cssi/SciSciGPT-SciSciNet huggingface dataset:
Maximizing the Opportunities of the Internet for International Trade

The last decade has witnessed remarkable developments in the digital economy, creating new opportunities for crossborder trade and investment and the ongoing emergence of novel and disruptive businesses models. At the same time, the Internet is transforming how goods and services are produced, delivered, and consumed both domestically and internationally. The transformation in the character of crossborder trade in goods and services, which are increasingly embedded, is also resulting from global value chains, made possible by the flow of immense amounts of data across borders. This has given rise to a growing overlap between the trade regime and other areas of domestic regulatory intervention — notably with respect to privacy and security. The present paper examines the challenges and opportunities that growth of the digital economy creates for trade and development. It seeks to identify supportive trade policy measures to enhance the benefits of digitization globally as well as avenues to establish regulatory practices that permit cross-border data flows and improved regulatory cooperation among countries. Following a discussion of the impact of the Internet on the nature of international trade and an overview of important regulatory and other barriers, the paper outlines recommendations on how policy-makers and interested stakeholders can address existing constraints and help create an enabling environment to realize the opportunities of the Internet and crossborder data flows for growing digital trade. The policy options are grouped under four categories: maximizing and updating WTO rules; negotiating a digital trade agreement; expanding and deepening regulatory cooperation on key related policy issues; and enhancing collaborative efforts between governments, the private sector, and civil society. The objective of this broad range of options is to gradually develop a comprehensive set of nternational trade rules and norms to ensure that the opportunities of the Internet for inclusive growth and development are exploited.
El dolo causal: Su repercusión en el contrato

En este trabajo, analizaremos la figura del dolo causal como modulo de distribucion de riesgos del contrato, lo que supone que su ocurrencia puede repercutir en el contenido del mismo y justificar el ejercicio de remedios por incumplimiento. En particular, el centro de atencion se situara en la compatibilidad de la pretension indemnizatoria con la ineficacia del contrato, potencial o declarada, y la naturaleza de la responsabilidad que pudiere surgir.
Identification and Characterization of a Series of Novel Jak2 Small Molecule Inhibitor Compounds.

Recent work from our lab has been aimed at identifying novel Jak2 tyrosine kinase inhibitor molecules. Here, we refined our previous Jak2 molecular model using information obtained from the crystal structures of the Jak2 and Jak3 kinase domains. A total of 223,481 compounds within the NIH small molecule database were then screened in silico using FlexX 1.13.2 in order to identify compounds that specifically bind and inhibit Jak2. In what is now our third generation of Jak2 inhibitors, analysis of the highest scoring compounds identified a set of structurally diverse molecules that potently inhibited Jak2 autophosphorylation not only at Tyr 1007, but at all 49 tyrosine residues. These compounds significantly inhibited proliferation of the human erythroleukemia (HEL) cells, which express the Jak2-V617F mutation on both alleles (Fig. 1). One compound in particular, herein designated as G6, was further examined in greater detail. The mechanism by which G6 inhibits Jak2-V617F dependent cell growth is via a marked increase in cellular apoptosis (Fig. 2). We found that G6 does not inhibit c-Src and Tyk2 autophosphorylation at doses that completely inhibit Jak2, therefore suggesting a high degree of specificity. We found that both the G6 and the G13 compounds significantly reduced ex vivo megakaryocyte colony formation of cells taken from a patient diagnosed with essential thrombocythemia and harboring the Jak2-V617F mutation. Finally, we examined the ability of G6 to inhibit red blood cell formation in C57BL/6 mice following acute hemolytic anemia. We found that treatment of animals with G6 (10 mg/kg/day for five days, IP) resulted in a marked inability of these animals to increase their hematocrits following acute anemia when compared to vehicle control animals. Additionally, histological analysis of the bone marrow of G6 injected animals exhibited erythroid hypoplasia resulting in a skewed M:E ratio when compared to vehicle control animals. Collectively, our data demonstrate that these small molecule compounds inhibit Jak2 function in vitro , ex vivo , and in vivo . As such, they may have therapeutic value in treating diseases that are caused by aberrant Jak2 kinase function. ![ Figure 1 ][1] Figure 1 ![ Figure 2 ][1] Figure 2 [1]: pending:yes
ZAP-70 Expression in Acute Lymphoblastic Leukemia: Association with the E2A/PBX1 Rearrangement and with the Pre-B Stage of Differentiation.

The zeta associated protein (ZAP) is a 70-kD molecule associated with the z chain of the CD3 receptorial complex which plays an important role in several signalling pathways following TCR ligation. Historically, this protein was thought to be specific of T and NK cells. A study based on nucleotide arrays on chronic lymphocytic leukemia (CLL) cells revealed the presence of ZAP-70 in CLL samples which carried an unmutated configuration of the IgV H genes. This finding opened a new area of investigation regarding the presence and putative role of ZAP-70 in B cells. In the present study, we evaluated the expression of ZAP-70 and Syk in acute lymphoblastic leukemia (ALL), using data derived from a series of 128 adult patients analyzed by oligonucleotide arrays and by the quantification of the protein levels. All samples, evaluated for gene expression profiling at the onset of the disease, contained over 90% leukemic cells and were enrolled in the Italian multicenter clinical trial GIMEMA 0496. Of the cases analyzed, 33 had T-ALL and 95 B-lineage ALL: within this latter group, 5 samples carried the E2A/PBX1 rearrangement, 10 the ALL1/AF4 rearrangement, 37 were BCR/ABL+ and 42 samples did not harbor any major molecular abnormality. As expected, ZAP-70 was found highly expressed in T-ALL and a highly significant difference was observed compared to B-lineage ALL (average values 752±268 and 309±105, respectively; p
Unraveling mechanics of armchair and zigzag graphene nanoribbons

The unraveling process of armchair and zigzag graphene nanoribbons (GNRs) was studied with molecular dynamics simulations using the Adaptive Intermolecular Reactive Empirical Bond Order Potential for carbon–carbon bond. Simulations were performed at 300°K, with GNR length and width varying from 2.5 nm to 15 nm in 2.5 nm increments. In these simulations, the unraveling of the GNRs was started from two positions; the corner or the middle of the top side. Force–displacement relationship was analyzed for the terminal atom of the unraveling chains. For armchair GNRs (AGNRs) that were unraveled from the corner, the force required for the onset of the unraveling is in the range of 4.279–5.045 eV/A, and the observed failure force in the carbon chain is in the range of 5.553–5.963 eV/A. Unraveling will not happen when AGNRs are unraveled from the middle, and zigzag GNRs (ZGNRs) are unraveled either from corner or middle. For the latter cases, the bond between the terminal atom and GNR sheet breaks under the stretc...
Chapter 5 – Hope as a Common Factor across Psychotherapy Approaches: A Lesson from the Dodo's Verdict

Publisher Summary Despite providing different explanations and targeting disparate symptoms, various psychological approaches for producing change appear to be equally effective. The chapter compares this phenomenon to the Dodo's verdict in “Alice in Wonderland,” in the end race. It explores the question—specifically, what mechanism (or mechanisms) underlie the equal, high efficacy produced by differing types of psychological interventions. Agency reflects people's thoughts about their capacity to use the pathways they have selected to reach their goals. Agency is crucial for the psychotherapy process because it provides mental energy so that a client can undertake various therapy-related activities. This type of goal-directed motivation is reflected in self-affirming mental statements. Operating across differing samples and methodologies, agentic thinking both initiates and helps sustain clients' improvements in psychotherapy. Furthermore, enlisting the literature on placebo effects to illustrate the impact of agentic thinking. The chapter demonstrates how agency alone propels clinical improvement. Agentic thought is the motivational force or engine in hope theory. All the mental energy imaginable, however, cannot guarantee successful goal attainment in psychotherapy. Perceptions that one can produce the routes to those goals is a second necessary component. The chapter also explores pathways thinking in the context of varying psychotherapies.
Presidential Institutions and Electoral Participation in Concurrent Elections in Latin America

Previous studies of voter turnout in Latin America have found weak and inconsistent evidence for the link between political institutions and electoral participation. In this article, I use data fro...
Parallel Separations in Microfabricated Channels With Capillary Electrophoretic Sample Introduction

We have developed a method to carry out small-scale electrophoretic separations by coupling electrophoresis in a capillary to electrophoresis in a narrow rectangular channel. This format allows rapid sequential separations or continuous analysis to be carried out on small-volume samples and with efficient heat dissipation. This approach has been developed for dynamic sampling of picoliter microenvironments (i.e., solution around single cells). Separations in 8-μm thick channels with electrochemical array detection provide low femtomole detection limits for separated catecholamines. We have also demonstrated separations in 0.6-μm channels and work with 0.2-μm channels is planned. The long-term goals of this methodology include continuous separations with sub-second time resolution, development of attomole detection limits, and new separation modes in these extremely narrow structures. Another goal of this work is to use this separation format to introduce and separate large numbers of DNA samples in parallel. Both of these goals require limiting the lateral spreading in the channel and, hence, we have developed channels with microlithgraphically defined partitions.
The Purdue Extension and Indiana CTSI’s Community Health Partnerships collaboration: An innovative, generalizable, state-wide model to help communities build a culture of health

The Indiana Clinical and Translational Sciences Institute's Community Engagement Partners-Purdue Extension collaborative model demonstrates tremendous potential for creating state-wide programmatic efforts and improvements in both the health culture and status of Indiana residents across the state. It can serve as a prototype not only for others interested in pursuing wide geographic health improvements through Clinical and Translational Sciences Award-Cooperative Extension partnerships but also for broader collaborations among United States Department of Agriculture, National Institutes of Health, Centers for Disease Control and Prevention, state and local health departments, and health foundation efforts to improve population health.
Treating Hallucinations and Delusions Associated With Parkinson's Disease Psychosis.

We discuss features of Parkinson’s disease psychosis (PDP) including symptomology and pathophysiology. Treatment options, including non-pharmacologic strategies, dose reduction of offending agents, and the addition of non-dopaminergic antipsychotics, are addressed. The efficacy of second-generation antipsychotics and novel agents is examined. Pimavanserin, a 5-HT2A/C receptor inverse agonist with no other receptor activity, has shown efficacy and tolerability and is now FDA approved for PDP treatment. Research into novel targets is ongoing. PDP is a morbid complication of Parkinson’s disease with complex incompletely understood mechanisms. Treatment is directed towards mitigation of psychosis without worsening of motor features.
A Honeybug for Automated Cyber Reasoning Systems

Automated cyber reasoning systems are susceptible to deceit and manipulation. In the Cyber Grand Challenge, the Rubeus system patched binaries with a honeybug that enticed competitor systems to pursue the honeybug instead of exploiting actual vulnerabilities. Surmising how these automated systems operated, we were able to take advantage of differences from the official scoring system to detect and manipulate their behavior. Methods for detecting and countering automation in the real world may be used to thwart the ability of malicious actors to find vulnerabilities.
Estrogen Receptor Activation by Ligand-Dependent and Ligand-Independent Pathways

Estrogens are a class of female sex steroid hormones important for the growth and differentiation of mammary and reproductive tissues and brain. The biological activities of these hormones are mediated by the estrogen receptor (ER), an intracellular phosphoprotein which binds a comparatively small molecular weight steroidal ligand and transduces its signal to the nuclear genetic apparatus. This protein belongs to a gene superfamily of ligand-activated transcription factors whose members are distinguished by the presence of three regions of homology, named C1, C2 and C3 (Carson-Jurica et al, 1990). The region of greatest conservation, C1, is composed of a sequence motif of 66-68 amino acids proposed to form two type II zinc fingers (Evans, 1988; Carson-Jurica et al, 1990; Green and Chambon, 1991 and references therein). Each finger contains 4 invariant cysteine residues thought to coordinate a single zinc atom and together these fingers in the context of the surrounding amino acid sequence determine the specificity of receptor binding to DNA (reviewed by Freedman, 1992). The characteristic homology of this region has been exploited to allow the rapid identification of new gene superfamily members in species as diverse as sea urchin (Chan et al, 1992), Drosophila (Mlodzik et al, 1990) and man (Wang et al, 1989), and although the final size of this superfamily is presently unknown, estimates suggest it may eventually encompass as many as 50 members (O’Malley and Conneely, 1992). Of the members identified to date, there are two major subgroups: those for which a ligand has been identified such as the steroidAhyroid/vitamin receptors, and those for which a putative ligand, if any, is currently unknown (O’Malley, 1990). These latter proteins, referred to as ‘orphan’ receptors, are the subject of ongoing investigations to determine their physiological ligand and/or other factors that may regulate their transcriptional activity.
Successful Systems for Out-of-Hospital Resuscitation

A patient with out-of-hospital cardiac arrest (CA) stands little chance for survival without prior organization and preparations for immediate resuscitation. Fortunately, many communities have achieved relative success with resuscitation since the 1970s. In the 1970s, cities such as Seattle and Milwaukee achieved overall survival-to-hospital discharge rates for the subgroup of patients with out-of-hospital ventricular fibrillation (VF) that exceeded 20 to 30% (1,2). Both of these communities used a classic deployment system for out-of-hospital CA that sent a three- to four-member firefighter crew as a neighborhood “first-responder” (FR) followed by a two- (or more) member paramedic ambulance crew. In cases of witnessed collapse in which the patient received immediate basic cardiopulmonary resuscitation (BCPR) by bystanders and presented to paramedics with VF, survival rates in these systems exceeded 40%. This finding was duplicated in several other communities, including the City of Houston Emergency Medical Services (EMS) system after a major restructuring in the 1980s (3).
Plenary panel: digital government research what we have learned about forging successful DG research projects

This panel session will feature a discussion of the challenges inherent in digital government research projects due to their interdisciplinary nature and practice-based settings. We aim to offer a future-oriented perspective that rests on an open discussion of past and current experiences, with a special focus on the key issues that make (or break) digital government research projects.
Random signals, linear systems, and power spectra

This chapter explores some basic principles and definitions essential for understanding additional approaches for analyzing random signals. Secondly, it introduces some basic concepts and applications of filtering. The important properties of some random signals reside in the frequency domain. It is obvious that the diseased heart has more energy at relatively higher frequencies than the normal heart. However, direct Fourier transformation is not sufficient for performing the frequency analysis. Other concepts based on the definition of signal power must be used. This leads to two nonparametric methods for frequency analysis: (1) the periodogram and Blackman–Tukey methods. Another different approach involving systems concepts is also commonly used and is called the parametric approach. This approach requires the estimation of system parameters. The intermediate step is to actually create a discrete time model for the signal being analyzed. For this, the chapter explains some basic principles of discrete time systems. It also presents a review of the system definition. It formalizes the concept of using a discrete time system to induce structure in a sequence. This is accomplished by using white noise as the input and the structured sequence as the output. The last section of the chapter discusses time series models for spectral density.
What is a Hay Baler

The issue that I wish to discuss is meaning in the law of contract. My point of departure is the question, “What is a hay baler?” The question, at first glance, may seem to be prosaic and its answer obvious. This question, however, arose in litigation, and did so in a particularly vexing way. It was vexing because it ensued that a machine does not necessarily have to be capable of baling hay in order for it to be, in the eyes of the law at least, a hay baler.
Analytical Techniques for the Study of Biological Membranes

Molecular studies of membrane biology have received extremely enthusiastic attention in recent years. This is in part due to the increasing awareness of membrane involvement in many aspects of life phenomena, such as neural transport, muscle action, metabolism, carcinogenesis, immunology, etc., and in part due to the rapid development of highly delicate analytical techniques for studying macromolecular phenomena. With these techniques much information not available a decade ago is now readily accessible. Although a thorough understanding of membrane biology is still far from reached, the information acquired so far does discern, more or less, the gross aspects of the mysterious puzzle.
Utilizing Resources At-Hand: Fitting Diverse Content from Diverse Content Providers into a Common System

University digital repositories represent a major challenge in that they require people from a variety of disciplines to conform to a set of standards to make their materials searchable. While each discipline is unique and each department has different financial and professional resources available, consistency across collections is necessary to produce an attractive and useful digital repository. Librarians can play a key role in helping departments across the university understand and implement metadata schema, archival scanning standards, and tools for effective accessibility to digital collections while working with the limited resources available to design a practical digitization plan. This paper describes development of a digitization plan for two different university departments whose resources and skills sets represent both ends of the resource spectrum. Collection needs were addressed by understanding the department goals and language, understanding of the materials to be digitized and the audience they will serve, and implementing standards that are consistent across collections yet applicable to the audience. This approach has worked to quickly launch several digital collections on a university campus that would otherwise remain hidden and unutilized because of challenges posed by limited departmental resources.
Assisted Reproductive Technology Practice Management

A basic knowledge of management issues is required in the operation of any medical practice. This chapter highlights the critical practice management principles necessary for effective interaction with other professionals in business management, human resources, payer organizations, legal counsel, accounting, and risk management who interface with the practice.
Preparation of Body Sections for the Study of Mediastinal Anatomy

The anatomy of the mediastinum is exceedingly complex, and therefore clinical and radiologic problems encountered daily require a knowledge of structural relationships that may not always be firmly in mind. Many excellent texts of anatomy and correlated radiographic anatomy are available to provide such information [1–8]. Obviously, the advent of computed tomography and magnetic resonance imaging has been a major stimulus for the development of many of these works and has resulted in a renewal of interest in such classical texts as authored by Eycleshymer and Schoemaker [4] and by Pernkopf [7].
The lineage decisions of helper T cells

After encountering antigen, helper T (T(H)) cells undergo differentiation to effector cells, which can secrete high levels of interferon-gamma, interleukin-4 (IL-4), IL-10 and other immunomodulators. How T(H) cells acquire, and remember, new patterns of gene expression is an area of intensive investigation. The process is remarkably plastic, with cytokines being key regulators. Extrinsic signals seem to be integrated into cell-intrinsic programming, in what is becoming an intriguing story of regulated development. We summarize the latest insights into mechanisms that govern the lineage choices that are made during T(H)-cell responses to foreign pathogens.
G0/G1 Switch 2 regulates a G1-lipid checkpoint dependent radiation sensitivity of human head and neck squamous cell carcinoma

A recent study reports the presence of a G1-lipid checkpoint that is dysregulated in clear cell renal carcinoma. A defective G1-lipid checkpoint forces these cells to utilize lipids as their energy source. Head and neck squamous cell carcinoma (HNSCC) cells with a higher percentage of G0/G1 cells (low proliferative index, LPI) are more resistant to radiation therapy compared to HNSCC cells with a lower percentage of G0/G1 cells (high proliferative index, HPI) 2. In this study, we investigated whether lipid metabolism regulates HNSCC cell cycle phase specific radiation sensitivity. Results from Fluorescent Ubiquitination-based Cell Cycle Indicator expressing Cal27 cells showed that cells in G0/G1 phase (LPI) are more resistant to radiation therapy compared to cells in S/G2/M phases (HPI). RNAseq and bioinformatics identified lipid and mitochondrial metabolism as the major intrinsic pathways that are different between HPI and LPI Cal27 cultures. Among the genes regulating lipid metabolism, mRNA levels of G0/G1 Switch 2 (G0S2) were found to be significantly higher in LPI compared to HPI Cal27 cultures. G0S2 was originally identified in blood mononuclear cells as a cell cycle protein of unknown functions3. Recent literature reports G0S2 as a negative regulator of the cytoplasmic neutral lipase, adipose triglyceride lipase (ATGL) 4. siG0S2 treatment of Cal27 LPI cultures recruited more cells into the proliferative cycle enhancing their radiation sensitivity. In contrast, inhibition of ATGL activity with atglistatin suppressed radiation induced toxicity. Furthermore, LPI cultures treated with palmitate enhanced mitochondrial respiration and increased ROS levels as well as lipid peroxidation resulting in radiation sensitization. These results support the hypothesis that G0S2 coordinates a G1-lipid checkpoint: G0/G1 cells prior to this checkpoint are resistant to radiation treatment, whereas S/G2/M cells that are beyond this checkpoint are radiation sensitive. We propose palmitate as a newly identified radiation sensitizer for HNSCC. (PMID:27956548; PMID:25229973; PMID:1930693; PMID:20676045)
Whole Woman's Health v. Hellerstedt and What It Means to Protect Women

This chapter tells the story of Whole Woman’s Health v. Hellerstedt, the 2016 case in which the Court invalidated a Texas law (H.B. 2) that imposed onerous regulations on abortion providers — and not on providers of other medical procedures of equal risk — in the name of protecting women’s health. The chapter focuses not only on the Court’s decision, but on actors such as Americans United for Life (AUL), an influential advocacy group partly responsible both for H.B. 2 and for the broader constitutional strategy that produced it. AUL has been tremendously successful in restricting women’s access to abortion in recent years by pursuing an incremental strategy that aims to “hollow[] out Roe,” not by challenging it directly but by promoting ever-stiffer abortion regulations and persuading courts to weaken constitutional protection for the abortion right. One of the chief ways AUL has pursued these goals is by casting abortion regulation as woman-protective, asserting that such regulation shields women and fetuses alike from a greedy and unscrupulous abortion industry. During the legislative debates over H.B. 2, legislators opposed to the law disputed that it was protective of women. They argued that there were no legitimate health justifications for the law, that it would actually hurt women by driving reproductive healthcare clinics out of business, and that the state’s poor track record when it came to protecting women’s health undermined its claim to be acting for that reason here. The central question in Whole Woman’s Health was whether the Court would defer to the legislature’s assertion that it was acting to protect women’s health or whether it would look to see whether the controverted regulation actually yielded health benefits. The Court did the latter: It examined whether Texas’s law actually served the state’s interest in protecting women’s health, and how the law affected women’s ability to exercise the abortion right. By scrutinizing the law and finding that the balance of interests weighed heavily in favor of invalidation, the Court handed AUL and other anti-abortion forces a defeat. But it did not take long for those forces to regroup, and it is not at all clear that they will lose the broader battle over abortion rights in the coming decades.
Intermittent treatment strategies using aromatase inhibitors: a preclinical study

5436 Three third-generation aromatase inhibitors (AIs), anastrozole (ANA), exemestane (EXE) and letrozole (LET), are important drugs for hormonal therapy of breast cancer in postmenopausal women. Currently, a major setback with using these drugs is the development of acquired resistance. In addition, we do not have a definitive answer as to whether a non-cross resistance between steroidal AI (i.e., EXE) and nonsteroidal AIs (i.e., ANA and LET) exists. With such considerations, our laboratory has initiated a preclinical research project which we believe will be valuable for the design of future clinical trials on AIs. MCF-7aro, an ER+ and aromatase over-expressing cell line, was used to generate a series of AI-resistant lines. Results generated so far from our laboratory indicate that mechanisms of inhibition and resistance of EXE are different from those of ANA and LET. Based on these findings, experiments have been carried out to test the hypothesis that intermittent use of a single AI, i.e., EXE will decrease/delay acquired resistance compared to conventional therapies. Three types of experiments have been performed. [1].MCF-7aro cells were cultured in the presence of T and an intermittent use of a single AI (e.g., one week on and one week off, two weeks on and one week off, etc.). The time to progression (resistance) for each condition was compared to that attained with continuous treatment of the AI. Results generated have revealed that resistance developed after continuous treatment of EXE for 8 - 10 weeks. On the other hand, acquired resistance was developed in the three intermittent groups after treatment for 32 weeks. [2].EXE-resistant MCF-7aro cells developed after continuous treatment were further treated with EXE in an intermittent manner. The cells initially responded to the intermittent treatment and became resistant after 8 weeks. [3].ANA-resistant MCF-7aro cells were treated with EXE intermittently. While these experiments are still ongoing, we have learned that ANA-resistant cells respond to EXE at least up to 6 weeks. We also compared the effects of continuous and intermittent use of a nonsteroidal AI, i.e., LET. The time to progression (resistance) was found to be identical for the two culture conditions for LET. Therefore, we have not observed any advantage for an intermittent use of LET. We believe that these results will serve as an important basis for the design of intermittent therapies using AIs such as EXE. While one may argue that results generated from such cell culture experiments cannot be immediately translated to clinical applications, the reality is that not enough valid information is available for the design of new clinical trials. The results generated from our proposed study will serve as an important basis to improve the efficacy of AIs in the treatment of hormone-dependent breast cancer (supported by NIH grants CA44735 and ES08258).
Flow About a Two-Dimensional Flat Plate

In the previous chapters, we have presented a general set of tools with which to obtain the flow field and the force and moment due to inviscid flow about a rigid body. In this chapter, we consider an important special case of this general problem: the rigid-body motion of an infinitely-thin flat plate of length c in two dimensions. As usual, we assume that the flow is incompressible and irrotational, except for one or more isolated vortex elements, as depicted in Fig. 8.1. We will first build from the results of Chap. 4 to seek an expression for the velocity field for this flow; then we will apply the results from Chap. 6 to obtain the force and moment on the plate in Sect. 8.3. Then, in Sect. 8.4, we will demonstrate the application of the Kutta condition to regularize the flow at just the trailing edge, or at both edges, and discuss the consequences of both. With all of these tools specialized to the particular geometry of a flat plate, we will find it straightforward in Sect. 8.5 to derive four of the classical results from unsteady aerodynamics, pertaining to small-amplitude perturbations of the plate’s motion or to the fluid environment through which it is traveling.
Risks of Cardiovascular Disease and Beyond in Prescription of Nonsteroidal Anti-Inflammatory Drugs:

Introduction:Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin, naproxen, diclofenac, and ibuprofen, as well as selective cyclooxygenase 2 inhibitors such as celecoxib. Their use is com...
An experimental determination of the quenching distance of methanol and iso-octanemethanol blends

Abstract An apparatus for determining quenching distances for reactive gas mixtures was devised. The test bomb is operated at constant volume and designed with electrodes flanged by circular quartz discs 2.54 cm in diameter. Experiments were performed with methane, methanol, iso-octane and iso-octane methanol blends over a range of equivalence ratios for several mixture initial temperatures and pressures. Quenching distances measured for methane agree well with previous data. New data are reported for methanol and iso-octane methanol blends. The fuel blends were found to have larger quenching distances than either pure fuel. In comparing the data with empirical correlations such as by Daniel or Hicks, et al. it was found that the temperature and pressure exponent of the quenching distance is dependent on fuel type.
Regulations, Policies and Guidelines Pertaining to the Use of Zebrafish in Biomedical Research

Abstract This chapter will briefly review the applicable regulatory oversight of the use of zebrafish in biomedical research in the United States. The responsible agencies and their policies and guidelines will be described. Basic institutional responsibilities are briefly reviewed. Some of the compliance challenges specific to the use of the zebrafish will be discussed.
Sixth Cranial Nerve Palsy as the Presenting Sign of Metastatic Cholangiocarcinoma.

Background Cholangiocarcinoma is a locally invasive, poorly treatable malignancy of the biliary tract that uncommonly metastasizes to the brain and rarely causes neuro-ophthalmologic complications. Case presentation A 34-year-old woman with an isolated sixth cranial nerve palsy underwent brain neuroimaging and was found to have a large sellar/suprasellar mass invading the cavernous sinus. Gross total resection was performed with improvement in the sixth cranial nerve nerve palsy. Next-generation sequencing and histology studies revealed an adenocarcinoma with a fibroblast growth factor receptor (FGFR)2-BICC1 gene mutation. Positron emission tomography/computed tomography scan demonstrated a large hypermetabolic partially necrotic hepatic mass with local invasion, and liver biopsy confirmed a diagnosis of cholangiocarcinoma. At three weeks after resection, the brain lesion recurred and the patient developed worsening diplopia. The patient then received stereotactic radiotherapy applied to the brain lesion and began treatment with gemcitabine and cisplatin. The patient was transitioned to FGFR-targeted therapy with pemigatinib, and the patient was alive at last follow-up, 49 weeks after diagnosis. Conclusion To our knowledge, this is the first report of cholangiocarcinoma presenting as a neuro-ophthalmologic finding, consisting of an isolated sixth cranial nerve palsy, which was the harbinger of a brain metastatic sellar/suprasellar mass. The case highlights the importance of prompt neuroimaging in isolated cranial nerve palsies, particularly in younger patients, and consideration of rare aggressive metastasis to the sellar region, where prompt surgery and pathology are critical in identifying the primary carcinoma and to instituting expedited therapy.
Safety of same-day discharge after uncomplicated, minimalist transcatheter aortic valve replacement in the COVID-19 era.

Objectives We sought to evaluate the safety, efficacy and feasibility of same-day discharge after uncomplicated, minimalist TAVR. Background At the start of the COVID-19 pandemic, we created a same-day discharge (SDD) pathway after conscious sedation, transfemoral (minimalist) TAVR to help minimize risk of viral transmission and conserve hospital resources. Studies support that next-day discharge (NDD) for carefully selected patients following minimalist TAVR is safe and feasible. There is a paucity of data regarding the safety of SDD after TAVR. Methods In-hospital and 30 day outcomes of consecutive patients meeting pre-specified criteria for SDD after minimalist TAVR at our institution between March and July of 2020 were reviewed. Outcomes were compared to a NDD cohort from July 2018 through July 2020 that would have met SDD criteria. Primary endpoints were mortality, delayed pacemaker placement, stroke and cardiovascular readmission at 30 days. Results Twenty nine patients were discharged via the SDD pathway after TAVR. 128 prior NDD patients were identified who met all criteria for SDD. The STS scores were similar between the two groups (SDD 2.6% ±1.5 vs. NDD 2.3% ± 1.2). There were no deaths at 30 days in either group. There was no significant difference in delayed pacemaker placement (SDD 0% vs. NDD 0.8%, p > .99) or cardiovascular readmission (SDD 0% vs. NDD 5.5%, p = .35) at 30 days. Conclusions Same day discharge following uncomplicated, minimalist TAVR in selected patients appears to be safe, achieving similar 30 day outcomes as a cohort of next day discharge patients.
Institutional heat wave analysis by building energy modeling fleet and meter data

Abstract Heat waves increase electric demand from buildings which can cause power outages. Modeling can help planners quantify the risk of such events. This study shows how Building Energy Modeling (BEM), meter data, and climate projections can estimate heat wave effect on energy consumption and electric peak load. The methodology assumes that a partial representation of BEM for an entire site of buildings is sufficient to represent the entire site. Two linear regression models of the BEM results are produced: 1) Energy use as a function of heat wave heat content and 2) Peak load as a function of maximum daily temperature. The uncertainty conveyed in meter data is applied to these regressions providing slope and intercept 95% confidence intervals. The methodology was applied using 97 detailed BEM, site weather data, 242 building meters, and NEX-DCP30 down-scaled climate data for an entire institution in Albuquerque, New Mexico. A series of heat waves that vary from 2019 weather to a peak increase of 5.9 °C was derived. The results of the study provided institutional planners with information needed for a site that is presently growing very rapidly. The resulting regression models are also useful for resilience analyses involving probabilistic risk assessments.
Incidence and Prognosis of Brain Metastases in Head and Neck Cancer Patients at Diagnosis.

OBJECTIVES Limited data is available on head and neck cancer (HNC) patients presenting with brain metastases (BM) at initial diagnosis. We sought to evaluate the incidence, management, and treatment outcomes of these patients using the National Cancer Database (NCDB). METHODS We identified 465,925 patients diagnosed with HNC between 2010 and 2015 in the NCDB. 14,583 of these patients presented with metastatic disease to any site. 440 of these patients had BM at the time of initial diagnosis. Overall survival was compared using the Kaplan-Meier method. Cox proportional hazard modeling, propensity score matching, and subgroup analyses were performed. RESULTS The median age overall was 62.0 years. Nasopharynx NOS (13.2%) and Parotid Gland (10.9%) were the most common anatomical sites with the highest frequency of BM. The overall median survival time was 7.1 months. Predictors for the presence of BM included distant metastasis to the bone, liver, or lung on univariate analysis, and bone or lung on multivariate analysis. High-risk Human Papilloma Virus status was associated with a lower chance of BM. No pattern was determined when comparing lymph node level involvement and BM. The median survival for patients receiving radiation therapy and multi-agent chemotherapy was 8.4 and 11.7 months, respectively. Immunotherapy administered as first course therapy did not influence median survival. Most patients received radiation (62.7%) therapy and chemotherapy (50.2%). CONCLUSIONS The data extracted and analyzed from the NCDB should work to aid in the surveillance and management of BM in patients with HNC. LEVEL OF EVIDENCE 4 Laryngoscope, 131:E2543-E2552, 2021.
Increasing proteomics throughput.

A new dimension for analyzing mass spectrometry data allows rapid quantification of up to 70% more peptides.
Validation of Double Transition Model by Analyzing Reward Distributions

To keep up with the world’s increasing complexity, we need ever-more sophisticated computational models that can help to make wiser decisions and accurately predict potential consequences. Validating and explaining these models is difficult, but very crucial in understanding their effectiveness and applicability. In this paper, we validate a computational model called the Double Transition Model by using data from the SCOUT dataset that captures human behaviors from pre-scripted scenarios controlling unmanned aerial vehicles. By applying the Double Transition Model on collected raw data, we gain insights about complex human decision-making processes after comparing the model’s behavior to reward distributions that are extracted using inverse reinforcement learning. We examine the reward distributions by addressing the following questions: 1) How are reward distributions different between individuals? 2) Do reward distributions follow the normal distribution? If not, how far do they deviate? 3) What information do these reward distributions represent? To capture different facets of model complexities, we compute both Kolmogorov Complexity and Information Entropy. From our empirical analysis, we obtained high correlations between the reward distributions and the complexities, thus confirming the validity of the Double Transition Models in capturing the dynamics of the SCOUT dataset correctly.
Multi-Source Multi-Domain Data Fusion for Cyberattack Detection in Power Systems

Modern power systems equipped with advanced communication infrastructure are cyber-physical in nature. The traditional approach of leveraging physical measurements for detecting cyber-induced physical contingencies is insufficient to reflect the accurate cyber-physical states. Moreover, deploying conventional rule-based and anomaly-based intrusion detection systems for cyberattack detection results in higher false positives. Hence, independent usage of detection tools of cyberattacks in cyber and physical sides has a limited capability. In this work, a mechanism to fuse real-time data from cyber and physical domains, to improve situational awareness of the whole system is developed. It is demonstrated how improved situational awareness can help reduce false positives in intrusion detection. This cyber and physical data fusion results in cyber-physical state space explosion which is addressed using different feature transformation and selection techniques. Our fusion engine is further integrated into a cyber-physical power system testbed as an application that collects cyber and power system telemetry from multiple sensors emulating real-world data sources found in a utility. These are synthesized into features for algorithms to detect cyber intrusions. Results are presented using the proposed data fusion application to infer False Data and Command Injection (FDI and FCI)-based Man-in-The-Middle attacks. Post collection, the data fusion application uses time-synchronized merge and extracts features. This is followed by pre-processing such as imputation, categorical encoding, and feature reduction, before training supervised, semi-supervised, and unsupervised learning models to evaluate the performance of the intrusion detection system. A major finding is the improvement of detection accuracy by fusion of features from cyber, security, and physical domains. Additionally, it is observed that the semi-supervised co-training technique performs at par with supervised learning methods with the proposed feature vector. The approach and toolset, as well as the dataset that is generated can be utilized to prevent threats such as false data or command injection attacks from being carried out by identifying cyber intrusions accurately.
Immersive Analytics: A User-Centered Perspective

Researchers have explored using VR and 3D data visualizations for analyzing and presenting data for several decades. Surveys of the literature in the field usually adopt a technical or systemic lens. We propose a survey of the Immersive Analytics literature from the user’s perspective that relates the purpose of the visualization to its technical qualities. We present our preliminary review to describe how device technologies, kinds of representation, collaborative features, and research design have been utilized to accomplish the purpose of the visualization. This poster demonstrates our preliminary investigation, inviting feedback from the VRST community. Our hope is the final version of our review will benefit designers, developers, and practitioners who want to implement immersive visualizations from a Human-Centered Design perspective, and help Immersive Analytics researchers get a better understanding of the gaps in current literature.
Gemcitabine/Antifol combinations in human tumor primary cultures: Potential role in gynecologic malignancies

4445 Objectives: Like most cancer susceptibility genes, BRCA1 and BRCA2 appear to be dominant genes with incomplete penetrance. Women with BRCA1 mutations have a 54% lifetime risk of developing ovarian cancer and BRCA2 mutation carriers have a 23% risk. The mechanism of BRCA1 second allele inactivation in a cohort of Jewish ovarian cancer patients with germline mutations. Methods: A cohort of 34 ovarian cancer patients with germline BRCA1 or BRCA2 mutations was previously identified. Tumor DNA was isolated from microdissected archival paraffin-embedded specimen. Archival specimens on 30 patients with germline mutations in either BRCA1 (n=21) or BRCA2 (n=9) were available for microdissection and DNA isolation. The presence of intact DNA was confirmed by ?-actin and GAPDH PCR. BRCA1 promoter methylation was screened by methylation specific PCR and loss of heterozygosity (LOH) was determined by PCR amplification using 3 fluorescent-labeled intragenic dinucleotide-repeat markers. Results: Second allele inactivation by promoter methylation was not observed in any BRCA1 or BRCA2 mutation carriers. 17 of 21 BRCA1 carriers were informative (heterozygous) for one or more BRC1 LOH markers. 16/17 (94%) informative BRCA1 carriers displayed BRCA1 LOH. 9/9 BRCA2 mutation carriers were informative at one or more BRCA1 markers. BRCA1 LOH was detected in 9/9 (100%) BRCA2 mutation carriers. Conclusions: These data indicate that LOH rather than promoter methylation is typically the mechanism responsible for BRCA1 second allele inactivation in Jewish epithelial ovarian cancer patients with inherited mutations. Furthermore, 100% incidence of BRCA1 LOH in BRCA2 mutation carriers implies that BRCA1 expression is frequently reduced or absent in BRCA2-associated ovarian cancers. These data suggest that BRCA1 LOH may be important in BRCA2-associated carcinogenesis or may be a consequence of impaired DNA break-repair and represent genome-wide allelic instability.
Shear waves and phase transformations

Shock wave studies of phase transformations generally involve normal impact of plates, or other means for generating strong compression waves. For these waves, the high pressures and the resulting increases in temperature can cause a phase transformation. The shear stresses, while not zero, play a minor role in driving the transformation. However, in martensitic transformations and in twinning, shear stresses are understood to be important. This paper presents some recent developments in stress wave experiments that make it possible to study material response under large shear stresses and large shear strains. Two configurations are considered — both involving pressure-shear impact of parallel plates. In one, a symmetric impact configuration, the impacting plates are identical and the wave profiles generated in the target plate are used to investigate its dynamic response. In the other, a thin specimen plate is sandwiched between two hard plates so that the dynamic response of the specimen can be measured under nominally homogeneous states of stress and deformation.