cssi/SciSciGPT-SciSciNet huggingface dataset:
Tissue-Specific HIF-1 and HIF-2 Regulatory Elements and Their Roles in Erythropoietin Gene Expression

Abstract 1303 Studies of the regulation of erythropoiesis by hypoxic induction of erythropoietin (EPO) transcription led to the discovery of oligonucleotide binding motifs, hypoxia responsive elements (HREs) essential for hypoxic upregulation of EPO. HREs bind hypoxia-inducible transcription factors (HIFs). HIFs are heterodimers of 3 α subunit isotypes; HIF-1α, HIF-2α, and HIF-3α, and a common β-subunit. EPO is expressed in diverse tissues, some regulated mainly by HIF-2 and others by HIF-1. Tissue-specific regulatory elements (i.e. Kidney Inducible Element KIE, Negative Regulatory Element NRE, and Negative Regulatory Liver specific Element NRLE) of the EPO gene spanning several kilobases were reported. Our in silico analysis of the human EPO genome found two additional canonical HIF-binding elements in the KIE and NRE regions, and comparative analysis of phylogenically conserved sequences of Epo genes refined these HIF-binding elements from several kbs to a few hundred nucleotides and further delineated them as mKIE, mNRE1, mNRE2, and mNRLE2. To further define the structure and function of these elements in vivo, we exposed mice to 8% O2 hypoxia and monitored hypoxic induction of Epo mRNA levels in the liver, kidney, brain, and spleen. Spleen, kidney, and brain had a peak induction of the Epo transcript at 3 hours of hypoxia treatment, while liver showed peak induction at 6 hours. At the end of the hypoxia treatment, the mice were sacrificed and organs were harvested, and in vivo chromatin immunoprecipitation (ChIPs) was performed with antibodies against HIF-1α and HIF-2α. The results from these studies are summarized below. “+” denotes presence and “−” absence of binding of HIF-1 and HIF-2. “Norm” - normoxia, “Hyp” - hypoxia. To further define the role of these elements in tissue-specific Epo expression, we cloned and mutated these elements with reporter constructs, and generated transgenic mouse strains. The reporter gene was expressed in renal tubules, the red pulp area of the spleen, and liver hepatocytes. By creating a designed point mutation to disrupt the function of KIE, we suppressed the hypoxia response in the kidney, while mutations of NRE1 and NRE2 abolished reporter expression in the liver. Studies of HREs in the brain are ongoing. In conclusion, we have refined the previously reported HREs to a few hundred bases (particularly, KIE is a 6 nucleotide bearing motif) and now demonstrate tissue-specific differential hypoxia-induced binding of HIF-1 and HIF-2 and their functional roles in EPO induction. This provides a background to examine the molecular basis of these elements in patients with aberrant EPO expression. Disclosures: Elliott:Amgen, Inc: Employment.
Platelet Function in Ovarian Cancer

A significant number of patients with ovarian cancer develop venous thromboembolism that is associated with a worse prognosis. The etiology of an increased frequency of venous thrombosis in cancer patients is not clear, and various hypotheses, including the presence of hyperreactive platelets, have been postulated. Hyperreactive platelets have a lower threshold for aggregation, and hence there is a higher number of degranulated platelets in circulation and a higher concentration of platelet granular contents in plasma. We compared ADP- and collagen-induced platelet aggregation in patients with ovarian cancer to those in patients with benign ovarian tumors. To reduce the effect of confounding factors such as surgery or chemotherapy, all blood samples were collected prior to any surgical interventions or chemotherapy. To detect hyperreactivity of platelets, we used both low and high doses of platelet agonists. To evaluate platelet preactivation at baseline, we measured the plasma concentration of b-thromboglobulin (b-TG) and platelet factor-4 (PF-4) as markers of platelet α granule secretion. All studies were approved by the Institutional Review Boards of the University of Texas, M.D. Anderson Cancer Center. Whole blood samples were collected from 34 patients with ovarian cancer and 19 patients with benign ovarian tumors into sodium citrate anticoagulant and processed within 2 hours after collection. Platelet rich plasma (PRP) was prepared by 15 min of 850 rpm centrifugation at room temperature. Aggregation studies were conducted in a light transmission aggregometer (Bio/Data Corporation), using ADP (at 2mM and 20 mM) and collagen (at 19 mg/ml and 190 mg/ml). Platelet poor plasma (PPP) was prepared by centrifuging PRP samples at 2500 rpm for 20 min at room temperature. All PPP samples were stored at -80oC and the quantity of b-TG and PF-4 was determined by ELISA. We found that platelets isolated from ovarian cancer patients showed aggregation responses similar to platelets from patients with benign ovarian tumors (Figure 1). There was a statistically significant difference in the high-dose collagen-induced platelet aggregation between cancer and benign tumor samples, with increased aggregation of platelets from patients with benign tumors (79 ± 4.9%) in comparison to aggregation of platelets from cancer platelets (69 ± 6.3%). To investigate preactivation of platelets in cancer patients, we measured b-TG and PF-4 in PPP samples. We did not detect a higher concentration of b-TG and PF-4 in cancer PPP samples (Figure 2). In fact, PPP from cancer patients had a lower concentration of both α granule constituents. In the case of PF-4, the difference was statistically significant (9.8 ± 1.5 ng/ml for cancer patients versus 11.7 ± 1.7 ng/ml for patients with non-malignant tumors). We conclude that platelets from ovarian cancer patients are not hyperreactive and are not degranulated or preactivated. Links between ovarian cancer, venous thromboembolism and platelets may be absent or may involve non-hemostatic platelet functions. Disclosures No relevant conflicts of interest to declare.
Quantification by nano liquid chromatography-parallel reaction monitoring-mass spectrometry of human apolipoprotein A-I, apolipoprotein B, and hemoglobin A1c in dried blood spots

Purpose : Proteomic analysis of blood proteins in DBS is gaining attention as a possible replacement for measurements in plasma/serum collected by venipuncture. We aimed to develop and provisionally validate a nanoflow LC-PRM-MS method for clinical use. Experimental design : We used Skyline to develop a nanoflow LC-PRM-MS method to quantify glycated hemoglobin-β, apolipoprotein A-I, and apolipoprotein B in DBS. Precision, linearity, interferences, and stability and were determined and the method was used to analyze samples from 36 human volunteers. The method was compared with clinically validated measurements in paired blood collected via venipuncture. Results : The method was relatively precise for these proteins (10-11% CV) and linear across the normal concentration ranges of these proteins. Interference from high total serum protein concentration (>8 g/dL) was noted for apolipoprotein A-I and apolipoprotein B. Proteins in DBS were stable for 14 d at temperatures below 25°C and trypsinized samples were stable for 48 h at 7°C. There was moderate correlation with clinical methods (r = 0.783-0.858) and significant bias in individual samples. Conclusions and clinical relevance : Although the method had adequate precision and linearity for a biomarker, the accuracy compared with clinically validated assays raises concerns regarding the use of DBS compared with venipuncture for clinical use. This article is protected by copyright. All rights reserved
Preparation and characterization of PHMB-based multifunctional microcapsules

Abstract Insects and microbes can cause disease and corrode materiel deployed in humid environments. Materials with multifunctional properties are highly desirable to the Army to create textile products that would inherently mitigate these issues and decrease Soldier load. Microcapsules (MCs) that encapsulate active compounds such as insect repellents are a potential platform to accomplish this. MCs that exhibit antibacterial and antifungal properties were prepared using an antimicrobial polymer, PHMB, as the shell, and the encapsulation of an insect repellent, picaridin, is reported. MCs are spherical, uniform, and demonstrate a positive zeta potential. FTIR analysis confirms the presence of both active components. MCs were studied for storage stability and their ability to impart functionality to a military relevant textile. Microscopy images demonstrate that MCs remain stable when stored in diH2O for at least six months. Antibacterial activity is observed for MC concentrations across two orders of magnitude in solution. MCs were adsorbed onto a 50:50 nylon:cotton blend (NyCo) as a model for functionalized materiel. GC data indicates that picaridin loading levels are more than ten times the required dose for deterring mosquitoes and both antibacterial and antifungal properties are exhibited. Treated fabric is resistant to fungal growth throughout a four week culture period. A four week storage study demonstrates no discernible loss in picaridin content, and NyCo swatches sustain at least a three log reduction in bacteria growth for all time points. The findings detailed in the following report suggest that these PHMB-based MCs could be used to functionalize materials against microbial organisms and mosquitoes, and are robust enough to endure storage in their crude form and as a coating.
Muscle stem cell activation in a mouse model of rotator cuff injury.

Rotator cuff (RC) tears are frequently complicated by muscle atrophy. Muscle stem cells (MuSCs) repair damaged myofibers following injury, but their role in the prevention or pathogenesis of atrophy following RC tears remains undefined. We hypothesized that the RC MuSC population would be affected by supraspinatus (SS) and infraspinatus (IS) tendon transection (TT) compared to uninjured muscle in a mouse model of RC tear. C57BL6/J mice underwent unilateral SS and IS TT and contralateral sham surgery. At 3, 8, or 14 weeks after injury, mice were euthanized and SS and IS were harvested for FACS sorting of CD31-/CD45-/Sca1-/ITGa7 + /VCAM+ MuSCs or histological analysis. Ki-67+ MuSCs from injured muscle increased 3.4 fold at 3 weeks (p = 0.03) and 8.1 fold at 8 weeks (p = 0.04) following TT injury, but returned to baseline by 14 weeks (p = 0.91). Myod1 remained upregulated 3.3 fold at 3 weeks (p = 0.03) and 2.0 fold at 14 weeks (p = 0.0003), respectively. Myofiber cross-sectional area was decreased at both 3 and 14 weeks after injury, but the number of MuSCs per fiber remained relatively constant at 3 (p = 0.3) and 14 (p = 0.6) weeks after TT. In this study, we characterized the longitudinal effect of RC tendon injury on the MuSC population in supraspinatus and infraspinatus muscles. MuSCs are transiently activated, and are not depleted, in spite of persistent muscle atrophy. This article is protected by copyright. All rights reserved
Alfalfa Weevil (Coleoptera: Curculionidae) Phenology with its Host Crop and Parasitoids in Virginia

Alfalfa weevil, Hypera postica (Gyllenhal), phenology is influenced by winter climate. In 1997 we initiated a 2-yr study of alfalfa weevil phenology with respect to its host crop and parasitoids in three geographically distinct locations of Virginia: the central Piedmont, Shenandoah Valley, and southwestern region. Alfalfa weevil populations from nine fields were sampled regularly from November until first harvest in each season. Eggs laid in December and January resulted in alfalfa weevil larval infestations in March and April at all locations. Because of warmer winter temperatures, eggs developed faster in the Piedmont compared with the higher elevations, and resulted in larval populations attacking alfalfa earlier in the season, when the crop was at an earlier growth stage. The adult parasitoid, Microctonus aethiopoides Loan, was synchronized poorly with alfalfa weevil populations in Virginia. At all locations studied, adult emergence of first generation M. aethiopoides occurred in April and early May,...
On the Location of the Intermediate Point in Taylor’s Theorem

It is here shown that, under suitable conditions, the intermediate point in Taylor’s theorem must lie in the left half of the interval considered.
High-resolution microscopic methods for the analysis of cellular movements in Drosophila embryos.

Publisher Summary This chapter outlines the various methods used for the observation and documentation of living fly embryos. It primarily focuses on high-resolution methods used for observing and recording images of living embryos that take advantage of a number of advancements in video microscopy and digital image processing. New advances in electronic image detection greatly facilitate image acquisition and manipulation so that high-quality electronic images now compete with the best photographic film images. Given appropriate instrumentation, an image can be easily acquired, manipulated, and transferred to hard copy in a fraction of the time required to produce comparable output by photographic methods. High-fidelity electronic imaging implies that resolution, ideally diffraction limited as output from the microscope, stays optimal throughout image recording, digital image processing, and image outputting to hard copy. A wide variety of algorithms designed to enhance contrast are available for manipulation of a digitally recorded image. This enhanced contrast can bring out detail in images crucial to evaluate relevant elements of structure in the developing embryo. Such algorithms compare individual pixels to those that surround them.
REM Sleep Anatomy and Physiology

The key brain structures for generating rapid eye movement (REM) sleep are the pons and adjacent portions of the midbrain. These areas and the hypothalamus contain cells that are maximally active in REM sleep, called REM-on cells, and cells that are minimally active in REM sleep, called REM-off cells. Subgroups of REM-on cells use the transmitter gamma-aminobutyric acid (GABA), acetylcholine, glutamate, or glycine. Subgroups of REM-off cells use the transmitter norepinephrine, epinephrine, serotonin, histamine, and GABA. Destruction of large regions within the midbrain and pons can prevent the occurrence of REM sleep. Damage to portions of the brainstem can cause abnormalities in certain aspects of REM sleep. Hypocretin neurons have an important role in the regulation of REM sleep and other sleep–wake phenomena.
pRS yeast vectors with a LYS2 marker

Vol. 36, No. 2 (2004) BioTechniques 213 We constructed two new general purpose cloning vectors for use in Saccharomyces cerevisiae. The new plasmids are pRS307, an integrating (YIp) vector with a LYS2 selectable marker, and pRS327, a multicopy (YEp) vector with a LYS2 marker and a 2-μm origin of replication. These plasmids, along with the previously described pRS317 plasmid, a single copy (YCp) vector with a LYS2 marker and a (centromeric) CEN element, provide a complete set of LYS2 plasmids with the Bluescript® polylinker that complement the widely used existing pRS vectors. Studies in yeast have been facilitated by sets of plasmid vectors with polylinkers that allow easy cloning. The YCplac/YIplac/YEplac set of vectors (1) contain the pUC polylinker (2) and a nutritional marker for selection in yeast. Thus, any fragment inserted into one of these vectors can be easily transferred to other versions, such as YCp, YIp, or YEp, or to a vector with a different selectable marker, either LEU2, TRP1, or URA3. The pRS set of plasmids (3,4) used the polylinker from the Bluescript plasmids (Stratagene, La Jolla, CA, USA) with YCp, YIp, and YEp versions constructed. Subsequently, pRS plasmids with the MET15 and ADE2 markers were constructed (5). Many commonly used yeast strains, including the BY strains (5) used to generate the complete collection of gene knockouts (6) have a lys2 mutation. Although the YCp plasmid with a LYS2 marker, pRS317, has been described (7), YIp and YEp versions have not been available. Here we describe the construction of YIp and YEp vectors with a LYS2 marker with the Bluescript polylinker. The integrating LYS2 plasmid pRS307 was constructed by ligation as follows. pRS317 was cleaved at the ApaLI site common to the pRS vectors, the ends were blunted with the Klenow fragment of DNA polymerase, the DNA was cleaved with EcoRI, and the 5.57-kb ApaLI (blunt)/EcoRI fragment was purified. pRS306 (4) was cleaved with NdeI, the ends were blunted with the Klenow fragment of DNA polymerase, cleaved with EcoRI, and the
SET-UP AND RUN-UP IN SHOALING BREAKERS

This paper reports the results of a series of laboratory experiments with periodic waves breaking on uniformly sloping impermeable beaches with the object of distinguishing set-up from dynamic shoreline motions due to partial reflection, the combination of which is normally referred to as 'run-up'. The principal findings are: 1. The mean set-up across the breaker zone was observed to be linear with mean slope proportional to the square of the bottom slope. The mean slope was independent of frequency over slopes of 0.04 or less, and increased with wave period over steeper slopes. 2. The dynamic run-up range was found to be proportional to the square of wave period times beach slope, in agreement with the equation of motion for a nearly frictionless block sliding on corresponding slopes under gravity. 3. The total run-up was poorly correlated with Hunt's empirical formula, nor could any reasonable deterministic justification of this formula be deduced from the present results. 4. Transient run-up was observed to considerably exceed steady-state values in most cases, suggesting that time-dependent momentum flux should be considered in the run-up of variable (natural) waves.
Template-Synthesized Vertical Needle Array as Injection Platform for Microalgae

Increasing numbers of studies in the past few decades have demonstrated vertically-oriented nanoneedles arrays (NNAs) as innovative tools to interrogate and manipulate biological cells, where the needles are inserted into the cells as functional probes for high-throughput detection and biomolecule delivery. However, majority of these studies use mammalian cells: leaving NNA application to plant cells still in its infancy and largely unexplored. This paper highlights our contributions in exploring the utility of NNAs to microalgae - a diverse group of aquatic, photosynthetic organisms studied intensively as bio-factories for producing high-value-added products such as fuels and pharmaceuticals. Microalgal strain development processes have long suffered from the hard cell wall that surrounds the cell and inhibits delivery of foreign materials into the cell. Conically-shaped, metallic NNAs were developed with template synthesis that successfully penetrate through the cell wall barrier and achieve material injection - using the widely studied model microalga, Chlamydomonas reinhardtii. Earlier works from mammalian cells are introduced and discussed to clarify the framework established in this field, while recent studies of both mammalian and microalgal cells are also referenced to examine the trends, challenges, and future perspectives of NNA application to microalgae.
Automatic Estimation of Parameters of a Reduced Order Electrochemical Model for Lithium-Ion Batteries at the Beginning-of-Life

This paper presents a procedure for automatic estimation of parameters of a lithium-ion battery at the beginning-of-life. Based on a reduced order electrochemical model, a two-step sensitivity analysis is employed to group the parameters and divide them using the best state-of-charge (SOC) window. Then, a genetic algorithm is applied to minimize a multi-objective function that is the L2 norm of the voltage error for each SOC window. Results of the procedure are validated against a multiple cycle and an actual driving cycle test, which keep the absolute voltage errors less than 12mV.
Abstract 707: Emerging role of mitochondrial pathway in crosstalk between ferroptosis and apoptosis

Introduction: Several processes lead to cell death; ferroptosis, apoptosis, necrosis, and autophagy are the primary mechanisms. Each type of biological death has been believed to have a distinct biochemical and morphological fingerprint. However, emerging evidence suggests that these different types of cell death often share common pathways. In this study, we investigated whether mitochondrial signaling pathways play an important role in the intracellular communication between ferroptosis and apoptosis. Methods: The human colorectal carcinoma HCT116 cell line was used to evaluate the interplay between cell death pathways. Cells were treated with the apoptotic agent TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) and ferroptotic agents such as artesunate and erastin. Cell death was determined by trypan blue exclusion assay. Apoptosis was measured by western blot. Ferroptosis was assessed using MDA assay. Bax oligomerization was performed by mitochondrial fractionation followed by SDS-PAGE under nondenaturing conditions. Results: We observed that the combinatorial treatment induced synergistic apoptosis, which was mediated through an increase in caspase activation. We also observed an increase in pro-apoptotic Bax oligomerization in the mitochondrial fraction. The combined treatment-induced apoptosis was suppressed in Bax-deficient HCT116 cells. Ferroptotic agents enhanced the intracellular level of anti-apoptotic Mcl-1. However, the combined treatment decreased the level of Mcl-1. Interestingly, the combined treatment-induced apoptosis was abolished in HCT116 cells with knockin of Mcl-1 phosphorylation site mutant (S121A/E125A/S159A/T163A). Conclusions: These data suggest a novel mechanism for the combined treatment of the apoptotic agent TRAIL and ferroptotic agent erastin/artesunate-induced synergistic apoptosis through the mitochondrial pathway. Citation Format: Yong J. Lee. Emerging role of mitochondrial pathway in crosstalk between ferroptosis and apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 707.
Venue Preference and Earthquake Mitigation Policy: Expanding the Micro‐Model of Policy Choice

Seismologists have reported that a majority of recent earthquakes in Oklahoma have been triggered by the activities of oil and gas companies. Despite this fact, there is evidence of strong opposition toward earthquake mitigation policy. In this article, we argue that how individuals define issues affect their policy choice. Furthermore, we incorporate the concept of venue shopping from the literature on macro theories of the policy process to investigate the effect of problem definition in shaping individual venue preference for policy choice. Using unique survey data, we find that problem definition, particularly issue causality and issue image, is strongly related to individual support for earthquake mitigation policy. However, a more nuanced relationship between individual problem definition and venue preference is observed. Our findings contribute to scholarly endeavors to understand the politics of problem definition at an individual level, which may be the precursor of understanding policy choices at the institutional level. 场地偏好和防震减灾政策：扩大政策选择的微观模式 地震学家表示，近期发生在俄克拉荷马州的大多数地震都由石油天然气公司的开采活动引起。除此之外，证据表明，防震减灾政策受到强烈反对。笔者在本文中主张，个人对问题的定义方式会影响其政策选择。此外，笔者将政策过程宏观理论文献中的场地竞争（venue shopping）概念纳入研究，以考察问题定义如何影响个人就政策选择所形成的场地偏好。通过使用独特调查数据，笔者发现，问题定义与个人对防震减灾政策的支持强烈相关，尤其当问题定义与问题的因果关系和形象相关时。然而，笔者发现，个人对问题的定义和对场地的偏好，二者之间存在更微妙的关系。本文从个人层面理解问题定义的相关政治，进而促进了学术贡献，这可能成为从制度层面理解政策选择的第一步。 Preferencia de la sede y politica de mitigacion de terremotos: expandiendo el micro‐modelo de eleccion de politicas los sismologos han informado que la mayoria de los terremotos recientes en Oklahoma se han desencadenado por actividades de companias de petroleo y gas. A pesar de este hecho, ha habido evidencia de una fuerte oposicion a la politica de mitigacion de terremotos. En este articulo, argumentamos que la forma en que los individuos definen los problemas afecta su eleccion de politica. Ademas, incorporamos el concepto de compras en el lugar de la literatura sobre macro teorias del proceso de politicas para investigar el efecto de la definicion del problema en la configuracion de la preferencia del lugar individual para la eleccion de politicas. Usando datos de encuestas unicos, encontramos que la definicion del problema, particularmente la causalidad del problema y la imagen del problema, esta fuertemente relacionada con el apoyo individual para la politica de mitigacion de terremotos. Sin embargo, se observa una relacion mas matizada entre la definicion del problema individual y la preferencia del lugar. Nuestros hallazgos contribuyen a los esfuerzos academicos para comprender las politicas de definicion de problemas a nivel individual, lo que puede ser el precursor de la comprension de las opciones de politicas a nivel institucional.
Categorization in the Perception of Breathy Voice Quality and Its Relation to Voice Production in Healthy Speakers

Purpose Previous studies of speech articulation have shown that individuals who can perceive smaller differences between similar-sounding phonemes showed larger contrasts in their productions of th...
Improved Accuracy Test Method for Mobile Eye Tracking in Usability Scenarios

Eye tracking has been used in usability testing for many years to gain objective measurements to inform label, instruction, and product design. With many different testing environments, possible pa...
Ergocalciferol Versus Cholecalciferol in Non-Dialysis Dependent Chronic Kidney Disease Patients: A Small Retrospective Cohort Study.

Purpose The purpose of this retrospective cohort study was to measure the difference between cholecalciferol and ergocalciferol in their ability to effect vitamin D, parathyroid hormone (PTH), calcium, and phosphorous serum concentrations in patients with stage 3 or 4 chronic kidney disease. Methods This was a retrospective cohort study conducted within a single-center ambulatory nephrology clinic. Patients eligible for the study were identified through medical records displaying each patient's initiation on either ergocalciferol or cholecalciferol from 2013 to 2016. Patients' baseline vitamin D, PTH, calcium, and phosphorous serum concentrations were taken prior to treatment initiation, and patients were reassessed with a second measurement within 12 months of therapy. Results Out of 149 eligible patients, 110 were excluded. There were 33 patients included on cholecalciferol and 6 patients on ergocalciferol. A significant difference was observed in the percent change of phosphorous serum concentrations from baseline following drug administration (p=0.03). The mean changes from baseline to final serum phosphorous concentrations (mg/dL) were 0.12 and -0.3 for cholecalciferol and ergocalciferol, respectively. There was no significant difference in vitamin D (14.9, 15.1, p=0.97), PTH (5.6, 2.3, p=0.72), or calcium (0.05, -0.17, p=0.08) serum concentrations between cholecalciferol and ergocalciferol, respectively. There was a statistically significant increase in the mean change in serum phosphorous concentrations within the cholecalciferol group compared to the ergocalciferol group. Conclusion In this small pilot study, cholecalciferol treatment appeared to increase serum phosphorous concentrations compared to ergocalciferol. These observations may warrant further large-scale studies that are appropriately powered to validate such findings.
Cargo capture and transport by colloidal swarms

Controlling active colloidal particle swarms could enable useful microscopic functions in emerging applications at the interface of nanotechnology and robotics. Here, we present a computational study of controlling self-propelled colloidal particle propulsion speeds to cooperatively capture and transport cargo particles, which otherwise produce random dispersions. By sensing swarm and cargo coordinates, each particle's speed is actuated according to a control policy based on multiagent assignment and path planning strategies that navigate stochastic particle trajectories to targets around cargo. Colloidal swarms are shown to dynamically cage cargo at their center via inward radial forces while simultaneously translating via directional forces. Speed, power, and efficiency of swarm tasks display emergent coupled dependences on swarm size and pair interactions and approach asymptotic limits indicating near-optimal performance. This scheme exploits unique interactions and stochastic dynamics in colloidal swarms to capture and transport microscopic cargo in a robust, stable, error-tolerant, and dynamic manner.
Plasma metabolite biomarkers predictive of radiation induced cardiotoxicity.

Abstract Purpose Although advancements in cancer treatments using radiation therapy (RT) have led to improved outcomes, radiation-induced heart disease (RIHD) remains a significant source of morbidity and mortality in survivors of cancers in the chest. Currently, there are no diagnostic tests in clinical use due to a lack of understanding of the natural history and mechanisms of RIHD development. Few studies have examined the utility of using metabolomics to prospectively identify cancer survivors who are at risk of developing cardiotoxicity. Methods We analyzed plasma and left ventricle heart tissue samples collected from a cohort of male Sprague Dawley (SD) rats that were either sham irradiated or received fractionated doses (9 Gy per day × 5 days) of targeted X-ray radiation to the heart. Metabolomic and lipidomic analyses were utilized as a correlative approach for delineation of novel biomarkers associated with radiation-induced cardiac toxicity. Additionally, we used high-resolution mass spectrometry to examine the metabolomic profiles of plasma samples obtained from patients receiving high dose thoracic RT for esophageal cancer. Results Metabolic alterations in the rat model and patient plasma profiles, showed commonalities of radiation response that included steroid hormone biosynthesis and vitamin E metabolism. Alterations in patient plasma profiles were used to develop classification algorithms predictive of patients at risk of developing RIHD. Conclusion Herein, we report the feasibility of developing a metabolomics-based biomarker panel that is associated with adverse outcomes of cardiac function in patients who received RT for the treatment of esophageal cancer.
Identification of genetic loci associated with forage quality in response to water deficit in autotetraploid alfalfa (Medicago sativa L.)

Alfalfa has been cultivated in many regions around the world as an important forage crop due to its nutritive value to livestock and ability to adapt to various environments. However, the genetic basis by which plasticity of quality-relevant traits influence alfalfa adaption to different water conditions remain largely unknown. In the present study, 198 accessions of alfalfa of the core collection for drought tolerance were evaluated for 26 forage quality traits in a field trial under an imposed deficit irrigation gradient. Regression analysis between quality traits and water stress revealed that values of fiber-related traits were negatively correlated with values of energy-related traits as water deficit increased. More than one hundred significant markers associated with forage quality under different water treatments were identified using genome-wide association studies with genotyping by sequencing. Among them, 131 markers associated with multiple traits in all the water deficit treatments. Most of the associated markers were dependent to the levels of water deficit, suggesting genetic controls for forage quality traits were dependent to the stress treatment. Twenty-four loci associated with forage quality were annotated to functional genes that may play roles in cell development or in response to water stress. This study addressed the genetic base of phenotypic variation of forage quality traits under water deficit. The SNP markers identified in this study will be useful in marker-assisted selection for the genetic improvement of alfalfa with enhanced drought tolerance while maintaining forage quality.
Stress Among a Sample of Returning Citizens Living with HIV and Substance Use Disorder: A Mixed Methods Analysis

This mixed-methods study asks: among a sample of returning citizens living with HIV and substance use disorder, how is stress experienced; and what are the leading stressors and stress-coping strategies? Data is from a parent study that randomized 36 people to a yoga intervention and 36 people to treatment as usual. Qualitative analysis found that securing basic life needs was more acute in early reentry, and challenges with HIV acceptance were greater among those with a more recent HIV diagnosis. Social support was the most widely employed coping strategy but many lacked social networks. Post-program, multiple regression found older age(β = − 0.38, p < .05), greater income(β = − 0.002, p < .01), shorter incarceration(β = .03, p < .01) and randomization to yoga(β = 6.92, p < .01) predicted lower levels of stress. Results indicate that reentry needs for people living with HIV and substance use disorder include basic life needs, social supports, and stress-coping interventions that address physical and mental stress symptoms (such as yoga).
Nonexponential Tunneling due to Mean-Field-Induced Swallowtails.

Typically, energy levels change without bifurcating in response to a change of a control parameter. Bifurcations can lead to loops or swallowtails in the energy spectrum. The simplest quantum Hamiltonian that supports swallowtails is a nonlinear $2\ifmmode\times\else\texttimes\fi{}2$ Hamiltonian with nonzero off-diagonal elements and diagonal elements that depend on the population difference of the two states. This work implements such a Hamiltonian experimentally using ultracold atoms in a moving one-dimensional optical lattice. Self-trapping and nonexponential tunneling probabilities, a hallmark signature of band structures that support swallowtails, are observed. The good agreement between theory and experiment validates the optical lattice system as a powerful platform to study, e.g., Josephson junction physics and superfluidity in ring-shaped geometries.
Is This Safe? Addressing Societal Concerns About CRISPR-Edited Foods Without Reinforcing GMO Framing

This is a call to science communicators. We have an opportunity to engage with the public and direct the future of a technological revolution. With an ever-growing CRISPR genome-editing toolbox, sc...
Parametric and sensitivity analysis of a PCM-integrated wall for optimal thermal load modulation in lightweight buildings

Abstract Load modulation in buildings is becoming increasingly important due to growing disparity in energy demand during peak and off-peak hours. Integrating phase change material (PCM) in building envelopes and using a controlled precooling strategy can provide substantial thermal load modulation; however, it may greatly increase the total energy use. Previous studies have employed PCM in building envelopes primarily for energy savings and, to some extent, peak load shedding and shifting. However, the load modulation capacity of a PCM-integrated envelope has not been well explored in the literature. In this study, we perform an extensive parametric and sensitivity analysis on PCM-integrated lightweight building walls and examine the combinatory effects of various PCM parameters on thermal load modulation and wall-related heat gains in buildings. Using numerical simulations, we investigate eight PCM parameters: PCM location in the wall, transition temperature, thickness, latent heat, transition range, density, specific heat, and thermal conductivity. We evaluate their impact and relative importance to achieve maximum load modulation in buildings without compromising occupants’ thermal comfort or total energy use. The results show that the optimized PCM proposed in this study can completely invert the transient heat gain profile of the wall, providing up to 70% reduction of wall-related heat gain during peak hours without a major increase in the cumulative heat gain.
Adaptive Therapy and the Cost of Drug-Resistant Mutants

The concept of adaptive cancer therapy proposes that the use of drugs at less than maximum tolerated dose can provide clinical benefits by allowing persisting drug-sensitive cells to competitively suppress drug-resistant cells; this can delay the outgrowth of these cell clones. The adaptive therapy concept has been developed with mathematical models and has subsequently been explored in clinical trials with promising results. In studies performed so far, a fitness cost of drug-resistant cells has been invoked for this treatment approach to be beneficial. In new work, it is shown that a clinical benefit can be achieved even in the absence of a fitness cost for resistant cells, which broadens the applicability of adaptive therapy.See related article by Strobl et al., p. 1135.
Genotype-Phenotype Correlations in Neurofibromatosis and Their Potential Clinical Use.

Objective Because clinically validated biomarkers for neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2) have not been identified, we aimed to determine whether genotype-phenotype correlations are useful in clinical trials in NF1 and NF2. Methods The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) Biomarker Group first performed a systematic literature search and reviewed existing data on genetic biomarkers in NF1 and NF2 and in in malignant peripheral nerve sheath tumors. The group then met during a series of consensus meetings to develop a joint report. Results We found that in NF2, the genetic severity score is clearly of potential clinical use. In NF1, despite over 3,000 constitutional variants having been described in the NF1 gene, only 4 actionable genotype-phenotype correlations exist. The diagnosis and treatment decision of these tumors should ideally include histopathology and compilation of some of the genetic markers. Conclusion We summarized emerging clinical use of genotype-phenotype correlations in neurofibromatosis.
Energy generation in the canal irrigation network in India: Integrated spatial planning framework on the Upper Ganga Canal corridor

Abstract An extensive canal irrigation network in South Asia has developed over the past 170 years that consists of thousands of kilometers of constructed channels and distributaries. These canals cut across many energy-poor regions along their paths. In India, this canal network provides a unique opportunity for renewable energy generation that is yet to be realized. Existing technologies for energy generation on canals include small hydropower on canal falls and, recently, canal-top solar panels. In addition, opportunities for hydrokinetic generation in irrigation canals have received limited attention. This paper develops a novel canal-network level framework for energy planning that integrates generation with local energy needs in a canal-corridor. This framework for integrated spatial assessment analyzes the supply of renewable energy generation potential and the demand of unmet energy needs in a canal-corridor, using the Upper Ganga Canal in Uttar Pradesh, India as a case study. We consider the theoretical and technological potential of hydropower and solar power generation and develop three indices to assess the agricultural, domestic, and composite unmet power demand of the canal-corridor. Our results show an overall theoretical potential of 149.1 MW and 13,213 MW for small hydropower and solar power, respectively, which could more than help meet the current 18 hours per day electricity service standard in Uttar Pradesh. The framework uses standardized irrigation and census datasets and therefore is generalizable for canal networks across India and South Asia more broadly.
When Welfare Disappears: The Case for Economic Human Rights

1. Introduction: Combating Poverty, Respecting Economic Human Rights 2. U.S. Welfare Policy: From Supporting Motherhood to a War against the Poor 3. Building Character through Adversity: General Outcomes of Welfare Reform 4. Varieties of Little-Noticed Suffering: Deconstructing Welfare-Reliant Families 5. Combating Family Poverty: How Other Affluent Nations Are More Successful and Why This Is So 6. Establishing Respect for Economic Human Rights in the United States
Assessment of Pain in Animals

Assessment of pain in animals presents problems not readily apparent to the unsophisticated observer. Most people do not realize that pain is a perception, that it has no definitive physical dimensions, and that it is probably the most modified of any sensory system of the body. A stimulus giving rise to the perception of pain in a human in one circumstance may not be painful in another circumstance to the same person or to another person. A strong mechanical stimulus applied to a conscious individual may be very painful; however, if the individual is anesthetized, no pain will be felt. It is therefore incorrect to use “pain” as an adjective in reference to a stimulus, as with a “painful” stimulus, unless the stimulus is actually perceived as being painful. Similarly it is incorrect to refer to “pain” fibers, reflexes, and pathways, because various stimuli may involve these neural mechanisms without the concomitant perception of pain. The conscious state of the individual is of paramount importance. Stimuli strong enough to be perceived as painful in a conscious individual will also produce activity in nerve fibers and pathways and possibly elicit reflexes in unconscious individuals totally unaware of the application of the stimulus.
Structural Comparison of the Hemoglobins of the Genus Equus with Those of Ruminants

Abstract The hemoglobin structures from domestic horse, tarpan horse, and przewalski's horse, donkey, and four subspecies of zebra are compared by peptide mapping and specific staining, with limited isolation of peptides followed by amino acid analysis. Peptide mapping techniques are used to indicate the "ambiguity" between phenylalanine and tyrosine at amino acid position α-24 in domestic horse. Such ambiguity at this position cannot be found in the α chain of 51 donkey hemoglobin samples, and is not evident in other equine species. Comparison of the hemoglobin polypeptide chains of the equine family reveals striking similarity among the β chains and a limited number of differences among the α chains. The number of amino acid interchanges accounting for species differences in the α chain are small in contrast to the numerous differences occurring in the α chains of the ruminants. Serine is present at position α-15 in the horse, donkey, and Hartmann's zebra hemoglobins, whereas glycine is present at α-15 in all the other zebra subspecies studied. The limited structural differences in the equine genus are contrasted to the recently reported variations which account for the polymorphic hemoglobins of ruminants. The genetic control of the hemoglobins of the horse, based upon three pairs of alleles for the two different α and single β chains is proposed and compared to a nonallelic scheme for sheep hemoglobins. The numerous evolutionarily effective amino acid substitutions seen in ruminant hemoglobins as compared to other species are accentuated by this comparison within the genus Equus.
MitraClip for severe symptomatic mitral regurgitation in patients at high surgical risk: a comprehensive systematic review.

1 Background The optimal treatment of patients with severe mitral regurgitation (MR) at high surgical risk (HSR) is unknown. Recently, the EVEREST II (Endovascular Valve Edge-to-Edge Repair) High Risk Study suggested MitraClip (MC) was a safe and effective treatment option. 2 Methods We performed a search strategy for MC or mitral valve surgery (MVS) in patients at HSR for surgical mortality (logistic EuroSCORE >18 or STS score > 10) using Medline databases, proceedings of international meetings, and the STS database. We identified 21 studies utilizing MC (n = 3,198) and MVS (n = 3,265, >90% from the STS database) from 2003 to 2013. Information about patient characteristics, surgical risk, and 30-day and 1-year outcomes were extracted. 3 Results Patients who underwent MC or MVS had a mean age of 74 ± 10 years with no differences in surgical risk, NYHA class, or MR grade (P = 0.46). Technical success was achieved in 96% of patients undergoing MC versus 98% in the MVS group (P = 0.45). Patients undergoing MC were treated with one or two MC in 90% (n = 2,878) with only a few requiring repeat MC (0.4%, n = 13) or mitral surgery (0.3%, n = 52) at 30 days. The pooled event rates for mortality was 3.2% (95% CI [2.5–4.2]), stroke was 1.1% (95% CI [0.7–0.2]) at 30 days. At 31 days to 1 year, the pooled event rate for mortality was 13.0% [95% CI (9–18.3)], stroke was 1.6% [95% CI (0.8–3.2)], and repeat MVS was 1.3% [95% CI (0.7–2.6)] with the majority of patients in the mild/moderate MR grade and NYHA class after MC. The 30-day event rates for mortality and stroke were 16.8% (95% CI [14–19]) and 4.5% (95% CI [3.9–5.3]) after MVS, respectively. 4 Conclusion Based on high risk MC studies and high risk MVS data predominantly from STS database, patients with severe MR who are at HSR can be effectively treated with MC or MVS. MC can be safely implanted in high risk patients with relatively low mortality and stroke risk. © 2014 Wiley Periodicals, Inc.
The influence of multiple firing events on the formation and stability of activity patterns in continuous attractor networks

Continuous attractor networks have been proposed to explain a variety of phenomena, including working memory and rodent entorhinal grid cells [1,2]. Typically, such networks consist of spatially-structured lattices of neurons in one or two dimensions with long-range inhibition and short-range excitation, which causes the network activity to spontaneously self-organize into one or more "bumps" of persistent activity. In two-dimensions, the activity patterns often take the form of triangular lattices, which bear a striking resemblance to the spatial patterns observed in recordings of entorhinal grid cells [3]. Rate-based neural field models of attractor networks predict the emergence of stable, stationary patterns [2,4], whereas simulations of integrate and fire neurons suggest a more complicated dynamical picture. In particular, synaptic timescales appear to play a crucial role [5,6] in that fast synapses tend to lead to transient, local synchronous activity, thus destabilizing activity patterns. Recent work on a model of V1 suggests that such "multiple firing events" (MFEs) may be a generic, emergent feature of spiking networks [7]. In this work, we investigate whether and how MFEs may affect pattern stability in continuous attractor networks. While the stability of spiking neuron-based attractor networks have been studied previously [5,6], the models studied to date contain neither seperate excitatory and inhibitory populations nor a mixture of synaptic timescales (as would be expected in more realistic settings), and the effects of these features on pattern stability are not known. To investigate these questions, we have implemented continuous attractor networks in both one and two dimensions using spiking, integrate-and-fire neurons with conductance-based synapses and seperate excitatory and inhibitory populations. Through simulations, we systematically assess the effect of MFEs on the formation and stability of spatiotemporal activity patterns ("bumps" and "grids"). We also investigate the effects of multiple synaptic timescales, noise, and network heterogeneity on the stability of these patterns. An overarching goal of this work is to obtain insights into how real neural systems might maintain stable persistent activity states, such as those needed for accurately integrating sensorimotor information. Furthermore, as 2-D attractor networks have been incorporated into a number of recent grid cell models [2,8], and the stability of grid cell activity may have a significant effect on place fields [9], understanding the stability of the grid patterns formed by these networks is highly relevant to studies of the rat spatial navigation system.