cssi/SciSciGPT-SciSciNet huggingface dataset:
The Ripper Correspondence: A Visual and Nonverbal Analysis

AbstractThis study investigated visual and nonverbal elements of the Ripper Correspondence. The letters attributed to Jack the Ripper that included visual and nonverbal elements were gathered and analyzed, to determine prevalent themes and attributes of this correspondence. This body of literature could be referred to as the Ripper correspondence, or the Ripper literature, because there was more than just letters. The Ripper sent messages on telegrams, pages from catalogues and a variety of other types of printed material. In this study we examined three visual and nonverbal dimensions of the Ripper letters: 1) Artistic letters, 2) Bloody items, and 3) Unusual lettering. We conclude that visual elements of the Ripper correspondence were characterized by certain stylistic themes and traits.
Cross-Accelerator Performance Profiling

The computing requirements of scientific applications have influenced processor design, and have motivated the introduction and use of many-core processors, i.e., accelerators, for high performance computing (HPC). Consequently, it is now common for the compute nodes of HPC clusters to be comprised of multiple computing devices, including accelerators. Although execution time can be used to compare the performance of different computing devices, there exists no standard way to analyze application performance across devices with very different architectural designs and, thus, understand why one outperforms another. Without this knowledge, a developer is handicapped when attempting to effectively tune application performance, as is a hardware designer when trying to understand how best to improve the design of computing devices. In this paper, we use the LULESH 1.0 proxy application to compare and analyze the performance of three different accelerators: the Intel® Xeon Phi™ and the NVIDIA Fermi and Kepler GPUs. Our study shows that LULESH 1.0 exhibits similar execution-time behavior across the three accelerators, but runs up to 7X faster on the Kepler. Despite the significant architectural differences between the Xeon Phi™ and the GPUs, and the differences in the metrics used to characterize their performance, we were able to quantify why the Kepler outperforms both the Fermi and the Xeon Phi™. To do this, we compared their achieved instructions per cycle and vectorization usage, as well as their memory behavior and power and energy consumption.
Meta-ethnography of autoethnographies: a worked example of the method using educational studies

ABSTRACTDespite questions about autoethnography in the ethnography and education research family, autoethnography is published in selective peer-reviewed journals in education and in the social and health sciences. Even critics of autoethnographic studies note their ‘rising acceptance in the past 15 years’ [Delamont, S. 2009. “The Only Honest Thing: Autoethnography, Reflexivity and Small Crises in Fieldwork.” Ethnography and Education 4 (1): 51–63]. However, there has been less effort towards qualitative meta-synthesis to learn what other insights might be gained from collections of studies. With the advent of meta-autoethnography [Ellis, C. 2009. Revision: Autoethnographic Reflections of Life and Work. Walnut Creek, CA: Left Coast Press], each author can find a way to synthesise her/his own autoethnographic works, however, synthesising autoethnographies of different authors has received no attention. This article examines a critical, systematic approach to the meta-ethnography of autoethnographies and of...
Enterovirus Concentration Using Automated Hollow Fiber Ultrafiltration

The Automated Hollow Fiber Ultrafiltration (AHFU) method is proposed here as a simple, efficient and rapid virus concentration technique from tap and drinking water sources. The results reported here extend the testing of the AHFU method to include two Picornaviruses [Poliovirus 2 (vaccine) and Echovirus 1] and Reovirus 3. Their respective mean virus recoveries from between 3 and 100 l of tap water is 88 ± 26, 79 ± 60, and 104 ± 48%. Various approaches including membrane surface modification, changes in backwash hydrodynamics, modification of the feed and backwash composition, and the use of S35-methionine labelled Poliovirus 2, are used to study the recovery of sorbed Poliovirus 2 from the hollow fiber/solution interface. An increase in the backwash pH to between 9.5 and 10.5 significantly improved Poliovirus 2 recovery. This, together with the labelled experiments, indicates that the virus-membrane interactions are probably electrostatic in nature. Convective polarization during filtration probably brings the virus close enough to the surface for these interactions to occur since virus losses were not detected for a non-permeation recycle experiment. Because very low Reynold's numbers are used, the flow is in the creeping-flow-regime for both filtration and backwashing (axial and radial). Unless significantly higher Reynolds could be used, enhanced recovery due to purely hydrodynamic forces is unlikely. High Reynold's numbers, of course, are limited by the pressure constraints of the hollow fibers.
El uso del gerundio en el español de Tejas

Este estudio sociolinguistico analiza, a traves de la descripcion oral de un dibujo, una entrevista grabada y dos cuestionarios linguisticos, la manera en que 40 hablantes bilingues de Tejas de tres grupos generacionales usan el gerundio espanol en la oralidad y en la escritura. Tambien se investigaron las formas que alternan con los gerundios que los informantes emplean. Se analizo ademas si en el uso de estar + -ndo existe una transferencia del gerundio ingles en el discurso oral y escrito y si los gerundios se relacionan con el sexo y el grupo generacional de los participantes. Finalmente, se evaluo la seguridad linguistica de los hablantes cuando estos diferencian entre gerundios “esperados” y gerundios “no esperados”. Los resultados revelaron que utilizan mas el gerundio estar +-ndo y con menor frecuencia la forma andar + -ndo y los gerundios independientes. Ademas, se hallo que en contextos variables los gerundios alternan con el presente, el imperfecto y el presente perfecto pero en contextos categoricos no ocurren esas alternancias. Asi mismo, se hallo una transferencia del gerundio ingles en el uso estar + -ndo en el habla controlada y el habla no controlada particularmente en la tercera generacion de hablantes. Por otro lado, no se identifico ninguna asociacion entre el sexo de los participantes, la generacion y los gerundios. Finalmente, se encontro que los hablantes tienen seguridad linguistica cuando usan el gerundio en forma escrita pero muestran inseguridad linguistica al seleccionar entre usos “esperados” y usos “no esperados” del gerundio.
Pharmacotherapeutic Considerations for Individuals with Down Syndrome

Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy. Individuals with DS may experience multiple comorbid health problems including congenital heart defects, endocrine abnormalities, skin and dental problems, seizure disorders, leukemia, dementia, and obesity. These associated conditions may necessitate pharmacotherapeutic management with various drugs. The complex pathobiology of DS may alter drug disposition and drug response in some individuals. For example, reports have documented increased rates of adverse drug reactions in patients with DS treated for leukemia and dementia. Intellectual disability resulting from DS may impact adherence to medication regimens. In this review, we highlight literature focused on pharmacotherapy for individuals with DS. We discuss reports of altered drug disposition or response in patients with DS and explore social factors that may impact medication adherence in the DS setting. Enhanced monitoring during drug therapy in individuals with DS is justified based on reports of altered drug disposition, drug response, and other characteristics present in this population.
Mitigating Crosstalk in Unterminated Channels

Based on the recognition that near-end crosstalk propagating to the far end is the primary source of crosstalk noise in short unterminated channels, an approach to improve the signal integrity on such channels significantly is described and demonstrated. The basic physics of crosstalk reduction by matrix matching is described and illustrated numerically. Then, large potential gains for three on-package interconnect application examples are shown. A nominal strip-line configuration based on standard package design rules and including realistic modeling assumptions yields 50.4% reduced channel power at equal performance. The same design can be converted into microstrip without degrading the eye height and channel power. For a dense multichip package with design of experiment simulation, the worst-case eye width is improved by 114%.
Abstract WP170: Infections Present on Admission and Stroke in the Young

Background and Purpose: Antecedent infections have been identified as possible risk factors and triggers for stroke, while infections after stroke lead to worse outcomes. The impact of infections present at the time of admission (IPOA) has not been well characterized. We hypothesized that IPOA would be associated with stroke severity and outcomes in young stroke patients. Methods: A retrospective review of consecutive ischemic stroke patients aged 18-40 years admitted between January 2008 and June 2014 was performed. IPOA were defined as present if the infection was diagnosed within the first 24 hours of admission. The primary outcomes were stroke severity using the National Institutes of Health Stroke Scale (NIHSS) and poor functional outcome at discharge (modified Rankin Scale (mRS) 3-6)). Results: Of 235 patients, 41 (17.4%) had IPOA. Patients with IPOA were more likely to be women (87.8% vs. 51.0%; p 30 years. In patients 18-30, after adjusting for age, sex, and NIHSS, IPOA was associated with a greater odds of poor outcome (OR 3.69, 95%CI 1.20-11.3); NIHSS was not associated with mRS 3-6 (OR 1.00, 95%CI 0.99-1.01). IPOA was not significantly associated with poor outcome after adjusting for age, sex and NIHSS in patients >30 years (OR 1.29, 95%CI 0.48-3.51). Discussion: Infections present at time of admission in young stroke patients are closely associated with NIHSS and subsequent poor outcomes at discharge. Further studies are needed to understand the role of infection and whether infections moderate the effect of stroke severity on stroke outcomes in young patients.
Abstract 2877: IKK-mediated signaling controls prostate tumor initiating cells

The heterogeneous nature of prostate cancer tumors is thought to play an important role in the decreased effectiveness of existing therapies. Tumor initiating cells (TICs) are capable of self-renewal and comprise a subset of the tumor mass. These cells are proposed to drive the growth and metastasis of tumors, and are considered to be resistant to traditional cytotoxic and targeted therapies. Several studies have shown that NF-κB signaling is increased in recurrent prostate cancer and enriched in prostate TICs. We sought to determine the potential of an IKK/NF-κB-driven mechanism for inherent or acquired resistance by IKK-mediated control of a subset of prostate tumor initiating cells. These studies were performed by using established prostate cancer cell lines, murine prostate organoids, and a murine prostate cancer animal model. We have found that inhibition of IKKα and IKKβ, upstream regulators of noncanonical and canonical NF-κB signaling, block self-renewal of several PTEN-deficient prostate cancer cell lines. Furthermore, we have also found that IKK is important for tumorigenicity and stemness seen in prostate cancer cells as measured by colony formation and extreme limiting dilution assays. Loss of canonical NF-κB (p65/RelA) decreased stemness while loss of noncanonical did not alter tumorsphere formation. Interestingly, Pten-/- tumors with loss of Ikkα or Ikkβ displayed decreased levels of self-renewing cells as measured by CD49fhigh expression, a known prostate basal cell marker. Isolated murine Pten-/- cells were 2x more efficient than Pten-/-Ikkα-/- or Pten-/-Ikkβ-/- cells in forming prostate organoids suggesting that loss of Ikk decreased the number of self-renewing cells needed for formation. Taken together, we conclude that IKK-mediated signaling is important for maintenance of prostate tumor initiating cells and further studies will address whether IKK-mediated signaling provides a mechanism for evading current therapies. Note: This abstract was not presented at the meeting. Citation Format: Sara E. Conard, Aaron Ebbs, Albert S. Baldwin. IKK-mediated signaling controls prostate tumor initiating cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2877. doi:10.1158/1538-7445.AM2017-2877
Macy-György Award Address--year 2000 a half-century inquiry into the immunobiology of human milk.

It is an honor to have been chosen by the International Society for Research in Human Milk and Lactation to be the recipient of the Macy-Gyorgy Award for Research in Human Milk and Lactation for the year 2000. The Award is of special significance because Icey Macy and Paul Gyorgy were pioneers in research concerning human milk and lactation and because the Society is the leading organization that deals with research in this aspect of human biology.
Urban consolidation solutions for parcel delivery considering location, fleet and route choice

Abstract Consolidation schemes can reduce the negative impacts of urban freight movements. For this reason, in recent years several city authorities have promoted different measures to foster the implementation of urban consolidation centers. However, only a few real-world publicly promoted initiatives have succeeded due to several operational, financial, and regulatory issues. In this paper, we investigate different city logistics solutions for a mail delivery service in the city of Austin, Texas. We do that by using a model for the multi-depot vehicle routing problem with heterogeneous vehicle fleet for urban consolidation centers (UCCs) based on metaheuristics. The model considers the total costs and the environmental impacts of alternative UCC configurations and policy scenarios. According to the results, combinations of regulations and subsidies addressing both traffic inbound and outbound the facilities could be the most efficient and environmental friendly approaches. Factors like demand and traffic congestion have a significant impact on the overall performance of the solutions.
Rapid Method of Microbial Susceptibility Testing

A rapid method of microbial susceptibility testing is described. Bacterial growth is measured by determining the incorporation of 14C-tryptophan into cellular protein in the presence of antimicrobial drugs.
Computational Creativity: Three Generations of Research and Beyond

In this article we have classified computational creativity research activities into three generations. Although the respective system developers were not necessarily targeting their research for computational creativity, we consider their works as contribution to this emerging field. Possibly, the first recognition of the implication of intelligent systems toward the creativity came with an AAAI Spring Symposium on AI and Creativity (Dartnall and Kim, 1993). We have here tried to chart the progress of the field by describing some sample projects. Our hope is that this article will provide some direction to the interested researchers and help creating a vision for the community.
Measuring State Variable Participation for Selective Modal Analysis 1

Abstract A simple scale-invariant criterion is proposed for picking out state variables that 'significantly participate' in the construction of selected modes of a linear time-invariant dynamical system. The criterion is of value in such approaches to modal reduction as Davison's method, singular perturbation methods, and our 'Selective Modal Analysis' framework (which in several respects extends the former two methods, and in which the proposed criterion arises in a natural way). Application to sampled-data systems is also considered.
Initiating a women's health physician–run rehabilitation clinic in the United States

Introduction/Background Pelvic dysfunction can lead to persistent impairment and disability when left untreated. While some diagnoses overlap with those seen in a general Physical Medicine and Rehabilitation (PM&R) outpatient setting and Obstetrics/Gynecology (Ob/Gyn), management varies with changes in biomechanics and function in contexts of fecundity, gravidity, post-partum status, post-menopause, history of surgical intervention, or history of sexual trauma. Material and method PM&R initiated a collaboration with Ob/Gyn to create a physician-run Women's Health Rehabilitation specialty clinic embedded within an established Ob/Gyn clinic at an academic university hospital in the United States. The clinic focuses on pelvic floor disorders and musculoskeletal issues associated with pregnant or post-partum women. Results Over 50 referrals were made from Ob/Gyn in the initial months of clinic launch. Diagnoses included low back pain and sacroiliac joint dysfunction related to pregnancy, pelvic floor instability, dyspareunia, post-partum thoracic back pain, and coccydynia. Management included education of biomechanics, referral to Pelvic Floor-specialized Physical Therapy (PFPT), medications, referral to Psychology, and injections. Despite significant enthusiasm from Ob/Gyn and the patients, initial referrals were delayed due misunderstanding regarding difference between PM&R and PT, failure to recall initiation of clinic, and flawed protocol with ancillary staff on scheduling process. Despite infrastructure of a large academic institution in a metropolitan area, there was a paucity of availability of PFPT multiple sites within the academic affiliation or the metropolitan area. Conclusion Comprehensive Women's Health Rehabilitation lead by physiatrists can address biomechanical issues, treat pain, perform interventional procedures, and coordinate care with PFPT and other professionals to address contributing factors, like mood disturbances and life situations. Our clinic aim is to expand collaborations with increased marketing, face-to-face interaction, and visibility at multidisciplinary events. We expect to increase referral sources and numbers as well as educate more of the medical community about our specialty.
Electrostatic Design and Conditioning of a Triple Point Junction Shield for a −200 kV DC High Voltage Photogun

Nuclear physics experiments performed at the Continuous Electron Beam Accelerator Facility (CEBAF) at the Jefferson Lab require a DC high voltage photogun to generate polarized electron beams from GaAs photocathodes. The photogun uses a tapered ceramic insulator that extends into the vacuum chamber and mechanically holds the cathode electrode. Increasing the operating voltage from nominal -130 kV to -200 kV will provide lower beam emittance, better transmission through injector apertures, and improved photocathode lifetime. This desire to increase the photogun operating voltage led to the design of a triple-point-junction shield electrode which minimizes the electric field at the delicate insulator-metal-vacuum interface and linearizes the potential across the insulator, thus reducing the risk of arcing along the ceramic insulator. This work describes the results obtained using COMSOL® electrostatic-field simulation software and presents the high voltage conditioning results of the upgraded -200 kV CEBAF photogun.
The Marmoset as a Model for Visual Neuroscience

Abstract The common marmoset (Callithrix jacchus) has been valuable as a primate model in biomedical research. Interest in this species has grown recently, in part due to the successful demonstration of transgenic marmosets. Here we examine the prospects of the marmoset model for visual neuroscience research, adopting a comparative framework to place the marmoset within a broader evolutionary context. We begin by reviewing how the eye, brain, and visually guided behaviors of primates differ from those of other mammals. We then focus on the marmoset, comparing and contrasting features of its visual system and behavior with the better-studied macaque. We consider experimental advantages and challenges of the marmoset model along with its potential to complement visual neuroscience studies in the macaque and the mouse. The marmoset's small brain bears most of the organizational features of other primates, and its smooth surface offers practical advantages over the macaque for areal mapping, laminar electrode penetration, and two-photon and optical imaging. Initial reports demonstrate that physiological responses to both simple and complex visual stimuli resemble those commonly observed in the macaque. Behaviorally, marmosets are more limited in their ability to perform regimented psychophysical tasks than macaques, but they do readily accept the head restraint that is necessary for accurate eye tracking and neurophysiology, and can be trained to perform simple visual discriminations. The natural gaze behavior of marmosets closely resembles those of macaques and humans, with a tendency to focus on objects of social interest including faces. Their immaturity at birth and routine twinning makes them ideal for the study of postnatal visual development. We argue that these experimental factors, together with the theoretical advantages inherent in comparing anatomy, physiology, and behavior across related species, make the marmoset an excellent model for visual neuroscience, offering new and complementary avenues to investigate the biology of human visual cognition.
Fault-Free Refinements for Interface Automata

A refinement preorder for a model of concurrent systems should be compositional (i.e. a precongruence for parallel composition) and should not introduce faults into a fault-free specification. Arguably, if these are the features of interest, the coarsest such precongruence is the optimal refinement preorder and often, it preserves additional properties. For the model of interface automata, originally faults are communication errors in the form of unexpected inputs. The respective optimal preorder has been characterized as the inclusion of two trace sets. Here, we extend these characterizations by regarding also quiescence (quiescence and divergence resp.) as faults. The latter preorder is coarser, i.e. better, than an earlier preorder regarding errors, quiescence and divergence. A conjunction operator allows to specify different facets of an overall specification by separate automata and then to combine them. We also present conjunction operators for our settings, avoiding flaws that can be found in the literature.
Transmission of the cri-du-chat syndrome from a maternal balanced translocation carrier, t(5p-;11q+).

A child with cri-du-chat syndrome, 46,XY,5p-, was born to a mother who had two normal children and two abortuses. The mother was shown to carry a balanced translocation. Giemsa and fluorescent banding demonstrate the exact location of the translocated segment. The deleted short arm of chromosome number 5 was shown to be attached to the long arm of chromosome number 11.
Electrolyte additives to enable nonaqueous polyelectrolyte solutions for lithium ion batteries

Nonaqueous polyelectrolyte solutions, in which a negatively charged macromolecule neutralized by lithium is dissolved in nonaqueous solvents, have shown promise as potential high transference number electrolytes. However, in battery-relevant carbonate solvents (ethylene carbonate/dimethyl carbonate blends), it has been shown that lithium ions do not readily dissociate from easily synthesized sulfonated polymers, despite the solvent's high dielectric constant (∼50). In this work, a range of additives are screened to improve conductivity, and we demonstrate that the addition of less than 5 vol% of 15-crown-5 achieves an order of magnitude conductivity increase by selectively improving lithium dissociation. Utilizing the optimized electrolyte, we show that polyelectrolyte solutions may be directly substituted for a standard electrolyte with commercial electrodes in a graphite/LiFePO4 cell, providing further motivation for future study of these new electrolytes.
A Novel PUF Architecture Against Non-Invasive Attacks

In this paper, a physical unclonable function (PUF)-advanced encryption standard (AES)-PUF is proposed as a new PUF architecture by embedding an AES cryptographic circuit between two conventional PUF circuits to conceal their challenge-to-response pairs (CRPs) against machine learning attacks. Moreover, an internal confidential data is added to the secret key of the AES cryptographic circuit in the new PUF architecture to update the secret key in real-time against side-channel attacks. As shown in the results, even if 1 million number of data are enabled by the adversary to implement machine learning or side-channel attacks, the proposed PUF can not be cracked. By contrast, only 100,000 (1,000) number of data are sufficient to leak the confidential information of a conventional PUF via machine learning (side-channel) attacks.
Lung Cancer Prevention

Lung cancer is the leading cause of cancer mortality in the United States, representing a greater number of deaths than the sum of the next three causes of cancer mortality combined. Despite a rapidly increasing understanding of the biology of lung cancer and the development of effective new targeted therapies and immunotherapy that improve survival for a significant subgroup of patients, lung cancer continues to represent a major societal burden in both high and low income countries. Although the long-term recognition of cigarette smoking as the major cause of lung cancer, with attendant policy shifts, has helped to curb the lung cancer epidemic in the USA, high use of tobacco products continues in other parts of the world. Early detection and prevention of lung cancer provide opportunities to reduce the global burden of this highly lethal disease.
Emotional responding: Integration of multiple constructs and association with psychological health.

OBJECTIVE Numerous psychological constructs exist to describe different facets of emotional responding, but they have rarely been examined together. We empirically modeled the associations between four psychological constructs (mindfulness, emotional nonacceptance, experiential avoidance, and anxiety sensitivity) of individuals' responses to their affective experience, hypothesizing that a bifactor model would fit the data best. METHOD We used exploratory structural equation modeling, a novel latent variable modeling framework, to compare five measurement models of emotional responding in an online community sample (N = 307). RESULTS A bifactor model including a general emotional responding factor had substantial factor loadings from nearly all items, with mixed results for specific factors. Exploratory analyses supported the significant association of avoidant emotional responding and psychopathology/well-being. CONCLUSION The general avoidant emotional responding factor appears to overlap most directly with experiential avoidance and may be a transtheoretical construct relevant to mental health.
Reduced Rank Multivariate Kernel Ridge Regression

In the multivariate regression, also referred to as multi-task learning in machine learning, the goal is to recover a vector-valued function based on noisy observations. The vector-valued function is often assumed to be of low rank. Although the multivariate linear regression is extensively studied in the literature, a theoretical study on the multivariate nonlinear regression is lacking. In this paper, we study reduced rank multivariate kernel ridge regression, proposed by \cite{mukherjee2011reduced}. We prove the consistency of the function predictor and provide the convergence rate. An algorithm based on nuclear norm relaxation is proposed. A few numerical examples are presented to show the smaller mean squared prediction error comparing with the elementwise univariate kernel ridge regression.
Safety and Efficacy of Topical Diclofenac and Subcutaneous Firocoxib, Ketoprofen, and Meloxicam in Smoky Jungle Frogs (Leptodactylus pentadactylus)

Abstract Although nonsteroidal anti-inflammatory drugs (NSAIDs) are often used in anurans, limited pharmacodynamic data are available regarding their value, particularly with regards to repeated do...
The Systolic Programming

The main subject of “systolic programming” is the realization of systolic algorithms on systolic processors and on multiprocessor systems. Systolic programming allows to answer the following questions: “How to construct a processor realizing a specific algorithm in minimal time with minimal hardware?” (which can be considered as a question on which extent we can approach to AT2-lower bounds) and “Is it possible to realize an algorithm on a processor of a given structure and/or given size?”
Functional Genomics In Vivo Reveal Metabolic Dependencies of Pancreatic Cancer Cells

Summary Pancreatic ductal adenocarcinoma (PDAC) cells require substantial metabolic rewiring to overcome nutrient limitations and immune surveillance. However, the metabolic pathways necessary for pancreatic tumor growth in vivo are poorly understood. To address this, we performed metabolism-focused CRISPR screens in PDAC cells grown in culture or engrafted in immunocompetent mice. While most metabolic gene essentialities are unexpectedly similar under these conditions, a small fraction of metabolic genes are differentially required for tumor progression. Among these, loss of heme synthesis reduces tumor growth due to a limiting role of heme in vivo, an effect independent of tissue origin or immune system. Our screens also identify autophagy as a metabolic requirement for pancreatic tumor immune evasion. Mechanistically, autophagy protects cancer cells from CD8+ T cell killing through TNFα-induced cell death in vitro. Altogether, this resource provides metabolic dependencies arising from microenvironmental limitations and the immune system, nominating potential anti-cancer targets.
196 Checkpoint blockade therapy for brain-metastatic non-small cell lung cancer: a comparative effectiveness analysis of national data

Background Management of advanced non-small cell lung carcinoma (NSCLC) has been transformed by PD-1/PD-L1 immune checkpoint inhibitors (ICI), with FDA approvals in 2015 (second-line) and 2016 (first-line). Despite ~40% of NSCLC patients developing brain metastases, these patients were disproportionately excluded from the pioneering ICI trials. Thus herein we evaluate the overall survival (OS) associated with ICI in NSCLC brain metastases nationally. Methods Patients newly-diagnosed with stage 4 NSCLC, including brain metastases, from 2010–2016 were identified from the National Cancer Database (comprising >70% of all newly-diagnosed cancers in the U.S.) Landmark survival analysis was used to address immortal time bias. Post-approval, median time from diagnosis to ICI was 58 days, and this timepoint was selected for all landmark survival analyses (OS estimated by Kaplan-Meier technique, and compared by logrank test and multivariable Cox regression) and for multivariable logistic regression to identify predictors of ICI utilization. Results 50,858 patients presented with advanced NSCLC that involved the brain: representing 27.6% of all newly-diagnosed stage 4 cases. Following initial FDA approvals in 2015, ICI use in brain metastasis patients rose from 7.2% in 2015 to 12.7% in 2016. OS for NSCLC brain metastasis patients diagnosed post-approval (i.e. 2015, median 6.3 months, 95% [confidence interval] CI: 6.0–6.6) was substantially better than those diagnosed pre-approval (median 5.5 months, 95%CI: 5.4–5.7, p Conclusions Nationally, the use of ICI for NSCLC brain metastasis patients is increasing, generally without significant socioeconomic barriers. Brain metastasis patients diagnosed in the post-approval second-line ICI era (2015) demonstrated significantly better OS than patients diagnosed pre-approval and even than patients diagnosed only in 2014. ICI was associated with a >60% relative increase in median OS. Together our findings from a real-world population demonstrate that the dramatic OS benefits of ICIs for advanced NSCLC also extended to brain metastasis patients.
Effects of graded increases in ethanol consumption on biochemical markers of bone turnover in young adult male cynomolgus macaques.

Abstract Chronic heavy alcohol use is often associated with reduced bone mineral density and altered bone turnover. However, the dose response effects of ethanol on bone turnover have not been established. This study examined the effects of graded increases of ethanol consumption on biochemical markers of bone turnover in young adult male cynomolgus macaques (Macaca fascicularis). For this study, 6.6-year-old (95% CI: 6.5, 6.7) male macaques were subjected to three 30-day sessions of increased ethanol intake over a 90-day interval. During the first 30 days, the monkeys drank a predetermined volume of ethanol corresponding to 0.5 g/kg/day, followed by 1.0 g/kg/day and 1.5 g/kg/day. Osteocalcin, a marker of bone formation, and carboxyterminal cross-linking telopeptide of type 1 collagen (CTX), a marker of resorption, were measured during each 30-day session. In addition, the ratio of osteocalcin to CTX was determined as a surrogate measure of global turnover balance. Mean osteocalcin decreased by 2.6 ng/mL (1.8, 3.5) for each one-half unit (0.5 g/kg/day) increase in dose (p
Flexible Runtime Reconfigurable Computing Overlay Architecture and Optimization for Dataflow Applications

Many computationally intensive applications are accelerated on FPGAs following the stream computing, also called dataflow computing, paradigm. This entails that data is streamed through different components of a given application in wide deep pipelines to maximize throughput. One of the main drawbacks of this computing paradigm is that it consumes a large number of hardware resources. Thus, in this work, we propose a partial runtime reconfigurable overlay on which to map any computationally intensive application given as a behavioral description for High-Level Synthesis (HLS) composed of multiple stages, which would typically fit the stream computing paradigm. This overlay uses the internal's FPGA BlockRAM to store the intermediate results of each stage in order to speed up the computation and time-multiplexes the different stages by reconfiguring the computational part. This work also includes a design methodology to optimize the micro-architectural implementation of each stage in order to balance the dataflow architecture as well as generating systems with unique area vs. performance trade-offs. The proposed architecture and methodology has been prototyped on a Xilinx Zedboard mounting a Zynq FPGA using a variety of synthetic dataflows and a case study of a JPEG encoder is presented highlighting the benefits of it. The overlay will be made public and open source after the publication of this paper.
Safely Social: Promoting and Sustaining Adolescent Engagement in Social Distancing During the COVID-19 Pandemic.

Abstract Purpose Adolescents are at risk for violating COVID-19 social distancing measures owing to salient developmental needs for autonomy and relatedness. This intensive longitudinal study investigated the initiation and sustainment of adolescents' daily social distancing behaviors. Methods Focus group and daily-diary approaches were used to collect 6,216 assessments from a nationwide American adolescent sample (n = 444; Mage = 15.1; 40% male; 42% black/African American, 40% white/European American, 10% Latinx, 6% Asian American, 2% Native American) over the course of 14 days at the onset of the COVID-19 pandemic. Results When adolescents were motivated by preventing others from getting sick, they were more likely to engage in social distancing (same day: B = .50, SE = .09, 95% confidence interval [CI] [.32, .68] p Conclusions Adolescents who were motivated by the desire to protect others were more likely to engage in social distancing. In addition, adolescents who learned about preventative health behaviors for mitigating COVID-19, received peer support, and remained virtually connected with friends were more likely to engage in daily social distancing at the onset of the pandemic.
An Unchained Dog of War: An Examination of the Lack of Constraint on Presidential Uses of Force in the Modern Era

Research on the constraint President’s face in matters of foreign policy is generally of the view that they are largely free to do as they please. Some research however posits that Congressional co...
Optimization II - the rise of distributed intelligence

This paper gives emphasis on the distributed intelligence and agent-based cooperative control systems. The near impossibility of totally centralized control for complex systems was discussed, including the need for decentralized control, in particular, decentralized control using simple strategies. Starting from first principles and using examples from nature for inspiration, the principles for, and future of, such systems were speculated.
Hypothalamo-adenohypophyseal-thyroid interrelationships in the chick embryo. IV. Immunocytochemical demonstration of TSH in the hypophyseal pars distalis.

Abstract The cells that synthesize thyroid-stimulating hormone (TSH) in the pars distalis of the chick embryo were identified immunocytochemically (immunoperoxidase and immunofluorescence) using anti-bovine TSH-β and anti-human TSH-β sera. TSH cells are first demonstrable on Day 6.5 of incubation. By Day 11.5, when the two lobes (rostral and caudal) of the pars distalis are easily recognized, TSH cells are confined exclusively to the rostral lobe. TSH cells identified by means of immunofluorescence were stained with the periodic acid-Schiff component of the performic acid-Alcian blue periodic acid-Schiff's Orange G stain. Immunoreactive TSH cells in the partes distales of Day 13.5 chick embryos, injected at 5.5 days of incubation with thiourea, were more intensely stained than their normal counterparts. The marked change in immunocytochemically demonstrable TSH on Day 11.5 corresponds with physiological and morphological events occurring within the hypothalamus, adenohypophysis, and the thyroid gland of the developing chick during this midincubational (midgestational) period. The data suggest that not only is hypophyseal TSH present in greater quantities after Day 10.5, but that adenohypophyseal synthesis and secretion of TSH may be stimulated by another factor (hypothalamic TRH) at this time, signaling functional maturation of the hypothalamo-adenohypophyseal-thyroid axis.
Analysis of developmentally homogeneous neural crest cell populations in vitro. I. Formation, morphology and differentiative behavior.

Abstract When early embryonic quail neural tubes are dissected free from surrounding tissues and placed in culture, small stellate neural crest cells usually migrate from the explant onto the substratum. This outgrowth has been reported to consist of a mixture of cells, some of which undergo melanogenesis, while the rest remain unpigmented. We have, in contrast to earlier observations, obtained a spatial separation of the two phenotypes. In these cultures the primary outgrowth of migrating cells remained almost free of pigment-forming cells, whereas small spherical clusters containing several hundred pigment-forming cells appeared on the explanted neural tubes. Whether the clusters remained with the tube explants or were subcultured, all cluster cells differentiated into melanocytes. Prior to melanogenesis, the appearance of the cultured cells from a cluster was indistinguishable from the cells in the outgrowth. The clusters provide a source of neural crest cells, that (1) can be easily obtained in comparatively large numbers, (2) is not contaminated with any other cell type, (3) can be isolated before the onset of differentiation, and (4) is developmentally homogeneous. Thus, the cluster population is well suited for many types of experiments, such as the identification of specific environmental factors that might control neural crest cell differentiation.
Effects of a Speed-of-Processing Intervention on Driving Performance: The ACCELERATE Study

Useful Field of View performance, as measured by UFOV, is a valid and reliable predictor of crash involvement among older drivers, and UFOV performance improves with Speed of Processing (SOP) training. The ACCELERATE Study is examining the effects of SOP training on other cognitive functions and on everyday mobility among older adults at risk for impaired mobility. To date, 59 participants have been randomly assigned to SOP training and 59 to an Internet training control group (total n = 118). At baseline and post-test, participants are given extensive cognitive, sensory, health, and mobility assessments, as well as driving assessments in either a driving simulator or an instrumented vehicle. Preliminary results indicate that performance on the UFOV improves significantly more in the SOP training group than in the control group. Furthermore, means on most other cognitive variables are in the direction of greater improvement for SOP trainees than controls, with significant transfer of training on select speeded measures. Preliminary analyses of driving indicate that relative to controls, SOP trainees have improved in the speed with which they are able to detect moving targets originating in the periphery and moving toward central vision, but not in the detection of static targets originating in central view. Thus, some driving tasks appear to benefit from SOP training, while others do not. Results suggest that Speed of Processing training may transfer to other cognitive functions as well as to everyday mobility performance, such as driving.
Ionizable Nitroxides for Studying Local Electrostatic Properties of Lipid Bilayers and Protein Systems by EPR

Electrostatic interactions are known to play a major role in the myriad of biochemical and biophysical processes. Here, we describe biophysical methods to probe local electrostatic potentials of proteins and lipid bilayer systems that are based on an observation of reversible protonation of nitroxides by electron paramagnetic resonance (EPR). Two types of probes are described: (1) methanethiosulfonate derivatives of protonatable nitroxides for highly specific covalent modification of the cysteine's sulfhydryl groups and (2) spin-labeled phospholipids with a protonatable nitroxide tethered to the polar head group. The probes of both types report on their ionization state through changes in magnetic parameters and degree of rotational averaging, thus, allowing the electrostatic contribution to the interfacial pKa of the nitroxide, and, therefore, the local electrostatic potential to be determined. Due to their small molecular volume, these probes cause a minimal perturbation to the protein or lipid system. Covalent attachment secures the position of the reporter nitroxides. Experimental procedures to characterize and calibrate these probes by EPR, and also the methods to analyze the EPR spectra by simulations are outlined. The ionizable nitroxide labels and the nitroxide-labeled phospholipids described so far cover an exceptionally wide range of ca. 2.5-7.0 pH units, making them suitable to study a broad range of biophysical phenomena, especially at the negatively charged lipid bilayer surfaces. The rationale for selecting proper electrostatically neutral interface for probe calibration, and examples of lipid bilayer surface potential studies, are also described.
An A-Z Guide to Pharmacogenomics. Michael G. Catania. Washington DC: AACC Press, 2006, 58 pp., $24 ($19 AACC members), softcover. ISBN 1-59425-047-2.

What is an allele or a genetic variant, and how is it related to drug dosing? What do the acronyms ADMET and RFLP mean? What is a CYP450 or its genetic variant? For those uninitiated into the new realm of “pharmacogenomics”, for whom the meanings of these words are not clear or need refreshing, this little book, packed with useful definitions, will be invaluable. Even those already involved in this discipline may benefit from the …
Mechanisms of left-right determination in vertebrates.

We would like to apologize for the impossibility of citing all relevant references due to space constraints. The authors would like to thank M. Brueckner, C. Rodriguez-Esteban, and J. Yost for stimulating discussions that have helped to shape some of the ideas presented in this review. K. J. V. is a Genetics Institute Fellow of the Life Sciences Research Foundation, and research in C. T.'s laboratory on this topic is supported by a grant from the NIH. Research on L/R development in J. C. I. B.'s laboratory is supported by grants from the NIH and the G. Harold and Leila Y. Mathers Charitable Foundation.
Sedimentation of the northwestern Gulf of Mexico

Six years of intensive study of the shallow water sediments of the northwestern Gulf of Mexico have indicated that there are many criteria by which ancient sediments deposited under similar conditions can be recognized. Thus the presence of echinoid fragments and of glauconite-filled Foraminifera tests favors marine shelf deposition over bay deposits; calcareous aggregates and grains of gypsum suggest high salinity bay deposits; abundance of wood fibers, high mica content, ferruginous aggregates, and well laminated sediments all are suggestive of deposition near river mouths; greater roundness distinguishes dunes from adjacent beach sands; and coarser grain size distinguishes beach sands from shallow shelf sands in the vicinity.
Habitat loss and modification due to gas development in the Fayetteville shale.

Hydraulic fracturing and horizontal drilling have become major methods to extract new oil and gas deposits, many of which exist in shale formations in the temperate deciduous biome of the eastern United States. While these technologies have increased natural gas production to new highs, they can have substantial environmental effects. We measured the changes in land use within the maturing Fayetteville Shale gas development region in Arkansas between 2001/2002 and 2012. Our goal was to estimate the land use impact of these new technologies in natural gas drilling and predict future consequences for habitat loss and fragmentation. Loss of natural forest in the gas field was significantly higher compared to areas outside the gas field. The creation of edge habitat, roads, and developed areas was also greater in the gas field. The Fayetteville Shale gas field fully developed about 2 % of the natural habitat within the region and increased edge habitat by 1,067 linear km. Our data indicate that without shale gas activities, forest cover would have increased slightly and edge habitat would have decreased slightly, similar to patterns seen recently in many areas of the southern U.S. On average, individual gas wells fully developed about 2.5 ha of land and modified an additional 0.5 ha of natural forest. Considering the large number of wells drilled in other parts of the eastern U.S. and projections for new wells in the future, shale gas development will likely have substantial negative effects on forested habitats and the organisms that depend upon them.