cssi/SciSciGPT-SciSciNet huggingface dataset:
Flexible fiberoptic sigmoidoscopy.

The technique is useful, easily performed, and more tolerable than conventional rigid sigmoidoscopy. In the coming decade, it will become the standard method for examining the left colon. Instrumentation is described.
Transfection of interleukin-12 cDNAs into tumor cells induces cytotoxic immune responses against native tumor: Implications for tumor vaccination

Interleukin-12 (IL-12) is a heterodimeric cytokine that is central to the development of T helper 1-dependent cellular immunity. Although this cytokine has potential therapeutic application as an antineoplastic agent, the systemic infusion of IL-12 has led to toxic fatalities; hence, restriction of expression of IL-12 to the microenvironment of target tumor cells has obvious appeal. In this study, we examined whether tumor cells that were liposome-transfected with IL-12 could enhance the induction of cytolytic lymphocyte immunity to the native tumor. The plasmid expression vector that we used has several useful features including replication to high copy number as an episome and a polycistronic message enabling the production of both the p35 and p40 subunits of IL-12 without alternative splicing; up to 3 ng/mL/10(6)/48 hours of IL-12 was produced following transfection. Tumor cells transfected with IL-12 were superior to untransfected cells in the induction of lymphocyte-mediated cytolysis. IL-12 transfectants induced a heterogeneous population of natural killer, lymphokine activated killer, and cytolytic T lymphocytes, the latter of which exhibited tumor-specific activity. Our studies suggest that liposome-mediated transfection of tumor cells with an episomal, high copy number plasmid vector expressing both IL-12 subunits is a promising approach to cancer vaccination, a strategy that could be implemented ex vivo in treating malignancies such as metastatic ovarian cancer.
Culture in clinical medicine.

Although many clinicians use a vague, common-sense approach to understanding the effects of social and cultural forces on patient care, there is now available a large and rapidly increasing body of research that provides a technical language and a rigorous analytic framework for making uncommon sens
Increasing HIV Incidence among Men Who Have Sex with Men in Jiangsu Province, China: Results from Five Consecutive Surveys, 2011–2015

Epidemics of HIV among men who have sex with men (MSM) are major public health concerns in most parts of China. This study examined the trends in HIV incidence and associated factors among MSM in Jiangsu Province. Five consecutive cross-sectional surveys were conducted among MSM from 2011 to 2015 in eight cities throughout Jiangsu Province. Participants were recruited from MSM venues or via the internet. Demographic and behavioral data were collected through HIV bio-behavioral surveys. Blood specimens were collected to test for HIV and syphilis. HIV incidence was estimated by the IgG-capture BED-EIA (BED) method and a chi-square trend test was used to compare differences over the years. Multivariate logistic regression analysis was used to identify factors associated with recent infection. A total of 2433, 2678, 2591, 2610 and 2541 participants were enrolled in 2011, 2012, 2013, 2014 and 2015, respectively. HIV incidence increased from 5.10% in 2011 to 6.62% in 2015 (p = 0.025). MSM who had an education level of junior high school or less (aOR = 1.472, p = 0.018), engaged in condomless anal sex in the past 6 months (aOR = 2.389, p < 0.001), did not have an HIV test in the past 12 months (aOR = 3.215, p < 0.001), and were currently infected with syphilis (aOR = 2.025, p = 0.001) were likely to be recently infected with HIV. HIV incidence is increasing among MSM in Jiangsu Province, China. Condom usage and HIV testing promotion should be prioritized when attempting to reduce HIV transmission among MSM in China.
Characterization of the Binding Interaction between ADAMTS13 and von Willebrand Factor (VWF).

Abstract VWF multimers are cleaved into smaller less thrombogenic fragments in plasma by ADAMTS13. Deficiency of ADAMTS13 activity leads to thombotic thrombocytopenic purpura (TTP), a disease characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological decline, and renal insufficiency. ADAMTS13 is a member of the A D isintegrin and M etalloprotease with T hrombo S pondin repeats family that has characteristic motifs including a signal sequence, a propeptide, a catalytic metalloprotease domain, a disintegrin domain, a thrombospondin-1 (TSP1) repeat, a cysteine-rich region, and a spacer domain. These domains are followed in ADAMTS13 by seven additional TSP1 repeats and two C-terminal CUB domains. Previous work has shown that ADAMTS13 truncated after the spacer domain retains proteolytic activity towards VWF, but little is known about the potential role of the additional C-terminal TSP1 and CUB domains in VWF binding or cleavage. We therefore developed an enzyme-linked immunosorbent assay (ELISA)-based system to study ADAMTS13-VWF binding. VWF was immobilized in microtiter wells and incubated with plasma or recombinant ADAMTS13 variants. Bound ADAMTS13 was detected directly by solubilization and Western blotting, or indirectly by ELISA. ADAMTS13 proteolytic activity towards VWF is enhanced by denaturation of VWF with urea or guanidine, but ADAMTS13 bound specifically to VWF without prior denaturation. EDTA increased the binding of ADAMTS13 to VWF and prevented proteolysis of the immobilized VWF. Binding was saturable and time-dependent with maximal binding in two hours. Binding was reversible with a half-time for dissociation of four hours. ADAMTS13 in normal human plasma but not in plasma from a patient with TTP bound immobilized VWF. The stoichiometry of VWF monomers to ADAMTS13 at saturation was approximately 2 (range 1–4) and the Kd of recombinant ADAMTS13 binding to VWF was 12 nM (range 5–26 nM). This Kd for binding is similar to the Km for VWF cleavage of 16 nM determined independently, and both are comparable to the estimated plasma ADAMTS13 concentration of 8 nM. The properties of C-terminally truncated ADAMTS13 constructs suggest a regulatory function for certain domains. Truncation after the 8th TSP1 domain decreased the Kd 2-fold. Further truncation after either the 6th or 7th TSP1 domain increased the Kd 2-fold relative to full-length ADAMTS13. Truncation after the spacer domain gave binding properties indistinguishable from full-length ADAMTS13. Truncation after the metalloprotease domain gave no detectable binding to VWF. Therefore, binding of ADAMTS13 to VWF requires sequences in the cysteine-rich or spacer domains, and is modulated by sequences in at least the 8th TSP1 repeat and the CUB domains.
Development of mixed-conducting oxides for gas separation

Abstract Mixed-conducting oxides have been used in many applications, including fuel cells, gas-separation membranes, sensors, and electrocatalysis. We are developing a mixed-conducting, dense ceramic membrane for selectively transporting oxygen and hydrogen. Ceramic membranes made of Sr-Fe-Co oxide, which has high combined electronic and oxygen ionic conductions, can be used to selectively transport oxygen during the partial oxidation of methane to synthesis gas (syngas, CO+H 2 ). We have measured the steady-state oxygen permeability of SrFeCo 0.5 O x as a function of oxygen partial-pressure gradient and temperature. At 900°C, oxygen permeability was ≈2.5 scc·cm −2 ·min −1 for a 2.9 mm thick membrane and this value increases as membrane thickness decreases. We have fabricated tubular SrFeCo 0.5 O x membranes and operated them at 900°C for >1000 h during conversion of methane into syngas. The hydrogen ion (proton) transport properties of Ba(Ce,Y)O 3− δ were investigated by impedance spectroscopy and open-cell voltage measurements. High proton conductivity and a high protonic transference number make Ba(Ce,Y)O 3− δ a potential membrane for hydrogen separation.
Deep down my enemy is good: Thinking about the true self reduces intergroup bias

Abstract Intergroup bias — preference for one's in-group relative to out-groups — is one of the most robust phenomena in all of psychology. Here we investigate whether a positive bias that operates at the individual-level, belief in a good true self, may be leveraged to reduce intergroup bias. We find that even stereotypically threatening out-group agents are believed to have a good true self (Experiment 1). More importantly, consideration of an in-group and out-group members' true self reduces intergroup bias, both in the form of explicit evaluative judgments (Experiment 2) and actual donation behavior (Experiment 3). Across studies, the palliative effects of thinking of an individual's true self generalize to that individual's entire group. In sum, a simple intervention — thinking about another's true self — reduces the gap in how people evaluate and treat out-group relative to in-group members. We discuss implications of these findings for conflict reduction strategies.
Sociodemographic Influences of Emergency Department Care for Anxiety Disorders

This study examines variations in content of care for anxiety-related emergency department (ED) visits in the USA across various sociodemographic strata. The 2009-2012 National Hospital Ambulatory Medical Care Survey was used to identify all visits to general hospital EDs in which an anxiety diagnosis was recorded (n = 1930). Content and equitability of care was assessed utilizing logistic regression models. There were an estimated 1,856,000 ED visits with anxiety-related discharge diagnoses in the USA annually. Content of care and disposition varied by age, race/ethnicity, and insurance status. Visits by Medicaid patients were more likely than visits by privately insured patients to include a toxicology screen (OR = 1.67, p < .05) and visits by patients with either Medicaid or Medicare were less likely to include an EKG (OR = 0.53, p < .05 and OR = 0.52, p < .05, respectively). Understanding variations in ED care for anxiety can identify opportunities for intervention, both in the ED and upstream in appropriate healthcare settings.
A Population-Based Cohort Analysis of Chemoradiation Versus Radiation Alone for Definitive Treatment of Stage I Anal Cancer in Older Patients.

Background Although the benefit of chemoradiation over radiation therapy alone has been shown in randomized trials for stage II to III squamous cell of the anus, this benefit is not clear for patients with stage I cancer. Nevertheless, most societal recommendations endorse chemoradiation for patients with stage I squamous cell carcinoma of the anus despite the lack of proven benefit and potential increase in toxicity. Objective The purpose of this study was to determine whether outcomes are improved with the addition of chemotherapy versus radiation alone for stage I squamous cell carcinoma of the anus. Design This was a cohort analysis using Surveillance, Epidemiology and End Results registry linked to Medicare from 1996 to 2011. Propensity-score methods were used to control for potential confounding. Settings This was a population-based study. Patients Medicare eligible patients (age >65 y or with an eligible disability) with stage I squamous cell carcinoma of the anus treated with either definitive radiation alone or chemoradiation were included. Interventions Radiation or chemoradiation was the intervention. Main outcome measures Overall survival, disease-free survival, cause-specific survival, colostomy-free survival, and acute or late toxicities were measured. Results A total of 200 patients with squamous cell carcinoma of the anus were identified who received chemoradiation versus 99 treated with lone radiotherapy. Median age was 72 years and did not differ by treatment (p = 0.6). Patients receiving chemoradiation had improved unadjusted overall survival compared with lone radiotherapy, but after adjustment using propensity-score methods there was no difference in overall survival (HR = 0.7 (95% CI, 0.4-1.0)), cause-specific survival (HR = 0.7 (95% CI, 0.3-1.6)), colostomy-free survival (HR = 1.1 (95% CI, 0.5-2.5)), or disease-free survival (HR = 0.9 (95% CI, 0.6-1.4)). Chemoradiation was associated with an increased risk of select early and late toxicities. Limitations This is a retrospective series from an anonymous database. The data might not be relevant for younger, healthier patients. Conclusions Lone radiation may be associated with adequate oncologic outcomes when used to treat older and sicker patients with stage I anal cancer. Physicians should discuss the potential benefits and harms of adding chemotherapy for the treatment of these patients. See Video Abstract at http://links.lww.com/DCR/A628.
Quel che resta di pulp in Stabat Mater di Tiziano Scarpa

Nel 2008 Tiziano Scarpa pubblica Stabat Mater con il quale vincera prima il Premio Mondello e poi lo Strega. La critica ha definito questo romanzo sorprendente, visto che non ha molto a che vedere ...
It’s all done with mirrors: Neurological and sociological integration in the case of limb transplants

For most sighted people, looking into a mirror helps to consolidate a visual and spatial concept of the self. This concept connects both theoretically and substantively to other elements of identit...
Interrelationship of Resistivity and Velocity Logs

The wide range of velocities associated with earth materials makes it difficult to relate such data to specific lithologies. A review of geologic parameters shows that depth, lithology and age are not as specifically related to velocities as are the physical parameters of density, elastic constants, pressure, temperature and porosity. The Nafe and Drake curves relating velocity to density and porosity are seen as the most effective theoretical—empirical equations in the present literature.
Long Term Appraisal of the Lemon-Foley Method of Chemotherapy of Solid Tumors of the Gastrointestinal Tract

One of the most difficult problems in the clinical judgement of cancer patients is the determination of the effectiveness of any treatment modality. This is particularly apparent in the evaluation of solid malignancies of the gastrointestinal tract. In 1966, Drs. Lemon and Foley proposed the slow infusion of one gram of 5FU for periods of eight hours daily for 14 days followed by weekly bolus I-V injections of .5 grams 5FU in l0cc of dilutent. They felt that this method was not only effective but also avoided the frequent severe iatrogenic complications of current anti-neoplastic chemotherapy.
Sarbanes-Oxley Five Years Later: A Canadian Perspective

For the first time in history, the majority of the largest international initial public offerings (“IPOs”) are taking place in London rather than New York. New York City Mayor Michael Bloomberg and New York Senator Charles Schumer have blamed this shift primarily on America’s over-regulation of capital markets.1 While the dominant discourse had assumed an international convergence on the American model of corporate and securities law,2 more recently American commentators and regulators are starting to ask what they can learn from other jurisdictions. In Canada, where securities regulation is a provincial matter, the entire Canadian securities system has been shifting away from the historical American template to a UK-style principles-based approach.3 At a general level, the UK approach places emphasis on normative guidelines rather than detailed rules. However, Canadian firms have also been directly impacted by American regulation. This article offers a beginning point for discussion by considering the issues from a Canadian perspective. Specifically, it examines the effect of the U.S.
Associative Increases in Amyotrophic Lateral Sclerosis Survival Duration With Non-invasive Ventilation Initiation and Usage Protocols

Objective: It is hypothesized earlier non-invasive (NIV) ventilation benefits Amyotrophic Lateral Sclerosis (ALS) patients. NIV typically consists of the removable bi-level positive airway pressure (Bi-PAP) for adjunctive respiratory support and/or the cough assist intervention for secretion clearance. Historical international standards and current USA insurance standards often delay NIV until percent predicted forced vital capacity (FVC %predict) is 8 hours/day (23.20 months) or any daily Bi-PAP usage with cough assist (25.73 months) significantly (p 8 h/day, daily cough assist usage) has a 30. 8 month survival median, which is double that of a "standard" NIV protocol (initiation FVC %predict 4 h/day, no cough assist). Earlier access to Bi-PAP and cough assist, prior to precipitous respiratory decline, is needed to maximize NIV synergy and associative survival benefit.
Publication trends in telesupervision: A content analysis study

Thirty-five empirical studies from 25 peer-reviewed journals and one book chapter were analyzed through a content analysis for trends in publication, methodological, and research foci in telesuperv...
Precision cyber weapon systems: An important component of a responsible national security strategy?

Given the advances made in conventional weapon capabilities, precision should by now be the accepted and expected norm in cyberspace as well. In this article I argue that developing precision cyber...
How can cultural sociology help us understand contemporary Chinese society

In this editorial for the Thematic Series: Cultural Sociology and China, we discuss the global growth of cultural sociology as a sociological sub-discipline, its current state and future prospects in mainland China, and the aims of this special issue in promoting the subfield’s further growth domestically in China.
Loss of Function, a Strategy for Adaptation in Arabidopsis

When thinking about adaptive processes, the concept of genetic innovation comes to mind. At the genomic scale, a lot of attention has been given to gene introgression, duplication, and novel functionalization to uncover the bases of adaptation. However, as the majority of genes are nonessential,
Heuristics of Numerical Choice in Economic Contexts

Many problems in the psychology of judgment and decision making that employ heuristics involve preferences between two or more alternatives. Other problems involve estimation of numerical quantities. In this chapter we discuss the heuristics of problems that combine both of these processes, in that they involve decisions among different amounts of a particular item. We review several examples of these kinds of heuristics applied to economic contexts, such as decisions about how much of an item to buy from a supplier or to sell to consumers. Then we discuss models and theories that can explain the use of these heuristics in decision making. These theories are partly based on behavioral data in memory and decision making, and partly based on neural networks that incorporate the functions of specific brain regions.
TCTAP C-145 Rota Burr Incarceration (Entrapment) During Percutaneous Coronary Intervention for a Long, Calcified Chronic Total Occlusion of Right Coronary Artery

### Patient Initials or Identifier Number ABC ### Relevant Clinical History and Physical Exam A 63 years male, hypertensive, diabetic presented with chronic stable angina for 6 months. An echocardiogram was showing good left ventricular systolic function (EF-65%) and no regional wall motion
A Laboratory Assessment of 120 Air Pollutant Emissions from Biomass and Fossil Fuel Cookstoves

Cookstoves emit many pollutants that are harmful to human health and the environment. However, most of the existing scientific literature focuses on fine particulate matter (PM2.5) and carbon monoxide (CO). We present an extensive data set of speciated air pollution emissions from wood, charcoal, kerosene, and liquefied petroleum gas (LPG) cookstoves. One-hundred and twenty gas- and particle-phase constituents-including organic carbon, elemental carbon (EC), ultrafine particles (10-100 nm), inorganic ions, carbohydrates, and volatile/semivolatile organic compounds (e.g., alkanes, alkenes, alkynes, aromatics, carbonyls, and polycyclic aromatic hydrocarbons (PAHs))-were measured in the exhaust from 26 stove/fuel combinations. We find that improved biomass stoves tend to reduce PM2.5 emissions; however, certain design features (e.g., insulation or a fan) tend to increase relative levels of other coemitted pollutants (e.g., EC ultrafine particles, carbonyls, or PAHs, depending on stove type). In contrast, the pressurized kerosene and LPG stoves reduced all pollutants relative to a traditional three-stone fire (≥93% and ≥79%, respectively). Finally, we find that PM2.5 and CO are not strong predictors of coemitted pollutants, which is problematic because these pollutants may not be indicators of other cookstove smoke constituents (such as formaldehyde and acetaldehyde) that may be emitted at concentrations that are harmful to human health.
Supernovae and Cosmology

I review the presently existing four partly independent methods of determining extragalactic distances through supernova investigations and conclude that, although each of these methods has its difficulties, application of all of them on the same class of objects provides the opportunity of obtaining unique redundancy in determinations of extragalactic distances and Hubble’s constant.
Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma

Hepatocyte growth factor (HGF) signaling through its receptor Met has been implicated in hepatocellular carcinoma tumorigenesis and progression. Met interaction with integrins is shown to modulate the downstream signaling to Akt and ERK (extracellular-regulated kinase). In this study, we developed a mechanistically detailed systems biology model of HGF/Met signaling pathway that incorporated specific interactions with integrins to investigate the efficacy of integrin-binding peptide, AXT050, as monotherapy and in combination with other therapeutics targeting this pathway. Here we report that the modeled dynamics of the response to AXT050 revealed that receptor trafficking is sufficient to explain the effect of Met-integrin interactions on HGF signaling. Furthermore, the model predicted patient-specific synergy and antagonism of efficacy and potency for combination of AXT050 with sorafenib, cabozantinib, and rilotumumab. Overall, the model provides a valuable framework for studying the efficacy of drugs targeting receptor tyrosine kinase interaction with integrins, and identification of synergistic drug combinations for the patients.
Phylogenomic analysis of UDP‐dependent glycosyltransferases provides insights into the evolutionary landscape of glycosylation in plant metabolism

Glycosylated metabolites generated by UDP-dependent glycosyltransferases (UGTs) play critical roles in plant interactions with the environment as well as human and animal nutrition. The evolution of plant UGTs has previously been explored, but with a limited taxon sampling. In this study, 65 fully sequenced plant genomes were analyzed, and stringent criteria for selection of candidate UGTs were applied to ensure a more comprehensive taxon sampling and reliable sequence inclusion. In addition to revealing the overall evolutionary landscape of plant UGTs, the phylogenomic analysis also resolved the phylogenetic association of UGTs from free-sporing plants and gymnosperms, and identified an additional UGT group (group R) in seed plants. Furthermore, lineage-specific expansions and contractions of UGT groups were detected in angiosperms, with the total number of UGTs per genome remaining constant generally. The loss of group Q UGTs in Poales and Brassicales, rather than functional convergence in the group Q containing species, was supported by a gene tree of group Q UGTs sampled from many species, and further corroborated by the absence of group Q homologs on the syntenic chromosomal regions in Arabidopsis thaliana (Brassicales). Branch-site analyses of the group Q UGT gene tree allowed for identification of branches and amino acid sites that experienced episodic positive selection. The positively selected sites are located on the surface of a representative group Q UGT (PgUGT95B2), away from the active site, suggesting their role in protein folding/stability or protein-protein interactions.
Neuroprognostication Practices in Postcardiac Arrest Patients: An International Survey of Critical Care Providers.

Objectives To characterize approaches to neurologic outcome prediction by practitioners who assess prognosis in unconscious cardiac arrest individuals, and assess compliance to available guidelines. Design International cross-sectional study. Setting We administered a web-based survey to members of Neurocritical Care Society, Society of Critical Care Medicine, and American Academy of Neurology who manage unconscious cardiac arrest patients to characterize practitioner demographics and current neuroprognostic practice patterns. Subjects Physicians that are members of aforementioned societies who care for successfully resuscitated cardiac arrest individuals. Interventions Not applicable. Measurements and main results A total of 762 physicians from 22 countries responses were obtained. A significant proportion of respondents used absent corneal reflexes (33.5%) and absent pupillary reflexes (36.2%) at 24 hours, which is earlier than the recommended 72 hours in the standard guidelines. Certain components of the neurologic examination may be overvalued, such as absent motor response or extensor posturing, which 87% of respondents considered being very or critically important prognostic indicators. Respondents continue to rely on myoclonic status epilepticus and neuroimaging, which were favored over median nerve somatosensory evoked potentials for prognostication, although the latter has been demonstrated to have a higher predictive value. Regarding definitive recommendations based on poor neurologic prognosis, most physicians seem to wait until the postarrest timepoints proposed by current guidelines, but up to 25% use premature time windows. Conclusions Neuroprognostic approaches to hypoxic-ischemic encephalopathy vary among physicians and are often not consistent with current guidelines. The overall inconsistency in approaches and deviation from evidence-based recommendations are concerning in this disease state where mortality is so integrally related to outcome prediction.
Serum neurofilament light as a prognostic marker for MS disability: Are we there yet?

Multiple sclerosis (MS) is an inflammatory disease of the CNS resulting in neurologic disability that often progresses over time. Because the prognosis varies highly among patients, prognostic markers can help guide treatment decisions. Neurofilament light (NfL) is a biomarker consisting of structural elements of neurons released in the CSF after axonal injury in various neurologic disorders.1 Nowadays, NfL can also reliably be quantified in serum by single-molecule array assays.1 This makes NfL the ideal candidate biomarker of acute and chronic axonal damage. Serum NfL increases in patients with MS during relapses2,3 and in the presence of gadolinium-enhancing lesions on MRI.3,4 Consequently, NfL has been the designated serum biomarker for MS disease activity and treatment response.
Feline infectious peritonitis virus-associated rhinitis in a cat

Case summaryThis report describes a cat with initial respiratory signs prior to developing fulminant feline infectious peritonitis (FIP) after adoption from an animal shelter. Histologic examinatio...
Shakespeare's “Vicious Blots” and the Diction of Later English Bible Translations

This essay examines the possible significance of blot variants in both Shakespeare's corpus and later English Bible translations, especially their increased use in l611 King James Version and the R...
Inequality-Constrained and Robust 3D Face Model Fitting.

Fitting 3D morphable models (3DMMs) on faces is a well-studied problem, motivated by various industrial and research applications. 3DMMs express a 3D facial shape as a linear sum of basis functions. The resulting shape, however, is a plausible face only when the basis coefficients take values within limited intervals. Methods based on unconstrained optimization address this issue with a weighted \(\ell _2\) penalty on coefficients; however, determining the weight of this penalty is difficult, and the existence of a single weight that works universally is questionable. We propose a new formulation that does not require the tuning of any weight parameter. Specifically, we formulate 3DMM fitting as an inequality-constrained optimization problem, where the primary constraint is that basis coefficients should not exceed the interval that is learned when the 3DMM is constructed. We employ additional constraints to exploit sparse landmark detectors, by forcing the facial shape to be within the error bounds of a reliable detector. To enable operation “in-the-wild”, we use a robust objective function, namely Gradient Correlation. Our approach performs comparably with deep learning (DL) methods on “in-the-wild” data that have inexact ground truth, and better than DL methods on more controlled data with exact ground truth. Since our formulation does not require any learning, it enjoys a versatility that allows it to operate with multiple frames of arbitrary sizes. This study’s results encourage further research on 3DMM fitting with inequality-constrained optimization methods, which have been unexplored compared to unconstrained methods.
Evidence that specific interactions play a role in the cholesterol sensitivity of G protein-coupled receptors

G protein-coupled receptors (GPCRs) are known to be modulated by membrane cholesterol levels, but whether or not the effects are caused by specific receptor-cholesterol interactions or cholesterol's general effects on the membrane is not well-understood. We performed coarse-grained molecular dynamics (CGMD) simulations coupled with structural bioinformatics approaches on the β2-adrenergic receptor (β2AR) and the cholecystokinin (CCK) receptor subfamily. The β2AR has been shown to be sensitive to membrane cholesterol and cholesterol molecules have been clearly resolved in numerous β2AR crystal structures. The two CCK receptors are highly homologous and preserve similar cholesterol recognition motifs but despite their homology, CCK1R shows functional sensitivity to membrane cholesterol while CCK2R does not. Our results offer new insights into how cholesterol modulates GPCR function by showing cholesterol interactions with β2AR that agree with previously published data; additionally, we observe differential and specific cholesterol binding in the CCK receptor subfamily while revealing a previously unreported Cholesterol Recognition Amino-acid Consensus (CRAC) sequence that is also conserved across 38% of class A GPCRs. A thermal denaturation assay (LCP-Tm) shows that mutation of a conserved CRAC sequence on TM7 of the β2AR affects cholesterol stabilization of the receptor in a lipid bilayer. The results of this study provide a better understanding of receptor-cholesterol interactions that can contribute to novel and improved therapeutics for a variety of diseases.
The Economy of the Gulf States: MATTHEW GRAY, (Newcastle Upon Tyne, UK: Agenda Publishing Limited, 2018), 254 pages; £60 hardback, £16.99 paperback.

Over the last decade, there has been an explosion of interest in the Arab monarchies of the Gulf, with an infusion of new scholars, who have challenged established theories while opening new fronti...
Is Asymptotic Cost Analysis Useful in Developing Practical Parallel Algorithms

Asymptotic analysis of runtime, and space, has been the cornerstone in the development of practical sequential algorithms. The analysis is not meant to predict runtimes on any particular machine, but rather to guide algorithm designers and implementors in the right direction, and let them better understand how algorithms might scale. Quicksort, Dijkstra's algorithm, dynamic programming, depth first search, for example, are fast in theory and in practice–-and scale pretty much as the theory predicts. All CS undergrads learn about these algorithms and techniques, and they are broadly implemented in many widely used libraries and applications. Over the years models have been extended to include the benefits of locality, allowing for a refined asymptotic analysis when needed. Unfortunately the jury is still out on the role of asymptotic analysis in the practice of parallel algorithms. There is no lack of theoretical work on analyzing the cost of parallel algorithms, with such work dating back almost fifty years, but these ideas have not been widely adopted in practice. There are various possible reasons, including inaccurate cost models, giant constants in the big-O, no adequate programming languages, lack of education on the topic, or perhaps parallel machines are just too complicated to model theoretically and we should just give up. In this talk I will describe how simple parallel models can be useful for developing practical parallel algorithms, and many of the theoretical ideas in parallel algorithms are useful, at least in the context of shared-memory multicore machines. I will cover work on developing practically efficient algorithms for a wide variety of applications of graphs, trees, computational geometry, and strings. As with sequential algorithms, the basic model does not account for locality, but I will discuss some simple ways to extend it.
The Impact of Outliers on Regression Coefficients: A Sensitivity Analysis

Empirical research analyzes real-life data that often do not conform to a normal distribution with statistical tools such as linear regressions that require the assumption of normality. The lack of...
Intraosseous hibernoma

We describe the imaging and pathological features of a rare case of sacral hibernoma that was discovered incidentally in a patient with low back pain. The benign-appearing, small intraosseous lesion in the sacrum was sclerotic on CT. MRI revealed that the lesion was heterogeneously hyperintense on T1W (lower in intensity than subcutaneous fat) and heterogeneously hypointense on fat-saturated T2W and STIR images. It showed mild heterogeneous enhancement on the post-contrast fat-saturated T1 MR images due to increased vascularity. A biopsy of the lesion was performed. The biopsy specimen demonstrated multivacuolated cells with immunohistochemical features of brown adipose tissue consistent with hibernoma.
Single-cell profiling of T lymphocytes in deficiency of adenosine deaminase 2

Deficiency of adenosine deaminase 2 (DADA2) is a monogenic vasculitis syndrome caused by autosomal-recessive loss-of-function mutations in the ADA2 gene (previously known as CECR1). Vasculitis, vasculopathy, and inflammation are dominant clinical features of this disease; the spectrum of manifestations includes immunodeficiency and lymphoproliferation as well as hematologic manifestations. ADA2 is primarily secreted by stimulated monocytes and macrophages. Aberrant monocyte differentiation to macrophages and neutrophils are important in the pathogenesis of DADA2, but little is known about T lymphocytes in this disease. We performed combined single-cell RNA sequencing and single-cell TCR sequencing in order to profile T cell repertoires in 10 patients with DADA2. Although there were no significant alterations of T cell subsets, we observed activation of both CD8+ and CD4+ T cells. There was no clonal expansion of T cells: most TCRs were expressed at basal levels in patients and healthy donors. TCR usage was private to individual patients and not disease specific, indicating as unlikely a common pathogenic background or predisposition to a common pathogen. We recognized activation of IFN pathways as a signature of T cells and STAT1 as a hub gene in the gene network of T cell activation and cytotoxicity. Overall, T cells in DADA2 patients showed distinct cell-cell interactions with monocytes, as compared with healthy donors, and many of these ligand-receptor interactions likely drove up-regulation of STAT1 in both T cells and other immune cells in patients. Our analysis reveals previously undercharacterized cell characteristics in DADA2.
5 – KINETIC STUDIES OF SYNTHETIC MULTIDENTATE MACROCYCLIC COMPOUNDS

Abstract : The recent literature on the kinetic properties of a variety of synthetic multidentate macrocyclic compounds has been reviewed and discussed. At the beginning of this chapter, a brief discussion of kinetic and mechanistic studies of antibiotics has been reviewed. Then the synthetic macrocyclic compounds are treated within the framework of their different classes; i.e. crown ethers, cryptates and macrocyclic tetramines. In addition to a review of the kinetic research, attempts were made to clarify certain aspects of the literature and to discuss similarities and differences between the various classes. Finally, the last section discusses possible kinetic studies of more novel Host molecules designed and synthesized by Cram.
Epineural Patch Applications in Dorsal Root Ganglion Decompression Model

Decompressive spinal procedures, such as lumbar laminectomy, are frequently performed to treat conditions such as spinal stenosis and disc herniations. Adequate decompression necessitates exposure of the dura, which results in the formation of postoperative peridural fibrosis. Excess formation of this type of scar tissue has been shown to result in leg and back pain secondary to tethering of the nerve roots and dura. In addition, the presence of the fibrous scar tissue makes revision spinal surgery challenging and increases the potential for complications. Therefore, prevention of peridural fibrosis and adhesion formation after spinal decompressive procedure is important for successful outcomes. There are a number of approaches used after spinal decompression to prevent fibrosis, adhesions, and scar tissue formation. These have included application of: thrombin-based hemostatic gelatin, caprolactone/lactide film (mesofol), mitomycin C and many others, all with various success.
Wave Packet Studies of the Predissociation of H3

The quantum dynamics of small molecules on multiple, coupled potential energy surfaces remains a challenging area of study. Even for the few systems for which accurate ground state potential surfaces are available, very little is typically known about the excited state surfaces, or the couplings among the ground and excited surfaces. However, recent advances in electronic structure theory have begun to make the characterization of these surfaces and couplings feasible, and improvements in dynamical methods allow them to be incorporated into a realistic description of the dynamics. In this paper we concentrate on the predissociation of H3, the simplest polyatomic system. We use ab initio methods to obtain the necessary excited state surfaces and non-adiabatic couplings, and a time-dependent wave packet treatment of the dynamics.
Taking the Framers Seriously

Walter Berns's Taking the Constitution Seriously' champions a familiar thesis: the original meaning of the Constitution, Berns contends, is readily understandable and remains binding today. In addition, as with most other leading proponents of original intent, Berns's conception of the framers' intent accords with a modern conservative political agenda. Among the elements of his constitutional jurisprudence are opposition to judicial activism, a belief that the proper role of the national government is a very limited one, a strong commitment to the rights of property, and a conviction that the individual states can support the "moral education" (p. 222) of their citizens without running afoul of the first amendment. Unlike most of the legal literature on original intent, however, the principal concern of Taking the Constitution Seriously is not with what the framers intended specific constitutional clauses to mean. Rather, Berns's principal concern is to reveal the political philosophy behind the Constitution, a philosophy which, he maintains, should inform our reading of the document. In delineating that philosophy, Berns relies on the constitutional text and on a handful of documents that either elucidate it, such as The Federalist Papers, or partake of the same world view as the Constitution, such as the Declaration of Independence. Behind Berns's conception of the Constitution is a recognition of the fact that the world of the framers was a world in transition. In late eighteenth century America, pre-modern, pre-commercial society was ending. In its place, modern liberal (using the word in
Modulation of the immune response by immunoglobulin for intravenous use. II. Inhibitory effects of sera from treated patients.

Abstract Sera were collected from patients with common varied immunodeficiency (CVI) prior to and following intravenous γ-globulin (IVGG) infusion. Cultures of pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cells from normal donors in medium containing post-IVGG infusion sera generated significantly fewer plaque-forming cells (PFC) than those cultures in medium containing the corresponding pre-IVGG infusion sera. However, preinfusion CVI sera were found to be similar to normal sera in their capacities to support PWM-induced PFC generation, despite the disparity in Ig levels between the two groups of sera. Furthermore, serum collected from a CVI patient 24 hr or more after IVGG infusion no longer possessed the same inhibitory capacity as serum collected 10 min after IVGG infusion despite elevated IgG levels compared to baseline. These studies suggest that IVGG infusion may induce an immunosuppressive effect which is transient in nature, raising the possibility of in vivo counterbalancing homeostatic mechanisms responding to this immune perturbation.
II. CONFIGURATION OF THE CHEST

1. Various chest measurements have been made on 174 normal children ranging in age from newborn to 18 years and on 22 children with cystic fibrosis. 2. The patterns of growth of the anteroposterior (AP) and transthoracic (TT) and the sternal length (SL) in relation to height differ from that of the biacromial. After birth there is a rapid increase in the transthoracic and antero-posterior diameters, especially the former. Following this the growth of these two and the sternal length are relatively slow, accelerating again with increasing size. 3. The growth of a thoracic volume index (AP2.TT.SL) correlates well with the growth of the lung volumes in the ages where both are measurable. In younger children the growth pattern of the thoracic volume index is dissimilar to an extrapolation of the lung volume growth line. 4. Patients with cystic fibrosis have an increase in the antero-posterior and transverse diameters and to a lesser extent in the sternal length when compared with normal children of the same height. Because the transverse diameter is increased, a more sensitive indication of an abnormal chest is obtained from the AP diameter-height ratio than from the usual thoracic index (AP/TT).
Learning to Choose a Reformulation for Numerical Optimization of Engineering Designs

It is well known that search-space reformulation can improve the speed and reliability of numerical optimization in engineering design. We argue that the best choice of reformulation depends on the design goal, and present a technique for automatically constructing rules that map the design goal into a reformulation chosen from a space of possible reformulations. We tested our technique in the domain of racing-yacht-hull design, where each reformulation corresponds to incorporating constraints into the search space. We used a standard inductive-learning algorithm, C4.5, to learn rules from a set of training data describing which constraints are active in the optimal design for each goal encountered in a previous design session. We then used these rules to choose an appropriate reformulation for each of a set of test cases. Our experimental results show that using these reformulations improves both the speed and the reliability of design optimization, outperforming competing methods and approaching the best performance possible.
Surgical risk factors for recurrence of inverted papilloma.

Objectives/Hypothesis To identify variations in surgical technique that impact the recurrence of inverted papilloma following endoscopic excision. Study Design Retrospective cohort. Methods Data from 127 consecutive patients who underwent endoscopic excision of inverted papilloma and oncocytic papilloma at a tertiary care medical center from 1998 to 2011 were reviewed. Patient demographics, comorbidities, tumor stage, and intraoperative details, including tumor location and management of the base, were evaluated to identify factors associated with tumor recurrence. Results Recurrence of papilloma occurred in 16 patients (12.6%). Mean time to recurrence was 31.0 months (range, 5.2–110.0 months). Mucosal stripping alone was associated with a recurrence rate of 52.2% (12/23 patients), compared to 4.9% (3/61 patients) when the tumor base was drilled, 4.7% (1/21 patients) when it was cauterized, and 0.0% (0/22 patients) when it was completely excised (P = .001). Increased recurrence rate was associated with tumors located in the maxillary sinus (P = .03), as well as the performance of endoscopic medial maxillectomy (P = .001) and external frontal approaches (P = .02). Conclusions Drilling, cauterizing, or completely excising the bone underlying the tumor base during endoscopic resection reduces the recurrence rate of inverted and oncocytic papilloma, when compared to mucosal stripping alone. Surgeons who perform endoscopic resection of these tumors should consider utilization of these techniques when possible. Level of Evidence 4 Laryngoscope, 126:796–801, 2016
Basic research and technology transfer

The problem of technology transfer, from government–sponsored and university–performed basic research into industrial use and commercialization, is examined in areas other than agriculture, defence and health. Technology transfer requires a pro–active attitude that takes into account and deals with the differing innovation perspectives of academe and industry. Several criteria for successful technology transfer are discussed and illustrated by means of examples.
Salmonella osteomyelitis and abnormal hemoglobin disease.

In reply to Dr. Hammond9s letter (Pediatrics, 21:162, January 1958) regarding our article on "Salmonella Osteomyelitis and Abnormal Hemoglobin Disease" may we point out that one of the authors (J.L.S.) not only saw the patient under discussion but took care of her during her hospitalization. She was discussed by Dr. Hammond at Grand Rounds at the University of California Hospital and at that time it was concluded that she probably had hemoglobin C-D disease. Subsequently, when the patient9s chart was abstracted (September, 1956) there was nothing to indicate that this conclusion had been altered. Therefore, we used the data as then available.
Protein Interactions in Hydrophobic Charge Induction Chromatography (HCIC)

A quantitative understanding of how proteins interact with hydrophobic charge induction chromatographic resins is provided. Selectivity on this mode of chromatography for monoclonal antibodies as compared to other model proteins is probed by means of a linear retention vs pH plot. The pH-dependent adsorption behavior on this mode of chromatography for a hydrophobic, charged solute is described by taking into account the equilibrium between a hydrophobic, charged solute and an ionizable, heterocyclic ligand. By analogy, an equation that is seen to adequately describe macromolecular retention under linear conditions over a range of pH is developed. A preparative, nonlinear isotherm that can capture both pH and salt concentration dependency for proteins is proposed by using an exponentially modified Langmuir isotherm model. This model is seen to successfully simulate adsorption isotherms for a variety of proteins over a range of pHs and mobile phase salt concentrations. Finally, the widely differing retention characteristics of two monoclonal antibodies are used to derive two different strategies for improving separations on this mode of chromatography. A better understanding of protein binding to this class of resins is seen as an important step to future exploitation of this mode of chromatography for industrial scale purification of proteins.