cssi/SciSciGPT-SciSciNet huggingface dataset:
Advances in antimicrobial therapy for respiratory tract infections.

Even at the turn of the millennium, respiratory infections exact a heavy toll on the American public. Pneumonia is the leading infectious disease cause of death, and influenza costs Medicare more than $1 billion each year. This article highlights some of the advances this past year in antimicrobial
Researchers’ Perceptions of Statistical Significance Contribute to Bias in Health and Exercise Science

ABSTRACTWe surveyed researchers in the health and exercise sciences to explore different areas and magnitudes of bias in researchers’ decision making. Participants were presented with scenarios (testing a central hypothesis with p = .06 or p = .04) in a random order and surveyed about what they would do in each scenario. Participants showed significant bias in deciding to randomize additional participants when p = .06 (24.5%) compared to when p = .04 (6.5%), χ2 = 19.86, odds ratio (OR) = 13.5. Based on this bias to randomize additional participants, we present statistical simulations showing the cumulative negative effect this bias has on the false positive rate for a field. While it is important for researchers to have flexibility in their data-processing decisions, there is a cost/benefit trade-off to experimenter degrees of freedom and it is important that these decisions be unbiased. These data highlight the importance of a priori analysis plans in research.
Relationship Between Plasma Prolactin and the Endocrine Microenvironment of the Developing Human Antral Follicle

The aim of the present study was to determine whether any obvious relationships exist between the circulating levels of prolactin at the time of ovariectomy and the endocrine microenvironment and developmental status of antral follicles. The concentrations of prolactin, follicle-stimulating hormone (FSH), and estradiol were measured in peripheral plasma and in antral fluid of follicles collected at varying stages of the menstrual cycle. In addition, the granulosa cells were recovered from each follicle (≥4mm in diameter) and their numbers were quantitated. When the plasma levels of prolactin ranged from 11 to 100ng/ml, the antral fluid levels of prolactin were uniformly low ( These findings suggest that hyperprolactinemia is associated with a marked reduction in intraovarian activity and that the extent of this reduction may not be always apparent from the levels of circulating estradiol.
Resource prospector drill performance during the integrated payload tests

The goal of the Lunar Resource Prospector (RP) is to capture and evaluate volatile species within the top meter of the lunar regolith. The RP drill has been designed to 1. Generate cuttings and place them on the surface for analysis by the Near InfraRed Volatiles Spectrometer Subsystem (NIRVSS), and 2. Capture cuttings and transfer them to the Oxygen and Volatile Extraction Node (OVEN) coupled with the Lunar Advanced Volatiles Analysis (LAVA) subsystem. The drill auger is designed to capture cuttings as opposed to cores. The lower auger section has deep and low pitch flutes for retaining of cuttings. The upper section has been designed to efficiently move the cuttings out of the hole. The drill uses a “bite” sampling approach where samples are captured in ∼10 cm intervals. The drill has been integrated with the NASA JSC RP rover prototype and tested in the summer of 2015. This paper describes the drill and test results.
High luminous efficacy green light-emitting diodes with AlGaN cap layer

We demonstrate very high luminous efficacy green light-emitting diodes employing Al0.30Ga0.70N cap layer grown on patterned sapphire substrates by metal organic chemical vapor deposition. The peak external quantum efficiency and luminous efficacies were 44.3% and 239 lm/w, respectively. At 20 mA (20 A/cm2) the light output power was 14.3 mW, the forward voltage was 3.5 V, the emission wavelength was 526.6 nm, and the external quantum efficiency was 30.2%. These results are among the highest reported luminous efficacy values for InGaN based green light-emitting diodes.
Clinical Presentation and Therapy of Arrhythmias

Arrhythmias can be classified based upon the site of origin of the arrhythmia (supraventricular or ventricular), the heart rate of the arrhythmia (tachyarrhythmia or bradyarrhythmia), the function or dysfunction of the AV node (atrioventricular block or dissociation), or the underlying mechanism of the arrhythmia (reentry or bypass tract, automatic focus, ion channel defect).
Expression of Erythropoietin and Erythropoietin Receptor in Squamous Cell Carcinomas of the Head and Neck: Levels of Erythropoietin Expression Correlate with Tumor Hypoxia.

Erythropoietin (EPO), an oxygen-regulated glycoprotein hormone, is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor EPOR. The recombinant form of human EPO is widely used in clinical practice for the prevention or treatment of anemia associated with cancer and chemo-radiation therapy. However, in a recent randomized, placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck, EPO treatment was associated with poorer loco-regional progression-free survival. The purpose of this study was to determine whether EPOR and its ligand EPO are expressed in primary squamous cell carcinomas of the head and neck. We also investigated the hypothesis that EPO expression in malignant cells may be associated with the presence of tumor hypoxia, an important factor involved in resistance to radiation treatment, tumor aggressiveness and poor prognosis. Twenty-one patients with squamous cell carcinoma of the head and neck were enrolled in a tumor hypoxia study under a research protocol approved by the Institutional Review Board at the University of North Carolina Hospitals. All patients provided signed informed consent. The patients received an intravenous infusion of the hypoxia marker pimonidazole hydrochloride (Hypoxyprobe-1™) prior to multiple tumor biopsies. Two or more biopsies were available from all except one primary tumor. The tissue specimen from one patient with laryngeal carcinoma was excluded because of availability of only a single, small and fragmented biopsy. Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for expression of EPOR and EPO as well as pimonidazole binding. We found EPOR expression in tumor cells in 97% of the biopsies. The pattern of EPOR immunoreactivity was predominantly cytoplasmic but was found to be localized to the membrane in some sections. Co-expression of EPO was observed in 90% of biopsies. Qualitative and semi-quantitative analyes for EPO staining and tumor hypoxia on a section-by-section basis revealed that EPO and pimonidazole adduct staining did not always co-localize within tumors but there was a significant positive correlation between levels of micro-regional EPO expression and pimonidazole binding (r = 0.736, P by two-tailed Spearman’s rank correlation analysis). These data demonstrate the co-expression of EPOR and its ligand EPO in squamous carcinoma cells suggesting that EPO may play a novel role as a potential autocrine or paracrine growth factor in head and neck cancer. Furthermore, EPO expression in tumor cells may be modulated, at least in part, by tumor hypoxia. The expression of EPOR needs to be taken into consideration in the design of future clinical trials investigating the role of recombinant human EPO in head and neck cancer.
A study of hybrid ventilation in an institutional building for predictive control

Abstract Hybrid ventilation can be employed to precool thermally massive buildings, reducing energy consumption for cooling the following day, particularly at night when the outdoor temperature is lower, and especially when its operation is done in a predictive manner by incorporating weather forecasts. An important requirement is defining the temperature low limit for admitting exterior cool air into a building through transition spaces, to ensure thermal comfort. This paper uses a case study of a 17-story high institutional building with a hybrid ventilation system. To develop a strategy for the admission of outside air into the building, this study focuses on the corridors as generic transition zones/buffer spaces with flexible thermal comfort limits and with the motorized facade openings to determine how the air temperature evolves with distance from the inlets. A developed thermal model, calibrated from a full-scale test, calculates the amount of heat removed from the 0.4 m thick concrete floor. Through 4 h of night cooling with an average local exterior temperature of 8.3 °C, the air temperature rises to about 12 °C in the transition corridor region at a time when occupancy in that area is expected to be nearly zero. Taking into consideration the flexibility in thermal comfort in the corridor transition spaces, control strategies are developed, based on exterior temperature and humidity. Using humidity ratio instead of relative humidity as criterion for admitting outdoor air potentially results in the system being active for 49% - 180% more hours during the year.
Abstract B068: Inhibition of GSK-3: A novel therapeutic approach for breast cancer treatment

NF-kappaB is known to regulate human breast cancer progression, metastasis and chemoresistance. Glycogen Synthase Kinase-3beta (GSK-3beta), a serine/threonine protein kinase, is an essential positive regulator of NF-kappaB transcriptional activity and thereby GSK-3beta may represent a potential therapeutic target in human breast cancer. Our objectives were to determine the expression pattern of GSK-3beta in human breast cancer, to assess the effect of GSK-3 inhibition on breast cancer cell proliferation, survival and chemoresistance, and to evaluate our lead GSK-3 inhibitors alone and in combination with chemotherapeutic drugs for the targeted therapy of breast cancer. Using nuclear/cytosolic fractionation, Western immunoblotting and immunohistochemical staining, we observed aberrant nuclear accumulation of GSK-3beta in five breast cancer cell lines and in 7 of 8 primary human breast carcinomas and corresponding lymph node metastases whereas no detectable expression of GSK-3beta was found in benign breast tissue. Pharmacological inhibition of GSK-3 led to a decrease in proliferation and survival of breast cancer cells. Our in vitro comparison studies demonstrated that our lead GSK-3 inhibitor 9-ING-41 was significantly (30 times) more effective than GSK-3 inhibitor LY2090314 (Eli Lilly), currently in mid-stage clinical trials, in terms of growth inhibition of breast cancer cells. Inhibition of GSK-3 resulted in decreased expression of the NF-kappaB target genes Bcl-2 and XIAP and induction of apoptosis. Moreover, our lead GSK-3 inhibitor 9-ING-41 and doxorubicin acted synergistically to suppress growth of breast cancer cells. Our preliminary in vivo experiments demonstrated that monotherapy with our lead GSK-3 inhibitor 9-ING-41 (20 mg/kg) for 48 hours inhibited proliferation (as shown by BrDU assay) and induced apoptosis (as shown by TUNEL assay) in MDA-MB-468 orthotopic xenograft tumors. Moreover, in vivo toxicology study demonstrated that intravenous injections of 9-ING-41 did not adversely affect mouse complete blood counts or cause overt pathological changes in mouse organs. Our results identify GSK-3beta as a new potential drug target in breast cancer and suggest that inhibition of GSK-3 is a novel therapeutic approach to overcome NF-kappaB-mediated chemoresistance in breast cancer. Citation Format: Andrey Ugolkov, Irina Gaisina, Dmitry Malin, Peter Kulesza, Alan Kozikowski, Vincent Cryns, Andrew Mazar. Inhibition of GSK-3: A novel therapeutic approach for breast cancer treatment. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr B068.
Sphingolipid Organization in the Plasma Membrane and the Mechanisms That Influence It.

Sphingolipids are structural components in the plasma membranes of eukaryotic cells. Their metabolism produces bioactive signaling molecules that modulate fundamental cellular processes. The segregation of sphingolipids into distinct membrane domains is likely essential for cellular function. This review presents the early studies of sphingolipid distribution in the plasma membranes of mammalian cells that shaped the most popular current model of plasma membrane organization. The results of traditional imaging studies of sphingolipid distribution in stimulated and resting cells are described. These data are compared with recent results obtained with advanced imaging techniques, including super-resolution fluorescence detection and high-resolution secondary ion mass spectrometry (SIMS). Emphasis is placed on the new insight into the sphingolipid organization within the plasma membrane that has resulted from the direct imaging of stable isotope-labeled lipids in actual cell membranes with high-resolution SIMS. Super-resolution fluorescence techniques revealed the biophysical behaviors of sphingolipids and the unhindered diffusion of cholesterol analogs in the membranes of living cells are ultimately in contrast to the prevailing hypothetical model of plasma membrane organization. High-resolution SIMS studies also conflicted with the prevailing hypothesis, showing sphingolipids are concentrated in micrometer-scale membrane domains, but cholesterol is evenly distributed within the plasma membrane. Reductions in cellular cholesterol decreased the number of sphingolipid domains in the plasma membrane, whereas disruption of the cytoskeleton eliminated them. In addition, hemagglutinin, a transmembrane protein that is thought to be a putative raft marker, did not cluster within sphingolipid-enriched regions in the plasma membrane. Thus, sphingolipid distribution in the plasma membrane is dependent on the cytoskeleton, but not on favorable interactions with cholesterol or hemagglutinin. The alternate views of plasma membrane organization suggested by these findings are discussed.
Abstract 108: TALEN-mediated Gene-Editing in Zebrafish for Studying Titin Biology

Background: Titin, the largest protein found in nature, has been found to be crucial for heart and muscle development and mutations on titin caused human diseases. Especially, truncated mutations on TITIN were found to be a major causative gene (more than 25%) for familiar dilated cardiomyopathy (DCM) but the mechanism is lacking. Due to the gigantic size and number of exons, genetic study of titin has been challenging. To facilitate genetic analysis of titin biology, we leveraged the Transcription Activator-Like Effects Nuclease (TALEN) technology in zebrafish to edit the titin gene directly. Results: We generated TALEN pairs targeting different domains of zebrafish titin, including Z-disc domain, N2B domain, and A domains. Because zebrafish contain two titin homologues, ttna and ttnb , TALEN pairs targeting the corresponding loci for both homologues were made. The mutations are efficiently introduced on the titin using TALENs. In addition to these truncated mutants, TALEN technology can also create internal deletions. The titin mutant fish were identified and further phenotypic analysis has been carried out. Conclusions: Combined with TALEN technology, zebrafish can provide a convenient vertebrate model for genetic studies of titin biology. Moreover, this gene-editing technology will facilitate the use of the zebrafish model as a powerful research tool for modeling human diseases and investigating their pathogenesis.
Two-Dimensional Oscillatory Neural Network Based on Room-Temperature Charge-Density-Wave Devices

We propose an oscillatory neural network implemented with two-dimensional (2-D) tantalum disulfide devices operating in the change density wave regime at room temperature. An elementary cell of the network consists of two 1T-TaS 2 devices connected in series. Such a cell has a constant output and oscillatory states. All cells have the same bias voltage. There is a constant current flowing through the cell in the constant output mode. The oscillations occur at a certain bias voltage due to the electrical-field triggered metal-to-insulator transition owing to the changes in the charge-density-wave phase in the 1T-TaS 2 channel. Two 1T-TaS 2 devices oscillate out-of-phase when one of the devices is in the insulator phase while the other one is in the metallic state. The nearest-neighbor cells are coupled via graphene transistors. The cells are resistively coupled if the graphene transistor is in the on state while they are capacitively coupled if the transistor is in the off state. The operation of the oscillatory neural network is simulated numerically for the 30 × 30 node network. We present the examples of pattern recognition on a template with the fixed coupling among the near-neighbor cells. We also present the results of our numerical modeling mimicking the Game of Life in the network with the time-varying coupling. The 2-D 1T-TaS 2 devices, utilized in the network, offer a unique combination of properties such as scalability, high operational frequency, fast synchronization speed, and radiation hardness, which makes them promising for both consumer electronic and defense applications.
Evaluating the use of nitric acid as a detergent in dairy cleaned-in-place systems.

A model cleaned-in-place system was constructed and an atomic absorption method used to evaluate the detergency of low concentrations of nitric acid. Results indicate that critical temperature-concentration combinations exist which will remove the calcium from stainless steel test plates soiled with a milk film to a level comparable to a standardized-control wash (0.0–0.2 ppm calcium in 30 ml solvent eluted from a 324 cm2 area). Stainless steel test plates soiled with milk became resistant to wetting with water after being washed with nitric acid. Bacteriological studies were made to determine if the surface of the plates washed with nitric acid retained enough nutrients to support bacterial growth. Longer washing times than those required for complete calcium removal were necessary to reduce effectively the number of bacteria which would multiply on the surface of the test plates. Tests on corrosion showed that low concentrations of nitric acid were noncorrosive to stainless steel type 304. Low concentra...
Trapped Without Choice: An Exploration of Abortion Access in the Southern U.S.

Porter, D. (Director). (2016). Trapped [Motion picture]. Brooklyn, NY: Big Mouth Productions.Slashing reproductive rights has been at the forefront of the conservative agenda in the United States, ...
Towards an Efficient Finite Element Method for the Integral Fractional Laplacian on Polygonal Domains

We explore the connection between fractional order partial differential equations in two or more spatial dimensions with boundary integral operators to develop techniques that enable one to efficiently tackle the integral fractional Laplacian. In particular, we develop techniques for the treatment of the dense stiffness matrix including the computation of the entries, the efficient assembly and storage of a sparse approximation and the efficient solution of the resulting equations. The main idea consists of generalising proven techniques for the treatment of boundary integral equations to general fractional orders. Importantly, the approximation does not make any strong assumptions on the shape of the underlying domain and does not rely on any special structure of the matrix that could be exploited by fast transforms. We demonstrate the flexibility and performance of this approach in a couple of two-dimensional numerical examples.
Impact of Simulation-Based Training on Radiology Trainee Education in Ultrasound-Guided Breast Biopsies

Abstract Purpose The aim of this study is to determine the impact of a simulation-based ultrasound-guided (USG) breast biopsy training session on radiology trainee procedural knowledge, comfort levels, and overall procedural confidence and anxiety. Methods Twenty-one diagnostic radiology residents from a single academic institution were recruited to participate in an USG breast biopsy training session. The residents filled out a questionnaire before and after the training session. Ten multiple-choice questions tested general knowledge in diagnostic breast ultrasound and USG breast biopsy concepts. Subjective comfort levels with ultrasound machine and biopsy device functionality, patient positioning, proper biopsy technique, image documentation, needle safety and overall procedural confidence and anxiety levels were reported on a 5-point Likert scale before and after training. Results Participants demonstrated significant improvement in number of correctly answered general knowledge questions after training ( P P P = .27). Conclusions A simulation-based USG breast biopsy training session may improve radiology trainee procedural knowledge, comfort levels, and overall procedural confidence.
Design, fabrication, and analysis of lattice exhibiting energy absorption via snap-through behavior

Abstract In this study, an energy absorption lattice, comprised of multiple tetra-beam-plate unit cells with negative stiffness, was designed, fabricated by selective laser sintering method, and analyzed both numerically and experimentally. Snap-through behavior of the unit cell developed due to negative stiffness caused by geometric nonlinearity from large deflection of the constituent elastic beams, resulting in energy absorption. A criterion for the unit cell to achieve the snap-through behavior was investigated numerically in terms of the beam slenderness ratio and the inclined angle. This approach was chosen to facilitate control of energy dissipation performance and further design space such as tuning force threshold. The unit cell with the selected geometric parameters was then created and used to construct the energy absorption lattice. Load-displacement relationships of the lattices obtained from cyclic loading tests disclosed an area enclosed by two distinct loading and unloading curves, which indicates energy dissipation. This was shown both numerically and experimentally. Drop tests were also performed to investigate energy loss of the lattices due to an impact. An energy absorption phenomenon was revealed by observing a reduced rebound height when the lattice exhibited the snap-through behavior.
Specialized specialists and the narrow niche fallacy: a tale of scale-feeding fishes.

Although rare within the context of 30 000 species of extant fishes, scale-feeding as an ecological strategy has evolved repeatedly across the teleost tree of life. Scale-feeding (lepidophagous) fi...
Molecular Modeling of Cross-Linked Polymers with Complex Cure Pathways: A Case Study of Bismaleimide Resins

To date, molecular modeling of cross-linking polymers has focused on those involving single-reaction cure mechanisms, such as epoxies and the epoxide–amine reaction. In this work, we have developed a novel cross-linking framework that is capable of undertaking complex cure mechanisms involving several simultaneous reaction pathways with minimal user input. As a case study, a bismaleimide (BMI) resin is considered herein which possesses multiple cure reactions and reaction pathways. Using an adaptable molecular dynamics simulation method, we highlight our framework by implementing five distinct cure reactions of Matrimid-5292 (a BMI resin) and predicting the corresponding thermomechanical properties. The method is used to establish the influence of different cure reactions and extent of curing on mass density, glass transition temperature, coefficient of thermal expansion, elastic moduli, and thermal conductivity. The developed method is further validated by comparison of these properties to experimentally...
SoundGlove: Multisensory Exploration of Everyday Objects for Creative Purposes

SoundGlove is a tool for exploring everyday objects through a tangible, synesthetic experience of sound. The device facilitates this exploration by allowing the user to physically record and mix sounds by grabbing them out of the air and dropping them into a bowl. Sounds deposited into the bowl are mixed together and can be played back, enhancing abilities not only in observation, but in sound creation, as well. This paper describes the design and implementation of the SoundGlove system and considers potential applications, as suggested from early testing with users.
Philosophy, Engineering, and Western culture

Engineering has long been treated with condescension in Western culture and this continues today even among those intellectuals who have discovered the cultural significance of science and, very recently, of technology. In a complementary essay to this one, I describe technology as a social process to which engineering contributes, but which is driven by institution-specific executive decisions that apply technical knowledge selectively to the accomplishment of managerial agendas.1 The practice of engineering, I argue there, is captive to social determinants of this process such that the definition of engineering problems, the determination of the means to be used in solving them, and the identification of what will count as solutions, all derive from the institutional context of engineering’s practice, not from the knowledge engineers possess, and certainly not from Nature.
The ruby anniversary: forty years of publication of Transplantation Proceedings - the first decade: the flowering of immunology and immunogenetics.

Abstract The fortieth—ruby—anniversary of publication of Transplantation Proceedings chronicles the major developments in this field of expanding scientific and clinical importance. The first decade of publication included seminal findings in immunogenetics of the major histocompatibility complex—HLA-A, -B, -C, and -D—and immunology of induction and expression of alloimmunity from single cell to mammalian organisms. Initial dissections of destructive versus acceptance mechanisms toward allografts revealed cytotoxic versus suppressive/enhancing cell-mediates and humoral vectors. Initial clinical successes revealed technical accomplishments that warranted broader application of this technology as described in the second decade of the Proceedings—the advent of cyclosporine.
Variations in Healthcare Provider Use of Public Health and Other Information Sources by Provider Type and Practice Setting During New York City's Response to the Emerging Threat of Zika Virus Disease, 2016.

The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) used multiple methods to provide guidance to healthcare providers on the management and prevention of Zika virus disease duri...
Obesity is not associated with hip failure in patients with articular surface replacement of the hip

Background:Our main aim was to investigate whether obese patients were at increased risk of elevated metal ion levels and/or adverse local tissue reaction (ALTR) after being treated with articular ...
Age-dependent pathogenesis of clade 2.3.4.4A H5N2 HPAIV in experimentally infected Broad Breasted White turkeys.

Abstract Highly pathogenic avian influenza (HPAI) is a viral disease with devastating consequences to the poultry industry as it results in high morbidity, mortality and international trade restrictions. In the present study, we characterized age-related differences in terms of pathology in commercial white broad breasted turkeys inoculated with A/turkey/Minnesota/12582/2015 (H5N2) HPAIV clade 2.3.4.4A, a virus from the largest HPAI poultry outbreak that affected the Unites States in 2014–2015. Turkeys infected at 6-weeks of age showed inapparent to little clinical signs with rapid disease progression, reaching 100% mortality at 3 days post infection (dpi). In contrast, turkeys infected at 16-weeks of age developed ataxia and lethargy and reached 100% mortality by 5 dpi. Infection in the 6-weeks old turkeys resulted in peracute lesions consistent of extensive hemorrhages, edema and necrosis, but inflammation was not prominent. In the 16-weeks old turkeys, necrosis and hemorrhages in tissues were accompanied by a more prominent subacute inflammatory infiltrate. Both age groups showed presence of avian influenza virus (AIV) nucleoprotein (NP) in multiple cell types including neurons, glial cells, ependymal cells, respiratory epithelial cells, air capillary epithelium and pulmonary macrophages, cardiac myocytes, smooth muscle fibers, pancreatic acini and ductal cells. Cells of the vascular walls stained strongly positive for viral antigens, but no positivity was found in the endothelial cells of any organs. These findings indicate that age is a determinant factor in the progression of the disease and delay of mortality during infection with the H5N2 clade 2.3.4.4A HPAI virus in naive white broad breasted turkeys.
Harnessing synthetic biology for sustainable development

Advances in synthetic biology have the potential to develop new products, materials and services that could contribute to the 2030 United Nations Sustainable Development Goals. Support for synthetic biology initiatives in developing countries is needed to ensure that these benefits are open to all.
Principles of Design for Information Systems

Three models for the design of information systems are presented: microanalytic, macroanalytic, and esoteric. Each model has characteristics which are illustrated by a discussion of systems selected from the literature. The underlying design principles of each model are identified and evaluated in terms of their effectiveness in solving the central design problem. This central problem is the encroachment of technology into areas which traditionally have been the sole domain of human thought. The result has been conflict between subconscious expectations of users and explicit system goals. The discussion emphasizes those principles of design which are most useful in identifying and resolving this conflict.
Rho kinase inhibitors reduce voltage-dependent Ca2+ channel signaling in aortic and renal microvascular smooth muscle cells.

Voltage-dependent L-type Ca2+ channels (L-VDCCs) and the RhoA/Rho kinase pathway are two predominant intracellular signaling pathways that regulate renal microvascular reactivity. Traditionally, th...
Onset of the Late Paleozoic Glacioeustatic Signal: A Stratigraphic Record from the Paleotropical, Oil-Shale-Bearing Big Snowy Trough of Central Montana, U.S.A.

Abstract In the Big Snowy Mountains of central Montana, USA, late Visean to Bashkirian strata preserve a nearly complete, but poorly documented, paleotropical stratigraphic succession that straddles the range of current estimates of the onset of the Late Paleozoic Ice Age (LPIA). Sedimentologic and stratigraphic investigation of the Otter (late Visean to Serpukhovian) and Heath (Serpukhovian) formations, with secondary focus on the overlying Tyler (late Serpukhovian to Bashkirian) and Alaska Bench (Bashkirian) formations, facilitated an appraisal of paleotropical environmental change preserved in this succession. Three facies associations reminiscent of environments currently forming in Shark Bay, Australia, were identified in the Otter Formation: shallow semi-restricted littoral platform, intertidal platform, and supratidal plain. Five facies associations broadly comparable to modern environments present in the Sunda Shelf and southern coast of the Persian Gulf were identified in the Heath Formation: offshore outer ramp, mid- to outer ramp, inner ramp, coastal plain, and sabkha. Facies associations preserved in the Heath Formation are here explained in the context of a protected, homoclinal carbonate ramp situated in a partially silled epicontinental embayment. A shift from low-magnitude relative sea-level oscillations preserved in the Otter Formation to a cyclothemic stratigraphic pattern entailing ≥ 6 fourth-order, high-frequency and high-magnitude relative sea-level fluctuations in the Heath Formation is here interpreted to record the main eustatic signal of the LPIA in central Montana. Current published biostratigraphic constraints for the observed stratigraphy estimate the main eustatic signal of the LPIA to have occurred approximately between 331 (base Serpukhovian) and 327 Ma in central Montana. A distinct upward transition from coal and paleosol-bearing depositional sequences in the lower Heath to evaporite and limestone-bearing depositional sequences in the upper Heath preserves a broad humid to arid paleoclimate shift during deposition of this unit, which influenced hydrographic circulation patterns and the resultant distribution of anoxic environments in the Big Snowy Trough during this time interval. Improved depositional and sequence stratigraphic models of the Heath Formation proposed in this study permit new insight into the theoretical distribution of, and water depth necessary to preserve, black, organic-rich claystone and shale in partially silled intracratonic basins, in addition to new temporal constraints on LPIA onset in paleotropical western Laurentia.
Experiments in Drag-Reducing Polymer Flows

Small amounts of high molecular weight polymers (a few parts per million by weight) dissolved in a solvent can reduce the turbulent flow frictional resistance from that of the pure solvent by as much as 90 percent. Since the viscosity of a polymer/solvent mix is slightly increased over that of the solvent alone, the fact that viscous drag is decreased is somewhat surprising. The study of these drag-reducing, non-Newtonian fluid flows received initial impetus from the study of Toms (1948). Since this work, the examination of the turbulent flow properties of dilute solutions of long chain high-molecular weight polymers has generated many hundreds of publications, of which a majority are experimental investigations. This preponderance of experimental studies is no doubt due to the difficult theoretical nature of the problem which must address not only the turbulent kinematics but also the interaction of a viscoelastic fluid with the turbulence. Several excellent reviews of the available experiments and possible explanations of this phenomenon have been published since Toms original work: Lumley (1969) & (1973), Hoyt (1972), Virk (1975), Little et al. (1975), and Berman (1978). Theoretical discussions of the drag reduction phenomenon can be found in Lumley (1973), Berman (1978) and a recent work by Ryskin (1987a). The text that follows includes a review of experimental methods utilized by both rheologists and fluid dynamicists in the examination of turbulent flows of drag-reducing polymer solutions. In addition, we review some of the major experimental findings and make recommendations for future research. Finally, we present some new measurements of wall pressure in a turbulent non-Newtonian channel flow.
Developing Lifelong Learners

Medical school education is but the beginning of a career as a physician. Although learning a breadth and depth of knowledge and skills is expected while a medical student, probably the most important skill required of a new physician is the ability and desire to continue to learn. With the exponential increase in scientific discoveries, the changing environment with its effects on organism mutation, and global “one health,” the future physician must be equipped to handle whatever new diseases develop and apply future therapeutics effectively.
Islam, Authoritarianism, and Underdevelopment

It is widely observed, seldom mentioned, and rarely examined with factual information: the Muslim majority countries are not achieving their social, political, and economic potentials. By all measu...
Core values of genomic citizen science: results from a qualitative interview study

Genomic citizen science initiatives that promote public involvement in the study or manipulation of genetic information are flourishing. These initiatives are diverse and range from data donation studies, to biological experimentation conducted in home and community laboratories, to self-experimentation. Understanding the values that citizen scientists associate with their activities and communities can be useful to policy development for citizen science. Here, we report values-relevant data from qualitative interviews with 38 stakeholders in genomic citizen science. Applying a theoretical framework that describes values as transcendent beliefs about desirable end states or behaviors that can be categorized according to the motivational goals they express and the interests they serve, we identified nine core values of genomic citizen science: altruism, autonomy, fun, inclusivity, openness, reciprocity, respect, safety, and solidarity.
Post-translational knockdown and post-secretional modification of EsxA determine contribution of EsxA membrane permeabilizing activity for mycobacterial intracellular survival.

Current genetic studies (e.g. gene knockout) have suggested that EsxA and EsxB function as secreted virulence factors that are essential for Mycobaterium tuberculosis (Mtb) intracellular survival, ...
The immediate effect of a single session of pain neuroscience education on pain and the autonomic nervous system in subjects with persistent pain, a pilot study.

Background The autonomic nervous system is a system that operates at the subconscious level and has been associated with neurobehavioral aspects of pain. Overall, persistent pain has a stimulating effect on the sympathetic nervous system. A promising emerging nonpharmacological treatment to manage persistent pain is neuroscience-based pain education. The overarching goal of neuroscience-based pain education is to change cognitions about pain and the pain experience through education. The aim was to determine the immediate and short-term impact of a neuroscience-based pain education video on the autonomic nervous system and pain in a subgroup of individuals with persistent pain. Methods A convenience sample of 26 subjects were recruited for this study. Each subject indicated their pain level at the time of testing using a Visual Analogue Scale. Automated pupillometry was utilized to measure pupil diameter. After two minutes of accommodation to the goggles, the pupil was measured continuously for 60 s. Following this a 5-minute video presentation "Understanding Pain" was watched, followed by a continuous pupil measurement for 60 s. Three minutes after this measure, the final pupil diameter measurement was taken for 60 s. After completing the final pupil measure, the subject was asked to fill out a second Visual Analogue Scale and a Global Rate of Change. Outcomes Each subject completed a Global Rating of Change Scale and the mean score was 1.14 (SD = 1.61 and a SEM = 0.), supporting the hypothesis of an overall self-perceived benefit from the intervention. There was a statistically significant difference in pain following the video, P < 0.01. A significant correlation was observed between the self-perceived decrease in pain level and the Global Rating of Change score, p = 0.02. There was no statistically significant difference in the mean pupil diameter following the video with p = 0.76 for the right eye and p = 0.250 for the left eye. Discussion This pilot study demonstrated that a 5-minute neuroscience-based pain education video reduced perceived pain in a small sample of subjects with persistent pain. Watching the neuroscience-based pain education video did not seem to result in an immediate generalized autonomic nervous system response. However, it resulted in a different reaction on each eye. This unequal response might be the result of the hemispheric lateralization of the ANS. This study supports the fact that the pain experience is determined by the balance between conscious cognitive processes and subconscious processes based on previous psychological experiences.
Centralized vs. Decentralized Competition for Price and Lead-Time Sensitive Demand

We study two firms that compete on price and lead-time decisions in a common market. We explore the impact of decentralizing these decisions, as made by the marketing and production departments, respectively, with either marketing or production as the leader. We compare scenarios in which none, one, or both of the firms are decentralized to see whether decentralization can be the equilibrium strategy. We find that under intense price competition, with intensity characterized by the underlying parameters of market demand, firms may suffer from a decentralized structure, particularly under high flexibility induced by high capacity, where revenue based sales incentives motivate sales/marketing to make aggressive price cuts that often erode profit margins. In contrast, under intense lead-time competition, a decentralized strategy with marketing as the leader can not only result in significantly higher profits, but it can also be the equilibrium strategy. Moreover, decentralization may no longer lead to lower prices or longer lead-times if the production department chooses capacity along with lead-time.
Requirements for observations from chemodynamical models

Chemodynamical models view the evolution of galaxies in the context of an ISM that is influenced both by the stars that it has made and the effects of the gravitational potential of the host system. While these models include complicated interactions within galaxies, they also exhibit general features, such as regulated star formation rates, mixing between various gas phases in the interstellar medium, and the transport of metals over large distances. These predictions are the basis for initial observational tests of the models, where good qualitative agreement is found, and offer a foundation for future quantitative comparisons with chemodynamical models.
Biotin-deficient growth of Bacillus polymyxa.

Abstract When Bacillus polymyxa, a wild-type biotin auxotroph, is grown in biotin-deficient medium, a retardation of cell division and consequential cell elongation are the initial detectable consequences of limited biotin. Subsequent events in biotin-deficient cells include, in chronological order: inhibition of net ribonucleic acid (RNA) synthesis and a simultaneous arithmetical accumulation of protein; loss of net RNA, deoxyribonucleic acid, and protein synthesis; morphological aberration, death, and lysis. Incorporation studies employing 32P-phosphate and 14CO2 demonstrate an initial selective inhibition of net ribosomal RNA synthesis over that of ribosomal protein or total protein. Biotin could not be replaced by various extracts from which biotin had been removed, nor could osmotic stabilizers be found which could prevent lysis of the culture.
Listeria monocytogenes ATCC 35152 and NCTC 7973 contain a nonhemolytic, nonvirulent variant.

Listeria monocytogenes NCTC 7973 and this same strain deposited as ATCC 35152 contain two phenotypes: hemolytic virulent colonies and nonvirulent colonies that show no zones of hemolysis when streaked on heart infusion agar containing 5% rabbit blood. Results of examinations of these virulent and nonvirulent strains by investigators at the Centers for Disease Control, Atlanta, Ga., the Pasteur Institute, Paris, France, and the University of Wurzburg, Federal Republic of Germany, support the conclusion that the avirulent strain is a nonhemolytic mutant of the virulent strain and that hemolysin is a virulence factor for L. monocytogenes.
An Introduction to Gerontology: Ageing and health

OVERVIEW This chapter examines common syndromes encountered in older patients, their assessment (principally using the comprehensive geriatric assessment), issues in the clinical management of older patients, the effects of vulnerability and co-morbidity, and the management of these. Introduction O son, help your father in his old age, and do not grieve him as long as he lives; even if he is lacking in understanding, show forbearance; in all your strength do not despise him. For kindness to a father will not be forgotten. Sirach 3:12–14 What is different about health in ageing people? Aren't all people simply as old as they feel? Does the approach to assessment and management differ from the approach recommended for younger people? Why are geriatric medicine specialists needed? When is care by a geriatrician appropriate and how old does one need to be before he or she should visit a geriatrician? Chapter 2 outlined the biological changes that occur with ageing. Anyone over 40 who needs reading glasses can attest to the fact that there are physiological and functional changes that occur with advancing age. These changes occur at different rates in different individuals and can be affected by lifestyle and environment, but on average by age 75 one becomes, in the strict sense of the word, ‘geriatric’. The manifestations of multiple concomitant chronic diseases and their subsequent management are different in older people and present additional challenges to the geriatricians and gerontological advanced practice professionals who care for these patients.
Doxycycline inhibition of interleukin-1 in the corneal epithelium

Purpose To evaluate the effect of doxycycline on the regulation of interleukin (IL)-1 expression and activity in human cultured corneal epithelium. Methods Human corneal limbal epithelium (HLE) was cultured from explants prepared from limbal rings of donor corneas. Primary cultured limbal epithelial cells were treated with either 10 microg/ml lipopolysaccharide (LPS), LPS with 10 microg/ml doxycycline, or LPS with 0.1 mg/ml methylprednisolone (MP) for 24 hours. The intracellular and supernatant protein amounts of IL-1alpha, the precursor and mature forms of IL-1beta, IL-1 receptor antagonist (IL-1 RA), and the intracellular level of IL-1beta-converting enzyme (ICE) were measured with enzyme-linked immunosorbent assays (ELISAs). Western blot analysis was performed to evaluate IL-1 RA protein. mRNA steady state amounts were determined by RNase protection assay (RPA) for IL-1alpha, IL-1beta, IL-1 RA, and ICE. Results LPS increased the mRNA and protein amounts of intracellular and released IL-1alpha, mature IL-1beta, and IL-1 RA. Doxycycline inhibited the LPS-induced IL-1beta increase in the mRNA and protein amounts in the corneal epithelium and upregulated the expression of the anti-inflammatory IL-1 RA protein. In addition, doxycycline reduced the steady state level of the cellular ICE protein but did not affect the level of ICE transcripts. IL-1beta secreted to the conditioned media of HLE was functionally active in inducing matrix metalloproteinase (MMP)-1 and MMP-3 in cultured corneal fibroblasts. Doxycycline significantly decreased IL-1beta bioactivity in the supernatants from LPS-treated corneal epithelial cultures. These effects were comparable to those induced by the corticosteroid, MP. Conclusions Doxycycline can suppress the steady state amounts of mRNA and protein of IL-beta and decrease the bioactivity of this major inflammatory cytokine. These data may partially explain the clinically observed anti-inflammatory properties of doxycycline. The observation that doxycycline was equally potent as a corticosteroid, combined with the relative absence of adverse effects, makes it a potent drug for a wide spectrum of ocular surface inflammatory diseases.