cssi/SciSciGPT-SciSciNet huggingface dataset:
Interview: Immunotherapeutic manipulation of the tumor microenvironment

Dario AA Vignali speaks to Katie Lockwood, Assistant Commissioning Editor Dario Vignali received his PhD in 1988 from the London School of Hygiene and Tropical Medicine, University of London, where he studied immunity to Schistosoma mansoni. He then held two postdoctoral positions from 1988 to 1993; first at the Institute for Immunology and Genetics, German Cancer Research Center (Heidelberg, Germany), with Gunter Hammerling, and then at the Department of Biochemistry and Molecular Biology, Harvard University (MA, USA), with Jack Strominger. He is currently Vice Chair and Member (Full Professor equivalent) of the Department of Immunology, St Jude Children’s Research Hospital (TN, USA), where he has been for 20 years. Dr Vignali’s research focuses on molecular and cellular aspects of Treg function, immune regulation by inhibitory receptors and inhibitory cytokines (IL-35) in tumor immunity, mucosal immunity and Type 1 diabetes. He also studies proximal events in T-cell receptor–CD3 signaling.
The Grant of Responsible Government to the Transvaal: More Notes on a Myth

THE article by Dr Ronald Hyam, 'Smuts and the Decision of the Liberal Government to Grant Responsible Government to the Transvaal', in the recent number of the Historical Journal1 proposes and amply documents the solution to a problem that has troubled historians for some years. Even with the best and most generous spirit, how could Prime Minister Sir Henry Campbell-Bannerman, within weeks of taking office, have accepted the arguments of an acknowledged dangerous enemy of his nation, the Boer Jan Christian Smuts, and persuaded his Cabinet colleagues to reverse their own considered policy and grant self-government to the citizens of the Transvaal? In fact was the grant of responsible government that, as Smuts put it, 'settled the future of Africa', entirely the work of one man? Dr Hyam suggests that it was no such thing. Smuts, he feels, overestimated his own influence on the prime minister. Throughout his life Smuts assumed that the series of events that culminated in I909 in the formation of the Union of South Africa had been set in train by his interview with the Liberal leader a few days before the Cabinet meeting of 8 February I906, which made the final decision for responsible government. Dr Hyam shows that the Liberals had been committed for many months to a policy leading to some form of responsible government. For some time members of the administration had been at work on modifications of the representative constitution issued under letters patent by the Unionist Colonial Secretary Alfred Lyttleton on 3I March I905. Campbell-Bannerman's contribution, he feels, was at most to compel a decision to discard the so-called 'Lyttleton Constitution' and to prepare instead a new document. The story that C.B. converted his Cabinet colleagues from some other more harsh policy he dismisses as a 'myth'. The question under consideration in this brief note is simply the origin of this myth. There is among the Spender Papers a letter from H. H. Asquith to his friend, the journalist J. A. Spender, suggesting that as late as I9I2 the question of whether Campbell-Bannerman should have been personally and solely credited with the grant of self-government was by no means settled. When read together with Lloyd George's statement to Lord Riddell, which came only about nine months later, the Asquith letter suggests that for a time two almost directly conflicting stories were in circulation. Then within a few years, certainly well before the end of his life, Asquith chose no longer to press his own version of the 8 February Cabinet meeting while Lloyd George promoted assiduously the story that Campbell-Bannerman alone was responsible for self-government in South Africa. Asquith's letter to Spender, sent from Downing Street on I5 June I9I2, offers the most convincing evidence that
Person-Centered Services and Organizational Context: Taking Stock of Working Conditions and Their Impact

Although the concept of person-centered services has gained much popularity, there are significant discrepancies in the extent to which service agencies are actually implementing it. Eight organizations, each of which was successfully providing person-centered services to at least some individuals, were examined. Some agencies were implementing the approach with significantly higher proportions of individuals receiving their services than were others. Interviews and participant observations were used to examine how the various organizational contexts contributed to these differences. Some organizations were found to be well-suited to the approach, whereas others posed significant limitations to the number of individuals who benefited or the rate at which they were likely to benefit from this approach.
The University Healthsystem Consortium clinical database: An emerging resource in colorectal surgery research

Abstract In the era of big data, many options exist for analysis of health care related outcomes. The University HealthSystem Consortium Clinical Database/Resource Manager (UHC CDB/RM) represents one such source. With over 400 hospitals participating, UHC comprises >95% of academic centers and their affiliates. Primarily used as an avenue for hospitals to meet requirements in quality assurance activities, it also makes available patient-level data on over 30 million inpatient encounters. In recent years, UHC has been increasingly used to assess quality and cost outcomes for surgical patients, many of which have been specific to colorectal procedures. Though it has limitations, it provides a useful source of data to assess quality and cost outcomes, especially at a time when these metrics are used to gauge surgeons and hospitals, as well as determine reimbursements for surgical procedures.
Criminal Appeals: Preservation & Plain Error

This nine-page 2008 article is titled “Criminal Appeals: Preservation & Plain Error.” It was published in the Maryland Criminal Defense Attorneys Association Newsletter. The article analyzes criminal appeals in cases in which the prosecution argues that an issue was not preserved for appellate review. If the prosecution prevails on non-preservation, the issue is whether the appellate court will take the issue as “plain error.” This article analyzes cases in which one side or the other prevailed on either or both of these issues.
Abstract CN06-01: Phase IIa trial of sulindac in individuals at increased risk for melanoma

Some epidemiological studies and several experimental publications suggest that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of melanoma. However, specific information on the ability of NSAIDs to reach melanocytes in vivo and to modulate key biomarkers in pre-neoplastic lesions such as dysplastic nevi have not been evaluated to date. Methods: We conducted a randomized, double-blind, placebo controlled trial of sulindac in individuals at risk for melanoma to determine whether sulindac and related metabolites are bioavailable in the nevi and whether sulindac intervention has an effect on apoptosis and vascular endothelial growth factor (VEGF) expression in atypical nevi (AN). Fifty healthy subjects with ≥ 4 large (≥5 mm and Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN06-01.
Structure of dihydrodipicolinate synthase from the commensal bacterium Bacteroides thetaiotaomicron at 2.1 Å resolution

Dihydrodipicolinate synthase (DapA) catalyzes the first committed step of the diaminopimelate biosynthetic pathway of lysine. It has been shown to be an essential enzyme in many bacteria and has been the subject of research to generate novel antibiotics. However, this pathway is present in both pathogenic and commensal bacteria, and antibiotics targeting DapA may interfere with normal gut colonization. Bacteroides thetaiotaomicron is a Gram-negative commensal bacterium that makes up a large proportion of the normal microbiota of the human gut. The structure of DapA from B. thetaiotaomicron (BtDapA) has been determined. This structure will help to guide the generation of selectively active antibiotic compounds targeting DapA.
Application of Sheet-metal Unfolding Based on Software Methods and Its Engineering Guidance

Based on practical experience and the accumulation, this paper not only explains the application in the aspect of sheet-metal unfolding by applying 3 kinds of popular softwares,but also contrasts their advantages and disadvantages by examples.The paper also points out their economical scope of application,which has strong guidance in different cases.
Distribution of T cell subsets in follicular fluid.

Examination of follicular fluid (FF) from in vitro fertilization patients revealed a significant difference in concentrations of lymphocytes and T cell subpopulations with increased oocyte maturation. A total of 111 follicles containing 82 oocytes were aspirated from 10 patients undergoing laparoscopic oocyte retrieval. FF from 61.3% of the follicles was classified as clear and 38.7% as bloody, based on gross and microscopic appearance. A mean of 1.78×10 6 lymphocytes/ml was obtained from peripheral blood (PB) as compared to 2.14×10 5 and 2.79×10 5 lymphocytes/ml for clear and bloody FF, respectively. There were 6.3×10 5 T 4 and 3.7×10 5 T 8 lymphocytes in PB, resulting in a T 4 /T 8 ratio of 1.72, which is not significantly different from that of the general population. The mean concentration of FF T 4 and T 8 lymphocytes decreased with increased oocyte maturation; the T 8 reduction was statistically significant ( P 4 to T 8 lymphocytes in FF remained unchanged and was unaffected by maturity of the oocyte. Although estradiol (E 2 ) did not vary with oocyte maturity, progesterone (P) increased and E 2 /P decreased. There was no correlation between E 2 or P levels and distribution of T cells. Fertilization rates were higher in more mature oocytes, but there was no correlation between fertilization and E 2 , P, E 2 /P, or T cell subpopulations. It remains to be determined what factors result in the decrease in lymphocytes with increased oocyte maturity and the observed difference in FF T 4 /T 8 compared to PB.
Viewpoint: Why Disclosure Matters.

R revelations about researchers failing to disclose industry funding of their work have raised the question: why does disclosure matter? An obvious answer is that if a journal has a disclosure policy, then failure to disclose violates that policy. But the issue is deeper than one of obeying rules; the important question is why those rules are necessary. The answer is that even if we think of ourselves as honest, objective, and independent, scientific evidence demonstrates that our research can be influenced by the sources of our funding. A robust literature, dating to the mideighties, has documented this “funding effect.” Specifically, when funders have a particular desired outcomethat is, that tobacco smoking does not cause pancreatic cancer; that a particular chemical does not exhibit estrogenic activity; or that hydraulic fracturing for oil and gas development does not contaminate groundwaterthe studies that industry funds are more likely to find that outcome than studies not so funded. The funding effect is particularly well documented in the domain of pharmaceuticals, where industry-funded studies have been shown to be significantly more likely to find outcomes favorable to the sponsors’ productsdefined as greater efficacy or less harm for the sponsor’s productthan studies with other sources of funding. The standard tools designed to prevent bias in clinical trials, such as blinding and randomization, do not prevent this effect. Many of us are reluctant to accept this finding, because it seems to imply that our colleaguesincluding individuals we may know and respecthave been corrupted. Corruption exists, but the funding effect may more often be the result of unconscious bias. Researchers make many choices in the design, implementation, and interpretation of their work that involve expert judgment, and this opens a pathway through which unconscious bias may exert itself, both in study design and in data interpretation. In theory, such bias should be noticed in peer review; in practice, these subtleties often escape notice until results are contested post-publication by other researchers, re-examined in litigation, or detected in later reviews and meta-studies. A well-documented example of this involves the choice of controls in experimental studies of suspected endocrinedisrupting chemicals. It may seem obvious that if the doses administered in an experiment are too low or the animal model is insensitive to the effect being studied, this can produce an
Combined Cystometry and Perineal Electromyography in the Diagnosis and Treatment of Neurogenic Urinary Incontinence

Abstract Function of the bladder and periurethral striated muscle was determined simultaneously by combined cystometry. and electromyography studies in 120 patients. The coordinated tests were extremely helpful in identifying the different types of periurethral striated muscle activity in neurogenic bladder dysfunction, diagnosing the mechanism of incontinence and determining the appropriate therapy.
A simple model predicts UGT-mediated metabolism.

Motivation Uridine diphosphate glucunosyltransferases (UGTs) metabolize 15% of FDA approved drugs. Lead optimization efforts benefit from knowing how candidate drugs are metabolized by UGTs. This paper describes a computational method for predicting sites of UGT-mediated metabolism on drug-like molecules. Results XenoSite correctly predicts test molecule's sites of glucoronidation in the Top-1 or Top-2 predictions at a rate of 86 and 97%, respectively. In addition to predicting common sites of UGT conjugation, like hydroxyl groups, it can also accurately predict the glucoronidation of atypical sites, such as carbons. We also describe a simple heuristic model for predicting UGT-mediated sites of metabolism that performs nearly as well (with, respectively, 80 and 91% Top-1 and Top-2 accuracy), and can identify the most challenging molecules to predict on which to assess more complex models. Compared with prior studies, this model is more generally applicable, more accurate and simpler (not requiring expensive quantum modeling). Availability and implementation The UGT metabolism predictor developed in this study is available at http://swami.wustl.edu/xenosite/p/ugt CONTACT: : swamidass@wustl.eduSupplementary information: Supplementary data are available at Bioinformatics online.
Computational Design and Preparation of Cation‐Disordered Oxides for High‐Energy‐Density Li‐Ion Batteries

Cation-disordered lithium-excess metal oxides have recently emerged as a promising new class of high-energy-density cathode materials for Li-ion batteries, but the exploration of disordered materials has been hampered by their vast and unexplored composition space. This study proposes a practical methodology for the identification of stable cation-disordered rocksalts. Here, it is established that the efficient method, which makes use of special quasirandom structures, correctly predicts cation-ordering strengths in agreement with accurate Monte-Carlo simulations and experimental observations. By applying the approach to the composition space of ternary oxides with formula unit LiA0.5B0.5O2 (A, B: transition metals), this study discovers a previously unknown cation-disordered structure, LiCo0.5Zr0.5O2, that may function as the basis for a new class of cation-disordered cathode materials. This computational prediction is confirmed experimentally by solid-state synthesis and subsequent characterization by powder X-ray diffraction demonstrating the potential of the computational screening of large composition spaces for accelerating materials discovery.
A Phase I Trial to Evaluate Antibody-Dependent Cellular Cytotoxicity of Cetuximab and Lenalidomide in Advanced Colorectal and Head and Neck Cancer

mAbs can induce antibody-dependent cellular cytotoxicity (ADCC) via the innate immune system's ability to recognize mAb-coated cancer cells and activate immune effector cells. Lenalidomide is an immunomodulatory agent with the capacity to stimulate immune cell cytokine production and ADCC activity. This phase I trial evaluated the combination of cetuximab with lenalidomide for the treatment of advanced colorectal and head and neck squamous cell cancers (HNSCC). This trial included patients with advanced colorectal cancer or HNSCC. Treatment consisted of cetuximab 500 mg/m(2) i.v. every two weeks with lenalidomide given orally days 1-21 on a 28-day cycle. Three dose levels of lenalidomide were evaluated (15, 20, 25 mg). Correlative studies included measurement of ADCC, FcγRIIIA polymorphism genotyping, measurement of serum cytokine levels, and flow cytometric analysis of immune cell subtypes. Twenty-two patients were enrolled (19 colorectal cancer, 3 HNSCC). Fatigue was the only dose-limiting toxicity. One partial response was observed and 8 patients had stable disease at least 12 weeks. The recommended phase II dose is cetuximab 500 mg/m(2) with lenalidomide 25 mg daily, days 1-21. Correlative studies demonstrated a dose-dependent increase in natural killer cytotoxic activity with increasing doses of lenalidomide. Cetuximab and lenalidomide were well tolerated. There was a lenalidomide dose-dependent increase in ADCC with higher activity in patients enrolled in cohort 3 than those enrolled in cohorts 1/2. Although response was not a primary endpoint, there was evidence of antitumor activity for the combination therapy. Further investigation of lenalidomide as an immunomodulator in solid tumors is warranted. Mol Cancer Ther; 15(9); 2244-50. ©2016 AACR.
Free and open-source automated 3-D microscope

Open-source technology not only has facilitated the expansion of the greater research community, but by lowering costs it has encouraged innovation and customizable design. The field of automated microscopy has continued to be a challenge in accessibility due the expense and inflexible, noninterchangeable stages. This paper presents a low-cost, open-source microscope 3-D stage. A RepRap 3-D printer was converted to an optical microscope equipped with a customized, 3-D printed holder for a USB microscope. Precision measurements were determined to have an average error of 10 μm at the maximum speed and 27 μm at the minimum recorded speed. Accuracy tests yielded an error of 0.15%. The machine is a true 3-D stage and thus able to operate with USB microscopes or conventional desktop microscopes. It is larger than all commercial alternatives, and is thus capable of high-depth images over unprecedented areas and complex geometries. The repeatability is below 2-D microscope stages, but testing shows that it is adequate for the majority of scientific applications. The open-source microscope stage costs less than 3-9% of the closest proprietary commercial stages. This extreme affordability vastly improves accessibility for 3-D microscopy throughout the world.
Doubled Ethics and Narrative Progression in The Wire

Rush looks at the handling of ethics in screenwriting through ideas of character and personal conflict. He suggests that the privileging of character conflict through concepts such as narrative ‘spine’ is limiting, and works at the expense of treatment of public conflict and wider social issues. Suggesting that some long-form television represents an alternative approach, Rush develops an analysis of the celebrated serial The Wire focused on what he terms a ‘doubled’ ethics, one that combines a focus on character growth alongside the larger, social world of the story. Drawing on narrative theory, especially the work of James Phelan, Rush develops an approach to character and narrative focused on concepts of narrative judgement and alignment. In making his argument, Rush teases out the relationship between personal and public conflict, and borrows from moral philosophy to show how personal conflict can be examined through an ethics of care, and public concept in terms of an ethics of justice. Rush also revisits theories of television as a ‘cultural forum’, showing how doubled ethics contributes to ethical debate.
Georg Forsters Werke, Band VII, Kleine Schriften zu Kunst und Literatur. Sakontala. Bearbeitet von Gerhard Steiner: Berlin: Akademie-Verlag, 1963. Pp. 642. DM. 39.

(1964). Georg Forsters Werke, Band VII, Kleine Schriften zu Kunst und Literatur. Sakontala. Bearbeitet von Gerhard Steiner. The Germanic Review: Literature, Culture, Theory: Vol. 39, No. 2, pp. 157-159.
A multi-channel outphasing ring combiner for multi-mode output and channel aggregation

In this paper, a rat-race coupler is used to enable mode-switching and channel aggregating communications. A novel 6-port modification to the rat-race coupler that allows simultaneous transmission of three channels with no TX/RX switch is presented. High power GaN power amplifiers are used to drive the combiner input ports and their phases are adjusted to drive separate channels to different outputs. This outphasing operation can produce one or more modulated waveforms at a single or multiple antenna ports, with the use of relative phase relationships between the different channels. The controllable channel and antenna selection is enabled via software control of the phasing relationships between the signals and enables the elimination of a traditional high power transfer switch, thereby increasing transmitter efficiency and reducing overall system implementation size. To validate the performance, two LTE signals were input to the combiner with center frequencies of 5.3 GHz and 5.4 GHz, respectively. The combiner shows >30 dB of rejection for the undesired signal at each port. The measured ACLR in both channels was < −30 dBc, while outputting and average output power and PAE of 27.6 dBm and 28%, respectively.
Understanding investors’ reliance on disclosures of nonfinancial information and mitigating mechanisms for underreliance

This study uses two experiments to examine whether nonprofessional investors rely on voluntarily disclosed nonfinancial information (NFI) and the factors that affect their reliance on such information. Results from experiment one suggest that nonfinancial disclosure affects high-experience (long-term) investors more than low-experience (short-term) investors. In addition, more investing experience seems to compensate the insensitivity to NFI caused by a short-term investment horizon. Results from experiment two suggest that merely requiring participants to evaluate firms’ performance separately based on the financial and nonfinancial measures (NFMs) – or merely presenting the NFMs in a more readable format – does not significantly alter the reliance on the nonfinancial disclosure for low-experience and short-term investors. However, when the two interventions are implemented simultaneously, NFI significantly affects the amount invested by those investors.
Energy efficiency barriers in commercial and industrial firms in Ukraine: An empirical analysis ☆

Abstract Improvement in energy efficiency is one of the main options to reduce energy demand and greenhouse gas emissions. However, large-scale deployment of energy-efficient technologies is constrained by several factors. Employing a survey of 509 industrial and commercial firms throughout Ukraine and a generalized ordered logit model, we quantified the economic, behavioral, and institutional barriers that may impede the deployment of energy-efficient technologies. Our analysis shows that behavioral barriers resulted from lack of information, knowledge, and awareness are major impediments to the adoption of energy-efficient technologies in Ukraine, and that financial barriers may further impede investments in these technologies especially for small firms. This suggests that carefully targeted information provisions and energy audits will enhance Ukrainian firms' investments in energy-efficient technologies to save energy consumption, improve productivity, and reduce carbon emissions from the productive sectors.
Using Natural Selection Concept Inventories in College Biology Classrooms to Improve Teaching and Learning

Abstract The purpose of this study was to investigate how assessment instruments could be used in the college biology classroom for purposes other than researching instructional strategies (as they have been used in the past). Through participatory action research, a science educator and a biology faculty member examined how the CINS (Concept Inventory of Natural Selection) could be incorporated into the biology faculty member's classroom instruction. This paper shows that biology faculty members can use assessment instruments to build in-class activities and labs, to formatively assess student knowledge, and to confront student misconceptions. Several recommendations for incorporating assessment instruments in biology instruction and assessment are provided.
Non-destructive evaluation and position tracking of flaws in conductive materials

This paper shows how positional and eddy-current data are combined to produce a C-scan of flaws in conductive materials. A system that consists of an eddy current probe, a position tracking mechanism, and basic data visualization capability was built and tested. Preliminary test results of the prototype are presented and briefly discussed. Improving the accuracy of the measurements using a three-mouse position sensing device is described.
Functional Neuroimaging in Startle Epilepsy

Researchers at the Epilepsy Unit, Hospital Clinic de Barcelona, Spain investigated brain areas involved in startle-induced seizures, using a functional neuroimaging approach in 4 adult patients whose seizures began at age 4 months to 10 years.
Lung transplantation in elderly patients

Consensus statements on the selection of lung transplant candidates have consistently identified older age as a relative contraindication to transplantation. A combination of population-level demographic changes, revision of the lung allocation score (LAS), and clearer data on outcomes in elderly transplant recipients has, however, driven a steady increase in the threshold at which age is taken into consideration. This article reviews the current state of lung transplantation in elderly patients with an emphasis on the factors that have increased lung transplantation in older age groups, their expected outcomes including survival and health-related quality of life, and the factors that go in to appropriate candidate and procedure selection in this population.
Nonspecific Esophageal Motility Disorders

Esophageal body and esophagogastric junction (EGJ) motor abnormalities are well characterized by the Chicago Classification version 3.0, which identifies disorders under the broad categories of EGJ outflow obstruction, major motor disorders not encountered in health, and minor motor disorders that can be associated with bolus transit abnormalities. However, abnormalities of the esophageal body peristaltic wave (contraction wave abnormalities), breaks in peristaltic integrity, and morphologic and motor EGJ abnormalities can be encountered when esophageal motor function is designated normal under the Chicago Classification. Other nonspecific motor abnormalities can be encountered in supragastric belching and rumination. This chapter elaborates these nonspecific disorders of esophageal and EGJ motor function, and describes potential relationships to symptoms.
Implementation of a generalized actuator line model for wind turbine parameterization in the Weather Research and Forecasting model

A generalized actuator line (GAL) wind turbine parameterization is implemented within the Weather Research and Forecasting model to enable high-fidelity large-eddy simulations of wind turbine interactions with boundary layer flows under realistic atmospheric forcing conditions. Numerical simulations using the GAL parameterization are evaluated against both an already implemented generalized actuator disk (GAD) wind turbine parameterization and two field campaigns that measured the inflow and near-wake regions of a single turbine. The representation of wake wind speed, variance, and vorticity distributions is examined by comparing fine-resolution GAL and GAD simulations and GAD simulations at both fine and coarse-resolutions. The higher-resolution simulations show slightly larger and more persistent velocity deficits in the wake and substantially increased variance and vorticity when compared to the coarse-resolution GAD. The GAL generates distinct tip and root vortices that maintain coherence as helical t...
Case 8: A Diabetic Patient for Inguinal Hernia Repair

A 54-year-old man is admitted for an inguinal hernia repair. He has been a type 1 diabetic for 18 years. Two years ago, he developed end-stage renal disease (ESRD), secondary to his diabetic kidney. He now required daily peritoneal dialysis. The peritoneal fluid used consisted of a glucose-containing dialysis fluid in the daytime and an overnight dialysis fluid using one exchange of 2 l peritoneal fluid containing Icodextrin (7.5% w/v) (Extraneal, Baxter Healthcare, Castlebar, Ireland). Icodextrin is a cornstarch-derived glucose polymer. His insulin regimen consisted of Human Insulatard (Novo Nordisk) before bed and Humalog (lispro) before his main meals.
Development of the SapI/AarI Incision Mediated Plasmid Editing Method

Abstract Plasmid engineering and molecular cloning is a virtually ubiquitous tool in biology. Although various methods have been developed for ligating DNA molecules or targeted mutagenesis of plasmids, each has its limitations. Many of the commonly used laboratory strategies are inefficient, while commercially available kits are quite costly and often specialized for highly specific circumstances. Here, we describe the S apI/AarI i ncision m ediated pl asmid e diting (SIMPLE) method, which allows users to perform site-directed mutagenesis, deletions, and even short insertions into any plasmid in a single PCR reaction, using just one restriction enzyme. In addition, the SIMPLE method can be adapted to insert any sized DNA fragment into a vector using a two-step PCR approach, and can be used to ligate any number of DNA fragments with non-compatible ends in the specific order desired. The SIMPLE method provides researches an efficient and powerful tool with a broad range of applications for molecular cloning.
Racemic & quasi-racemic protein crystallography enabled by chemical protein synthesis

A racemic protein mixture can be used to form centrosymmetric crystals for structure determination by X-ray diffraction. Both the unnatural d-protein and the corresponding natural l-protein are made by total chemical synthesis based on native chemical ligation-chemoselective condensation of unprotected synthetic peptide segments. Racemic protein crystallography is important for structure determination of the many natural protein molecules that are refractory to crystallization. Racemic mixtures facilitate the crystallization of recalcitrant proteins, and give diffraction-quality crystals. Quasi-racemic crystallization, using a single d-protein molecule, can facilitate the determination of the structures of a series of l-protein analog molecules.
Monet and the Pillars of Nature: Articulation and Embodiment

From the very beginning of the painter Claude Monet’s career there was an emphasis on the experience of seeing, and this led Monet to the coloristic style known as Impressionism which embodied the fugitive aspects of contemporary life and the light that revealed it, but this outward directed Impressionism became for Monet a means of inward investigation. His paintings express what it means to have one’s senses in tune with the world of nature, to make it a part of oneself both consciously and subconsciously. In his late years Monet tried to emphasize that it was light and light-shot atmosphere that was his fascination and nothing else. It was this and this alone, he would have us believe, that resulted in an emphasis being placed on color as it never had been before. Notwithstanding what was at times a nearly scientific attitude toward his investigations into color and light, color remains the most emotionally potent aspect of painting.2 The cool dispassionate investigator that Monet made himself out to be by self-consciously and diligently avoiding revelatory statements regarding his personal and private life contradicted the passionate man he in fact was, and what he obscured verbally was not to be denied altogether in paint. Had he been successful in keeping his paintings free of passion, with no hints of his private inner life, Monet’s work would have lost its dimension of underlying intrigue which serves to continually fascinate even if remaining unexplained.
Thermal Inertia of a Building as Virtual Energy Storage: A Sustainable Solution for Smart Grids

In this paper we have theoretically and experimentally investigated the potential of the thermal mass of a residential building to act as virtual energy storage (VES) in a microgrid environment. Developing a simulation framework in Simulink and calibrating the model parameters through extensive experimental trials, we have explored the critical design space and operational criteria for both VES and the microgrid. We have also proposed a load management scheme to shift the thermal load by preheating or pre-cooling the building that depends on renewable generation, real-time main grid pricing and weather forecasting. Through the simulation based study, we have measured the benefit of our developed scheme that shows promising results such as a cost benefit of ~$0.67 per day.
Russia's Indirect Grand Strategy

Abstract Modern Russia is a revisionist, if not a revanchist, nation-state. It seeks to end the efficacy of the post-World War II institutionalized rules-based international order, which was created and maintained by the U.S.-led Western alliance. Russia pursues this objective to reclaim great power status and dominate the region and its borders. However, it lacks the strength to achieve this goal directly. To be successful, Russia must devise a strategy for bringing about cumulative changes in the relative power of the United States and Russia. And, it must do so while avoiding direct confrontation. A model for such an indirect approach exists.
OpenOA: An Open-Source Code Base for Operational Analysis of Wind Power Plants

Abstract. As global wind capacity continues to grow, the need for accurate operational analyses of a rapidly growing fleet of wind power plants has increased in proportion. The wind energy industry at present, however, is not ideally positioned to address this need. First, there is a lack of best practices and limited published standards for performing operational analyses. Second, operational data and methods are typically proprietary and not shared among the wind energy community. Consequently, there is considerable duplication of effort in developing methods as well as uncertainty in the calculated metrics. To address these problems, the National Renewable Energy Laboratory has publicly released OpenOA, an open-source code base for performing operational analyses on wind plant data. The intent of OpenOA is to provide a framework in which best practices can be developed, refined, and disseminated. Ultimately, such collaboration is expected to lead to a working example (i.e. reference implementation) of methods from which a published standard may develop. This article provides an overview of OpenOA, highlighting its release as a public repository, modular software architecture, current functionality, and planned functionality in subsequent releases. It is our goal for OpenOA to evolve into an indispensable tool for performing operational analyses that is used and supported by a large community of wind energy experts.
Teneurins and latrophilins: two giants meet at the synapse.

Teneurins and latrophilins are both conserved families of cell adhesion proteins that mediate cellular communication and play critical roles in embryonic and neural development. However, their mechanisms of action remain poorly understood. In the past several years, three-dimensional structures of teneurins and latrophilins have been reported at atomic resolutions and revealed distinct protein folds and unique structural features. In this review, we discuss these structures which, together with structure-guided biochemical and functional analyses, provide hints for the mechanisms of trans-cellular communication at the synapse and other cell–cell contact sites.
A network of nuclear envelope proteins and cytoskeletal force generators mediates movements of and within nuclei throughout Caenorhabditis elegans development

Nuclear migration and anchorage, together referred to as nuclear positioning, are central to many cellular and developmental events. Nuclear positioning is mediated by a conserved network of nuclea...
Prolonged survival in a patient with a cervical spine H3K27M-mutant diffuse midline glioma

We report a case of prolonged survival in a patient with known cervical intramedullary H3K27M-mutant diffuse midline glioma. A 39-year-old man presented for evaluation with several months of progressive upper extremity pain and weakness. MRI of the cervical spine revealed an intramedullary ring-enhancing lesion centred at C3-C4. Following subtotal surgical resection, a diagnosis of glioblastoma (GBM) was confirmed. Subsequent testing at a later date revealed an H3K27M mutation. He was initially treated with radiation and concomitant and adjuvant temozolomide. He had multiply recurrent disease and was treated with various regimens, including the histone deacetylase inhibitor valproic acid. The patient passed away 31 months (~2.5 years) after diagnosis. Our case is one of few reported adult spinal cord GBMs possessing the H3K27M mutation, and one with the longest reported overall survival in the literature to date.
Analytical Performance Evaluation of Aptima Herpes Simplex Virus 1 and 2 Assay Using Hologic Panther Instrument.

OBJECTIVE Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are responsible for a variety of human diseases. Therefore, rapid detection of these viruses in clinical laboratory is important. Recently Aptima Herpes Simplex 1 and 2 assay has been approved by the FDA. We evaluated analytical performance of this assay by comparing results obtained by analysis of cultures. MATERIALS AND METHODS Aptima Herpes Simplex assay is a nucleic acid amplification test that can be fully automated using the Hologic Panther instrument. This is a qualitative test providing either positive or negative result. We analyzed 115 specimens collected from anogenital locations using the new Aptima Herpes Simplex assay and our current tissue culture method. RESULTS We observed good correlation between results obtained by using Aptima assay and the tissue culture method in 101 specimens but 14 specimens showed discordant results. Further testing in a reference laboratory using PCR (polymerase chain reaction) showed results in agreement with the Aptima assay but not the tissue culture method. The cause of discordance was misidentification of HSV-2 as HSV-1 by the tissue culture method. CONCLUSIONS Aptima Herpes simplex assay on the Hologic Panther instrument is suitable for rapid detection of herpes simplex virus in clinical laboratory.
On the k-Strong Roman Domination Problem

Abstract The Roman domination problem (RDP) aims to find an optimal strategy to defend a graph or network with the least number of defenders. Although it holds great application potential to many fields, the RDP is mostly studied from theoretical aspects. In this paper, we extend the RDP and bridge the gap between theory and practice. Specifically, we define the k -strong Roman domination problem ( k -SRDP), where defenders are assigned to a network to repel multiple simultaneous attacks. We propose an integer programming formulation of the problem, as well as a two-stage stochastic formulation using Benders decomposition. We show that the problem scale grows rapidly as the instance becomes larger. We prove the integrality of the second stage and propose two algorithms based on the L -shaped method. The algorithms are compared using randomly generated graph instances. Experimental results suggest that the proposed algorithms can solve the k -SRDP efficiently.
Impact of Delay in Appendectomy on the Outcome of Appendicitis: A Post Hoc Analysis of an EAST Multicenter Study.

Background: Association between time-to-appendectomy and clinical outcomes is controversial with conflicting data regarding risk of perforation. The purpose of this study was to explore the associa...
An experimental method to characterize the relationship between aperture image and ray directions in microscope optics

We propose a direct experimental method to calibrate the relationship between ray directions in object space and their positions in the aperture plane of a light field microscope. The calibration improves the interpretation of light field images, which contain information from both types of image planes, the field plane and the aperture plane of the ray path in the microscope. Our method is based on the diffraction of line gratings of known periodicities and provides accurate results with subpixel resolution. The method can be custom-tailored to most any optical configuration, including standard light microscopy setups, whenever correct mapping between ray parameters in the object/image plane and the aperture plane is needed.
Finite-temperature scaling of magnetic susceptibility and the geometric phase in the XY spin chain

We study the magnetic susceptibility of the 1D quantum XY model, and show that when the temperature approaches zero, the magnetic susceptibility exhibits finite-temperature scaling behavior. The scaling behavior of the magnetic susceptibility in the 1D quantum XY model, due to the quantum-classical mapping, can easily be experimentally tested. Furthermore, the universality in the critical properties of the magnetic susceptibility in the quantum XY model is verified. Our study also reveals the close relation between the magnetic susceptibility and the geometric phase in some spin systems, where the quantum phase transitions are driven by an external magnetic field.
Upper-Extremity Venous Thromboembolism Following Operative Treatment of Distal Radius Fractures: An Uncommon but Dangerous Complication.

Purpose Distal radius fractures are the most common long bone fracture in the United States, with an estimated incidence of 640,000 cases per year. Operative fixation presents a theoretical risk factor for the development of upper-extremity venous thromboembolism (UE-VTE). Additionally, patients presenting with distal radius fracture commonly have preexisting comorbidities that further increase the risk of UE-VTE. Finally, UE-VTE is considered the highest risk for eventual development of pulmonary embolism . Despite this, scant attention has been paid to studying UE-VTE in this population. The purpose of this study was to measure the incidence of this complication and to identify possible medical factors that increased the risk of developing UE-VTE. Methods We queried the Truven MarketScan Commercial Claims and Encounters Database for all patients who experienced a distal radius fracture and were subsequently treated with open reduction and internal fixation between 2012 and 2016. Patients were identified using relevant Common Procedural Terminology codes. Demographic and medical variables were tabulated. Our primary outcome was the development of ipsilateral UE-VTE or pulmonary embolism in the first 60 days after surgery. Results The study included 24,494 patients. The mean age was 50.7 years (range, 18–91), and 58% were women. There were 79 cases (0.3%) of UE-VTE and 19 cases of pulmonary embolism in the study population (24.1% of all UE-VTE cases; 0.08% of total sample). Multivariable logistic regression showed that coexisting heart failure and estrogen use were associated with increased risk of UE-VTE. Conclusions Although uncommon, the development of UE-VTE after open reduction and internal fixation for distal radius fractures is a concerning complication. Coexisting heart failure and estrogen use are associated with increased risk of UE-VTE. Type of study/level of evidence Prognostic II.
Precision Nuclear Medicine: The Evolving Role of PET in Melanoma

The clinical management of melanoma patients has been rapidly evolving with the introduction of new targeted immuno-oncology (IO) therapeutics. The current diagnostic paradigms for melanoma patients begins with the histopathologic confirmation of melanoma, initial staging of disease burden with imaging and surgical approaches, treatment monitoring during systemic cytotoxic chemotherapy or IO therapeutics, restaging after completion of adjuvant systemic, surgical, and/or external radiation therapy, and the detection of recurrent malignancy/metastatic disease following therapy. New and evolving imaging approaches with positron-emission tomography (PET) imaging technologies, imaging methodologies, image reconstruction, and image analytics will likely continue to improve tumor detection, tumor characterization, and diagnostic confidence, enabling novel precision nuclear medicine practices for managing melanoma patients. This review will examine current concepts and challenges with existing PET imaging diagnostics for melanoma patients and introduce exciting new opportunities for PET in the current era of IO therapeutics.
Pregnancy Related Disorders

Critical illness is an uncommon but potentially devastating complication of pregnancy. In Western nations about 1 % of obstetric patients will require admission to an ICU. Mortality of critically ill obstetric patients ranges from 12 to 20 % [1]. The most common cause of maternal death in the ICU is ARDS [1].
Selective Autophagy in the Pathogenesis of Parkinson's Disease

Publisher Summary This chapter explores various aspects of selective autophagy in the pathogenesis of Parkinson's disease. Compensatory activation of the autophagosomal system in general has been reported in many protein conformational disorders. Expression of huntingtin, the protein found in protein inclusions associated with Huntington's disease, results in upregulation of macroautophagy along with the general stimulation of endosomal–lysosomal activity. Two groups have independently shown that the selective suppression of basal macroautophagy in mouse brain causes diffuse accumulation of ubiquitinated abnormal proteins and ubiquitin-positive inclusions, thereby leading to neuronal toxicity and neurodegeneration. Macroautophagy is initially induced in most of these diseases to protect neurons against abnormal toxic proteins, stress and damaged organelles that may cause cell toxicity and apoptosis. It is observed that pharmacological blockage of the catalytic activities of the proteasome results in upregulation of macroautophagy. It is suggested that macroautophagy can be tracked in cultured cells using recombinant Atg proteins fused to ﬂuorescent proteins which allows identiﬁcation of autophagosomes, the intracellular compartments directly linked to macroautophagy.