom

2006-01-01

Although best known for cooperation, insect societies also manifest many potential conflicts among individuals. These conflicts involve both direct reproduction by individuals and manipulation of the reproduction of colony members. Here we review five major areas of reproductive conflict in insect societies: (a) sex allocation, (b) queen rearing, (c) male rearing, (d) queen-worker caste fate, and (e) breeding conflicts among totipotent adults. For each area we discuss the basis for conflict (potential conflict), whether conflict is expressed (actual conflict), whose interests prevail (conflict outcome), and the factors that reduce colony-level costs of conflict (conflict resolution), such as factors that cause workers to work rather than to lay eggs. Reproductive conflicts are widespread, sometimes having dramatic effects on the colony. However, three key factors (kinship, coercion, and constraint) typically combine to limit the effects of reproductive conflict and often lead to complete resolution.

New insight on the water management in Ica Valley-Peru

NASA Astrophysics Data System (ADS)

Guttman, Joseph; Berger, Diego

2014-05-01

The Andes divide Peru into three natural drainage basins: Pacific basin, Atlantic basin and Lake Titicaca basin. According to the National Water Authority (ANA), the Pacific basin is the driest basin. The bulk of water that feed the local aquifers in the coastal Pacific region is coming from rivers that flow west from the Andes. One of them is the Ica River- source of the Ica Aquifer and the Pampas de Villacuri Aquifer. The Ica River flows in a graben that was created by a series of faults. The graben is filled with sand and gravel with interbeded and lenses of clay. The aquifer thickness varies between 25 meters to more than 200 meters. The Ica Valley has an extension of 7700 km2 and belongs to the Province of Ica, the second larger economic center in Peru. The Valley is located in the hyperarid region of the Southern Coastal area of Peru with a few millimeters of precipitation per year. The direct recharge is almost zero. The recharge into the Ica Valley aquifer is comes indirectly by infiltration of storm water through the riverbed generates in the Andes, through irrigation canals and by irrigation return flow. In this hyperarid region, local aquifers like the Ica Valley are extremely valuable resources to local populations and are the key sources of groundwater for agriculture and population needs. Therefore, these aquifers play a crucial role in providing people with water and intense attention should be given to manage the water sector properly and to keep the aquifer sustainable for future generations. The total pumping (from rough estimations) is much greater than the direct and indirect recharge. The deficit in the water balance is reflected in large water level decline, out of operation of shallow wells and the ascending of saline water from deeper layers. The change from flood irrigation that contributes about 35-40% of the water to the aquifer, to drip irrigation dramatically reduces the amount of water that infiltrates into the sub-surface from the irrigation canals and returns flow and increases the water balance deficit. In principal there are two ways to improve the hydrological conditions of the aquifers. One is to reduce dramatically the pumping from the aquifers to a level close to the calculated recharge. This will reduce the rate of decline of the water level and bring the aquifer to a new equilibrium. As there is no alternative source to bridge the gap in demand, this would lead to the collapse of local agriculture and thus is impractical. The second way is to improve (indirectly) the hydrological situation of the aquifers by artificially increasing the recharge into the aquifers together with encouraging sustainable water-based policies and restrictions on the drilling of new wells. Our recommendation is the second way to treat municipal effluents to a tertiary level and to recharge them along with excess runoff from the Ica River into the subsurface.

Into the Curriculum. Creative Dramatics: Valentine Lip Sync Book Charades; Language Arts/Social Studies: Found Poetry from Primary Sources; Reading/Language Arts: A Thematic Activity To Herald in the New Year; Science: Asian Elephant Life Cycles; Social Studies: Conservation of Animal Species-Asian Elephants; Social Studies: What Makes a Leader?

ERIC Educational Resources Information Center

Shugar, Candace; Robinson, Alice A.

2003-01-01

Provides six fully developed library media activities that are designed for use with specific curriculum units in creative dramatics, language arts, social studies, reading, and science. Library media skills, curriculum objectives, grade levels, resources, instructional roles, activities and procedures, evaluation, and follow-up are described for…

Illuminating the Way.

ERIC Educational Resources Information Center

Murphy, Peter

1997-01-01

Details the dramatic changes in school lighting. Describes how lighting will be more closely integrated into the "smart" school building of tomorrow and how lighting systems will evolve with schools as technology changes. Claims that direct/indirect lighting systems will serve computer users as well as reduce energy and maintenance costs. (RJM)

Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies.

PubMed

Pimpin, Laura; Cortez-Pinto, Helena; Negro, Francesco; Corbould, Emily; Lazarus, Jeffrey V; Webber, Laura; Sheron, Nick

2018-05-16

The burden of liver disease in Europe continues to grow. We aimed to describe the epidemiology of liver diseases and their risk factors in European countries, and identify public health interventions that could impact on these risk factors to reduce the burden of liver disease. As part of the HEPAHEALTH project, commissioned by EASL, we extracted information on historical and current prevalence and mortality from national and international literature and databases on liver disease in 35 countries in the WHO European region, as well as historical and recent prevalence data on their main determinants; alcohol consumption, obesity and hepatitis B and C virus infections. We extracted information from peer-reviewed and grey literature to identify public health interventions targeting these risk factors. The epidemiology of liver disease is diverse and countries cluster with similar pictures, although the exact composition of diseases and the trends in risk factors which drive them is varied. Prevalence and mortality data indicate that increasing cirrhosis and liver cancer may be linked to dramatic increases in harmful alcohol consumption in Northern European countries, and viral hepatitis epidemics in Eastern and Southern European countries. Countries with historically low levels of liver disease may experience an increase in non-alcoholic fatty liver disease in the future, given the rise of obesity across the majority of European countries. Interventions exist for curbing harmful alcohol use, reducing obesity, preventing or treating viral hepatitis, and screening for liver disease at an early stage. Liver disease in Europe is a serious issue, with increasing cirrhosis and liver cancer. The public health and hepatology communities are uniquely placed to implement measures aimed at reducing their causes: harmful alcohol consumption, child and adult obesity prevalence and chronic infection with hepatitis viruses, which will in turn reduce the burden of liver disease. The European region has seen dramatic increases in liver disease mortality and morbidity in recent decades as a result of changes in the underlying risk factors: excessive alcohol consumption, obesity and viral hepatitis. However, there are highly effective ways to combat these, for example increasing the price of alcohol, making it less readily available, reducing the number of calories, sugar and fat in foods we consume, or screening people earlier to treat them more effectively. The time is now for governments, the health system and individuals to implement the changes required to substantially reduce the burden of liver disease. Copyright © 2018. Published by Elsevier B.V.

High tides and rising seas: potential effects on estuarine waterbirds

USGS Publications Warehouse

Erwin, R.M.; Sanders, G.M.; Prosser, D.J.; Cahoon, D.R.; Greenberg, Russell; Maldonado, Jesus; Droege, Sam; McDonald, M.V.

2006-01-01

Coastal waterbirds are vulnerable to water-level changes especially under predictions of accelerating sea-level rise and increased storm frequency in the next century. Tidal and wind-driven fluctuations in water levels affecting marshes, their invertebrate communities, and their dependent waterbirds are manifested in daily, monthly, seasonal, annual, and supra-annual (e.g., decadal or 18.6-yr) periodicities. Superimposed on these cyclic patterns is a long-term (50?80 yr) increase in relative sea-level rise that varies from about 2?4 + mm/yr along the Atlantic coastline. At five study sites selected on marsh islands from Cape Cod, Massachusetts to coastal Virginia, we monitored marsh elevation changes and flooding, tide variations over time, and waterbird use. We found from longterm marsh core data that marsh elevations at three of five sites may not be sufficient to maintain pace with current sea-level rise. Results of the short-term (3?4 yr) measures using surface elevation tables suggest a more dramatic difference, with marsh elevation change at four of five sites falling below relative sea-level rise. In addition, we have found a significant increase (in three of four cases) in the rate of surface marsh flooding in New Jersey and Virginia over the past 70?80 yr during May?July when waterbirds are nesting on or near the marsh surface. Short-term, immediate effects of flooding will jeopardize annual fecundity of many species of concern to federal and state agencies, most notably American Black Duck (Anas rubripes), Nelson?s Sharp-tailed Sparrow (Ammodramus nelsoni), Saltmarsh Sharp-tailed Sparrow (A. caudacutus), Seaside Sparrow (A. maritima), Coastal Plain Swamp Sparrow (Melospiza georgiana nigrescens), Black Rail (Laterallus jamaicensis), Forster?s Tern (Sterna forsteri), Gull-billed Tern (S. nilotica), Black Skimmer (Rynchops niger), and American Oystercatcher (Haemotopus palliatus). Forster?s Terns are probably most at risk given the large proportion of their breeding range in the mid-Atlantic and their saltmarsh specialization. At a scale of 1?2 decades, vegetation changes (saltmeadow cordgrass [Spartina patens] and salt grass [Distichlis spicata] converting to smooth cordgrass [Spartina alternifl ora]), interior pond expansion and erosion of marshes will reduce nesting habitat for many of these species, but may enhance feeding habitat of migrant shorebirds and/or migrant or wintering waterfowl. At scales of 50?100 yr, reversion of marsh island complexes to open water may enhance populations of open-bay waterfowl, e.g., Bufflehead (Bucephala albeola) and Canvasback (Aythya valisneria), but reduce nesting habitats dramatically for the above named marsh-nesting species, may reduce estuarine productivity by loss of the detrital food web and nursery habitat for fish and invertebrates, and cause redistribution of waterfowl, shorebirds, and other species. Such scenarios are more likely to occur in the mid- and north Atlantic regions since these estuaries are lower in sediment delivery on average than those in the Southeast. A simple hypothetical example from New Jersey is presented where waterbirds are forced to shift from submerged natural marshes to nearby impoundments, resulting in roughly a 10-fold increase in density. Whether prey fauna are sufficiently abundant to support this level of increase remains an open question, but extreme densities in confined habitats would exacerbate competition, increase disease risk, and possibly increase predation.

Observations of biomass burning tracers in PM2.5 at two megacities in North China during 2014 APEC summit

NASA Astrophysics Data System (ADS)

Zhang, Zhisheng; Gao, Jian; Zhang, Leiming; Wang, Han; Tao, Jun; Qiu, Xionghui; Chai, Fahe; Li, Yang; Wang, Shulan

2017-11-01

To evaluate the effectiveness of biomass burning control measures on PM2.5 reduction, day- and nighttime PM2.5 samples were collected at two urban sites in North China, one in Beijing (BJ) and the other in Shijiazhuang (SJZ), during the 2014 Asia-Pacific Economic Cooperation (APEC) summit. Typical biomass burning aerosol tracers including levoglucosan (LG), Mannosan (MN), and water-soluble potassium (K+), together with other water-soluble ions and carbonaceous species were determined. The levels of biomass burning tracers dropped dramatically during the APEC period when open biomass burning activities were well controlled in North China, yet they increased sharply to even higher levels during the post-APEC period. Distinct linear regression relationships between LG and MN were found with lower LG/MN ratios from periods with much reduced open biomass burning activities. This was likely resulted from the reduced open crop residues burning and increased residential wood burning emissions, as was also supported by the simultaneous decrease in K+/LG ratio. The positive matrix factorization and air quality model simulation analyses suggested that PM2.5 concentration produced from biomass burning sources was reduced by 22% at BJ and 46% at SJZ during the APEC period compared to pre-APEC period, although they increased to higher levels after APEC mainly due to increased residential biomass burning emissions in winter heating season. Biomass burning was also found to be the most important contributor to carbonaceous species that might cause significant light extinction in this region. This study not only suggested implementing biomass burning controls measures were helpful to reduce PM2.5 in North China, but also pointed out both open crop residues burning and indoor biomass burning activities could make substantial contributions to PM2.5 and its major components in urban areas in North China.

The homozygous VHL(D126N) missense mutation is associated with dramatically elevated erythropoietin levels, consequent polycythemia, and early onset severe pulmonary hypertension.

PubMed

Sarangi, Susmita; Lanikova, Lucie; Kapralova, Katarina; Acharya, Suchitra; Swierczek, Sabina; Lipton, Jeffrey M; Wolfe, Lawrence; Prchal, Josef T

2014-11-01

von Hippel-Lindau (VHL) protein is the principal negative regulator of hypoxia sensing mediated by transcription factors. Mutations in exon 3 of the VHL gene lead to Chuvash (VHL(R200W)) and Croatian (VHL(H191D)) polycythemias. Here, we describe an infant of Bangladesh ethnicity with a novel homozygous VHL(D126N) mutation with congenital polycythemia and dramatically elevated erythropoietin (EPO) levels, who developed severe fatal pulmonary hypertension. In contrast to Chuvash polycythemia, erythroid progenitors (BFU-Es) did not reveal a marked EPO hypersensitivity. Further, NF-E2 and RUNX1 transcripts that correlate with BFU-Es EPO hypersensitivity in polycythemic mutations were not elevated. © 2014 Wiley Periodicals, Inc.

Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells.

PubMed

Lee, Andrew W; Hertel, Laura; Louie, Ryan K; Burster, Timo; Lacaille, Vashti; Pashine, Achal; Abate, Davide A; Mocarski, Edward S; Mellins, Elizabeth D

2006-09-15

Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are susceptible to productive infection by human CMV (HCMV). To investigate the impact of infection on this cell type, we examined HLA-DR biosynthesis and trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA-DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of HLA-DR was independent of expression of unique short US2-US11 region gene products by HCMV. Indeed, exposure to UV-inactivated virus, but not to conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature LC, implicating particle binding/penetration in this effect. Reduced surface levels reflected an altered distribution of HLA-DR because total cellular HLA-DR was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells, as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was implicated, as endocytosis of surface HLA-DR was not increased. Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR and revealed markedly fewer HLA-DR-positive dendritic projections in infected mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the dendrites themselves and immunofluorescence revealed that cytoskeletal elements crucial for the formation and maintenance of dendrites are disrupted in viral Ag-positive cells. Consistent with these dendrite effects, HCMV-infected mature LC exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus, HCMV impedes MHC class II molecule trafficking, dendritic projections, and migration of mature LC. These changes likely contribute to the reduced activation of CD4+ T cells by HCMV-infected mature LC.

Effects of Persistent Atrial Fibrillation-Induced Electrical Remodeling on Atrial Electro-Mechanics – Insights from a 3D Model of the Human Atria

PubMed Central

Adeniran, Ismail; MacIver, David H.; Garratt, Clifford J.; Ye, Jianqiao; Hancox, Jules C.; Zhang, Henggui

2015-01-01

Aims Atrial stunning, a loss of atrial mechanical contraction, can occur following a successful cardioversion. It is hypothesized that persistent atrial fibrillation-induced electrical remodeling (AFER) on atrial electrophysiology may be responsible for such impaired atrial mechanics. This simulation study aimed to investigate the effects of AFER on atrial electro-mechanics. Methods and Results A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4 states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2–3 months after cardioversion (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodeled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+ content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+ transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished. Conclusions This study provides novel insights into understanding atrial electro-mechanics illustrating that AFER impairs atrial contraction due to reduced intracellular Ca2+ transients. PMID:26606047

Phosphorylation-related modification at the dimer interface of 14-3-3ω dramatically alters monomer interaction dynamics.

PubMed

Denison, Fiona C; Gökirmak, Tufan; Ferl, Robert J

2014-01-01

14-3-3 proteins are generally believed to function as dimers in a broad range of eukaryotic signaling pathways. The consequences of altering dimer stability are not fully understood. Phosphorylation at Ser58 in the dimer interface of mammalian 14-3-3 isoforms has been reported to destabilise dimers. An equivalent residue, Ser62, is present across most Arabidopsis isoforms but the effects of phosphorylation have not been studied in plants. Here, we assessed the effects of phosphorylation at the dimer interface of Arabidopsis 14-3-3ω. Protein kinase A phosphorylated 14-3-3ω at Ser62 and also at a previously unreported residue, Ser67, resulting in a monomer-sized band on native-PAGE. Phosphorylation at Ser62 alone, or with additional Ser67 phosphorylation, was investigated using phosphomimetic versions of 14-3-3ω. In electrophoretic and chromatographic analyses, these mutants showed mobilities intermediate between dimers and monomers. Mobility was increased by detergents, by reducing protein concentration, or by increasing pH or temperature. Urea gradient gels showed complex structural transitions associated with alterations of dimer stability, including a previously unreported 14-3-3 aggregation phenomenon. Overall, our analyses showed that dimer interface modifications such as phosphorylation reduce dimer stability, dramatically affecting the monomer-dimer equilibrium and denaturation trajectory. These findings may have dramatic implications for 14-3-3 structure and function in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

Underlying mechanisms and effects of hydrated lime and selenium application on cadmium uptake by rice (Oryza sativa L.) seedlings.

PubMed

Huang, Gaoxiang; Ding, Changfeng; Guo, Fuyu; Li, Xiaogang; Zhang, Taolin; Wang, Xingxiang

2017-08-01

A pot experiment was conducted to investigate the effects of selenium (Se) and hydrated lime (Lime), applied alone or simultaneously (Se+Lime), on growth and cadmium (Cd) uptake and translocation in rice seedlings grown in an acid soil with three levels of Cd (slight, mild, and moderate contamination). In the soil with 0.41 mg kg -1 Cd (slight Cd contamination), Se addition alone significantly decreased Cd accumulation in the root and shoot by 35.3 and 40.1%, respectively, but this tendency weakened when Cd level in the soil increased. However, Se+Lime treatment effectively reduced Cd accumulation in rice seedlings in the soil with higher Cd levels. The results also showed that Se application alone strongly increased Cd concentration in the iron plaque under slight Cd contamination, which was suggested as the main reason underlying the inhibition of Cd accumulation in rice seedlings. Se+Lime treatment also increased the ability of the iron plaques to restrict Cd uptake by rice seedlings across all Cd levels and dramatically decreased the available Cd concentration in the soil. These results suggest that Se application alone would be useful in the soil with low levels of Cd, and the effect would be enhanced when Se application is combined with hydrated lime at higher Cd levels.

Effects of kidney or kidney-pancreas transplantation on plasma pentosidine.

PubMed

Hricik, D E; Schulak, J A; Sell, D R; Fogarty, J F; Monnier, V M

1993-02-01

Tissue and plasma concentrations of pentose-derived glycation end-products ("pentosidine") are elevated in diabetic patients with normal renal function and in both diabetic and nondiabetic patients with end-stage renal disease. To determine the effects of correcting hyperglycemia and/or renal failure on the accumulation of pentosidine, we used reverse phase and ion exchange high performance liquid chromatography to measure this advanced glycation end-product in plasma proteins of diabetic and nondiabetic transplant recipients at various time intervals after kidney-pancreas or kidney transplantation. Changes in plasma pentosidine levels after transplantation were compared to changes in simultaneously obtained glycohemoglobin levels. Both kidney and kidney-pancreas transplantation were accompanied by a dramatic, but incomplete, reduction of plasma pentosidine concentrations within three months of transplantation. Kidney-pancreas transplantation resulted in normal glycohemoglobin levels within three months but offered no advantage over kidney transplantation alone in the partial correction of plasma pentosidine levels. There was no correlation between posttransplant plasma pentosidine and glycohemoglobin levels in either diabetic or nondiabetic transplant recipients. We conclude that renal failure is the major factor accounting for the accumulation of pentosidine in both diabetic and nondiabetic patients with end-stage renal disease. Restoration of euglycemia after kidney-pancreas transplantation provides no additional benefit in reducing plasma pentosidine levels to that achieved by correction of renal failure after kidney transplantation alone.

Dramatic secretion of recombinant protein expressed in tobacco cells with a designer glycopeptide tag is highly impacted by medium composition.

PubMed

Zhang, Ningning; Dolan, Maureen; Wu, Di; Phillips, Gregory C; Xu, Jianfeng

2016-12-01

Cell growth medium composition has profound impacts on the O -glycosylation of a "designer" arabinogalactan protein-based module; full glycosylation is essential in directing efficient extracellular secretion of the tagged recombinant protein. Expression of recombinant proteins in plant cells as fusion with a de novo designed hydroxyproline (Hyp)-O-glycosylated peptide (HypGP) tag, termed HypGP engineering technology, resulted in dramatically increased secreted protein yields. This is due to the function of the HypGP tag as a molecular carrier in promoting efficient transport of conjoined proteins into culture media. To optimize the cell culture to achieve the best secreted protein yields, the medium effects on the cell growth and protein secretion were investigated using as a model system the tobacco BY-2 cell expressing enhanced green fluorescence protein (EGFP) fused with a (SP) 32 tag (32 tandem repeats of "Ser-Pro" motif). The (SP) 32 tag was found to undergo two-stage Hyp-O-glycosylation in plant cells with the dramatic secretion of the conjoined EGFP correlating with the triggering of the second-stage glycosylation. The BY-2 cell culture in SH medium generated a high secreted protein yield (125 mg/L) with a low cell biomass accumulation (~7.5 gDW/L). In contrast, very low secreted protein yields (~1.5 mg/L) with a high cell biomass accumulation (13.5 gDW/L) were obtained in MS medium. The macronutrients, specifically, the nitrogen supply greatly impacted the glycosylation of the (SP) 32 tag and subsequent protein secretion. Modified MS medium with reduced nitrogen levels boosted the secreted EGFP yields to 168 mg/L. This study demonstrates the profound impacts of medium composition on the secreted yields of a HypGP-tagged protein, and provides a basis for medium design to achieve the highest productivity of the HypGP engineering technology.

Crime and violence in Brazil: Systematic review of time trends, prevalence rates and risk factors☆

PubMed Central

Murray, Joseph; Cerqueira, Daniel Ricardo de Castro; Kahn, Tulio

2013-01-01

Between 1980 and 2010 there were 1 million homicides in Brazil. Dramatic increases in homicide rates followed rises in inequality, more young men in the population, greater availability of firearms, and increased drug use. Nevertheless, disarmament legislation may have helped reduce homicide rates in recent years. Despite its very high rate of lethal violence, Brazil appears to have similar levels of general criminal victimization as several other Latin American and North American countries. Brazil has lower rates of drug use compared to other countries such as the United States, but the prevalence of youth drug use in Brazil has increased substantially in recent years. Since 1990, the growth of the Brazilian prison population has been enormous, resulting in the fourth largest prison population in the world. Through a systematic review of the literature, we identified 10 studies assessing the prevalence of self-reported offending in Brazil and 9 studies examining risk factors. Levels of self-reported offending seem quite high among school students in Brazil. Individual and family-level risk factors identified in Brazil are very similar to those found in high-income countries. PMID:24027422

TM9/Phg1 and SadA proteins control surface expression and stability of SibA adhesion molecules in Dictyostelium.

PubMed

Froquet, Romain; le Coadic, Marion; Perrin, Jackie; Cherix, Nathalie; Cornillon, Sophie; Cosson, Pierre

2012-02-01

TM9 proteins form a family of conserved proteins with nine transmembrane domains essential for cellular adhesion in many biological systems, but their exact role in this process remains unknown. In this study, we found that genetic inactivation of the TM9 protein Phg1A dramatically decreases the surface levels of the SibA adhesion molecule in Dictyostelium amoebae. This is due to a decrease in sibA mRNA levels, in SibA protein stability, and in SibA targeting to the cell surface. A similar phenotype was observed in cells devoid of SadA, a protein that does not belong to the TM9 family but also exhibits nine transmembrane domains and is essential for cellular adhesion. A contact site A (csA)-SibA chimeric protein comprising only the transmembrane and cytosolic domains of SibA and the extracellular domain of the Dictyostelium surface protein csA also showed reduced stability and relocalization to endocytic compartments in phg1A knockout cells. These results indicate that TM9 proteins participate in cell adhesion by controlling the levels of adhesion proteins present at the cell surface.

A simple simulation model as a tool to assess alternative health care provider payment reform options in Vietnam.

PubMed

Cashin, Cheryl; Phuong, Nguyen Khanh; Shain, Ryan; Oanh, Tran Thi Mai; Thuy, Nguyen Thi

2015-01-01

Vietnam is currently considering a revision of its 2008 Health Insurance Law, including the regulation of provider payment methods. This study uses a simple spreadsheet-based, micro-simulation model to analyse the potential impacts of different provider payment reform scenarios on resource allocation across health care providers in three provinces in Vietnam, as well as on the total expenditure of the provincial branches of the public health insurance agency (Provincial Social Security [PSS]). The results show that currently more than 50% of PSS spending is concentrated at the provincial level with less than half at the district level. There is also a high degree of financial risk on district hospitals with the current fund-holding arrangement. Results of the simulation model show that several alternative scenarios for provider payment reform could improve the current payment system by reducing the high financial risk currently borne by district hospitals without dramatically shifting the current level and distribution of PSS expenditure. The results of the simulation analysis provided an empirical basis for health policy-makers in Vietnam to assess different provider payment reform options and make decisions about new models to support health system objectives.

How tough is Brittle Bone? Investigating Osteogenesis Imperfecta in Mouse Bone††

PubMed Central

Carriero, A.; Zimmermann, E. A.; Paluszny, A.; Tang, S. Y.; Bale, H.; Busse, B.; Alliston, T.; Kazakia, G.

2015-01-01

The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (oim), which has homotrimeric α1(I) collagen. At the molecular level we attribute the loss in toughness to a decrease in the stabilizing enzymatic crosslinks and an increase in non-enzymatic crosslinks, which may break prematurely inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack-deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous oim bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales. PMID:24420672

Environmental management requirements/defensible costs project. Final report

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

NONE

1996-02-01

Lockheed Idaho Technologies Company (LITCO) used a systems engineering approach to develop the first formal requirements baseline for Idaho National Engineering Laboratory (INEL) Environmental Management (EM) Programs. The recently signed Settlement Agreement with the State of Idaho (Batt Agreement), along with dramatically reduced EM funding targets from Department of Energy (DOE) headquarters, drove the immediacy of this effort. Programs have linked top-level requirements to work scope to cost estimates. All EM work, grouped by decision units, was scrubbed by INEL EM programs and by an independent {open_quotes}Murder Board.{close_quotes} Direct participation of upper level management from LITCO and the DOE-Idaho Operationsmore » Office ensured best information and decisions. The result is a scrubbed down, defensible budget tied to top-level requirements for use in the upcoming DOE-Headquarters` budget workout, the Internal Review Board, the FY98 Activity Data Sheets submittal, and preparation of the FY97 control accounts and out-year plans. In addition to the remarkable accomplishments during the past eight weeks, major issues were identified and documented and follow-on tasks are underway which will lead to further improvements in INEL EM program management.« less

CO Pollution: a comparative study during high traffic conditions in the cities of Athens, Naples and Islamabad. Health impacts

NASA Astrophysics Data System (ADS)

Polichetti, Juliano; Grigoropoulos, Konstantinos; Ferentinos, George; Tselentis, Vasilios; Nastos, Panagiotis; Xatzioakeimidis, Konstantinos; Dimas, Konstantinos; Khan, Ubaidullah

2010-05-01

Since the 19th century anthropogenic activities in urban areas have increased dramatically due to socio-economic evolution, increased urbanization and transport needs. Fifty seven years ago London experienced the impacts of an acute atmospheric pollution episode, due to elevated levels of black carbon aerosols (BC) and SO2, leading to the realization that uncontrolled emissions to the atmosphere lead to severe impacts on human health. Many large cities (Mega cities) in the developed and developing world have, for the last two decades, been plagued by high levels of atmospheric pollution, a problem that the European and worldwide scientific community are at present studying with measurable success. However, due to rapid industrial development and the ever increasing traffic, many more studies are required to support decision makers and governments on measures to reduce atmospheric pollution and mitigate the associated serious health effects on the population. Registered health problems are numerous and dramatic in all ages groups, but particularly so in infants, and patients suffering from chronic diseases due to increased levels of pollutants and nocive substance inhaled, entering the lungs and blood stream and finally being deposited in several organs. Recent studies indicate that cardiac arrhythmias associated to increased atmospheric pollution pose a serious threat to human health. K.N.Grigoropoulos,et al.2008. This study is based on monitoring and mapping CO levels in six areas 3 different cities i.e. Athens, Naples and Islamabad, the objective being to present and analyze the spatial and temporal variability of carbon monoxide (CO) levels leading to the estimation of the concentration levels and the quantities inhaled by pedestrians on a daily basis. It is well know that exposure to carbon monoxide concentration values in excess of 200ppm for 2-3 h usually create headaches, tiredness, fatigue and nausea, whereas human exposure of values of 800 ppm for over three hours, are fatal. The findings of this research indicate that although CO concentrations remain at low levels throughout the measurement period, several peaks of high CO concentration are obtained, in many instances of several minutes duration, which are incompatible with public health levels and conditions for the afore mentioned cities. This research is yet another reminder that it is timely and necessary for the European Community to re examinate and evaluate the framework pertinent to CO emissions and levels in the urban ambient atmosphere.

Anti-HIV Drugs Decrease the Expression of Matrix Metalloproteinases in Astrocytes and Microglia

ERIC Educational Resources Information Center

Liuzzi, G. M.; Mastroianni, C. M.; Latronico, T.; Mengoni, F.; Fasano, A.; Lichtner, M.; Vullo, V.; Riccio, P.

2004-01-01

The introduction of potent antiretroviral drugs for the treatment of patients with human immunodeficiency virus (HIV) infection has dramatically reduced the prevalence of HIV-associated neurological disorders. Such diseases can be mediated by proteolytic enzymes, i.e. matrix metalloproteinases (MMPs) and, in particular gelatinases, released from…

ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone

DTIC Science & Technology

2009-07-01

formation rate and bone mineral density (severe osteoporosis) that persists throughout life. The expression of both osteocalcin (Ocn) and bone sialoprotein ...established that ATF4 is critical for osteoblast differentiation as demonstrated by dramatically reduced expression of osteocalcin and bone sialoprotein mRNA

Planting native oak in the Pacific Northwest

Treesearch

Warren D. Devine; Constance A. Harrington

2010-01-01

The extent of oak woodland and savanna habitat in the Pacific Northwest has been dramatically reduced since settlement in the mid-1800s. This report presents a practical guide for landowners and managers who are interested in reestablishing native oak by planting seedlings. Keys to successful establishment are (1) planting quality...

Maize chromosomal knobs are located in gene-dense areas and suppress local recombination

USDA-ARS?s Scientific Manuscript database

Knobs are conspicuous heterochromatic regions found on the chromosomes of maize and its relatives. The number, locations, and sizes vary dramatically, with most lines containing between four and eight knobs in mid-arm positions. Prior data suggest that some knobs may reduce recombination, but prev...

Development of a Mechanically Mediated RF to Optical Transducer

DTIC Science & Technology

2017-05-22

in radio astronomy receivers could be replaced by this noise- tolerant transducer, thus dramatically reducing the system’s size and cost [7]. Such a...conversion between microwave and optical light. Nat. Phys. 10, 321-326 (2014). [7] Kraus, J.D., Radio Astronomy (McGraw, 1966). [8] DARPA Optical Radiation

Research Technology

NASA Image and Video Library

1999-10-21

Pictured is an artist's concept of an advanced chemical propulsion system called Pulse Detonation. Long term technology research in this advanced propulsion system has the potential to dramatically change the way we think about space propulsion systems. This research is expected to significantly reduce the cost of space travel within the next 25 years.

Reinventing School Finance: Falling Forward

ERIC Educational Resources Information Center

Picus, Lawrence O.; Odden, Allan R.

2011-01-01

States and school districts are facing unprecedented financial pressure due to the continued poor performance of the United States's economy. Dramatic shortfalls in funding due to reduced tax collections were held off for 2 years thanks to federal stimulus funds, but with these revenues already consumed and little likelihood of more in the near…

The legacy of deer overabundance: long-term delays in herbaceous understory recovery

Treesearch

Thomas H. Pendergast; Shane M. Hanlon; Zachary M. Long; Alex Royo; Walter P. Carson

2016-01-01

Decades of white-tailed deer (Odocoileus virginianus (Zimmermann, 1780)) overpopulation have dramatically homogenized forests across much of the eastern United States, creating depauperate forest understory communities. The rate at which these communities recover once deer browsing has been reduced remains an open question. We evaluate overbrowsing...

Schoolwide Enrichment Model: Challenging All Children to Excel

ERIC Educational Resources Information Center

Beecher, Margaret

2010-01-01

This article summarizes how the components of the Schoolwide Enrichment Model were used to dramatically reduce the achievement gap in a school with a high at-risk student population. The theories of enrichment and instructional differentiation replaced an existing remedial paradigm and a strength-based methodology was embraced by the school…

BULK AND TEMPLATE-FREE SYNTHESIS OF SILVER NANOWIRES USING CAFFEINE AT ROOM TEMPERATURE

EPA Science Inventory

A simple eco-friendly one-pot method is described to synthesize bulk quantities of nanowires of silver (Ag) using caffeine without the need of reducing agent, surfactants, and/or large amounts of insoluble templates. Chemical reduction of silver salts with caffeine dramatically c...

Applications of Slow Light in Telecommunications

DTIC Science & Technology

2006-04-01

that the distortion of the transmitted waveform can be dramatically reduced by using frequency-flattened gain profiles [ Stenner et al.]. Time [ns...Express 13, 7872 (2005). >> K.Y. Song et al. Opt. Express 13, 83 (2005). >> M.D. Stenner et al. Opt. Express 13, 9995 (2005). >> X. Zhao et al. Opt

Megafauna moves nutrients uphill.

PubMed

Gross, Michael

2016-01-11

Large animals have a disproportionate capacity to transport nutrients along gradients and against water flow directions, making them more available to ecosystems and ultimately saving them from disappearing in sea floor sediments. Megafauna extinctions have reduced this capacity dramatically, while humans and their livestock aren’t stepping in to restore this important ecosystem service.

Anger Control Bibliotherapy with a Convicted Murderer under Life Sentence: A Clinical Report.

ERIC Educational Resources Information Center

Daniel, Chris

1992-01-01

Used personalized bibliotherapy intervention approach to prevent build up of aggression in inmate with low tolerance to perceived provocation. Follow-up data over six-month period revealed dramatic decrease in discipline reports following therapy. Interview and questionnaire feedback from client indicated reduced incidence of feelings of…

Financial and Economic Analysis of Reduced Impact Logging

Treesearch

Tom Holmes

2016-01-01

Concern regarding extensive damage to tropical forests resulting from logging increased dramatically after World War II when mechanized logging systems developed in industrialized countries were deployed in the tropics. As a consequence, tropical foresters began developing logging procedures that were more environmentally benign, and by the 1990s, these practices began...

Stratification of soil chemical and microbial properties under no-till management after lime amendment

USDA-ARS?s Scientific Manuscript database

Adoption of no-till (NT) technology in the dryland cropping region of the inland Pacific Northwest (iPNW) has dramatically reduced soil erosion compared to conventional tillage. Soils under continuous NT, however, often produce stratified soil acidification compared with conventional tillage due to ...

Effective dust control systems on concrete dowel drilling machinery.

PubMed

Echt, Alan S; Sanderson, Wayne T; Mead, Kenneth R; Feng, H Amy; Farwick, Daniel R; Farwick, Dawn Ramsey

2016-09-01

Rotary-type percussion dowel drilling machines, which drill horizontal holes in concrete pavement, have been documented to produce respirable crystalline silica concentrations above recommended exposure criteria. This places operators at potential risk for developing health effects from exposure. United States manufacturers of these machines offer optional dust control systems. The effectiveness of the dust control systems to reduce respirable dust concentrations on two types of drilling machines was evaluated under controlled conditions with the machines operating inside large tent structures in an effort to eliminate secondary exposure sources not related to the dowel-drilling operation. Area air samples were collected at breathing zone height at three locations around each machine. Through equal numbers of sampling rounds with the control systems randomly selected to be on or off, the control systems were found to significantly reduce respirable dust concentrations from a geometric mean of 54 mg per cubic meter to 3.0 mg per cubic meter on one machine and 57 mg per cubic meter to 5.3 mg per cubic meter on the other machine. This research shows that the dust control systems can dramatically reduce respirable dust concentrations by over 90% under controlled conditions. However, these systems need to be evaluated under actual work conditions to determine their effectiveness in reducing worker exposures to crystalline silica below hazardous levels.

An Essential Role of INI1/hSNF5 Chromatin Remodeling Protein in HIV-1 Posttranscriptional Events and Gag/Gag-Pol Stability

PubMed Central

La Porte, Annalena; Cano, Jennifer; Wu, Xuhong; Mitra, Doyel

2016-01-01

ABSTRACT INI1/hSNF5/SMARCB1/BAF47 is an HIV-specific integrase (IN)-binding protein that influences HIV-1 transcription and particle production. INI1 binds to SAP18 (Sin3a-associated protein, 18 kDa), and both INI1 and SAP18 are incorporated into HIV-1 virions. To determine the significance of INI1 and the INI1-SAP18 interaction during HIV-1 replication, we isolated a panel of SAP18-interaction-defective (SID)-INI1 mutants using a yeast reverse two-hybrid screen. The SID-INI1 mutants, which retained the ability to bind to IN, cMYC, and INI1 but were impaired for binding to SAP18, were tested for their effects on HIV-1 particle production. SID-INI1 dramatically reduced the intracellular Gag/Gag-Pol protein levels and, in addition, decreased viral particle production. The SID-INI1-mediated effects were less dramatic in trans complementation assays using IN deletion mutant viruses with Vpr-reverse transcriptase (RT)-IN. SID-INI1 did not inhibit long-terminal-repeat (LTR)-mediated transcription, but it marginally decreased the steady-state gag RNA levels, suggesting a posttranscriptional effect. Pulse-chase analysis indicated that in SID-INI1-expressing cells, the pr55Gag levels decreased rapidly. RNA interference analysis indicated that small hairpin RNA (shRNA)-mediated knockdown of INI1 reduced the intracellular Gag/Gag-Pol levels and further inhibited HIV-1 particle production. These results suggest that SID-INI1 mutants inhibit multiple stages of posttranscriptional events of HIV-1 replication, including intracellular Gag/Gag-Pol RNA and protein levels, which in turn inhibits assembly and particle production. Interfering INI1 leads to a decrease in particle production and Gag/Gag-Pol protein levels. Understanding the role of INI1 and SAP18 in HIV-1 replication is likely to provide novel insight into the stability of Gag/Gag-Pol, which may lead to the development of novel therapeutic strategies to inhibit HIV-1 late events. IMPORTANCE Significant gaps exist in our current understanding of the mechanisms and host factors that influence HIV-1 posttranscriptional events, including gag RNA levels, Gag/Gag-Pol protein levels, assembly, and particle production. Our previous studies suggested that the IN-binding host factor INI1 plays a role in HIV-1 assembly. An ectopically expressed minimal IN-binding domain of INI1, S6, potently and selectively inhibited HIV-1 Gag/Gag-Pol trafficking and particle production. However, whether or not endogenous INI1 and its interacting partners, such as SAP18, are required for late events was unknown. Here, we report that endogenous INI1 and its interaction with SAP18 are necessary to maintain intracellular levels of Gag/Gag-Pol and for particle production. Interfering INI1 or the INI1-SAP18 interaction leads to the impairment of these processes, suggesting a novel strategy for inhibiting posttranscriptional events of HIV-1 replication. PMID:27558426

Alpha-fetoprotein is a biomarker of unfolded protein response and altered proteostasis in hepatocellular carcinoma cells exposed to sorafenib.

PubMed

Houessinon, Aline; Gicquel, Albane; Bochereau, Flora; Louandre, Christophe; Nyga, Rémy; Godin, Corinne; Degonville, James; Fournier, Emma; Saidak, Zuzana; Drullion, Claire; Barbare, Jean-Claude; Chauffert, Bruno; François, Catherine; Pluquet, Olivier; Galmiche, Antoine

2016-01-28

Sorafenib is the treatment of reference for advanced hepatocellular carcinoma (HCC). A decrease in the serum levels of Alpha-fetoprotein (AFP) is reported to be the biological parameter that is best associated with disease control by sorafenib. In order to provide a biological rationale for the variations of AFP, we analyzed the various steps of AFP production in human HCC cell lines exposed to sorafenib. Sorafenib dramatically reduced the levels of AFP produced by HCC cells independently of its effect on cell viability. The mRNA levels of AFP decreased upon sorafenib treatment, while the AFP protein remained localized in the Golgi apparatus. Sorafenib activated the Regulated Inositol-Requiring Enzyme-1α (IRE-1α) and the PKR-like ER Kinase (PERK)-dependent arms of the Unfolded Protein Response (UPR). The inhibition of IRE-1α partially restored the mRNA levels of AFP upon treatment with sorafenib. The inhibition of both pathways partially prevented the drop in the production of AFP induced by sorafenib. The findings provide new insights on the regulation of AFP, and identify it as a biomarker suitable for the exploration of HCC cell proteostasis in the context of therapeutic targeting. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Polyamine levels as related to growth, differentiation and senescence in protoplast-derived cultures of Vigna aconitifolia and Avena sativa

NASA Technical Reports Server (NTRS)

Kaur Sawhney, R.; Shekhawat, N. S.; Galston, A. W.

1985-01-01

We have previously reported that aseptically cultured mesophyll protoplasts of Vigna divide rapidly and regenerate into complete plants, while mesophyll protoplasts of Avena divide only sporadically and senesce rapidly after isolation. We measured polyamine titers in such cultures of Vigna and Avena, to study possible correlations between polyamines and cellular behavior. We also deliberately altered polyamine titer by the use of selective inhibitors of polyamine biosynthesis, noting the effects on internal polyamine titer, cell division activity and regenerative events. In Vigna cultures, levels of free and bound putrescine and spermidine increased dramatically as cell division and differentiation progressed. The increase in bound polyamines was largest in embryoid-forming callus tissue while free polyamine titer was highest in root-forming callus. In Avena cultures, the levels of total polyamines decreased as the protoplast senesced. The presence of the inhibitors alpha-difluoromethyl-arginine (specific inhibitor of arginine decarboxylase), alpha-difluoromethylornithine (specific inhibitor of ornithine decarboxylase) and dicyclohexylamine (inhibitor of spermidine synthase) reduced cell division and organogenesis in Vigna cultures. Addition of low concentration of polyamines to such cultures containing inhibitors or removal of inhibitors from the culture medium restored the progress of growth and differentiation with concomitant increase in polyamine levels.

High-Density Lipoprotein-Targeted Therapy and Apolipoprotein A-I Mimetic Peptides.

PubMed

Uehara, Yoshinari; Chiesa, Giulia; Saku, Keijiro

2015-01-01

Numerous randomized clinical trials have established statins as the major standard therapy for atherosclerotic diseases because these molecules decrease the plasma level of low-density lipoprotein (LDL) cholesterol and moderately increase that of plasma high-density lipoprotein (HDL) cholesterol. The reverse cholesterol transport pathway, mediated by HDL particles, has a relevant antiatherogenic potential. An important approach to HDL-targeted therapy is optimization of the HDL-cholesterol level and enhanced removal of plasma cholesterol, together with the prevention and mitigation of inflammation related to atherosclerosis. Small-molecule inhibitors of cholesteryl ester transfer protein (CETP) increase the HDL-cholesterol level in subjects with normal or low HDL-cholesterol. However, CETP inhibitors do not seem to reduce the risk of atherosclerotic diseases. HDL therapies using reconstituted HDL, including apolipoprotein (Apo) A-I Milano, ApoA-I mimetics, or full-length ApoA-I, are dramatically effective in animal models. Of those, the ApoA-I-mimetic peptide called FAMP effectively removes cholesterol via the ABCA1 transporter and acts as an antiatherosclerotic agent by enhancing the biological functions of HDL without elevating the HDL-cholesterol level. Our review of the literature leads us to conclude that HDL-targeted therapies have significant atheroprotective potential and thus may effectively treat patients with cardiovascular diseases.

Effect of altitude on brain intracellular pH and inorganic phosphate levels

PubMed Central

Shi, Xian-Feng; Carlson, Paul J.; Kim, Tae-Suk; Sung, Young-Hoon; Hellem, Tracy L.; Fiedler, Kristen K.; Kim, Seong-Eun; Glaeser, Breanna; Wang, Kristina; Zuo, Chun S.; Jeong, Eun-Kee; Renshaw, Perry F.; Kondo, Douglas G.

2015-01-01

Normal brain activity is associated with task-related pH changes. Although central nervous system syndromes associated with significant acidosis and alkalosis are well understood, the effects of less dramatic and chronic changes in brain pH are uncertain. One environmental factor known to alter brain pH is the extreme, acute change in altitude encountered by mountaineers. However, the effect of long-term exposure to moderate altitude has not been studied. The aim of this two-site study was to measure brain intracellular pH and phosphate-bearing metabolite levels at two altitudes in healthy volunteers, using phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Increased brain pH and reduced inorganic phosphate (Pi) levels were found in healthy subjects who were long-term residents of Salt Lake City, UT (4720 ft/1438 m), compared with residents of Belmont, MA (20 ft/6 m). Brain intracellular pH at the altitude of 4720 ft was more alkaline than that observed near sea level. In addition, the ratio of inorganic phosphate to total phosphate signal also shifted toward lower values in the Salt Lake City region compared with the Belmont area. These results suggest that long-term residence at moderate altitude is associated with brain chemical changes. PMID:24768210

N-Acylethanolamine metabolism interacts with abscisic acid signaling in Arabidopsis thaliana seedlings.

PubMed

Teaster, Neal D; Motes, Christy M; Tang, Yuhong; Wiant, William C; Cotter, Matthew Q; Wang, Yuh-Shuh; Kilaru, Aruna; Venables, Barney J; Hasenstein, Karl H; Gonzalez, Gabriel; Blancaflor, Elison B; Chapman, Kent D

2007-08-01

N-Acylethanolamines (NAEs) are bioactive acylamides that are present in a wide range of organisms. In plants, NAEs are generally elevated in desiccated seeds, suggesting that they may play a role in seed physiology. NAE and abscisic acid (ABA) levels were depleted during seed germination, and both metabolites inhibited the growth of Arabidopsis thaliana seedlings within a similar developmental window. Combined application of low levels of ABA and NAE produced a more dramatic reduction in germination and growth than either compound alone. Transcript profiling and gene expression studies in NAE-treated seedlings revealed elevated transcripts for a number of ABA-responsive genes and genes typically enriched in desiccated seeds. The levels of ABI3 transcripts were inversely associated with NAE-modulated growth. Overexpression of the Arabidopsis NAE degrading enzyme fatty acid amide hydrolase resulted in seedlings that were hypersensitive to ABA, whereas the ABA-insensitive mutants, abi1-1, abi2-1, and abi3-1, exhibited reduced sensitivity to NAE. Collectively, our data indicate that an intact ABA signaling pathway is required for NAE action and that NAE may intersect the ABA pathway downstream from ABA. We propose that NAE metabolism interacts with ABA in the negative regulation of seedling development and that normal seedling establishment depends on the reduction of the endogenous levels of both metabolites.

Extracellular vesicles from bone marrow-derived mesenchymal stem cells protect against murine hepatic ischemia/reperfusion injury.

PubMed

Haga, Hiroaki; Yan, Irene K; Borrelli, David A; Matsuda, Akiko; Parasramka, Mansi; Shukla, Neha; Lee, David D; Patel, Tushar

2017-06-01

Hepatic ischemia/reperfusion injury (IRI) and associated inflammation contributes to liver dysfunction and complications after liver surgery and transplantation. Mesenchymal stem cells (MSCs) have been reported to reduce hepatic IRI because of their reparative immunomodulatory effects in injured tissues. Recent studies have highlighted beneficial effects of extracellular vesicles from mesenchymal stem cells (MSC-EV) on tissue injury. The effects of systemically administered mouse bone marrow-derived MSC-EV were evaluated in an experimental murine model of hepatic IRI induced by cross-clamping the hepatic artery and portal vein for 90 minutes followed by reperfusion for periods of up to 6 hours. Compared with controls, intravenous administration of MSC-EV 30 minutes prior to IRI dramatically reduced the extent of tissue necrosis, decreased caspase 3-positive and apoptotic cells, and reduced serum aminotransferase levels. MSC-EV increased hepatic messenger RNA (mRNA) expression of NACHT, LRR, and PYD domains-containing protein 12, and the chemokine (C-X-C motif) ligand 1, and reduced mRNA expression of several inflammatory cytokines such as interleukin 6 during IRI. MSC-EV increased cell viability and suppressed both oxidative injury and nuclear factor kappa B activity in murine hepatocytes in vitro. In conclusion, the administration of extracellular vesicles derived from bone marrow-derived MSCs may ameliorate hepatic IRI by reducing hepatic injury through modulation of the inflammatory response.Liver Transplantation 23 791-803 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Arabidopsis ACCELERATED CELL DEATH2 Modulates Programmed Cell DeathW⃞

PubMed Central

Yao, Nan; Greenberg, Jean T.

2006-01-01

The Arabidopsis thaliana chloroplast protein ACCELERATED CELL DEATH2 (ACD2) modulates the amount of programmed cell death (PCD) triggered by Pseudomonas syringae and protoporphyrin IX (PPIX) treatment. In vitro, ACD2 can reduce red chlorophyll catabolite, a chlorophyll derivative. We find that ACD2 shields root protoplasts that lack chlorophyll from light- and PPIX-induced PCD. Thus, chlorophyll catabolism is not obligatory for ACD2 anti-PCD function. Upon P. syringae infection, ACD2 levels and localization change in cells undergoing PCD and in their close neighbors. Thus, ACD2 shifts from being largely in chloroplasts to partitioning to chloroplasts, mitochondria, and, to a small extent, cytosol. ACD2 protects cells from PCD that requires the early mitochondrial oxidative burst. Later, the chloroplasts of dying cells generate NO, which only slightly affects cell viability. Finally, the mitochondria in dying cells have dramatically altered movements and cellular distribution. Overproduction of both ACD2 (localized to mitochondria and chloroplasts) and ascorbate peroxidase (localized to chloroplasts) greatly reduces P. syringae–induced PCD, suggesting a pro-PCD role for mitochondrial and chloroplast events. During infection, ACD2 may bind to and/or reduce PCD-inducing porphyrin-related molecules in mitochondria and possibly chloroplasts that generate reactive oxygen species, cause altered organelle behavior, and activate a cascade of PCD-inducing events. PMID:16387834

CLABSI Conversations: Lessons From Peer-to-Peer Assessments to Reduce Central Line-Associated Bloodstream Infections.

PubMed

Pham, Julius Cuong; Goeschel, Christine A; Berenholtz, Sean M; Demski, Renee; Lubomski, Lisa H; Rosen, Michael A; Sawyer, Melinda D; Thompson, David A; Trexler, Polly; Weaver, Sallie J; Weeks, Kristina R; Pronovost, Peter J

2016-01-01

A national collaborative helped many hospitals dramatically reduce central line-associated bloodstream infections (CLABSIs), but some hospitals struggled to reduce infection rates. This article describes the development of a peer-to-peer assessment process (CLABSI Conversations) and the practical, actionable practices we discovered that helped intensive care unit teams achieve a CLABSI rate of less than 1 infection per 1000 catheter-days for at least 1 year. CLABSI Conversations was designed as a learning-oriented process, in which a team of peers visited hospitals to surface barriers to infection prevention and to share best practices and insights from successful intensive care units. Common practices led to 10 recommendations: executive and board leaders communicate the goal of zero CLABSI throughout the hospital; senior and unit-level leaders hold themselves accountable for CLABSI rates; unit physicians and nurse leaders own the problem; clinical leaders and infection preventionists build infection prevention training and simulation programs; infection preventionists participate in unit-based CLABSI reduction efforts; hospital managers make compliance with best practices easy; clinical leaders standardize the hospital's catheter insertion and maintenance practices and empower nurses to stop any potentially harmful acts; unit leaders and infection preventionists investigate CLABSIs to identify root causes; and unit nurses and staff audit catheter maintenance policies and practices.

Intestinal inflammation reduces expression of DRA, a transporter responsible for congenital chloride diarrhea.

PubMed

Yang, H; Jiang, W; Furth, E E; Wen, X; Katz, J P; Sellon, R K; Silberg, D G; Antalis, T M; Schweinfest, C W; Wu, G D

1998-12-01

The pathogenesis of diarrhea in intestinal inflammatory states is a multifactorial process involving the effects of inflammatory mediators on epithelial transport function. The effect of colonic inflammation on the gene expression of DRA (downregulated in adenoma), a chloride-sulfate anion transporter that is mutated in patients with congenital chloridorrhea, was examined in vivo as well as in an intestinal epithelial cell line. DRA mRNA expression was diminished five- to sevenfold in the HLA-B27/beta2m transgenic rat compared with control. In situ hybridization showed that DRA, which is normally expressed in the upper crypt and surface epithelium of the colon, was dramatically reduced in the surface epithelium of the HLA-B27/beta2m transgenic rat, the interleukin-10 (IL-10) knockout mouse with spontaneous colitis, and in patients with ulcerative colitis. Immunohistochemistry demonstrated that mRNA expression of DRA reflected that of protein expression in vivo. IL-1beta reduced DRA mRNA expression in vitro by inhibiting gene transcription. The loss of transport function in the surface epithelium of the colon by attenuation of transporter gene expression, perhaps inhibited at the level of gene transcription by proinflammatory cytokines, may play a role in the pathogenesis of diarrhea in colitis.

Enhancing Outcomes for Outpatient Percutaneous Coronary Interventions

PubMed Central

Spruce, Kevin; Butler, Chondra

2017-01-01

Purpose and Objectives: A quality improvement project was conducted to create a sustainable continuum of care for increased volumes of outpatients receiving percutaneous coronary interventions. Dramatic growth exposed system vulnerabilities and left staff overwhelmed. Four postinterventional project objectives included reducing preprocedural preparation times, reducing bleeding complications, reducing hospital length of stay, and collectively increasing patient satisfaction. Description of the Project: Amidst creating a specialized postintervention coronary recovery area and acquiring and training existing preregistration and recovery nurses, a fragmented system of care was united. The clinical nurse specialist–led project used a systematic and evidence-based implementation process to harmoniously acclimate perioperative staff. An evaluation process further defined new opportunities to support a growing service line. Outcomes: Postimplementation data were collected over a 3-month period. An overall improvement was found in all targeted objectives, despite an upsurge in case volumes. A moderately significant correlation (r [105] = 0.424, P < .001) was found between bleeding occurrences and hospital length of stay. Conclusion: The synergy between interdepartmental collaboration and strategic staffing reallocation was shown to be invaluable to alleviate procedural areas of service, such as the cardiac catheterization laboratory. As a project champion, the clinical nurse specialist is an essential catalyst to identify and creatively surmount system-level challenges. PMID:28991015

Opportunities and challenges for harvest weed seed control in global cropping systems.

PubMed

Walsh, Michael J; Broster, John C; Schwartz-Lazaro, Lauren M; Norsworthy, Jason K; Davis, Adam S; Tidemann, Breanne D; Beckie, Hugh J; Lyon, Drew J; Soni, Neeta; Neve, Paul; Bagavathiannan, Muthukumar V

2017-11-28

The opportunity to target weed seeds during grain harvest was established many decades ago following the introduction of mechanical harvesting and the recognition of high weed-seed retention levels at crop maturity; however, this opportunity remained largely neglected until more recently. The introduction and adoption of harvest weed seed control (HWSC) systems in Australia has been in response to widespread occurrence of herbicide-resistant weed populations. With diminishing herbicide resources and the need to maintain highly productive reduced tillage and stubble-retention practices, growers began to develop systems that targeted weed seeds during crop harvest. Research and development efforts over the past two decades have established the efficacy of HWSC systems in Australian cropping systems, where widespread adoption is now occurring. With similarly dramatic herbicide resistance issues now present across many of the world's cropping regions, it is timely for HWSC systems to be considered for inclusion in weed-management programs in these areas. This review describes HWSC systems and establishing the potential for this approach to weed control in several cropping regions. As observed in Australia, the inclusion of HWSC systems can reduce weed populations substantially reducing the potential for weed adaptation and resistance evolution. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Caffeinol at the receptor level; Anti-ischemic effect of NMDA receptor blockade is potentiated by caffeine

PubMed Central

Zhao, Xiurong; Strong, Roger; Piriyawat, Paisith; Palusinski, Robert; Grotta, James C.; Aronowski, Jaroslaw

2010-01-01

Background and Purpose Although caffeinol (combination of low dose of caffeine and ethanol) was shown to robustly reduce stroke damage in experimental models and is now in clinical evaluation for treatment of ischemic stroke, little is known about the potential mechanism of its action. Methods We have used an in vivo excitotoxicity model based on intracortical infusion of NMDA and model of reversible focal ischemia to demonstrate NMDA receptor inhibition as one potential mechanism of Caffeinol anti-ischemic activity. Results Caffeinol reduced the size of excitotoxic lesion and substitution of ethanol in Caffeinol with CNS-1102 and MK-801, but not with MgSO4, produced treatment with strong synergistic effect that was at least as robust in reducing ischemic damage as Caffeinol. This NMDA receptor antagonist and caffeine combination showed long window of opportunity, activity in spontaneously hypertensive rats, and unlike Caffeinol was fully effective in animals chronically pre-treated with ethanol. Conclusions Our study suggests that anti-excitotoxic properties may underlie some of the anti-ischemic effect of Caffeinol. This study provides strong evidence that the anti-ischemic effect of NMDA receptor blockers in general can be dramatically augmented by caffeine, thus opening a possibility for new utilization of NMDA-based pharmacology in the treatment of stroke. PMID:20044532

Reduction of Diffusion-Weighted Imaging Contrast of Acute Ischemic Stroke at Short Diffusion Times.

PubMed

Baron, Corey Allan; Kate, Mahesh; Gioia, Laura; Butcher, Kenneth; Emery, Derek; Budde, Matthew; Beaulieu, Christian

2015-08-01

Diffusion-weighted imaging (DWI) of tissue water is a sensitive and specific indicator of acute brain ischemia, where reductions of the diffusion of tissue water are observed acutely in the stroke lesion core. Although these diffusion changes have been long attributed to cell swelling, the precise nature of the biophysical mechanisms remains uncertain. The potential cause of diffusion reductions after stroke was investigated using an advanced DWI technique, oscillating gradient spin-echo DWI, that enables much shorter diffusion times and can improve specificity for alterations of structure at the micron level. Diffusion measurements in the white matter lesions of patients with acute ischemic stroke were reduced by only 8% using oscillating gradient spin-echo DWI, in contrast to a 37% decrease using standard DWI. Neurite beading has recently been proposed as a mechanism for the diffusion changes after ischemic stroke with some ex vivo evidence. To explore whether beading could cause such differential results, simulations of beaded cylinders and axonal swelling were performed, yielding good agreement with experiment. Short diffusion times result in dramatically reduced diffusion contrast of human stroke. Simulations implicate a combination of neuronal beading and axonal swelling as the key structural changes leading to the reduced apparent diffusion coefficient after stroke. © 2015 American Heart Association, Inc.

Toona sinensis Inhibits Murine Leukemia WEHI-3 Cells and Promotes Immune Response In Vivo.

PubMed

Yang, Hsin-Ling; Thiyagarajan, Varadharajan; Liao, Jiunn-Wang; Chu, Yu-Lin; Chang, Chia-Ting; Huang, Pei-Jane; Hsu, Chih-Jung; Hseu, You-Cheng

2017-09-01

Toona sinensis (TS) is one of the most popular vegetarian dishes in Taiwan. It has been shown to exhibit antioxidant, antiangiogenic, antiatherosclerotic, and anticancer properties. In this study, we demonstrated the ability of aqueous leaf extracts from TS to promote immune responses in BALB/c mice and to exhibit anti-leukemia activity in murine WEHI-3 cells. BALB/c mice were injected intravenously with WEHI-3 cells and then treated orally with TS (50 mg/kg). In vivo study showed that TS treatment reduced liver and spleen enlargement in WEHI-3 bearing mice compared with the untreated group. Furthermore, TS also decreased white blood cells (WBC), indicating inhibition of differentiation of the precursor of macrophages in WEHI-3 bearing mice. Treatment of WEHI-3 cells with TS (0-75 μg/mL for 24 hours) significantly reduced cell viability. Furthermore, TS treatment-induced late apoptosis was confirmed by Annexin-V/PI staining. Western blot analyses revealed that treatment of WEHI-3 cells with TS statistically increased the protein expression level of cytochrome c in the cytoplasm and activates caspase-3. Notably, TS treatment caused a dramatic reduction in Bcl-2 and increase in Bax protein levels. TS may disturb the Bcl-2 and Bax protein ratio and induce apoptosis. This reports confirms the antitumor activity of this nutritious vegetable potentially against leukemia.

Histone posttranslational modifications and cell fate determination: lens induction requires the lysine acetyltransferases CBP and p300

PubMed Central

Wolf, Louise; Harrison, Wilbur; Huang, Jie; Xie, Qing; Xiao, Ningna; Sun, Jian; Kong, Lingkun; Lachke, Salil A.; Kuracha, Murali R.; Govindarajan, Venkatesh; Brindle, Paul K.; Ashery-Padan, Ruth; Beebe, David C.; Overbeek, Paul A.; Cvekl, Ales

2013-01-01

Lens induction is a classical embryologic model to study cell fate determination. It has been proposed earlier that specific changes in core histone modifications accompany the process of cell fate specification and determination. The lysine acetyltransferases CBP and p300 function as principal enzymes that modify core histones to facilitate specific gene expression. Herein, we performed conditional inactivation of both CBP and p300 in the ectodermal cells that give rise to the lens placode. Inactivation of both CBP and p300 resulted in the dramatic discontinuation of all aspects of lens specification and organogenesis, resulting in aphakia. The CBP/p300−/− ectodermal cells are viable and not prone to apoptosis. These cells showed reduced expression of Six3 and Sox2, while expression of Pax6 was not upregulated, indicating discontinuation of lens induction. Consequently, expression of αB- and αA-crystallins was not initiated. Mutant ectoderm exhibited markedly reduced levels of histone H3 K18 and K27 acetylation, subtly increased H3 K27me3 and unaltered overall levels of H3 K9ac and H3 K4me3. Our data demonstrate that CBP and p300 are required to establish lens cell-type identity during lens induction, and suggest that posttranslational histone modifications are integral to normal cell fate determination in the mammalian lens. PMID:24038357

Short-term effects of povidone iodine and sodium fluoride therapy on plaque levels and microbiome diversity.

PubMed

Reilly, C; Goettl, M; Steinmetz, M; Nikrad, J; Jones, R S

2016-03-01

The objective of this study is to evaluate the effect of short-term changes in the oral microbial ecology of dental plaque and plaque levels after topical treatment of a combination of 10% povidone iodine (PI) and 5% sodium fluoride varnish (FV). A single group design intervention study on 12 pediatric patients, who underwent two baseline plaques samplings before the intervention, were enrolled in the study. A modified mixed dentition Silness-Löe plaque index score was used to assess plaque accumulation and microbial composition was assessed by amplicon sequencing analysis of the 16S rRNA V4 region. Dental plaque accumulation (P = 0.0424) was reduced after 1 week using PI/FV application. This reduction was not observed between the two double-baseline visits. 16S rRNA analysis showed that the single PI/FV therapy did not have dramatic shifts in the plaque microbiome community depicted by hierarchical cluster and principle component analysis. More subtle changes were found when analyzing the Shannon diversity index after the application of PI/FV vs two baselines prior to combination therapy. The bacteria within the dental biofilms showed resilience in maintaining the overall community diversity but reduced biofilm accumulation following PI/FV therapy. Repeated uses of PI/FV may augment plaque control during dental rehabilitation in children. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

cld and lec23 are disparate mutations that affect maturation of lipoprotein lipase in the endoplasmic reticulum.

PubMed

Briquet-Laugier, V; Ben-Zeev, O; White, A; Doolittle, M H

1999-11-01

The mutations cld (combined lipase deficiency) and lec23 disrupt in a similar manner the expression of lipoprotein lipase (LPL). Whereas cld affects an unknown gene, lec23 abolishes the activity of alpha-glucosidase I, an enzyme essential for proper folding and assembly of nascent glycoproteins. The hypothesis that cld, like lec23, affects the folding/assembly of nascent LPL was confirmed by showing that in cell lines homozygous for these mutations (Cld and Lec23, respectively), the majority of LPL was inactive, displayed heterogeneous aggregation, and had a decreased affinity for heparin. While inactive LPL was retained in the ER, a small amount of LPL that had attained a native conformation was transported through the Golgi and secreted. Thus, Cld and Lec23 cells recognized and retained the majority of LPL as misfolded, maintaining the standard of quality control. Examination of candidate factors affecting protein maturation, such as glucose addition and trimming, proteins involved in lectin chaperone cycling, and other abundant ER chaperones, revealed that calnexin levels were dramatically reduced in livers from cld/cld mice; this finding was also confirmed in Cld cells. We conclude that cld may affect components in the ER, such as calnexin, that play a role in protein maturation. Whether the reduced calnexin levels per se contribute to the LPL deficiency awaits confirmation.

The paradox of extreme high-altitude migration in bar-headed geese Anser indicus

PubMed Central

Hawkes, L. A.; Balachandran, S.; Batbayar, N.; Butler, P. J.; Chua, B.; Douglas, D. C.; Frappell, P. B.; Hou, Y.; Milsom, W. K.; Newman, S. H.; Prosser, D. J.; Sathiyaselvam, P.; Scott, G. R.; Takekawa, J. Y.; Natsagdorj, T.; Wikelski, M.; Witt, M. J.; Yan, B.; Bishop, C. M.

2013-01-01

Bar-headed geese are renowned for migratory flights at extremely high altitudes over the world's tallest mountains, the Himalayas, where partial pressure of oxygen is dramatically reduced while flight costs, in terms of rate of oxygen consumption, are greatly increased. Such a mismatch is paradoxical, and it is not clear why geese might fly higher than is absolutely necessary. In addition, direct empirical measurements of high-altitude flight are lacking. We test whether migrating bar-headed geese actually minimize flight altitude and make use of favourable winds to reduce flight costs. By tracking 91 geese, we show that these birds typically travel through the valleys of the Himalayas and not over the summits. We report maximum flight altitudes of 7290 m and 6540 m for southbound and northbound geese, respectively, but with 95 per cent of locations received from less than 5489 m. Geese travelled along a route that was 112 km longer than the great circle (shortest distance) route, with transit ground speeds suggesting that they rarely profited from tailwinds. Bar-headed geese from these eastern populations generally travel only as high as the terrain beneath them dictates and rarely in profitable winds. Nevertheless, their migration represents an enormous challenge in conditions where humans and other mammals are only able to operate at levels well below their sea-level maxima. PMID:23118436

Repression of gibberellin biosynthesis or signaling produces striking alterations in poplar growth, morphology, and flowering.

PubMed

Zawaski, Christine; Kadmiel, Mahita; Pickens, Jim; Ma, Cathleen; Strauss, Steven; Busov, Victor

2011-12-01

We modified gibberellin (GA) metabolism and signaling in transgenic poplars using dominant transgenes and studied their effects for 3 years under field conditions. The transgenes that we employed either reduced the bioactive GAs, or attenuated their signaling. The majority of transgenic trees had significant and in many cases dramatic changes in height, crown architecture, foliage morphology, flowering onset, floral structure, and vegetative phenology. Most transgenes elicited various levels of height reduction consistent with the roles of GA in elongation growth. Several other growth traits were proportionally reduced, including branch length, internode distance, and leaf length. In contrast to elongation growth, stem diameter growth was much less affected, suggesting that semi-dwarf trees in dense stands might provide high levels of biomass production and carbon sequestration. The severity of phenotypic effects was strongly correlated with transgene expression among independent transgenic events, but often in a non-linear manner, the form of which varied widely among constructs. The majority of semi-dwarfed, transgenic plants showed delayed bud flush and early bud set, and expression of a native GAI transgene accelerated first time flowering in the field. All of the phenotypic changes observed in multiple years were stable over the 3 years of field study. Our results suggest that transgenic modification of GA action may be useful for producing semi-dwarf trees with modified growth and morphology for horticulture and other uses.

The paradox of extreme high-altitude migration in bar-headed geese Anser indicus

USGS Publications Warehouse

Hawkes, L.A.; Balachandran, S.; Batbayar, N.; Butler, P.J.; Chua, B.; Douglas, David C.; Frappell, P.B.; Hou, Y.; Milsom, W.K.; Newman, S.H.; Prosser, D.J.; Sathiyaselvam, P.; Scott, G.R.; Takekawa, John Y.; Natsagdorj, T.; Wikelski, M.; Witt, M.J.; Yan, B.; Bishop, C.M.

2012-01-01

Bar-headed geese are renowned for migratory flights at extremely high altitudes over the world's tallest mountains, the Himalayas, where partial pressure of oxygen is dramatically reduced while flight costs, in terms of rate of oxygen consumption, are greatly increased. Such a mismatch is paradoxical, and it is not clear why geese might fly higher than is absolutely necessary. In addition, direct empirical measurements of high-altitude flight are lacking. We test whether migrating bar-headed geese actually minimize flight altitude and make use of favourable winds to reduce flight costs. By tracking 91 geese, we show that these birds typically travel through the valleys of the Himalayas and not over the summits. We report maximum flight altitudes of 7290 m and 6540 m for southbound and northbound geese, respectively, but with 95 per cent of locations received from less than 5489 m. Geese travelled along a route that was 112 km longer than the great circle (shortest distance) route, with transit ground speeds suggesting that they rarely profited from tailwinds. Bar-headed geese from these eastern populations generally travel only as high as the terrain beneath them dictates and rarely in profitable winds. Nevertheless, their migration represents an enormous challenge in conditions where humans and other mammals are only able to operate at levels well below their sea-level maxima.

Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization.

PubMed

Muntean, Andrew G; Pang, Liyan; Poncz, Mortimer; Dowdy, Steven F; Blobel, Gerd A; Crispino, John D

2007-06-15

Endomitosis is a unique form of cell cycle used by megakaryocytes, in which the latter stages of mitosis are bypassed so that the cell can increase its DNA content and size. Although several transcription factors, including GATA-1 and RUNX-1, have been implicated in this process, the link between transcription factors and polyploidization remains undefined. Here we show that GATA-1-deficient megakaryocytes, which display reduced size and polyploidization, express nearly 10-fold less cyclin D1 and 10-fold increased levels of p16 compared with their wild-type counterparts. We further demonstrate that cyclin D1 is a direct GATA-1 target in megakaryocytes, but not erythroid cells. Restoration of cyclin D1 expression, when accompanied by ectopic overexpression of its partner Cdk4, resulted in a dramatic increase in megakaryocyte size and DNA content. However, terminal differentiation was not rescued. Of note, polyploidization was only modestly reduced in cyclin D1-deficient mice, likely due to compensation by elevated cyclin D3 expression. Finally, consistent with an additional defect conferred by increased levels of p16, inhibition of cyclin D-Cdk4 complexes with a TAT-p16 fusion peptide significantly blocked polyploidization of wild-type megakaryocytes. Together, these data show that GATA-1 controls growth and polyploidization by regulating cyclin D-Cdk4 kinase activity.

Cyclin D–Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization

PubMed Central

Muntean, Andrew G.; Pang, Liyan; Poncz, Mortimer; Dowdy, Steven F.; Blobel, Gerd A.

2007-01-01

Endomitosis is a unique form of cell cycle used by megakaryocytes, in which the latter stages of mitosis are bypassed so that the cell can increase its DNA content and size. Although several transcription factors, including GATA-1 and RUNX-1, have been implicated in this process, the link between transcription factors and polyploidization remains undefined. Here we show that GATA-1–deficient megakaryocytes, which display reduced size and polyploidization, express nearly 10-fold less cyclin D1 and 10-fold increased levels of p16 compared with their wild-type counterparts. We further demonstrate that cyclin D1 is a direct GATA-1 target in megakaryocytes, but not erythroid cells. Restoration of cyclin D1 expression, when accompanied by ectopic overexpression of its partner Cdk4, resulted in a dramatic increase in megakaryocyte size and DNA content. However, terminal differentiation was not rescued. Of note, polyploidization was only modestly reduced in cyclin D1–deficient mice, likely due to compensation by elevated cyclin D3 expression. Finally, consistent with an additional defect conferred by increased levels of p16, inhibition of cyclin D-Cdk4 complexes with a TAT-p16 fusion peptide significantly blocked polyploidization of wild-type megakaryocytes. Together, these data show that GATA-1 controls growth and polyploidization by regulating cyclin D-Cdk4 kinase activity. PMID:17317855

Parallel elastic elements improve energy efficiency on the STEPPR bipedal walking robot

DOE PAGES

Mazumdar, Anirban; Spencer, Steven J.; Hobart, Clinton; ...

2016-11-23

This study describes how parallel elastic elements can be used to reduce energy consumption in the electric motor driven, fully-actuated, STEPPR bipedal walking robot without compromising or significantly limiting locomotive behaviors. A physically motivated approach is used to illustrate how selectively-engaging springs for hip adduction and ankle flexion predict benefits for three different flat ground walking gaits: human walking, human-like robot walking and crouched robot walking. Based on locomotion data, springs are designed and substantial reductions in power consumption are demonstrated using a bench dynamometer. These lessons are then applied to STEPPR (Sandia Transmission-Efficient Prototype Promoting Research), a fully actuatedmore » bipedal robot designed to explore the impact of tailored joint mechanisms on walking efficiency. Featuring high-torque brushless DC motors, efficient low-ratio transmissions, and high fidelity torque control, STEPPR provides the ability to incorporate novel joint-level mechanisms without dramatically altering high level control. Unique parallel elastic designs are incorporated into STEPPR, and walking data shows that hip adduction and ankle flexion springs significantly reduce the required actuator energy at those joints for several gaits. These results suggest that parallel joint springs offer a promising means of supporting quasi-static joint torques due to body mass during walking, relieving motors of the need to support these torques and substantially improving locomotive energy efficiency.« less

Toona sinensis Inhibits Murine Leukemia WEHI-3 Cells and Promotes Immune Response In Vivo

PubMed Central

Yang, Hsin-Ling; Thiyagarajan, Varadharajan; Liao, Jiunn-Wang; Chu, Yu-Lin; Chang, Chia-Ting; Huang, Pei-Jane; Hsu, Chih-Jung; Hseu, You-Cheng

2016-01-01

Toona sinensis (TS) is one of the most popular vegetarian dishes in Taiwan. It has been shown to exhibit antioxidant, antiangiogenic, antiatherosclerotic, and anticancer properties. In this study, we demonstrated the ability of aqueous leaf extracts from TS to promote immune responses in BALB/c mice and to exhibit anti-leukemia activity in murine WEHI-3 cells. BALB/c mice were injected intravenously with WEHI-3 cells and then treated orally with TS (50 mg/kg). In vivo study showed that TS treatment reduced liver and spleen enlargement in WEHI-3 bearing mice compared with the untreated group. Furthermore, TS also decreased white blood cells (WBC), indicating inhibition of differentiation of the precursor of macrophages in WEHI-3 bearing mice. Treatment of WEHI-3 cells with TS (0-75 μg/mL for 24 hours) significantly reduced cell viability. Furthermore, TS treatment–induced late apoptosis was confirmed by Annexin-V/PI staining. Western blot analyses revealed that treatment of WEHI-3 cells with TS statistically increased the protein expression level of cytochrome c in the cytoplasm and activates caspase-3. Notably, TS treatment caused a dramatic reduction in Bcl-2 and increase in Bax protein levels. TS may disturb the Bcl-2 and Bax protein ratio and induce apoptosis. This reports confirms the antitumor activity of this nutritious vegetable potentially against leukemia. PMID:27151590

AIDS vaccines that allow HIV-1 to infect and escape immunologic control: a mathematic analysis of mass vaccination.

PubMed

van Ballegooijen, Marijn; Bogaards, Johannes A; Weverling, Gerrit-Jan; Boerlijst, Maarten C; Goudsmit, Jaap

2003-10-01

Cytotoxic T lymphocyte (CTL)-based HIV vaccine concepts shown to reduce viremia and postpone disease but not to prevent infection in monkeys are currently in human phase 1 trials. To evaluate the potential efficacy of vaccines that cannot prevent HIV-1 to infect and escape immunologic control, we designed a mathematic model that correlates the level of viremia to both infectiousness and disease progression. We speculate that vaccinees will have a virologic set point and disease progression rates comparable to untreated HIV-1-infected individuals with the best prognosis. Our model (illustrated with R0 = 3) shows that a sexually active population can ultimately be reduced to 26% of its initial size as a result of AIDS-related mortality in the absence of treatment or vaccination. Start of vaccination when HIV-1 prevalence is still low might postpone the peak incidence of infection and the dramatic decline in population size by up to 22 years. In conclusion, CTL-based vaccines that do not prevent HIV-1 infection but do postpone the time to onset of AIDS have considerable potential to curb the spread of HIV-1 and to postpone high AIDS-related mortality on a population level. The number of long-term survivors is substantially increased only when vaccination is initiated early in an AIDS epidemic, however.

Physical constraints in the condensation of eukaryotic chromosomes. Local concentration of DNA versus linear packing ratio in higher order chromatin structures.

PubMed

Daban, J R

2000-04-11

The local concentration of DNA in metaphase chromosomes of different organisms has been determined in several laboratories. The average of these measurements is 0.17 g/mL. In the first level of chromosome condensation, DNA is wrapped around histones forming nucleosomes. This organization limits the DNA concentration in nucleosomes to 0. 3-0.4 g/mL. Furthermore, in the structural models suggested in different laboratories for the 30-40 nm chromatin fiber, the estimated DNA concentration is significantly reduced; it ranges from 0.04 to 0.27 g/mL. The DNA concentration is further reduced when the fiber is folded into the successive higher order structures suggested in different models for metaphase chromosomes; the estimated minimum decrease of DNA concentration represents an additional 40%. These observations suggest that most of the models proposed for the 30-40 nm chromatin fiber are not dense enough for the construction of metaphase chromosomes. In contrast, it is well-known that the linear packing ratio increases dramatically in each level of DNA folding in chromosomes. Thus, the consideration of the linear packing ratio is not enough for the study of chromatin condensation; the constraint resulting from the actual DNA concentration in metaphase chromosomes must be considered for the construction of models for condensed chromatin.

Parallel elastic elements improve energy efficiency on the STEPPR bipedal walking robot

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

Mazumdar, Anirban; Spencer, Steven J.; Hobart, Clinton

This study describes how parallel elastic elements can be used to reduce energy consumption in the electric motor driven, fully-actuated, STEPPR bipedal walking robot without compromising or significantly limiting locomotive behaviors. A physically motivated approach is used to illustrate how selectively-engaging springs for hip adduction and ankle flexion predict benefits for three different flat ground walking gaits: human walking, human-like robot walking and crouched robot walking. Based on locomotion data, springs are designed and substantial reductions in power consumption are demonstrated using a bench dynamometer. These lessons are then applied to STEPPR (Sandia Transmission-Efficient Prototype Promoting Research), a fully actuatedmore » bipedal robot designed to explore the impact of tailored joint mechanisms on walking efficiency. Featuring high-torque brushless DC motors, efficient low-ratio transmissions, and high fidelity torque control, STEPPR provides the ability to incorporate novel joint-level mechanisms without dramatically altering high level control. Unique parallel elastic designs are incorporated into STEPPR, and walking data shows that hip adduction and ankle flexion springs significantly reduce the required actuator energy at those joints for several gaits. These results suggest that parallel joint springs offer a promising means of supporting quasi-static joint torques due to body mass during walking, relieving motors of the need to support these torques and substantially improving locomotive energy efficiency.« less

Production of Siderophores Increases Resistance to Fusaric Acid in Pseudomonas protegens Pf-5

PubMed Central

Ruiz, Jimena A.; Bernar, Evangelina M.; Jung, Kirsten

2015-01-01

Fusaric acid is produced by pathogenic fungi of the genus Fusarium, and is toxic to plants and rhizobacteria. Many fluorescent pseudomonads can prevent wilt diseases caused by these fungi. This study was undertaken to evaluate the effect of fusaric acid on P. protegens Pf-5 and elucidate the mechanisms that enable the bacterium to survive in the presence of the mycotoxin. The results confirm that fusaric acid negatively affects growth and motility of P. protegens. Moreover, a notable increase in secretion of the siderophore pyoverdine was observed when P. protegens was grown in the presence of fusaric acid. Concomitantly, levels of enzymes involved in the biosynthesis of pyoverdine and enantio-pyochelin, the second siderophore encoded by P. protegens, increased markedly. Moreover, while similar levels of resistance to fusaric acid were observed for P. protegens mutants unable to synthesize either pyoverdine or enanto-pyochelin and the wild type strain, a double mutant unable to synthesize both kinds of siderophores showed a dramatically reduced resistance to this compound. This reduced resistance was not observed when this mutant was grown under conditions of iron excess. Spectrophotometric titrations revealed that fusaric acid binds not only Fe2+ and Fe3+, but also Zn2+, Mn2+ and Cu2+, with high affinity. Our results demonstrate that iron sequestration accounts at least in part for the deleterious effect of the mycotoxin on P. protegens. PMID:25569682

Selective Regulation of Human Immunodeficiency Virus-Infected CD4+ Lymphocytes by a Synthetic Immunomodulator Leads to Potent Virus Suppression In Vitro and in hu-PBL-SCID Mice

PubMed Central

Bahr, George M.; Darcissac, Edith C. A.; Castéran, Nathalie; Amiel, Corinne; Cocude, Cécile; Truong, Marie-José; Dewulf, Joëlle; Capron, André; Mouton, Yves

2001-01-01

We have previously observed that the synthetic immunomodulator Murabutide inhibits human immunodeficiency virus type 1 (HIV-1) replication at multiple levels in macrophages and dendritic cells. The present study was designed to profile the activity of Murabutide on CD8-depleted phytohemagglutinin-activated lymphocytes from HIV-1-infected subjects and on the outcome of HIV-1 infection in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice). Maintaining cultures of CD8-depleted blasts from 36 patients in the presence of Murabutide produced dramatically reduced levels of viral p24 protein in the supernatants. This activity correlated with reduced viral transcripts and proviral DNA, was evident in cultures harboring R5, X4-R5, or X4 HIV-1 isolates, was not linked to inhibition of cellular DNA synthesis, and did not correlate with β-chemokine release. Moreover, c-myc mRNA expression was down-regulated in Murabutide-treated cells, suggesting potential interference of the immunomodulator with the nuclear transport of viral preintegration complexes. On the other hand, daily treatment of HIV-1-infected hu-PBL-SCID mice with Murabutide significantly reduced the viral loads in plasma and the proviral DNA content in human peritoneal cells. These results are the first to demonstrate that a clinically acceptable synthetic immunomodulator with an ability to enhance the host's nonspecific immune defense mechanisms against infections can directly regulate cellular factors in infected lymphocytes, leading to controlled HIV-1 replication. PMID:11435574

AMPK attenuates microtubule proliferation in cardiac hypertrophy.

PubMed

Fassett, John T; Hu, Xinli; Xu, Xin; Lu, Zhongbing; Zhang, Ping; Chen, Yingjie; Bache, Robert J

2013-03-01

Cell hypertrophy requires increased protein synthesis and expansion of the cytoskeletal networks that support cell enlargement. AMPK limits anabolic processes, such as protein synthesis, when energy supply is insufficient, but its role in cytoskeletal remodeling is not known. Here, we examined the influence of AMPK in cytoskeletal remodeling during cardiomyocyte hypertrophy, a clinically relevant condition in which cardiomyocytes enlarge but do not divide. In neonatal cardiomyocytes, activation of AMPK with 5-aminoimidazole carboxamide ribonucleotide (AICAR) or expression of constitutively active AMPK (CA-AMPK) attenuated cell area increase by hypertrophic stimuli (phenylephrine). AMPK activation had little effect on intermediate filaments or myofilaments but dramatically reduced microtubule stability, as measured by detyrosinated tubulin levels and cytoskeletal tubulin accumulation. Importantly, low-level AMPK activation limited cell expansion and microtubule growth independent of mTORC1 or protein synthesis repression, identifying a new mechanism by which AMPK regulates cell growth. Mechanistically, AICAR treatment increased Ser-915 phosphorylation of microtubule-associated protein 4 (MAP4), which reduces affinity for tubulin and prevents stabilization of microtubules (MTs). RNAi knockdown of MAP4 confirmed its critical role in cardiomyocyte MT stabilization. In support of a pathophysiological role for AMPK regulation of cardiac microtubules, AMPK α2 KO mice exposed to pressure overload (transverse aortic constriction; TAC) demonstrated reduced MAP4 phosphorylation and increased microtubule accumulation that correlated with the severity of contractile dysfunction. Together, our data identify the microtubule cytoskeleton as a sensitive target of AMPK activity, and the data suggest a novel role for AMPK in limiting accumulation and densification of microtubules that occurs in response to hypertrophic stress.

AMPK attenuates microtubule proliferation in cardiac hypertrophy

PubMed Central

Fassett, John T.; Hu, Xinli; Xu, Xin; Lu, Zhongbing; Zhang, Ping; Chen, Yingjie

2013-01-01

Cell hypertrophy requires increased protein synthesis and expansion of the cytoskeletal networks that support cell enlargement. AMPK limits anabolic processes, such as protein synthesis, when energy supply is insufficient, but its role in cytoskeletal remodeling is not known. Here, we examined the influence of AMPK in cytoskeletal remodeling during cardiomyocyte hypertrophy, a clinically relevant condition in which cardiomyocytes enlarge but do not divide. In neonatal cardiomyocytes, activation of AMPK with 5-aminoimidazole carboxamide ribonucleotide (AICAR) or expression of constitutively active AMPK (CA-AMPK) attenuated cell area increase by hypertrophic stimuli (phenylephrine). AMPK activation had little effect on intermediate filaments or myofilaments but dramatically reduced microtubule stability, as measured by detyrosinated tubulin levels and cytoskeletal tubulin accumulation. Importantly, low-level AMPK activation limited cell expansion and microtubule growth independent of mTORC1 or protein synthesis repression, identifying a new mechanism by which AMPK regulates cell growth. Mechanistically, AICAR treatment increased Ser-915 phosphorylation of microtubule-associated protein 4 (MAP4), which reduces affinity for tubulin and prevents stabilization of microtubules (MTs). RNAi knockdown of MAP4 confirmed its critical role in cardiomyocyte MT stabilization. In support of a pathophysiological role for AMPK regulation of cardiac microtubules, AMPK α2 KO mice exposed to pressure overload (transverse aortic constriction; TAC) demonstrated reduced MAP4 phosphorylation and increased microtubule accumulation that correlated with the severity of contractile dysfunction. Together, our data identify the microtubule cytoskeleton as a sensitive target of AMPK activity, and the data suggest a novel role for AMPK in limiting accumulation and densification of microtubules that occurs in response to hypertrophic stress. PMID:23316058

Regulation of hormonal responses of sweet pepper as affected by salinity and elevated CO2 concentration.

PubMed

Piñero, María Carmen; Houdusse, Fabrice; Garcia-Mina, Jose M; Garnica, María; Del Amor, Francisco M

2014-08-01

This study examines the extent to which the predicted CO2 -protective effects on the inhibition of growth, impairment of photosynthesis and nutrient imbalance caused by saline stress are mediated by an effective adaptation of the endogenous plant hormonal balance. Therefore, sweet pepper plants (Capsicum annuum, cv. Ciclón) were grown at ambient or elevated [CO2] (400 or 800 µmol mol(-1)) with a nutrient solution containing 0 or 80 mM NaCl. The results show that, under saline conditions, elevated [CO2] increased plant dry weight, leaf area, leaf relative water content and net photosynthesis compared with ambient [CO2], whilst the maximum potential quantum efficiency of photosystem II was not modified. In salt-stressed plants, elevated [CO2 ] increased leaf NO3(-) concentration and reduced Cl(-) concentration. Salinity stress induced ABA accumulation in the leaves but it was reduced in the roots at high [CO2], being correlated with the stomatal response. Under non-stressed conditions, IAA was dramatically reduced in the roots when high [CO2] was applied, which resulted in greater root DW and root respiration. Additionally, the observed high CK concentration in the roots (especially tZR) could prevent downregulation of photosynthesis at high [CO2], as the N level in the leaves was increased compared with the ambient [CO2], under salt-stress conditions. These results demonstrate that the hormonal balance was altered by the [CO2], which resulted in significant changes at the growth, gas exchange and nutritional levels. © 2013 Scandinavian Plant Physiology Society.

Predictors of Online Learning Success in a Rural Community College

ERIC Educational Resources Information Center

McPhaul-Moore, Elizabeth

2013-01-01

The number of courses offered online and the level of students enrolled in online courses has dramatically increased over the last several years. The National Education Center for Education Statistics reports that during the 2006-2007 school term, 97% of public two-year institutions across the nation offered college-level distance learning…

Infusion of oxytocin induces successful delivery in prostanoid FP-receptor-deficient mice.

PubMed

Kawamata, Masaki; Yoshida, Masahide; Sugimoto, Yukihiko; Kimura, Tadashi; Tonomura, Yutaka; Takayanagi, Yuki; Yanagisawa, Teruyuki; Nishimori, Katsuhiko

2008-02-13

The dramatic increase of oxytocin (OT) receptor (OTR) in the myometrium as well as circulating progesterone withdrawal has been thought to be the most important factor in the induction and accomplishment of parturition since delivery fails in prostaglandin F2alpha receptor (FP) knockout (FP KO) mice. The expression levels of OTR mRNA/protein were not dramatically increased in the near-term uteri of FP KO mice. However, OT-induced myometrial contractions and the concentration-response curves in FP KO in vitro were almost similar to those in wild-type (WT) mice. OT-infusion (0.3 U/day) enabled FP KO mice to experience successful delivery, and furthermore the duration until the onset was hastened by a higher dose of OT (3 U/day). The plasma progesterone levels of FP KO females were maintained at high levels, but decreased during labor by OT-infusion (3 U/day). These results suggest that OT has potentials to induce strong myometrial contractions in uterus with low expression levels of OTR and luteolysis in ovary, which enabled FP KO females to undergo successful delivery.

Decadal Changes in Ozone and Emissions in Central California and Current Issues

NASA Astrophysics Data System (ADS)

Tanrikulu, S.; Beaver, S.; Soong, S.; Tran, C.; Cordova, J.; Palazoglu, A.

2011-12-01

The relationships among ozone, emissions, and meteorology are very complex in central California, and must be well studied and understood in order to facilitate better air quality planning. Factors significantly impacting changes in emissions such as economic and population growth, and adopted emission controls make the matter even more complex. Here we review the history of ozone pollution in central California since the 1970s to plan for the future. Since the 1970s, changes in emissions have been accompanied by likewise dramatic changes in region-to-region differences in air quality. We focus on the coastal San Francisco Bay Area (SFBA) and the inland San Joaquin Valley (SJV). In the 1970s, the SFBA population was approaching 5 million people while the considerably larger and more rural SJV population remained below 2 million. The SFBA population was mostly confined to coastal locations. Peak ozone levels occurred mostly around the population centers and especially over the Bay itself. Hourly average ozone levels routinely approached 160 ppb. These high ozone levels promoted regulations under which SFBA emissions were continuously reduced through the present. By the 1990s, SFBA emissions had been reduced considerably despite the region's population growing to around 6 million. Relative to the 1970s, in 1990s the SFBA had lower peak ozone levels that were shifted to inland locations where much of the population growth was occurring. The SFBA still exceeded the federal 1-hour standard. A rapidly changing economic landscape in the 1970s promoted vast changes in the central California population distribution. In the SJV, the OPEC oil crisis promoted significant development of petroleum resources. Meanwhile, family farms were quickly being replaced with commercial-scale farming operations. The SJV population rapidly expanded to around 3 million people by the early 1990s. During this time, SJV emissions increased considerably, largely from increases in mobile source activities. The previously sparsely populated SJV had quickly developed an even more severe ozone problem than previous years. From 1990 to 2010, the SFBA population expanded to inland locations and then even further into the sheltered SJV. SFBA emissions for ROG and NOx were decreased around 40% and 15%, respectively during this period. High ozone levels became rather infrequent for coastal SFBA locations. During the same period, the SJV population continued to expand rapidly while emissions decreased, especially for ROG. Peak ozone levels remained around 100 ppb and shifted to locations downwind of Fresno and Bakersfield. Central California has experienced perhaps the most dramatic population growth and shifts in the United States during the contemporary economic era. These changes in population have led to some of the most difficult air quality management problems faced by regulators in the United States. Lessons learned from central California highlight the potential benefits of acting early and also the necessity for a long-term, flexible approach using sustained regulations to accompany population changes.

Effects of Different Modes of Hypobaric Hypoxia on the Content of Epigenetic Factors in the Rat in Neurons of Rat Neocortex.

PubMed

Samoilov, M O; Churilova, A V; Glushchenko, T S; Rybnikova, E A

2017-04-01

We studied the effects of different modes of hypobaric hypoxia on the content of epigenetic factors acH3K24, meH3K9, and meDNA modulating conformational characteristics of chromatin and gene expression in neurons of associative complex of rat parietal neocortex. Severe destructive hypoxia dramatically reduced the level of acH3K24 in 3 h after the end of exposure and increased meH3K9 and meDNA content. By contrast, 3-fold (but not single) adaptive exposure to moderate hypobaric hypoxia that produced a neuroprotective effect enhanced neuronal acH3K24 expression and decreased both meH3K9 and meDNA levels. Elevated acH3K24 content facilitates, while increased content of meH3K9 hampers binding of transcription factors to the target genes. At the same time, increased expression of meDNA suppresses transcription. The role of modification of epigenetic mechanisms in the regulation of proadaptive genes under the effects of hypoxic exposure according to various protocols is discussed.

Health Risks of Hypovitaminosis D: A Review of New Molecular Insights

PubMed Central

Ricca, Sergio; Currò, Monica; Ientile, Riccardo

2018-01-01

Hypovitaminosis D has become a pandemic, being observed in all ethnicities and age groups worldwide. Environmental factors, such as increased air pollution and reduced ultraviolet B (UVB) irradiation, as well as lifestyle factors, i.e., decreased outdoor activities and/or poor intake of vitamin D-rich food, are likely involved in the etiology of a dramatic reduction of vitamin D circulating levels. The insufficiency/deficiency of vitamin D has long been known for its association with osteoporosis and rickets. However, in the last few decades it has become a serious public health concern since it has been shown to be independently associated with various chronic pathological conditions such as cancer, coronary heart disease, neurological diseases, type II diabetes, autoimmune diseases, depression, with various inflammatory disorders, and with increased risk for all-cause mortality in the general population. Prevention strategies for these disorders have recently involved supplementation with either vitamin D2 or vitamin D3 or their analogs at required daily doses and tolerable upper-limit levels. This review will focus on the emerging evidence about non-classical biological functions of vitamin D in various disorders. PMID:29562608

Health Risks of Hypovitaminosis D: A Review of New Molecular Insights.

PubMed

Caccamo, Daniela; Ricca, Sergio; Currò, Monica; Ientile, Riccardo

2018-03-17

Hypovitaminosis D has become a pandemic, being observed in all ethnicities and age groups worldwide. Environmental factors, such as increased air pollution and reduced ultraviolet B (UVB) irradiation, as well as lifestyle factors, i.e., decreased outdoor activities and/or poor intake of vitamin D-rich food, are likely involved in the etiology of a dramatic reduction of vitamin D circulating levels. The insufficiency/deficiency of vitamin D has long been known for its association with osteoporosis and rickets. However, in the last few decades it has become a serious public health concern since it has been shown to be independently associated with various chronic pathological conditions such as cancer, coronary heart disease, neurological diseases, type II diabetes, autoimmune diseases, depression, with various inflammatory disorders, and with increased risk for all-cause mortality in the general population. Prevention strategies for these disorders have recently involved supplementation with either vitamin D2 or vitamin D3 or their analogs at required daily doses and tolerable upper-limit levels. This review will focus on the emerging evidence about non-classical biological functions of vitamin D in various disorders.

Cap-proximal nucleotides via differential eIF4E binding and alternative promoter usage mediate translational response to energy stress.

PubMed

Tamarkin-Ben-Harush, Ana; Vasseur, Jean-Jacques; Debart, Françoise; Ulitsky, Igor; Dikstein, Rivka

2017-02-08

Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing the contribution of cap-proximal TSS nucleotides, we found dramatic effect on translation only upon stress. As eIF4E levels were reduced, we determined its binding to capped-RNAs with different initiating nucleotides and found the lowest affinity to 5'cytidine in correlation with the translational stress-response. In addition, the number of differentially translated APs was elevated following stress. These include novel glucose starvation-induced downstream transcripts for the translation regulators eIF4A and Pabp, which are also translationally-induced despite general translational inhibition. The resultant eIF4A protein is N-terminally truncated and acts as eIF4A inhibitor. The induced Pabp isoform has shorter 5'UTR removing an auto-inhibitory element. Our findings uncovered several levels of coordination of transcription and translation responses to energy stress.

Controlled insertional mutagenesis using a LINE-1 (ORFeus) gene-trap mouse model.

PubMed

O'Donnell, Kathryn A; An, Wenfeng; Schrum, Christina T; Wheelan, Sarah J; Boeke, Jef D

2013-07-16

A codon-optimized mouse LINE-1 element, ORFeus, exhibits dramatically higher retrotransposition frequencies compared with its native long interspersed element 1 counterpart. To establish a retrotransposon-mediated mouse model with regulatable and potent mutagenic capabilities, we generated a tetracycline (tet)-regulated ORFeus element harboring a gene-trap cassette. Here, we show that mice expressing tet-ORFeus broadly exhibit robust retrotransposition in somatic tissues when treated with doxycycline. Consistent with a significant mutagenic burden, we observed a reduced number of double transgenic animals when treated with high-level doxycycline during embryogenesis. Transgene induction in skin resulted in a white spotting phenotype due to somatic ORFeus-mediated mutations that likely disrupt melanocyte development. The data suggest a high level of transposition in melanocyte precursors and consequent mutation of genes important for melanoblast proliferation, differentiation, or migration. These findings reveal the utility of a retrotransposon-based mutagenesis system as an alternative to existing DNA transposon systems. Moreover, breeding these mice to different tet-transactivator/reversible tet-transactivator lines supports broad functionality of tet-ORFeus because of the potential for dose-dependent, tissue-specific, and temporal-specific mutagenesis.

Nutrient digestibility of Mucuna (Mucuna pruriens var. utilis) bean in guinea fowl (Numida meleagris, L): Effects of heat treatment and levels of incorporation in diets.

PubMed

Dahouda, M; Toléba, S S; Youssao, A K I; Hambuckers, A; Dangou-Sapoho, R; Martin, G B; Fillet, M; Hornick, J-L

2009-09-01

1. Mucuna pruriens var. utilis is a legume, the seeds of which are scarcely used in animal diets owing to their high content of 3,4-dihydroxy-L-phenylalanine (L-Dopa). 2. Experiments were conducted on guinea fowl to assess the effects of two types of heat processing (cooking and toasting) on chemical composition and nutrient digestibility of Mucuna seeds offered alone or incorporated at three concentrations (40, 120 or 200 g/kg) in complete diets. 3. Diets containing 200 g/kg seeds had more crude fibre and less ether extract. L-Dopa content increased with the amount of Mucuna inclusion. Cooking reduced markedly L-Dopa content while toasting had no effect. When fed alone, Mucuna seeds dramatically decreased feed intake. 4. Feed intake (FI) and body weight gain (BWG) were not influenced by the complete diets. Cooking significantly increased crude fibre digestibility. 5. It is suggested that cracked and cooked Mucuna bean can be incorporated at a safe level of 120 g/kg in complete diets for guinea fowl production.

Hepatic FGF21 expression is induced at birth via PPARalpha in response to milk intake and contributes to thermogenic activation of neonatal brown fat.

PubMed

Hondares, Elayne; Rosell, Meritxell; Gonzalez, Frank J; Giralt, Marta; Iglesias, Roser; Villarroya, Francesc

2010-03-03

Plasma FGF21 levels and hepatic FGF21 gene expression increase dramatically after birth in mice. This induction is initiated by suckling, requires lipid intake, is impaired in PPARalpha null neonates, and is mimicked by treatment with the PPARalpha activator, Wy14,643. Neonates exhibit reduced FGF21 expression in response to fasting, in contrast to the upregulation occurring in adults. Changes in FGF21 expression due to suckling or nutritional manipulations were associated with circulating free fatty acid and ketone body levels. We mimicked the FGF21 postnatal rise by injecting FGF21 into fasting neonates, and found that this enhanced the expression of genes involved in thermogenesis within brown fat, and increased body temperature. Brown adipocytes treated with FGF21 exhibited increased expression of thermogenic genes, higher total and uncoupled respiration, and enhanced glucose oxidation. We propose that the induction of FGF21 production by the liver mediates direct activation of brown fat thermogenesis during the fetal-to-neonatal transition. 2010 Elsevier Inc. All rights reserved.

Photoluminescence and capacitance voltage characterization of GaAs surface passivated by an ultrathin GaN interface control layer

NASA Astrophysics Data System (ADS)

Anantathanasarn, Sanguan; Hasegawa, Hideki

2002-05-01

A novel surface passivation technique for GaAs using an ultrathin GaN interface control layer (GaN ICL) formed by surface nitridation was characterized by ultrahigh vacuum (UHV) photoluminescence (PL) and capacitance-voltage ( C- V) measurements. The PL quantum efficiency was dramatically enhanced after being passivated by the GaN ICL structure, reaching as high as 30 times of the initial clean GaAs surface. Further analysis of PL data was done by the PL surface state spectroscopy (PLS 3) simulation technique. PL and C- V results are in good agreement indicating that ultrathin GaN ICL reduces the gap states and unpins the Fermi level, realizing a wide movement of Fermi level within the midgap region and reduction of the effective surface recombination velocity by a factor of 1/60. GaN layer also introduced a large negative surface fixed charge of about 10 12 cm -2. A further improvement took place by depositing a Si 3N 4 layer on GaN ICL/GaAs structure.

The Histone Acetyltransferase MOF Promotes Induces Generation of Pluripotent Stem Cells.

PubMed

Mu, Xupeng; Yan, Shaohua; Fu, Changhao; Wei, Anhui

2015-08-01

Histone modification plays an important role in maintaining pluripotency and self-renewal of embryonic stem cells (ESCs). The histone acetyltransferase MOF is a key regulator of ESCs; however, the role of MOF in the process of reprogramming back to induced pluripotent stem cells (iPSCs) remains unclear. In this study, we investigated the function of MOF on the generation of iPSCs. We show that iPSCs contain high levels of MOF mRNA, and the expression level of MOF protein is dramatically upregulated following reprogramming. Most importantly, overexpression of MOF improves reprogramming efficiency and facilitates the formation of iPSCs, whereas small hairpin RNA (shRNA)-mediated knockdown of MOF impairs iPSCs generation during reprogramming. Further investigation reveals that MOF interacts with the H3K4 methyltransferase Wdr5 to promote endogenous Oct4 expression during the reprogramming process. Knockdown of MOF reduces H4K16ac and H3K4me3 modification at the Oct4 promoter. In conclusion, our data indicate that MOF is an important epigenetic regulator that is critical for efficient reprogramming.

Parental Monitoring Moderates the Importance of Genetic and Environmental Influences on Adolescent Smoking

PubMed Central

Dick, Danielle M.; Viken, Richard; Purcell, Shaun; Kaprio, Jaakko; Pulkkinen, Lea; Rose, Richard J.

2006-01-01

Although there is a substantial literature on the role of parenting on adolescent substance use, most parenting effects have been small in magnitude and studied outside the context of genetically informative designs, raising debate and controversy about the influence that parents have on their children (D. C. Rowe, 1994). Using a genetically informative twin-family design, we studied the role of parental monitoring on adolescent smoking at age 14. Although monitoring had only small main effects, consistent with the literature, there were dramatic moderation effects associated with parental monitoring: at high levels of parental monitoring environmental influences were predominant in the etiology of adolescent smoking, but at low levels of parental monitoring, genetic influences assumed far greater importance. These analyses demonstrate that the etiology of adolescent smoking varies dramatically as a function of parenting. PMID:17324032

Benchmarking Dutch and U.S. Naval Shipbuilding: Reducing U.S. Naval Shipbuilding Costs Using Collaborative PLM and 3D Imaging

DTIC Science & Technology

2012-11-02

Scanning Technology (3D LST) and Collaborative Product Lifecycle Management (CPLM) are two technologies that are currently being leveraged by international ... international ship construction organizations to achieve significant cost savings. 3D LST dramatically reduces the time required to scan ship surfaces as...technology does not meet the accuracy requirements, 0.030” accuracy minimum , for naval shipbuilding. The report delivered to the CSNT shows that if the

[Outline and effectiveness of support system in the surgical center by supply, processing and distribution center (SPD)].

PubMed

Ito, Nobuko; Chinzei, Mieko; Fujiwara, Haruko; Usui, Hisako; Hanaoka, Kazuo; Saitoh, Eisho

2006-04-01

Supply, Processing and Distribution system had been introduced to surgical center (the University of Tokyo Hospital) since October of 2002. This system had reduced stock for medicine and materials and decreased medical cost dramatically. We designed some kits for therapeutic drugs related to anesthesia. They were prepared for general anesthesia, epidural and spinal anesthesia, and cardiovascular anesthesia, respectively. One kit had been used for one patient, and new kits were prepared in the anesthesia preparation room by pharmaceutical department staffs. Equipment, for general anesthesia as well as epidural and spinal anesthesia, and central catheter set were also designed and provided for each patient by SPD system. According to the questionnaire of anesthesia residents before and after introduction of SPD system, the time spent for anesthesia preparation had been reduced and 92.3% residents had answered that preparation for anesthesia on the previous day was getting easier. Most of the anesthesia residents had been less stressed after introduction of SPD system. Beside the dramatic economical effect, coordination with SPD system and pharmaceutical department reduced anesthesia preparation time and stress of the staff. Introduction of Support system of SPD to surgical center is important for safe and effective management of operating rooms.

MitoNEET Deficiency Alleviates Experimental Alcoholic Steatohepatitis in Mice by Stimulating Endocrine Adiponectin-Fgf15 Axis.

PubMed

Hu, Xudong; Jogasuria, Alvin; Wang, Jiayou; Kim, Chunki; Han, Yoonhee; Shen, Hong; Wu, Jiashin; You, Min

2016-10-21

MitoNEET (mNT) (CDGSH iron-sulfur domain-containing protein 1 or CISD1) is an outer mitochondrial membrane protein that donates 2Fe-2S clusters to apo-acceptor proteins. In the present study, using a global mNT knock-out (mNTKO) mouse model, we investigated the in vivo functional role of mNT in the development of alcoholic steatohepatitis. Experimental alcoholic steatohepatitis was achieved by pair feeding wild-type (WT) and mNTKO mice with Lieber-DeCarli ethanol-containing diets for 4 weeks. Strikingly, chronically ethanol-fed mNTKO mice were completely resistant to ethanol-induced steatohepatitis as revealed by dramatically reduced hepatic triglycerides, decreased hepatic cholesterol level, diminished liver inflammatory response, and normalized serum ALT levels. Mechanistic studies demonstrated that ethanol administration to mNTKO mice induced two pivotal endocrine hormones, namely, adipose-derived adiponectin and gut-derived fibroblast growth factor 15 (Fgf15). The elevation in circulating levels of adiponectin and Fgf15 led to normalized hepatic and serum levels of bile acids, limited hepatic accumulation of toxic bile, attenuated inflammation, and amelioration of liver injury in the ethanol-fed mNTKO mice. Other potential mechanisms such as reduced oxidative stress, activated Sirt1 signaling, and diminished NF-κB activity also contribute to hepatic improvement in the ethanol-fed mNTKO mice. In conclusion, the present study identified adiponectin and Fgf15 as pivotal adipose-gut-liver metabolic coordinators in mediating the protective action of mNT deficiency against development of alcoholic steatohepatitis in mice. Our findings may help to establish mNT as a novel therapeutic target and pharmacological inhibition of mNT may be beneficial for the prevention and treatment of human alcoholic steatohepatitis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The effect of signal acquisition and processing choices on ApEn values: towards a "gold standard" for distinguishing effort levels from isometric force records.

PubMed

Forrest, Sarah M; Challis, John H; Winter, Samantha L

2014-06-01

Approximate entropy (ApEn) is frequently used to identify changes in the complexity of isometric force records with ageing and disease. Different signal acquisition and processing parameters have been used, making comparison or confirmation of results difficult. This study determined the effect of sampling and parameter choices by examining changes in ApEn values across a range of submaximal isometric contractions of the first dorsal interosseus. Reducing the sample rate by decimation changed both the value and pattern of ApEn values dramatically. The pattern of ApEn values across the range of effort levels was not sensitive to the filter cut-off frequency, or the criterion used to extract the section of data for analysis. The complexity increased with increasing effort levels using a fixed 'r' value (which accounts for measurement noise) but decreased with increasing effort level when 'r' was set to 0.1 of the standard deviation of force. It is recommended isometric force records are sampled at frequencies >200Hz, template length ('m') is set to 2, and 'r' set to measurement system noise or 0.1SD depending on physiological process to be distinguished. It is demonstrated that changes in ApEn across effort levels are related to changes in force gradation strategy. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Constant light affects retinal dopamine levels and blocks deprivation myopia but not lens-induced refractive errors in chickens.

PubMed

Bartmann, M; Schaeffel, F; Hagel, G; Zrenner, E

1994-01-01

Chickens were raised with either translucent occluders or lenses, both under normal light cycles (12-h light/12-h dark) and in constant light (CL). Under normal light cycles, eyes with occluders became very myopic, and eyes with lenses became either relatively hyperopic (positive lenses) or myopic (negative lenses). After the treatment, retinal dopamine (DA), DOPAC, and serotonin levels were measured by high-pressure liquid chromatography (HPLC-EC). A significant drop in daytime retinal DOPAC (-20%) was observed after 1 week of deprivation, and in both DOPAC (-40%) and DA (-30%) after 2 weeks of deprivation. No changes in retinal serotonin levels were found. Retinal DA or DOPAC content remained unchanged after 2 or 4 days of lens wearing even though the lenses had already exerted their maximal effect on axial eye growth. When the chickens were raised in CL, development of deprivation myopia was reduced (8 days CL) or entirely blocked (13 days CL). Lens-induced changes in eye growth were not different after either 6 or 11 days in CL, compared to animals raised in a normal light cycle. Thirteen days of CL resulted in a dramatic reduction of DA and DOPAC levels, but serotonin levels were also lowered. The results suggest that lens-induced changes in refraction may not be dependent on dopaminergic pathways whereas deprivation myopia requires normal diurnal DA rhythms to develop.

Seventh-day syndrome: a catastrophic event after liver transplantation: case report.

PubMed

Pereira, M; Ferreira, I; Gandara, J; Ferreira, S; Lopes, V; Coelho, A; Vizcaino, R; Marinho, A; Daniel, J; Miranda, H P

2015-05-01

Seventh-day syndrome (7DS) is an early serious complication of liver transplantation, characterized by sudden failure of a previously normally functioning liver graft ∼1 week after the surgery. Although it is an uncommon event, it has major associated mortality. As its etiology is yet to be recognized, the only currently available treatment is retransplantation. We present 3 cases of orthotopic liver transplantation recipients who had an initial uneventful recovery after surgery followed by a dramatic rise of serum liver enzyme levels ∼7 days later and hepatic failure with subsequent graft loss and death despite high-dose immunosuppressive therapy. Histologic findings showed massive centrolobular hemorrhage and hepatocellular necrosis with reduced inflammation. It is essential to review and accumulate more clinical and laboratory information to better understand this syndrome and to better prevent and treat it. Copyright © 2015 Elsevier Inc. All rights reserved.

Low noise and conductively cooled microchannel plates

NASA Technical Reports Server (NTRS)

Feller, W. B.

1990-01-01

Microchannel plate (MCP) dynamic range has recently been enhanced for both very low and very high input flux conditions. Improvements in MCP manufacturing technology reported earlier have led to MCPs with substantially reduced radioisotope levels, giving dramatically lower internal background-counting rates. An update is given on the Galileo low noise MCP. Also, new results in increasing the MCP linear counting range for high input flux densities are presented. By bonding the active face of a very low resistance MCP (less than 1 megaohm) to a substrate providing a conductive path for heat transport, the bias current limit (hence, MCP output count rate limit) can be increased up to two orders of magnitude. Normal pulse-counting MCP operation was observed at bias currents of several mA when a curved-channel MCP (80:1) was bonded to a ceramic multianode substrate; the MCP temperature rise above ambient was less than 40 C.

Ice recrystallization inhibition in ice cream by propylene glycol monostearate.

PubMed

Aleong, J M; Frochot, S; Goff, H D

2008-11-01

The effectiveness of propylene glycol monostearate (PGMS) to inhibit ice recrystallization was evaluated in ice cream and frozen sucrose solutions. PGMS (0.3%) dramatically reduced ice crystal sizes in ice cream and in sucrose solutions frozen in a scraped-surface freezer before and after heat shock, but had no effect in quiescently frozen solutions. PGMS showed limited emulsifier properties by promoting smaller fat globule size distributions and enhanced partial coalescence in the mix and ice cream, respectively, but at a much lower level compared to conventional ice cream emulsifier. Low temperature scanning electron microscopy revealed highly irregular crystal morphology in both ice cream and sucrose solutions frozen in a scraped-surface freezer. There was strong evidence to suggest that PGMS directly interacts with ice crystals and interferes with normal surface propagation. Shear during freezing may be required for its distribution around the ice and sufficient surface coverage.

Social work services in Army medical treatment facilities: are they reorganizing?

PubMed

Hamlin, E R; Pehrson, K L; Gemmill, R

1996-01-01

The end of the Cold War and the fall of Communism in Europe resulted in profound changes in U.S. defense policy. Those changes led to dramatic reductions in personnel and programs within the Army. The Army Medical Department (AMEDD) is also being reduced in size and reorganized. At the same time, the AMEDD is facing escalating health care costs associated with demand and access to medical care. Social work services in Army medical treatment facilities are being directly affected by these system changes. Therefore, the question is raised whether changes in the organization and delivery of social work services are being initiated or anticipated. To what extent are social work chiefs of service involved in these decisions at the medical treatment facility level, and what are the positive and negative effects of reorganization on social work staff and the clients they serve?

Identification and functional analysis of endogenous nitric oxide in a filamentous fungus.

PubMed

Pengkit, Anchalee; Jeon, Seong Sil; Son, Soo Ji; Shin, Jae Ho; Baik, Ku Yeon; Choi, Eun Ha; Park, Gyungsoon

2016-07-18

In spite of its prevalence in animals and plants, endogenous nitric oxide (NO) has been rarely reported in fungi. We present here our observations on production of intracellular NO and its possible roles during development of Neurospora crassa, a model filamentous fungus. Intracellular NO was detected in hypha 8-16 hours after incubation in Vogel's minimal liquid media and conidiophores during conidiation using a fluorescent indicator (DAF-FM diacetate). Treatment with cPTIO, an NO scavenger, significantly reduced fluorescence levels and hindered hyphal growth in liquid media and conidiation, whereas exogenous NO enhanced hyphal extension on VM agar media and conidia formation. NO scavenging also dramatically diminished transcription of con-10 and con-13, genes preferentially expressed during conidiation. Our results suggest that intracellular NO is generated in young hypha growing in submerged culture and during conidia development and regulate mycelial development and conidia formation.

[Nanotechnology: a big revolution from the small world].

PubMed

Bassi, Matteo; Santinello, Irene; Bevilacqua, Andrea; Bassi, Pierfrancesco

2013-01-01

Nanotechnology is a multidisciplinary field originating from the interaction of several different disciplines, such as engineering, physics, biology and chemistry. New materials and devices effectively interact with the body at molecular level, yielding a brand new range of highly selective and targeted applications designed to maximize the therapeutic efficiency while reducing the side effects. Liposomes, quantum dots, carbon nanotubes and superparamagnetic nanoparticles are among the most assessed nanotechnologies. Meanwhile, other futuristic platforms are paving the way toward a new scientific paradigm, able to deeply change the research path in the medical science. The growth of nanotechnology, driven by the dramatic advances in science and technology, clearly creates new opportunities for the development of the medical science and disease treatment in human health care. Despite the concerns and the on-going studies about their safety, nanotechnology clearly emerges as holding the promise of delivering one of the greatest breakthroughs in the history of medical science.

Networks of military alliances, wars, and international trade

PubMed Central

Jackson, Matthew O.; Nei, Stephen

2015-01-01

We investigate the role of networks of alliances in preventing (multilateral) interstate wars. We first show that, in the absence of international trade, no network of alliances is peaceful and stable. We then show that international trade induces peaceful and stable networks: Trade increases the density of alliances so that countries are less vulnerable to attack and also reduces countries’ incentives to attack an ally. We present historical data on wars and trade showing that the dramatic drop in interstate wars since 1950 is paralleled by a densification and stabilization of trading relationships and alliances. Based on the model we also examine some specific relationships, finding that countries with high levels of trade with their allies are less likely to be involved in wars with any other countries (including allies and nonallies), and that an increase in trade between two countries correlates with a lower chance that they will go to war with each other. PMID:26668370

Networks of military alliances, wars, and international trade.

PubMed

Jackson, Matthew O; Nei, Stephen

2015-12-15

We investigate the role of networks of alliances in preventing (multilateral) interstate wars. We first show that, in the absence of international trade, no network of alliances is peaceful and stable. We then show that international trade induces peaceful and stable networks: Trade increases the density of alliances so that countries are less vulnerable to attack and also reduces countries' incentives to attack an ally. We present historical data on wars and trade showing that the dramatic drop in interstate wars since 1950 is paralleled by a densification and stabilization of trading relationships and alliances. Based on the model we also examine some specific relationships, finding that countries with high levels of trade with their allies are less likely to be involved in wars with any other countries (including allies and nonallies), and that an increase in trade between two countries correlates with a lower chance that they will go to war with each other.

SIRT1, 2, 3 protect mouse oocytes from postovulatory aging.

PubMed

Zhang, Teng; Zhou, Yang; Li, Li; Wang, Hong-Hui; Ma, Xue-Shan; Qian, Wei-Ping; Shen, Wei; Schatten, Heide; Sun, Qing-Yuan

2016-04-01

The quality of metaphase II oocytes will undergo a time-dependent deterioration following ovulation as the result of the oocyte aging process. In this study, we determined that the expression of sirtuin family members (SIRT1, 2, 3) was dramatically reduced in mouse oocytes aged in vivo or in vitro. Increased intracellular ROS was observed when SIRT1, 2, 3 activity was inhibited. Increased frequency of spindle defects and disturbed distribution of mitochondria were also observed in MII oocytes aged in vitro after treatment with Nicotinamide (NAM), indicating that inhibition of SIRT1, 2, 3 may accelerate postovulatory oocyte aging. Interestingly, when MII oocytes were exposed to caffeine, the decline of SIRT1, 2, 3 mRNA levels was delayed and the aging-associated defective phenotypes could be improved. The results suggest that the SIRT1, 2, 3 pathway may play a potential protective role against postovulatory oocyte aging by controlling ROS generation.

The bradykinin B2 receptor in the early immune response against Listeria infection.

PubMed

Kaman, Wendy E; Wolterink, Arthur F W M; Bader, Michael; Boele, Linda C L; van der Kleij, Desiree

2009-02-01

The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B(2) (B(2)R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B(2)R (B(2)R(-/-) mice) were shown to suffer from increased hepatic bacterial burden and concomitant dramatic weight loss during infection with Listeria monocytogenes. Levels of cytokines known to play a pivotal role in the early phase immune response against L. monocytogenes, IL-12p70 and IFN-gamma, were reduced in B(2)R(-/-) mice. To extend these findings to the human system, we show that bradykinin potentiates the production of IL-12p70 in human monocyte-derived dendritic cells. Thus, we show that bradykinin and the B(2)R play a role in early innate immune functions during bacterial infection.

Retinal Origin of Direction Selectivity in the Superior Colliculus

PubMed Central

Shi, Xuefeng; Barchini, Jad; Ledesma, Hector Acaron; Koren, David; Jin, Yanjiao; Liu, Xiaorong; Wei, Wei; Cang, Jianhua

2017-01-01

Detecting visual features in the environment such as motion direction is crucial for survival. The circuit mechanisms that give rise to direction selectivity in a major visual center, the superior colliculus (SC), are entirely unknown. Here, we optogenetically isolate the retinal inputs that individual direction-selective SC neurons receive and find that they are already selective as a result of precisely converging inputs from similarly-tuned retinal ganglion cells. The direction selective retinal input is linearly amplified by the intracollicular circuits without changing its preferred direction or level of selectivity. Finally, using 2-photon calcium imaging, we show that SC direction selectivity is dramatically reduced in transgenic mice that have decreased retinal selectivity. Together, our studies demonstrate a retinal origin of direction selectivity in the SC, and reveal a central visual deficit as a consequence of altered feature selectivity in the retina. PMID:28192394

Increased apomixis expression concurrent with genetic and epigenetic variation in a newly synthesized Eragrostis curvula polyploid

NASA Astrophysics Data System (ADS)

Zappacosta, Diego C.; Ochogavía, Ana C.; Rodrigo, Juan M.; Romero, José R.; Meier, Mauro S.; Garbus, Ingrid; Pessino, Silvina C.; Echenique, Viviana C.

2014-04-01

Eragrostis curvula includes biotypes reproducing through obligate and facultative apomixis or, rarely, full sexuality. We previously generated a ``tetraploid-dihaploid-tetraploid'' series of plants consisting of a tetraploid apomictic plant (T), a sexual dihaploid plant (D) and a tetraploid artificial colchiploid (C). Initially, plant C was nearly 100% sexual. However, its capacity to form non-reduced embryo sacs dramatically increased over a four year period (2003-2007) to reach levels of 85-90%. Here, we confirmed high rates of apomixis in plant C, and used AFLPs and MSAPs to characterize the genetic and epigenetic variation observed in this plant in 2007 as compared to 2003. Of the polymorphic sequences, some had no coding potential whereas others were homologous to retrotransposons and/or protein-coding-like sequences. Our results suggest that in this particular plant system increased apomixis expression is concurrent with genetic and epigenetic modifications, possibly involving transposable elements.

Robust Optimization Design for Turbine Blade-Tip Radial Running Clearance using Hierarchically Response Surface Method

NASA Astrophysics Data System (ADS)

Zhiying, Chen; Ping, Zhou

2017-11-01

Considering the robust optimization computational precision and efficiency for complex mechanical assembly relationship like turbine blade-tip radial running clearance, a hierarchically response surface robust optimization algorithm is proposed. The distribute collaborative response surface method is used to generate assembly system level approximation model of overall parameters and blade-tip clearance, and then a set samples of design parameters and objective response mean and/or standard deviation is generated by using system approximation model and design of experiment method. Finally, a new response surface approximation model is constructed by using those samples, and this approximation model is used for robust optimization process. The analyses results demonstrate the proposed method can dramatic reduce the computational cost and ensure the computational precision. The presented research offers an effective way for the robust optimization design of turbine blade-tip radial running clearance.

Identification and functional analysis of endogenous nitric oxide in a filamentous fungus

PubMed Central

Pengkit, Anchalee; Jeon, Seong Sil; Son, Soo Ji; Shin, Jae Ho; Baik, Ku Yeon; Choi, Eun Ha; Park, Gyungsoon

2016-01-01

In spite of its prevalence in animals and plants, endogenous nitric oxide (NO) has been rarely reported in fungi. We present here our observations on production of intracellular NO and its possible roles during development of Neurospora crassa, a model filamentous fungus. Intracellular NO was detected in hypha 8–16 hours after incubation in Vogel’s minimal liquid media and conidiophores during conidiation using a fluorescent indicator (DAF-FM diacetate). Treatment with cPTIO, an NO scavenger, significantly reduced fluorescence levels and hindered hyphal growth in liquid media and conidiation, whereas exogenous NO enhanced hyphal extension on VM agar media and conidia formation. NO scavenging also dramatically diminished transcription of con-10 and con-13, genes preferentially expressed during conidiation. Our results suggest that intracellular NO is generated in young hypha growing in submerged culture and during conidia development and regulate mycelial development and conidia formation. PMID:27425220

Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice

PubMed Central

Ishimoto, Takuji; Lanaspa, Miguel A.; Le, MyPhuong T.; Garcia, Gabriela E.; Diggle, Christine P.; MacLean, Paul S.; Jackman, Matthew R.; Asipu, Aruna; Roncal-Jimenez, Carlos A.; Kosugi, Tomoki; Rivard, Christopher J.; Maruyama, Shoichi; Rodriguez-Iturbe, Bernardo; Sánchez-Lozada, Laura G.; Bonthron, David T.; Sautin, Yuri Y.; Johnson, Richard J.

2012-01-01

Fructose intake from added sugars correlates with the epidemic rise in obesity, metabolic syndrome, and nonalcoholic fatty liver disease. Fructose intake also causes features of metabolic syndrome in laboratory animals and humans. The first enzyme in fructose metabolism is fructokinase, which exists as two isoforms, A and C. Here we show that fructose-induced metabolic syndrome is prevented in mice lacking both isoforms but is exacerbated in mice lacking fructokinase A. Fructokinase C is expressed primarily in liver, intestine, and kidney and has high affinity for fructose, resulting in rapid metabolism and marked ATP depletion. In contrast, fructokinase A is widely distributed, has low affinity for fructose, and has less dramatic effects on ATP levels. By reducing the amount of fructose for metabolism in the liver, fructokinase A protects against fructokinase C-mediated metabolic syndrome. These studies provide insights into the mechanisms by which fructose causes obesity and metabolic syndrome. PMID:22371574

An overview of autonomous rendezvous and docking system technology development

NASA Astrophysics Data System (ADS)

Nelson, Kurt D.

The Centaur upper stage was selected for an airborne avionics modernization program. The parts used in the existing avionics units were obsolete. Continued use of existing hardware would require substantial redesign, yet would result in the use of outdated hardware. Out of date processes, with very expensive and labor intensive technologies, were being used for manufacturing. The Atlas/Centaur avionics were to be procured at a fairly high rate that demanded the use of modern components. The new avionics also reduce size, weight, power, and parts count with a dramatic improvement in reliability. Finally, the cost leverage derived from upgrading the avionics as opposed to any other subsystem for the existing Atlas/Centaur was a very large consideration in the upgrade decision. The upgrade program is a multiyear effort that began in 1989. It includes telemetry, guidance and navigation, control electronics, thrust vector control, and redundancy levels.

Energy Savings by Treating Buildings as Systems

NASA Astrophysics Data System (ADS)

Harvey, L. D. Danny

2008-09-01

This paper reviews the opportunities for dramatically reducing energy use in buildings by treating buildings as systems, rather than focusing on device efficiencies. Systems-level considerations are relevant for the operation of heat pumps (where the temperatures at which heat or coldness are distributed are particularly important); the joint or separate provision of heating, cooling, and ventilation; the joint or separate removal of sensible heat and moisture; and in the operation of fluid systems having pumps. Passive heating, cooling, and ventilation, as well as daylighting (use of sunlight for lighting purposes) also require consideration of buildings as systems. In order to achieve the significant (50-75%) energy savings that are possible through a systems approach, the design process itself has to involve a high degree of integration between the architect and various engineering disciplines (structural, mechanical, electrical), and requires the systematic examination and adjustment of alternative designs using computer simulation models.

Genomic prediction unifies animal and plant breeding programs to form platforms for biological discovery.

PubMed

Hickey, John M; Chiurugwi, Tinashe; Mackay, Ian; Powell, Wayne

2017-08-30

The rate of annual yield increases for major staple crops must more than double relative to current levels in order to feed a predicted global population of 9 billion by 2050. Controlled hybridization and selective breeding have been used for centuries to adapt plant and animal species for human use. However, achieving higher, sustainable rates of improvement in yields in various species will require renewed genetic interventions and dramatic improvement of agricultural practices. Genomic prediction of breeding values has the potential to improve selection, reduce costs and provide a platform that unifies breeding approaches, biological discovery, and tools and methods. Here we compare and contrast some animal and plant breeding approaches to make a case for bringing the two together through the application of genomic selection. We propose a strategy for the use of genomic selection as a unifying approach to deliver innovative 'step changes' in the rate of genetic gain at scale.

Logging cuts the functional importance of invertebrates in tropical rainforest

PubMed Central

Ewers, Robert M.; Boyle, Michael J. W.; Gleave, Rosalind A.; Plowman, Nichola S.; Benedick, Suzan; Bernard, Henry; Bishop, Tom R.; Bakhtiar, Effendi Y.; Chey, Vun Khen; Chung, Arthur Y. C.; Davies, Richard G.; Edwards, David P.; Eggleton, Paul; Fayle, Tom M.; Hardwick, Stephen R.; Homathevi, Rahman; Kitching, Roger L.; Khoo, Min Sheng; Luke, Sarah H.; March, Joshua J.; Nilus, Reuben; Pfeifer, Marion; Rao, Sri V.; Sharp, Adam C.; Snaddon, Jake L.; Stork, Nigel E.; Struebig, Matthew J.; Wearn, Oliver R.; Yusah, Kalsum M.; Turner, Edgar C.

2015-01-01

Invertebrates are dominant species in primary tropical rainforests, where their abundance and diversity contributes to the functioning and resilience of these globally important ecosystems. However, more than one-third of tropical forests have been logged, with dramatic impacts on rainforest biodiversity that may disrupt key ecosystem processes. We find that the contribution of invertebrates to three ecosystem processes operating at three trophic levels (litter decomposition, seed predation and removal, and invertebrate predation) is reduced by up to one-half following logging. These changes are associated with decreased abundance of key functional groups of termites, ants, beetles and earthworms, and an increase in the abundance of small mammals, amphibians and insectivorous birds in logged relative to primary forest. Our results suggest that ecosystem processes themselves have considerable resilience to logging, but the consistent decline of invertebrate functional importance is indicative of a human-induced shift in how these ecological processes operate in tropical rainforests. PMID:25865801

The microRNA-processing enzyme Dicer is essential for thyroid function.

PubMed

Frezzetti, Daniela; Reale, Carla; Calì, Gaetano; Nitsch, Lucio; Fagman, Henrik; Nilsson, Ola; Scarfò, Marzia; De Vita, Gabriella; Di Lauro, Roberto

2011-01-01

Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the post-transcriptional level. To explore the functional role of miRNAs in thyroid gland function, we generated a thyrocyte-specific Dicer conditional knockout mouse. Here we show that development and early differentiation of the thyroid gland are not affected by the absence of Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight and shortened life span. Histological and molecular characterization of knockout mice reveals a dramatic loss of the thyroid gland follicular architecture associated with functional aberrations and down-regulation of several differentiation markers. The data presented in this study show for the first time that an intact miRNAs processing machinery is essential for thyroid physiology, suggesting that deregulation of specific miRNAs could be also involved in human thyroid dysfunctions.

Logging cuts the functional importance of invertebrates in tropical rainforest.

PubMed

Ewers, Robert M; Boyle, Michael J W; Gleave, Rosalind A; Plowman, Nichola S; Benedick, Suzan; Bernard, Henry; Bishop, Tom R; Bakhtiar, Effendi Y; Chey, Vun Khen; Chung, Arthur Y C; Davies, Richard G; Edwards, David P; Eggleton, Paul; Fayle, Tom M; Hardwick, Stephen R; Homathevi, Rahman; Kitching, Roger L; Khoo, Min Sheng; Luke, Sarah H; March, Joshua J; Nilus, Reuben; Pfeifer, Marion; Rao, Sri V; Sharp, Adam C; Snaddon, Jake L; Stork, Nigel E; Struebig, Matthew J; Wearn, Oliver R; Yusah, Kalsum M; Turner, Edgar C

2015-04-13

Invertebrates are dominant species in primary tropical rainforests, where their abundance and diversity contributes to the functioning and resilience of these globally important ecosystems. However, more than one-third of tropical forests have been logged, with dramatic impacts on rainforest biodiversity that may disrupt key ecosystem processes. We find that the contribution of invertebrates to three ecosystem processes operating at three trophic levels (litter decomposition, seed predation and removal, and invertebrate predation) is reduced by up to one-half following logging. These changes are associated with decreased abundance of key functional groups of termites, ants, beetles and earthworms, and an increase in the abundance of small mammals, amphibians and insectivorous birds in logged relative to primary forest. Our results suggest that ecosystem processes themselves have considerable resilience to logging, but the consistent decline of invertebrate functional importance is indicative of a human-induced shift in how these ecological processes operate in tropical rainforests.

Predictable Unpredictability: the Problem with Basing Medicare Policy on Long-Term Financial Forecasting.

PubMed

Glied, Sherry; Zaylor, Abigail

2015-07-01

The authors assess how Medicare financing and projections of future costs have changed since 2000. They also assess the impact of legislative reforms on the sources and levels of financing and compare cost forecasts made at different times. Although the aging U.S. population and rising health care costs are expected to increase the share of gross domestic product devoted to Medicare, changes made in the program over the past decade have helped stabilize Medicare's financial outlook--even as benefits have been expanded. Long-term forecasting uncertainty should make policymakers and beneficiaries wary of dramatic changes to the program in the near term that are intended to alter its long-term forecast: the range of error associated with cost forecasts rises as the forecast window lengthens. Instead, policymakers should focus on the immediate policy window, taking steps to reduce the current burden of Medicare costs by containing spending today.

The jellification of north temperate lakes.

PubMed

Jeziorski, Adam; Tanentzap, Andrew J; Yan, Norman D; Paterson, Andrew M; Palmer, Michelle E; Korosi, Jennifer B; Rusak, James A; Arts, Michael T; Keller, Wendel Bill; Ingram, Ron; Cairns, Allegra; Smol, John P

2015-01-07

Calcium (Ca) concentrations are decreasing in softwater lakes across eastern North America and western Europe. Using long-term contemporary and palaeo-environmental field data, we show that this is precipitating a dramatic change in Canadian lakes: the replacement of previously dominant pelagic herbivores (Ca-rich Daphnia species) by Holopedium glacialis, a jelly-clad, Ca-poor competitor. In some lakes, this transformation is being facilitated by increases in macro-invertebrate predation, both from native (Chaoborus spp.) and introduced (Bythotrephes longimanus) zooplanktivores, to which Holopedium, with its jelly coat, is relatively invulnerable. Greater representation by Holopedium within cladoceran zooplankton communities will reduce nutrient transfer through food webs, given their lower phosphorus content relative to daphniids, and greater absolute abundances may pose long-term problems to water users. The dominance of jelly-clad zooplankton will likely persist while lakewater Ca levels remain low. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Far-infrared laser vibration-rotation-tunneling spectroscopy of water clusters in the librational band region of liquid water

NASA Astrophysics Data System (ADS)

Keutsch, Frank N.; Fellers, Ray S.; Viant, Mark R.; Saykally, Richard J.

2001-03-01

We report the first high resolution spectrum of a librational vibration for a water cluster. Four parallel bands of (H2O)3 were measured between 510 and 525 cm-1 using diode laser vibration-rotation-tunneling (VRT) spectroscopy. The bands lie in the "librational band" region of liquid water and are assigned to the nondegenerate out of plane librational vibration. The observation of at least three distinct bands within 8 cm-1 originating in the vibrational ground state is explained by a dramatically increased splitting of the rovibrational levels relative to the ground state by bifurcation tunneling and is indicative of a greatly reduced barrier height in the excited state. This tunneling motion is of special significance, as it is the lowest energy pathway for breaking and reforming of hydrogen bonds, a salient aspect of liquid water dynamics.

Netrin-4 regulates thalamocortical axon branching in an activity-dependent fashion.

PubMed

Hayano, Yasufumi; Sasaki, Kensuke; Ohmura, Nami; Takemoto, Makoto; Maeda, Yurie; Yamashita, Toshihide; Hata, Yoshio; Kitada, Kazuhiro; Yamamoto, Nobuhiko

2014-10-21

Axon branching is remodeled by sensory-evoked and spontaneous neuronal activity. However, the underlying molecular mechanism is largely unknown. Here, we demonstrate that the netrin family member netrin-4 (NTN4) contributes to activity-dependent thalamocortical (TC) axon branching. In the postnatal developmental stages of rodents, ntn4 expression was abundant in and around the TC recipient layers of sensory cortices. Neuronal activity dramatically altered the ntn4 expression level in the cortex in vitro and in vivo. TC axon branching was promoted by exogenous NTN4 and suppressed by depletion of the endogenous protein. Moreover, unc-5 homolog B (Unc5B), which strongly bound to NTN4, was expressed in the sensory thalamus, and knockdown of Unc5B in thalamic cells markedly reduced TC axon branching. These results suggest that NTN4 acts as a positive regulator for TC axon branching through activity-dependent expression.

Physiological Measures of Emotion from a Developmental Perspective: State of the Science

ERIC Educational Resources Information Center

Dennis, Tracy A.; Buss, Kristin A.; Hastings, Paul D.; Bell, Martha Ann; Diaz, Anjolii; Adam, Emma K.; Miskovic, Vladimir; Schmidt, Louis A.; Feldman, Ruth; Katz, Lynn Fainsilber; Rigterink, Tami; Strang, Nicole M.; Hanson, Jamie L.; Pollak, Seth D.; Dahl, Ronald E.; Silk, Jennifer S.; Siegle, Greg J.; Beauchaine, Theodore P.; Cicchetti, Dante; Rogosch, Fred A.; Fox, Nathan A.; Kirwan, Michael; Reeb-Sutherland, Bethany; Gunnar, Megan R.; Obradovic, Jelena; Boyce, W. Thomas; Molenaar, Peter C. M.; Gates, Kathleen M.

2012-01-01

In the past decade, there has been a dramatic growth in research examining the development of emotion from a physiological perspective. However, this widespread use of physiological measures to study emotional development coexists with relatively few guiding principles, thus reducing opportunities to move the field forward in innovative ways. The…

Oregon's High School Dropouts: Examining the Economic and Social Costs. Research Brief

ERIC Educational Resources Information Center

Foundation for Educational Choice, 2010

2010-01-01

The Foundation for Educational Choice recently commissioned a new study to examine the economic and social costs of Oregon's high school dropouts. Emily House, the study's author, analyzed how dropouts in the state dramatically impact state finances through reduced tax revenues, increased Medicaid costs, and high incarceration rates. House's study…

Test Group Rethinks Questions

ERIC Educational Resources Information Center

Gewertz, Catherine

2012-01-01

A group that is developing tests for half the states in the nation has dramatically reduced the length of its assessment in a bid to balance the desire for a more meaningful and useful exam with concerns about the amount of time spent on testing. The decision by the Smarter Balanced Assessment Consortium reflects months of conversation among its…

Effect of Seeding Rate on Weed Suppression Activity and Yield of Indica and Tropical Japonica Rice Cultivars.

USDA-ARS?s Scientific Manuscript database

Weeds are ubiquitous and costly pests in U.S. rice production systems. Although most rice cultivars do not suppress weeds dramatically, certain indica cultivars and commercial hybrids have been shown to suppress barnyardgrass (Echinochloa crus-galli) in conventional as well as reduced-herbicide and ...

Synchrotron microtomography of xylem embolism in Sequoia sempervirens seedlings during cycles of drought and recovery

USDA-ARS?s Scientific Manuscript database

The formation of emboli in xylem conduits can dramatically reduce hydraulic capacity and represents one of the principal mechanisms of drought induced mortality in woody plants. Some angiosperm species possess a mechanism to rapidly repair embolism by dissolving gas back into solution. However, it i...

Guardian Caps: What's the Impact?

ERIC Educational Resources Information Center

Jenny, Seth E.; Rouse, Wardell; Seibles, Ashlie

2017-01-01

Reported sport-related concussion rates have dramatically increased recently. In response, the Guardian company has emerged as a leading manufacturer of soft-shell helmet covers. The "Guardian Cap" is a foam padded covering that fits over a helmet that aims to reduce the impact of collisions and lessen the chance of a concussion. The…

Higher Education and Reentry: The Gifts They Bring. Reentry Research in the First Person

ERIC Educational Resources Information Center

Halkovic, Alexis; Fine, Michelle; Bae, John; Campbell, Leslie; Evans, Desheen; Gary, Chaka; Greene, Andrew; Ramirez, Marc; Riggs, Robert; Taylor, Michael; Tebout, Ray; Tejawi, Aenora

2013-01-01

Virtually every study of the impact of college on incarcerated and formerly incarcerated people demonstrates a positive effect on income, civic engagement, family, and personal health, as well as dramatically reduced recidivism rates. College in and after prison offers a singularly effective strategy for redeveloping individuals, families and…

A forest manager's guide to butternut

Treesearch

Keith Woeste; Lenny Farlee; Michael Ostry; James McKenna; Sally Weeks

2009-01-01

Exotic insect pests and pathogens have dramatically reduced the quantity and quality of several trees species in North America. Butternut (Juglans cinerea L.) is one such species. This review discusses the identification of butternut, the current status of butternut, and the nature of the threats that influence its survival, all in the context of...

Clementine. Mining new uses for SDI technology

NASA Astrophysics Data System (ADS)

Rustan, Pedro L.

1994-01-01

Using ballistic missile defense technologies for NASA science missions can dramatically reduce program costs and development time. Described is the Clementine spacecraft scheduled for launch to flight-qualify advanced lightweight technologies. The 500-lb spacecraft, which uses lightweight components and minimal redundancy, was built by the Naval Research Laboratory in less than two years.

Clarifying muddy water: probing the linkages to municipal water quality.

Treesearch

Sally Duncan

2003-01-01

In the Pacific Northwest, several recent and dramatic "muddy waters" events have created major problems for water utilities. Resulting from floods and measures to retrofit dams to reduce impacts on temperature, these events also have focused public and scientific attention on interactions among dams, forest-land use, and municipal water supplies. Far from...

The nurse advocate and care for the caregivers.

PubMed

Loomer, A H; Jacoby, J; Schader, J A

1993-02-01

Dramatic improvement in morale, increased retention and an enhanced atmosphere of optimism resulted from introduction of a Nurse Advocate role in an acute care hospital. Within the context of a collaborative governance model, the Nurse Advocate was able to empower individuals and groups to immediate successes. Use of registry nurses was reduced by 99 percent!

Changing Mental Models of the IT Professions: A Theoretical Framework

ERIC Educational Resources Information Center

Agosto, Denise E.; Gasson, Susan; Atwood, Michael

2008-01-01

It is widely recognized that the current and projected shortage of adequately-educated IT professionals could be greatly reduced if more female and minority students would major in IT disciplines, yet the dramatic under-representation of these populations appears to be worsening. This under-representation is reflected in Drexel University's…

Hubless satellite communications networks

NASA Technical Reports Server (NTRS)

Robinson, Peter Alan

1994-01-01

Frequency Comb Multiple Access (FCMA) is a new combined modulation and multiple access method which will allow cheap hubless Very Small Aperture Terminal (VSAT) networks to be constructed. Theoretical results show bandwidth efficiency and power efficiency improvements over other modulation and multiple access methods. Costs of the VSAT network are reduced dramatically since a hub station is not required.

Characterization of escherichia coli O157:H7 strains from contaminated raw beef trim during “high event periods”

USDA-ARS?s Scientific Manuscript database

The development and implementation of effective antimicrobial interventions by the beef processing industry in the United States have dramatically reduced the incidence of beef trim contamination by Escherichia coli O157:H7. However, individual processing plants still experience sporadic peaks in co...

Why Cool Roofs?

ScienceCinema

Chu, Steven

2017-12-27

By installing a cool roof at DOE, the federal government and Secretary Chu are helping to educate families and businesses about the important energy and cost savings that can come with this simple, low-cost technology. Cool roofs have the potential to quickly and dramatically reduce global carbon emissions while saving money every month on consumers' electrical bills.

Innoculating against Depression. Connect for Kids: Guidance for Grown-Ups.

ERIC Educational Resources Information Center

Louv, Richard

This article focuses on how parents and institutions can create a positive climate for children's emotional health. An increasing number of mental health professionals believe that parents and adults can dramatically reduce the amount of depression and suicide among children and teenagers by modeling and promoting learned optimism. Values also…

Community Mental Health Systems Generate New Chronics: The Study of a Pure Case.

ERIC Educational Resources Information Center

Lieberman, Harvey J.; And Others

1988-01-01

Study indicated that, although well-integrated comprehensive community mental health system (CMHS) dramatically reduces utilization of long-stay inpatient beds compared to traditional health care systems, it does not banish appearance of "new chronic" patients from a catchment area. CMHS new chronic patients were younger, mostly male,…

Employee assistance programs: a preventive, cost-effective benefit.

PubMed

Cohen, G S; Gard, L H; Heffernan, W R

1998-01-01

Employee Assistance Programs (EAPs) provide a much-needed service to the employees of corporations. In these times of reduced benefits and diminished community resources, EAPs can dramatically compensate for those shortages. This article will explore the role of an EAP, the models of service available, and the selection process for choosing a program.

Cryogenic fountain development at NIST and INRIM: preliminary characterization.

PubMed

Levi, Filippo; Calosso, Claudio; Calonico, Davide; Lorini, Luca; Bertacco, Elio K; Godone, Aldo; Costanzo, Giovanni A; Mongino, Barbara; Jefferts, Steven R; Heavner, Thomas P; Donley, Elizabeth A

2010-03-01

This paper describes the new twin laser-cooled Cs fountain primary frequency standards NIST-F2 and ITCsF2, and presents some of their design features. Most significant is a cryogenic microwave interrogation region which dramatically reduces the blackbody radiation shift. We also present a preliminary accuracy evaluation of IT-CsF2.

How Small Can We Go: Exploring the Limitations and Scaling laws of Air-Microfluidic Particulate Matter Sensors

EPA Science Inventory

Air-microfluidics is a field that has the potential to dramatically reduce the size, cost, and power requirements of future air quality sensors. Microfabrication provides a suite of relatively new tools for the development of micro electro mechanical systems (MEMS) that can be ap...

Growing Gaps: Educational Inequality around the World

ERIC Educational Resources Information Center

Attewell, Paul, Ed.; Newman, Katherine S., Ed.

2010-01-01

The last half century has seen a dramatic expansion in access to primary, secondary, and higher education in many nations around the world. Educational expansion is desirable for a country's economy, beneficial for educated individuals themselves, and is also a strategy for greater social harmony. But has greater access to education reduced or…

Implementing and Evaluating Effective Professional Development in Functional Behavioral Assessment in Rural Schools.

ERIC Educational Resources Information Center

Mitchem, Katherine; Richards, Ann; Wells, Deborah

The use of positive behavior supports (PBS) based on functional behavioral assessment (FBA) has produced dramatic improvements in problem behaviors of challenging students. This approach is a long-term strategy to reduce inappropriate behavior, teach more appropriate behavior, and provide contextual supports necessary for successful outcomes. Yet…

Emergency power for fish produced in intensive, pond-based systems

USDA-ARS?s Scientific Manuscript database

Power failure in a heavily stocked and fed pond-based culture system can result in massive fish losses within minutes. Even in a conventional pond with a stand-by tractor powered aerator, the shock of a sudden loss of power can dramatically affect production resulting in mortalities and reduced perf...

Indiana State University Graduates to Advanced Plastic Cooling Towers

ERIC Educational Resources Information Center

Sullivan, Ed

2012-01-01

Perhaps more than many other industries, today's universities and colleges are beset by dramatically rising costs on every front. One of the areas where overhead can be contained or reduced is in the operation of the chilled water systems that support air conditioning throughout college campuses, specifically the cooling towers. Like many…

Mitochondrial genomic dysfunction causes dephosphorylation of Sch9 in the yeast Saccharomyces cerevisiae.

PubMed

Kawai, Shigeyuki; Urban, Jörg; Piccolis, Manuele; Panchaud, Nicolas; De Virgilio, Claudio; Loewith, Robbie

2011-10-01

TORC1-dependent phosphorylation of Saccharomyces cerevisiae Sch9 was dramatically reduced upon exposure to a protonophore or in respiration-incompetent ρ(0) cells but not in respiration-incompetent pet mutants, providing important insight into the molecular mechanisms governing interorganellar signaling in general and retrograde signaling in particular.

Rapidly Progressive Osteoarthritis: a Review of the Clinical and Radiologic Presentation.

PubMed

Flemming, Donald J; Gustas-French, Cristy N

2017-07-01

The purpose of this paper is to review the distinct clinical and radiographic features that may lead to prompt diagnosis of rapidly progressive osteoarthritis (RPOA) and thus obviate unnecessary and costly diagnostic workup. RPOA is uncommon but is more frequently seen in practice because of the aging population. RPOA is a destructive arthropathy that occurs most commonly in elderly women but can also be seen in patients that have sustained trauma. The dramatic radiologic manifestations of RPOA can lead to diagnostic confusion with other arthropathies, infection, and osteonecrosis. RPOA was originally described in the hip but may also involve the shoulder. The etiology of RPOA is not well understood, but subchondral fracture probably plays a role in the development of dramatic destruction of the joint that is seen in affected patients. Early diagnosis may reduce the complexity of surgical management. RPOA is an uncommon condition that occurs most frequently in elderly woman or in patients who have sustained trauma. Prompt recognition of the clinical and radiologic features of this arthropathy can reduce unnecessary diagnostic workup and complexity of surgical intervention.

Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages.

PubMed

Lichtenstein, Laeticia; Mattijssen, Frits; de Wit, Nicole J; Georgiadi, Anastasia; Hooiveld, Guido J; van der Meer, Roelof; He, Yin; Qi, Ling; Köster, Anja; Tamsma, Jouke T; Tan, Nguan Soon; Müller, Michael; Kersten, Sander

2010-12-01

Dietary saturated fat is linked to numerous chronic diseases, including cardiovascular disease. Here we study the role of the lipoprotein lipase inhibitor Angptl4 in the response to dietary saturated fat. Strikingly, in mice lacking Angptl4, saturated fat induces a severe and lethal phenotype characterized by fibrinopurulent peritonitis, ascites, intestinal fibrosis, and cachexia. These abnormalities are preceded by a massive acute phase response induced by saturated but not unsaturated fat or medium-chain fat, originating in mesenteric lymph nodes (MLNs). MLNs undergo dramatic expansion and contain numerous lipid-laden macrophages. In peritoneal macrophages incubated with chyle, Angptl4 dramatically reduced foam cell formation, inflammatory gene expression, and chyle-induced activation of ER stress. Induction of macrophage Angptl4 by fatty acids is part of a mechanism that serves to reduce postprandial lipid uptake from chyle into MLN-resident macrophages by inhibiting triglyceride hydrolysis, thereby preventing macrophage activation and foam cell formation and protecting against progressive, uncontrolled saturated fat-induced inflammation. Copyright © 2010 Elsevier Inc. All rights reserved.

Hsp90 activator Aha1 drives production of pathological tau aggregates

PubMed Central

Shelton, Lindsey B.; Baker, Jeremy D.; Zheng, Dali; Sullivan, Leia E.; Solanki, Parth K.; Webster, Jack M.; Sun, Zheying; Sabbagh, Jonathan J.; Nordhues, Bryce A.; Koren, John; Ghosh, Suman; Blagg, Brian S. J.; Dickey, Chad A.

2017-01-01

The microtubule-associated protein tau (MAPT, tau) forms neurotoxic aggregates that promote cognitive deficits in tauopathies, the most common of which is Alzheimer’s disease (AD). The 90-kDa heat shock protein (Hsp90) chaperone system affects the accumulation of these toxic tau species, which can be modulated with Hsp90 inhibitors. However, many Hsp90 inhibitors are not blood–brain barrier-permeable, and several present associated toxicities. Here, we find that the cochaperone, activator of Hsp90 ATPase homolog 1 (Aha1), dramatically increased the production of aggregated tau. Treatment with an Aha1 inhibitor, KU-177, dramatically reduced the accumulation of insoluble tau. Aha1 colocalized with tau pathology in human brain tissue, and this association positively correlated with AD progression. Aha1 overexpression in the rTg4510 tau transgenic mouse model promoted insoluble and oligomeric tau accumulation leading to a physiological deficit in cognitive function. Overall, these data demonstrate that Aha1 contributes to tau fibril formation and neurotoxicity through Hsp90. This suggests that therapeutics targeting Aha1 may reduce toxic tau oligomers and slow or prevent neurodegenerative disease progression. PMID:28827321

Integration and manufacture of multifunctional planar lightwave circuits

NASA Astrophysics Data System (ADS)

Lipscomb, George F.; Ticknor, Anthony J.; Stiller, Marc A.; Chen, Wenjie; Schroeter, Paul

2001-11-01

The demands of exponentially growing Internet traffic, coupled with the advent of Dense Wavelength Division Multiplexing (DWDM) fiber optic systems to meet those demands, have triggered a revolution in the telecommunications industry. This dramatic change has been built upon, and has driven, improvements in fiber optic component technology. The next generation of systems for the all optical network will require higher performance components coupled with dramatically lower costs. One approach to achieve significantly lower costs per function is to employ Planar Lightwave Circuits (PLC) to integrate multiple optical functions in a single package. PLCs are optical circuits laid out on a silicon wafer, and are made using tools and techniques developed to extremely high levels by the semi-conductor industry. In this way multiple components can be fabricated and interconnected at once, significantly reducing both the manufacturing and the packaging/assembly costs. Currently, the predominant commercial application of PLC technology is arrayed-waveguide gratings (AWG's) for multiplexing and demultiplexing multiple wavelength channels in a DWDM system. Although this is generally perceived as a single-function device, it can be performing the function of more than 100 discrete fiber-optic components and already represents a considerable degree of integration. Furthermore, programmable functions such as variable-optical attenuators (VOAs) and switches made with compatible PLC technology are now moving into commercial production. In this paper, we present results on the integration of active and passive functions together using PLC technology, e.g. a 40 channel AWG multiplexer with 40 individually controllable VOAs.

An evaluation of traffic-awareness campaign videos: empathy induction is associated with brain function within superior temporal sulcus.

PubMed

Zelinková, Jana; Shaw, Daniel J; Mareček, Radek; Mikl, Michal; Urbánek, Tomáš; Havlíčková, Darina; Zámečník, Petr; Haitová, Petra; Brázdil, Milan

2014-08-12

Acting appropriately within social contexts requires an ability to appreciate others' mental and emotional states. Indeed, some campaign programs designed to reduce anti-social behaviour seek to elicit empathy for the victims. The effectiveness of these campaigns can be evaluated according to the degree to which they induce such responses, but by applying neuroscientific techniques this can be done at the behavioural and neurophysiological level. Neuroimaging studies aimed at identifying the neural mechanisms behind such socio-cognitive and -emotional processes frequently reveal the role of the superior temporal sulcus (STS). We applied this knowledge to assess the effectiveness of traffic-awareness campaign adverts to induce empathic expression. Functional magnetic resonance imaging (fMRI) data were acquired from 20 healthy male volunteers as they watched these campaign videos consisting of a dramatic sequence of events and catastrophic endings, and control videos without such dramatic endings. Among other structures, a significantly greater neural response was observed within bilateral STS, particularly within the right hemisphere, during the observation of campaign relative to control videos. Furthermore, activation in these brain regions correlated with the subjects' empathic expression. Our results develop our understanding of the role of STS in social cognition. Moreover, our data demonstrate the utility of neuroscientific methods when evaluating the effectiveness of campaign videos in terms of their ability to elicit empathic responses. Our study also demonstrates the utility of these specific stimuli for future neuroscientific research.

An evaluation of traffic-awareness campaign videos: empathy induction is associated with brain function within superior temporal sulcus

PubMed Central

2014-01-01

Acting appropriately within social contexts requires an ability to appreciate others’ mental and emotional states. Indeed, some campaign programs designed to reduce anti-social behaviour seek to elicit empathy for the victims. The effectiveness of these campaigns can be evaluated according to the degree to which they induce such responses, but by applying neuroscientific techniques this can be done at the behavioural and neurophysiological level. Neuroimaging studies aimed at identifying the neural mechanisms behind such socio-cognitive and -emotional processes frequently reveal the role of the superior temporal sulcus (STS). We applied this knowledge to assess the effectiveness of traffic-awareness campaign adverts to induce empathic expression. Functional magnetic resonance imaging (fMRI) data were acquired from 20 healthy male volunteers as they watched these campaign videos consisting of a dramatic sequence of events and catastrophic endings, and control videos without such dramatic endings. Among other structures, a significantly greater neural response was observed within bilateral STS, particularly within the right hemisphere, during the observation of campaign relative to control videos. Furthermore, activation in these brain regions correlated with the subjects’ empathic expression. Our results develop our understanding of the role of STS in social cognition. Moreover, our data demonstrate the utility of neuroscientific methods when evaluating the effectiveness of campaign videos in terms of their ability to elicit empathic responses. Our study also demonstrates the utility of these specific stimuli for future neuroscientific research. PMID:25118071

In situ diagnosis of pulsed UV laser surface ablation of tungsten carbide hardmetal by using laser-induced optical emission spectroscopy

NASA Astrophysics Data System (ADS)

Li, Tiejun; Lou, Qihong; Wei, Yunrong; Huang, Feng; Dong, Jingxing; Liu, Jingru

2001-12-01

Surface ablation of cobalt cemented tungsten carbide hardmetal with pulsed UV laser has been in situ diagnosed by using the technique of laser-induced optical emission spectroscopy. The dependence of emission intensity of cobalt lines on number of laser shots was investigated at laser fluence of 2.5 J/cm 2. As a comparison, the reliance of emission intensity of cobalt lines as a function of laser pulse number by using pure cobalt as ablation sample was also studied at the same laser condition. It was found that for surface ablation of tungsten carbide hardmetal at laser fluence of 2.5 J/cm 2, the intensities of cobalt lines fell off dramatically in the first 300 consecutive laser shots and then slowed down to a low stable level with even more shots. For surface ablation of pure cobalt at the same laser condition, the intensities of cobalt lines remained constant more or less even after 500 laser shots and then reduced very slowly with even more shots. It was concluded that selective evaporation of cobalt at this laser fluence should be responsible for the dramatic fall-off of cobalt lines with laser shots accumulation for surface ablation of tungsten carbide hardmetal. In contrast, for surface ablation of pure cobalt, the slow reduction of cobalt lines with pulse number accumulation should be due to the formation of laser-induced crater effect.

A small amount of dietary carbohydrate can promote the HFD-induced insulin resistance to a maximal level.

PubMed

Mei, Shuang; Yang, Xuefeng; Guo, Huailan; Gu, Haihua; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Bennett, Brian J; He, Ling; Cao, Wenhong

2014-01-01

Both dietary fat and carbohydrates (Carbs) may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD) or HFD containing 0.1-25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1%) induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level.

A Small Amount of Dietary Carbohydrate Can Promote the HFD-Induced Insulin Resistance to a Maximal Level

PubMed Central

Guo, Huailan; Gu, Haihua; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Bennett, Brian J.; He, Ling; Cao, Wenhong

2014-01-01

Both dietary fat and carbohydrates (Carbs) may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD) or HFD containing 0.1–25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1%) induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level. PMID:25055153

Effects of early life exposure to ultraviolet C radiation on mitochondrial DNA content, transcription, ATP production, and oxygen consumption in developing Caenorhabditis elegans

PubMed Central

2013-01-01

Background Mitochondrial DNA (mtDNA) is present in multiple copies per cell and undergoes dramatic amplification during development. The impacts of mtDNA damage incurred early in development are not well understood, especially in the case of types of mtDNA damage that are irreparable, such as ultraviolet C radiation (UVC)-induced photodimers. Methods We exposed first larval stage nematodes to UVC using a protocol that results in accumulated mtDNA damage but permits nuclear DNA (nDNA) repair. We then measured the transcriptional response, as well as oxygen consumption, ATP levels, and mtDNA copy number through adulthood. Results Although the mtDNA damage persisted to the fourth larval stage, we observed only a relatively minor ~40% decrease in mtDNA copy number. Transcriptomic analysis suggested an inhibition of aerobic metabolism and developmental processes; mRNA levels for mtDNA-encoded genes were reduced ~50% at 3 hours post-treatment, but recovered and, in some cases, were upregulated at 24 and 48 hours post-exposure. The mtDNA polymerase γ was also induced ~8-fold at 48 hours post-exposure. Moreover, ATP levels and oxygen consumption were reduced in response to UVC exposure, with marked reductions of ~50% at the later larval stages. Conclusions These results support the hypothesis that early life exposure to mitochondrial genotoxicants could result in mitochondrial dysfunction at later stages of life, thereby highlighting the potential health hazards of time-delayed effects of these genotoxicants in the environment. PMID:23374645

Proteasome inhibition blocks NF-κB and ERK1/2 pathways, restores antigen expression and sensitizes resistant human melanoma to TCR-engineered CTLs

PubMed Central

Jazirehi, Ali R.; Economou, James S.

2012-01-01

Adoptive cell transfer (ACT) of ex vivo engineered autologous lymphocytes encoding high-affinity MART-1/HLA-A*0201-specific T-cell receptor (TCR) α/β chains (F5 CTL), densely infiltrate into sites of metastatic disease, mediating dramatic but partial clinical responses in melanoma patients. We hypothesized that MART-1 down-modulation in addition to aberrant apoptotic/survival signaling could confer resistance to death signals delivered by transgenic CTLs. To explore this hypothesis, we established an in vitro model of resistant (R) lines from MART-1+/HLA-A*0201+ F5 CTL-sensitive parental (P) lines under serial F5 CTL-selective pressure. We have recently reported that several melanoma R lines, while retaining MART-1 expression, exhibited constitutive NF-κB activation and over-expression of NF-κB-dependent resistance factors. Another established melanoma cell line M244, otherwise sensitive to F5 CTL, yielded R lines after serial F5 CTL selective pressure which had both reduced MART-1 expression levels, thus, could not be recognized, and were resistant to CTL-delivered apoptotic death signals. The proteasome inhibitor bortezomib blocked NF-κB activity, decreased phopspho-ERK1/2, increased phospho-JNK levels, reduced expression of resistance-factors, restored MART-1 expression to sufficient levels, which in combination allowed M244R lines be sensitized to F5 CTL-killing. These findings suggest that proteasome inhibition in immune resistant tumors can restore proapoptotic signaling and improve tumor antigen expression. PMID:22532603

A Nampt inhibitor FK866 mimics vitamin B3 deficiency by causing senescence of human fibroblastic Hs68 cells via attenuation of NAD(+)-SIRT1 signaling.

PubMed

Song, Tuzz-Ying; Yeh, Shu-Lan; Hu, Miao-Lin; Chen, Mei-Yau; Yang, Nae-Cherng

2015-12-01

Vitamin B3 (niacin) deficiency can cause pellagra with symptoms of dermatitis, diarrhea and dementia. However, it is unclear whether the vitamin B3 deficiency causes human aging. FK866 (a Nampt inhibitor) can reduce intracellular NAD(+) level and induce senescence of human Hs68 cells. However, the mechanisms underlying FK866-induced senescence of Hs68 cells are unclear. In this study, we used FK866 to mimic the effects of vitamin B3 deficiency to reduce the NAD(+) level and investigated the mechanisms of FK866-induced senescence of Hs68 cells. We hypothesized that FK866 induced the senescence of Hs68 cells via an attenuation of NAD(+)-silent information regulator T1 (SIRT1) signaling. We found that FK866 induced cell senescence and diminished cellular NAD(+) levels and SIRT1 activity (detected by acetylation of p53), and these effects were dramatically antagonized by co-treatment with nicotinic acid, nicotinamide, or NAD(+). In contrast, the protein expression of SIRT1, AMP-activated protein kinase, mammalian target of rapamycin, and nicotinamide phosphoribosyltransferase (Nampt) was not affected by FK866. In addition, the role of GSH in the FK866-induced cells senescence may be limited, as N-acetylcysteine did not antagonize FK866-induced cell senescence. These results suggest that FK866 induces cell senescence via attenuation of NAD(+)-SIRT1 signaling. The effects of vitamin B3 deficiency on human aging warrant further investigation.

A geostatistics-informed hierarchical sensitivity analysis method for complex groundwater flow and transport modeling: GEOSTATISTICAL SENSITIVITY ANALYSIS

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

Dai, Heng; Chen, Xingyuan; Ye, Ming

Sensitivity analysis is an important tool for quantifying uncertainty in the outputs of mathematical models, especially for complex systems with a high dimension of spatially correlated parameters. Variance-based global sensitivity analysis has gained popularity because it can quantify the relative contribution of uncertainty from different sources. However, its computational cost increases dramatically with the complexity of the considered model and the dimension of model parameters. In this study we developed a hierarchical sensitivity analysis method that (1) constructs an uncertainty hierarchy by analyzing the input uncertainty sources, and (2) accounts for the spatial correlation among parameters at each level ofmore » the hierarchy using geostatistical tools. The contribution of uncertainty source at each hierarchy level is measured by sensitivity indices calculated using the variance decomposition method. Using this methodology, we identified the most important uncertainty source for a dynamic groundwater flow and solute transport in model at the Department of Energy (DOE) Hanford site. The results indicate that boundary conditions and permeability field contribute the most uncertainty to the simulated head field and tracer plume, respectively. The relative contribution from each source varied spatially and temporally as driven by the dynamic interaction between groundwater and river water at the site. By using a geostatistical approach to reduce the number of realizations needed for the sensitivity analysis, the computational cost of implementing the developed method was reduced to a practically manageable level. The developed sensitivity analysis method is generally applicable to a wide range of hydrologic and environmental problems that deal with high-dimensional spatially-distributed parameters.« less

Regulatory circuitry of TWEAK-Fn14 system and PGC-1α in skeletal muscle atrophy program.

PubMed

Hindi, Sajedah M; Mishra, Vivek; Bhatnagar, Shephali; Tajrishi, Marjan M; Ogura, Yuji; Yan, Zhen; Burkly, Linda C; Zheng, Timothy S; Kumar, Ashok

2014-03-01

Skeletal muscle wasting attributed to inactivity has significant adverse functional consequences. Accumulating evidence suggests that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and TNF-like weak inducer of apoptosis (TWEAK)-Fn14 system are key regulators of skeletal muscle mass in various catabolic states. While the activation of TWEAK-Fn14 signaling causes muscle wasting, PGC-1α preserves muscle mass in several conditions, including functional denervation and aging. However, it remains unknown whether there is any regulatory interaction between PGC-1α and TWEAK-Fn14 system during muscle atrophy. Here we demonstrate that TWEAK significantly reduces the levels of PGC-1α and mitochondrial content (∼50%) in skeletal muscle. Levels of PGC-1α are significantly increased in skeletal muscle of TWEAK-knockout (KO) and Fn14-KO mice compared to wild-type mice on denervation. Transgenic (Tg) overexpression of PGC-1α inhibited progressive muscle wasting in TWEAK-Tg mice. PGC-1α inhibited the TWEAK-induced activation of NF-κB (∼50%) and dramatically reduced (∼90%) the expression of atrogenes such as MAFbx and MuRF1. Intriguingly, muscle-specific overexpression of PGC-1α also prevented the inducible expression of Fn14 in denervated skeletal muscle. Collectively, our study demonstrates that TWEAK induces muscle atrophy through repressing the levels of PGC-1α. Overexpression of PGC-1α not only blocks the TWEAK-induced atrophy program but also diminishes the expression of Fn14 in denervated skeletal muscle.

Ultrafast DNA sequencing on a microchip by a hybrid separation mechanism that gives 600 bases in 6.5 minutes.

PubMed

Fredlake, Christopher P; Hert, Daniel G; Kan, Cheuk-Wai; Chiesl, Thomas N; Root, Brian E; Forster, Ryan E; Barron, Annelise E

2008-01-15

To realize the immense potential of large-scale genomic sequencing after the completion of the second human genome (Venter's), the costs for the complete sequencing of additional genomes must be dramatically reduced. Among the technologies being developed to reduce sequencing costs, microchip electrophoresis is the only new technology ready to produce the long reads most suitable for the de novo sequencing and assembly of large and complex genomes. Compared with the current paradigm of capillary electrophoresis, microchip systems promise to reduce sequencing costs dramatically by increasing throughput, reducing reagent consumption, and integrating the many steps of the sequencing pipeline onto a single platform. Although capillary-based systems require approximately 70 min to deliver approximately 650 bases of contiguous sequence, we report sequencing up to 600 bases in just 6.5 min by microchip electrophoresis with a unique polymer matrix/adsorbed polymer wall coating combination. This represents a two-thirds reduction in sequencing time over any previously published chip sequencing result, with comparable read length and sequence quality. We hypothesize that these ultrafast long reads on chips can be achieved because the combined polymer system engenders a recently discovered "hybrid" mechanism of DNA electromigration, in which DNA molecules alternate rapidly between repeating through the intact polymer network and disrupting network entanglements to drag polymers through the solution, similar to dsDNA dynamics we observe in single-molecule DNA imaging studies. Most importantly, these results reveal the surprisingly powerful ability of microchip electrophoresis to provide ultrafast Sanger sequencing, which will translate to increased system throughput and reduced costs.

Ultrafast DNA sequencing on a microchip by a hybrid separation mechanism that gives 600 bases in 6.5 minutes

PubMed Central

Fredlake, Christopher P.; Hert, Daniel G.; Kan, Cheuk-Wai; Chiesl, Thomas N.; Root, Brian E.; Forster, Ryan E.; Barron, Annelise E.

2008-01-01

To realize the immense potential of large-scale genomic sequencing after the completion of the second human genome (Venter's), the costs for the complete sequencing of additional genomes must be dramatically reduced. Among the technologies being developed to reduce sequencing costs, microchip electrophoresis is the only new technology ready to produce the long reads most suitable for the de novo sequencing and assembly of large and complex genomes. Compared with the current paradigm of capillary electrophoresis, microchip systems promise to reduce sequencing costs dramatically by increasing throughput, reducing reagent consumption, and integrating the many steps of the sequencing pipeline onto a single platform. Although capillary-based systems require ≈70 min to deliver ≈650 bases of contiguous sequence, we report sequencing up to 600 bases in just 6.5 min by microchip electrophoresis with a unique polymer matrix/adsorbed polymer wall coating combination. This represents a two-thirds reduction in sequencing time over any previously published chip sequencing result, with comparable read length and sequence quality. We hypothesize that these ultrafast long reads on chips can be achieved because the combined polymer system engenders a recently discovered “hybrid” mechanism of DNA electromigration, in which DNA molecules alternate rapidly between reptating through the intact polymer network and disrupting network entanglements to drag polymers through the solution, similar to dsDNA dynamics we observe in single-molecule DNA imaging studies. Most importantly, these results reveal the surprisingly powerful ability of microchip electrophoresis to provide ultrafast Sanger sequencing, which will translate to increased system throughput and reduced costs. PMID:18184818

Internet Technology in Electronic Commerce

NASA Astrophysics Data System (ADS)

Zhanys, A. B.; Tursinbaeva, A. F.

2018-05-01

Informatization is an active process of acquiring information as a valuable resource for development using Informatics tools in order to dramatically increase the intellectual level of civilization on this basis – humanistic reconstruction of the whole human life.

Pumilacidin-Like Lipopeptides Derived from Marine Bacterium Bacillus sp. Strain 176 Suppress the Motility of Vibrio alginolyticus

PubMed Central

Xiu, Pengyuan; Liu, Rui

2017-01-01

ABSTRACT Bacterial motility is a crucial factor during the invasion and colonization processes of pathogens, which makes it an attractive therapeutic drug target. Here, we isolated a marine bacterium (Vibrio alginolyticus strain 178) from a seamount in the tropical West Pacific that exhibits vigorous motility on agar plates and severe pathogenicity to zebrafish. We found that V. alginolyticus 178 motility was significantly suppressed by another marine bacterium, Bacillus sp. strain 176, isolated from the same niche. We isolated, purified, and characterized two different cyclic lipopeptides (CLPs) from Bacillus sp. 176 using high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. The two related CLPs have a pumilacidin-like structure and were both effective inhibitors of V. alginolyticus 178 motility. The CLPs differ by only one methylene group in their fatty acid chains. In addition to motility suppression, the CLPs also induced cell aggregation in the medium and reduced adherence of V. alginolyticus 178 to glass substrates. Notably, upon CLP treatment, the expression levels of two V. alginolyticus flagellar assembly genes (flgA and flgP) dropped dramatically. Moreover, the CLPs inhibited biofilm formation in several other strains of pathogenic bacteria without inducing cell death. This study indicates that CLPs from Bacillus sp. 176 show promise as antimicrobial lead compounds targeting bacterial motility and biofilm formation with a low potential for eliciting antibiotic resistance. IMPORTANCE Pathogenic bacteria often require motility to establish infections and subsequently spread within host organisms. Thus, motility is an attractive therapeutic target for the development of novel antibiotics. We found that cyclic lipopeptides (CLPs) produced by marine bacterium Bacillus sp. strain 176 dramatically suppress the motility of the pathogenic bacterium Vibrio alginolyticus strain 178, reduce biofilm formation, and promote cellular aggregation without inducing cell death. These findings suggest that CLPs hold great promise as potential drug candidates targeting bacterial motility and biofilm formation with a low overall potential for triggering antibiotic resistance. PMID:28389538

Pumilacidin-Like Lipopeptides Derived from Marine Bacterium Bacillus sp. Strain 176 Suppress the Motility of Vibrio alginolyticus.

PubMed

Xiu, Pengyuan; Liu, Rui; Zhang, Dechao; Sun, Chaomin

2017-06-15

Bacterial motility is a crucial factor during the invasion and colonization processes of pathogens, which makes it an attractive therapeutic drug target. Here, we isolated a marine bacterium ( Vibrio alginolyticus strain 178) from a seamount in the tropical West Pacific that exhibits vigorous motility on agar plates and severe pathogenicity to zebrafish. We found that V. alginolyticus 178 motility was significantly suppressed by another marine bacterium, Bacillus sp. strain 176, isolated from the same niche. We isolated, purified, and characterized two different cyclic lipopeptides (CLPs) from Bacillus sp. 176 using high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. The two related CLPs have a pumilacidin-like structure and were both effective inhibitors of V. alginolyticus 178 motility. The CLPs differ by only one methylene group in their fatty acid chains. In addition to motility suppression, the CLPs also induced cell aggregation in the medium and reduced adherence of V. alginolyticus 178 to glass substrates. Notably, upon CLP treatment, the expression levels of two V. alginolyticus flagellar assembly genes ( flgA and flgP ) dropped dramatically. Moreover, the CLPs inhibited biofilm formation in several other strains of pathogenic bacteria without inducing cell death. This study indicates that CLPs from Bacillus sp. 176 show promise as antimicrobial lead compounds targeting bacterial motility and biofilm formation with a low potential for eliciting antibiotic resistance. IMPORTANCE Pathogenic bacteria often require motility to establish infections and subsequently spread within host organisms. Thus, motility is an attractive therapeutic target for the development of novel antibiotics. We found that cyclic lipopeptides (CLPs) produced by marine bacterium Bacillus sp. strain 176 dramatically suppress the motility of the pathogenic bacterium Vibrio alginolyticus strain 178, reduce biofilm formation, and promote cellular aggregation without inducing cell death. These findings suggest that CLPs hold great promise as potential drug candidates targeting bacterial motility and biofilm formation with a low overall potential for triggering antibiotic resistance. Copyright © 2017 American Society for Microbiology.

Total Control – Pollen Presentation and Floral Longevity in Loasaceae (Blazing Star Family) Are Modulated by Light, Temperature and Pollinator Visitation Rates

PubMed Central

Henning, Tilo; Weigend, Maximilian

2012-01-01

Stamen movements can be understood as a mechanism influencing pollen presentation and increasing outbreeding success of hermaphroditic flowers via optimized male function. In this study we experimentally analyzed the factors regulating autonomous and thigmonastic (triggered by flower visitors) stamen movements in eight species of Loasaceae. Both types of stamen movements are positively influenced by light and temperature and come to a virtual standstill in the dark and at low temperatures (12°C). Pollen presentation is thus discontinued during periods where pollinators are not active. Overall stamen presentation increases with increasing flower age. Contrary to expectation, no geometrical correlation between the floral scale stimulated and the stamen fascicle reacting exists, indicating that the stimulus is transmitted over the receptacle and stamen maturation dictates which and how many stamens react. Thigmonastic stamen presentation is dramatically accelerated compared to autonomous movement (3–37 times), indicating that the rate of stamen maturation can be adjusted to different visitation schedules. Flowers can react relatively uniformly down to stimulation intervals of 10–15 min., consistently presenting comparable numbers of stamens in the flower c. 5 min. after the stimulus and can thus keep the amount of pollen presented relatively constant even under very high visitation frequencies of 4–6 visits/h. Thigmonastic pollen presentation dramatically reduces the overall duration of the staminate phase (to 1/3rd in Nasa macrothyrsa). Similarly, the carpellate phase is dramatically reduced after pollination, down to 1 d from 4 d. Overall flower longevity is reduced by more than 2/3rds under high visitation rates (<3 d versus 10 d under visitor exclusion) and depleted and pollinated flowers are rapidly removed from the pool. Complex floral behaviour in Loasaceae thus permits a near-total control over pollen dispensation schedules and floral longevity of the individual flower by an extraordinary fine-tuning to both biotic and abiotic factors. PMID:22916102

The Demand for Shadow Education in China: Mainstream Teachers and Power Relations

ERIC Educational Resources Information Center

Zhang, Wei

2014-01-01

As in other parts of the world, private tutoring has expanded significantly in Mainland China during the past decade. This has been driven by factors including dramatic economic growth, high-stakes examinations, and the traditions of a Confucian culture at the macro-level, and school leadership and family incomes, at the micro-level. This paper…

Future Educational Programs and Employment Prospects in Information Technology

ERIC Educational Resources Information Center

Pollack, Thomas A.

2005-01-01

Over the past several years, we have experienced a rather dramatic downward turn in demand for entry level information technology (IT) professionals. However, reports of trends at the end of 2004 indicated that job postings for IT workers reached their highest levels since 2001. This occurs at a time when the number of four year degree programs in…

Developmentally Appropriate Soccer Activities for Elementary School Children

ERIC Educational Resources Information Center

Quinn, Ronald; Carr, David

2006-01-01

The sport of soccer has seen significant growth across multiple levels for the past two decades. Nowhere has this growth been more dramatic than at the youth level. It is estimated that well over 20 million children have some involvement with the game each year. As a result of this growth in community youth soccer, elementary school students are…

Social insect genomes exhibit dramatic evolution in gene composition and regulation while preserving regulatory features linked to sociality

PubMed Central

Simola, Daniel F.; Wissler, Lothar; Donahue, Greg; Waterhouse, Robert M.; Helmkampf, Martin; Roux, Julien; Nygaard, Sanne; Glastad, Karl M.; Hagen, Darren E.; Viljakainen, Lumi; Reese, Justin T.; Hunt, Brendan G.; Graur, Dan; Elhaik, Eran; Kriventseva, Evgenia V.; Wen, Jiayu; Parker, Brian J.; Cash, Elizabeth; Privman, Eyal; Childers, Christopher P.; Muñoz-Torres, Monica C.; Boomsma, Jacobus J.; Bornberg-Bauer, Erich; Currie, Cameron R.; Elsik, Christine G.; Suen, Garret; Goodisman, Michael A.D.; Keller, Laurent; Liebig, Jürgen; Rawls, Alan; Reinberg, Danny; Smith, Chris D.; Smith, Chris R.; Tsutsui, Neil; Wurm, Yannick; Zdobnov, Evgeny M.; Berger, Shelley L.; Gadau, Jürgen

2013-01-01

Genomes of eusocial insects code for dramatic examples of phenotypic plasticity and social organization. We compared the genomes of seven ants, the honeybee, and various solitary insects to examine whether eusocial lineages share distinct features of genomic organization. Each ant lineage contains ∼4000 novel genes, but only 64 of these genes are conserved among all seven ants. Many gene families have been expanded in ants, notably those involved in chemical communication (e.g., desaturases and odorant receptors). Alignment of the ant genomes revealed reduced purifying selection compared with Drosophila without significantly reduced synteny. Correspondingly, ant genomes exhibit dramatic divergence of noncoding regulatory elements; however, extant conserved regions are enriched for novel noncoding RNAs and transcription factor–binding sites. Comparison of orthologous gene promoters between eusocial and solitary species revealed significant regulatory evolution in both cis (e.g., Creb) and trans (e.g., fork head) for nearly 2000 genes, many of which exhibit phenotypic plasticity. Our results emphasize that genomic changes can occur remarkably fast in ants, because two recently diverged leaf-cutter ant species exhibit faster accumulation of species-specific genes and greater divergence in regulatory elements compared with other ants or Drosophila. Thus, while the “socio-genomes” of ants and the honeybee are broadly characterized by a pervasive pattern of divergence in gene composition and regulation, they preserve lineage-specific regulatory features linked to eusociality. We propose that changes in gene regulation played a key role in the origins of insect eusociality, whereas changes in gene composition were more relevant for lineage-specific eusocial adaptations. PMID:23636946

Recent Advances in Nanotechnology for Diabetes Treatment

PubMed Central

DiSanto, Rocco Michael; Subramanian, Vinayak; Gu, Zhen

2015-01-01

Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to “closed-loop” insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels. “Closing the loop” between blood glucose level (BGL) measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed. PMID:25641955

Control of total GFP expression by alterations to the 3′ region nucleotide sequence

PubMed Central

2013-01-01

Background Previously, we distinguished the Escherichia coli type II cytoplasmic membrane translocation pathways of Tat, Yid, and Sec for unfolded and folded soluble target proteins. The translocation of folded protein to the periplasm for soluble expression via the Tat pathway was controlled by an N-terminal hydrophilic leader sequence. In this study, we investigated the effect of the hydrophilic C-terminal end and its nucleotide sequence on total and soluble protein expression. Results The native hydrophilic C-terminal end of GFP was obtained by deleting the C-terminal peptide LeuGlu-6×His, derived from pET22b(+). The corresponding clones induced total and soluble GFP expression that was either slightly increased or dramatically reduced, apparently through reconstruction of the nucleotide sequence around the stop codon in the 3′ region. In the expression-induced clones, the hydrophilic C-terminus showed increased Tat pathway specificity for soluble expression. However, in the expression-reduced clone, after analyzing the role of the 5′ poly(A) coding sequence with a substituted synonymous codon, we proved that the longer 5′ poly(A) coding sequence interacted with the reconstructed 3′ region nucleotide sequence to create a new mRNA tertiary structure between the 5′ and 3′ regions, which resulted in reduced total GFP expression. Further, to recover the reduced expression by changing the 3′ nucleotide sequence, after replacing selected C-terminal 5′ codons and the stop codon in the ORF with synonymous codons, total GFP expression in most of the clones was recovered to the undeleted control level. The insertion of trinucleotides after the stop codon in the 3′-UTR recovered or reduced total GFP expression. RT-PCR revealed that the level of total protein expression was controlled by changes in translational or transcriptional regulation, which were induced or reduced by the substitution or insertion of 3′ region nucleotides. Conclusions We found that the hydrophilic C-terminal end of GFP increased Tat pathway specificity and that the 3′ nucleotide sequence played an important role in total protein expression through translational and transcriptional regulation. These findings may be useful for efficiently producing recombinant proteins as well as for potentially controlling the expression level of specific genes in the body for therapeutic purposes. PMID:23834827

Ectopic expression of pumpkin gibberellin oxidases alters gibberellin biosynthesis and development of transgenic Arabidopsis plants.

PubMed

Radi, Abeer; Lange, Theo; Niki, Tomoya; Koshioka, Masaji; Lange, Maria João Pimenta

2006-02-01

Immature pumpkin (Cucurbita maxima) seeds contain gibberellin (GA) oxidases with unique catalytic properties resulting in GAs of unknown function for plant growth and development. Overexpression of pumpkin GA 7-oxidase (CmGA7ox) in Arabidopsis (Arabidopsis thaliana) resulted in seedlings with elongated roots, taller plants that flower earlier with only a little increase in bioactive GA4 levels compared to control plants. In the same way, overexpression of the pumpkin GA 3-oxidase1 (CmGA3ox1) resulted in a GA overdose phenotype with increased levels of endogenous GA4. This indicates that, in Arabidopsis, 7-oxidation and 3-oxidation are rate-limiting steps in GA plant hormone biosynthesis that control plant development. With an opposite effect, overexpression of pumpkin seed-specific GA 20-oxidase1 (CmGA20ox1) in Arabidopsis resulted in dwarfed plants that flower late with reduced levels of GA4 and increased levels of physiological inactive GA17 and GA25 and unexpected GA34 levels. Severe dwarfed plants were obtained by overexpression of the pumpkin GA 2-oxidase1 (CmGA2ox1) in Arabidopsis. This dramatic change in phenotype was accompanied by a considerable decrease in the levels of bioactive GA4 and an increase in the corresponding inactivation product GA34 in comparison to control plants. In this study, we demonstrate the potential of four pumpkin GA oxidase-encoding genes to modulate the GA plant hormone pool and alter plant stature and development.

Combined effects of plant competition and insect herbivory hinder invasiveness of an introduced thistle.

PubMed

Suwa, Tomomi; Louda, Svata M

2012-06-01

The biotic resistance hypothesis is a dominant paradigm for why some introduced species fail to become invasive in novel environments. However, predictions of this hypothesis require further empirical field tests. Here, we focus on evaluating two biotic factors known to severely limit plants, interspecific competition and insect herbivory, as mechanisms of biotic resistance. We experimentally evaluated the independent and combined effects of three levels of competition by tallgrass prairie vegetation and two levels of herbivory by native insects on seedling regeneration, size, and subsequent flowering of the Eurasian Cirsium vulgare, a known invasive species elsewhere, and compared its responses to those of the ecologically similar and co-occurring native congener C. altissimum. Seedling emergence of C. vulgare was greater than that of C. altissimum, and that emergence was reduced by the highest level of interspecific competition. Insect leaf herbivory was also greater on C. vulgare than on C. altissimum at all levels of competition. Herbivory on seedlings dramatically decreased the proportion of C. vulgare producing flower heads at all competition levels, but especially at the high competition level. Competition and herbivory interacted to significantly decrease plant survival and biomass, especially for C. vulgare. Thus, both competition and herbivory limited regeneration of both thistles, but their effects on seedling emergence, survival, size and subsequent reproduction were greater for C. vulgare than for C. altissimum. These results help explain the unexpectedly low abundance recorded for C. vulgare in western tallgrass prairie, and also provide strong support for the biotic resistance hypothesis.

From sample-to-answer: integrated genotyping and immunological analysis microfluidic platforms for the diagnostic and treatment of coeliac disease

NASA Astrophysics Data System (ADS)

Jung, M.; Höth, J.; Erwes, J.; Latta, D.; Strobach, X.; Hansen-Hagge, T.; Klemm, R.; Gärtner, C.; Demiris, T. M.; O'Sullivan, C.; Ritzi-Lehnert, M.; Drese, K. S.

2011-02-01

Taking advantage of microfluidics technology, a Lab-on-Chip system was developed offering the possibility of performing HLA (Human Leukocyte Antigen) typing to test genetic predisposition to coeliac disease and measure the level of immunodeficiency at the point-of-care. These analysis procedures are implemented on two different microfluidic cartridges, both having identical interfacial connections to the identical automated instrument. In order to assess the concentration of the targeted analytes in human blood, finger prick samples are processed to either extract genomic DNA carrying the coeliac disease gene or blood plasma containing the disease specific antibodies. We present here the different microfluidic modules integrated in a common platform, capable of automated sample preparation and analyte detection. In summary, this new microfluidic approach will dramatically reduce the costs of materials (polymer for the disposable chips and minute amount of bio-reagents) and minimize the time for analysis down to less than 20 minutes. In comparison to the state of the art detection of coeliac disease this work represents a tremendous improvement for the patient's quality of live and will significantly reduce the cost burden on the health care system.

In Situ Determination of Bisphenol A in Beverage Using a Molybdenum Selenide/Reduced Graphene Oxide Nanoparticle Composite Modified Glassy Carbon Electrode.

PubMed

Shi, Rongguang; Liang, Jing; Zhao, Zongshan; Liu, Yi; Liu, Aifeng

2018-05-22

Due to the endocrine disturbing effects of bisphenol A (BPA) on organisms, rapid detection has become one of the most important techniques for monitoring its levels in the aqueous solutions associated with plastics and human beings. In this paper, a glassy carbon electrode (GCE) modified with molybdenum selenide/reduced graphene oxide (MoSe₂/rGO) was fabricated for in situ determination of bisphenol A in several beverages. The surface area of the electrode dramatically increases due to the existence of ultra-thin nanosheets in a flower-like structure of MoSe₂. Adding phosphotungstic acid in the electrolyte can significantly enhance the repeatability (RSD = 0.4%) and reproducibility (RSD = 2.2%) of the electrode. Under the optimized condition (pH = 6.5), the linear range of BPA was from 0.1 μM⁻100 μM and the detection limit was 0.015 μM (S/ N = 3). When using the as-prepared electrode for analyzing BPA in beverage samples without any pretreatments, the recoveries ranged from 98⁻107%, and the concentrations were from below the detection limit to 1.7 μM, indicating its potential prospect for routine analysis of BPA.

Reduced production of creatinine limits its use as marker of kidney injury in sepsis.

PubMed

Doi, Kent; Yuen, Peter S T; Eisner, Christoph; Hu, Xuzhen; Leelahavanichkul, Asada; Schnermann, Jürgen; Star, Robert A

2009-06-01

Although diagnosis and staging of acute kidney injury uses serum creatinine, acute changes in creatinine lag behind both renal injury and recovery. The risk for mortality increases when acute kidney injury accompanies sepsis; therefore, we sought to explore the limitations of serum creatinine in this setting. In mice, induction of sepsis by cecal ligation and puncture in bilaterally nephrectomized mice increased markers of nonrenal organ injury and serum TNF-alpha. Serum creatinine, however, was significantly lower in septic animals than in animals subjected to bilateral nephrectomy and sham cecal ligation and puncture. Under these conditions treatment with chloroquine decreased nonrenal organ injury markers but paradoxically increased serum creatinine. Sepsis dramatically decreased production of creatinine in nephrectomized mice, without changes in body weight, hematocrit, or extracellular fluid volume. In conclusion, sepsis reduces production of creatinine, which blunts the increase in serum creatinine after sepsis, potentially limiting the early detection of acute kidney injury. This may partially explain why small absolute increases in serum creatinine levels are associated with poor clinical outcomes. These data support the need for new biomarkers that provide better measures of renal injury, especially in patients with sepsis.

Binary partition tree analysis based on region evolution and its application to tree simplification.

PubMed

Lu, Huihai; Woods, John C; Ghanbari, Mohammed

2007-04-01

Pyramid image representations via tree structures are recognized methods for region-based image analysis. Binary partition trees can be applied which document the merging process with small details found at the bottom levels and larger ones close to the root. Hindsight of the merging process is stored within the tree structure and provides the change histories of an image property from the leaf to the root node. In this work, the change histories are modelled by evolvement functions and their second order statistics are analyzed by using a knee function. Knee values show the reluctancy of each merge. We have systematically formulated these findings to provide a novel framework for binary partition tree analysis, where tree simplification is demonstrated. Based on an evolvement function, for each upward path in a tree, the tree node associated with the first reluctant merge is considered as a pruning candidate. The result is a simplified version providing a reduced solution space and still complying with the definition of a binary tree. The experiments show that image details are preserved whilst the number of nodes is dramatically reduced. An image filtering tool also results which preserves object boundaries and has applications for segmentation.

Realizing zT of 2.3 in Ge1-x-y Sbx Iny Te via Reducing the Phase-Transition Temperature and Introducing Resonant Energy Doping.

PubMed

Hong, Min; Chen, Zhi-Gang; Yang, Lei; Zou, Yi-Chao; Dargusch, Matthew S; Wang, Hao; Zou, Jin

2018-03-01

GeTe with rhombohedral-to-cubic phase transition is a promising lead-free thermoelectric candidate. Herein, theoretical studies reveal that cubic GeTe has superior thermoelectric behavior, which is linked to (1) the two valence bands to enhance the electronic transport coefficients and (2) stronger enharmonic phonon-phonon interactions to ensure a lower intrinsic thermal conductivity. Experimentally, based on Ge 1- x Sb x Te with optimized carrier concentration, a record-high figure-of-merit of 2.3 is achieved via further doping with In, which induces the distortion of the density of states near the Fermi level. Moreover, Sb and In codoping reduces the phase-transition temperature to extend the better thermoelectric behavior of cubic GeTe to low temperature. Additionally, electronic microscopy characterization demonstrates grain boundaries, a high-density of stacking faults, and nanoscale precipitates, which together with the inevitable point defects result in a dramatically decreased thermal conductivity. The fundamental investigation and experimental demonstration provide an important direction for the development of high-performance Pb-free thermoelectric materials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The in vitro protective effects of curcumin and demethoxycurcumin in Curcuma longa extract on advanced glycation end products-induced mesangial cell apoptosis and oxidative stress.

PubMed

Liu, Ji-ping; Feng, Liang; Zhu, Mao-mao; Wang, Ru-Shang; Zhang, Ming-hua; Hu, Shao-ying; Jia, Xiao-bin; Wu, Jin-Jie

2012-11-01

Curcuma longa L. (CLL), a traditional herbal medicine, has been widely used for the prevention of diabetic vascular complications in recent years. However, the protective effects of curcuminoids in CLL on the AGEs-induced damage to mesangial cell are not fully understood. In this present study, dihydroethidium, superoxide dismutase kit, malondialdehyde kit, and acridine orange/ethidium bromide staining methods were used to evaluate the activities of curcumin and demethoxycurcumin (10(-11)-10(-9) M) on AGEs-induced oxidative stress and apoptosis, which were associated with the damage to mesangial cell. The results showed that these two compounds could significantly restore advanced glycation end products (AGEs)-induced apoptosis to normal levels (IC50 = 3.874 × 10(-11) M for curcumin and IC50 = 6.085 × 10(-11) M for demethoxycurcumin) and reduce remarkably reactive oxygen species generation in mesangial cell. Furthermore, curcumin and demethoxycurcumin dramatically elevated AGEs-decreased superoxide dismutase activity while significantly reducing AGEs-increased malondialdehyde content in cell culture supernatant. Our results suggest that both curcumin and demethoxycurcumin have a significant protective potential to the prevention of diabetic nephropathy. Georg Thieme Verlag KG Stuttgart · New York.

The protective role of quercetin and arginine on gold nanoparticles induced hepatotoxicity in rats.

PubMed

Abdelhalim, Mohamed Anwar K; Moussa, Sherif A Abdelmottaleb; Qaid, Huda Abdo Yahya

2018-01-01

The aim of the study was to confirm the hepatotoxicity induced by small-sized gold nanoparticles (GNPs) and evaluate the role of quercetin (Qur) and arginine (Arg) against hepatotoxicity caused by GNPs. Twenty-five healthy male Wistar-Kyoto rats were used. GNPs were administered intraperitoneally to these rats at the dose of 50 μL for seven consecutive days. The role of Qur and Arg antioxidants against toxicity induced by GNPs was detected through the measurement of serum liver function and oxidative stress biomarkers in the liver tissues. Coadministration of Qur and Arg along with GNPs significantly induced dramatic alterations in the biochemical parameters. Levels of malondialdehyde, gamma-glutamyl transferase, alanine aminotransferase, alkaline phosphatase, and total protein increased significantly in the GNPs injected group than in the control group, while reduced glutathione was greatly reduced in the GNPs group than in the control group. It also significantly decreased liver enzymes and the oxidative stress, therefore improving the liver damage and hepatotoxicity induced by GNPs. This study demonstrated that Qur and Arg antioxidants effectively improved the hepatic oxidative damage induced by GNPs. It also substantiates the application of Qur and Arg as protecting stand-in against GNPs' hepatotoxicity.

Effects of a crude oil spill on the benthic invertebrate community in the Gasconade River, Missouri

USGS Publications Warehouse

Poulton, Barry C.; Finger, Susan E.; Humphrey, S.A.

1997-01-01

Effects of a 3.3-million–L crude oil spill on the benthic macroinvertebrate community of the Gasconade River, a large river in Missouri, were evaluated by comparing several macroinvertebrate community indices in riffle and backwater habitats above and below the spill. Concentrations of total petroleum hydrocarbons (TPH) in sediments decreased dramatically in riffle habitats within 6 months of the spill, but elevated hydrocarbon levels (TPH = 80–270 μg/g) were still present in backwater habitats at the end of the study. Correspondingly, riffle macroinvertebrate communities recovered rapidly, but overall benthic diversity continued to be reduced in backwater areas until the end of the study 18 months after the spill. In addition, statistical analysis of benthic functional feeding groups revealed that both scrapers and shredders were reduced in backwater habitats below the oil spill. Decreased abundance of shredders and scrapers in these habitats is likely caused by oil contamination of aquatic sediments and associated organic matter required by these groups for food and substrate. Results of this study suggest that the persistence of oil in backwater habitats has a negative effect on the benthic community in large rivers.

Extraordinary wavelength reduction in terahertz graphene-cladded photonic crystal slabs

PubMed Central

Williamson, Ian A. D.; Mousavi, S. Hossein; Wang, Zheng

2016-01-01

Photonic crystal slabs have been widely used in nanophotonics for light confinement, dispersion engineering, nonlinearity enhancement, and other unusual effects arising from their structural periodicity. Sub-micron device sizes and mode volumes are routine for silicon-based photonic crystal slabs, however spectrally they are limited to operate in the near infrared. Here, we show that two single-layer graphene sheets allow silicon photonic crystal slabs with submicron periodicity to operate in the terahertz regime, with an extreme 100× wavelength reduction from graphene’s large kinetic inductance. The atomically thin graphene further leads to excellent out-of-plane confinement, and consequently photonic-crystal-slab band structures that closely resemble those of ideal two-dimensional photonic crystals, with broad band gaps even when the slab thickness approaches zero. The overall photonic band structure not only scales with the graphene Fermi level, but more importantly scales to lower frequencies with reduced slab thickness. Just like ideal 2D photonic crystals, graphene-cladded photonic crystal slabs confine light along line defects, forming waveguides with the propagation lengths on the order of tens of lattice constants. The proposed structure opens up the possibility to dramatically reduce the size of terahertz photonic systems by orders of magnitude. PMID:27143314

Measurement of the Antineutrino Double-Differential Charged-Current Quasi-Elastic Scattering Cross Section at MINERvA

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

Patrick, Cheryl

Next-generation neutrino oscillation experiments, such as DUNE and Hyper-Kamiokande, hope to measure charge-parity (CP) violation in the lepton sector. In order to do this, they must dramatically reduce their current levels of uncertainty, particularly those due to neutrino-nucleus interaction models. As CP violation is a measure of the difference between the oscillation properties of neutrinos and antineutrinos, data about how the less-studied antineutrinos interact is especially valuable. We present the MINERvA experiment's first double-differential scattering cross sections for antineutrinos on scintillator, in the few-GeV range relevant to experiments such as DUNE and NOvA. We also present total antineutrino-scintillator quasi-elastic crossmore » sections as a function of energy, which we compare to measurements from previous experiments. As well as being useful to help reduce oscillation experiments' uncertainty, our data can also be used to study the prevalence of various cor relation and final-state interaction effects within the nucleus. We compare to models produced by different model generators, and are able to draw first conclusions about the predictions of these models.« less

Community Economic Identity: The Coal Industry and Ideology Construction in West Virginia

ERIC Educational Resources Information Center

Bell, Shannon Elizabeth; York, Richard

2010-01-01

Economic changes and the machinations of the treadmill of production have dramatically reduced the number of jobs provided by extractive industries, such as mining and timber, in the United States and other affluent nations in the post-World War II era. As the importance of these industries to national, regional, and local economies wanes,…

Energy Projects for Young Scientists.

ERIC Educational Resources Information Center

Gardner, Robert

Energy is a vital topic. Energy costs have risen dramatically during the last decade and home owners are concerned about their energy bills and the costs associated with heating or cooling their homes. An understanding of energy, its sources and ways to reduce its use or improve the efficiency with which people use it will become more important as…

Choice, Charters, and Public School Competition

ERIC Educational Resources Information Center

Hanushek, Eric A.

2006-01-01

In the last century, public schools changed in ways that dramatically reduced the control that parents have over their local schools. Regaining that control is one key to improving the quality of our schools, and giving students a choice of schools is one way of increasing the influence that parents have over the way schools are run. Several…

Wood adhesives : vital for producing most wood products

Treesearch

Charles R. Frihart

2011-01-01

A main route for the efficient utilization of wood resources is to reduce wood to small pieces and then bond them together (Frihart and Hunt 2010). Although humankind has been bonding wood since early Egyptian civilizations, the quality and quantity of bonded wood products has increased dramatically over the past 100 years with the development of new adhesives and...