cssi/SciSciGPT-SciSciNet huggingface dataset:
A review of the microbiological techniques for the isolation and identification of streptococci.

(1976). A Review of The Microbiological Techniques for the Isolation and Identification of Streptococci. CRC Critical Reviews in Clinical Laboratory Sciences: Vol. 6, No. 4, pp. 287-317.
Site specificity of bleomycin-mediated single-strand scissions and alkali-labile damage in duplex DNA

Form II PM2 DNA, which contained bleomycin-mediated single-strand breaks, was purified and treated with the extracellular endonuclease from Alteromonas BAL 31. This enzyme cleaves the phosphodiester backbone opposite a single-strand break to yield a double-strand break. The locations of these double-strand breaks were determined relative to the cleavage sites produced by the restriction enzyme HindIII. The experimental procedure was as follows. Form I PM2 DNA was treated with bleomycin to produce alkali-labile bonds. These were hydrolyzed by alkali treatment and the DNA, now containing single-strand breaks, was purified and treated with the BAL 31 enzyme and the HindIII enzyme to determine the positions of the original alkali-labile bonds. It was found that the single-strand breaks and alkali-labile bonds were introduced at preferred sites on the PM2 genome, since electrophoretic analyses of the DNA after the HindIII digestion revealed DNA bands of discrete sizes. The molecular weights of the DNA fragments produced by these treatments indicate that single-strand breaks and alkali-labile bonds occur at the same sites as those previously determined for direct double-strand scissions introduced by bleomycin at neutral pH. Some of the specific sites of double-strand scissions mediated by bleomycin at neutral pH (Lloyd et al., 1978b) are also shown here to be relatively more reactive than other sites when the DNA contains superhelical turns.
Fighting organized crimes: using shortest-path algorithms to identify associations in criminal networks

Effective and efficient link analysis techniques are needed to help law enforcement and intelligence agencies fight organized crimes such as narcotics violation, terrorism, and kidnapping. In this paper, we propose a link analysis technique that uses shortest-path algorithms, priority-first-search (PFS) and two-tree PFS, to identify the strongest association paths between entities in a criminal network. To evaluate effectiveness, we compared the PFS algorithms with crime investigators' typical association-search approach, as represented by a modified breadth-first-search (BFS). Our domain expert considered the association paths identified by PFS algorithms to be useful about 70% of the time, whereas the modified BFS algorithm's precision rates were only 30% for a kidnapping network and 16.7% for a narcotics network. Efficiency of the two-tree PFS was better for a small, dense kidnapping network, and the PFS was better for the large, sparse narcotics network.
Using Slocum gliders for coordinated spatial sampling

Buoyancy driven Autonomous Underwater Vehicles (AUVs), such as the Slocum glider, allow for a prolonged presence to study the oceans. They can operate for weeks or even months recording oceanographic data for a fraction of the cost of research vessels. However, the vehicles are limited to the number of sensors that can be carried onboard. Alternatively, a group of AUVs performing formation flight, where AUVs maintain particular positions relative to each other, could be used to observe ocean conditions and phenomena at a high spatiotemporal resolution carrying a variety of sensors. The vehicles can conceptually act as a single science instrument that can be easier and less expensive to deploy than higher cost, large AUVs. In this paper we propose and evaluate, using simulations, an effective coordination strategy for formation flight which monitors the formation quality using underwater communication. If an AUV drifts out of formation, all vehicles are instructed through underwater communication to resurface in order to reestablish the formation. Overall, this strategy is able to keep a formation of gliders longer than the traditional approach and can gather significantly more data samples, which corresponds to an overall decrease in the per sample energy cost.
Modeling and measurements of novel monolithic inductors and transformers

This paper presents the analysis, modeling, and measurements of a novel configuration of spiral inductors and transformers to enhance the figure of merits. The present configuration utilizes a Z-shaped multilayer metalization to increase the Q of the monolithic inductors, and increase K without sacrificing the Q of the monolithic transformers. A simple two-port lumped-circuit model derived from inductor S-parameters is used to illustrate the potential of the new design. Several on-chip transformers have been fabricated using the Motorola 0.18-micron copper process. The experimental data shows good agreement with predicted data obtained using the HFSS software simulator. A noticeable increase of mutual coupling and Q is achieved. The transformer can be optimized to achieve high Q or high K or both. © 2004 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2005.
Named entity recognition from Arabic Wikipedia

Abstract Named Entity Recognition (NER) is the problem of locating mentions to entities such as persons, locations and organizations. The named entity information is helpful for reducing the complexity of monolingual and multilingual processing tasks, such as information extraction, parsing and machine translation. We investigate the Arabic NER problem from the Arabic Wikipedia text. We employ statistical sequence labeling methods for solving the NER task. Previous studies suggest that sequence labeling methods, such as Conditional Random Fields, are the state of the art NER frameworks. The sequence labeling methods require human labeled training data. Most ofthe Arabic human labeled data for NER belong to the political news domain and the consequent trained models are biased towards the news domain. In contrast, our target test data (Arabic Wikipedia articles) has a very diverse set of topics. The domain mismatch between the train and test data results in poor NER performance. In order to reduce the coverage problem, we present three techniques: (1) we use the Wikipedia network structure to collect additional information about the text. Information such as monolingual and cross-lingual hyperlinks and text formatting lead us to use new features of the Wikipedia text in NER models. Moreover, we use cross-lingual projection to collect named entity information from English Wikipedia. (2) We use a domain adaptation technique to shift the model from the baseline political domain to domains relevant to our test data. Our model adaptation uses a small set of in-house-labeled Arabic Wikipedia articles. (3) We use self-training to port from a fully supervised to a semi-supervised learning framework: we collect a large volume of unlabeled Arabic Wikipedia articles to expand the underlying NER domain to new text domains. Our model expansion is gradual and iterative. In each iteration we add a new set of unlabeled articles to the training and use the current model to label and construct a larger model. Our NER evaluations are based on the standard precision and recall metrics.We evaluate our proposed framework in four different text domains ofArabic Wikipedia.
Relationships between Family Communication and Consumer Activities of Adolescents: An Exploratory Study

This study uses a multitrait, multi-informant approach to examine the relationships between family communication and adolescent involvement in consumer activity using two measures of family communication, one that measures the general quality of communication between parents and adolescents, and another that measures the frequency of consumption-specific communication between parents and adolescents. In addition, the perceptions of mothers, fathers, and adolescents are used in the analysis. Findings show that the two communication constructs are conceptually distinct. Positive relationships between the communication constructs and adolescents’ consumer activities are found; however, the presence of significant relationships depends on which individual family members’ or family member dyads’ perceptions are used in the analysis. On the basis of the findings, several suggestions for future research are discussed.
Von der Langzeitbehandlung im psychiatrischen Krankenhaus zur Integration in die Gesellschaft: Historischer Hintergrund und Problemstellung

Der Verlauf der Schizophrenie ist unterschiedlich. Eine besondere Gruppe chronischer Falle — die derzeitige Population entspricht in etwa der Gruppe, die vor Einfuhrung der Neuroleptika Anfang der funfziger Jahre in den psychiatrischen Krankenhausern war — zeigt verschiedene Formen einer mehr oder weniger schweren Behinderung in medizinischer wie sozialer Hinsicht. Ziel dieses Symposiums uber eine Standortbestimmung (»reconnaissance workshop«) ist es, Behandlungsstrategien fur diese Gruppe von schwerkranken Patienten zu diskutieren.
Observational Searches for Galaxies at z > 6

Although the universe at redshifts greater than six represents only the first one billion years ( 6, with spectroscopically confirmed galaxies out to nearly z = 9. Using these large samples, we have begun to gain a physical insight into the processes inherent in galaxy evolution at early times. In this review, I will discuss i) the selection techniques for finding distant galaxies, including a summary of previous and ongoing ground and space-based searches, and spectroscopic followup efforts, ii) insights into galaxy evolution gleaned from measures such as the rest-frame ultraviolet luminosity function, the stellar mass function, and galaxy star-formation rates, and iii) the effect of galaxies on their surrounding environment, including the chemical enrichment of the universe, and the reionization of the intergalactic medium. Finally, I conclude with prospects for future observational study of the distant universe, using a bevy of new state-of-the-art facilities coming online over the next decade and beyond.
Harbinger of the 24-Hour Knowledge Factory

Recent academic and policy studies focus on offshoring as a cost-of-labor driven activity that has a direct impact on employment opportunities in the countries involved. This paper broadens this perspective by introducing and evaluating the 24-hour knowledge factory as a model of information systems offshoring that leverages other strategic factors beyond cost savings. A true 24-hour knowledge factory ensures that progress is being made on information systems related tasks at all times of day by utilizing talented information systems professionals around the globe. Many organizations currently implement other variants of offshoring that appear similar but are fundamentally distinct. The typical model is a service provider framework in which an offshore site provides service to the central site, often with two centers and a distinction between a primary center and secondary center. Entire tasks are often outsourced to the lower-cost overseas site and sent back when completed. In contrast, the 24-hour knowledge factory involves continuous and collaborative round-the-clock knowledge production achieved by sequentially and progressively distributing the knowledge creation task around the globe, completing one cycle every 24 hours. Thus, the 24-hour knowledge factory creates a virtual distributed team, in contrast to a team that is collocated in one site, either onshore or offshore. By organizing knowledge tasks in this way, the 24-hour knowledge factory has the potential to work faster, to provide cheaper solutions, and to achieve better overall performance. Previous studies have examined individual teams over time and explored various benefits of distributing work to distant teams, but have not directly compared the effect of collocation versus geographic distribution on the use of information systems and the overall performance over time of two real-world teams working on a similar task in controlled conditions. This paper highlights the concept of the 24-hour knowledge factory and tests the model in a controlled field experiment that directly compares the use of information systems and subsequent performance in collocated and globally distributed software development teams. The central finding is that while collocation versus geographic distribution changes the way teams use information systems and interact at key points during a project, each type of team has the potential to use information systems to leverage its inherent advantages, to overcome disadvantages, and ultimately, to perform equally well. In other words, one organizational structure is not inherently superior nor must structure pre-determine performance. Geographic distance introduces new challenges but these can be overcome and even leveraged for strategic advantage. In sum, our findings suggest that firms can apply the 24-hour knowledge factory model to transition from a service provider framework in which offshoring is a short-term and unilateral cost-saving tactic to a strategic partnership between centers in which offshoring becomes a core component of a global corporate strategy.
Stalked by the past: the influence of ethnicity on health.

Ethnicity impacts the course of illness and medical treatment. There are enormous ethnic differences in care delivered to patients who are treated for pain. However, in addition to these social forces, there are enormous ethnic differences in physiological response to stimuli as diverse as diet, exp
Cellular and Subcellular Effects of Petroleum Hydrocarbons on Mosquito Larvae

A comparative study of the pathological effects of hypoxia and certain petroleum hydrocarbons was made to clarify the mechanism of petroleum hydrocarbon action on mosquito larvae. Light and electron microscopy revealed that both hypoxia and petroleum hydrocarbon treatment produced a generalized tissue response in mosquito larvae. Similar, but not identical, pathologic changes occurred in all tissues studied (muscle, nerve, caecum, midgut, and salivary gland) regardless of their type and position in the larvae. These data suggest that the petroleum derivatives studied, or toxic components thereof, probably penetrated the tracheal membrane. Pathological effects were primarily nuclear, manifested by chromatin clumping and loss of the granular matrix. Cytoplasmic alterations appeared to be minimal, with the rough-surfaced endoplasmic reticulum showing little degenerative change and the mitochondria exhibiting changes ranging from normal appearance to the complete loss of the cristae. A similarity in the pathological effects in larvae exposed to hypoxia and to petroleum hydrocarbons was found, indicating that these derivatives of petroleum may initiate their larvicidal action by producing an irreversible hypoxia.
Facilitation of noradrenaline release from rat brain slices by beta-adrenoceptors.

The present study examined whether stimulation of \-adrenoceptors facilitated noradrenaline release in the rat brain. Electrical stimulation-evoked overflow of tritium from rat cerebral cortical, hypothalamic and hippocampal slices labelled with 3H-noradrenaline was measured during superfusion for 100 min. Tissue slices were electrically simulated (1 Hz, 20 mA, 2 ms, 2 min), at 20(S1) and 70(S2) min after the onset of superfusion. The nonselective \-adrenoceptor agonist isoproterenol (0.1 – 10 nM) enhanced stimulation-evoked overflow of tritium from slices of cerebral cortex, hypothalamus and hippocampus in a concentration-dependent manner; mean S2/S1 ratios with 10 nM isoproterenol were 161 +- 11%, 142 +- 15% and 143 - 12% of control, respectively, in the three brain regions. The facilitatory effect of isoproterenol in cerebral cortical slices was antagonized by propranolol (50 nM), a nonselective \sb-adrenoceptor antagonist, and by the \sb1- and \sb2-selective adrenoceptor antagonists ICI 89,406 (1 nM) and ICI 118,551(1 nM), respectively. The \sb1- and \sb2-selective adrenoceptor agonists prenalterol and albuterol (0.1 \2- 10 nM), respectively, also increased stimulation-evoked overflow of tritium from cerebral cortical slices; these effects were antagonized by \sb-adrenoceptor antagonists. These findings suggest that stimulation of \sb-adrenoceptors enhance noradrenaline release from rat cerebral cortical, hypothalamic and hippocampal slices; this release mechanism appears to involve both \sb1- and \sb2-adrenoceptor subtypes. These facilitating presynaptic receptors may be involved in mediating the antidepressant-like behavioral effects of \sb2-adrenoceptor agonists.
Expression of the neurofibromatosis type 1 (NF1) gene during mouse embryonic development.

Publisher Summary This chapter identifies the von Recklinghausen neurofibromatosis type 1 (NF1) gene by positional cloning; it was found to be a tumor suppressor gene expressed most abundantly in brain. One isoform of NFl (type 2 NFl) contains an additional 21 amino acids inserted into a region of the protein that is involved in the regulation of p21- ras. To study the role of the NF1 gene in mammalian development, the expression of the NFl gene and protein product, neurofibromin, during mouse embryonic development was determined in the experiment discussed in the chapter. NFl mRNA and neurofibromin expression was detectable by Northern and Western analysis, respectively, after day 10 of murine embryogenesis and remained elevated throughout development. Type 2 NFl mRNA expression predominated before day 10, after which e type 1 NF1 mRNA was the predominant isoform detected. The protein expression of the type 2 isoform was similar to overall neurofibromin expression by Western blot analysis, with greatest expression in adult brain. Despite a similar tissue distribution pattern, type 2 neurofibromin was not found to be associated with brain cytoplasmic microtubules. These experiments suggest that the switch from type 2 to type 1 eurofibromin isoform predominance during embryogenesis may have significant functional consequences.
Determination of HCV-Specific T-Cell Activity

The magnitude and breadth of T-cell responses against HCV are associated with the outcome of HCV infection. Parameters of HCV-specific T-cell responses that are frequently assessed in clinical immunological studies include proliferation of T cells in response to HCV antigens, frequency of HCV-specific T cells secreting cytokines, and changes in antigen specificity during the course of HCV infection. Common techniques for assessing these parameters such as (3)H-thymidine incorporation assay, cytokine ELISpot assay, and strategies for epitope mapping and identification of minimal optimal epitopes are outlined, and detailed protocols are described.
Measurement and Correlation of Isochoric P-V-T Behavior of a Binary H2-Ch4 Mixture from Near Ambient to Cryogenic Temperatures and Pressures to 700 ATM

The separation of synthesis gas consisting of various concentrations of hydrogen and carbon monoxide from methane and other light hydrocarbons is a major step in the manufacture of SNG from coal. Since the separation(s) must be conducted at cryogenic temperatures, it is energy intensive. Information leading to improved efficiencies in synthesis gas/hydrocarbon separation is highly desirable. Thus, this laboratory has conducted phase and volumetric studies of gas mixtures comprised of the principal components in methane/synthesis gas mixtures. To date, extensive vapor-liquid equilibrium data (200 experimental points) have been reported1. A second, complementary study of the volumetric properties is underway and whose current findings are discussed herein.
The Contributions of Controllability and Observability to Test

Structural testing is based on the notions of controllability and observability. Controllability generally refers to the application of circuit stimulus such that the presence of a fault will cause some site(s) in the circuit to be logically different than when the fault is absent. Observability concerns the causation of a condition whereby the difference at the site(s) would force a logical difference at some circuit output where it can be directly measured. These quantities will be more formally defined in a later section.
Decentralization, Fiscal Structure, and Local State Capacity in Late-Imperial Russia

Investments in the fiscal, legal, and infrastructural “capacity” of the state have come to be seen as key determinants of economic development. Central authorities may make these investments, but local public sector institutions also play a role in building state capacity. This chapter examines the interaction between central and local capacity in the context of Tsarist Russia after the end of serfdom. We describe the structure of local government and, drawing on a variety of new sources, provide preliminary evidence on the extent of capacity building by various public sector actors. Our findings are suggestive of a particularly rich interaction between central authorities and decentralized institutions at the local level when it comes to providing public goods and services. We argue that interpretations of early modern and modern state building are remiss if they focus exclusively on the central government without considering the importance of locally determined efforts.
Observations on the Cycles in US Foreign Policy

Henriksen concludes that the US foreign policy yawing between cycles of interventionism and retrenchment conformed to presidential tenures. Each president came into office determined to zig where his predecessor had zagged. Each campaigned with a set of foreign policy prescriptions. The major political parties—Democrat and Republican—ascribe to at least general principles. These factors underline the importance of the president’s political party, the president’s own foreign policy views, and the sentiments of the voting coalition assembled to win the White House. The two major parties have held differing international philosophies since the divisive Vietnam War, which partially explains the cycles in US foreign policy. As professors Schlesinger and Klingberg proposed, cyclicity offers an element for interpreting the past and for predicting likely future directions.
Researching Technology Markets in a Fast-Cycle World

Information gathering can and should start early. Early, as in long before the product is launched, and if possible before the product is conceived — ideally, at the point when a generic technology comes into existence. This generic technology may be capable of generating many products in many different, and perhaps new, industries.
Occipitocervical Surgery Complication

Indications for occipitocervical fusion include spinal cord compression and instability of the osteoligamentous complex. Etiologies may include trauma, tumor, infection, inflammatory disorders, degenerative disorders, and congenital disorders. X-ray, CT, and MRI modalities may play a role in diagnosing occipitocervical instability, cord compression, and basilar invagination. A thorough understanding of the anatomy is requisite for surgical success. This includes the bony and ligamentous anatomy as well as the vascular anatomy of the vertebral and internal carotid artery. This chapter reviews pearls and pitfalls in complication avoidance of the occipitocervical junction.
Vasospasm in the setting of traumatic bilateral carotid-cavernous fistulas and its effect on treatment.

Background Direct, Type A, cavernous-carotid fistulas (CCFs) are predominantly caused by head trauma, especially when basilar skull fractures are present. Transarterial endovascular treatment of direct CCFs is the preferred method of treatment. Bilateral CCFs are estimated to be present in 1-2% of the cases. The treatment of bilateral CCFs is difficult often requiring a combination of endovascular and open surgical approaches. Case description We present a case of traumatic bilateral CCFs presenting with vasospasm of the anterior circulation seen on the initial angiogram on day 1 and our treatment paradigm. Conclusion This case illustrates the challenges in managing bilateral CCFs as well as the changes in collateral circulation because of cerebral vasospasm which affected our treatment paradigm.
Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.

Abstract Introduction Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. Methods A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. Results Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. Conclusions Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma.
To live and drink in Los Angeles

Many cities rely on not just traditional delivery systems for potable water, but also standard economic models for valuing those systems. Both must be questioned to ensure future water security in drought-challenged urban regions.
Trends in the Information Technologies Markets-The Future

This presentation deals with Information Technologies and their Markets. More specifically, the Computer Industry is described in global terms and its evolution over the years is briefly presented. Recent technological developments in hardware and software, as well as discernible trends are discussed. Attention is paid to technological developments and trends in Semiconductors, Large Computers, Workstations, Small Computers, as well as in Software. It is emphasized that successful companies in these industries are those that develop and exploit technology for products and services, but also have clear and visionary strategies in Marketing. The presentation anticipates the future by extrapolating lasting trends and anticipated technological developments.
What it all Means

The differences denoted by the MNCs in their preferences for the various elements of the Investment Attraction Package of the three focus countries have been commented upon under the foregoing headings related to initial investors motivation and quantum-level of investment. It is via the comparison of segmented groups that the significance of the dependent variables are brought to light. It is the differences in the dependent variables that are the object of the search. Discovery of differences permits focus on customers needs and fosters the attempts to understand. For continuity and focus of this section, the findings of differences in the IAP preferences of initial-investment MNCs as related to strategic motivation, to quantum, and to quantum/motivation are discussed under the appropriate “Motivation” heading. The interpretations of findings for Hypothesis #2 (motivation) are included with the findings of Hypothesis #3 (quantum-level and motivation) in order to increase their specificity and to add dimension.
The Generalization of the Boltzmann Equation to Higher Densities

The problem of the generalization of the Boltzmann equation to higher densities is discussed. The difficulties encountered in including in a systematic way multiple particle collisions are described. The present status of the problem is indicated.
Maintenance Adalimumab Concentrations Are Associated with Biochemical, Endoscopic, and Histologic Remission in Inflammatory Bowel Disease.

A treat-to-target therapeutic approach is emerging as the new standard of care for treating inflammatory bowel disease (IBD), Crohn’s disease (CD), and ulcerative colitis (UC). We aimed to investigate the association of serum adalimumab concentrations during maintenance therapy with biochemical, endoscopic, and histologic remission in IBD. This retrospective multicenter study included consecutive IBD patients on adalimumab maintenance therapy who had a C-reactive protein (CRP) within 1 week and/or endoscopic evaluation within 12 weeks of therapeutic drug monitoring between July 2013 and December 2016. Biochemical remission was defined as a normal CRP (≤ 5 mg/L). Endoscopic remission was defined as the absence of any ulceration/erosion or a Rutgeerts score of ≤ i1 for patients with an ileocolonic resection for CD and a Mayo endoscopic score of ≤ 1 for UC. Histologic remission was defined as the absence of any sign of active inflammation. Adalimumab concentrations were measured using the homogeneous mobility shift assay. Ninety-one CRP levels and 72 colonoscopies from 98 IBD patients [CD: n = 72 (73%)] were evaluated. Based on receiver operating characteristic analyses, we identified an adalimumab concentration threshold of 11.8, 12, and 12.2 μg/mL in CD and 10.5, 16.2, and 16.2 μg/mL in UC to stratify patients with or without biochemical, endoscopic, or histologic remission, respectively. Adalimumab concentrations ≥ 12 μg/mL (OR 8; 95% CI 2–31.9; p = 0.003) and ≥ 12.2 μg/mL (OR 9.6; 95% CI 1.7–56.1; p = 0.012) were independently associated with endoscopic and histologic remission in CD, respectively. This study demonstrates that higher maintenance adalimumab concentrations are associated with objective therapeutic outcomes in IBD.
Opportunities for Collaboration and the Adoption of Local Government Investment Pools

ABSTRACTThis study examines the determinants of state adoption of local government investment pools (LGIPs) for commingling public funds for investment. It uses aggregate local government panel dat...
T Cell Receptors-Gene-Modified T Cells for Cancer: Methods, Data, and Challenges

Cellular immunotherapy is currently one of the most exciting and promising new cancer treatments to reach the clinic. Expanded knowledge of T cell biology and new developments in synthetic biology have led to an ability to engineer T cells to express antibody-like recognition molecules linked to T cell-activating domains (chimeric antigen receptors, CARs) and tumor-specific T cell receptors (TCRs) which redirect patient-derived T cells toward their cancers. In this chapter, we will review the biology of T cell receptors, describe the rationale for generating affinity-enhanced TCRs with particular emphasis on the development of the affinity-enhanced NY-ESO-1-specific TCR. We also review clinical trials using TCR-engineered autologous T cells and highlight some important toxicities that have been observed in these studies. Finally, we provide an overview of some of the opportunities and challenges for wider application of this technology.
Visual Evidence: Increasing Usability of Systematic Reviews in Health Systems Guidelines Development.

Background Integration of evidence from systematic reviews is an essential step in the development of clinical guidelines. The current practice for reporting uses a static structure that does not allow for dynamic investigation. A need exists for an alternate reporting modality to facilitate dynamic visualization of results to match different end-users' queries. Objectives We developed a dynamic visualization of data from a systematic review using the commercial product Tableau and assessed its potential to permit customized inquiries. Methods Data were selected and extracted from a previously completed systematic review. The resulting dataset was then used to develop an interactive, web-based report designed for use by a guidelines development committee. Results A novel example of combining existing reporting standards for systematic review data and modern reporting tools was developed to investigate potential benefits of a dynamic report. Demonstrations of the report to clinicians sitting on previous and future guideline committees received positive feedback for its potential benefit in guidelines development. The report received a runner-up award during the design challenge at the 2018 Workshop on Visual Analytics in Health Care. Conclusion The use of interactive, accessible data may increase the use of systematic reviews and aid decision makers in developing evidence-based practice changes.
When the going gets tough, the tough turn female: injury and sex expression in a sex-changing tree

Premise Plant sex is usually fixed, but in rare cases, sex expression is flexible and may be influenced by environmental factors. Theory links female sex expression to better health, but manipulative work involving the experimental change of health via injury is limited, particularly in sexually plastic species. A better understanding of mechanisms influencing shifts in sex is essential to our understanding of life history theory regarding trade-offs in sex allocation and differential mortality. Methods We investigated the relationship between physiological stress and sex expression in sexually plastic striped maple trees (Acer pensylvanicum) by inflicting damage of various intensities (crown pruning, defoliation, and hydraulic restriction). We then monitored the sex expression of injured and control individuals for 2 years to assess the extent to which injury may cue changes in sex expression. Results We found that severe damage such as full defoliation or severe pruning increased odds of changing sex to female and decreased odds of changing to male. In fact, no pruned male trees flowered male 2 years later, while all males in the control group flowered partially or fully male. After full defoliation, trees had 4.5 times higher odds of flowering female. Not all injury is equal; less-severe physical trauma did not affect the frequency of sex change to femaleness. Conclusions This work demonstrates that physical trauma in striped maple appears to exhibit a threshold effect in which only the most stressful of physiological cues instigate changes in sex expression, a phenomenon previously unknown, and that damage stress is strongly correlated with switching to femaleness. These findings have implications for population sex ratios and sustainability within an increasing stressful climate regime.
Investigating the linkages between pregnancy outcomes and climate in sub-Saharan Africa

Poor pregnancy outcomes include miscarriages, stillbirths, and low birth weights. Stress from heat and lack of resources play a potentially important role in producing these poor outcomes. Women and couples who experience these poor outcomes rather than a healthy birth suffer psychological, physical, social, and financial costs as well. We use detailed reproductive data in combination with fine-scale climate data to examine pregnancy outcomes among women in sub-Saharan Africa, a region that shelters some of the poorest families in the world. Fine-scale precipitation and temperature data allow each pregnancy to be matched to the relevant climate exposures. We investigate the linkages between climate and pregnancy outcomes using linear probability models with fixed effects to minimize confounding due to factors that vary by location, season, and year. We analyze retrospective pregnancy data from more than 65,000 pregnancies recorded in 23 surveys across 15 African countries. Our results indicate that pregnancy outcomes are indeed impacted by exposure to hot days even after considering other individual-level characteristics. This research provides insight into the linkages between climate and a major adverse health outcome faced by women. In doing so, this research expands scientific understanding of the impact of environmental factors on fertility outcomes.
Mapping movements: a call for qualitative social network analysis:

Social network analysis (SNA) is an interdisciplinary method that takes as its starting point the premise that social life is created primarily and most importantly by relations and the patterns fo...
Development of a fluorescence based, high-throughput SARS-CoV-2 3CLpro reporter assay

ABSTRACT In late 2019 a human coronavirus, now known as SARS-CoV-2, emerged, likely from a zoonotic reservoir. This virus causes COVID-19 disease, has infected millions of people, and has led to hundreds of thousands of deaths across the globe. While the best interventions to control and ultimately stop the pandemic are prophylactic vaccines, antiviral therapeutics are important to limit morbidity and mortality in those already infected. At this time, only one FDA approved anti-SARS-CoV-2 antiviral drug, remdesivir, is available and unfortunately, its efficacy appears to be limited. Thus, the identification of new and efficacious antivirals is of highest importance. In order to facilitate rapid drug discovery, flexible, sensitive, and high-throughput screening methods are required. With respect to drug targets, most attention is focused on either the viral RNA-dependent RNA polymerase or the main viral protease, 3CLpro. 3CLpro is an attractive target for antiviral therapeutics as it is essential for processing newly translated viral proteins, and the viral lifecycle cannot be completed without protease activity. In this work, we present a new assay to identify inhibitors of the SARS-CoV-2 main protease, 3CLpro. Our reporter is based on a GFP-derived protein that only fluoresces after cleavage by 3CLpro. This experimentally optimized reporter assay allows for antiviral drug screening in human cell culture at biosafety level-2 (BSL2) with high-throughput compatible protocols. Using this screening approach in combination with existing drug libraries may lead to the rapid identification of novel antivirals to suppress SARS-CoV-2 replication and spread. IMPORTANCE The COVID-19 pandemic has already led to more than 400,000 deaths and innumerable changes to daily life worldwide. Along with development of a vaccine, identification of effective antivirals to treat infected patients is of the highest importance. However, rapid drug discovery requires efficient methods to identify novel compounds that can inhibit the virus. In this work, we present a method for identifying inhibitors of the SARS-CoV-2 main protease, 3CLpro. This reporter-based assay allows for antiviral drug screening in human cell culture at biosafety level-2 (BSL2) with high-throughput compatible sample processing and analysis. This assay may help identify novel antivirals to control the COVID-19 pandemic.
Behavioral effects of four novel synthetic cathinone analogs in rodents.

A new generation of novel cathinone compounds has been developed as stimulant substitutes to avoid drug control laws and detection of use by blood tests. Dipentylone, N-ethylhexedrone, 4-chloroethcathinone (4-CEC), and 4'-methyl-α-pyrrolidinohexiophenone (MPHP) were tested for in vivo psychostimulant-like effects to assess their abuse liability. Locomotor activity was assessed in an open-field assay using Swiss-Webster mice to screen for locomotor stimulant effects and to identify behaviorally-active dose ranges, times of peak effect, and durations of action. Discriminative stimulus effects were assessed in separate groups of Sprague-Dawley rats trained to discriminate cocaine or methamphetamine from vehicle. Dipentylone, N-ethylhexedrone, 4-CEC, and MPHP dose-dependently increased locomotor activity. Dipentylone, N-ethylhexedrone, and MPHP produced maximal stimulant effects similar to cocaine and methamphetamine. 4-CEC was less efficacious, producing peak stimulant effects of about 74% of that of methamphetamine. The compounds were less potent than methamphetamine and approximately equipotent with cocaine. The doses of cocaine, methamphetamine, dipentylone, and 4-CEC that produced peak effects lasted 2 to 3 h, the peak dose of N-ethylhexedrone lasted 4 h, and the peak dose of MPHP lasted 6 h. All four compounds fully substituted for the discriminative stimulus effects of methamphetamine and cocaine, although full substitution by 4-CEC occurred at doses that substantially decreased response rate. Only 4-CEC fully substituted for MDMA. These data provide evidence that the novel cathinone compounds dipentylone, N-ethylhexedrone, 4-CEC, and MPHP demonstrate potential for abuse as psychostimulants, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of methamphetamine and cocaine.
A Simplified Approach to Deep Learning for Image Segmentation

Leaping into the rapidly developing world of deep learning is an exciting and sometimes confusing adventure. All of the advice and tutorials available can be hard to organize and work through, especially when training specific models on specific datasets, different from those originally used to train the network. In this short guide, we aim to walk the reader through the techniques that we have used to successfully train two deep neural networks for pixel-wise classification, including some data management and augmentation approaches for working with image data that may be insufficiently annotated or relatively homogenous.
Developing an Integrated Energy System Interface for Electricity-Hydrogen Hybrid Nuclear Operations:

Nuclear power plants are looking towards integrated energy systems to address the challenges faced by increasing competition from renewable energy and cheap natural gas in wholesale electricity mar...
Automated Pacing Artifact Removal in Electrocardiograms

Electrocardiogram (ECG) is a basic and ubiquitous clinical tool to evaluate the electrical activity of the heart. Research and commercial software make automated calculations and interpretations from ECGs that have clinical value. An artificial pacemaker can however change the ECG and invalidate routine interpretation. Automated evaluation of paced ECGs is further hampered by electrical pacing artifacts that distort the physiological electrical signal. Sophisticated pacing systems like cardiac resynchronization therapy further complicate the problem by introducing pacing artifacts that are not only preceding but are also within the relevant ECG signal where they simply cannot be ignored. The pacing spike generates outliers that skews results and hinders both regression analysis and principal component analysis of the physiological signal. This is the first paper to show effective elimination of pacing spike outliers in ECGs. In order to eliminate pacing spikes, this paper proposes a novel filter and compares to prior techniques used in alternate fields. This filter uses modified Z-scores calculated from detrended data to locate outliers and replaces the spikes with a hyperbolic cosine function that connects the gap created from removing the spikes. The filtering improves the QRS area measurement by over 46% compared to median filtering and 65.2 % compared to unfiltered ECGs. The filter is fast (7.53 ms) and inexpensive.
Nonoperative Management of Subclavian Artery Thrombosis in Pediatric Clavicle Fractures: A Case Report.

CASE A 12-year-old patient presented after a fall onto her upper extremity. She was found to have a mildly displaced clavicle fracture with a subclavian artery thrombosis. Given the reconstitution of flow distal to the thrombosis, the patient was treated nonoperatively in consultation with vascular surgery with anticoagulation and a sling for immobilization. CONCLUSION This case highlights the importance of a thorough neurovascular examination even in a mildly displaced fracture. Nonoperatively managed thromboses may be treated successfully without orthopaedic fixation or vascular intervention, although the natural history of this injury is likely not fully understood.
Characterization of subtype selective cannabinoid cb2 receptor agonists as potential anti-inflammatory agents

Activation of the CB2 receptor has been shown to have anti-inflammatory and antinociceptive effects without causing psychoactive effects. Previously, we reported that the compound ethyl 2(2-(N-(2,3-dimethylphenyl) phenylsulfonamido)acetamido)benzoate (ABK5) is a CB2 subtype selective agonist with anti-inflammatory and antinociceptive effects. In the present study, we tested four ABK5 derivatives, ABK5-1, ABK5-2, ABK5-5, and ABK5-6, to analyze the structure of ABK5 to obtain CB2-selective agonists with higher affinity and efficacy. Affinity, subtype selectivity, and G-protein coupling were determined by radioligand binding assays. Selected compounds were then subjected to evaluation of anti-inflammatory effects using two different cell lines, Jurkat (ABK5-1 and 5-2) and BV-2 cells (ABK5-1), which are models of T cells and microglia, respectively. ABK5-1, ABK5-2, and ABK5-6 had comparable CB2 binding affinity with ABK5 (and stimulated G-protein coupling), while only ABK5-1 and ABK5-2 maintained CB2-subtype selectivity. ABK5-5 did not bind CB2 in the detectable range. RT-PCR and ELISA analysis showed that the two compounds also inhibit IL-2 and TNF-α production, and they were more efficacious than ABK5 in inhibiting TNF-α production. CXCL-12 mediated chemotaxis was also evaluated by the transwell migration assay, and both ABK5-1 and ABK5-2 inhibited chemotaxis with a stronger effect observed in ABK5-1. In the microglia cell line BV-2, ABK5-1 inhibited IL-1β and IL-6 production, which suggests this compound has anti-inflammatory effects through targeting multiple immune cells, and may be a candidate for treatment of inflammation.
Treprostinil reduces mitochondrial injury during rat renal ischemia-reperfusion injury.

BACKGROUND Renal ischemia-reperfusion injury (IRI) is a major factor contributing to acute kidney injury and it is associated with a high morbidity and mortality if untreated. Renal IRI depletes cellular and tissue adenosine triphosphate (ATP), which compromises mitochondrial function, further exacerbating renal tubular injury. Currently, no treatment for IRI is available. This study investigates the protective role of treprostinil in improving mitochondria biogenesis and recovery during rat renal IRI. METHODS Male Sprague Dawley rats were randomly assigned to groups: control, sham, IRI-placebo or IRI-treprostinil and subjected to 45 min of bilateral renal ischemia followed by 1-72 h reperfusion. Placebo or treprostinil (100 ng/kg/min) was administered subcutaneously via an osmotic minipump. RESULTS Treprostinil significantly reduced peak elevated serum creatinine (SCr) levels and accelerated normalization relative to IRI-placebo (p < 0.0001). Treatment with treprostinil also inhibited IRI-mediated renal apoptosis, mitochondrial oxidative injury (p < 0.05), and the release of cytochrome c (p < 0.01) vs. IRI-placebo. In addition, treprostinil preserved renal mitochondrial DNA copy number (p < 0.0001) and renal ATP levels (p < 0.05) to nearly those of sham-operated animals. Non-targeted semi-quantitative proteomics showed reduced levels of ATP synthase subunits in the IRI-placebo group which were restored to sham levels by treprostinil treatment (p < 0.05). Furthermore, treprostinil reduced renal IRI-induced upregulated Drp1 and pErk protein levels, and restored Sirt3 and Pgc-1α levels to baseline (p < 0.05). CONCLUSIONS Treprostinil reduces mitochondrial-mediated renal apoptosis, inhibits mitochondria fission, and promotes mitochondria fusion, thereby accelerating mitochondrial recovery and protecting renal proximal tubules from renal IRI. These results support the clinical investigation of treprostinil as a viable therapy to reduce renal IRI.