cssi/SciSciGPT-SciSciNet huggingface dataset:
Combinatorial approach to cancer immunotherapy: strength in numbers

Immune-checkpoint blockade therapy with antibodies targeting CTLA-4 and PD-1 has revolutionized melanoma treatment by eliciting responses that can be remarkably durable and is now advancing to other malignancies. However, not all patients respond to immune-checkpoint inhibitors. Extensive preclinical evidence suggests that combining immune-checkpoint inhibitors with other anti-cancer treatments can greatly improve the therapeutic benefit. The first clinical success of the combinatorial approach to cancer immunotherapy was demonstrated using a dual-checkpoint blockade with CTLA-4 and PD-1 inhibitors, which resulted in accelerated FDA approval of this therapeutic regimen. In this review, we discuss the combinations of current and emerging immunotherapeutic agents in clinical and preclinical development and summarize the insights into potential mechanisms of synergistic anti-tumor activity gained from animal studies. These promising combinatorial partners for the immune-checkpoint blockade include therapeutics targeting additional inhibitory receptors of T cells, such as TIM-3, LAG-3, TIGIT, and BTLA, and agonists of T cell costimulatory receptors 4-1BB, OX40, and GITR, as well as agents that promote cancer cell recognition by the immune system, such as tumor vaccines, IDO inhibitors, and agonists of the CD40 receptor of APCs. We also review the therapeutic potential of regimens combining the immune-checkpoint blockade with therapeutic interventions that have been shown to enhance immunogenicity of cancer cells, including oncolytic viruses, RT, epigenetic therapy, and senescence-inducing therapy.
Dual effects of PACAP on guinea pig gallbladder muscle via PACAP-preferring and VIP/PACAP-preferring receptors

The aims of this study were to determine the effect and mechanism of action of pituitary adenylate cyclase-activating peptide (PACAP) on gallbladder muscle. Guinea pig gallbladder muscle strips were studied isometrically. In noncontracted muscle strips, PACAP-27 and PACAP-38 caused dose-dependent contractions, whereas vasoactive intestinal peptide (VIP) caused dose-dependent relaxation. PACAP-27 contractions were resistant to tetrodotoxin, atropine, and the substance P receptor antagonist [D-Arg1,D-Trp7,9,Leu11]substance P (Spantide) but were inhibited by the selective PACAP receptor antagonist PACAP-(6-38) and slightly increased with the VIP receptor antagonist [4-chloro-D-Phe6,Leu17]VIP. In cholecystokinin-precontracted muscle strips, both VIP and PACAP caused relaxations. This relaxant effect of PACAP-27 was inhibited by PACAP-(6-38) and [4-chloro-D-Phe6,Leu17]VIP, but not by tetrodotoxin. These studies suggest that PACAP has dual excitatory and inhibitory effects on guinea pig gallbladder muscle. The contractile effect of PACAP is a direct action on muscle through PACAP-preferring receptors. The relaxant effect of PACAP is seen in precontracted muscle strips and mediated through VIP/ PACAP-preferring receptors.
As Cultures Collide

The voices of English-language learners (ELLs) and their families and communities are often marginalized in the discourse regarding the education of linguistic-minority students. Moreover, efforts aimed at improving educational outcomes for ELLs are often rooted in a deficit perspective that views linguistically diverse students of color as inferior and undesirable. Therefore, in an effort to foreground their voices and, at the same time, to critique inaccurate assumptions regarding this community, our chapter utilizes an unorthodox methodology to ensure the inclusion of frequently silenced voices. Our approach draws from cultural sources including print media, documentary films, personal experience, family stories, and academic research. Our approach parallels the “counter-story” methodology described by Solorzano and Yosso (2002) as a “tool for exposing, analyzing, and challenging majoritarian stories” (p. 23) by centering the experiences and voices of marginalized peoples. In this chapter, we forward the subaltern voices of current and former ELL students, as well as their family and community members, with the goal of contributing to a more complex understanding of ELLs and the sociopolitical context of their education. As multicultural teacher educators, we concur with Les Back (1996) that “these muted voices must be integrated into any understanding of the contemporary politics of culture and identity” (p. 6) and, further, that today’s teachers must understand their work in relation to ELLs’ personal and collective struggles, for example, for cultural survival, educational equity, and social justice.
Accuracy and Quality of Spirometry in Primary Care Offices

Rationale: Spirometry is necessary for the optimal management of patients with respiratory disease. The quality of spirometry performed in the primary care setting has been inconsistent.Objectives: We aimed to evaluate spirometer accuracy, determine the clinical significance of inaccurate spirometers, and assess the quality of spirograms obtained in primary care offices.Methods: We tested 17 spirometers used in primary care offices with a waveform generator; accuracy and precision were assessed using American Thoracic Society criteria. The clinical significance of inaccurate instruments was determined by applying the FEV1/FVC error from an obstructed waveform to a clinical data set. Spirogram quality was determined by grading spirograms using acceptability and repeatability criteria. The relationship between the number of tests performed by a clinic and test quality was assessed.Measurements and Main Results: Only 1 of 17 spirometers met accuracy criteria, with mean errors for FVC, FEV1, and FEV1/FVC rang...
Predicted Outcome Value Theory

Predicted outcome value theory proposes a rewards–costs analysis of interpersonal relationships focused exclusively on the motivating force and effects of outcome value forecasts for potential relational futures. Originally developed as a theory of initial interaction behavior and to provide an alternative interpretation of uncertainty reduction theory phenomena, the theory has since expanded to encompass interpersonal relationships across their life span. Keywords: communication theory; computer-mediated communication; interpersonal communication; interpersonal theory; relational communication
Lack of impact of umbilical cord blood unit processing techniques on clinical outcomes in adult double cord blood transplant recipients

Abstract Background aims Despite widespread use of umbilical cord blood (UCB) transplantation and distinct practice preferences displayed by individual UCB banks and transplant centers, little information exists on how processing variations affect patient outcomes. Methods We reviewed 133 adult double UCB transplants performed at a single center: 98 after reduced-intensity and 35 after myeloablative conditioning. Processing associated with contributing UCB banks and units was surveyed to identify differences in practice. We analyzed effect of selected variables on clinical outcomes of engraftment, dominance, transplant-related mortality, and survival. Results Eighty-eight percent of banks queried currently practice red blood cell (RBC) depletion before cryopreservation. This reflects a shift in practice because previously 65% of banks employed RBC-replete processing methods (i.e., cryopreservation or plasma/volume reduction). Neither neutrophil nor platelet engraftment was affected by processing conditions analyzed. RBC depletion was not associated with clinical outcomes, except in 17 recipients of 2 RBC-replete units, where survival was better than that observed in 116 recipients of ≥1 RBC-depleted units (hazard ratio 3.26, P = 0.004). When analyzed by attributes of the dominant unit, RBC depletion, time in storage, bank years in existence, and inventory size did not affect clinical outcomes. Postthaw viability and CD34 dose were factors impacting engraftment. Notably, all RBC-replete units in this cohort were washed in dextran-human serum albumin before infusion. Discussion These findings support continued utilization of the entire existing pool of cord blood units, despite recent trends in processing, and have important implications for banking resources and UCB selection practices.
Stochastic initiation and termination of calcium-mediated triggered activity in cardiac myocytes.

Abstract Cardiac myocytes normally initiate action potentials in response to a current stimulus that depolarizes the membrane above an excitation threshold. Aberrant excitation can also occur due to spontaneous calcium (Ca2+) release (SCR) from intracellular stores after the end of a preceding action potential. SCR drives the Na+/Ca2+ exchange current inducing a “delayed afterdepolarization” that can in turn trigger an action potential if the excitation threshold is reached. This “triggered activity” is known to cause arrhythmias, but how it is initiated and terminated is not understood. Using computer simulations of a ventricular myocyte model, we show that initiation and termination are inherently random events. We determine the probability of those events from statistical measurements of the number of beats before initiation and before termination, respectively, which follow geometric distributions. Moreover, we elucidate the origin of randomness by a statistical analysis of SCR events, which do not follow a Poisson process observed in other eukaryotic cells. Due to synchronization of Ca2+ releases during the action potential upstroke, waiting times of SCR events after the upstroke are narrowly distributed, whereas SCR amplitudes follow a broad normal distribution with a width determined by fluctuations in the number of independent Ca2+ wave foci. This distribution enables us to compute the probabilities of initiation and termination of bursts of triggered activity that are maintained by a positive feedback between the action potential upstroke and SCR. Our results establish a theoretical framework for interpreting complex and varied manifestations of triggered activity relevant to cardiac arrhythmias.
Effectiveness of an Extended Yoga Treatment for Women with Chronic Posttraumatic Stress Disorder

Abstract Background: Yoga has been found to be an effective posttraumatic stress disorder (PTSD) treatment for a variety of trauma survivors, including females with chronic PTSD. Aim/Purpose: The current study builds on extant research by examining an extended trauma-sensitive yoga treatment for women with chronic PTSD. The study sought to optimize the results of a treatment protocol examined in a recent randomized controlled trial with a shorter duration and without assignment or monitoring of home practice. Materials and Methods: The authors examined a 20-week trauma-sensitive yoga treatment in a non-randomized single-group treatment feasibility study for women with chronic treatment-resistant PTSD (N = 9). The authors examined PTSD and dissociation symptom reduction over several assessment periods. Results: The results indicate that participants experienced significant reductions in PTSD and dissociative symptomatology above and beyond similar treatments of a shorter duration. Conclusions: The findings...
Impact of aggressive fin width scaling on FinFET device characteristics

Fin width scaling is required to improve FinFET electrostatics for future technology nodes. This paper studies the benefits, trade-offs and limitations of aggressive fin width (W) scaling on logic and SRAM device characteristics. TCAD analysis is used to understand the impact of gate length (Lg)scaling along with fin width scaling to optimize AC performance. In this paper, W was scaled from 8nm to 1.6nm. It was found that there is a critical fin width (Wc)at ∼4nm. In the W>Wc region, due to better electrostatics from narrower fin, drain-induced barrier lowering (DIBL), DC performance and SRAM Vt mismatch (Vtmm) were improved. As W was scaled down further to W c ∼ 4nm.
Data-driven optimization of railway maintenance for track geometry

Abstract Railway big data technologies are transforming the existing track inspection and maintenance policy deployed for railroads in North America. This paper develops a data-driven condition-based policy for the inspection and maintenance of track geometry. Both preventive maintenance and spot corrective maintenance are taken into account in the investigation of a 33-month inspection dataset that contains a variety of geometry measurements for every foot of track. First, this study separates the data based on the time interval of the inspection run, calculates the aggregate track quality index (TQI) for each track section, and predicts the track spot geo-defect occurrence probability using random forests. Then, a Markov chain is built to model aggregated track deterioration, and the spot geo-defects are modeled by a Bernoulli process. Finally, a Markov decision process (MDP) is developed for track maintenance decision making, and it is optimized by using a value iteration algorithm. Compared with the existing maintenance policy using Markov chain Monte Carlo (MCMC) simulation, the maintenance policy developed in this paper results in an approximately 10% savings in the total maintenance costs for every 1 mile of track.
Biophysical AV Data Transfer

The subject of perception has long been an area of sharp controversy among psychologists and biophysicists. The current diversity of these views is exhibited with dramatic force in English and foreign language research reports. Most of these papers have some common area of agreement, but one is more impressed by their differences which reflect a set of contrasting assumptions within the common field of investigation. This holds true especially in the biophysical field: in a sense, it holds the key to effective audiovisual instructional technique, as distinguished from other instructional methods in general. Unfortunately, as it stands, the increased AV-type research activities supported in the past several years both by major educational foundations and by the Federal Government-especially under the provisions of Title VII of the National Defense Education Act-include no elaborate studies on the instrumentation philosophy and application of biophysical-type systems to audiovisual use. Instead, due to a lack of something better, responsible personnel continue to wring out the semifixed possibilities of antiquated machines and Gestalt-type psychological concepts. It is in this connection that this paper-which, however, is not intended to be completely definitive or inclusive
Global Governance: From Organizations to Networks or Not?

During the second half of the nineteenth century, activists concerned with the expansionist tendencies of industrial capitalism planted the first seeds of what we now call “global governance” by convincing national governments to hold conferences that led to an ever-expanding universe of international organizations. Around the same time, scientists and engineers invented the processes of “voluntary consensus standard setting” (VCSS) that have long been used to set industrial standards and, more recently, to establish standards for social and environmental integrity that are monitored by another constellation of new organizations. Both parts of this system were built on Western models. Today, when many of the most vital centers of industrial growth are in Asia, some observers believe that this “Western” focus on rules and formal organizations should be supplemented or replaced by an “Asian” system of less-formal networks that will produce and monitor pragmatic, ad hoc agreements (see the summary of scholarly, policy-maker, and activist views in Mahbubani and Chesterman 2010).
Plants and somatic embryos in space: what have we learned?

Space provides a unique environment that can affect the interplay between cell cycle controls and environment and can thus modify the processes of cell division, development and growth. It is proposed that the chromosomal and nuclear abnormalities frequently encountered in cells of various plants exposed to space are due to a combination of factors including the biological status of the systems and the way in which they are grown, exposed to, and ultimately, the way in which they experience multiple stresses. The extent to which space-specific changes become manifest is dependent on the extent of pre-existing stresses in the system. This has become evident in a variety of plant species grown in space but has been particularly amenable to study using in vitro systems, especially in developing embryoids. The following observations allow us to harmonize disparate results from a variety of space experiments:- (a) the more completely developed a system, the less likely it is to show cell stress during growth; the less morphologically complex, the greater the vulnerability; (b) the size/"packaging" of the genome (karyotype) are significant experimental variables; plants with larger genomes (e.g. polyploids) seem to be more space-stress tolerant; (c) a single space-associated stress is inadequate to produce a significant adverse response unless the stress is severe, or a biological parameter necessary to 'amplify' it exists. On this view, an appropriate "stress match" with other non-equilibrium determinants, much like a 'tug of war', can result in genomic variations in space. All this emphasizes that fastidiously-controlled growing environments must be devised if one is to resolve the matter of direct versus indirect effects of space. Better understanding of the novel physico-chemical equilibrium phenomena associated with space will allow those interested in space cell and developmental biology to pick and choose procedures best suited to their exploitation for specific objectives.
Colonialization and One-Party Rule to Civil War and “Conflict Diamonds”

This chapter provides an in-depth analysis of Sierra Leone, from a British rule and a one-party state until the outbreak of civil war in the early 1990s. Beevers focuses on the country’s history and the political, economic and social landscape that formed the modern state, which is deeply intertwined with natural resources, most prominently including diamonds. The chapter describes the Sierra Leonean civil war and documents the emergence of natural resources, and most prominently, the so-called conflict diamonds, as leading causes of the conflict.
Discrepancies in Kappa Opioid Agonist Binding Revealed through PET Imaging.

Kappa opioid receptor (KOR) modulation has been pursued in many conceptual frameworks for the treatment of human pain, depression, and anxiety. As such, several imaging tools have been developed to characterize the density of KORs in the human brain and its occupancy by exogenous drug-like compounds. While exploring the pharmacology of KOR tool compounds using positron emission tomography (PET), we observed discrepancies in the apparent competition binding as measured by changes in binding potential (BPND, binding potential with respect to non-displaceable uptake). This prompted us to systematically look at the relationships between baseline BPND maps for three common KOR PET radioligands, the antagonists [11C]LY2795050 and [11C]LY2459989, and the agonist [11C]GR103545. We then measured changes in BPND using kappa antagonists (naloxone, naltrexone, LY2795050, JDTic, nor-BNI), and found BPND was affected similarly between [11C]GR103545 and [11C]LY2459989. Longitudinal PET studies with nor-BNI and JDTic wer...
Comparison of time- and angular-domain scatter rejection in mesoscopic optical projection tomography: a simulation study.

Optical imaging offers exquisite sensitivity and resolution for assessing biological tissue in microscopy applications; however, for samples that are greater than a few hundred microns in thickness (such as whole tissue biopsies), spatial resolution is substantially limited by the effects of light scattering. To improve resolution, time- and angular-domain methods have been developed to reject detection of highly scattered light. This work utilizes a modified version of a commonly used Monte Carlo light propagation software package (MCML) to present the first comparison of time- and angular-domain improvements in spatial resolution with respect to varying sample thickness and optical properties (absorption and scattering). Specific comparisons were made at various tissue thicknesses (1-6 mm) assuming either typical (average) soft tissue scattering properties, μs ' = 10 cm-1, or low scattering properties, μs ' = 3.4 cm-1, as measured in lymph nodes.
THEOPHYLLINE INDUCED CHANGES OF RESPIRATORY CHAIN FUNCTION IN RABBIT PAPILLARY MUSCLE

In addition to its contractile role, Ca ++ may also serve as an important messenger in coordinating the rate of substrate catabolism and mechanical energy expenditure. The sources/pools usually considered to play a dominate role in providing contractile Ca ++ are the slow inward current, sarcolemmal Na + –Ca ++ exchange, and the sarcoplasmic reticulum. Data from previous studies indicate that the slow inward current may augment the Ca ++ associated with coordinating the rate of catabolism with mechanical power and that Na + – Ca ++ - exchange does not appreciably contribute. This chapter presents the results of studies in which theophylline (THEO) was used to affect mobilization of sarcoplasmic reticulum Ca ++ . The data show that THEO significantly increases the sensitivity of the major catabolic pathways to changes in contractile power. The effect of this change was to greatly decrease the extent of oxidation of the respiratory chain (RC) accompanying an increase in power expenditure or, especially with glucose, actually produce a reduction. In the study, experiments were performed on isometrically mounted rabbit papillary muscles immersed in Ringer solution. The redox state of the RC was noninvasively monitored by measuring the mitochondrial pyridine nucleotide (PN) fluorescence. As is evident, the presence of THEO reduced the developed tension and significantly decreased the extent of P MX . With 10 mM THEO, P MX was negative indicating that a reduction of PN and the RC accompanied the onset of contractile activity. The cumulative results show that THEO marginally affects mechanical performance. At 5 and 10 mM THEO, the extent of PN oxidation accompanying an increase in contractile performance was significantly decreased particularly with glucose or butyric acid as the substrate.
Palatability of beef strip loin steaks representing various marbling and maturity levels from grain-fed beef.

This study compared palatability traits of beef strip loin steaks with varying marbling scores from young and mature grain-fed beef. Strip loins (n = 150) were selected from grain fed cattle representing ten treatments with the following USDA marbling scores: Slightly Abundant or greater (SLAB+), Moderate or Modest (MD/MT), Small (SM), Slight (SL), and Traces or Practically Devoid (TR/PD) from young “A” maturity carcasses (Y) and mature “C” or greater maturity carcasses (M). Subprimals were fabricated into 2.5-cm steaks at 21 d postmortem and stored frozen until further analysis. Consumer (n = 120) sensory panelists evaluated cooked steaks for tenderness, juiciness, flavor liking, and overall liking. Trained panelists (n = 15 sessions) evaluated each sample for initial and sustained juiciness, initial and sustained tenderness, flavor intensity, and off-flavor intensity. For all traits, consumer and trained panelists’ scores generally decreased with decreasing marbling score, regardless of maturity. According to consumers, maturity had no effect on juiciness or flavor liking within each marbling score, except flavor liking of SLAB+ was greater (P < 0.05) for young than mature carcasses. Conversely, young carcasses had greater tenderness scores than mature within all marbling categories except SM, which translated to greater overall liking of MD/MT, SL, and TR/PD of young compared to their mature counterparts (P < 0.05). Trained panelists detected very few differences between young and mature samples within their respective marbling score; however, M-MD/MT had lower initial and sustained tenderness coupled with greater off-flavor intensity than Y-MD/MT (P < 0.05). Mature samples with SLAB+ and MD/MT marbling were rated greater than or equal to Y-SM for all traits, indicating the presence of marbling from feeding a grain diet prior to harvest may elicit a similar eating experience to young beef by offsetting negative palatability traits often associated with mature beef.
Accessible by Design: An Opportunity for Virtual Reality

Too often, the accessibility of technology to people with disabilities is an afterthought (if it is considered at all); post-hoc or third-party patches to accessibility, while better than no solution, are less optimal than interface designs that consider ability-based concerns from the start [31]. Virtual Reality (VR) technologies are at a crucial point of near-maturity, with emerging, but not yet widespread, commercialization; as such, VR technologies have an opportunity to integrate accessibility as a fundamental, developing cross-industry standards and guidelines to ensure high-quality, inclusive experiences that could revolutionize the power and reach of this medium. In this position paper, we discuss the needs, opportunities, and challenges of creating accessible VR.
A retrospective chart review of outcomes resulting from a three-day tramadol taper for acute opioid withdrawal.

AbstractThe purpose of the study was to describe patient outcomes with a 3-day tramadol taper for acute opioid withdrawal on the detoxification unit at Summa Health System. The primary endpoint was...
Antibacterial activity of varying UMF-graded Manuka honeys.

Honey has been used as a traditional remedy for skin and soft tissue infections due to its ability to promote wound healing. Manuka honey is recognized for its unusually abundant content of the antibacterial compound, methylglyoxal (MGO). The Unique Manuka Factor (UMF) grading system reflects the MGO concentration in Manuka honey sold commercially. Our objective was to observe if UMF values correlated with the antibacterial activity of Manuka honey against a variety of pathogens purchased over the counter. The antibacterial effect of Manuka honey with UMF values of 5+, 10+, and 15+ from the same manufacturer was assessed by the broth microdilution method. Minimum inhibitory concentration (MIC) values were determined against 128 isolates from wound cultures representing gram-positive, gram-negative, drug-susceptible, and multi-drug resistant (MDR) organisms. Lower MICs were observed with UMF 5+ honey for staphylococci (n = 73, including 25 methicillin-resistant S. aureus) and Pseudomonas aeruginosa (n = 22, including 10 MDR) compared to UMF 10+ honey (p<0.05) and with UMF 10+ compared to UMF 15+ (p = 0.01). For Enterobacteriaceae (n = 33, including 14 MDR), MIC values were significantly lower for UMF 5+ or UMF 10+ compared to UMF 15+ honey (p<0.01). MIC50 for UMF 5+, UMF 10+, and UMF 15+ honey against staphylococci was 6%, 7%, and 15%, and for Enterobacteriaceae was 21%, 21%, and 27%, respectively. For Pseudomonas aeruginosa MIC50 was 21% and MIC90 was 21–27% for all UMFs. Manuka honey exhibited antimicrobial activity against a spectrum of organisms including those with multi-drug resistance, with more potent activity overall against gram-positive than gram-negative bacteria. Manuka honey with lower UMF values, in our limited sampling, paradoxically demonstrated increased antimicrobial activity among the limited samples tested, presumably due to changes in MGO content of honey over time. The UMF value by itself may not be a reliable indicator of antibacterial effect.
Basic Principles of Safe Laparoscopic Cholecystectomy

Careful dissection and accurate decision-making is the key to performing a safe laparoscopic cholecystectomy. The focus of this chapter is to describe standard safety maneuvers in order to achieve the goals of this operation. Careful patient selection, appropriate timing of the operation, and adherence to safe principles, namely, achieving all three aspects of the critical view of safety (CVS) and recognizing triggers for a “safety pause,” are paramount to preventing vascular or biliary injuries.
Geotechnical properties of calcareous rocks of southern Florida

This paper presents the geotechnical properties of young calcareous rocks of southern Florida. The rocks covered are Miami, Key Largo, and Fort Thompson limestones. The paper briefly details the formation and areal extentof the rocks and then evaluates several samplers for obtaining maximum recovery in a relatively undisturbed form. Evaluation of the properties is based on field and laboratory tests. The field tests included seismic refraction studies, downhole and crosshole wave velocity studies, and Menard Pressuremeter tests. The laboratory tests comprised index tests and strength and deformation evaluation tests. In addition to the usual unconfined compression tests, this investigation reports the results of the K o -triaxial tests on the rock specimens. The range of values for porosity, compressive strength, and modulus from various tests is presented. The discusion provides a rationale for the difference in values obtained from the tests. The suitability of various tests in providing a representative mechanical behavior is discussed.
Histone H3 K4/9/27 Trimethylation Levels Affect Wound Healing and Stem Cell Dynamics in Adult Skin

Epigenetic mechanisms controlling adult mammalian stem cell (SC) dynamics might be critical for tissue regeneration but are poorly understood. Mouse skin and hair follicle SCs (HFSCs) display reduced histone H3 K4me3, K9me3, and K27me3 methylation levels (hypomethylation) preceding hair growth. Chemical inhibition of relevant histone demethylases impairs subsequent differentiation and growth of HFs and delays wound healing. In wounding, this impairs epithelial cell differentiation and blood vessel recruitment, but not proliferation and fibroblast recruitment. With Aspm-CreER as a newfound inter-follicular epidermis lineage-labeling tool, and Lgr5-CreER for hair follicles, we demonstrate a reduced contribution of both lineages to wound healing after interfering with hypomethylation. Blocked hypomethylation increases BMP4 expression and selectively upregulates H3 K4me3 on the Bmp4 promoter, which may explain the effects on HFSC quiescence, hair cycle, and injury repair. Thus, transient hypomethylation of histone H3 K4/9/27me3 is essential for adult skin epithelial SC dynamics for proper tissue homeostasis and repair.
An Overview of Social and Behavioral Determinants of STI

Sexually transmitted infections (STI), including human immunodeficiency virus (HIV), remain an important source of morbidity and mortality in the 21st century, with estimates of global burden running to approximately 1 million cases a day as of 2012. Prevention of STI and HIV therefore remains critical to global health; however, understanding of the determinants of STI is a necessary prerequisite. In this chapter, we focus on interlinked categories of behavioral and social determinants of STI. Sexual behaviors and practices are proximate causes of STI acquisition and transmission, and other individual-level behaviors also contribute to risk. Social determinants provide the essential context for behaviors and can either facilitate or hinder the effects of individual behaviors.
Progressive glomerulosclerosis develops in transgenic mice chronically expressing growth hormone and growth hormone releasing factor but not in those expressing insulinlike growth factor-1

An increase in glomerular size occurs in normal maturation after subtotal renal ablation and disease states such as diabetes mellitus. The role that growth hormone (GH), growth hormone releasing factor (GHRF), and insulinlike growth factor-1 (IGF-1) play in these processes has been investigated using transgenic mice chronically expressing these hormones. The glomeruli were enlarged in all 3 strains of mice. Mesangial proliferation followed by progressive glomerulosclerosis was observed in the GH and GHRF animals only. In the IGF-1 mice the large glomeruli remained morphologically normal except for the enlargement. These data suggest that the glomerulosclerosis was due, in part, to disordered mesangial cell growth in response to circulating GH. The mesangial lesions in mice with chronically high plasma GH levels mimicked those in human diabetes mellitus. These models provide a means to study the hormonal regulation of glomerular growth and the role that specific hormones might play in the pathogenesis of glomerulosclerosis.
Web-based authentic inquiry experiences in large introductory classes consistently associated with significant learning gains for all students

Continuous calls for reform in science education emphasize the need to provide science experiences in lower-division courses to improve the retention of STEM majors and to develop science literacy and STEM skills for all students. Open or authentic inquiry and undergraduate research are effective science experiences leading to multiple gains in student learning and development. Most inquiry-based learning activities, however, are implemented in laboratory classes and the majority of them are guided inquiries. Although course-based undergraduate research experiences have significantly expanded the reach of the traditional apprentice approach, it is still challenging to provide research experiences to nonmajors and in large introductory courses. We examined student learning through a web-based authentic inquiry project implemented in a high-enrollment introductory ecology course for over a decade. Results from 10 years of student self-assessment of learning showed that the authentic inquiry experiences were consistently associated with significant gains in self-perception of interest and understanding and skills of the scientific process for all students—both majors and nonmajors, both lower- and upper-division students, both women and men, and both URM and non-URM students. Student performance in evaluating the quality of an inquiry report, before and after the inquiry project, also showed significant learning gains for all students. The authentic inquiry experiences proved highly effective for lower-division students, nonmajors, and women and URM students, whose learning gains were similar to or greater than those of their counterparts. The authentic inquiry experiences were particularly helpful to students who were less prepared with regard to the ability to evaluate a scientific report and narrowed the performance gap. These findings suggest that authentic inquiry experiences can serve as an effective approach for engaging students in high-enrollment, introductory science courses. They can facilitate development of science literacy and STEM skills of all students, skills that are critical to students’ personal and professional success and to informed engagement in civic life.
Regulation of Hepatitis B Virus Virion Release and Envelopment Timing by Nucleocapsid and Envelope Interactions.

Interactions between the N-terminal (assembly) domain (NTD) and the linker region of the hepatitis B virus (HBV) capsid protein and the large (L) envelope protein are required for virion formation, which occurs via budding of cytoplasmic mature nucleocapsids (NCs) containing the relaxed circular (RC) DNA genome into an intracellular membrane compartment containing viral envelope proteins. L-capsid interactions also negatively regulates covalently closed circular (CCC) DNA formation, which occurs after RC DNA release from mature NCs and nuclear import. We have now found that L could increase RC DNA in cytoplasmic mature NCs that are destabilized due to mutations in the NTD or the linker, even in those that apparently fail to support secretion of complete virions extracellularly. Other mutations in the capsid linker could block the effects of L on both cytoplasmic NC DNA and nuclear CCC DNA. Furthermore, the maturity of RC DNA in cytoplasmic NCs that was enhanced by L or found in secreted virions was modulated by the capsid linker sequence. The level and maturity of the cytoplasmic RC DNA was further influenced by the efficiency of extracellular virion secretion dependent on viral genotype-specific envelope proteins. These results suggest that interactions between the capsid and envelope proteins regulate one or more steps during virion secretion beyond initial capsid envelopment, and highlights the critical role of the capsid linker in regulating capsid-envelope interaction, including the timing of envelopment during NC maturation. Importance Hepatitis B virus (HBV) is a major human pathogen causing serious liver diseases including cancer. The interactions between the HBV capsid and the large (L) envelope protein is required for formation of infectious viral particles and also negatively regulate formation of an HBV DNA episome in the host cell nucleus, which serves as the sole transcriptional template capable of supporting all viral gene expression to sustain HBV replication and therefore, is the molecular basis of HBV persistence. Here, we report evidence indicating that L-capsid interactions modulate the timing of formation of infectious HBV particles during replication and facilitate extracellular release following their formation. Furthermore, a short linker sequence in the capsid protein plays a critical role in these processes as well as controls the amplification of the nuclear episome. These findings inform fundamental mechanisms of HBV replication as well as antiviral development targeting the HBV capsid and DNA episome.
Quantifying the Connectivity of the Language-Specific Cerebrocebellar Network (LSCN)

Language was arguably a key influence in the evolution of the human brain and the evolution of this behavior in humans was likely associated with gross morphological changes and novel neural networ...
Reducing the Overhead of Dynamic Analysis

Abstract Dynamic analysis (instrumenting programs with code to detect and preven errors during program execution) can be an effective approach to debugging, as well as an effective means to prevent harm being caused by malicious code. One problem with this approach is the runtime overhead introduced by the instrumentation. We define several techniques that involve using the results of static analysis to identify some cases where instrumentation can safely be removed. While we have designed the techniques with a specific dynamic analysis in mind (that used by the Runtime Type-Checking tool), the ideas may be of more general applicability.
Ryan and Jeanne White

(2005). Ryan and Jeanne White. Journal of HIV/AIDS & Social Services: Vol. 3, No. 3, pp. 105-112.
In What Sense is the Energy Spectrum a Universal Property of Extreme Energy Cosmic Rays

I examine the question, whether at highest energies the cosmic ray energy spectrum may be ‘universall, as the 2.7K microwave background is thought to be. If so, then the GZK cutoff will be a dominant and potentially useful feature. I argue that the present failure to observe this cutoff is explained by defects in the assumptions made by GZK and their followers, who have over-estimated the flux received from many ‘distant’ sources, compared to that from a few ‘local’ sources. I suggest a methodological approach for separating distant and local source contributions, when improved data are made available by the Pierre Auger ground observatories, and by observations from space by means of EUSO and its successor spacecraft.
Detrending daily natural gas consumption series to improve short-term forecasts

This paper presents a novel detrending algorithm that allows long-term natural gas demand signals to be used effectively to generate high quality short-term natural gas demand forecasting models. Short data sets in natural gas forecasting inadequately represent the range of consumption patterns necessary for accurate short-term forecasting. In contrast, longer data sets present a wide range of customer characteristics, but their long-term historical trends must be adjusted to resemble recent data before models can be developed. Our approach detrends historical natural gas data using domain knowledge. Forecasting models trained on data detrended using our algorithm are more accurate than models trained using nondetrended data or data detrended by benchmark methods. Forecasting accuracy improves using detrended longer-term signals, while forecast accuracy decreases using non-detrended long-term signals.
Mutants of Escherichia coli Defective in Membrane Phospholipid Synthesis: Mapping of sn-Glycerol 3-Phosphate Acyltransferase Km Mutants

plsB mutants of Escherichia coli are sn -glycerol 3-phosphate auxotrophs which owe their requirement to a K m defect in sn -glycerol 3-phosphate acyltransferase, the first enzyme in the phospholipid biosynthetic pathway. We have located the plsB gene at minute 69 of the E. coli genetic map, far removed from the gene defined by mutants with a temperature-sensitive sn -glycerol 3-phosphate acyltransferase. The plsB gene was cotransduced with the dctA locus, and the transduction data indicated that the clockwise gene order is asd, plsB, dctA, xyl. plsB − is recessive to plsB + and all acyltransferase K m mutants tested lie very close to the plsB locus. Effective supplementation of plsB mutants was shown not to require a defective glpD gene.
Reactions of π-cyclopentadienyltriphenylphosphinemetal diiodides and π-cyclopentadienylcarbonylmetal diiodides (M = Co, Rh, Ir) with 1,4-dilithio-1,2,3,4-tetraphenylbutadiene

Abstract Reactions between π-cyclopentadienyltriphenylphosphinemetal diiodides (M = Rh and Ir) and 1,4-dilithio-l,2,3,4-tetraphenylbutadiene result in the formation of 1-(π-cyclopentadienyl)-l-triphenylphosphine-2,3,4,5-tetraphenylrhodole and 1-(π-cyclopentadienyl)-1-triphenylphosphine-2,3,4,5-tetraphenyliridole, respectively, in low yield. Reactions between π-cyclopentadienyltriphenylphosphinecobalt diiodide or π-cyclopentadienylcarbonylcobalt diiodide do not produce the expected cobaltacyclopentadiene complexes, but instead a low yield of π-cyclopentadienyl-(π-tetraphenylcyclobutadiene)cobalt. The trimeric rhodium complex (π-C 5 H 5 Rh) 3 (CO)(PhCCPh) has been isolated from a reaction between 1,4-dilithio-l,2,3,4-tetraphenylbutadiene and π-cyclopentadienylcarbonylrhodium diiodide. The importance of metallocyclic intermediates in the formation of polynuclear complexes of this type is discussed.
An analysis of cavity nucleation in superplasticity

Superplastic alloys possess either a quasi-single phase or a microduplex microstructure: in quasi-single phase alloys, cavities are observed to nucleate predominantly at coarse grain boundary particles whereas in microduplex alloys, cavities tend to form at interphase boundaries and at triple point junctions. A general analysis is presented for cavity nucleation, in both microstructures, under the stress concentrations caused by bursts of grain boundary sliding during superplastic deformation. In quasi-single phase alloys, calculations indicate the cavities nucleate at coarse particles located at grain boundaries because local interphase diffusion creep cannot accommodate the stress concentrations sufficiently rapidly. The analysis demonstrates that it is possible for cavities to nucleate at grain boundary ledges under some limited experimental conditions. It is demonstrated also that the present analysis is in agreement with the available experimental data on a quasi-single phase Cu-based superplastic alloy and a microduplex superplastic Zn-22% Al eutectoid alloy. Calculations show that small pre-existing cavities, if present, are likely to be sintered rapidly prior to superplastic deformation at elevated temperatures.
THE GENETIC BASIS OF MALE POTENCY IN VOLVOX CARTERI F. NAGARIENSIS (CHLOROPHYCEAE)1,2

SUMMARY Sexual males of Volvox carteri Stein f. nagariensis Iyengar secrete a hormone which induces sexual rather than asexual development in the next generation. Male recombinants from the original strains isolated from Japan showed an increase in potency of up to 100 times that of the original male clone, with later descendants showing potencies ranging from 100 times to 1/1000 the potency of this male. Potency is defined as the extent to which the hormone produced in 1 ml of medium by one parental spheroid containing 16 male spheroids can be diluted and retain its capacity to induce sexual differentiation. This is recorded as the percent of female response in the tube of limiting dilution, asexual females of the normal female strain being used as assay inoculum in a 1 in 10 dilution series of samples of male fluid containing the sexual hormone. Investigation of the genetic basis for potency in this species included selection of high and low potency male clones and crossing with sib females or backcrossing with original female. Results of the various crosses are interpreted as multigenic system not linked with sex, with more than one genotypic class per dilution level and with more than one genotypic class per apparent phenotypic class. Possible genic interactions are described in their relevance to the biosynthesis of a glycoprotein molecule, the sexual hormone having been characterized as a glycoprotein by Starr and Jaenicke (18).
A low-voltage and temperature compensated ring VCO design

A low-voltage, two-stage ring voltage-controlled oscillator (VCO) which can tolerate temperature variation is presented in this paper. Designed using a 0.13 μm CMOS technology, this VCO is capable of operating at 1-V power supply voltage not only for low power consumption, but also to reduce hot-carrier effects and improve reliability and lifetime. It incorporates coarse and fine frequency tuning mainly for tolerance of process variations while achieving small control-voltage-to-frequency gain and enough tuning range of the VCO. Most importantly, a new temperature compensation technique which is suitable for low power supply voltage design is proposed to enable continuous operation of the VCO in variable ambient temperatures environment. Simulations show that with the proposed techniques, the VCO can tolerate process variations, dynamically adapt to different temperatures, and achieve a low temperature sensitivity of 34 ppm/°C over the range from −40°C to 120 °C.
The female X-inactivation mosaic in systemic lupus erythematosus

Abstract Most sufferers of systemic lupus erythematosus (SLE) are female. While hormones are generally thought responsible, gender differences extend far beyond the hormonal level. These differences may be particularly important for the immune system. The sexes present radically different self-antigen profiles to the immune system because females are X-chromosome-inactivation mosaics. Here, Jeff Stewart argues that it is this mosaicism that induces SLE.
Pharmacologic management of ischemic heart disease with β-blockers and calcium channel blockers

In myocardial ischemia beta-blockers reduce myocardial oxygen demand, improve flow toward ischemic regions, and have mild antiplatelet and antiarrhythmic effects. These agents are effective in chronic stable angina and unstable angina. In chronic myocardial ischemia, the beta-blockers timolol, metoprolol, atenolol, and propranolol have cardioprotective effects, reducing overall mortality and the incidence of recurrent myocardial infarction. Calcium channel blockers, which reduce myocardial oxygen demand and improve oxygen supply, are effective in the treatment of chronic stable angina, vasospastic angina, and unstable angina. Although calcium channel blockers generally have no effect or adverse effects when used as primary therapy for acute myocardial infarction, diltiazem (when used concomitantly with nitrates or beta-blockers) has been shown to reduce the incidence of reinfarction in patients after non-Q wave myocardial infarction.