cssi/SciSciGPT-SciSciNet huggingface dataset:
Discovery and biochemical characterization of tyrosyl-DNA phosphodiesterase I inhibitors

B219 Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a recently discovered enzyme that catalyzes the hydrolysis of 39-phosphotyrosyl bonds. Such linkages form in vivo following the DNA processing activity of DNA topoisomerase I (Top1). For this reason, Tdp1 has been implicated in the repair of irreversible Top1-DNA covalent complexes and has been regarded as a potential therapeutic co-target of Top1 in that it seemingly counteracts the effects of Top1 inhibitors, such as camptothecin and its clinically used derivatives. By reducing the repair of Top1-DNA lesions, Tdp1 inhibitors have the potential to augment the anticancer activity of Top1 inhibitors. Using novel high-throughput screening assays, we have identified several specific Tdp1 inhibitors from the "Diversity Set" of 1981 compounds from the Developmental Therapeutics Program of the National Cancer Institute. One of the positive hits, NSC 88915, a steroid derivative containing a tosylate substituent, has been confirmed and further characterized by traditional gel-based assays using several artificial Tdp1 substrates. NSC 88915 has been counter-screened against the enzyme APE1 and shown to be selective for Tdp1. In addition, fragmentation of NSC 88915 into discrete functional groups (i.e. the steroid moiety and the tosylate moiety) reveals that both components are required for inhibition of Tdp1 activity. Moreover, the synthesis of NSC 88915 analogues has provided insights into the structural prerequisites for inhibition of Tdp1. Based on the chemical structure of NSC 88915, we propose that the compound is a competitive inhibitor, which mimics the Tdp1 substrate. More specifically, the phosphate participating in the 39-phospotyrosyl of the Tdp1 substrate is replaced by the sulfite moiety of NSC 88915, while the phenyl bromide and steroid moieties of the compound substitute for the DNA and peptide groups of the Tdp1 substrate, respectively. In general, biochemical inhibitors of Tdp1 should enhance the cytotoxicity of camptothecins and delay the removal of Top1 cleavage complexes in cell culture, thereby providing a cellular step for compound selection. The overall therapeutic goal is the development of new drugs that would selectively enhance the activity of Top1 inhibitors in tumors with preexisting DNA repair and cell cycle checkpoint deficiencies.
Toward a Making Community of Practice: The Social Aspects of Elementary Classroom-Based Making

As Making moves from informal settings, such as museums and libraries to formal learning contexts, such as the classroom, questions arise with regard to the sustainability of the practice of Making. Learning in the classroom is continuous over time, while the integration of Making currently tend to be necessarily insular and in snapshot interventions. The development of a Making community of practice among students in the classroom is important for classroom-based Making to be sustainable. Grounded in literature on Lave and Wenger's communities of practice and Vygotsky's zone of proximal development, the work presented in this paper investigate the social aspects of Making in 5th grade science classes as indicators of the possible formation of a Making community of practice among the students. Our findings elicited different types of social roles that the students adopted, and various ways by which learning was socially mediated, and showed how help received and given varied according to student roles and over time. We discuss and conclude with the importance of pursuing further research into this topic area for Making into the classroom.
The Evolution and Genetics of Carotenoid Processing in Animals

Coloration is one of the most conspicuous traits that varies among organisms. Carotenoid pigments are responsible for many of the red, orange, and yellow colors in the natural world and, at least for most animals, these molecules must be acquired from their environment. Identifying genes important for carotenoid transport, deposition, and processing has been difficult, in contrast to the well-characterized genes involved in the melanogenesis pathways. We review recent progress in the genetics of carotenoid processing, advances owing in part to the application of high-throughput sequencing data. We focus on examples from several classes of genes coding for scavenger receptors, β-carotene oxygenases, and ketolases. We also review comparative studies that have revealed several important findings in the evolution of these genes. Namely, that they are conserved across deep phylogenetic timescales, are associated with gene/genome duplications, and introgression has contributed to their movement between several taxa.
TNF Inhibitors for Psoriasis and Psoriatic Arthritis

A growing body of research highlights the use of TNF inhibitors in the treatment of psoriasis and psoriatic arthritis. We aim to review the literature, compile psoriasis efficacy data for TNF inhibitors, and offer advice regarding the approach to treating this condition. The results of randomized placebo-controlled studies indicate that TNF inhibitors are efficacious and well tolerated in the treatment of psoriasis. There is a greater prevalence of anxiety, depression, cardiovascular disease, obesity, diabetes, hypertension, dyslipidemia, fatty liver disease, metabolic syndrome, and inflammatory bowel disease in psoriasis patients than in the general population. Severe psoriasis portends an increased risk of mortality. Although patients with mild-to-moderate psoriasis do not have an increased mortality rate, the inherent inflammatory nature of psoriasis and its association with serious comorbid conditions may warrant the use of systemic medications, such as TNF inhibitors.
Implications of Sponsored Data Program for Providers and Users of Nonsponsored Contents

Every major mobile service provider (MSP) in the US has now introduced a sponsored data program that allows content providers to pay for bandwidth usage on behalf of their customers. However, not every content provider (CP) is in the position to be a sponsor, leading to the concern that these programs may be detrimental to the welfare of users and providers of nonsponsored contents. We develop a model-based analysis that characterizes conditions under which a sponsorship program may or may not lead to higher costs for users to access nonsponsored contents, or deliver a negative demand shock to their providers. We capture the situation without a sponsorship program by a commodity bundling model, in which users pay a single price for a data plan for accessing all contents, analogous to buying a ``bundle'' of commodities. A sponsorship program removes a subset of contents from the bundle, and hence reduces users' willingness to pay for the plan. There is no guarantee that the change will lead the MSP to reduce the price of the data plan to accommodate this change. In fact, as we demonstrate by example, there exist cases where the MSP improves its profit by raising the price. Nevertheless, we argue that such situations may not be typical by showing that for many distributions of consumer types, it is in the MSP's best interest to lower the price of the data plan, reducing consumers' costs of accessing nonsponsored contents. On the other hand, providers of these contents may still be negatively affected by smaller demand if the price is not reduced sufficiently to fully compensate for the decline of willingness to pay. We develop conditions for such situations to occur and discuss related insights.
Looking at Data – Numerical Summaries

Archaeological data come in all sizes, shapes, and quantities ranging from Egyptian pyramids (large in size, small in the number of specimens) to micro-debitage from a lithic workshop or molecular residues in a ceramic bowl. Because the questions we ask of the data are different, our representations of those data differ. One way of representing the data dominates however, because it is so flexible. That is a rectangular arrangement of data so that each row represents an observation and each column represents a measurement on that observation. Some of those measurements can be counts, and each count is a potential observation for another data table. For example, we may have located a variety of archaeological sites in a river valley. One data table could consist of the grid units that were surveyed so that each row of the table is a grid square (e.g., 100 m on a side). The columns of the data set include the coordinates of the unit and the number of sites and isolated artifact finds discovered during the survey. There could be other columns identifying when the unit was surveyed and information about the location of the unit with respect to topographic features such as dominant soil type, major waterways, lakes, and so on. This data set would be relevant to exploring questions about site density. For example, are there more sites near water features and fewer in upland areas away from any water source? Each of the counts in this data set is a potential row in another data set. That data set consists of a row for each site and columns for the location of the site, the area of the site, the physical characteristics around the site (e.g., slope, elevation, aspect, soil type), and the number of different kinds of artifacts and features found on the site. This data set would be relevant to questions regarding where sites are located and how the artifacts and features found on sites differ. Each of the artifacts and features in the site data set is a potential row in another data set (or more likely multiple data sets). At this point it may make sense to create separate data sets for projectile points, flakes, cores, pottery sherds, shells, bones, and other categories of material.
The Ag+ state falls below 3Ag- at carotenoid-relevant conjugation lengths

Abstract Spectroscopy of all-trans linear polyenes is characterized by a one-photon electronic transition to a bright S2 state and two-photon transition to a lower-lying dark S1 state. We apply ab initio quantum chemistry to distinguish additional diffuse dark singlet states. Building on a systematic implementation of CASSCF and DMRGSCF coupled to strongly-contracted NEVPT2, we report the excitation energies for a series of polyenes from butadiene to C16H18 at optimized S0, S1 and S2 geometries. Ionic/covalent state inversion within each manifold is identified at seven conjugated double bonds, making the B u - a dark intermediate state at its optimized geometry and the A g + the S3 state at the S0 optimized geometry. The relevance of these results to the function of carotenoids in photosynthetic light harvesting is discussed.
Grading the DOJ's 'FCPA Corporate Enforcement Policy'

In November 2017, the Department of Justice issued a policy document titled "FCPA Corporate Enforcement Policy." Like previous DOJ FCPA efforts, the policy is "aimed at providing additional benefits to companies based on their corporate behavior once they learn of misconduct." This article grades the Corporate Enforcement Policy (CEP) and highlights the following issues: (i) the obvious logical gap in the CEP; (ii) how the CEP, both in terms of rhetoric and substance, is really nothing new; (iii) ten specific reasons why the corporate community should take the CEP with a grain of salt; and (iv) how the CEP falls short of accomplishing the laudable goals articulated by the DOJ compared to other alternatives previously advanced.
Acute neurologic complications of cardiac catheterization: clinical syndromes and outcomes (P6.296)

Objective: To characterize neurologic syndromes after left heart catheterization (LHC) and their outcomes. Background: Acute ischemic stroke is a known, potential complication of LHC. However, the nature and frequency of other neurologic complications are not well characterized. Design/Methods: This is a retrospective case-control study of adults admitted to a tertiary care center between 2008 and 2014 who developed neurologic symptoms within one day following LHC, prompting urgent neurologic consultation. We collected data on baseline demographics, past medical history, periprocedural medications, procedure details, neurologic symptoms, imaging findings, NIH stroke scale, final neurologic diagnoses, and clinical outcomes at one year. Comparative statistics were performed with Fisher’s exact test. Results: Our study included 48 subjects who developed neurologic symptoms after left heart catheterization. 50% had symptoms due to cerebrovascular diseases (CVD) including ischemic stroke (n=16), transient ischemic attack (n=7), and intracerebral hemorrhage (n=1). The remaining 50% had non-cerebrovascular diagnoses including migraine (n=12), encephalopathy (n=8), and others (n=4). Unilateral weakness was strongly associated with CVD (p Conclusions: In this study, half of post-LHC neurologic syndromes prompting neurology consultation were cerebrovascular and half were non-cerebrovascular in nature. Hemiparesis was strongly associated with CVD, and positive visual phenomena were strongly associated with migraine aura. Disclosure: Dr. Horn has nothing to disclose. Dr. Selim has nothing to disclose. Dr. Leung has nothing to disclose.
DETERMINATION OF ACCESSIBILITY AND CRYSTALLINITY OF CELLULOSE

The determination of cellulose accessibility and crystallinity has been extensively reviewed. The various techniques available for estimating the proportions of ordered and disordered regions have been summarized into three general categories: physical methods, chemical swelling methods, and non-swelling chemical methods. Of the physical methods, X-ray diffraction and infrared spectroscopy have received a large proportion of the attention of previous investigators. Only crystallinities of a certain size will contribute to the X-ray diffraction maxima. The infrared crystallinity ratio, derived from the relative absorbance of bands in infrared spectra, has been used for estimates of degrees of order in cellulose. Two sets of band ratios, the a 1429 cm −1 /a 893 cm −1 and the a 1429 cm −1 /a 2900 cm −1 , have shown good correlation with the X-ray crystallinity index. Sorption studies have also proven useful for estimating cellulose order. The percent accessibility has been derived from the maximum vapor moisture regain of cellulose samples. Deuteration techniques have also been applied for estimating accessible regions in cellulose. The close correlation between moisture sorption and D 2 O vapor exchange strongly indicates that the two methods measure exactly the same quantity. Iodine and bromine sorption have been utilized to varying degrees of success for the estimation of cellulose accessibility. The various techniques give quite different estimates of order and disorder in cellulose. However, a definite pattern is shown for the fibrous celluose samples and the following qualitatively indicates the degrees of crystallinity of celluloses in descending order, cotton > wood pulp > mercerized cotton > regenerated celluloses.
Secretory pathway calcium ATPase 1 (SPCA1) controls mouse neural tube closure by regulating cytoskeletal dynamics.

ABSTRACT Neural tube closure relies on the apical constriction of neuroepithelial cells. Research in frog and fly embryos has found links between the levels of intracellular calcium, actomyosin dynamics and apical constriction. However, genetic evidence for a role of calcium in apical constriction during mammalian neurulation is still lacking. Secretory pathway calcium ATPase (SPCA1) regulates calcium homeostasis by pumping cytosolic calcium into the Golgi apparatus. Loss of function in Spca1 causes cranial exencephaly and spinal cord defects in mice, phenotypes previously ascribed to apoptosis. However, our characterization of a novel allele of Spca1 revealed that neurulation defects in Spca1 mutants are not due to cell death, but rather to a failure of neuroepithelial cells to apically constrict. We show that SPCA1 influences cell contractility by regulating myosin II localization. Furthermore, we found that loss of Spca1 disrupts actin dynamics and the localization of the actin remodeling protein cofilin 1. Taken together, our results provide evidence that SPCA1 promotes neurulation by regulating the cytoskeletal dynamics that promote apical constriction and identify cofilin 1 as a downstream effector of SPCA1 function.
Lethal Combination of Clenbuterol and Taurine in a Young Body-Builder

Background Sudden cardiac death risk from stimulants clenbuterol and taurine for athletes is unknown. Description A 30-year-old body-builder who took clenbuterol and taurine for one week and was otherwise healthy without any cardiovascular disease was found unresponsive, requiring five external defibrillations for ventricular fibrillation (VF) to restore sinus rhythm. The left ventricular ejection fraction was 22% immediately after resuscitation and improved to 49% in 3 days. Coronary angiogram did not show any coronary artery disease and cardiac-magnetic-resonance was unremarkable. ECG showed no abnormal findings. Discussion Clenbuterol, a performance-enhancing drug, is a beta-2 agonist that increases fat metabolism and aerobic capacity and can cause hypertension and tachycardia. Taurine, found in energy drinks, can cause ventricular arrhythmias. Clenbuterol depletes taurine, so athletes take these in combination. While many people take sports supplements, few have sudden death. The VF is likely attributed to unknown underlying myocardial vulnerability and is precipitated by the combination of clenbuterol and taurine. Subcutaneous implantable cardioverter defibrillator (ICD) was placed in this patient for secondary prevention of sudden cardiac death. Conclusion Clenbuterol and taurine, used as performance-enhancing drugs in athletes, may trigger VF and heart failure in those with predisposing substrate.
“Shifting” the black abolitionist panorama: subversive realism in Pauline Hopkins’s Winona

“The free air of the land of the prairies was not polluted by the foul breath of slavery. We find but one account of slaves brought into the country, and they were soon freed. But the free Negro wa...
A Rare Case of Pembrolizumab-Induced Reactivation of Hepatitis B

Hepatitis B virus (HBV) infection is common across the world, especially in Asia, Africa, Southern Europe, and Latin America. The association of HBV infection in patients suffering from different oncological conditions is well established. Many cases of HBV reactivation have been reported in patients on immunosuppressive chemotherapy and in patients undergoing hematopoietic bone marrow transplantations. Only one case has been reported so far of HBV reactivation in a patient treated with programmed cell death receptor 1 (PD-1) checkpoint inhibitors in the setting of HIV status. We report a case of a 51-year-old male, former smoker, diagnosed with stage IV poorly differentiated adenocarcinoma of the lung, and started on pembrolizumab, who developed reactivation of chronic hepatitis requiring antiviral therapy.
Development of manganese-rich cathodes as alternatives to nickel-rich chemistries

Abstract High-energy, inexpensive and safe electrochemistries have been the main goals of lithium-ion battery research for many years. Historically, manganese-based cathodes have long been studied for their attractive cost and safety characteristics [1]. However, due to issues related to both surface and bulk instabilities, manganese-rich electrodes have yet to find substantial success in the high-energy lithium-ion battery market. With current trends in cathode chemistries leaning heavily toward Ni-rich compositions, the factors of cost and safety are again at the forefront of research and development efforts. This paper reports the recent progress made at Argonne National Laboratory (USA) to stabilize manganese-rich cathode structures and surfaces with a specific focus on composite materials with intergrown layered and spinel components; it presents an overview of their electrochemical properties in terms of capacity, energy, and cycle-life in cells with metallic lithium, graphite, and Li4Ti5O12 anodes. These layered-spinel cathodes show promise as alternatives to highly nickel-rich electrode compositions, which bodes well for continued advances.
Dynamic Assessment: Promoting In-Service teachers’ conceptual development and pedagogical beliefs in the L2 classroom

This article on teacher cognition explores the implementation of an interactionist Dynamic Assessment (DA) model for mediating and ascertaining in-service L2 teachers’ microgenetic conceptual development after being exposed to Concept- Based Instruction (CBI). Although the effectiveness of this instructional approach in the development of L2 instructors (van Compernolle and Henery, 2015; Williams, Abraham, and Negueruela, 2013), and the use of DA to facilitate L2 development (Anton, 2009; Davin, 2013; Lantolf and Poehner, 2011, 2014; Poehner, 2008) have been both investigated, there is no research addressing the role of DA in fostering the development of in-service L2 teachers’ conceptual language awareness after being exposed to CBI. This article intends to address this gap by exploring the case study of Glinda (pseudonym), an experienced in-service teacher of Spanish whose L1 was also Spanish, and her developing linguistic and pedagogical beliefs regarding the concept of aspect before and after conceptual instruction.
A Laurasian origin for a pantropical bird radiation is supported by genomic and fossil data (Aves: Coraciiformes).

The evolution of pantropically distributed clades has puzzled palaeo- and neontologists for decades regarding the different hypotheses about where they originated. In this study, we explored how a ...
Theories and Research Designs Linking Family Behavior and Child Development: A Critical Overview

A critique of research and theory, linking family behavior and child development, is offered. The critique faults child psychology as essentially personological, still uni-directional, parent moldi...
Atomristors: Non-Volatile Resistance Switching in 2D Monolayers

Since the discovery of graphene, two-dimensional (2D) materials have drawn much attention as a promising candidate in the next-generation electron devices, optoelectronics and bioelectronics1, 2. Over the last few years, researchers have proved the existence of the non-volatile resistance switching (NVRS) behavior in various 2D materials, including graphene oxide, functionalized MoS 2 , partially degraded black phosphorus and multi-layer hexagonal boron-nitride (h-BN), etc.3–6, where the resistance can be switched between a high-resistance state (HRS) and a low-resistance state (LRS) and maintained for a long time without power supply 7. In 2015, Sangwan et al. discovered that grain boundaries in single-layer MoS 2 can produce NVRS based on planar (horizontal) structure8. However, the planar structure without 3D stacking ability has the limitation of low integration density. Therefore, to overcome vertical scaling obstacle in NVRS based on conventional metal-insulator-metal (MIM) structure, it is desired to find out the thinnest materials that can produce the resistance switching behavior based on vertical device structure. Recently, we discovered that NVRS phenomenon is accessible in a variety of single-layer transition metal dichalcogenides (TMDs) and single-layer h-BN in vertical MIM configuration9–12. Compared with other 2D material-based NVRS devices, single-layer h-BN has only one atomic layer and ∼0.33 nm in thickness, which is the thinnest active layer in non-volatile resistance memory. These devices can be collectively labelled as “atomristor”, which means the memristor effect in atomically thin nanomaterials. The TMDs and h-BN atomristors have been studied using a crossbar or a litho-free & transfer-free structure, demonstrating forming-free switching with large on/off ratio (up to 6 orders of magnitude) and low switching voltage (down to 15 dB) up to 100 GHz. The operating frequencies cover the RF, 5G, and mm-wave bands, making this a promising low-power switch for diverse communication and connectivity front-end systems. The results of this work indicate a potential universal resistive switching behavior in 2D monolayers, which is applicable to memory technology, neuromorphic computing, RF switch and flexible electronics.
The Design of Vaccines Based on the Shielding of Antigenic Site Ø of a Respiratory Syncytial Virus Fusion Protein Immunogen.

Respiratory syncytial virus (RSV), for which there is currently no licensed vaccine, displays a fusion (F) protein that is considered a vaccine target. This protein has an antigenic site called site O, which has been shown to elicit potent, neutralizing antibodies and has therefore been considered important in the formulation of RSV vaccines. However, this site is also the least conserved region on the F protein across RSV subtypes. Therefore, directing the immune response away from site O and refocusing it toward more conserved parts of the RSV F protein might serve to better elicit broadly neutralizing antibodies. To demonstrate that directing the immune response away from site O is a viable approach, a prefusion F-based vaccine based on an F protein with a shielded site O is generated. Sera from mice immunized with multivalent scaffolds presenting this immunogen is capable of neutralizing RSV of both subtypes. This result may have application in the development of an effective and broadly protective RSV vaccine.
Transcriptional changes in peanut-specific CD4+ T cells over the course of oral immunotherapy.

Abstract Oral immunotherapy (OIT) can successfully desensitize allergic individuals to offending foods such as peanut. Our recent clinical trial ( NCT02103270 ) of peanut OIT allowed us to monitor peanut-specific CD4+ T cells, using MHC-peptide Dextramers, over the course of OIT. We used a single-cell targeted RNAseq assay to analyze these cells at 0, 12, 24, 52, and 104 weeks of OIT. We found a transient increase in TGFβ-producing cells at 52 weeks in those with successful desensitization, which lasted until 117 weeks. We also performed clustering and identified 5 major clusters of Dextramer+ cells, which we tracked over time. One of these clusters appeared to be anergic, while another was consistent with recently described TFH13 cells. The other 3 clusters appeared to be Th2 cells by their coordinated production of IL-4 and IL-13, but they varied in their expression of STAT signaling proteins and other markers. A cluster with high expression of STAT family members also showed a possible transient increase at week 24 in those with successful desensitization. Single cell TCRαβ repertoire sequences were too diverse to track clones over time. Together with increased TGFβ production, these changes may be mechanistic predictors of successful OIT that should be further investigated.
Excising culture history from contemporary archaeology

Abstract North American archaeologists must reconsider their implicit adherence to the culture history paradigm. The long-standing role of this approach to situate archaeological remains in space and time is far outweighed by the negative impacts of its underlying assumptions about the correspondence of biological and cultural groups, intragroup uniformity, discrete spatial boundaries, primordialism, and sequential change. These discredited assumptions divert attention from variability, privilege certain research questions and interpretations, hinder dialogue with other disciplines, and facilitate the misuse of archaeology for political purposes. We recommend alternative perspectives that recognize the importance of space-time context, accommodate the complexity of new suites of archaeological data, and are more consistent with what we now know about past and present social relations.
Hepatitis B Virus Awareness, Infection, and Screening Multiethnic Community Intervention for Foreign-Born Populations

Hepatitis B virus (HBV) is a potentially deadly viral infection that can lead to liver cancer. Many refugee immigrants resettled in the US come from countries known to have a high prevalence of HBV infections. Unfortunately, most infected refugee immigrants are unaware of their HBV status. The disease is highly preventable through a vaccine, but chronic HBV is incurable once the disease has developed. For the purposes of this cross-sectional study, we conducted analysis of data collected through the Building Bridges Initiative (BBI) to assess HBV awareness, vaccination status, screening, and infection among multiethnic, primarily refugee, immigrant populations living in North Texas. Overall, 74% of study participants reported having heard about HBV, but only 31% knew their HBV status. Whereas 69% of study participants lacked awareness about their HBV status and self-reported prevalence of chronic HBV among study participants was 4%. For the vaccine, only 26% reported to have received at least one dose; 53% did not know, while 21% had not ever received it. For those unaware of their HBV status, the BBI offered participants free HBV screening and assistance for vaccination as needed. 76% of participants that accepted HBV screening from BBI were never screened before (enrollment in BBI). Chronic HBV positivity rate for participants was 6%, which is twenty times higher than the national prevalence of chronic HBV (0.3%). High prevalence of HBV, low awareness and low vaccination rates seen in this study highlights the need for increased HBV prevention among foreign born populations.
Optimization of Multiple Reservoir System

A method is developed to determine the optimal design of any system of reservoirs with series and parallel connections. The original problem is decomposed by successive approximations into a series of subproblems in such a way that the sequence of optimizations over the subproblems converges back to the original one. The optimal design is obtained by maximizing the net benefits. Incremental dynamic programming is used to find the optimal operating policy. The theories developed are applied to a real system, i.e., the Eel River Ultimate Project in northern California.
Repair pathway crosstalk in genome stability maintenance through BRCA1/2-mediated homologous recombination (352.1)

XPG is an endonuclease required for nucleotide excision repair with important non-enzymatic roles in base excision repair (BER) and transcription-coupled repair (TCR). XPG enzymatic defects cause cancer-prone xeroderma pigmentosum (XP), while truncating mutations cause the progeroid disorder Cockayne syndrome (CS). We now reveal an unexpected XPG role in homologous recombination (HR). XPG loss elevates the DNA damage response and causes double-strand break (DSB) formation with pronounced genomic instability. XPG knockdown (KD) cells have impaired recovery from replicative stress, and DNA fiber analysis reveals inability to restart stalled replication forks. XPG interacts directly with the HR proteins RAD51, BRCA2, and PALB2 in a stable complex, and XPG KD results in their reduced chromatin loading and in decreased HR at site-specific DSBs. Placing its role in HR upstream of BRCA2, XPG KD also reduces single-strand annealing and increases chromatin-bound BRCA1 and BRCA1 foci. Thus, loss of XPG function imp...
Offshoring Digital Work, but Not Physical Output: Differential Access to Task Objects and Coordination in Globally Distributed Automotive Engineering and Graphic Design Work

When scholars and practitioners consider the implications of off shoring work, their primary concern is often the impact off shoring has on communication between people at different sites. When time zones and geographic boundaries separate employees, communication is limited, making it difficult for remote colleagues to form trusting and familiar relationships with one another. However, off shoring not only obstructs person-to-person interactions, it also impedes person-to-object interactions. This is potentially problematic as many organizations today still produce physical products, such as printed marketing collaterals, computers, home deecor, or automobiles. Though organizations that create physical outputs may engage in digital work processes, people at these organizations may still rely on interactions with the physical objects that they produce in order to complete tasks. In this paper we investigate impeded person-to-object interactions at two offshore work sites representing two different occupations: automotive engineering and graphic design.
Appearance of woven cloth

The appearance of a particular fabric is produced by variations in both large-scale reflectance and small-scale texture as the viewing and illumination angles change across the surface. This thesis presents a study of the reflectance and texture of woven cloth that aims to identify and model the most important optical features of cloth appearance. New measurements are reported for a range of fabrics including natural and synthetic fibers as well as staple and filament yarns. A new scattering model for woven cloth is introduced that describes the reflectance and the texture based on all analysis of specular reflection from the fibers. Unlike data-based models, our procedural model requires no image data. It can handle a wide range of fabrics using a small set of physically meaningful parameters that describe the characteristics of the fibers, the geometry of the yarns, and the pattern of the weave. The model is validated against the measurements and by comparisons to high-resolution video of the real fabrics.
Circadian Disruption and Diet-Induced Obesity Synergize to Promote Development of β-Cell Failure and Diabetes in Male Rats

There are clear epidemiological associations between circadian disruption, obesity, and pathogenesis of type 2 diabetes. The mechanisms driving these associations are unclear. In the current study, we hypothesized that continuous exposure to constant light (LL) compromises pancreatic β-cell functional and morphological adaption to diet-induced obesity leading to development of type 2 diabetes. To address this hypothesis, we studied wild type Sprague Dawley as well as Period-1 luciferase reporter transgenic rats (Per1-Luc) for 10 weeks under standard light-dark cycle (LD) or LL with concomitant ad libitum access to either standard chow or 60% high-fat diet (HFD). Exposure to HFD led to a comparable increase in food intake, body weight, and adiposity in both LD- and LL-treated rats. However, LL rats displayed profound loss of behavioral circadian rhythms as well as disrupted pancreatic islet clock function characterized by the impairment in the amplitude and the phase islet clock oscillations. Under LD cycle, HFD did not adversely alter diurnal glycemia, diurnal insulinemia, β-cell secretory function as well as β-cell survival, indicating successful adaptation to increased metabolic demand. In contrast, concomitant exposure to LL and HFD resulted in development of hyperglycemia characterized by loss of diurnal changes in insulin secretion, compromised β-cell function, and induction of β-cell apoptosis. This study suggests that circadian disruption and diet-induced obesity synergize to promote development of β-cell failure, likely mediated as a consequence of impaired islet clock function.
Efficacy of Plantar Loading Parameters During Gait in Terms of Reliability, Variability, Effect of Gender and Relationship Between Contact Area and Plantar Pressure

Background: The purpose of this study was to determine plantar pressure and contact areas of the foot inside the athletic shoe during activity. The objectives were to determine if plantar pressure ...
Respiratory syncytial virus-induced acute and chronic airway disease is independent of genetic background: An experimental murine model

Respiratory syncytial virus (RSV) is the leading respiratory viral pathogen in young children worldwide. RSV disease is associated with acute airway obstruction (AO), long-term airway hyperresponsiveness (AHR), and chronic lung inflammation. Using two different mouse strains, this study was designed to determine whether RSV disease patterns are host-dependent. C57BL/6 and BALB/c mice were inoculated with RSV and followed for 77 days. RSV loads were measured by plaque assay and polymerase chain reaction (PCR) in bronchoalveolar lavage (BAL) and whole lung samples; cytokines were measured in BAL samples. Lung inflammation was evaluated with a histopathologic score (HPS), and AO and AHR were determined by plethysmography. Viral load dynamics, histopathologic score (HPS), cytokine concentrations, AO and long-term AHR were similar in both strains of RSV-infected mice, although RSV-infected C57BL/6 mice developed significantly greater AO compared with RSV-infected BALB/c mice on day 5. PCR detected RSV RNA in BAL samples of RSV infected mice until day 42, and in whole lung samples through day 77. BAL concentrations of cytokines TNF-α, IFN-γ, and chemokines MIG, RANTES and MIP-1α were significantly elevated in both strains of RSV-infected mice compared with their respective controls. Viral load measured by PCR significantly correlated with disease severity on days 14 and 21. RSV-induced acute and chronic airway disease is independent of genetic background.
First-trimester exposure to bupropion and risk of cardiac malformations.

Purpose Bupropion is a drug uniquely used both to treat depression and as an aid to smoking cessation. We investigated previously reported associations between first-trimester exposure to bupropion and cardiac defects. Methods Using data gathered since 2003 by the Slone Epidemiology Center's Case-control Birth Defects Study, we classified subjects with cardiac defects into subgroups. Exposure categories included first-trimester bupropion alone or in combination with other antidepressants, first-trimester antidepressants other than bupropion, and no exposure to any antidepressant at any time from 2 months prior to pregnancy through delivery. We calculated odds ratios and 95% confidence intervals, controlling for confounding using logistic regression. Results There were 8611 non-malformed infants and 7913 infants with cardiac defects. Eight cardiac subgroups had sufficient subjects (two or more exposed cases) for analysis. The adjusted odds ratio (aOR) for first-trimester bupropion use in relation to ventricular septal defect (VSD) was slightly elevated (1.6, 95% confidence interval 1.0–2.8); for exposure to bupropion alone, the aOR was 2.5 (95% confidence interval 1.3–5.0). Risks were not materially elevated for bupropion in relation to the other seven cardiac subgroups. Conclusions We did not confirm previously reported associations for left-sided defects overall but had too few exposed cases to evaluate specific defects in this category. We did observe an elevated risk of VSD following first-trimester bupropion use, particularly when used without other antidepressants. This pattern for bupropion alone was observed in all our risk comparisons and was not explained by higher doses or gestational timing. Copyright © 2014 John Wiley & Sons, Ltd.
CATER: an online problem tracking facility for SLC

An online facility has been developed for SLC to organize and simplify the management of all problems encountered in the operation of the accelerator. CATER (Computer Aided Trouble Entry and Reporting) may be used to make the initial entry of a problem, to enter one or more solutions to a problem, to modify or closeout a problem, to generate a variety of pre-defined reports giving status and statistical summaries, and to allow anyone to browse the database. All phases of CATER can take place on the operator console, workstations, or on any ANSI compatible terminal. The user interface is designed around a menu driven windowed environment with a large amount of context sensitive help information to alleviate the need for consulting user documentation. Currently, the CATER database contains information on more than 30,000 problems entered since it went online in January of 1988. The features of the software and some implementation details are presented. >
Focal Adhesion Kinase as a Regulator of Cell Tension in the Progression of Cancer

Growing evidence indicates that critical steps in cancer progression such as cell adhesion, migration, and cell cycle progression are regulated by the composition and organization of the microenvironment. The adhesion of cancer cells to components of the microenvironment and the forces transmitted to the cells via the actinomyosin network and the signaling complexes organized within focal adhesions allow cancer cells to sense the local topography of the extracellular matrix and respond efficiently to proximal growth and migration promoting cues. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is over expressed in a variety of cancers and plays an important role in cell adhesion, migration, and anchorage-dependent growth. In this review, we summarize evidence which implicate FAK in the ability of cells to sense and respond to local forces from the microenvironment through the regulation of adhesion dynamics and actinomyosin contractility, and we discuss the potential roles of FAK as a mechanosensor in the progression of cancer.
Theory of induced birefringence in materials with memory

Isotropic materials with memory, discussing induced birefringence theory to account for memory and nonlinearity effects in dielectric properties dependence on deformation history
Covariances of symmetric statistics

Abstract We examine the second-order structure arising when a symmetric function is evaluated over intersecting subsets of random variables. The original work of Hoeffding is updated with reference to later results. New representations and inequalities are presented for covariances and applied to U -statistics.
Argumentativeness, Avoidance, Verbal Aggressiveness, and Verbal Benevolence as Predictors of Partner Perceptions of an Individual's Conflict Style

This study addressed two main questions. First, are the traits of argumentativeness, verbal aggressiveness, avoidance, and verbal benevolence reflected in conflict styles such that they are perceived by others? Second, how do these traits predict the five conflict styles in the dual concern model? These questions were tested using dyadic data from a simulated downsizing activity. Results showed that participants perceived their partners differently depending on the traits their partners endorsed. For example, people who reported being avoidant or verbally aggressive were less likely to be perceived as using the compromising style. Overall, the results suggested that the four traits investigated in this study are likely to be associated with observable behavior. Findings also demonstrated that these traits help differentiate the five conflict styles in more nuanced ways than predicted by the dual concern model. Finally, the results supported the idea that conflict styles are not only shaped by one's own traits but also by the traits of others and the interaction between two people's traits.
Gravitino and other spin-3/2 quasinormal modes in Schwarzschild-AdS spacetime

We investigate quasinormal mode frequencies ${\ensuremath{\omega}}_{n}$ of gravitinos and generic massive spin-$\frac{3}{2}$ fields in a Schwarzschild-${\mathrm{AdS}}_{D}$ background in spacetime dimension $Dg3$, in the black brane (large black hole) limit appropriate to many applications of the AdS/CFT correspondence. First, we find asymptotic formulas for ${\ensuremath{\omega}}_{n}$ in the limit of large overtone number $n$. Asymptotically, ${\ensuremath{\omega}}_{n}\ensuremath{\simeq}n\mathrm{\ensuremath{\Delta}}\ensuremath{\omega}+O(\mathrm{ln}n)+O({n}^{0})$, where $\mathrm{\ensuremath{\Delta}}\ensuremath{\omega}$ is a known constant, and here we compute the $O(\mathrm{ln}n)$ and $O({n}^{0})$ corrections to the leading $O(n)$ behavior. Then we compare to numerical calculations of exact quasinormal mode frequencies. Along the way, we also improve the reach and accuracy of an earlier, similar analysis of spin-$\frac{1}{2}$ fields.
Thermal Conductivity of Carbon Nanotube Aerogels With Different Filling Gases

We report on measurements of thermal conductivity in single-walled carbon nanotube (SWCNT) aerogels in vacuum, and as infiltrated by different gases. The remarkable thermal, mechanical and electrical properties of single CNTs have led to great interest in bulk carbon nanotube materials, including the CNT aerogels. Carbon nanotube aerogels are light-weight (7–8kg/m3) and porous, which means that heat will be conducted in parallel through the SWCNT matrix and the filling gas. The overall thermal conductivity of the aerogel was measured with helium, and argon filling gases, using a modified 3ω method designed to interrogate low thermal effusivity materials. Measurements of thermal conductivity at vacuum are 0.023 W/m-K and at atmospheric pressure infiltrated SWCNT aerogels have thermal conductivities in helium of 0.19 W/m-K and in argon of 0.039 W/m-K. Our vacuum measurement suggests that transport within the aerogel is limited by the thermal interface resistance between SWCNTs, rather than by phonon transport within the SWCNT itself. We have also extracted the mean distance traveled by gas molecules between collisions with SWCNT aerogel by fitting the gas contribution to thermal conductivity using a kinetic theory based model.Copyright © 2012 by ASME
Nitroaromatic actuation of mitochondrial bioelectrocatalysis for self-powered explosive sensors

Oligomycin-inhibited mitochondria-modified electrodes were used to electrochemically sense the presence of nitroaromatics owing to the selective ability of nitroaromatics to decouple the inhibition of pyruvate metabolism by the mitochondria. These oligomycin inhibited mitochondria-modified electrodes were employed as the bioanode in a pyruvate/air biofuel cell. This sensing mechanism could be used as a traditional electrochemical sensor or as a self-powered sensor.
Pulmonary function in bronchial asthma

Abstract Methods for the study of pulmonary function have been applied by a number of workers in patients with bronchial asthma and have gone far to elucidate the changes which occur during the asthmatic attack. Although valuable information concerning the severity of asthma can usually be obtained with a spirometer, coupled with measurements designed to assess the obstruction to air flow, a much deeper understanding of the functional defect can be derived from tests which also measure abnormalities of distribution of the inspired gas, and the changes which occur in the arterial blood.
QFAX: An Interactive Viewdata System for Quality Communications

QFAX is a microcomputer system for communicating information in a manner which emulates broadcast teletext (e.g., CEEFAX, ORACLE) in appearance, operation and facilities. It grew out of a need to inform and involve people in quality improvement activities, and its aim is to increase awareness of product, system and personal quality performance. Each QFAX unit is independent and the page contents can be edited locally. Experience in Mullard with eight units has demonstrated that the interactive nature of the system and its familiar format invites attention and is particularly suitable for being the facts centre for small quality‐awareness discussion groups.
Separation of Presampling and Postsampling Modulation Transfer Functions in Infrared Sensor Systems

New methods of measuring the modulation transfer function (MTF) of electro-optical sensor systems are investigated. These methods are designed to allow the separation and extraction of presampling and postsampling components from the total system MTF. The presampling MTF includes all the effects prior to the sampling stage of the imaging process, such as optical blur and detector shape. The postsampling MTF includes all the effects after sampling, such as interpolation filters and display characteristics. Simulation and laboratory measurements are used to assess the utility of these techniques. Knowledge of these components and inclusion into sensor models, such as the U.S. Army RDECOM CERDEC Night Vision and Electronic Sensors Directorate's NVThermIP, will allow more accurate modeling and complete characterization of sensor performance.