cssi/SciSciGPT-SciSciNet huggingface dataset:
Progesterone-Mediated Calcium Influx and Acrosome Reaction of Human Spermatozoa: Pharmacological Investigation of T-Type Calcium Channels

The mechanisms of the progesterone (P4)-activated Ca21 influx and the relationship between the intracellular free Ca21 concentration ([Ca21]i) and the acrosome reaction (AR) were investigated in this study. We compared the [Ca21]i of uncapacitated and capacitated human sperm populations in response to P4 stimulation; characterized the effects of the pharmacological agents pimozide and mibefradil, inhibitors of T-type voltage-operated calcium channels (VOCCT), on the P4-activated Ca21 influx; and determined the effects of these drugs on the P4-initiated AR. Since pimozide can also inhibit calmodulin-dependent enzymes, we examined the effects of the calmodulin antagonist, calmidazolium, on the above-mentioned events. The basal [Ca21]i and the amplitude of the P4-activated Ca21 influx were significantly (p , 0.05) higher in capacitated sperm populations. Also, in capacitated sperm populations, all three pharmacological agents significantly (p , 0.05) inhibited the P4-activated Ca21 influx (IC50): calmidazolium (0.7 mM) . pimozide (8 mM) . mibefradil (11 mM). By contrast, the effects of these drugs on the P4-initiated AR were varied: pimozide (10 and 20 mM) significantly (p , 0.05) increased the percentage of AR spermatozoa, calmidazolium was without effect, and mibefradil (20 mM) significantly (p , 0.05) inhibited the AR. These disparate results do not allow us to reach any definitive conclusion concerning the role of a sperm VOCCT in the mechanism of the P4-initiated AR. However, the differences between the [Ca21]i and AR effects, in particular the inverse relationship in the case of pimozide, suggest a dissociation between the amplitude of the P4-stimulated Ca21 signal and the downstream biological effect of that signal, the AR.
Relations of Discretionary and Nondiscretionary Leadership to Performance and Satisfaction in a Complex Organization

Leadership was conceptualized as consisting of a discretionary and nondiscretionary component. Discretionary leadership was that under control of the leader. Nondiscretionary leadership was that invoked by the organizational setting in which the leader operated. The setting was conceptualized in terms of twelve dimensions of the Organizational Practices Questionnaire. Leadership consisted of two reward and two sanctions dimensions. Interactive and noninteractive relationships of these leadership components with performance and satisfaction were investigated. With one exception, all relationships with the criteria were noninteractive. Results were discussed in terms of theoretical significance and their implications for management training and organizational design approaches. Suggestions for further research were included.
Temporal dynamics of motivation-cognitive control interactions revealed by high-resolution pupillometry

Motivational manipulations, such as the presence of performance-contingent reward incentives, can have substantial influences on cognitive control. Previous evidence suggests that reward incentives may enhance cognitive performance specifically through increased preparatory, or proactive, control processes. The present study examined reward influences on cognitive control dynamics in the AX-Continuous Performance Task (AX-CPT), using high-resolution pupillometry. In the AX-CPT, contextual cues must be actively maintained over a delay in order to appropriately respond to ambiguous target probes. A key feature of the task is that it permits dissociable characterization of preparatory, proactive control processes (i.e., utilization of context) and reactive control processes (i.e., target-evoked interference resolution). Task performance profiles suggested that reward incentives enhanced proactive control (context utilization). Critically, pupil dilation was also increased on reward incentive trials during context maintenance periods, suggesting trial-specific shifts in proactive control, particularly when context cues indicated the need to overcome the dominant target response bias. Reward incentives had both transient (i.e., trial-by-trial) and sustained (i.e., block-based) effects on pupil dilation, which may reflect distinct underlying processes. The transient pupillary effects were present even when comparing against trials matched in task performance, suggesting a unique motivational influence of reward incentives. These results suggest that pupillometry may be a useful technique for investigating reward motivational signals and their dynamic influence on cognitive control.
The Alcator C-Mod lower hybrid current drive experiment low power microwave and active control system

A 3 MW (upgradeable to 4 MW) 4.6 GHz Lower Hybrid Current Drive (LHCD) system is being implemented on Alcator C-Mod to control and sustain current profile evolution. The LHCD low-power microwave and active control system, using fast vector modulators, will provide a phase and amplitude controlled driver for each of twelve 4.6 GHz, 250 kW klystrons. Resulting phase and power outputs of each klystron will be monitored by I-Q detectors and made available for closed-loop control of the klystron phase and amplitude during plasma shots. Synchronized digital controllers will be implemented for each control loop and operation will be coordinated with external fast protection circuitry provided in the LHCD transmitter and coupler protection systems.
Efficacy of Hospital Germicides against Adenovirus 8, a Common Cause of Epidemic Keratoconjunctivitis in Health Care Facilities

The inactivation of virus-contaminated nonporous inanimate surfaces was investigated using adenovirus type 8, a common cause of epidemic keratoconjunctivitis. A 10-microl inoculum of adenovirus was placed onto each stainless steel disk (1-cm diameter), and the inoculum was allowed to air dry for 40 min. Twenty-one different germicides (including disinfectants and antiseptics) were selected for this study based on their current uses in health care. After a 1- or 5-minute exposure to 50 microl of the germicide, the virus-germicide test mixture was neutralized and assayed for infectivity. Using an efficacy criterion of a 3-log10 reduction in the titer of virus infectivity and regardless of the virus suspending medium (i.e., hard water, sterile water, and hard water with 5% fetal calf serum), only five disinfectants proved to be effective against the test virus at 1 min: 0.55% ortho-phthalaldehyde, 2.4% glutaraldehyde, 2.65% glutaraldehyde, approximately 6,000 ppm chlorine, and approximately 1,900 ppm chlorine. Four other disinfectants showed effectiveness under four of the five testing conditions: 70% ethanol, 65% ethanol with 0.63% quaternary ammonium compound, 79.6% ethanol with 0.1% quaternary ammonium compound, and 0.2% peracetic acid. Of the germicides suitable for use as an antiseptic, 70% ethanol achieved a 3-log10 reduction under four of the five test conditions. These results emphasize the need for proper selection of germicides for use in disinfecting noncritical surfaces and semicritical medical devices, such as applanation tonometers, in order to prevent outbreaks of epidemic keratoconjunctivitis.
Preclinical in vivo Evaluation of an Extracorporeal HIFU Device for Ablation of Pancreatic Tumors

Extracorporeal high-intensity focused ultrasound (HIFU) can be used to ablate tissue noninvasively by delivering focused ultrasound energy from an external source. HIFU for clinical treatment of pancreatic cancer has been reported; however, systematic evaluation of the safety and efficacy of pancreatic ablation with HIFU has not been performed. The objectives of this in vivo study are as follows: (1) assess the safety and feasibility of targeting and ablating pancreatic tissue using the FEP-BY02 HIFU system (Yuande Bio-Medical Engineering, Beijing, China); (2) evaluate a method for estimating in situ acoustic treatment energy in an in vivo setting; and (3) identify the optimal treatment parameters that result in safe and effective ablation of the pancreas. The pancreata of 12 common swine were treated in vivo. Prior to therapy, blood was drawn for laboratory analysis. Animals were then treated with extracorporeal HIFU at three different acoustic treatment energies (750, 1000 and 1250 J). Endoscopy was performed prior to and immediately following HIFU therapy to assess for gastric injury. Blood was drawn after completion of the treatment and on days 2 and 7 following treatment to assess for biochemical evidence of pancreatitis. Animals were then euthanized 7 d following treatment and a necropsy was performed to assess for unintended injury and to obtain pancreatic tissue for histology to assess efficacy of HIFU ablation. Histologic scoring of pancreatic tissue changes was performed by a pathologist blinded to the treatment energy delivered. The degree of ablation identified on histology correlated with the treatment energy. No collateral tissue damage was seen at treatment energies of 750 and 1000 J. At 1250 J, thermal injury to the abdominal muscles and gastric ulcers were observed. There were no premature deaths, serious illnesses, skin burns or evidence of pancreatitis on biochemical analysis. HIFU treatment of the pancreas is feasible, safe and can be used to ablate tissue noninvasively. A clinical trial in humans examining the use of extracorporeal HIFU for palliation of pain related to pancreatic cancer is planned.
Sympathetic nervous system response to intake

Meals increase the activity of the sympathetic nervous system (SNS) above the activity level observed in the postabsorptive state. Pharmacologic blockade of the thermogenic effect of norepinephrine, the primary neurotransmitter of the SNS, suggests that this response accounts for 20% of the thermic response to food. Energy expenditure increases after several days of sustained overeating. There is no convincing evidence that this response is mediated by increased SNS activity in humans, as it is in some animals. Energy expenditure decreases within a few days of energy deprivation. When sodium balance is maintained, energy deprivation also reduces SNS activity. The reduced SNS activity may contribute to the decreased energy expenditure, but cannot explain it completely. The contribution of the SNS to total energy expenditure is small in normal subjects consuming a weight-maintenance diet, probably < 5%. A few studies have suggested that SNS activity is reduced in obese humans, suggesting that low energy expenditure associated with reduced SNS activity may contribute to obesity. However, a critical evaluation of the available evidence indicates that this hypothesis is untenable.
Characterization of thermosetting materials by torsional braid analysis

Experimental examination by torsional braid analysis (TEA) of the phenomena of gelation and vitrification which occur in the formation of thermosets leads to a general way of regarding both thermoplastics and thermosets. In particular,- it is demonstrated that the thermosetting process is characterized by two transition temperatures, Tff and Tg∞. Implications of this finding are discussed for cross-linking systems in general.
A signal-processing algorithm for the extraction of thin freshwater-ice thickness from short pulse radar data

A radar data processing algorithm is presented which can estimate freshwater ice thicknesses both greater than and less than the normal minimum resolvable thickness. The basis for the algorithm is a model of the geophysical system and the resulting phase signature of the transfer function. The algorithm attempts to isolate this signature and estimate the relevant parameters. In principle, the method can be used to detect layering in other dielectric media. The algorithm was based on a simple model for scattering from a thin-ice layer and refined using radar returns taken over a range of thin-ice thicknesses in a laboratory environment. The method was also applied to data obtained with two different radar frequencies and over a wide range of thickness and surface roughness. The results were compared to thickness estimates from classical deconvolution methods. >
Parasite stress, ethnocentrism, and life history strategy

Fincher & Thornhill (F&T) present a compelling argument that parasite stress underlies certain cultural practices promoting assortative sociality. However, we suggest that the theoretical framework proposed is limited in several ways, and that life history theory provides a more explanatory and inclusive framework, making more specific predictions about the trade-offs faced by organisms in the allocation of bioenergetic and material resources.
Conserved Elements Containing NF-E2 and Tandem GATA Binding Sites are Required for Erythroid-Specific Chromatin Structure Reorganization within the Human Beta-Globin Locus Control Region

Proper expression of the genes of the human beta-globin gene locus requires the associated locus control region (LCR). Structurally, the LCR is defined by the presence of four domains of erythroid-specific chromatin structure. These domains, which have been characterized as DNase I hypersensitive sites (HSs), comprise the active elements of the LCR. The major focus of this research is to define the cis -acting elements which are required for the formation of these domains of unique chromatin structure. Our previous investigations on the formation of LCR HS4 demonstrated that NF-E2 and tandem, inverted GATA binding sites are required for the formation of the native HS. Similarly arranged NF-E2 and tandem GATA sites are present within the core regions of the other human LCR HSs and are evolutionarily conserved. Using site-directed mutagenesis of human HSs 2 and 3 we have tested the hypothesis that these NF-E2 and GATA sites are common requirements for the formation of all LCR HSs. We find that mutation of these elements, and particularly the GATA elements, results in a decrease or complete loss of DNase I hypersensitivity. These data imply the presence of common structural elements within the core of each LCR HS which are required for erythroid-specific chromatin structure reorganization.
Oxidized Low-Density Lipoprotein and Atherosclerosis

Chance and serendipity play major roles in the history of science. Too often, though, their contributions do not show up in formal publications. We all tend to shape history according to the styles of the times and according to our own biases. Acknowledged or unacknowledged, there is a tendency to want the scientific “story” to be neat and more or less linear. The genesis of the oxidized low-density lipoprotein (OxLDL) hypothesis owed a great deal to happenstance, but that may not be readily apparent from the formal articles. We take this opportunity to tell the whole story, at least as we remember it. Several apparently unrelated events occurring at about the same time in Oslo, Norway; in Cleveland, Ohio; in La Jolla, California; in New York, New York; and in Dallas, Texas converged to lay the groundwork for the hypothesis that oxidative modification of LDL might be important in atherogenesis. Later developments regarding the relationship between OxLDL and the immune system in atherogenesis, again, were often smiled on by chance and serendipity. In 1979, a young Norwegian researcher, Tore Henriksen, got in touch with our laboratory asking whether he could come to La Jolla to learn more about lipoproteins. He and his colleagues in Oslo had observed that under certain conditions, LDL was highly toxic for endothelial cells in culture, leading to cell death in just 24 hours.1 Almost simultaneously and independently, Chisolm and coworkers in Cleveland made very similar observations.2 Both groups noted that addition of whole serum or purified high-density lipoprotein to the medium completely prevented the toxic effects of the LDL, but the mechanism(s) involved remained unclear. Henriksen arrived in La Jolla in the summer of 1980 and demonstrated to us how drastically LDL affected the cultured cells. We agreed that the phenomenon was worth …
Coupled bunch motion in large size rings

The growth of the quasi-steady-state motion of the coupled bunch oscillations in storage rings has been studied by means of a normal mode analysis to determine the beam stability. In this type of analysis, the initial amplitude displacements of the bunches are first written as a sum of the normal modes of the multiple bunch system, and then the stability of each mode is determined. If the amplitude of all modes decay then the amplitude of all of the individual bunches must eventually decay, and the motion is considered stable. However, if the beat frequency between the different modes is sufficiently high, compared to the decay rate of the modes, it is possible for the amplitude of some of the bunches to grow temporarily before eventually decaying. >
Current leadership training in dermatology residency programs: A survey

Background Residents and physicians frequently find themselves in leadership roles. Current residency curricula focus on the development of clinical knowledge and technical skills. A previous survey of Penn State Dermatology graduates demonstrated the perceived need and benefit of a formalized leadership curriculum in this selected group. Objectives We sought to identify and measure the perceived need and benefit of formalized leadership training and investigate opinions regarding leadership theory from the perspective of dermatology residency program directors and chief residents nationally. Methods A survey containing 26 questions related to leadership theory and training were mailed to all US dermatology residency programs. Results In all, 91% of program directors and chief residents agreed that leadership skills could be taught through observation and training. A total of 78% of respondents agreed that leadership training is important during dermatology residency training. In all, 66% agreed that a formalized leadership curriculum would help residents become better resident supervisors and physicians. Only 13% reported having a formalized leadership curriculum. Participants most frequently reported learning leadership through observation and modeled behavior. A total of 15% of chief residents believed their faculty did not effectively model leadership, whereas only 2% of the program directors believed the same ( P = .01). Limitations In all, 62% (68/109) of programs surveyed returned at least one response from the program director or chief resident. A total of 39% (42/109) had responses from both the program director and the chief resident. Because of the voluntary nature of the survey, response bias could not be excluded. Conclusion Most program directors and chief residents believe leadership skills can be cultivated through observation and training. Leadership curriculum is not part of most residency programs.
Falling Body Impact Behavior of Fiberglass Stepladders With Plastic Knee Braces

According to estimates reported in the U.S. Consumer Product Safety Commission’s National Electronic Injury Surveillance System, there were greater than 10,000 stepladder related injuries treated in hospital emergency rooms nationwide per year in the period from 2009 through 2013. Research and experience have sought to correlate specific stepladder damage patterns to the causes of some injuries involving stepladders. Prior studies have associated a specific damage pattern — inward deformation of the stepladder’s front side rails — with impact loading of a user’s body onto the lower portion of a front side rail following a fall from the stepladder. Those prior studies were conducted using stepladders with metal knee braces and with the ladder cap simply supported during impact testing. Currently sold fiberglass stepladders often have plastic rather than metal knee braces. In our study, side rail impact testing was performed in order to evaluate how a design change from metal knee braces to plastic knee braces affects impact damage patterns in fiberglass stepladders. Biomechanics simulations were used to inform the selection of the weights used for impact testing and allowed the test results to be evaluated in the context of potential body contact scenarios that could produce equivalent loading of the side rail. Our study demonstrates that depending on the weight of the impacting body, fiberglass ladders with plastic knee braces show different dynamic responses to impact loading than do their metal counterparts. Additionally, the test methods in this study incorporate realistic dynamics in that the weight impacted the lower portion of the stepladder’s front side rail while the stepladder was actively tipping with only two of its feet in contact with the ground and with the top cap unsupported.The results indicate that ladders with metal knee braces can permanently deform when impacted with loads less than that required to permanently deform the ladders tested with plastic knee braces. The absence of permanent side rail deformation in the plastic knee braced stepladders tested even after undergoing significant elastic deformation during testing gives rise to new questions about the potential for damage that is not observable based on a visual examination.Copyright © 2015 by ASME
Taxation Silos: Embedded Intangibles and Embedded Services

In this report, Doernberg discusses the proposed transfer pricing regulation containing a special rule for services transactions that effect a transfer of intangible property - the so-called embedded intangibles rule.
Insights into Acetone Photochemistry on Rutile TiO2(110). 2. New Photodesorption Channel with CH3 Ejection along the Surface Normal

Angle-resolved photon-stimulated desorption (PSD) combined with infrared reflection–absorption spectroscopy and temperature-programmed desorption reveal two distinct channels in the photochemistry of acetone on rutile TiO2(110). During UV irradiation of coadsorbed oxygen and acetone molecules, nonthermal methyl radicals (CH3) are ejected in two different directions: (i) normal to the surface and (ii) off-normal at ∼±66° to the surface normal in the [110] azimuth (i.e., perpendicular to the O and Ti rows). The direction of the “off-normal” PSD component is consistent with the orientation of the C–CH3 bonds in the η2-acetone diolate—a photoactive form of acetone chemisorption on the oxidized TiO2(110) surface proposed in earlier studies. The direction of the “normal” PSD component requires an orientation of a C–CH3 bond which is not consistent with the η2-acetone diolate structure. The “off-normal” PSD component dominates at lower acetone coverage (<0.2 ML), but does not increase at higher coverages in acc...
Radionuclide Interaction with Clays in Dilute and Heavily Compacted Systems: A Critical Review

Given the unique properties of clays (i.e., low permeability and high ion sorption/exchange capacity), clays or clay formations have been proposed either as an engineered material or as a geologic ...
A CHANGING PARADIGM IN THE ETIOLOGY OF PERICARDIAL EFFUSIONS? A 12 YEAR STUDY OF PERICARDIOCENTESIS FROM THE CLEVELAND CLINIC

Etiologies for pericardial effusions have been well described with the majority of cases attributed to idiopathic, infectious and neoplastic causes. Effusion due to post-pericardiotomy syndrome (PPS) has not been reported as a common etiology. We describe the characteristics, etiologies and outcomes
Localization of 99mTc-labeled pyrophosphate and calcium in mycoardial infarcts after temporary coronary occlusion in dogs.

SummaryThe location and magnitude of 99mTc concentration was assessed following 15 or 40 min of temporary coronary occlusion to evaluate uptake with respect to irreversible vs reversible ischemic cell injury and with respect to the presence or absence of increased myocardial Ca2+ content. 99mTc did not accumulate in any samples after 15 min of ischemia (reversible injury). 99mTc uptake was observed in 6 of 10 dogs following 40 min of occlusion and the high 99mTc ratios were associated with massive tissue calcification. The results indicate that 99mTc accumulation is specific for irreversible ischemic injury and is associated with tissue calcification.
Effect of Opioid on Adult Hippocampal Neurogenesis

During the past decade, the study of the mechanisms and functional implications of adult neurogenesis has significantly progressed. Many studies focus on the factors that regulate proliferation and fate determination of adult neural stem/progenitor cells, including addictive drugs such as opioid. Here, we review the most recent works on opiate drugs’ effect on different developmental stages of adult hippocampal neurogenesis, as well as the possible underlying mechanisms. We conclude that opiate drugs in general cause a loss of newly born neural progenitors in the subgranular zone of dentate gyrus, by either modulating proliferation or interfering with differentiation and maturation. We also discuss the consequent impact of regulation of adult neurogenesis in animal’s opioid addiction behavior. We further look into the future directions in studying the convergence between the adult neurogenesis field and opioid addiction field, since the adult-born granular cells were shown to play a role in neuroplasticity and may help to reduce the vulnerability to drug craving and relapse.
Input space-dependent controller for multi-hazard mitigation

Semi-active and active structural control systems are advanced mechanical devices and systems capable of high damping performance, ideal for mitigation of multi-hazards. The implementation of these devices within structural systems is still in its infancy, because of the complexity in designing a robust closed-loop control system that can ensure reliable and high mitigation performance. Particular challenges in designing a controller for multi-hazard mitigation include: 1) very large uncertainties on dynamic parameters and unknown excitations; 2) limited measurements with probabilities of sensor failure; 3) immediate performance requirements; and 4) unavailable sets of input-output during design. To facilitate the implementation of structural control systems, a new type of controllers with high adaptive capabilities is proposed. It is based on real-time identification of an embedding that represents the essential dynamics found in the input space, or in the sensors measurements. This type of controller is termed input-space dependent controllers (ISDC). In this paper, the principle of ISDC is presented, their stability and performance derived analytically for the case of harmonic inputs, and their performance demonstrated in the case of different types of hazards. Results show the promise of this new type of controller at mitigating multi-hazards by 1) relying on local and limited sensors only; 2) not requiring prior evaluation or training; and 3) adapting to systems non-stationarities.
Panel on cost-effectiveness in health and medicine.

As the content of Dr. Weinstein's presentation is being published elsewhere (by prior agreement), thefollowing is a summary of the Panel's mission and activities written by the Project Director Readers who wish to know more about the Panel's deliberations and conclusions are directed to the full publication: Gold MR, Siegel JE, Russel LB, Weinstein MC, eds. Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996.
Survivorship of male and female Bactrocera dorsalis in the field and the effect of male annihilation technique

Male annihilation technique (MAT) is a key component of management of the Oriental fruit fly, Bactrocera dorsalis Hendel (Diptera: Tephritidae), because of the ‘strong’ attraction of males to the lure methyl eugenol. The optimal application density for MAT has not been investigated for this economically important pest species. We tested the effect of two levels of MAT application density compared to a no‐MAT control on the daily survivorship of male and female B. dorsalis estimated by mark‐release‐recapture (MRR) using a 1‐km² passive sampling network. Estimated daily survivorship from two separate MRR trials under control (no MAT) conditions was 0.751 for males and 0.948 for females. Male survivorship was similar under control (no MAT) and high application density (256 spots km⁻²; daily survivorship 0.704). However, estimated male survivorship was significantly lower under the low application density (100 spots km⁻²; daily survivorship 0.211). A similar pattern was observed in estimated female survivorship, with a significant reduction in survivorship under the low rate compared with control and high application density (low‐density estimated survivorship 0.652, high density 0.881). The results suggest that a lower application density may be more effective against B. dorsalis than the high application density. A lower application density for effective MAT would benefit growers and the public with respect to management of B. dorsalis through reduced labor and material costs, limiting potential environmental impacts, and increased logistical simplicity finding application sites in urban environments.
The role of monoclonal paraproteins in Systemic Capillary Leak Syndrome (SCLS)

The Systemic Capillary Leak Syndrome (SCLS) is a rare, orphan disease characterized by bouts of acute, reversible plasma extravasation into tissues, which leads to hemoconcentration, hypoalbuminemia, hypotension, and vascular collapse. Although the cause of SCLS is unknown, 80–95 % of SCLS patients have a monoclonal gammopathy of unknown significance (MGUS), in which clonal plasma cells secretes large amounts of monoclonal immunoglobulins or “paraproteins”. MGUS is a premalignant precursor to multiple myeloma (MM) and is notably detected in most SCLS patient sera. Another marked distinction is that acute, but not basal SCLS sera contain elevated concentrations of inflammatory mediators known to promote endothelial permeability, notably Vascular Endothelial Growth Factor (VEGF) and Angiopoietin 2 (Angpt2). To address these findings experimentally, we purified whole IgG from patient and control sera to examine whether these immunoglobulins have an impact on endothelial cell barrier function and performed functional assays to characterize the observed changes in morphology. Preliminary data suggest that patient IgG binds to endothelial cells and elicits significant F-actin stress fiber formation and VE-cadherin internalization. SCLS IgG seems to be critical in triggering endothelial dysfunction and dissecting the underlying signaling mechanisms involved will help us better understand disease pathogenesis and potentially pave the way for therapeutic target development.
Identification of pharmacogenetic target genes associated with chemotherapy-induced peripheral neuropathy.

e13541 Background: Chemotherapy-induced Peripheral Neuropathy (CIPN) is a dose-limiting toxicity of many anticancer drugs, including taxanes, vinca alkaloids and platinating agents. There are no effective means to predict which patients are at risk for CIPN nor are there effective treatments. Therefore, we have used a whole genome approach in lymphoblastoid cell lines (LCLs) alone or combined with clinical study data to identify target genes associated with CIPN that we tested further in Neuroscreen-1 (NS-1: rat pheochromocytoma) cells and human neurons derived from induced pluripotent stem cells (iCell neurons). Methods: For selecting candidate target genes, we compared published genome-wide association studies (GWAS) results of sensory peripheral neuropathy in cancer patients receiving paclitaxel with GWAS results of pharmacologic phenotypes in LCLs after paclitaxel treatment. We evaluated neurotoxic drug-induced cell growth inhibition using Cell Titer Glo and neurite parameters of outgrowth, processes ...
Subauroral Polarization Streams (SAPS) Duration as Determined From Van Allen Probe Successive Electric Drift Measurements

We examine a characteristic feature of the magnetosphere-ionosphere coupling, namely, the persistent and latitudinally narrow bands of rapid westward ion drifts called the Sub-Auroral Polarization Streams (SAPS). Despite countless works on SAPS, information relative to their durations is lacking. Here, we report on the first statistical analysis of more than 200 near-equatorial SAPS observations based on more than two years of Van Allen Probe electric drift measurements. First, we present results relative to SAPS radial locations and amplitudes. Then, we introduce two different ways to estimate SAPS durations. In both cases, SAPS activity is estimated to last for about nine hours on average. However, our estimates for SAPS duration are limited either by the relatively long orbital periods of the spacecraft or by the relatively small number of observations involved. 50 % of the events fit within the time interval [0;18] hours.
Lipid Testing and Statin Prescriptions Among Medicaid Recipients With Systemic Lupus Erythematosus or Diabetes Mellitus and the General Medicaid Population

Objective Cardiovascular disease (CVD) risks in systemic lupus erythematosus (SLE) are similar to those in diabetes mellitus (DM). We investigated whether the numbers of lipid tests and statin prescriptions in patients with SLE are comparable with those in patients with DM and those in individuals without either disease. Methods Using Analytic eXtract files from 29 states for 2007-2010, we identified a cohort of US Medicaid beneficiaries, ages 18-65 years, with prevalent SLE. Each SLE patient was matched for age and sex with 2 patients with DM and 4 individuals in the general Medicaid population who did not have either SLE or DM. We compared the proportions of patients in each cohort who received ≥1 lipid test and ≥1 statin prescription during 1-year follow-up. We used multivariable logistic regression to calculate the odds of lipid testing and receiving prescriptions for statins and conditional logistic regression to compare the matched cohorts. Results We identified 3 Medicaid cohorts: 25,950 patients with SLE, 51,900 patients with DM, and 103,800 Medicaid recipients without either condition. In these cohorts, lipid testing was performed in 24% of patients in the SLE group, 43% of patients in the DM group, and 16% of individuals in the group with neither condition, and statin prescriptions were dispensed in 11%, 33%, and 7% of these groups, respectively. SLE patients were 66% less likely (odds ratio [OR] 0.34, 95% confidence interval [95% CI] 0.34-0.35) to have lipid tests and 82% less likely (OR 0.18, 95% CI 0.18-0.18) to fill a statin prescription compared with DM patients. SLE patients were also less likely (OR 0.89, 95% CI 0.84-0.94) to fill a statin prescription compared with individuals in the general Medicaid population. Conclusion Despite having an elevated risk of CVD, SLE patients received less lipid testing and received fewer statin prescriptions compared with age- and sex-matched DM patients and individuals in the general Medicaid population; this gap should be a target for improvement.
A First-in-Human, Phase I Study of Neural Stem Cell Transplantation for Chronic Spinal Cord Injury

Summary We tested the feasibility and safety of human-spinal-cord-derived neural stem cell (NSI-566) transplantation for the treatment of chronic spinal cord injury (SCI). In this clinical trial, four subjects with T2–T12 SCI received treatment consisting of removal of spinal instrumentation, laminectomy, and durotomy, followed by six midline bilateral stereotactic injections of NSI-566 cells. All subjects tolerated the procedure well and there have been no serious adverse events to date (18–27 months post-grafting). In two subjects, one to two levels of neurological improvement were detected using ISNCSCI motor and sensory scores. Our results support the safety of NSI-566 transplantation into the SCI site and early signs of potential efficacy in three of the subjects warrant further exploration of NSI-566 cells in dose escalation studies. Despite these encouraging secondary data, we emphasize that this safety trial lacks statistical power or a control group needed to evaluate functional changes resulting from cell grafting.
Quantum-induced solid-solid transitions and melting in the Lennard-Jones LJ38 cluster.

The solid-solid and melting transitions that occur in Lennard-Jones LJn clusters have been both fascinating and challenging for the computational physics community over the last several decades. A number of attempts to extend these studies to the quantum case have also been made. Particularly interesting is the exploration of the parallel between the thermally induced and quantum-induced transitions. Yet, both numerically accurate and systematic studies of the latter are still lacking. In this paper, we apply the diffusion Monte Carlo method to the especially difficult case of LJ38. Starting with the truncated octahedral global minimum configuration, as the de Boer quantum delocalization parameter Λ increases, the system undergoes two consecutive solid-solid transitions, switching to anti-Mackay configurations. At sufficiently large values of Λ, the cluster is completely “melted,” which is manifested by delocalization of the ground state wavefunction over a very large number of minima that represent several structural motifs.The solid-solid and melting transitions that occur in Lennard-Jones LJn clusters have been both fascinating and challenging for the computational physics community over the last several decades. A number of attempts to extend these studies to the quantum case have also been made. Particularly interesting is the exploration of the parallel between the thermally induced and quantum-induced transitions. Yet, both numerically accurate and systematic studies of the latter are still lacking. In this paper, we apply the diffusion Monte Carlo method to the especially difficult case of LJ38. Starting with the truncated octahedral global minimum configuration, as the de Boer quantum delocalization parameter Λ increases, the system undergoes two consecutive solid-solid transitions, switching to anti-Mackay configurations. At sufficiently large values of Λ, the cluster is completely “melted,” which is manifested by delocalization of the ground state wavefunction over a very large number of minima that represent sever...
An updated Lagrangian LBM–DEM–FEM coupling model for dual-permeability fissured porous media with embedded discontinuities

Abstract Many engineering applications and geological processes involve embedded discontinuities in porous media across multiple length scales (e.g. rock joints, grain boundaries, deformation bands and faults). Understanding the multiscale path-dependent hydro-mechanical responses of these interfaces across length scales is of ultimate importance for applications such as CO2 sequestration, hydraulic fracture and earthquake rupture dynamics. While there exist mathematical frameworks such as extended finite element and assumed strain to replicate the kinematics of the interfaces, modeling the cyclic hydro-mechanical constitutive responses of the interfaces remains a difficult task. This paper presents a semi-data-driven multiscale approach that obtains both the traction-separation law and the aperture-porosity–permeability relation from micro-mechanical simulations performed on representative elementary volumes in the finite deformation range. To speed up multiscale simulations, the incremental constitutive updates of the mechanical responses are obtained from discrete element simulations at the representative elementary volume whereas the hydraulic responses are generated from a neural network trained with data from lattice Boltzmann simulations. These responses are then linked to a macroscopic dual-permeability model. This approach allows one to bypass the need of deriving multi-physical phenomenological laws for complex loading paths. More importantly, it enables the capturing of the evolving anisotropy of the permeabilities of the macro- and micro-pores. A set of numerical experiments are used to demonstrate the robustness of the proposed model.
Changes that Challenge the Soul

It is hard to dispute many of the descriptive elements of David Bartlett's vision of future electronic journalism. Modern communications technologies, which are abundant rather than scarce, are, indeed, undermining old communications industries and forcing revision of the laws and policies that have traditionally governed them. Communications and computing continue to converge and, in the process, old industry structures distinguishing among print, broadcasting, cable television, and data processing become less relevant. The work of journalists and the role they play in society are changing dramatically. Journalists are less able to function as authoritative gatekeepers. News consumers can already circumvent gates, obtain more "raw" information unprocessed by journalists, and demand information content and packaging custom-tailored to their tastes and perceived information needs. These changes, already present but likely to accelerate, can empower information consumers, profoundly transforming the world of the journalist and the information consumer alike.
Exploring the Use of Driver Attributes to Characterize Heterogeneity in Naturalistic Driving Behavior

Microsimulation models are powerful tools for exploring the impact of human driving behavior on the transportation system. One of the most heavily researched components of microsimulation models are car-following models, where human behavior is approximated using driver specific calibration coefficients. Inter-driver heterogeneity in calibration parameters has been observed in naturalistic data, but few studies have explored methods to characterize this heterogeneity. This research utilizes an 85-driver sample from the second Strategic Highway Research Program Naturalistic Driving Study dataset to calibrate over 100-hours of car-following data to three different car-following models: Gipps, Wiedemann 99, and Intelligent Driver Model. This enables a detailed exploration of the degree to which driver attributes—such as age, gender, and income—can be leveraged to account for inter-driver heterogeneity in car-following. The sample is segmented into smaller subsamples of data as a function of driver attributes. Statistically significant differences in parameter values are observed between the subsamples of data when age, miles driven last year, and income are used as characterizing traits. Moreover, it is shown that no single model outperforms the other models for all categories of data.
Abstract 688: Differential Matricellular Protein (CCN) Expression in Atherosclerotic and Aneurysmal Smooth Muscle Cells

Introduction: Recent evidence implicates reduced activity of CCN3 as a mediator of MMP production and aortic wall degeneration in the process of model aortic aneurysm. We have previously shown that...
Pivoting Isn’t Enough? Managing Strategic Reorientation in New Ventures

New ventures often experience deviations from their plans that oblige them to reorient in pursuit of a better fit between their evolving products and their target customers. Yet, research is largel...
Properties and Recent Applications in Spectral Graph Theory

There are numerous applications of mathematics, specifically spectral graph theory, within the sciences and many other fields. This paper is an exploration of recent applications of spectral graph theory, including the fields of chemistry, biology, and graph coloring. Topics such as the isomers of alkanes, the importance of eigenvalues in protein structures, and the aid that the spectra of a graph provides when coloring a graph are covered, as well as others. The key definitions and properties of graph theory are introduced. Important aspects of graphs, such as the walks and the adjacency matrix are explored. In addition, bipartite graphs are discussed along with properties that apply strictly to bipartite graphs. The main focus is on the characteristic polynomial and the eigenvalues that it produces, because most of the applications involve specific eigenvalues. For example, if isomers are organized according to their eigenvalues, a pattern comes to light. There is a parallel between the size of the eigenvalue (in comparison to the other eigenvalues) and the maximum degree of the graph. The maximum degree of the graph tells us the most carbon atoms attached to any given carbon atom within the structure. The Laplacian matrix and many of its properties are discussed at length, including the classical Matrix Tree Theorem and Cayley’s Tree Theorem. Also, an alternative approach to defining the Laplacian is explored and compared to the traditional Laplacian.
Relationship Between Organizational Leadership and Health Care Employee Burnout and Satisfaction

Abstract Objective To explore the relationship between immediate supervisor leadership behaviors and burnout and professional satisfaction of health care employees. Participants and Methods From October 2 to 20, 2017, we surveyed nonphysician health care employees. The survey included 2 items from the Maslach Burnout Inventory and items on their immediate supervisor leadership behaviors. Logistic regression was performed to evaluate the relationship between the leadership score and the prevalence of burnout and satisfaction after adjusting for age, sex, duration of employment, and job category. Sensitivity analysis was performed using mixed models with a random intercept for work unit to assess the impact of the correlation within work units on burnout and satisfaction with the organization. Results Of the 57,414 employees surveyed, 39,896 (69.5%) responded and answered the leadership questions. Supervisor scores in each dimension and composite leadership scores correlated with burnout and satisfaction of employees (P Conclusion Leadership qualities of immediate supervisors relate to burnout and satisfaction of nonphysician health care employees working in a large organization. Further studies are needed to determine whether strategies to monitor and improve supervisor leadership scores result in reduction in burnout and improved satisfaction among health care employees.
National survey of physicians' perspectives on pharmacogenetic testing in solid organ transplantation.

Author(s): Deininger, Kimberly M; Tsunoda, Shirley M; Hirsch, Jan D; Anderson, Heather; Lee, Yee Ming; McIlvennan, Colleen K; Page, Robert L; Tran, Jacinda N; Aquilante, Christina L | Abstract: IntroductionOur objective was to evaluate physicians' perspectives on the clinical utility of pharmacogenetic (PGx) testing in kidney, liver, heart, and lung transplantation (KLHL-Tx).MethodsA 36-question web-based survey was developed and administered to medical and surgical directors of US KLHL-Tx centers.ResultsThere were 82 respondents (10% response rate). The majority were men (78%), non-Hispanic whites (70%), medical directors (72%), and kidney transplant physicians (35%). Although 78% of respondents reported having some PGx education, most reported lack of confidence in their PGx knowledge and ability to apply a PGx test. Participants reported mixed views about the clinical utility of PGx testing-most agreed with the efficacy of PGx testing, but not the benefits relative to the risks or standard of care. While 55% reported that testing was available at their institution, only 38% ordered a PGx test in the past year, most commonly thiopurine-S-methyltransferase. Physician-reported barriers to PGx implementation included uncertainty about the clinical value of PGx testing and patient financial burden.ConclusionTogether, our findings suggest prospective PGx research and pilot implementation programs are needed to elucidate the clinical utility and value of PGx in KLHL-Tx. These initiatives should include educational efforts to inform the use of PGx testing.