cssi/SciSciGPT-SciSciNet huggingface dataset:
Validation of elastic cross section models for space radiation applications

Abstract The space radiation field is composed of energetic particles that pose both acute and long-term risks for astronauts in low earth orbit and beyond. In order to estimate radiation risk to crew members, the fluence of particles and biological response to the radiation must be known at tissue sites. Given that the spectral fluence at the boundary of the shielding material is characterized, radiation transport algorithms may be used to find the fluence of particles inside the shield and body, and the radio-biological response is estimated from experiments and models. The fidelity of the radiation spectrum inside the shield and body depends on radiation transport algorithms and the accuracy of the nuclear cross sections. In a recent study, self-consistent nuclear models based on multiple scattering theory that include the option to study relativistic kinematics were developed for the prediction of nuclear cross sections for space radiation applications. The aim of the current work is to use uncertainty quantification to ascertain the validity of the models as compared to a nuclear reaction database and to identify components of the models that can be improved in future efforts.
Spectral Energy Distributions of Circumstellar Gas in Algols

Developments in computers now have made it practical to treat the gas flow and radiation problem in matter-transferring binaries. The computation consists of four separable parts: (1) gas flow, (2) radiative properties, in particular, emission line strengths and profiles, (3) generation of spectral energy distributions by spatial integration with Doppler shifts and eclipses, and (4) adjustment of model parameters based on comparisons with observational data. Our hydrodynamical code is a 3—dimensional Lagrangian scheme which eliminates the memory and computing limitations of finite-difference methods, and does not constrain the global geometry of the system artificially. The gravitational acceleration of the gas is computed via Newtonian mechanics. Viscous and pressure effects are included and can be followed continuously in time over many cycles. Viscous interaction among gas particles is effected by allowing neighboring particles to exchange momentum. Pressure gradients are computed by smoothed particle hydrodynamics.
A comparison theory for the stability analysis of general hybrid systems

Abstract In some of our recent work, a general model for hybrid dynamical systems was proposed whose states are defined on arbitrary metric space and evolve along some notion of generalized abstract time . By transforming this class of hybrid dynamical systems into another class of dynamical systems with equivalent qualitative properties, but defined on real time, we established the Principal Lyapunov Stability Results as well as Lagrange Stability Results. Making use of stability preserving mappings, results which comprise a general comparison theory for hybrid dynamical systems can be developed and these results can be specialized by employing vector Lyapunov functions. It then can be shown that the latter results can be used to yield the Principal Lyapunov Stability Results discussed above as special cases. Due to space limitations, only a summary of the paper is presented.
‘Everything has been put together wrong’: Dragan Kujundžić’s The First Sail and the ‘remains’ of deconstruction*

The First Sail depicts literary critic J. Hillis Miller as a personification of the Derridean concept of ‘remains’ – the displacement of the mortal human subject by an archive of figures for readin...
The ceramide synthase 2b gene mediates genomic sensing and regulation of sphingosine levels during zebrafish embryogenesis.

Humans and other animals need a variety of fat molecules known as lipids to survive and grow. For example, members of a large family of lipids called sphingolipids play crucial roles in many cell processes and are essential for tissues and organs to form as animal embryos develop. A molecule called sphingosine is the basic building block of most sphingolipids. An enzyme known as sphingosine kinase 2 (Sphk2) converts sphingosine into a sphingolipid called sphingosine 1-phosphate, which is released from cells and regulates communication between cells. Another enzyme called ceramide synthase 2b (Cers2b) converts sphingosine into ceramide, which is required for the membrane surrounding individual cells to work properly. Excess levels of particular sphingolipids can be toxic to cells so animals carefully control the levels of these molecules in their bodies. However, it was not clear how animal cells sense the molecules and regulate their production and breakdown. Mendelson et al. addressed this question by studying mutant zebrafish embryos that fail to produce Sphk2 and thus produce little or no sphingosine 1-phosphate. It was thought that the mutant zebrafish may experience the toxic effects of high levels of sphingosine because they are unable to convert it to sphingosine 1-phosphate. However, the experiments show that the mutant embryos are able to avoid this toxicity by increasing the production of the Cers2b enzyme. Somehow the gene that encodes this enzyme is able to sense high levels of sphingosine and responds by increasing its own production, which in turn increases the conversion of sphingosine into the non-toxic ceramide. Further experiments found that this mechanism for sensing and removing excess sphingosine is already operating at an earlier stage of development when the zebrafish is just an egg. Further work is needed to understand exactly how this sphingosine sensing mechanism works. These findings may help us to develop new treatments for diseases caused by an imbalance in sphingolipids, such as diabetes and cancer. This work may also help to increase the success of in vitro fertilization (IVF) and other fertility therapies by enhancing the survival of human egg cells.
Pazopanib therapy for desmoid tumors in adolescent and young adult patients

Background Desmoid tumors/aggressive fibromatosis (DT/AF) lack a reliably effective medical therapy. Surgical resection may be morbid and does not preclude recurrence. Radiation may carry severe late effects, particularly detrimental in young patients. At our institution, we recently observed promising results with pazopanib therapy for DT/AF in adolescent and young adult (AYA) patients. Procedure Retrospective single-institution chart review. Results Six DT/AF patients of 3-21 years with previously treated DT/AF received pazopanib; 31 DT/AF patients received established therapies only. In both groups, median age at diagnosis was 16 years, female patients comprised 50%, and most common DT/AF site was extremity. Established therapies showed few objective responses and most patients therefore received multiple therapies. Surgical resection had a 68% recurrence rate. Of eight patients who received vinblastine/methotrexate, only one had a partial response (PR) by RECIST 1.1 and five had stable disease (SD); 62.5% required additional therapy. Of seven patients who received sulindac/tamoxifen, none showed objective improvement. In contrast, pazopanib demonstrated best responses by RECIST of PR in two of seven and SD in six of seven tumors. A PR of 66% was observed in a patient who had failed multiple prior therapies. The mesenteric DT/AF also showed PR. Maximum volumetric decrease by T2-weighted magnetic resonance imaging (MRI) was 97%. Dramatically increased fibrosis was seen on T2-weighted MRI. Patients reported pain relief and improvement in function within 1 month. Except for one case of edema, all other toxicities responded to dose reduction without sacrificing objective treatment response. Conclusion Pazopanib provides a promising, well-tolerated therapy for DT/AF in the AYA population and warrants further study.
Monitoring snowbank processes and cornice fall avalanches with time-lapse photography

Abstract Time-lapse photography was employed to monitor a snowbank at 3640 m above sea level in the Uinta Mountains, Utah, USA. The snowbank forms against a 35-m high, east-facing escarpment and is nourished by wind redistribution of snow from an alpine plateau. The snowbank is capped by a large cornice, and its central core persists through the summer in most years. An automated, solar-powered digital camera was deployed between October 2016 and June 2017, and programmed to capture 5 photographs each day between 8:00 and 16:00, local time. Although cold temperatures affected the batteries during the winter, a total of 812 photographs were collected, for an overall average of 3.4 per day. These images were combined in an animation displaying the growth of the snowbank and associated cornice over the course of the winter. The debris fields resulting from nineteen cornice fall avalanches were noted in the sequence of photographs. Data collected at a nearby automated weather station reveal that 12 avalanches (between early December and early April) were preceded by significant increases in snow depth, snow water equivalent, and precipitation, with sustained windspeeds above the winter average. In contrast, six of the last seven events (between late April and early June) occurred in the absence of new snowfall, but were associated with rapid rises in temperature and notable decreases in snow water equivalent. The average interval between recorded avalanches is 10 days, with a maximum of 29 days and a minimum of 2 h. Recurrence intervals were shorter in December/January, in late March/early April, and in late April/early May. Only one avalanche occurred in the 56 days between 27 January and 24 March. Time-lapse photography is a powerful tool for monitoring nival processes.
Modeling the Archean Atmosphere and Climate

The Archean atmosphere was likely a weakly reduced mixture composed predominantly of N 2 and CO 2 , with smaller concentrations of H 2 , CO, and CH 4 . Both CO 2 and N 2 may have been present in abundances exceeding today's values, by a factor of 2 or more for N 2 and by factors of 100 or more for CO 2 . Published upper limits on CO 2 from paleosols and banded iron formations are probably invalid; hence, CO 2 could have been the dominant greenhouse gas that compensated for the fainter young Sun. The Archean greenhouse effect was likely supplemented by CH 4 , which could have risen to levels of 1000 ppmv or more once methanogens had evolved. Warming by CH 4 was limited to approximately 10–12°, however, by formation of organic haze. The key to analyzing Archean atmospheric composition is to understand the hydrogen budget of the atmosphere in which outgassing of H 2 and other reduced gases from volcanoes was balanced by loss of hydrogen to space and burial of organic carbon in sediments. The mixing ratio of O 2 in such a weakly reduced atmosphere would have been extremely low, roughly 10 − 13 at the surface, increasing to ~ 10 − 3 in the upper stratosphere. A rise in O 2 just after the end of the Archean may have eliminated the methane greenhouse and triggered the Paleoproterozoic glaciations.
Expression of a Chronic Granulomatous Disease-Like Defect by Fluoride-Exhausted Neutrophils

Neutrophils incubated with 20 mM F- express a respiratory burst without degranulating or performing phagocytosis. After 60 min of F- treatment, the burst is exhausted and cannot be restarted. Neutrophils so treated have a microbicidal defect similar to that of chronic granulomatous disease (CGD): they kill Str. mitis at a nearly normal rate, but show a marked impairment in the destruction of S. aureus. They differ from CGD neutrophils in that they also display a defect in motility. This defect, however, is not so severe as to seriously impair their ability to kill bacteria by mechanisms that are independent of endogenously generated microbicidal oxidants.
Dry and Moist Static Stability

Nearly 80 % of the soundings over the tropical oceans contain a lower tropospheric inversion. In the regions of the trade winds this is often referred to as a trade wind inversion. The strongest inversions are found over the eastern regions of the oceans. Convection, clouds, and turbulent mixing constantly work to erode them. Evidently, however, there are strong restoring forces that counteract the eroding effects and act to maintain the inversion.
Reimagining political economy as a foundation for archaeologies of the past, present and future

SUMMARY: This paper examines some of the philosophical and epistemological issues surrounding current theories of political economy. By focusing on the historicism that postcolonial theorists have employed to critique the writings of Karl Marx and the lack of focus on the environment on the part of many political theorists, this paper argues for a political economy that accommodates the role of the disenfranchised and the environment as part of an archaeology of the future.
Objective Assessment of the Early Stages of the Learning Curve for the Senhance Surgical Robotic System

OBJECTIVE The purpose of this research is to study the early stages of the Senhance learning curve to report how force feedback impacts learning rate. This serves as an exploratory investigation into assumptions that fellows and faculty will adjust faster to the Senhance in comparison with residents, and that force feedback will not hinder skill acquisition. DESIGN In this study, participants completed the peg transfer and precision cutting task from the Fundamentals of Laparoscopic Surgery (FLS) manual skills assessment five times each using the Senhance while instrument motion was tracked. SETTING This study took place in the Surgical Education and Activities Laboratory at Duke University Medical Center. PARTICIPANTS Participants for this study were residents, fellows, and faculty from Duke University Medical Center in general surgery and gynecology specialties (N = 16). RESULTS Postulated linear mixed effects models with participant level random effects showed significant improvement with additional attempts for the peg transfer task after adjusting for surgical experience and force feedback respectively for the primary FLS score metric. The secondary metric of total instrument path length also showed improvement (significant decreases) in path length with additional attempts after respectively adjusting for surgical experience and force feedback. CONCLUSIONS This study investigates the early stages of the learning curve of the Senhance. Exploratory modeling indicates that residents, fellows, and faculty surgeons rapidly adapt to the controls of the Senhance regardless of experience level and force feedback engagement. The results from this study may serve as motivation for future prospective studies that achieve sufficient statistical power with a larger sample size and strict experimental design.
The Importance of Adolescent Self-Report in Autism Spectrum Disorder: Integration of Questionnaire and Autonomic Measures

Anxiety and sensory symptoms are highly prevalent and meaningful in the daily lives of individuals with autism spectrum disorder (ASD). Despite the importance of carefully measuring, researching, and treating these symptoms, current methods in ASD seldom include self-report. This study investigated the consistency of adolescent and parent reports of anxiety and auditory sensitivity in individuals with ASD, and examined their validity via comparisons with sympathetic arousal at baseline and in response to an auditory challenge. Fifty adolescent-parent dyads (n = 26 ASD, n = 24 typically developing; 12–16 years old; IQ>80) completed parallel versions of both anxiety and auditory hypersensitivity scales, which were compared to heart rate collected at rest and during an aversive noise task. Adolescents with ASD exhibited greater anxiety and auditory hypersensitivity than their peers, based on both self and parent report. Across groups, self-report was higher than parent report. In individuals with ASD, a significant relationship was found between self-reported anxiety and autonomic arousal at rest, and between self-reported auditory sensitivity and autonomic reactivity during the noise task. These relationships were not significant for parent-report. These findings extend past work by demonstrating greater self-reported (than parent-reported) anxiety and sensory symptoms. Furthermore, the presence of significant correlations between self-reported symptoms and sympathetic arousal supports the validity of self-report in adolescents with ASD with average or above average cognitive abilities. This indicates that adolescents with ASD have a unique perspective on their internal experience, which can complement parent reports and provide a more comprehensive assessment of symptoms in research and clinical settings.
A wearable ECG monitoring system for real-time arrhythmia detection

This study develops a wearable medical system for real-time arrhythmia detection, which acquires electrocardiogram (ECG) data through a three-lead ECG sensor. It performs ECG signal processing and immediately alerts the patient's health care provider of an arrhythmia via wireless messaging. In particular, a common form of arrhythmia known as premature ventricular contractions (PVCs) are identified using the Pan-Tompkins and the wavelet-based template-matching algorithms. When three or more consecutive PVCs are detected, the device sends urgent report email to a patient’s health care provider. In the experimental study, the design has been successfully validated using benchmark records from the MIT-BIH arrhythmia database. A low-cost Texas Instruments TMS320C5515 and Raspberry Pi 3 Model B are chosen to be the hardware platform. This study suggests a viable, low-complexity solution for real-time heart monitoring and arrhythmia detection.
Strategies for linking ocean state uncertainty to acoustic uncertainty

Estimating uncertainty of underwater sound fields caused by partially known environmental conditions is a broad topic with many branches because acoustic fields have many characteristics and many descriptors. Specific field characteristics, each uncertain, influence sound use in specific ways. Multiple descriptors (parameters) of signals of interest, and noise, need to be adequately known to examine use scenarios. This is also true for field simulation, processor simulation, field uncertainty simulation, and processor uncertainty simulation. Parameters should be prioritized for efficient quantification of uncertainty. For example, spatial coherence uncertainty applies to array processing but possibly not to single-sensor processing. Linking environmental uncertainty to field uncertainty, then to task performance uncertainty suffers from the many degrees of freedom present in the environment, and the interconnected effects of the many variable environmental parameters. Here, linkage frameworks for sound within internal waves propagating in variable conditions are examined. Methods appropriate for deterministically defined wave groups are explored, as well as statistically described wave fields. First, wave parameters and parameter uncertainty are specified, then effects on the sound parameters are estimated, as well as derived quantities like probability of detection and direction of arrival. Canyon environments that we have studied with models provide one test bed.
Atypical Prefrontal-Amygdala Circuitry Following Childhood Exposure to Abuse: Links With Adolescent Psychopathology

Adverse childhood experiences have been associated with more negative coupling between the ventromedial prefrontal cortex (vmPFC) and amygdala, a brain network involved in emotion regulation in both children and adults. This pattern may be particularly likely to emerge in individuals exposed to threatening experiences during childhood (e.g., exposure to child abuse), although this has not been examined in prior research. We collected functional magnetic resonance imaging data on 57 adolescents during an emotion regulation task. Greater negative functional connectivity between vmPFC and amygdala occurred during viewing of negative compared to neutral images. This vmPFC-amygdala task-related functional connectivity was more negative in adolescents exposed to physical, sexual, or emotional abuse than those without a history of maltreatment and was associated with abuse severity. This pattern of more negative functional connectivity was associated with higher levels of externalizing psychopathology concurrently and 2 years later. Greater negative connectivity in the vmPFC-amygdala network during passive viewing of negative images may reflect disengagement of regulatory responses from vmPFC in situations eliciting strong amygdala reactivity, potentially due to stronger appraisals of threat in children exposed to early threatening environments. This pattern may be adaptive in the short term but place adolescents at higher risk of psychopathology later in life.
Legacies of more frequent drought in ponderosa pine across the western United States

Despite widespread interest in drought legacies-multiyear impacts of drought on tree growth-the key implication of reported drought legacies remains unaddressed: as impaired growth and slow recovery associated with drought legacies are pervasive across forest ecosystems, what is the impact of more frequent drought conditions? We investigated the assumption that either multiple drought years occurring during a short period (multiyear droughts), or droughts occurring during the recovery period from previous drought (compounded droughts), are detrimental to subsequent growth. There is evidence that drought responses may vary among populations of widespread species, leading us to examine regional differences in responses of the conifer Pinus ponderosa to historic drought frequency in the western United States. More frequent drought conditions incurred additional growth declines and shifts in growth-climate sensitivities in the years following drought relative to single-drought events, with 'triple-droughts' being worse than 'double-droughts'. Notably, prediction skill was not strongly reduced when ignoring compounded droughts, a consequence of the temporally comprehensive formulation of our stochastic antecedent model that accounts for the climatic memory of tree growth. We argue that incorporating drought-induced temporal variability in tree growth sensitivities can aid inference gained from statistical models, where more simplistic models could overestimate the severity of drought legacies. We also found regional differences in response to repeated drought, and suggest plastic post-drought sensitivities and climatic memory may represent beneficial physiological adjustments in interior regions. Within-species variability may thus mediate forest responses to increasing drought frequency under future climate change, but experimental approaches using more species are necessary to improve our understanding of the mechanisms that underlie drought legacy effects on tree growth.
Lipogenic activity of intramuscular and subcutaneous adipose tissues from steers produced by different generations of angus sires.

Simmental and Hereford cows (n = 74) were inseminated with semen from purebred Angus bulls from the 1960s or with semen from purebred Angus bulls from the 1980s. The F1 calves provided the foundation for two investigations, one addressing growth and carcass characteristics, and another measuring the impact of sire generation on lipid metabolism and adiposity. Calves sired by the 1980s-type bulls had greater (P .05) in any measure of fatness between groups (adjusted fat thickness, kid- ney, pelvic, and heart fat, or marbling scores), but yield grade was higher numerically ( P < .l) for the 1980s steers. The second aspect of this research addressed the influence of different generations of Angus sires on specific carcass traits and adipose tissue metabolism. A subset of six steers for each generation type (from Simmental cows) were selected and samples were collected at slaughter for measure- ments in vitro. For both generation types, intramuscu- lar (i . m. adipocytes had lesser ( P < .05) cell volumes than subcutaneous (s.c. adipose tissue. Correspond- ingly, i.m. adipose tissue exhibited lower (P < .05) rates of 14C-labeled acetate incorporation into lipids as measured immediately after slaughter. Intramuscular and S.C. adipocytes from 1980s-type steers were smaller (P < .05) than those from the 1960s-types steers, with correspondingly more cells per gram of tissue. Thus, the newer generation-type steers required more adipocytes to achieve the same amounts of i.m. and S.C. fat. There was no difference between generation types in 14C-labeled acetate incor- poration into neutral lipids and, of the lipogenic enzyme activities measured, only 6-phosphogluconate dehydrogenase was significantly lower in adipose tissues of the 1980s-type steers. Thus, in spite of differences in sire generation and cellularity, carcass traits associated with fatness and in vitro measures of lipogenesis were not different between 1960s- and 1980s-type Angus crossbred steers.
Bone formation by hemopoietic tissue: separation of preosteoblast from hemopoietic stem cell function in the rat.

The bone marrow preosteoblast was studied using bone formation by subcutaneously placed syngeneic grafts of hemopoietic tissue as the test for the presence of the preosteoblast. The hind limbs of rats were irradiated with 0, 300, 600, or 900 rads, and the femoral and tibial marrow were removed and grafted 4 hr-90 days following irradiation. Grafts of the irradiated marrow, adjusted to match the unirradiated grafts in number of cells or weight of tissue, showed a marked decrease to absence of bone-forming ability over the 90-day period. The hemopoietic cells of this marrow 90 days following irradiation, except for a decrease in cellularity by one quarter, were thought to be normal as judged by differential counts and the presence of hemopoietic stem cells. The interpretations of this separation of the hemopoietic from the bone-forming function of marrow are that the preosteoblast is a nonmigrating cell and that it is not derived from the hemopoietic stem cell.
Mineral carbonate dissolution with increasing CO2 pressure measured by underwater laser induced breakdown spectroscopy and its application in carbon sequestration

In this study, the ability of laser-induced breakdown spectroscopy (LIBS) to measure the in situ aqueous dissolution of various mineral carbonates with increasing CO2 pressure was examined. Dissolution experiments included four geologically common mineral carbonates (CaCO3, MgCO3, MnCO3, SrCO3) and the CO2 pressure ranged from ambient to 250 bar. The ensuing plasma emission was spectrally analyzed, and the intensities of Ca, Mg, Mn, and Sr emission lines were used to monitor the respective metal cations released to the aqueous solution. The strong emission lines of Ca (Ca II 393.36, Ca II 396.84, Ca I 422.67 nm), Mg (unresolved magnesium doublet: Mg I 383.230, Mg I 383.829 nm), Mn (unresolved manganese triplet: Mn I 403.076, Mn I 403.307, Mn I 403.449 nm), and Sr (Sr II 407.77, Sr II 421.55, Sr I 460.73 nm) were identified in the spectra. The amounts of metals released from their respective carbonates were estimated at different time intervals following the CO2 injection (5 m, 1, 2, 3, 4, 24 h) and at different pressures (50, 100, 150, 200, 250 bar) using calibration models developed at corresponding pressure settings. The results demonstrated that the pressure-induced dissolution of all carbonates was consistent with their expected and selective pH-dependent solubility. The dissolution rate of CaCO3, MgCO3, and SrCO3 was found to be higher than that of MnCO3. The dissolution of constituents in a Mt. Simon sandstone associated with a deep saline reservoir at elevated CO2 pressure was also studied and Ca release was quantified. The results demonstrated that real-time monitoring of carbonate dissolution by LIBS may provide a useful indirect detection system indicative of CO2 leakage from geologic carbon storage sites.
The rebar repair for radial meniscus tears: a biomechanical comparison of a reinforced suture repair versus parallel and cross-stitch techniques

Radial meniscus tears can cause the meniscus to be completely incompetent. This serious type of meniscus tear can be difficult to repair. Techniques have been developed that juxtapose the meniscus tear edges and are able to withstand high loads. The purpose of this study was to determine the load to failure of a reinforced suture bar repair (Rebar Repair) for radial meniscus tear and compare it to the parallel suture technique and cross-stitch technique and to compare mode of failure among all three groups. The hypothesis was that the Rebar Repair will have a higher load to failure than both the parallel technique and the cross-stitch technique and that the Rebar Repair would have a lower rate of suture cutting through the meniscus. Forty-eight menisci were tested from 24 human knee specimens, with 16 menisci in each group evenly distributed between medial and lateral menisci. Radial mid body meniscal tears were recreated and repaired with one of three inside-out techniques: the 2-parallel suture technique, 2 cross-stitch sutures, and the Rebar Repair. The specimens were cycled between 5 N to 30 N and axially loaded to failure perpendicularly across the repair site. The average load to failure of the parallel group, cross-stitch group and Rebar Repair was 85.5 N ± 22.0, 76.2 N ± 28.8 and 124.1 N ± 27.1 respectively. The Rebar Repair had a higher load to failure than the parallel group (p < 0.01) and cross-stitch group (p < 0.01). There was no difference in the load to failure between the cross-stitch and parallel group (p = 0.49). The failure mechanism was different when comparing the 3 groups (p < 0.01). The predominant mode of failure for both the parallel and cross-stitch group was suture cutout through the meniscus (88% and 94% respectively). The Rebar Repair failed due to suture rupture in 50% and suture cutout through the meniscus in 50%. The Rebar Repair for radial meniscus tear has a higher load to failure and a lower rate of suture cutout through the meniscus than the parallel technique and cross-stitch technique. Radial meniscus tears lead to decreased hoop stresses of the meniscus and effectively a non-functional meniscus. Newer techniques may have a higher load to failure leading to more successful repairs.
An Investigation of Electrocatalytic CO2 Reduction Using a Manganese Tricarbonyl Biquinoline Complex

The subject of this study, [fac-Mn(bqn)(CO)3(CH3CN)]+ (bqn = 2,2’-biquinoline), is of particular interest as the bqn ligand exhibits both steric and electronic influence over the fundamental redox properties of the complex and, consequently, its related catalytic properties with respect to the activation of CO2. While not a particularly efficient catalyst for CO2 to CO conversion, in-situ generation and activity measurements of the [fac-Mn(bqn)(CO)3]– active catalyst allows for a better understanding of ligand design at the Mn center. By making direct comparisons to the related 2,2’-bipyridyl (bpy), 1,10-phenanthroline (phen), and 2,9-dimethyl-1,10-phenanthroline (dmphen) ligands via a combination of voltammetry, infrared spectroelectrochemistry, controlled potential electrolysis and computational analysis, the role of steric vs electronic influences on the nucleophilicity of Mn-based CO2 reduction electrocatalysts is discussed.
Blast Preconditioning Protects Retinal Ganglion Cells and Reveals Targets for Prevention of Neurodegeneration Following Blast-Mediated Traumatic Brian Injury.

Purpose The purpose of this study was to examine the effect of multiple blast exposures and blast preconditioning on the structure and function of retinal ganglion cells (RGCs), to identify molecular pathways that contribute to RGC loss, and to evaluate the role of kynurenine-3-monooxygenase (KMO) inhibition on RGC structure and function. Methods Mice were subjected to sham blast injury, one single blast injury, or three blast injuries separated by either 1 hour or 1 week, using a blast intensity of 20 PSI. To examine the effect of blast preconditioning, mice were subjected to sham blast injury, one single 20-PSI injury, or three blast injuries separated by 1 week (5 PSI, 5 PSI, 20 PSI and 5 PSI, 5 PSI, 5 PSI). RGC structure was analyzed by optical coherence tomography (OCT) and function was analyzed by the pattern electroretinogram (PERG). BRN3A-positive cells were quantified to determine RGC density. RNA-seq analysis was used to identify transcriptional changes between groups. Results Analysis of mice with multiple blast exposures of 20 PSI revealed no significant differences compared to one 20-pounds per square inch (PSI) exposure using OCT, PERG, or BRN3A cell counts. Analysis of mice exposed to two preconditioning 5-PSI blasts prior to one 20-PSI blast showed preservation of RGC structure and function. RNA-seq analysis of the retina identified multiple transcriptomic changes between conditions. Pharmacologic inhibition of KMO preserved RGC responses compared to vehicle-treated mice. Conclusions Preconditioning protects RGC from blast injury. Protective effects appear to involve changes in KMO activity, whose inhibition is also protective.
Effect of Acupuncture vs Sham Procedure on Chemotherapy-Induced Peripheral Neuropathy Symptoms: A Randomized Clinical Trial.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most common and debilitating long-term adverse effect of neurotoxic chemotherapy that significantly worsens cancer survivors’ quality of life. Well-tolerated, evidence-based interventions for CIPN are needed.1
Methylenedioxymethamphetamine-like discriminative stimulus effects of pyrrolidinyl cathinones in rats:

Background:Synthetic cathinone derivatives are used as alternatives both for stimulant drugs such as cocaine and methamphetamine and for club drugs such as 3,4-methylenedioxymethamphetamine (MDMA),...
Pharmacokinetic Modeling of the Impact of P-glycoprotein on Ondansetron Disposition in the Central Nervous System

Modulation of 5-HT3 receptor in the central nervous system (CNS) is a promising approach for treatment of neuropathic pain. The goal was to evaluate the role of P-glycoprotein (Pgp) in limiting exposure of different parts of the CNS to ondansetron (5-HT3 receptor antagonist) using wild-type and genetic knockout rat model. Plasma pharmacokinetics and CNS (brain, spinal cord, and cerebrospinal fluid) disposition was studied after single 10 mg/kg intravenous dose. Pgp knockout resulted in significantly higher concentrations of ondansetron in all tested regions of the CNS at most of the time points. The mean ratio of the concentrations between KO and WT animals was 2.39–5.48, depending on the region of the CNS. Male and female animals demonstrated some difference in ondansetron plasma pharmacokinetics and CNS disposition. Mechanistic pharmacokinetic model that included two systemic disposition and three CNS compartments (with intercompartmental exchange) was developed. Pgp transport was incorporated as an efflux from the brain and spinal cord to the central compartment. The model provided good simultaneous description of all data sets, and all parameters were estimated with sufficient precision. The study provides important quantitative information on the role of Pgp in limiting ondansetron exposure in various regions of the CNS using data from wild-type and Pgp knockout rats. CSF drug concentrations, as a surrogate to CNS exposure, are likely to underestimate the effect of Pgp on drug penetration to the brain and the spinal cord.
Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer.

Abstract Tumor hypoxia has been widely explored over the years as a diagnostic and therapeutic marker. Herein, we have reported the design and synthesis of a series of dinitrobenzamide mustards (DNBM) based on the PR-104A hypoxia-selective prodrug. Specifically, we explored the impact of various leaving groups and the introduction of a carboxylic acid group on the biological performance of the DNBM constructs. Once in hand, the Log D values, cytotoxicity in PC-3 and DU-145 human prostate cancer cells lines and the hypoxia selectivities of the DNBM analogs were examined. Overall, the DNBM constructs were found to be tolerant to modifications with none of the explored modifications substantially degrading the cytotoxic potential of the constructs.
Optimizing task scheduling in human-robot collaboration with deep multi-agent reinforcement learning

Abstract Human-Robot Collaboration (HRC) presents an opportunity to improve the efficiency of manufacturing processes. However, the existing task planning approaches for HRC are still limited in many ways, e.g., co-robot encoding must rely on experts’ knowledge and the real-time task scheduling is applicable within small state-action spaces or simplified problem settings. In this paper, the HRC assembly working process is formatted into a novel chessboard setting, in which the selection of chess piece move is used to analogize to the decision making by both humans and robots in the HRC assembly working process. To optimize the completion time, a Markov game model is considered, which takes the task structure and the agent status as the state input and the overall completion time as the reward. Without experts’ knowledge, this game model is capable of seeking for correlated equilibrium policy among agents with convergency in making real-time decisions facing a dynamic environment. To improve the efficiency in finding an optimal policy of the task scheduling, a deep-Q-network (DQN) based multi-agent reinforcement learning (MARL) method is applied and compared with the Nash-Q learning, dynamic programming and the DQN-based single-agent reinforcement learning method. A height-adjustable desk assembly is used as a case study to demonstrate the effectiveness of the proposed algorithm with different number of tasks and agents.
Nuclear Magnetic Resonance Studies of Intracellular pH and Myocardial Contractility during Ischemia

Most investigators in the field of molecular cardiology define myocardial ischemia in terms of a metabolic supply demand imbalance. Normal cell function is observed when supply is equal to or greater than demand. However, if coronary flow is reduced such that oxygen supply cannot meet the metabolic demands for the aerobic production of ATP (and phosphocreatine), then there must be a reduction in cell function1. In other words, cell function is in a delicate balance between metabolic (energetic) supply and its physiological demands, as illustrated by Equation 1.
Biosphere 2: A Closed Bioregenerative Life Support System, an Analog for Long Duration Space Missions

This paper examines the Biosphere 2 Agriculture System, a two year experiment in the design and operation of a closed system agriculture. Several problems/challenges associated with bioregenerative life support system design are presented and discussed with repect to their applicability to long duration space missions such as would be required to establish and maintain a human presence on Mars or the moon. Specific examples as experienced during the Biosphere 2 experiment are presented including health effects of a low fat, calorie restricted, yet nutrient dense diet that resulted from a lower-than-expected crop production. Medical problems associated with oxygen depletion in Biosphere 2 are also discussed. Biosphere 2 is an interesting case study for closed bioregenerative life support systems and has many lessons to be learned for space exploration.
Stress response of Escherichia coli to elevated hydrostatic pressure.

Abstract The response of exponentially growing cultures of Escherichia coli to abrupt shifts in hydrostatic pressure was studied. A pressure upshift to 546 atm (55,304 kPa) of hydrostatic pressure profoundly perturbed cell division, nucleoid structure, and the total rate of protein synthesis. The number of polypeptides synthesized at increased pressure was greatly reduced, and many proteins exhibited elevated rates of synthesis relative to total protein synthesis. We designated the latter proteins pressure-induced proteins (PIPs). The PIP response was transient, with the largest induction occurring approximately 60 to 90 min postshift. Fifty-five PIPs were identified. Many of these proteins are also induced by heat shock or cold shock. The PIP demonstrating the greatest pressure induction was a basic protein of 15.6 kDa. High pressure inhibits growth but does not inhibit the synthesis of stringently controlled proteins. Cold shock is the only additional signal which has been found to elicit this type of response. These data indicate that elevated pressure induces a unique stress response in E. coli, the further characterization of which could be useful in delineating its inhibitory nature.
System design of a low-power I/O link

In this paper, we present a detailed analysis of the system design choices available for low-power high-speed I/O link transceivers. Using the transceiver power dissipation as the metric, we compare three equalization schemes (linear equalizer, decision-feedback equalizer, and transmit pre-emphasis) in combination with three pulse amplitude modulation (PAM) schemes (2-PAM, 4-PAM, and 8-PAM). The input signal levels and the filter lengths in the equalizer are chosen to minimize the power dissipation while meeting a bit error rate constraint. We show that, for a typical 20" intersymbol interference dominated link, transmit pre-emphasis in combination with 4-PAM results in 75 data rates.
Pharmacological treatment for generalized anxiety disorder in adults: an update.

Introduction: Modest response and remission rates for the selective serotonin reuptake inhibitors and the serotonin-norepinephrine reuptake inhibitors, coupled with mounting evidence that the tolerability of the antidepressants (ADs) may have been overstated in the literature, has contributed to changes in prescribing patterns for generalized anxiety disorder (GAD). New interest in the absence of evidence that supports these standard therapies as superior to benzodiazepines stimulated a review of the literature.Areas covered: A literature search was conducted in the MedLine database with search terms ‘generalized anxiety disorder’ and ‘treatment’ for purposes of including relevant literature related to pharmacologic treatment of GAD. Aside from a review of pivotal literature, the authors also included newer studies that evaluated novel drug treatments. Last, the database was searched for benzodiazepine comparisons to standard therapy secondary to concerns that such literature is sparse. The review of newe...
Differential expression of protein phosphatase 1 isoforms in mammalian brain

Rat cDNAs encoding neuronal isoforms of protein phosphatase 1 (PP1) were isolated and their primary structures elucidated. The derived amino acid sequences allowed us to design synthetic C-terminal peptides that were used to raise antibodies. Isoform-specific anti-peptide antibodies against PP1 alpha and PP1 gamma 1 were used to investigate the tissue distribution of PP1 isoforms by immunoblotting. Both isoforms were ubiquitously expressed in mammalian tissues, with the highest levels being observed in brain. Of all neuronal tissues examined, PP1 alpha and PP1 gamma 1 were found to be most abundantly expressed in the striatum. Lesion experiments with kainic acid indicated that both the alpha and the gamma 1 isoforms of protein phosphatase 1 were relatively enriched in the medium-size spiny neurons of the striatum. "In situ" hybridization to rat brain slices using highly sensitive riboprobes also showed PP1 alpha, PP1 beta, and PP1 gamma 1 to be widely expressed in mammalian brain. However, some interesting differences were observed. For example, PP1 alpha and PP1 gamma 1 were found to be expressed in the striatum, where DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, M(r) = 32,000 Da) is also known to be highly expressed. PP1 beta appeared to be relatively less abundant in the same cells, as judged both by "in situ" hybridization and by the apparent absence of PP1 beta clones from the striatal cDNA libraries used.
In vitro enzymatic stability of dendritic peptides.

PEGylated polyamidoamine (PAMAM) dendrimers as drug carriers have been a topic of interest because of their biomedically favorable features, including minimal toxicity, reduced immunogenicity, and excellent solubility in aqueous and most organic solutions. A PEG shell on dendrimer surface may provide steric hindrance, known as stealth properties of PEG, to stabilize drug molecules to be delivered. In this article, the effects of PEG and coupling sequence of drug, PEG, and dendrimer in modulating the stability of delivered drug molecules were evaluated. N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide was chosen as a model peptide. Dendritic peptides, that is, peptide-dendrimer, peptide-PAMAM-PEG, and peptide-PEG-dendrimer, were constructed based on Starburst™ G3.0 PAMAM dendrimer and characterized by 1H-NMR spectroscopy. Hydrolysis of dendritic peptides was catalyzed by α-chymotrypsin in pH 7.4 PBS buffer containing 5% DMF (v/v) at room temperature. The enzymatic stability of dendritic peptides was peptide-PAMAM-PEG > peptide-PAMAM > free peptide > peptide-PEG-PAMAM. The ratio of PEG/peptide could be reduced for increasing peptide loading while maintaining the delivered peptides' relatively high enzymatic stability. The quantitative analysis of dendritic peptide/enzyme interactions provided the understandings of the molecular structure/stability relationships of dendrimer/drug for the design of an optimal PEGylated dendrimer-based drug-delivery system. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Crystal structures of histone Sin mutant nucleosomes reveal altered protein–DNA interactions

Here we describe 11 crystal structures of nucleosome core particles containing individual point mutations in the structured regions of histones H3 and H4. The mutated residues are located at the two protein–DNA interfaces flanking the nucleosomal dyad. Five of the mutations partially restore the in vivo effects of SWI/SNF inactivation in yeast. We find that even nonconservative mutations of these residues (which exhibit a distinct phenotype in vivo) have only moderate effects on global nucleosome structure. Rather, local protein–DNA interactions are disrupted and weakened in a subtle and complex manner. The number of lost protein–DNA interactions correlates directly with an increased propensity of the histone octamer to reposition with respect to the DNA, and with an overall destabilization of the nucleosome. Thus, the disruption of only two to six of the ∼120 direct histone–DNA interactions within the nucleosome has a pronounced effect on nucleosome mobility and stability. This has implications for our understanding of how these structures are made accessible to the transcription and replication machinery in vivo.
Developmentally appropriate parent training for families with young children

In an effort to explore the value and feasibility of teaching the principles behind developmentally appropriate practices to parents, 53 families with young children were studied. Parents were randomly assigned to participate or not participate in a three month-long, weekly, parent training program. Following completion of the program members of participating families were less likely to engage in conflict during a puzzle solving task than were members of nonparticipating families. Parents who participated were more likely to take a supportive leadership role and have age-appropriate expectations during a puzzle solving task than were nonparticipating parents. Children in participating families showed better social skills than children in nonparticipating families. Portions of the increase in social skills were related to reductions in family conflict and to the development of a task orientation that was more appropriately focused on process than outcome. Lower family conflict was also related to better gross motor skills in children.