cssi/SciSciGPT-SciSciNet huggingface dataset:
Induction of Antigen-Specific Th1-Type Immune Responses by Gamma-Irradiated Recombinant Brucella abortus RB51

Brucella abortus strain RB51 is an attenuated rough mutant used as the live vaccine against bovine brucellosis in the United States and other countries. We previously reported the development of strain RB51 as a bacterial vaccine vector for inducing Th1-type immune responses against heterologous proteins. Because safety concerns may preclude the use of strain RB51-based recombinant live vaccines, we explored the ability of a gamma-irradiated recombinant RB51 strain to induce heterologous antigen-specific immune responses in BALB/c mice. Exposure of strain RB51G/LacZ expressing Escherichia coli β-galactosidase to a minimum of 300 kilorads of gamma radiation resulted in complete loss of replicative ability. These bacteria, however, remained metabolically active and continued to synthesize β-galactosidase. A single intraperitoneal inoculation of mice with 109 CFU equivalents of gamma-irradiated, but not heat-killed, RB51G/LacZ induced a β-galactosidase-specific Th1-type immune response. Though no obvious differences were detected in immune responses to B. abortus-specific antigens, mice vaccinated with gamma-irradiated, but not heat-killed, RB51G/LacZ developed significant protection against challenge with virulent B. abortus. In vitro experiments indicated that gamma-irradiated and heat-killed RB51G/LacZ induced maturation of dendritic cells; however, stimulation with gamma-irradiated bacteria resulted in more interleukin-12 secretion. These results suggest that recombinant RB51 strains exposed to an appropriate minimum dose of gamma radiation are unable to replicate but retain their ability to stimulate Th1 immune responses against the heterologous antigens and confer protection against B. abortus challenge in mice.
Applying spectral methods to software clustering

The application of spectral methods to the software clustering problem has the advantage of producing results that are within a known factor of the optimal solution. Heuristic search methods, such as those supported by the Bunch clustering tool, only guarantee local optimality which may be far from the global optimum. In this paper, we apply the spectral methods to the software clustering problem and make comparisons to Bunch using the same clustering criterion. We conducted a case study, involving 13 software systems, to draw our comparisons. There is a dual benefit to making these comparisons. Specifically, we gain insight into (1) the quality of the spectral methods solutions; and (2) the proximity of the results produced by Bunch to the optimal solution.
An Asian perspective on the management of distal radius fractures.

There is little data with regards to the epidemiology, pathology, or management of distal radius fractures from centers in Asia. Asia includes five advanced economies, namely Hong Kong SAR, Japan, Korea, Singapore, and Taiwan and a number of emerging economies prominent among which are China, India, Malaysia, Philippines, and Thailand. This article examines the available epidemiological data from Asia, and compares the management of distal radius fractures in the advanced and emerging Asian economies and how they match up to the current management in the west. It concludes by offering solutions for improving outcomes of distal radius fractures in both the advanced and emerging economies of Asia.
Isolation of Staphylococcus aureus from the urinary tract: association of isolation with symptomatic urinary tract infection and subsequent staphylococcal bacteremia

Background. Staphylococcus aureus is frequently isolated from urine samples obtained from long-term care patients. The significance of staphylococcal bacteriuria is uncertain. We hypothesized that S. aureus is a urinary pathogen and that colonized urine could be a source of future staphylococcal infection. Methods. We performed a cohort study of 102 patients at a long-term care Veterans Affairs facility for whom S. aureus had been isolated from clinical urine culture. Patients were observed via urine and nasal cultures that were performed every 2 months. We determined the occurrence of (1) symptomatic urinary tract infection concurrent with isolation of S. aureus (by predetermined criteria), (2) staphylococcal bacteremia concomitant with isolation of S. aureus from urine, and (3) subsequent episodes of staphylococcal infection. Results. Of 102 patients, 82% had undergone recent urinary catheterization. Thirty-three percent of patients had symptomatic urinary tract infection at the time of initial isolation of S. aureus, and 13% were bacteremic. Eight-six percent of the initial urine isolates were methicillin-resistant S. aureus. Seventy-one patients had followup culture data; 58% of cultures were positive for S. aureus at 2 months (median duration of staphylococcal bacteriuria, 4.3 months). Sixteen patients had subsequent staphylococcal infections, occurring up to 12 months after initial isolation of S. aureus; 8 late-onset infections were bacteremic. In 5 of 8 patients, the late blood isolate was found to have matched the initial urine isolate by pulsed-field gel electrophoresis typing. Conclusions. S. aureus is a cause of urinary tract infection among patients with urinary tract catheterization. The majority of isolates are methicillin-resistant S. aureus. S. aureus bacteriuria can lead to subsequent invasive infection. The efficacy of antistaphylococcal therapy in preventing late-onset staphylococcal infection in patients with persistent staphylococcal bacteriuria should be tested in controlled trials.
Experiences of frequent visits to the emergency department by residents with dementia in assisted living

Assisted living (AL) is a growing option for housing for older adults with dementia in the United States. Typically, nurses are not employed in AL in California. The purpose of this paper is to describe the health care incidents and experiences of residents and their family members who are transferred from AL to an (emergency department) ED. Data were collected from two dementia-only AL communities in California over a period of six months. In this study, only 32% of ED visits resulted in admission to acute care. Of the 71 residents, eight (11%) were responsible for 47% of the ED visits. Qualitative interviews with 3 employees and 9 family members and focus groups with 11 employee caregivers were conducted to augment the quantitative data. The qualitative theme of frustration and helplessness by family and staff to prevent repeated falling and ED transfers was identified, which complemented the quantitative findings.
Screening for abdominal aortic aneurysms

Ultrasonography remains the screening modality of choice for abdominal aortic aneurysms despite many advances in imaging modalities. Several randomized trials were performed that demonstrated the effectiveness of ultrasound-based screening to reduce aneurysm-related mortality. Ultrasound is both cost effective and low risk. Controversies do persist in selecting the appropriate populations for screening, and several national societies have set recommendations.
Automatic assessment of OCR quality in historical documents

Mass digitization of historical documents is a challenging problem for optical character recognition (OCR) tools. Issues include noisy backgrounds and faded text due to aging, border/marginal noise, bleed-through, skewing, warping, as well as irregular fonts and page layouts. As a result, OCR tools often produce a large number of spurious bounding boxes (BBs) in addition to those that correspond to words in the document. This paper presents an iterative classification algorithm to automatically label BBs (i.e., as text or noise) based on their spatial distribution and geometry. The approach uses a rule-base classifier to generate initial text/noise labels for each BB, followed by an iterative classifier that refines the initial labels by incorporating local information to each BB, its spatial location, shape and size. When evaluated on a dataset containing over 72,000 manually-labeled BBs from 159 historical documents, the algorithm can classify BBs with 0.95 precision and 0.96 recall. Further evaluation on a collection of 6,775 documents with ground-truth transcriptions shows that the algorithm can also be used to predict document quality (0.7 correlation) and improve OCR transcriptions in 85% of the cases.
Performance as liminality: Between reality and possibility:

This study reflects upon the way in which an economy of extraction is indicated in the Bible, and the several ways in which the tradition of faith responds to such an economy in emancipatory and an...
Beyond Treaties and Regulation: Using Market Forces to Control Dual Use Technologies

WMD technologies are increasingly available from commercial firms located all over the world. Scholars point out that traditional political initiatives based on regulation and treaty will have difficulty controlling this complex environment. By comparison, market forces routinely impose uniform, worldwide standards (e.g. Windows software, Blu-Ray video players) in many high tech industries. Recently, the companies in one such industry (artificial DNA) used these same economic forces to develop and implement a biosecurity standard. Surprisingly, the resulting standard is more stringent – and at least arguably more enforceable – than the US government’s own official guidelines. This article begins by presenting a short history of how private and public standards evolved in the artificial DNA industry. It then goes beyond this motivating example to ask whether we can expect private non-proliferation standards to be similarly effective in other industries. Next, it reviews what modern theories have to say about standard-setting in both government and the private sector. This analysis suggests that private standards should be reasonably feasible, stringent, and enforceable for many dual use industries. Furthermore, theory suggests that private standards will often reflect society’s risk preferences at least as well as public regulation. The article concludes by suggesting specific reforms for improving private and public standards-setting still further.
Toward risk assessment 2.0: Safety supervisory control and model-based hazard monitoring for risk-informed safety interventions

Abstract Probabilistic Risk Assessment (PRA) is a staple in the engineering risk community, and it has become to some extent synonymous with the entire quantitative risk assessment undertaking. Limitations of PRA continue to occupy researchers, and workarounds are often proposed. After a brief review of this literature, we propose to address some of PRA׳s limitations by developing a novel framework and analytical tools for model-based system safety, or safety supervisory control, to guide safety interventions and support a dynamic approach to risk assessment and accident prevention. Our work shifts the emphasis from the pervading probabilistic mindset in risk assessment toward the notions of danger indices and hazard temporal contingency. The framework and tools here developed are grounded in Control Theory and make use of the state-space formalism in modeling dynamical systems. We show that the use of state variables enables the definition of metrics for accident escalation, termed hazard levels or danger indices, which measure the “proximity” of the system state to adverse events, and we illustrate the development of such indices. Monitoring of the hazard levels provides diagnostic information to support both on-line and off-line safety interventions. For example, we show how the application of the proposed tools to a rejected takeoff scenario provides new insight to support pilots’ go/no-go decisions. Furthermore, we augment the traditional state-space equations with a hazard equation and use the latter to estimate the times at which critical thresholds for the hazard level are (b)reached. This estimation process provides important prognostic information and produces a proxy for a time-to-accident metric or advance notice for an impending adverse event. The ability to estimate these two hazard coordinates, danger index and time-to-accident, offers many possibilities for informing system control strategies and improving accident prevention and risk mitigation. Finally we develop a visualization tool, termed hazard temporal contingency map, which dynamically displays the “coordinates” of a portfolio of hazards. This tool is meant to support operators’ situational awareness by providing prognostic information regarding the time windows available to intervene before hazardous situations become unrecoverable, and it helps decision-makers prioritize attention and defensive resources for accident prevention. In this view, emerging risks and hazards are dynamically prioritized based on the temporal vicinity of their associated accident(s) to being released, not on probabilities or combination of probabilities and consequences, as is traditionally done (off-line) in PRA. This approach offers novel capabilities, complementary to PRA, for improving risk assessment and accident prevention. It is hoped that this work helps to expand the basis of risk assessment beyond its reliance on probabilistic tools, and that it serves to enrich the intellectual toolkit of risk researchers and safety professionals.
Abstract A98: Rgs16: HTS biomarker for pancreas development, diabetes, and PDAC.

Rgs16::GFP is a novel and early reporter of GPCR signaling during beta-cell expansion and pancreatic ductal adenocarcinoma (PDAC). Novel approaches are needed to understand the contributions of endocrine progenitors and b-cell regeneration during islet expansion, and to discover new therapeutics for diabetes that will not promote PDAC. G-protein signaling is an excellent target for therapeutics but is not well understood in pancreas development and disease. Regulators of G-protein signaling (RGS) proteins can serve as biomarkers for active G protein coupled receptor (GPCR) signaling. Rgs16 is expressed in pancreatic progenitor and endocrine cells during development, then extinguish in normal glycemic weanlings (DMM 3:567). Rgs16 is reactivated in models of diabetes and PDAC. RNA-Seq was used to identify 63 GPCRs (28 orphans) expressed in PDAC cells, whose expression profile is closely related to embryonic duct and endocrine progenitors. PDAC cells have been validated for 384-well high throughput screens (HTS). A putative GPCR-ligand stimulated Rgs16::GFP expression in 90% of PDAC cells, and in islets in a regenerative model of type 1 diabetes. Mouse models of diabetes and PDAC will be used to validate small molecules identified in HTS. Rgs16 may control islet progenitor cell activation, differentiation and migration during ductal and islet expansion in embryos and metabolically stressed adults. Funding: NIH (GM61395) and Welch Foundation (I-1382) to TMW Citation Format: Thomas M. Wilkie, Ozhan Ocal, Lee B. Rivera, Rolf A. Brekken. Rgs16: HTS biomarker for pancreas development, diabetes, and PDAC. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A98.
Flow Study of Restart of Waxy Crude Oil

The calculation of restart of waxy crude oil make for safety restart and restart design.Pressure propagating,crude oil yield progress,viscidity vary,clearing the oil plug from the pipe are developed.The coupled model is studied continuity equation,motion equation and theology equation.The restart model takes into account the compressibility and longitudinal variations.The theology of the gelled oil is modeled based on Bingham model,yield stress varies with time.Both laminar and turbulent flows are considered in the model.Result is calculated by numerical procedure,the present model gives a more realistic prediction.
The vertical fingerprint of earthquake cycle loading in southern California

Vertical crustal motions during the earthquake cycle are poorly constrained for strike–slip faults. Analysis of GPS data from the San Andreas Fault shows that the crust flexes over hundreds of kilometres due to locking of the fault at depth.
The Tumor Microenvironment as a Metastasis Biomarker in Breast Cancer

Distant metastasis is the primary cause of death in breast cancer, and metastasis often occurs despite potentially curative local therapy of the primary tumor. Prognostic factors for distant recurrence after local therapy are largely “tumor-centric”. Defining the interactions between tumor cells and their microenvironment, and identifying the molecular mechanisms that define their interactions, provides a basis for development of metastasis biomarkers, and the ability to therapeutically target individual steps in the metastatic cascade. In vivo imaging modalities and other techniques have facilitated identification of the steps required for metastasis. These initial steps include streaming of tumor cells toward endothelial cells in collaboration with tumor-associated macrophages, formation of microanatomic structures consisting of tumor cells, macrophages, and endothelial cells, and transendothelial migration of tumor cells at these sites resulting in intravasation and dissemination to distant sites. Metastasis biomarkers that have been associated with distant recurrence in humans, and are based on observations of the tumor microenvironment, include a multiplex immunofluorescence assay that measures invasive isoforms of the actin regulatory protein Mena (a marker which we call “Menacalc”) that enable tumor cell streaming. Multiplex immunohistochemical assays that identify where Mena-expressing tumor cells, endothelial cells, and macrophages form microanatomic structures can serve as platforms for transendothelial migration, intravasation, and metastasis (which we call “TMEM” for tumor microenvironment of metastasis). An understanding of the signaling molecules that drive these interactions may provide a foundation for developing therapeutic strategies to prevent metastasis. There is potential for these biomarkers to both exhibit clinical utility by more accurately characterizing prognosis and thus the potential to benefit from standard therapies. They could also to predict benefit from novel interventions that prevent metastasis.
The Location of Anterior Cruciate Ligament Tears: A Prevalence Study Using Magnetic Resonance Imaging.

Background:Over the past decade, there has been a resurgence of interest in anterior cruciate ligament (ACL) preservation. Proximal and distal avulsion tears have been treated with arthroscopic primary repair, while augmented repair, remnant tensioning, primary repair with biological scaffold, and remnant preservation have been proposed for different types of midsubstance tears. Currently, the incidence of these different tear types is unknown.Purpose:To propose a magnetic resonance imaging (MRI) classification system for different tear types based on clinical relevance and to assess the distribution of these different ACL tear types.Study Design:Case series; Level of evidence, 4.Methods:A retrospective search in an institutional radiographic database was performed for patients who underwent knee MRI at our institution between June 2014 and June 2016. Patients younger than 18 years and those with reports of chronic tears, partial tears, multiligamentous injuries, were excluded. Tear types were graded as p...
Spiritual, but not religious?: On the nature of spirituality and its relation to religion

Recent years have seen a rise in those who describe themselves as “spiritual, but not religious”. At a popular level, there has been a lot of debate about this label and what it represents. But philosophers have in general paid little attention to the conceptual issues it raises. What is spirituality, exactly, and how does it relate to religion? Could there be a non-religious spirituality? In this paper, I try to give an outline account of the nature of spirituality and of religion, and then close with some thoughts on the prospects for a non-religious spirituality.
Normative best-corrected values of the visual image quality metric VSX as a function of age and pupil size

The visual image quality metric the visual Strehl ratio (VSX) combines a comprehensive description of the optics of an eye (wavefront error) with an estimate of the photopic neural processing of the visual system, and has been shown to be predictive of subjective best focus and well correlated with change in visual performance. Best-corrected visual image quality was determined for 146 eyes, and the quantitative relation of VSX, age, and pupil size is presented, including 95% confidence interval norms for age groups between 20 and 80 years and pupil diameters from 3 to 7 mm. These norms were validated using an independently collected population of wavefront error measurements. The best visual image quality was found in young eyes at smaller pupil sizes. Increasing pupil size caused a more rapid decrease in VSX than increasing age. These objectively determined benchmarks represent the best theoretical levels of visual image quality achievable with a sphere, cylinder, and axis correction in normal eyes and can be used to evaluate both traditional and wavefront-guided optical corrections provided by refractive surgery, contact lenses, and spectacles.
The Radiology of Upper Tract Collecting System Neoplasms

While excretory pyelography, ultrasound, PET-CT, and MRI all have roles in the assessment of upper tract neoplasms, the workhouse is the CT. Ultrasound allows for dynamic assessment of masses and PET-CT allows for assessment of metabolic activity which allows for neoplasms to be detected in what would be otherwise normal appearing lymph nodes. MRI urography can be useful but is limited by expense, length of exam, and interpretative expertise. In CT, both pre- and post-contrast imaging is needed. Split bolus techniques have allowed for the reduction of radiation. The examination can be tailored to optimally opacify the collecting system to allow for detection of filling defects. It also permits for accurate assessment of extrarenal extension of disease. Appearance of the neoplasm can be varied that include mural and polypoid and often have an irregular surface. Not only can the masses be seen but also the effect on surrounding structures causing obstructions. A wide range of non-neoplastic conditions can have a similar appearance but will present with a different clinical picture. Close collaboration between the radiologist and urologist is therefore required.
The stability of human beta-globin mRNA is dependent on structural determinants positioned within its 3' untranslated region

Controls that act at both transcriptional and posttranscriptional levels assure that globin genes are highly expressed in developing erythroid cells. The extraordinary stabilities of alpha- and beta-globin mRNAs permit globin proteins to accumulate to substantial levels in these cells, even in the face of physiologic transcriptional silencing. Structural features that determine alpha-globin mRNA stability have recently been identified within its 3'UTR; in contrast, the structural features that determine beta-globin mRNA stability remain obscure. The current study begins to define the structural basis for beta-globin mRNA stability. Two tandem antitermination mutations are introduced into the wild-type human beta-globin gene that permit ribosomes to read into the 3'UTR of the encoded beta-globin mRNA. The readthrough beta-globin mRNA is destabilized in cultured erythroid cells, indicating that, as in human alpha-globin mRNA, an unperturbed 3'UTR is crucial to maintaining mRNA stability. Additional experiments show that the beta-globin and alpha-globin mRNA 3'UTRs provide equivalent levels of stability to a linked beta-globin mRNA coding region, suggesting a parallel in their functions. However, destabilization of the antiterminated beta-globin mRNA is independent of active translation into the 3'UTR, whereas translation into the alpha-globin mRNA 3'UTR destabilizes a linked beta-globin coding region in a translationally dependent manner. This indicates that the alpha- and beta-globin 3'UTRs may stabilize linked mRNAs through distinct mechanisms. Finally, it is shown that neither of the two mutations that, in combination, destabilize the beta-globin mRNA have any effect on beta-globin mRNA stability when present singly, suggesting potential redundancy of stabilizing elements. In sum, the current study shows that a functionally intact beta-globin mRNA 3'UTR is crucial to maintaining beta-globin mRNA stability and provides a level of stability that is functionally equivalent to, although potentially mechanistically distinct from, the previously characterized alpha-globin mRNA 3'UTR stability element.
The molecular basis for cytolytic T lymphocyte function: analysis with blocking monoclonal antibodies.

Cytolytic T lymphocytes (CTL) were identified during the late 1960’s (1,2) and are thought to be important effector cells in immunity to viruses (3) and in allograft rejection (4), Despite considerable effort during the past decade, little has been learned about the biochemical basis for the killing event. Not only do the presumed molecular mediators remain unidentified, but fundamental physiological questions remain unanswered.
Risk of CNS adverse events (CNS-AEs) for patients with non-small cell lung cancer (NSCLC) and melanoma brain metastases (BM) treated with CNS radiation (CNS-RT) and immune checkpoint inhibitors (CPIs).

2010Background: CPIs are widely used in the treatment of both metastatic melanoma and NSCLC. BM frequently occur and are treated with CNS-RT. Since both CNS-RT and CPIs can cause neuro-inflammation...
Impact of Precision Medicine on Drug Repositioning and Pricing: A Too Small to Thrive Crisis

The pricing of targeted medicines continues to be a major area of contention in healthcare economics. This issue is further complicated by redefining the role of molecular testing in precision medicine. Currently, whilst pricing of clinical laboratory diagnostics is cost-based, drug pricing is value-based. The pricing for molecular testing is under pressure to change the traditional business model, for it has a critical subsidiary role in determining the final value of targeted medicines. The market size for drugs is reduced by molecular testing when patients with the same disease are stratified based on their genetics, it is critical to determine the value of this new enhanced drug specificity to realize its full pricing potential. However, these value-based pricing strategies require a careful understanding of changing market conditions, especially, in the context of stratified patient segments made possible by precision medicine. In this article, we discuss the various factors impacting pricing decisions, and consider evolving economic trends in precision medicine.
Implementation of Nonlinear Fractional Order Fuzzy Logic Controller for PID with Second Order Transfer Function

Now a day the requirement of controllers in every field of engineering is exponentially increased. From the conventional area of controllers, PID controller is widely used. Any practical system consist of combination of sub-systems and these sub-systems behave as non-linear systems. To control any non-linear system, conventional PID is not so successful from stability point of view. To improve the efficiency of this fractional order PID controller, this is further controlled with fuzzy logic controllers (FLC). Implementation of FLC improves the efficiency as well as the stability of system.
Looking for new gluon physics at the Tevatron

Abstract CDF data from the 1988–1989 Tevatron run are used to constrain the characteristic scale of physics beyond the Standard Model which couples to gluons. New gluonic physics would cause the inclusive jet cross section to deviate from that of pure QCD at high transverse jet energies. We find that the CDF data place a lower bound of 2.03 TeV at 95% CL on the characteristic scale of new gluon sector physics.
Synthesis of difluoroalkylpyrrolic compounds from (diethylamino)sulfur trifluoride and acylpyrroles

Abstract Several difluoroalkylpyrrolic compounds with different functional groups have been synthesized by the reaction of DAST ((diethylamino)sulfur trifluoride) with the corresponding NH protected acylpyrroles in 68–87% yields. It was found that NH protection was necessary to make the reactions successful.
Improved Diagnosis Methodology for Multi-Defect Scenarios in High Compression Scan based Designs

Need for competitive part with reduced cost of build is pushing the boundaries of scan compression adoption in high volume designs. This opens up multiple challenges in effective failure diagnosis, especially in deep sub nanometer designs with higher defect densities and higher probabilities of multi-defect failures. While there are many conventional methods available to address this challenge, they largely suffer from poor accuracy or are time intensive; more particularly at higher scan compression. In this paper, we present a new robust multiple defect diagnosis algorithm and methodology, aimed at achieving high accuracy and resolution in the presence of multiple defects independent of the compression solution implemented. We also present summary from a detailed evaluation conducted to study the efficacy of the proposed diagnostic methodology. Experimental results on a 45nm industrial design indicate significant improvement in accuracy and resolution at 450X high scan compression using the proposed methodology.
Anti-Janus: Or, Impasses of the Differential Approach

This chapter examines some contemporary theories whose philosophical positions share identifiable family resemblances with one another. I name their shared orientation ‘the differential approach’ to decolonizing knowledge. I first provide a very brief account as to why the poststructuralist concept of difference has gained so much traction, and then explain why I have chosen the domains of ontology, philosophy of religion, and philosophy of truth as the sites of critical inquiry for this chapter. Ultimately, Chap. 3 discloses a number of the contradictions, paradoxes, and aporias that lie at the heart of the differential approach.
Co-crystal structures of HIV TAR RNA bound to lab-evolved proteins show key roles for arginine relevant to the design of cyclic peptide TAR inhibitors.

RNA-protein interfaces control key replication events during the HIV-1 life cycle. The viral trans-activator of transcription (Tat) protein uses an archetypal arginine-rich motif (ARM) to recruit the host positive transcription elongation factor b (pTEFb) complex onto the viral trans-activation response (TAR) RNA, leading to activation of HIV transcription. Efforts to block this interaction have stimulated production of biologics designed to disrupt this essential RNA-protein interface. Here, we present four co-crystal structures of lab-evolved TAR-binding proteins (TBPs) in complex with HIV-1 TAR. Our results reveal that high-affinity binding requires a distinct sequence and spacing of arginines within a specific β2-β3 hairpin loop that arose during selection. Although loops with as many as five arginines were analyzed, only three arginines could bind simultaneously with major-groove guanines. Amino acids that promote backbone interactions within the β2-β3 loop were also observed to be important for high-affinity interactions. Based on structural and affinity analyses, we designed two cyclic peptide mimics of the TAR-binding β2-β3 loop sequences present in two high-affinity TBPs (KD values of 4.2 ± 0.3 and 3.0 ± 0.3 nm). Our efforts yielded low-molecular weight compounds that bind TAR with low micromolar affinity (KD values ranging from 3.6 to 22 μm). Significantly, one cyclic compound within this series blocked binding of the Tat-ARM peptide to TAR in solution assays, whereas its linear counterpart did not. Overall, this work provides insight into protein-mediated TAR recognition and lays the ground for the development of cyclic peptide inhibitors of a vital HIV-1 RNA-protein interaction.
Rapid On-Site Cytologic Evaluation: A Feasibility Study Using Ancillary Interventional Pulmonary Personnel.

BACKGROUND Ancillary health professionals helping in a procedural service is a common practice everywhere. OBJECTIVES This was a proof-of-concept study to assess feasibility of using ancillary personnel for rapid on-site cytologic evaluation (ROSE) at interventional pulmonary procedures. METHODS After a training interval, a respiratory therapist (RT) performed ROSE on consecutive interventional pulmonary specimens. Sample sites included lymph nodes, lung, liver, and the left adrenal gland. RT findings were subsequently correlated with blinded cytopathology-performed ROSE and with final histopathology results, with primary foci of adequacy and the presence or absence of malignancy. RESULTS Seventy consecutive cases involved 163 separate sites for ROSE analysis. Adequacy: There was a high level of concordance between RT-performed ROSE (RT-ROSE) and cytopathology ROSE (CYTO-ROSE). They agreed upon the adequacy of 159 specimens. The Cohen's κ coefficient ± asymptotic standard error (ASE) was 0.74 ± 0.175, with p < 0.0001. Malignancy: RT-ROSE concurred highly with CYTO-ROSE, with agreement on 150 (92%) of the 163 specimens. Cohen's κ coefficient ± ASE was 0.83 ± 0.045, with p < 0.0001. When the comparison was for malignancy by case rather than individual site, Cohen's κ coefficient ± ASE was 0.68 ± 0.08, with p < 0.0001. CONCLUSION This study demonstrates that ancillary personnel supporting an interventional pulmonary service can be trained to perform initial ROSE. Cytopathology can be called after sampling and staining have produced adequate samples. This setup streamlines ROSE evaluation with regard to time and cost.
Challenges to Religious Experience

“Challenges to Religious Experience” In this chapter, the author’s focus is on the types of religious experience that might engender independent belief in a higher power, specifically, the direct perception of the divine. Lorkowski raises substantive problems against such experiences. First, the author points out that, because such events are private, mental phenomena, natural explanations, especially hallucinations and self-hypnosis, cannot be adequately ruled out. This is exacerbated by problems inherent to the private nature of mental perceptions disanalogous to those given by the senses. Lastly, the author points out the fundamentally asymmetrical nature of the evidence provided by religious experience, that even if it is sufficient for the subject to believe, this in no way transfers to someone who receives mere testimony of the experience.
A cost-effectiveness analysis of universal hepatitis C screening in all United States pregnancies.

To evaluate the cost-effectiveness of universal screening for HCV among all pregnant women in the United States.We designed a decision-analytic model to evaluate the cost-effectiveness and outcomes...
Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 : A Prospective Cohort Study.

Background Patients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear. Objective To determine the immunogenicity of mRNA-based SARS-CoV-2 vaccines in patients with CID. Design Prospective observational cohort study. Setting Two U.S. CID referral centers. Participants Volunteer sample of adults with confirmed CID eligible for early COVID-19 vaccination, including hospital employees of any age and patients older than 65 years. Immunocompetent participants were recruited separately from hospital employees. All participants received 2 doses of mRNA vaccine against SARS-CoV-2 between 10 December 2020 and 20 March 2021. Participants were assessed within 2 weeks before vaccination and 20 days after final vaccination. Measurements Anti-SARS-CoV-2 spike (S) IgG+ binding in all participants, and neutralizing antibody titers and circulating S-specific plasmablasts in a subset to assess humoral response after vaccination. Results Most of the 133 participants with CID (88.7%) and all 53 immunocompetent participants developed antibodies in response to mRNA-based SARS-CoV-2 vaccination, although some with CID developed numerically lower titers of anti-S IgG. Anti-S IgG antibody titers after vaccination were lower in participants with CID receiving glucocorticoids (n = 17) than in those not receiving them; the geometric mean of anti-S IgG antibodies was 357 (95% CI, 96 to 1324) for participants receiving prednisone versus 2190 (CI, 1598 to 3002) for those not receiving it. Anti-S IgG antibody titers were also lower in those receiving B-cell depletion therapy (BCDT) (n = 10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites (n = 48), tumor necrosis factor inhibitors (n = 39), and Janus kinase inhibitors (n = 11); however, 95% CIs were wide and overlapped. Neutralization titers seemed generally consistent with anti-S IgG results. Results were not adjusted for differences in baseline clinical factors, including other immunosuppressant therapies. Limitations Small sample that lacked demographic diversity, and residual confounding. Conclusion Compared with nonusers, patients with CID treated with glucocorticoids and BCDT seem to have lower SARS-CoV-2 vaccine-induced antibody responses. These preliminary findings require confirmation in a larger study. Primary funding source The Leona M. and Harry B. Helmsley Charitable Trust, Marcus Program in Precision Medicine Innovation, National Center for Advancing Translational Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.
On-device Prior Knowledge Incorporated Learning for Personalized Atrial Fibrillation Detection

Atrial Fibrillation (AF), one of the most prevalent arrhythmias, is an irregular heart-rate rhythm causing serious health problems such as stroke and heart failure. Deep learning based methods have been exploited to provide an end-to-end AF detection by automatically extracting features from Electrocardiogram (ECG) signal and achieve state-of-the-art results. However, the pre-trained models cannot adapt to each patient’s rhythm due to the high variability of rhythm characteristics among different patients. Furthermore, the deep models are prone to overfitting when fine-tuned on the limited ECG of the specific patient for personalization. In this work, we propose a prior knowledge incorporated learning method to effectively personalize the model for patient-specific AF detection and alleviate the overfitting problems. To be more specific, a prior-incorporated portion importance mechanism is proposed to enforce the network to learn to focus on the targeted portion of the ECG, following the cardiologists’ domain knowledge in recognizing AF. A prior-incorporated regularization mechanism is further devised to alleviate model overfitting during personalization by regularizing the fine-tuning process with feature priors on typical AF rhythms of the general population. The proposed personalization method embeds the well-defined prior knowledge in diagnosing AF rhythm into the personalization procedure, which improves the personalized deep model and eliminates the workload of manually adjusting parameters in conventional AF detection method. The prior knowledge incorporated personalization is feasibly and semi-automatically conducted on the edge, device of the cardiac monitoring system. We report an average AF detection accuracy of 95.3% of three deep models over patients, surpassing the pre-trained model by a large margin of 11.5% and the fine-tuning strategy by 8.6%.
The Art of Dancing with Change

At present North American English seems to prevail over British English in international communication. Probably this has occurred due to economic and technological advantages, like ever since the advent of the World Wide Web, societies have reeled under the impact of needing to communicate rapidly and effectively with other countries. In the worldwide effort to improve communication, the language begun to establish what may become known as international English. This chapter highlights the differences between British English and North American English, like: differences in grammar, spellings (, and style. International English seems to be moving toward faster and more direct communication. An important part of this trend in science journals is the use of active voice instead of passive voice along with the use of simple present tense, both in the name of getting messages across directly and quickly.
Anthropometry of Women of the U.S. Army

A new anthropometric survey of U. S. Army women was planned and carried out in 1976-1977 in response to the need for current and comprehensive body size data for the women who make up an increasingly large part of the United States Army. The main purpose of the survey was to obtain and develop statistical data on the body sizes and proportions of Army women. As a result, new anthropometric data now are available for Army women, as well as workspace and strength measurements. While there has been relatively little change in the body dimensions of Army women between 1946 and 1977, comparisons of data for men and women clearly show that serious design and sizing problems will be encountered in the development of clothing and equipment intended for use by both Army men and women. Language: en
Granting and Hedging Employee Stock Options: A Tax Motivation and Empirical Tests

We present a tax motivation for the use of employee stock options (ESO) in compensation schemes, based on the advantageous treatment allowed for a firm hedging positions written on its own securities. In a binomial option framework, we show that a cost saving on the order of 10-15% of compensation can be achieved if a company hedges its ESO liability by repurchasing its own shares and issuing debt in a dynamic manner. The financial and popular press has noted both an increase in ESO usage and a tendency by firms to repurchase their shares. It is presumed that the objective of firms' stock repurchases is to hedge their ESO positions and avoid further diluting the stakes of their non-ESO shareholders. However, classic finance paradigms suggest that in the absence of informational effects and market frictions, (preventing) dilution should have little or no impact on the wealth of shareholders. Our model indicates that the stock repurchases and debt related tax benefits associated with hedging activity should favorably impact share prices, thereby providing a value- based justification for reducing dilution. Empirical results we present are consistent with our model. In particular, the data show that ESO usage is positively related to leverage increases and to share repurchases. In addition, although research has found that stock repurchases tend to follow price declines, we find that pre-repurchase stock rates-of-return are greater for firms with more ESO. This finding is expected in a hedging framework, since option values and share repurchases tend to increase with share prices.
Sentinel lymph node biopsy after neo-adjuvant chemotherapy in breast cancer.

: The timing of sentinel node biopsy in the setting of neo-adjuvant chemotherapy for breast cancer is controversial. Sentinel node biopsy performed after neo-adjuvant chemotherapy may save patients with a nodal response the morbidity of an axillary lymph node dissection. A retrospective review of prospectively collected data compared sentinel node biopsies performed after patients had received neo-adjuvant chemotherapy with patients who had not received neo-adjuvant chemotherapy. Demographic factors, tumor characteristics, and the results of the sentinel node biopsies and completion lymph node dissections (when applicable) were compared. A total of 231 axillary procedures (224 patients) were evaluated. The patients who received neo-adjuvant chemotherapy (NEO; N = 52) were younger, had higher grade tumors, were more likely to have a mastectomy, and were more likely to have ER-negative and HER-2/neu positive tumors than the patients who did not receive neo-adjuvant chemotherapy (NON; N = 179). The mean clinical tumor size in the neo-adjuvant group was 4.5 cm (±1.8) prior to chemotherapy; the post-chemotherapy pathologic size was 1.4 cm (±1.3). A sentinel node was identified in all cases. There were no significant differences between the groups in the mean number of sentinel nodes removed (NEO = 3.3; NON = 3.1; p = 0.545), the percentage of positive axillae (NEO = 24%; NON = 21%; p = 0.776) or the mean number of positive sentinel nodes (NEO = 1.3; NON = 1.5; p = 0.627). There was no difference in the percentage of completion lymph node dissections with additional positive nodes (NEO = 20%; NON = 35%; p = 0.462); there was a difference in the number of nodes removed in the completion lymph node dissections (mean NEO = 12.0; NON = 16.4; p = 0.047). Sentinel node biopsy performed after neo-adjuvant chemotherapy appears to be an oncologically sound procedure and may save some patients the morbidity of a complete lymph node dissection.
The University of Pennsylvania RoboCup Legged Soccer Team

This was a “building” year for the UPennalizers, where we focused on developing a solid foundation of interconnected modules that could be easily customized and upgraded as our team progressed.We suffered two hard fought losses in early competition, and so did not make it to the playoff rounds. We worked on developing our own walking routines- at first, relying on quasi-static stability, and more recently moving towards fully dynamic walking gaits. We also were the only team to develop an audio communication protocol that could be used to transfer small pieces of information (3-4 bits per second). Lastly, we developed new visual tracking routines that allowed for greater flexibility in how we track the ball and perform localizations.
Isoenzymes of horse liver alcohol dehydrogenase active on ethanol and steroids : cDNA cloning, expression, and comparison of active sites

Horse liver alcohol dehydrogenase occurs as isoenzymes: E is active on ethanol but not steroids; S is active on ethanol and steroids. The cDNAs for these isoenzymes were cloned; both were 1.8-kilobase long and contained complete coding sequences. Both enzymes were expressed in Escherichia coli, and the purified proteins had properties similar to those of the natural enzymes. The amino acid sequence deduced from the open reading frame of the E-type cDNA agreed with the amino acid sequence of the E isoenzyme determined by protein sequencing and x-ray crystallography. When compared with the E-type cDNA, the coding region of the S-type cDNA contains 24 substitutions and 3 deletions, giving rise to an amino acid sequence for the S. isoenzyme that differs from that of the E isoenzyme at 10 positions: nine conservative substitutions and one deletion, of Asp-115. These changes can be accommodated in the three-dimensional structure of the E isoenzyme, and models of the E and S isoenzymes complexed with a 3 beta-hydroxy-5 beta-steroid were built. The modeling shows that Leu-116 apparently sterically hinders binding of steroids in the E isoenzyme, and deletion in the S isoenzyme of Asp-115 moves Leu-116 and relieves the hindrance. The human gamma and rat liver enzymes are also active on steroids, but they have a different constellation of amino acid residues in the substrate pocket. Thus, there are multiple bases for the activity on steroids.