cssi/SciSciGPT-SciSciNet huggingface dataset:
T Cell Modulation Combined with Intratumoral CpG Cures Lymphoma without the Need for Chemotherapy.

Introduction: We have previously shown that intratumoral injection of CpG oligodeoxynucleotide plus systemic chemotherapy can induce T cell immunity against lymphoma and serve as a therapeutic vaccine to cure tumors in a murine lymphoma model (Li et al., J Immunol. 2007). CpG is a Toll-like receptor 9 agonist capable of activating tumor-infiltrating dendritic cells and/or tumor B cells to force tumor antigen presentation in situ when injected intratumorally. Here, we demonstrate that antibody-mediated modulation of T cells enhances the efficacy of CpG vaccination, thereby eliminating the need for chemotherapy. Materials and Methods: Mice were inoculated s.c. with A20 lymphoma tumor cells at two sites (right and left abdomen). Only one site was injected with CpG allowing us to evaluate the systemic anti-tumor response at the distant site. Treatment started when tumors became palpable. CpG was administered intratumorally. T cell modulation was accomplished using systemic (i.p.) administration of monoclonal antibodies against T cell targets: - Regulatory T cells were depleted using anti-Folate Receptor 4 (FR4) antibody or functionally blocked using anti-GITR antibody, - Effector T cells were stimulated using anti-OX40 antibody (to trigger their costimulatory molecule) or anti-CTLA4 antibody (to block inhibitory signals). Results: Treatment with intratumoral injection of CpG alone did not cure any mice. Treatment with CpG and a single antibody (anti-OX40, anti-CTLA4, anti-FR4, or anti-GITR) cured 20–30% of mice. Interestingly, some combinations of antibodies (anti-OX40+anti-CTLA4, anti-OX40+anti-FR4, anti-CTLA4+anti-GITR) potentiated T cell modulation and further enhanced the efficacy of CpG vaccination. In particular, the combination of anti-OX40 and anti-CTLA4 appeared to be especially potent when combined with intratumoral CpG. Indeed, this combination (CpG+anti-OX40+anti-CTLA4) induced anti-tumor T cells capable of secreting IFN-γ in response to overnight culture with A20 tumor cells; it cured more than 80% of mice bearing large and systemic lymphoma tumors without the need for chemotherapy (effective therapy required both CD4 and CD8 T cells); finally, this therapy produced high numbers of anti-tumor memory T cells and provided long-lasting immunity against tumor re-challenge. Conclusions: Our results show that antibody-mediated T cell modulation greatly enhances the therapeutic efficacy of intratumoral vaccination with CpG. Importantly, we show that T cell modulation can be potentiated by appropriate combinations of antibodies against T cell targets. As these reagents (CpG, anti-OX40 and anti-CTLA4 notably) are becoming available for human clinical trials, the combination of intratumoral CpG and immunomodulatory T cell antibodies holds promise for therapeutic vaccination against lymphoma.
The Paris Agreement and next steps in limiting global warming

The Paris Climate Agreement sets out an aggressive goal of limiting global average warming to well below 2 °C. As a first step, virtually all countries have put forth greenhouse gas emission reduction pledges in the form of nationally determined contributions, or NDCs, for the 2030 timeframe. Our analysis looks beyond the NDCs to explore potential post-2030 regional emissions reduction participation and ambition. For each scenario, we examine the implications for global emissions and long-term temperature. We then evaluate the regional consequences for energy systems and ensuing costs. We conclude by reflecting on the additional global abatement costs of tightening temperature goals. Overall, this study provides a multidimensional characterization of the scale of regional effort supporting climate outcomes, details important to decision-makers as they consider mid-century emissions targets, and long-run climate objectives.
Tensions in naturalistic, evolutionary explanations of aesthetic reception and production

Abstract Aesthetic universals may plausibly reflect biases in aesthetic reception that arose through evolutionary pressure. However, the role universals play in high-level aesthetic creativity is not well understood. After reviewing evolutionary aspects of aesthetics, some specific proposed aesthetic universals, and the nature of creativity in aesthetic domains, I examine a creative dynamic in which long-term pressure for novelty leads to inexorable tensions with canalized aesthetic biases. Examining the role of aesthetic universals in individuals’ creative processes, as well as more thorough trans -historical assessments of the development of universals, are proposed as methodological strategies for gaining traction on this issue. Such investigations have the potential to inform the role of the audience in shaping the evolution of artist styles, how universals play out in high versus low art, the possibility of identifying new aesthetic universals (perhaps particularly with conceptual art), and the relative value of novelty versus adaptive value in aesthetic creativity.
Fundamentals of Passive Circuit Analysis

This chapter analyzes the first-order passive RC and RL circuits and the second-order passive RLC circuits encountered in all Printed Circuit Boards (PCB). The general understanding of passive circuits in time and frequency domains also establishes a vital background for more complex circuits that contain active elements such as diodes and transistors.
In Vivo Imaging Reveals a Tumor-Associated Macrophage-Mediated Resistance Pathway in anti-PD-1 Therapy

Monoclonal antibodies (mAbs) targeting the immune checkpoint anti–programmed cell death protein 1 (aPD-1) have demonstrated impressive benefits for the treatment of some cancers; however, these drugs are not always effective, and we still have a limited understanding of the mechanisms that contribute to their efficacy or lack thereof. We used in vivo imaging to uncover the fate and activity of aPD-1 mAbs in real time and at subcellular resolution in mice. We show that aPD-1 mAbs effectively bind PD-1 + tumor-infiltrating CD8 + T cells at early time points after administration. However, this engagement is transient, and aPD-1 mAbs are captured within minutes from the T cell surface by PD-1 − tumor-associated macrophages. We further show that macrophage accrual of aPD-1 mAbs depends both on the drug’s Fc domain glycan and on Fcγ receptors (FcγRs) expressed by host myeloid cells and extend these findings to the human setting. Finally, we demonstrate that in vivo blockade of FcγRs before aPD-1 mAb administration substantially prolongs aPD-1 mAb binding to tumor-infiltrating CD8 + T cells and enhances immunotherapy-induced tumor regression in mice. These investigations yield insight into aPD-1 target engagement in vivo and identify specific Fc/FcγR interactions that can be modulated to improve checkpoint blockade therapy.
Arthroscopic Panlabral Repair With Remplissage of Hill-Sachs Lesion

Recurrent shoulder instability in young contact athletes has been well established. The importance of bipolar bone loss in instability has come to the forefront in terms of proper management of this condition. It remains controversial, however, which patients would be better served with an arthroscopic versus open procedure and when additional procedures may reduce the risk of failure (i.e., remplissage). We present our arthroscopic technique of a panlabral repair with concomitant remplissage using the double-pulley technique. The purpose of this article is to provide insight into obtaining superior visualization while reviewing surgical pearls and pitfalls to efficiently perform a panlabral repair and remplissage.
Chapter Twenty-Four – Case History: Kalydeco® (VX-770, Ivacaftor), a CFTR Potentiator for the Treatment of Patients with Cystic Fibrosis and the G551D-CFTR Mutation

Abstract Cystic fibrosis (CF) is caused by mutations in the CFTR gene of an epithelial ion channel, the CF transmembrane conductance regulator (CFTR). We initiated efforts to discover potentiators of mutated CFTR. Potentiators are small molecules that increase the flow of ions through activated CFTR in the cell membrane. In-house HTS campaigns led to the identification of multiple hits. Extensive medicinal chemistry efforts driven by phenotypic assays led to the discovery of VX-770 (ivacaftor). VX-770 was found to be a potent, selective, orally bioavailable potentiator of G551D -CFTR, displaying excellent pharmacokinetic and safety profiles in rodents and nonrodents. Due to poor aqueous solubility, extensive formulation efforts were required and resulted in a spray-dried dispersion of VX-770 suitable for clinical development. After successful clinical trials, ivacaftor was approved by the FDA in 2012 for the treatment of people with CF who have a G551D mutation in the CFTR gene.
Commercial Near-Earth Space Launcher: Understanding System Integration

Before there can be any space exploration, there must first be an ability to reach low Earth orbit (LEO) from Earth’s surface.
Risk factors for low high-density lipoprotein among Asian Indians in the United States.

AIM To examine the differences in metabolic risk factors (RFs) by gender in the Asian Indian (AI) population in the United States. METHODS Using cross-sectional data from 1038 randomly selected Asian Indians, we investigated the relationship between metabolic syndrome (MetS) RFs, cardiovascular disease, and diabetes. RESULTS A greater percent of women in this group had increased waist circumference and low high density lipoprotein (HDL) levels than men, but AI males had increased blood glucose, increased blood pressure, and increased triglycerides compared to females. Those individuals who met the MetS criteria had increased cardiovascular disease. One of the biggest single RFs for cardiovascular disease and diabetes reported in the literature for AIs is low HDL. CONCLUSION Our results show that lack of knowledge about diabetes, low physical activity, increased body mass index, and age were the factors most significantly correlated with low HDL in this population. Future studies and prospective trials are needed to further elucidate causes of the MetS and diabetes in AIs.
Native Language Identification using Phonetic Algorithms

In this paper, we discuss the results of the IUCL system in the NLI Shared Task 2017. For our system, we explore a variety of phonetic algorithms to generate features for Native Language Identification. These features are contrasted with one of the most successful type of features in NLI, character n-grams. We find that although phonetic features do not perform as well as character n-grams alone, they do increase overall F1 score when used together with character n-grams.
The Not-So-Marginal Value of Weather Warning Systems

AbstractKnowing the benefits of creating or expanding programs is important for determining optimal levels of investment. Yet estimates of the benefits of weather warning systems are sparse, perhaps because there is often no clear counter-factual of how individuals would have fared without a particular warning system. This paper enriches the literature and informs policy decisions by using conditional variation in the initial broadcast dates of the National Oceanic and Atmospheric Administration’s Weather Radio All Hazards (NWR) transmitters to produce both cross sectional and fixed effects estimates of the causal impact of expanding the NWR transmitter network. Results suggest that from 1970-2014, expanding NWR coverage to a previously untreated county was associated with an almost 40% reduction in injuries and as much as a 50% reduction in fatalities. The benefits associated with further expansion of this system have likely declined over time.
Sanctuaries, Solidarities, and Boundary Crossings: Empathetic Justice and Plural/Personal Peacebuilding in Fan Fiction

Fan fiction is a bridge space and allows ethical journeys that focus on issues of diversity, inclusion, and social justice in everyday life. Fan writing activities are microforms of political action. Fan writers are bringing people of color, those with disabilities, and LGBTQ characters into key roles in Panem and the wizarding world. Changing the original narrative to make it more inclusive is a peace practice, but such practices must also be investigated for how well they avoid liberal peacebuilding pitfalls including orientalism. The fan writers’ lack of concern with originality, copyright, or recognition helps make fan fiction a ‘third space’ of mixing where new ideas about peace may arise. Spaces of sanctuary and of poststructural pluralist peace(s) are shown to have been created by fans.
A systematic review of epidemiologic studies of styrene and cancer

Previous epidemiology reviews of exposure to styrene and the risk of cancer considered studies published through 13 November 2013. Since then, additional relevant research has been published. No review has included meta-analyses. The current systematic review considered research published through June 2017; included meta-analyses of the relationship between any exposure to styrene and cancers identified as being of concern, including non-Hodgkin lymphoma (NHL), leukemia and cancers of the esophagus, pancreas, lung and kidney; and evaluated several other forms of cancer. Meta-relative risks for all studies were 1.14 (95% confidence interval (CI), 0.91-1.43) for NHL, 1.00 (95% CI, 0.80-1.26) for multiple myeloma, 0.98 (95% CI, 0.87-1.09) for all leukemia, 1.03 (95% CI, 0.92-1.15) for esophageal cancer, 1.02 (95% CI, 0.93-1.12) for pancreatic cancer, 1.09 (95% CI, 0.95-1.24) for lung cancer and 1.10 (95% CI, 0.99-1.22) for kidney cancer. Individual studies provided little evidence of exposure-response or induction time trends. Limitations of the available research and of the meta-analyses included reliance in most studies on mortality data rather than on incidence data, lack of quantitative estimates of styrene exposure for individual subjects and lack of information on lifestyle factors. Consideration of all pertinent data, including substantial recent research, indicates that the epidemiologic evidence on the potential carcinogenicity of styrene is inconclusive and does not establish that styrene causes any form of cancer in humans.
Performance of a high-level copper-62 generator and remote system for [Cu-62]-Cu(PTSM) synthesis

We have now constructed Zn-62/Cu-62 generators at high activity levels (>300 mCi) and report here a remote control system for rapidly synthesizing (Cu-62)-Cu(PTSM) from the acidic generator eluent. Zinc-62 (9.26 hour half-life) can be readily obtained by the Cu-63 (p, 2n) Zn-62 nuclear reaction using a medium energy cyclotron. The Zn-62 was loaded onto a prepurified Dowex 1 x 8 (200-400 mesh) anion exchange column (4 cm x 0.7 cm diameter or 2 cm x 1.0 cm diameter) from which the Cu-62 daughter can be selectivity and efficiently eluted with 2N HCl. Over an 18-20 hour time frame after loading, generator performance was evaluated concurrently with its use to provide Cu-62 for Cu(PTSM) PET studies. Following elution of the system void volume, > 80% of available Cu-62 was obtained in 2-3 mL of eluate. Zinc-62 breakthrough was typically < 0.001% of eluted copper-62 activity. (author).
Design and Planning of Datacenter Networks

The increase in demand and sophistication of Internet and Cloud services requires providers to constantly expand the compute, storage and networking capabilities in their data centers. In this paper we outline our architecture and planning approach to build scalable datacenter networks.
ROLE OF NATURAL KILLER CYTOTOXIC FACTORS (NKCF) IN THE MECHANISM OF NK CELL MEDIATED CYTOTOXICITY

Publisher Summary This chapter examines the role of natural killer cytotoxic factors (NKCF) in the mechanism of natural killer (NK)-cell-mediated cytotoxicity. The characteristics of the effector cell, which releases NKCF during coculture with YAC-1 stimulator cells, are compared to those of the NK effector cell. Both cell types are plastic nonadherent spleen cells and are not present in thymocytes. Mutant beige mouse spleen cells show a decrease in their ability to release NKCF and in their ability to lyse NK targets in a four-hour CMC assay. The effector cell in both assays is equally sensitive to treatment with anti-asialo GM1 and complement and is not a mature T cell because nude mouse spleen cells show high activity. In a study described in the chapter, emetine treatment of effector cells neither inhibited NKCF release nor NKCMC reactions. Though interferon-pretreated spleen cells release increased levels of NKCF, this increase required protein synthesis during the pretreatment period. This is in agreement with the results that indicated that protein synthesis was required during the pretreatment period to observe interferon-induced augmentation of NK activity.
Animal cruelty and bullying: Behavioral markers of delinquency risk or causal antecedents of delinquent behavior?

Abstract Objective The purpose of this study was to determine whether animal cruelty and bullying, in addition to serving as behavioral markers of delinquency risk, may also serve as causal antecedents of future delinquent behavior. It was hypothesized that these two behaviors would predict an increase in future offending via a rise in proactive criminal thinking, as measured by moral disengagement, one of its facets, but not via a rise in reactive criminal thinking or cognitive impulsivity. Methods All 1170 male members of the Pathways to Desistance study (mean age = 16.05 years) served as participants in this study. The first three waves of data from the Pathways study were used to perform a causal mediation path analysis. Results The results of this study supported the main research hypothesis. Specifically, the indirect effects of animal cruelty and bullying on future delinquency were mediated by moral disengagement but not cognitive impulsivity. Furthermore, the difference between moral disengagement and cognitive impulsivity mediation of the animal cruelty–delinquency relationship achieved statistical significance. Conclusions Findings from this study suggest that animal cruelty and bullying not only serve as early behavioral markers of delinquency risk but also play a potentially important role in delinquency growth and persistence.
Adrenal insufficiency in neonates undergoing cardiopulmonary bypass and postoperative hypothalamic-pituitary-adrenal function after prophylactic glucocorticoids

OBJECTIVES Determine incidence of preoperative adrenal insufficiency in neonates >35 weeks gestation with congenital heart disease undergoing cardiothoracic surgery with bypass and effects of prophylactic methylprednisolone on postoperative hypothalamic-pituitary-adrenal function and hemodynamic stability. DESIGN Prospective observational study in 36 neonates with preoperative adrenocorticotrophic hormone stimulation tests and serial total cortisol and adrenocorticotrophic hormone measurements before and after surgery. Data analyses: analysis of variance and regression. RESULTS Baseline circulating adrenocorticotrophic hormone and cortisol were unchanged 4-20 days postnatal (P > 0.1); however, cortisol levels rose with increasing adrenocorticotrophic hormone, P = 0.02. Ten neonates (29%) demonstrated preoperative adrenal insufficiency (∆cortisol ≤9 µg/dl); one had postoperative hemodynamic instability. Growth-restricted neonates had lower baseline cortisol, but normal stimulation tests and responded well to surgical stresses. Seventy-five percent of neonates receiving perioperative methylprednisolone demonstrated postoperative hypothalamic-pituitary-adrenal inhibition. CONCLUSION Adrenal insufficiency appears common in neonates >35 weeks gestation with congenital heart disease, but did not contribute to postoperative hemodynamic instability despite hypothalamic-pituitary-adrenal inhibition.
The Hahn-Banach theorem

Many of the important applications of the theory of topological linear spaces concern the relations between a space ℰ and the space of continuous linear functionals on ℰ. This space is known as the conjugate space or dual space of ℰ and will be denoted by ℰ* in the sequel. (When ℰ is a normed space, ℰ* = ℒ(ℰ, ℂ) is a Banach space (Prop. 12.2); otherwise ℰ* will simply denote a vector space (Prob. 12U).)
Greek Military Service in the Ancient Near East, 401–330 BCE

This is the first monograph dedicated to the history of Greek military service for the Achaemenid Persian Empire and the Kingdom of Egypt from the rebellion of Cyrus the Younger to the conquests of Alexander the Great. Through careful analysis of the political contexts of their recruitment and detailed reconstructions of their performances as soldiers and generals on the battlefield, Jeffrey Rop overturns the traditional view that the Greeks who fought in the Near East were mercenaries hired for their superior military skills as heavily armored hoplites. The presence of unprecedented numbers of Greek infantry in the armies of Persia and Egypt is not evidence that the levies of these states were militarily inferior or deficient, but a clear sign of unprecedented foreign political influence among the most powerful leaders and cities of Greece for much of the fourth century.
Parameterization of the building downwash and sidewash effect using a mixture model

Abstract Widely used for permitting new emission sources (e.g., power plants) and assessing human exposure, atmospheric dispersion models do not perform well when the facility stack is relatively low and the pollution plume would be affected by the building wake, such as biomass boilers, diesel backup generators and residential woodstoves, which was also known as building downwash. The current building downwash preprocessor, Plume Rise Model Enhancements (PRIME), in a regulatory model, AMS/EPA Regulatory Model (AERMOD), tends to underestimate the ground-level concentrations (GLCs). Our flow visualization indicated that the flow pattern under the oblique wind was featured by a sidewash-downwash (S-D) vortex, which determines the near-wake concentration field. Thus, we introduced the concept of “sidewash” to highlight the effect of oblique wind conditions, which can cause higher GLCs than those under the perpendicular wind. We presented a new parameterization method, named the mixture model, to represent the concentration field in the downstream of a box-shape building with a short stack under different wind directions. This model was developed on the flow and concentration fields analysis using a computational fluid dynamics (CFD) technique, Embedded Large Eddy Simulation (ELES), and evaluated against experimental data. With both downwash and sidewash, the new parameterization showed promising performance for the low stack height under both perpendicular and oblique wind directions and successfully captured the lateral shifts of the plume under oblique wind directions and continuous concentration distribution along the longitudinal ground-level receptors, which could not be reflected by using the current PRIME. We showed that CFD-generated training data do not need to perfect to provide valuable insight into the parameterization.
Optimization of Cervical and Ocular Vestibular Evoked Myogenic Potential Testing Using an Impulse Hammer in Adults, Adolescents, and Children.

Objective To characterize cervical and ocular vestibular evoked myogenic potential (c- and oVEMP) responses using an impulse hammer (IH) in adults and pediatrics at standardized force levels and evaluate: the relationship of force level on VEMP amplitude, sternocleidomastoid (SCM) contraction on cVEMP amplitude, required number of tap stimuli, and subject comfort. Using these data, optimal testing parameters were selected. Study design Prospective study. Setting Tertiary referral center. Patients Seventy-eight healthy adults, adolescents, and children with no hearing or vestibular deficits. Interventions All subjects received c- and oVEMP testing using IH and 500 Hz tone burst air conduction stimuli. Adults received hard, medium, and soft force levels. Adolescents and children received medium and soft force levels. A comfort questionnaire was administered pre- and post-testing. Main outcome measures IH VEMP response parameters (response rates, latency, cVEMP pre-stimulus SCM Electromyography [EMG], and peak-to-peak amplitude) were assessed per force level. Subjective reporting for patient comfort was also assessed. Results VEMP response rates ranged from 92 to 100%. Force had a linear relationship with VEMP amplitude. SCM contraction had a linear relationship with raw cVEMP amplitude; however, dissipated with amplitude normalization. Force level did not impact the number of taps needed. A minimum peak force of 15 to 20 N, accounting for SCM contraction, and using a lower EMG monitoring limit for cVEMP is recommended to elicit reliable responses. Conclusions Overall, IH VEMP is appropriate and comfortable to use in adults and pediatrics and can be useful when an air conduction stimulus is contraindicated or not preferred.
Position-dependent effective masses in semiconductor theory. II.

A compound semiconductor possessing a slowly varying position-dependent chemical composition is considered. An effective-mass equation governing the dynamics of electron (or hole) motion using the Kohn-Luttinger representation and canonical transformations is derived. It is shown that, as long as the variation in chemical composition may be treated as a perturbation, the effective masses become constant, position-independent quantities. The effective-mass equation derived here is identical to the effective-mass equation derived previously by von Roos (1983), using a Wannier representation.
Circadian Regulation of Light-Evoked Attraction and Avoidance Behaviors in Daytime- versus Nighttime-Biting Mosquitoes

Mosquitoes pose widespread threats to humans and other animals as disease vectors [1]. Day- versus night-biting mosquitoes occupy distinct time-of-day niches [2, 3]. Here, we explore day- versus night-biting female and male mosquitoes' innate temporal attraction/avoidance behavioral responses to light and their regulation by circadian circuit and molecular mechanisms. Day-biting mosquitoes Aedes aegypti, particularly females, are attracted to light during the day regardless of spectra. In contrast, night-biting mosquitoes, Anopheles coluzzii, specifically avoid ultraviolet (UV) and blue light during the day. Behavioral attraction to/avoidance of light in both species change with time of day and show distinct sex and circadian neural circuit differences. Males of both diurnal and nocturnal mosquito species show reduced UV light avoidance in anticipation of evening onset relative to females. The circadian neural circuits of diurnal/day- and nocturnal/night-biting mosquitoes based on PERIOD (PER) and pigment-dispersing factor (PDF) expression show similar but distinct circuit organizations between species. The basis of diurnal versus nocturnal behaviors is driven by molecular clock timing, which cycles in anti-phase between day- versus night-biting mosquitoes. Observed differences at the neural circuit and protein levels provide insight into the fundamental basis underlying diurnality versus nocturnality. Molecular disruption of the circadian clock severely interferes with light-evoked attraction/avoidance behaviors in mosquitoes. In summary, attraction/avoidance behaviors show marked differences between day- versus night-biting mosquitoes, but both classes of mosquitoes are circadian and light regulated, which may be applied toward species-specific control of harmful mosquitoes.
Diabetes and acculturation in African immigrants to the United States: analysis of the 2010-2017 National Health Interview Survey (NHIS).

Objective: This study sought to assess the association between unidimensional acculturation and diabetes, and analyze mediating pathways of the association in African immigrants to the United State...
Air-core Coil Gradiometer for Biomagnetic Sensing in Non-shielded Environments

Magnetic fields emitted from the human body can serve as indicators of diverse health conditions. However, such fields are very small, making it hard to detect. Devices used to date for capturing these fields are bulky, expensive, and require additional equipment such as heaters, coolers, lasers, and/or shielding rooms. In this work, we report a lightweight miniature air-core coil gradiometer that is combined with advanced Digital Signal Processing (DSP) to capture biomagnetic fields in non-shielded environments. In vitro experimental results show that our gradiometer can pick up 50-Hz signals as low as 76 fT by averaging 5 min of raw data. Notably, the gradiometer's coil has an outer diameter of only 14.5 mm, height of 10 mm and weight of 1.64 g. In the future, this design can be modified to detect in vivo biomagnetic signals including: magnetomyography (MMG), magnetocardiography (MCG), magnetoencephalography (MEG), and magnetospinography (MSG).
Enabling Design Technology Co-Optimization of SRAMs through Open-Source Software

OpenRAM is an open-source memory compiler infrastructure that can enable Design Technology Co-Optimization of SRAMs. SRAM DTCO is often plagued by limited access to robust, featured memory compilers. In particular, each technology often "reinvents the wheel" whereas using open-source memory compilation can leverage recurring needs of verification, circuit implementation, and tool compatibility to give a true insight from technology all the way to design.
Sebaceous Carcinoma of the Eyelid

Sebaceous carcinoma (SC) is a malignant neoplasm that frequently affects the eyelids. It is an aggressive malignancy with metastasis rates as high as 25%. Historical studies have shown that mortality rates could be as high as 83%, but with the advent of increased detection, diagnosis, and treatment options, mortality rates have dropped substantially. A major issue with obtaining a proper diagnosis of SC is that it can mimic many other benign and malignant pathologies. Consequently, a delay in the diagnosis of SC can result in a poor prognosis and outcome for patients. The standard of care for SC is surgical excision, however, there is a reoccurrence rate of approximately 4% after excision. In these cases, it is necessary to treat patients with further excision and possibly radiation. Not all patients can have their tumors treated with surgery. In cases where there is diffuse intraepithelial seeding of the tumor cells, metastasis, or orbital invasion, other methods such as chemotherapy, radiation, and exenteration must be performed. It is essential that we elucidate the cellular mechanisms regarding the etiology of SC to develop better methods of diagnosis and treatment for the future. In this chapter, we will focus on the clinically relevant topics regarding SC, signaling pathways involved in the pathogenesis, and how miRNAs interact with these cascades. Both Wnt and TGF-β signaling have been implicated in the developing sebaceous glands and SC. Several miRNAs have been studied in this disease and downstream targets include: NF-κB, PTEN, c-Myc, and AKT2. These miRNAs may be used as biomarkers for SC or they may be potential therapeutic targets for patients who do not benefit from current interventions.
Katie Hindmarch-Watson. Serving a Wired World: London’s Telecommunications Workers and the Making of an Information Capital . Oakland: University of California Press, 2020. 288p. Hardcover, $29.95 (ISBN 978-0-5203-4473-0).

Serving a Wired World: London’s Telecommunications Workers and the Making of an Information Capital is a scholarly work, rather than one on professional practice. Library professionals have a vast range of reading available to us as information stewards and conduits in the 21st century, and we serve ourselves by including historical scholarship in the bounty of ideas we consider. This is especially true when a scholarly work provides a window into past information workers’ regulated and agentive roles in the communications systems they were charged to operate. Here, cultural historian Katie Hindmarch-Watson explores how embodied labor and categories of gender informed the nascent telecommunications industry in 19th-century London and via networks across Britain. How were these telecommunications workforces feminized and controlled through administrative processes and how did some groups push against these constraints? If these questions resonate for you, read on.
The chemistry of Harry B. Gray

Harry B. Gray is one of the towering figures in modern inorganic chemistry. As the author of 18 books and more than 950 research articles, he has had an impact on nearly every aspect of inorganic chemistry. Over a 60-year career, he has made seminal contributions to electronic structure theory, inorganic spectroscopy, bioinorganic chemistry, and sustainable energy research.
Cognitive behavioral therapy in children with anxiety disorders

Abstract This chapter focuses on the efficacy of cognitive behavioral therapy (CBT) in the treatment of pediatric anxiety disorders. The chapter will first outline the presentation of anxiety disorders in youth, which are among the most common mental disorders in pediatric populations. It will then describe the core components of CBT, which has been demonstrated to be an efficacious treatment for youth anxiety, with lower dropout and fewer adverse events compared to other treatment options. Key supporting evidence will then be reviewed, along with important treatment considerations such as treatment format, treatment intensity, and comorbidity. CBT can also be applied to many neurodevelopmental conditions and challenges. Given the potential for chronic mental illness and associated risk of adverse outcomes in adulthood, it is imperative that pediatric anxiety be properly diagnosed and treated.
Assessing the impact of expert knowledge on ICH M7 (Q)SAR predictions. Is expert review still needed

The ICH M7 (R1) guideline recommends the use of complementary (Q)SAR models to assess the mutagenic potential of drug impurities as a state-of-the-art, high-throughput alternative to empirical testing. Additionally, it includes a provision for the application of expert knowledge to increase prediction confidence and resolve conflicting calls. Expert knowledge, which considers structural analogs and mechanisms of activity, has been valuable when models return an indeterminate (equivocal) result or no prediction (out-of-domain). A retrospective analysis of 1002 impurities evaluated in drug regulatory applications between April 2017 and March 2019 assessed the impact of expert review on (Q)SAR predictions. Expert knowledge overturned the default predictions for 26% of the impurities and resolved 91% of equivocal predictions and 75% of out-of-domain calls. Of the 261 overturned default predictions, 15% were upgraded to equivocal or positive and 79% were downgraded to equivocal or negative. Chemical classes with the most overturns were primary aromatic amines (46%), aldehydes (45%), Michael-reactive acceptors (37%), and non-primary alkyl halides (33%). Additionally, low confidence predictions were the most often overturned. Collectively, the results suggest that expert knowledge continues to play an important role in an ICH M7 (Q)SAR prediction workflow and triaging predictions based on chemical class and probability can improve (Q)SAR review efficiency.
Louise Pound: Scholar, Athlete, Feminist Pioneer

Reviewed Medium: book Authors: Robert Cochran Year: 2009 Pages: 334 Publisher: University of Nebraska Press ISBN: 978-0-8032-1546-7 (hard cover). Prices: $40.00 USD(hard cover).
Only multimers of a synthetic peptide of human apolipoprotein E are biologically active.

Plasma apolipoprotein E (apoE) is a ligand for the cellular uptake of cholesterol-rich plasma lipoproteins. ApoE also inhibits mitogen-stimulated lymphocyte proliferation and gonadotropin-stimulated ovarian theca/interstitial cell androgen production. To address the mechanism(s) by which apoE is active and to understand its interaction with the target cells, we prepared and examined the inhibitory activity of a series of apoE synthetic peptides. ApoE peptides representing amino acid residues 93-112, 141-155, 161-171, 172-182, and 174-193 were not active in either bioassay. However, specific inhibition of both lymphocyte proliferation and ovarian androgen production was observed with a self-conjugate of peptide-(141-155). Furthermore, a synthesized dimeric peptide representing two repeats of sequence-(141-155) (i.e. (141-155)-(141-155] was active as well. In both bioassays, the inhibition observed was not a result of direct cell killing. Furthermore, these apoE peptides exhibited activities with characteristics that were shared with those of native apoE. The results indicate that amino acid residues 141-155 of apoE are responsible for the biological activity of apoE. Furthermore, the results suggest that dimers or multimers of native apoE may be a biologically important species.
Automated radiometric detection of bacteria in 2,967 blood cultures.

A new radiometric method for the automatic detection of bacterial growth in blood cultures has been compared with conventional methods. A total of 2,967 cultures from 1,280 patients suspected of having bacteremia were studied. A 2-ml amount of blood was inoculated into culture media in which the glucose was labeled with carbon-14. The release of 14CO2 by bacterial metabolism was checked hourly for 18 to 24 hr, daily for the next 2 days, and, on the 12th day, with an automated instrument. A 10-ml amount of blood was studied by conventional bacteriological techniques. In 125 cultures from 50 patients, there was bacterial growth in at least one of the routine media. Of these, the radiometric method detected 102 cultures from 40 patients. In 111 cultures from 48 patients, there was radiometric detection of bacterial growth. In all of these cultures, there was detection of bacterial growth in subcultures from the radioactive medium. Of these, the routine laboratory detected 98 cultures from 40 patients. Neither method detected all patients with bacteremia. Among the 57 patients positive by one or both methods, routine techniques detected bacteria in 87% and the radiometric method detected bacteria in 85%. Seventy per cent of the cultures were detected first by the radiometric method, 65% on the day of inoculation. Our results suggest that the radiometric method is faster than conventional techniques and comparable in accuracy. Its great advantage is that it is simple, automatic, and can be extended to automatic detection of bacterial sensitivity to antibiotics.
SSD Architecture and PCI Express Interface

Flash-memory-based solid-state drives (SSDs) provide faster random access and data transfer rates than electromechanical drives and today can often serve as rotating-disk replacements, but the host interface to SSDs remains a performance bottleneck. PCI Express (PCIe)-based SSDs together with the standard called NVMe (Non-Volatile Memory express) solves this interface bottleneck. This chapter walks the reader through the SSD block diagram, from the NAND memory to the Flash controller (including wear leveling, bad block management, and garbage collection). PCIe basics and different PCIe SSD architectures are reviewed. Finally, an overview on the standardization effort around PCI Express is presented.
Inheritance of resistance to viral diseases in plants.

Publisher Summary This chapter focuses on plant resistance to viral diseases. Breeding for resistance has become an increasingly common practice in the development of methods for the control of viral diseases in economically important plants. Resistance to disease, as controlled by single or multiple genes in inheritance, may be of a number of kinds and of various degrees of efficiency. It may be absolute, constituting natural immunity. It may involve a tendency to escape infection despite inoculation. It may involve prompt death of invaded tissues (hypersensitivity), with or without the limitation of virus movement (localization of virus) and with or without the rapid inactivation of virus already formed. It also may be characterized by a tendency of not showing obvious disease (tolerance); usually this form of resistance is achieved by the partial suppression of viral multiplication, suppression of systemic spread, or both. The resistances to various diseases, such as cucumber mosaic, tobacco mosaic, and spotted wilt, in several hosts such as cucumber, tomato, and muskmelon are discussed in the chapter. It discusses the difficulties that arise during the breeding for disease resistance crops. The breeding difficulties may be posed by linkages between genes and nutritional defects in food plants. Future problems in the acquisition of resistances to disease are also discussed in the chapter.
Value-driven design and sensitivity analysis of hybrid energy systems using surrogate modeling

A surrogate modeling and analysis methodology is applied to study dynamic hybrid energy systems (HES). The effect of battery size on the smoothing of variability in renewable energy generation is investigated. Global sensitivity indices calculated using surrogate models show the relative sensitivity of system variability to dynamic properties of key components. A value maximization approach is used to consider the tradeoff between system variability and required battery size. Results are found to be highly sensitive to the renewable power profile considered, demonstrating the importance of accurate renewable resource modeling and prediction. The documented computational framework and preliminary results represent an important step towards a comprehensive methodology for HES evaluation, design, and optimization.
The impact of PPS legislation on the systematic risk of hospitals

In 1983 the government passed legislation implementing a new method of paying hospitals for Medicare inpatient services, the Prospective Payment System (PPS). Under this system the changes in economic incentives to hospitals affected the market conditions under which hospitals operate. This article investigates the impact of PPS on the financial riskiness of hospitals. Using the capital asset pricing model (CAPM), this study analyzes the systematic risk of a portfolio of four publicly traded acute care hospitals in the pre-PPS and post-PPS periods, as well as four control portfolios. It covers a pre-PPS period from 1976 to the passage of the Tax Equity and Fiscal Responsibility Act (TEFRA) and a post-PPS period through 1988. The systematic risk for publicly traded acute care hospitals increased significantly in the post-PPS period. However, the control groups also showed significant changes in systematic risk.
The revolution of StarCraft network traffic

StarCraft II uses a client-server architecture while StarCraft I uses a peer-to-peer architecture. StarCraft I clients utilize more outgoing bandwidth for each additional player in the game, while StarCraft II clients maintain constant client-to-server bandwidth regardless of the number of players. StarCraft I and StarCraft II exhibit distinct packet size and inter-packet size distributions. For StarCraft II, we model inter-packet time distributions for both client-to-server and server-to-client traffic regardless of the number of players. The packet size distribution for client-to-server traffic also remains constant regardless of the number of players while the packet size distribution for server-to-client traffic shifts with regard to the number of players. We segmented each of these distributions, and fit each segment with a uniform, beta, gamma or triangular distribution, constructing the model for StarCraft II network traffic.
Molecular components of the mitotic spindle

Mitotic spindles constitute the machinery responsible for equidistribution of the genetic material into each daughter cell during cell division. They are transient and hence quite labile structures, changing their morphology even while performing their function. Biochemical, immunological and genetic analyses of mitotic cells have allowed us to identify a variety of molecules that are recruited to form the spindle at the onset of mitosis. Evaluation of the roles of these molecules in both the formation and in the dynamics of spindle microtubules should be important for understanding the molecular basis of mitosis and its regulation. We have recently identified a novel mitosis-specific microtubule-associated protein (MAP) using a monoclonal antibody probe raised against the mitotic spindles isolated from cultured mammalian cells. This 95/105 kDa antigen represents a unique component of the spindle distinct from any of the other MAPs reported so far. Antibody microinjection resulted in mitotic inhibition in a stage-specific and dose-dependent manner, indicating that the protein is an essential spindle component.
Discovery analysis of TCGA data reveals association between germline genotype and survival in ovarian cancer patients.

Background Ovarian cancer remains a significant public health burden, with the highest mortality rate of all the gynecological cancers. This is attributable to the late stage at which the majority of ovarian cancers are diagnosed, coupled with the low and variable response of advanced tumors to standard chemotherapies. To date, clinically useful predictors of treatment response remain lacking. Identifying the genetic determinants of ovarian cancer survival and treatment response is crucial to the development of prognostic biomarkers and personalized therapies that may improve outcomes for the late-stage patients who comprise the majority of cases. Methods To identify constitutional genetic variations contributing to ovarian cancer mortality, we systematically investigated associations between germline polymorphisms and ovarian cancer survival using data from The Cancer Genome Atlas Project (TCGA). Using stage-stratified Cox proportional hazards regression, we examined 650,000 SNP loci for association with survival. We additionally examined whether the association of significant SNPs with survival was modified by somatic alterations. Results Germline polymorphisms at rs4934282 (AGAP11/C10orf116) and rs1857623 (DNAH14) were associated with stage-adjusted survival ( = 1.12e-07 and 1.80e-07, FDR = 1.2e-04 and 2.4e-04, respectively). A third SNP, rs4869 (C10orf116), was additionally identified as significant in the exome sequencing data; it is in near-perfect LD with rs4934282. The associations with survival remained significant when somatic alterations. Conclusions Discovery analysis of TCGA data reveals germline genetic variations that may play a role in ovarian cancer survival even among late-stage cases. The significant loci are located near genes previously reported as having a possible relationship to platinum and taxol response. Because the variant alleles at the significant loci are common (frequencies for rs4934282 A/C alleles = 0.54/0.46, respectively; rs1857623 A/G alleles = 0.55/0.45, respectively) and germline variants can be assayed noninvasively, our findings provide potential targets for further exploration as prognostic biomarkers and individualized therapies.
Molecular and genetic features of a labeled class of spinal substantia gelatinosa neurons in a transgenic mouse

Genetic incorporation in a mouse of a transgene containing the prion promoter and the green fluorescent protein (GFP) coding sequence labels a set of substantia gelatinosa (SG) neurons (SG-GFP) homogenous in morphology, electrophysiology, and γ-amino-butyric acid expression. In the present analysis the SG-GFP neurons are established to have protein kinase C-βII immunoreactivity and to lack evidence for the presence of calbindin D-28k, parvalbumin, and protein kinase C-γ. These neurons were hyperpolarized by mediators of descending control, norepinephrine and serotonin. Sequential polymerase chain reactions established the insertion of the transgene to be in the receptor protein tyrosine phosphatase kappa (RPTP-κ) and the laminin receptor 1 (ribosomal protein SA) pseudogene 1 locus. RPTP-κ expression in both GFP-labeled dorsal root ganglia and SG neurons raises the possibility that homophilic interactions of RPTP-κ contribute to establishment of connections between specific classes of primary afferent and SG neurons. J. Comp. Neurol. 492:90–100, 2005. © 2005 Wiley-Liss, Inc.