cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of low-sodium diet on regulation of platelet alpha 2-adrenergic receptors in young and elderly humans

To examine whether there are age differences in agonist-mediated alpha 2-adrenergic receptor (alpha 2-AR) regulation, we studied the effect of a sustained increase in plasma norepinephrine (pNE) during a 7-day 10-meq Na+/day diet on platelet alpha 2-AR binding and its linked adenylate cyclase (AC) activity in 11 elderly and 11 young healthy subjects. In the young, a 41% increase in mean pNE after a low-sodium diet was correlated with a decline in receptor density (Bmax; r = -0.816; P less than 0.01) and was accompanied by a reduction in the maximal percent inhibition of sodium fluoride-stimulated AC activity by epinephrine (%AC INH; 33 +/- 4 vs. 24 +/- 4%, mean +/- SE; P less than 0.05 vs. normal diet). Despite a comparable 39% increase in mean pNE in the elderly, neither Bmax nor %AC INH was significantly reduced after a low-sodium diet. The amount of pertussis toxin substrate (Gi protein) was similar in both groups before and after dietary sodium restriction. At comparable pNE, %AC INH in the groups was similar (young, 24 +/- 4 vs. elderly, 18 +/- 4%; P = NS). We postulate that higher basal pNE levels in the elderly on normal diet may account for the lack of further downregulation of platelet alpha 2-AR density and response after low-sodium diet.
Method of Secret Communication for Embedded System

This article describes a system frame for communiction between embedded equipments. Security and encryption technology the system frame used is advanced and applicable .
On the Stability of Charge-Pump Phase-Locked Loops

This paper employs a time-variant model to determine the exact small-signal loop transmission of second-order charge-pump phased-locked loops. The model predicts that a loop bandwidth of close to half the input frequency can be achieved. The large-signal behavior is also analyzed and two modes of oscillation are identified. The results are confirmed by means of circuit simulations.
Effects of the length of central cancer registry operations on identification of subsequent cancers and on survival estimates.

Abstract Background Population-based cancer survival analyses have traditionally been based on the first primary cancer. Recent studies have brought this practice into question, arguing that varying registry reference dates affect the ability to identify earlier cancers, resulting in selection bias. We used a theoretical approach to evaluate the extent to which the length of registry operations affects the classification of first versus subsequent cancers and consequently survival estimates. Methods Sequence number central was used to classify tumors from the New York State Cancer Registry, diagnosed 2001–2010, as either first primaries (value = 0 or 1) or subsequent primaries (≥2). A set of three sequence numbers, each based on an assumed reference year (1976, 1986 or 1996), was assigned to each tumor. Percent of subsequent cancers was evaluated by reference year, cancer site and age. 5-year relative survival estimates were compared under four different selection scenarios. Results The percent of cancer cases classified as subsequent primaries was 15.3%, 14.3% and 11.2% for reference years 1976, 1986 and 1996, respectively; and varied by cancer site and age. When only the first primary was included, shorter registry operation time was associated with slightly lower 5-year survival estimates. When all primary cancers were included, survival estimates decreased, with the largest decreases seen for the earliest reference year. Conclusions Registry operation length affected the identification of subsequent cancers, but the overall effect of this misclassification on survival estimates was small. Survival estimates based on all primary cancers were slightly lower, but might be more comparable across registries.
Design and Prototype of an Automated Column-Switching HPLC System for Radiometabolite Analysis

Column-switching high performance liquid chromatography (HPLC) is extensively used for the critical analysis of radiolabeled ligands and their metabolites in plasma. However, the lack of streamlined apparatus and consequently varying protocols remain as a challenge among positron emission tomography laboratories. We report here the prototype apparatus and implementation of a fully automated and simplified column-switching procedure to allow for the easy and automated determination of radioligands and their metabolites in up to 5 mL of plasma. The system has been used with conventional UV and coincidence radiation detectors, as well as with a single quadrupole mass spectrometer.
Dynamic regimes of neocortical activity linked to corticothalamic integrity correlate with outcomes in acute anoxic brain injury after cardiac arrest.

Objective Recognition of potential for neurological recovery in patients who remain comatose after cardiac arrest is challenging and strains clinical decision making. Here, we utilize an approach that is based on physiological principles underlying recovery of consciousness and show correlation with clinical recovery after acute anoxic brain injury. Methods A cohort study of 54 patients admitted to an Intensive Care Unit after cardiac arrest who underwent standardized bedside behavioral testing (Coma Recovery Scale – Revised [CRS-R]) during EEG monitoring. Blinded to all clinical variables, artifact-free EEG segments were selected around maximally aroused states and analyzed using a multi-taper method to assess frequency spectral content. EEG spectral features were assessed based on pre-defined categories that are linked to anterior forebrain corticothalamic integrity. Clinical outcomes were determined at the time of hospital discharge, using Cerebral Performance Categories (CPC). Results Ten patients with ongoing seizures, myogenic artifacts or technical limitations obscuring recognition of underlying cortical dynamic activity were excluded from primary analysis. Of the 44 remaining patients with distinct EEG spectral features, 39 (88%) fit into our predefined categories. In these patients, spectral features corresponding to higher levels of anterior forebrain corticothalamic integrity correlated with higher levels of consciousness and favorable clinical outcome at the time of hospital discharge (P = 0.014). Interpretation Predicted transitions of neocortical dynamics that indicate functional integrity of anterior forebrain corticothalamic circuitry correlate with clinical outcomes in postcardiac-arrest patients. Our results support a new biologically driven approach toward better understanding of neurological recovery after cardiac arrest.
Demand for Law and the Security of Property Rights: The Case of Post-Soviet Russia

Studies of property rights overwhelmingly focus on whether states expropriate or protect property, overlooking the crucial issue of whether private sector actors will use state institutions. By contrast, I argue that the “supply” of formal legal institutions often fails to ensure firms will rely on the state for property rights protection. Instead, firms frequently avoid formal legal institutions and turn to illegal strategies based on violence or corruption. Whether firms adopt legal strategies depends on: (1) firm-level practices and beliefs that impede the use of law, (2) the effectiveness of illegal strategies, and (3) coordination problems resulting from firms’ expectations about each other’s strategies. Drawing on interviews with firms, lawyers, and private security agencies, as well as an original survey of Russian enterprises, I illustrate how “demand-side” factors led to a surprising increase in Russian firms’ reliance on formal legal institutions over the past two decades. The findings suggest that comprehensive understanding of property rights and the rule of law requires not only attention to state institutions’ effectiveness, but also to private actors’ strategies.
Trends in Volunteer Mentoring in the United States: Analysis of a Decade of Census Survey Data

Over the past decade, considerable resources have been devoted to recruiting volunteer mentors and expanding mentoring programs. It is unclear whether these efforts have helped to counter the broader national trends of declining volunteer rates. The current study uses data from the Volunteering Supplement of the Current Population Survey (CPS), sponsored by the U.S. Census Bureau and U.S. Bureau of Labor Statistics, to explore population-level trends in mentoring over the past decade. Results suggest that mentoring rates have remained relatively stable over the past decade, but that the population of mentors has changed somewhat in terms of age, ethnicity, educational background, and region of the United States. In addition, certain sectors of the mentor population show higher rates of attrition from 1 year to the next. Findings have important implications for the development of recruitment, training, and mentor support practices within mentoring organizations, as well as policies designed to meet the needs of at-risk youth in the U.S.
Guidelines for Interpreting and Reporting Subscores

Recent research has proposed a criterion to evaluate the reportability of subscores. This criterion is a value-added ratio (VAR), where values greater than 1 suggest that the true subscore is better approximated by the observed subscore than by the total score. This research extends the existing literature by quantifying statistical significance and effect size for using VAR to provide practical guidelines for subscore interpretation and reporting. Findings indicate that subscores with VAR ≥ 1.1 are a minimum requirement for a meaningful contribution to a user's score interpretation; subscores with .9 < VAR < 1.1 are redundant with the total score and subscores with VAR ≤ .9 would be misleading to report. Additionally, we discuss what to do when subscores do not add value, yet must be reported, as well as when VAR ≥ 1.1 may be undesirable.
The effects of tether placement on antibody stability on surfaces

Despite their potential benefits, antibody microarrays have fallen short of performing reliably and have not found widespread use outside of the research setting. Experimental techniques have been unable to determine what is occurring on the surface of an atomic level, so molecular simulation has emerged as the primary method of investigating protein/surface interactions. Simulations of small proteins have indicated that the stability of the protein is a function of the residue on the protein where a tether is placed. The purpose of this research is to see whether these findings also apply to antibodies, with their greater size and complexity. To determine this, 24 tethering locations were selected on the antibody Protein Data Bank (PDB) ID: 1IGT. Replica exchange simulations were run on two different surfaces, one hydrophobic and one hydrophilic, to determine the degree to which these tethering sites stabilize or destabilize the antibody. Results showed that antibodies tethered to hydrophobic surfaces were in general less stable than antibodies tethered to hydrophilic surfaces. Moreover, the stability of the antibody was a function of the tether location on hydrophobic surfaces but not hydrophilic surfaces.
Far from Standardized: Using Surgical Videos to Identify Variation in Technique for Laparoscopic Sleeve Gastrectomy

Abstract Background: Video assessment is an emerging tool for understanding variation in surgical technique. Methods: Representative videos of laparoscopic sleeve gastrectomy (LSG) were voluntarily submitted by 20 surgeons who participated in a statewide quality improvement collaborative. The amount of time required to complete the salient steps of the operation was measured and variations in the tasks performed during each step were captured. Results: Twenty-two videos of LSG were submitted and 11 videos included concurrent hiatal hernia repair. Data obtained from video analysis identified variation in time to complete each step of the procedure: prestapling dissection of stomach (5–25 minutes), gastric stapling (8–20 minutes), and management of the staple line (1–25 minutes). Time required to perform a hiatal hernia repair also varied (1–26 minutes), as did the type of repair: 55% were performed with a posterior cruropexy, 27% were performed with an anterior cruropexy, and 18% were performed with both. ...
Virtual proteomics of pathology specimens: Mass spectrometric detection of multiple proteins in formalin-fixed paraffin-embedded tissue.

A9 The goal of personalized medicine is to deliver the best treatment to the patient. In clinical oncology, proteomics can evaluate differential expression and post-translational modifications of proteins in healthy and diseased states. Given that many novel anticancer therapies are designed to target tumor proteins, proteomic analysis of tumor tissue should complement conventional genomic or immunohistochemical (IHC) analyses in delivering information relevant for diagnosis, prognosis and predicting tumor response to treatment. Formalin fixation and paraffin embedding (FFPE) of diagnostic specimens is the preparation method of choice for pathological assessment. We undertook this study to identify differentially expressed proteins in FFPE specimens from various pathological states of breast tissue and to compare expression of select known tumor biomarkers in normal and diseased states. Tissue was extracted using an improved protocol that results in enhanced protein yields. We examined FFPE archival breast tissue specimens including 23 normal samples from reduction mammoplasties (control group), 21 fibroadenomas, 25 node negative breast cancers, and 22 node positive breast cancers (test group). Histological subtype and the expression status of estrogen and progesterone receptors, HER2, p53, and Ki-67 were evaluated in the breast cancer specimens. Ten micron FFPE sections were microdissected, de-paraffinized, digested with trypsin, and analyzed by liquid chromatography electrospray ionization mass spectrometry (LC-ESI MS). We developed a novel strategy for MS data mining referred to as “virtual proteomics”, which encompassed diverse mathematical operations on data sets. First, we identified differentially expressed mass/time signals, which were subjected to on- and off-line MS analysis. Data were searched against on-line protein data libraries for the identifications of likely target proteins based on the observed peptide sequences (discovery mode). In parallel, we interrogated the MS data with virtual probes derived from theoretical tryptic digests of known cancer biomarkers (hypothesis testing mode). In the discovery mode, we identified over 5 proteins that were present in >50% specimens in >1 test groups with >10-fold relative differences in expression in comparison with the controls, Mowse scores of >70 (p
Advances in Melanoma: The Rationale for the Melanoma Nursing Initiative .

This article provides an overview of this supplement, outlining the needs assessment process the Melanoma Nursing Initiative (MNI) used to determine the immunotherapy and targeted therapy topics for discussion as well as the process for developing the consensus statements. The article provides specific discussion of a unique feature of the MNI, the care step pathways (CSPs) for management of adverse events (AEs) associated with melanoma therapies, and looks to the future in terms of the potential benefits of engaging and enabling oncology nurses to adopt a standardized approach to AE management and adherence promotion for melanoma therapies.
Do we need a new CT scan for retreatment of intracranial SRS patients

Purpose To determine if the treatment planning computed tomography scan (CT) from an initial intracranial stereotactic radiosurgery (SRS) treatment can be used for repeat courses of SRS. Methods and materials Twenty-five patients with 40 brain metastases that received multiple courses of SRS were retrospectively studied. Magnetic resonance scans from repeat SRS (rMR) courses were registered to CT scans from the initial SRS (iCT) and repeat SRS (rCT). The CT scans were then registered to find the displacement of the rMR between iCT and rCT registrations. The distance from each target to proximal skull surface was measured in 16 directions on each CT scan after registration. The mutual information (MI) coefficients from the registration process were used to evaluate image set similarity. Targets and plans from the rCTs were transferred to the iCTs, and doses were recalculated on the iCT for repeat plans. The two dose distributions were compared through 3D gamma analysis. Results The magnitude of the mean linear translations from the MR registrations was 0.6 ± 0.3 mm. The mean differences in distance from target to skull on a per target basis were 0.3 ± 0.2 mm. The MI was 0.582 ± 0.042. Registration between a comparison group of 30 CT scans that had the same data resampled and 30 scans that were intercompared with different patients gave MI = 0.721 ± 0.055 and MI = 0.359 ± 0.031, respectively. The mean gamma passing rates were 0.997 ± 0.007 for 1 mm/1% criteria. Conclusions The rMR can be aligned to the iCT to accurately define targets. The skull shows minimal change between scans so the iCT can be used for set-up at repeat treatments. The dosimetry provided by the iCT dose calculation is adequate for repeat SRS. Treatment based on iCT is feasible.
Parents’ Preferences Regarding Public Reporting of Outcomes in Congenital Heart Surgery

Background Calls for public reporting of outcomes in congenital heart surgery have led to several different reporting schemes, including a star rating system and benchmark procedure-specific mortality data tables. Important unanswered questions remain about the optimal format and content of public reporting of congenital heart surgery outcomes. Methods In conjunction with three parent advocacy groups, we developed a questionnaire to gauge parents' attitudes regarding the format and content of an "optimal" public reporting scheme. Parents were solicited for participation through email lists of members of parent advocacy groups and from a cohort of parents whose children had undergone an STS benchmark procedure of the Society of Thoracic Surgeons at the Children's Hospital of Philadelphia after January 1, 2007. Results The 1,297 responses received provided complete data for analysis. Nearly all the participants were mothers of children with congenital heart disease, and most were white. About half of the children were diagnosed prenatally, and 63% underwent initial repair of the defect in the neonatal period. Parents identified survival statistics, surgeon-specific experience, and complication rates as most important. Presented with three display formats for mortality rates, most parents (89%) identified a numeric procedure-based approach as the best format, and more than half identified the hospital star rating system as the worst format. Conclusions Parents of children with congenital heart disease identify survival statistics, surgeon-specific experience, and complication rates as the most important outcome measures to report publicly. Additionally, parents preferred mortality data to be presented in a procedure-specific format using a numeric procedure-based approach, as opposed to the star rating system.
Clinical Practice Update: The Use of Per-Oral Endoscopic Myotomy in Achalasia: Expert Review and Best Practice Advice From the AGA Institute

The purpose of this review is to describe a place for per-oral endoscopic myotomy (POEM) among the currently available robust treatments for achalasia. The recommendations outlined in this review are based on expert opinion and on relevant publications from PubMed and EMbase. The Clinical Practice Updates Committee of the American Gastroenterological Association proposes the following recommendations: 1) in determining the need for achalasia therapy, patient-specific parameters (Chicago Classification subtype, comorbidities, early vs late disease, primary or secondary causes) should be considered along with published efficacy data; 2) given the complexity of this procedure, POEM should be performed by experienced physicians in high-volume centers because an estimated 20−40 procedures are needed to achieve competence; 3) if the expertise is available, POEM should be considered as primary therapy for type III achalasia; 4) if the expertise is available, POEM should be considered as treatment option comparable with laparoscopic Heller myotomy for any of the achalasia syndromes; and 5) post-POEM patients should be considered high risk to develop reflux esophagitis and advised of the management considerations (potential indefinite proton pump inhibitor therapy and/or surveillance endoscopy) of this before undergoing the procedure.
In-111 Zevalin biodistribution: Evaluation of single vs. multiple imaging studies

2127 Objectives : In-111 Zevalin imaging is necessary to determine biodistribution prior to administration of Y-90 Zevalin radioimmunotherapy. The imaging protocol for In-111 Zevalin has recently been changed by the manufacturer from multiple imaging scans to one scan. Our laboratory evaluated the clinical implications related to changing the imaging protocol. Methods : The original clinical protocol includes the administration of In-111 Zevalin, a murine monoclonal antibody, following pretreatment with rituximab (Rituxin). In-111 Zevalin imaging studies are then obtained at 2-24 hours, 48-72 hours and 90-120 hours (optional) after infusion. If biodistribution is acceptable, patients are infused with rituximab followed by Y-90 Zevalin therapy at 7-9 days. The new clinical protocol requires only one scan at 48-72 hours after In-111 Zevalin infusion. However, a number of clinical patient factors can alter the biodistribution of radiolabeled monoclonal antibodies and, if they occur fairly early after antibody administration, the altered biodistribution may be missed with delayed imaging times. Results : Murine monoclonal antibodies have been known to cause a human antimurine antibody response (HAMA) in patients. High patient HAMA titers can significantly alter early biodistribution of radiolabeled monoclonal antibodies. In In-111 monoclonal antibodies, high HAMA titers can drastically reduce blood pool activity and significantly increase liver activity. The new clinical protocol imaging acquisition at 48-72 hours may not be able to detect the altered early biodistribution characteristics and as a result, could adversely affect radiolabeled monoclonal antibody therapy. Conclusions : The new clinical imaging protocol, which includes one delayed imaging time at 48-72 hours, may not be able to elucidate early altered biodistribution of radiolabeled monoclonal antibodies caused by high patient HAMA titers. As a result, our nuclear medicine department has continued to utilize the original imaging protocol for In-111 Zevalin, with imaging times at 2-24 hours, 48-72 hours, and 90-120 hours.
Of Cultural Backlash and Economic Insecurity in the 2016 American Presidential Election

Given the strong support of evangelical Christian voters to Donald Trump’s 2016 presidential campaign, many have wondered how, exactly, the pro-religious Trump campaign managed to prevail in an increasingly secular society. This article considers two conceptual models, offered by Ronald Inglehart and Pippa Norris, to bring some understanding to the Trump phenomena: the economic insecurity perspective and the cultural backlash thesis. Each will be considered in terms of three related and interlocking sets of issue clusters: the overall secular direction of the American population, the rural-urban cleavage, and empathy for the forgotten man and woman.
Separation of saturated fatty acids and fatty acid methyl esters with epoxy nanofiltration membranes

Epoxy nanofiltration membranes were fabricated by the step polymerization of a primary diamine and a diepoxide or triepoxide conomomer. Membrane selectivity and flux were tuned by changing the identity of the diepoxides and by increasing the concentration of triepoxides in the polymerization. The membranes were used to separate even chain length saturated fatty acids (FAs) and saturated fatty acid methyl esters (FAMEs) that possessed molecular weights between 80–300 g mol−1. Our membranes show excellent selectivities of up to 100 : 1 for the separation of the C4–C18 FAMEs. The flux of the FAMEs through the membranes showed an exponential dependence based on the number of carbons. Fabrication of thin epoxy membranes with thicknesses of 150 nm allowed for an increase in flux of FAMEs through the membrane and demonstrated that these separations can be used under industrially relevant conditions.
Atopic dermatitis: a review of topical nonsteroid therapy.

Background Atopic dermatitis is a chronic inflammatory skin condition that affects up to 20% of children and 3% of adults globally. Although topical corticosteroids are considered to be the first-line agents, they can be associated with cutaneous and systemic adverse effects. Since the early 2000s, two new classes of nonsteroid topical therapies, topical calcineurin inhibitors and phosphodiesterase 4 (PDE4) inhibitors, have been introduced and provide a safe treatment alternative. Method We performed a search and review of clinical trials that examined the safety and efficacy of topical calcineurin inhibitors and PDE4 inhibitors. The search was conducted using the PubMed database as well as preselected keywords and filters. This review focuses on the safety and efficacy of each therapy. Results Sixty-nine clinical trials identified in this study have demonstrated the efficacy and safety of topical calcineurin and a single novel PDE4 inhibitor in the treatment of atopic dermatitis. Topical calcineurin inhibitors have been shown to be effective in both achieving lesion clearance as well as reducing relapse when used long-term and proactively. Similarly, in clinical trials the PDE4 inhibitor showed success in lesion clearance and symptom management. All three therapies (pimecrolimus, tacrolimus, crisaborole) are associated with low systemic absorption. No clinical trials to date have shown an increased risk of systemic adverse events or malignancy such as lymphoma. The most commonly reported treatment-related adverse event across all three therapies was application-site discomfort, pain or pruritus. It is important to note that long-term studies are not yet available for the novel PDE4 inhibitor. Discussion Topical calcineurin inhibitors provide a safe and effective alternative to topical corticosteroid use in the treatment of atopic dermatitis. Although the US Food and Drug Administration (FDA) black box warning for topical calcineurin inhibitors remains, studies have not shown an increased risk of malignancy. These warnings have caused a decline in use in favor of topical steroids. A novel PDE4 inhibitor has shown efficacy and safety in studies up to one year. Further long-term safety data is needed.
Stress Echocardiography with Vasoactive Agents

Exercise and dobutamine stress induce ischemia by increasing myocardial oxygen requirements to a level which exceeds the ability of a stenosed coronary artery to satisfy the increased demand (see Chapters 3 and 4). Ischemia in most ambulatory situations is caused by oxygen demand outstripping supply, but it may be combined with reduction in coronary supply due to vasospasm or coronary steal. This “supply-side” ischemia may be replicated during stress testing, either using dipyridamole as a convenient form of pharmacologic stress, or using ergotamine to specifically investigate the presence of a vasoactive mechanism of ischemia.
P40: Platelet activation in the presence of nitrite, nitric oxide and heme

Background NO stimulates intercellular cGMP production leading to a reduction in platelet activation. Nitrite is reduced to nitric oxide (NO) by deoxygenated hemoglobin and therefore acts as a potential source of biological NO. Nitrite in the presence of red blood cells (RBCs) has been shown to reduce platelet aggregation and this reduction in aggregation is enhanced when RBCs are deoxygenated. In addition nitrite in the presences of deoxygenated RBCs has been shown to reduce platelet expression of p-selectin when platelets are activated by ADP. Methods Platelet rich plasma was separated from whole blood by centrifugation at 120 g for 10 min. Plasma was diluted 10-fold into phosphate buffered saline and exposed to nitrite, NO, and/or RBC, as indicated. Platelets were then activated by ADP After 10 min of incubation with ADP, platelets were labeled with fluorescent antibodies for platelet recognition (CD41 or CD61) and activation (Pac-1 or CD62P) and measured using flow cytometry. Results Here we confirm NO reduces platelet activation. However, in the presence of oxyhemoglobin (Hb) NO no longer reduces platelet activation. MetHb, which does not rapidly scavenge NO does not affect platelet activation reduction by NO. In our research we see similar trends in decreased platelet activation with increasing concentrations of nitrite in the presences on RBCs. However our results are not as sensitive to nitrite concentrations as previously published data. In addition we see trends of decreasing platelet activation with increasing nitrite concentration in the presence of Hb. Conclusions Our results verify the effect of NO on platelet activation. They also show a trend which agrees with previously published data showing a decrease in platelet activation in the presence of nitrite and red blood cells. Additionally we see the same trend in the presence of nitrite and cell free Hb. Disclosure Supported by NIH Grants HL058091 and HL098032.
The Mankote Mangrove: Microcosm of the Caribbean

Wetlands in Latin America and the Caribbean have sustained human activity since pre-Columbian times (Davidson and Gauthier 1993, Lugo 2002, Smardon 2006), but it is only recently that wetland protection policies have been addressed (Davidson and Gauthier 1993, Castro 1995). In 1985 the International Waterfowl and Wetlands Research Bureau (IWRB), with support from other agencies, coordinated the first comprehensive survey of Neotropical wetlands of international importance. This work resulted in the publication of the Directory of Neotropical Wetlands (Scott and Carbonell 1986), which lists and describes wetlands in each Latin American and Caribbean country. This directory was used as a baseline for identifying wetlands in Central America, with emphasis on those wetlands of importance to humans as well as high biological diversity.
Some Reflections on Philosophy of Science

During the last 50 years or so, European and American universities (and those in Japan) have introduced two new disciplines that did not exist before. Granted, however, there have always been academicians interested in these fields: the history and philosophy of science. In some universities and colleges the history of science was sharply distinguished from the so-called philosophy of science, and today almost all academic institutions in this country and abroad offer courses in both subjects. These courses either are organized in autonomous, independent departments or are very often attached to existing scientific or humanistic departments.
Solutions for Model Boltzmann Equations Proposed by Ziff

In recent issues of Physical Review Letters and Physical Review, Robert M. Ziff presented a family of kernels P(y,z;x) where by the kinetic equation forms a variety of Boltzmann-type models. We establish that if F 0 (x) is a continuous bounded function on [0,∞) with and if P is a kernel in the family proposed by Ziff, then there is a solution in the space BC[0,∞) for the associated model with F(x,0) = F 0 (x). The solution exists for all t ≥ 0.
Coenzyme content of purified alanine racemase from Pseudomonas

Abstract Alanine racemase, induced in Pseudomonas putida by growth on DL -alanine, was purified about 1000-fold to homogeneity. The purified enzyme contains approximately one molar equivalent of pyridoxal phosphate by absorbance, fluorescence, and microbiological assay. No evidence for the presence of a flavin coenzyme was found.
Modulation of appetitive motivation by prefrontal cortical mu-opioid receptors is dependent upon local dopamine D1 receptor signaling.

Abstract Opioid neurotransmission has been implicated in psychiatric disorders featuring impaired control over appetitive motivation, such as addiction and binge-eating disorder. We have previously shown that infusions of the μ-opioid receptor (μOR) agonist DAMGO into the ventromedial prefrontal cortex (vmPFC) induced hyperphagia, increased motor activity, and augmented sucrose-reinforced responding in the task progressive ratio (PR) task, which assesses the motivational value of an incentive. These effects were not reproduced by intra-PFC infusion of a variety of dopamine (DA) agonists and antagonists, suggesting that manipulation of intra-PFC DA systems alone is not sufficient to reproduce μOR-like effects. Nevertheless, this does not rule out interactions between PFC DA and μ-opioid systems. Here we used intra-vmPFC drug cocktails containing DAMGO and SCH 23390 (a DA D1 receptor antagonist) to determine whether increases in appetitive motivation and motor activity elicited by intra-vmPFC μOR stimulation require intact signaling through vmPFC D1 receptors. Blockade of D1 receptors with SCH 23390 attenuated the enhancement of PR breakpoint, and increases in exploratory-like behavior and feeding initiation elicited by intra-vmPFC μOR stimulation. These results establish that intra-vmPFC D1 signaling is required for the expression of behavioral effects evoked by μOR stimulation within the PFC, and further suggest that D1 tone plays an enabling or permissive role in the expression of μOR –elicited effects. Simultaneous targeting of both μ-opioid and D1 systems may represent a more efficacious treatment strategy (compared to μOR blockade alone) for psychiatric disorders characterized by dysregulated appetitive motivation.
Moving Beyond a One-Size-Fits-All View of Positive Affect in Health Research:

Although the literature that connects positive affect (PA) to health has exploded over the last 20 years, the approach to studying this topic has remained simplistic. Specifically, researchers over...
Lung-Enriched Mutations in the p53 Tumor Suppressor: A Paradigm for Tissue-Specific Gain of Oncogenic Function.

Lung cancer, the leading cause of cancer-related mortality in the US, occurs primarily due to prolonged exposure to an array of carcinogenic compounds in cigarette smoke. These carcinogens create bulky DNA adducts, inducing alterations including missense mutations in the tumor suppressor gene TP53. TP53 is the most commonly mutated gene in many human cancers, and a specific set of these variants are enriched in lung cancer (at amino acid residues V157, R158, and A159). This perspective postulates that lung-enriched mutations can be explained, in part, by biological selection for oncogenic gain-of-function (GOF) mutant p53 alleles at V157, R158, and A159. This hypothesis explaining tissue-specific TP53 mutations, is further supported by mouse model studies of the canonical TP53 hotspots showing that tumor spectra and GOF activities are altered with mutation type. Therefore, while smoking-related lung cancer unequivocally arises due to the mutagenic environment induced by tobacco carcinogens, this perspective provides a rationale for the preferential selection of lung-enriched V157, R158, and A159 mutant p53.
Altered A-type potassium channel function in the nucleus tractus solitarii in acquired temporal lobe epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death in epilepsy, and dysfunction in central autonomic neurons may play a role. In a mouse model of acquired epilepsy, GABAergic n...
Does a history of childhood abuse moderate the association between symptoms of posttraumatic stress disorder and borderline personality disorder in survivors of intimate partner violence

Objective This study examined whether a history of childhood abuse (CA) strengthened the association between borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) in the aftermath of intimate partner violence (IPV). This hypothesis arises from clinical literature but has not been examined empirically. We predicted that a history of CA would enhance associations between BPD features and PTSD symptoms. Method Dimensional assessment of both PTSD and BPD was made in a sample of 211 women who sought mental health services following IPV. Two analyses were conducted using clinician-assessed DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) PTSD symptoms: (a) total score and (b) symptom clusters. Results Using path analysis, results indicated significant associations between BPD features and PTSD symptoms, but no significant interaction between BPD and CA in either analysis. Conclusions Results are discussed given current understanding of comorbidities involving PTSD, with particular attention to potential implications for clinical practice. Areas for future research are proposed.
Method Comparison for Detection and Measurement of Rotator Cuff Tears: Office-based Bedside Ultrasonography by a Single Physiatrist versus Imaging Center-based Ultrasonography by Two Expert Musculoskeletal Radiologists.

INTRODUCTION There is increasing interest among physiatrists in using bedside ultrasonography to assess rotator cuff tears. OBJECTIVE To conduct a method comparison between ultrasonography performed by a single physiatrist at bedside and two validated expert musculoskeletal radiologists at an imaging center. DESIGN Prospective, blinded comparison study. SETTING Academic outpatient clinic and imaging center. PATIENTS Seventy-two unilateral shoulders were scanned. Inclusion criteria included pain or weakness with rotator cuff testing and compliance with repeat ultrasonography. INTERVENTIONS Ultrasonography performed by the physiatrist was done at bedside during the patient's clinical visit, while the radiologists' scan was performed afterwards in an imaging center. The radiologists trained the physiatrist who was performing the scans. MAIN OUTCOME MEASUREMENTS The primary outcome was integrity of the rotator cuff (intact, partial tear, full tear). When a posterior cuff (supraspinatus, infraspinatus, teres minor) tear was detected, measurements of length, width, and distance from the biceps tendon were taken. RESULTS With use of the radiologists' scan as a criterion standard, bedside ultrasonography performed by the physiatrist for detection of posterior cuff tears had a percent perfect agreement of 72.2% for categorization as no tear, partial tear, or full tear. When evaluating dichotomously for presence of a full tear, sensitivity was 82.1% and specificity was 93.9%. Seven (18%) full-thickness tears were missed, and all were essentially small (<15 mm). When physiatrist and radiologist measurements were compared, the mean ± standard deviation (SD) difference in length was 3.4 ± 4.7 mm, width was 2.7 ± 6.7 mm, and distance to the biceps tendon was -0.8 ± 7.5 mm. CONCLUSIONS Office-based bedside ultrasonography is a reasonable modality to rule out medium/large full-thickness posterior cuff tears. However, physicians should be aware that a percentage of small full-thickness tears can be missed. Further imaging should be considered in suspected partial tears and full tears that may be appropriate for surgical repair.
Multi-omics Data Integration for Identifying Osteoporosis Biomarkers and Their Biological Interaction and Causal Mechanisms.

Summary Osteoporosis is characterized by low bone mineral density (BMD). The advancement of high-throughput technologies and integrative approaches provided an opportunity for deciphering the mechanisms underlying osteoporosis. Here, we generated genomic, transcriptomic, methylomic, and metabolomic datasets from 119 subjects with high (n = 61) and low (n = 58) BMDs. By adopting sparse multiple discriminative canonical correlation analysis, we identified an optimal multi-omics biomarker panel with 74 differentially expressed genes (DEGs), 75 differentially methylated CpG sites (DMCs), and 23 differential metabolic products (DMPs). By linking genetic data, we identified 199 targeted BMD-associated expression/methylation/metabolite quantitative trait loci (eQTLs/meQTLs/metaQTLs). The reconstructed networks/pathways showed extensive biomarker interactions, and a substantial proportion of these biomarkers were enriched in RANK/RANKL, MAPK/TGF-β, and WNT/β-catenin pathways and G-protein-coupled receptor, GTP-binding/GTPase, telomere/mitochondrial activities that are essential for bone metabolism. Five biomarkers (FADS2, ADRA2A, FMN1, RABL2A, SPRY1) revealed causal effects on BMD variation. Our study provided an innovative framework and insights into the pathogenesis of osteoporosis.
Congenital Neurologic Disease

Congenital neurologic diseases that affect the larynx include a broad range of disorders. Children with laryngeal anomalies typically present with airway and/or swallowing difficulties in infancy and early childhood and then voice complaints in later childhood. The two most common laryngeal anomalies in infants both have a neurologic basis, namely, laryngomalacia and vocal fold motion disorders. Management of these disorders depends on severity and underlying etiology. Of utmost importance in these patients is establishing a safe airway.
Language dominance predicts cognate effects and metalinguistic awareness in preschool bilinguals

The current work investigates whether language dominance predicts transfer of skills across cognitive-linguistic levels from the native language (Spanish) to the second language (English) in biling...
The Evolution of the Tang Political Elite and its Marriage Network

How did the Tang political elite evolve between the seventh and ninth centuries? Using network analysis and a large prosopographic database, this article approaches this question from four perspectives: the marriage network of political elites, the backgrounds of chief ministers, the composition of the capital elite during three time slices, and the makeup of the provincial elite. Despite important continuities in the elite marriage network's basic structure, there were also significant discontinuities. Between the seventh and eighth centuries, Luoyang emerged as a secondary political center, and Luoyang-based families—including so-called “marriage-ban” clans—acquired a renewed significance, partly at the expense of old southern clans, whose political significance declined over the course of the dynasty. In addition, the political divide between capital and provinces grew over time, culminating in the ninth century with capital-based men occupying nearly all significant provincial posts and provincials serving only locally and in second-tier offices.
Diagnostic yield of repeat evaluation for asymptomatic microscopic hematuria after negative initial workup.

Abstract Purpose The American Urological Association guideline for asymptomatic microhematuria recommends in patients with a negative initial workup, repeat workup should be considered for those with persistent/recurrent microhematuria. However, there is little data on the yield of repeat evaluation. Our hypothesis was that repeat workup yields a low detection rate of urologic malignancy. Materials and Methods We retrospectively reviewed all patients at our institution who underwent microhematuria workup with cystoscopy and upper tract imaging from May 2010 to June 2016. Microhematuria was defined as ≥3 RBCs/HPF on a properly collected specimen in the absence of a benign cause. Demographics, age, smoking history, history of radiation, and findings on repeat cystoscopy and imaging were collected. Our primary endpoint was a new diagnosis of urologic malignancy. Results Our initial cohort included 1,332 patients, of whom 21 were diagnosed with urothelial carcinoma and 7 with suspicious renal masses on initial workup. A total of 637 patients with negative initial workup had persistent/recurrent microhematuria. Repeat cystoscopy was performed in 161 (25%) patients at a median of 39 months, and repeat upper tract imaging was performed in 317 (50%) patients at a median of 39 months. Overall, repeat cystoscopy revealed new bladder cancer in 2 (1.2%) patients and repeat imaging revealed new suspicious renal mass in 4 (1.3%) patients. Conclusions We observed a low number of newly diagnosed malignancies among patients with persistent/recurrent asymptomatic microhematuria who had a prior negative workup. Additional research is required to determine the utility of a repeat AMH workup.
The legacy of natural disasters: The intergenerational impact of 100 years of disasters in Latin America

Abstract Disasters can have long lasting effects, but understanding the breadth, variety and longevity of their effects can be challenging. This paper examines the long term effects and subsequent intergenerational transmission of exposure in childhood to the natural disasters that have occurred in Latin America in the last 100 years. The identification strategy exploits the exogenous variation in geographic location, timing and exposure of different birth cohorts to natural disasters. This study measures individuals' exposure to each disaster based on their geographic location at birth to avoid any bias in the estimates due to possible selective migration caused by each disaster. The main results indicate that children in utero and young children are the most vulnerable to natural disasters and suffer the most long-lasting negative effects. These effects include less human capital accumulation, worse health and fewer assets when they are adults. Effects are found to have a non-linear relationship with the level of development of each country. Furthermore, the results provide evidence of the intergenerational transmission of shocks, indicating that children born to mothers who had been exposed to natural disasters also have less education and increased child labor.
Multi Voltage High Performance Bidirectional Buffer in a Low Voltage CMOS process

The fundamental challenge in designing high performance input/output circuits stems from interface voltages not scaling at the same rate as the microprocessor core voltages. This typically translates to designing multi-voltage interface circuits with single lower voltage gate oxide components to reduce mask cost. While numerous topologies exist to overcome the associated gate oxide reliability challenges, they invariably run into bottlenecks when targeted for high performance. In this paper, a multi-voltage bidirectional buffer built using just 1.8V transistors in a 65nm process is presented. Proposed solution includes two novel schemes consisting of (1) a replica driver based pre-driver compensation scheme for output buffer, and (2) a new reduced crowbar contention based low skew input buffer. These circuits in conjunction not only help achieve 200MHz operational frequency, but also do so with competitive area while eliminating gate oxide and channel hot carrier associated reliability constraints.
Antibody-induced glomerulonephritis is amplified by RTEC-intrinsic IL-17 signaling and restrained by IL-17-mediated induction of the endoribonuclease Regnase-1 (Zc3h12a)

Antibody-mediated glomerulonephritis (AGN) is a clinical manifestation of many autoimmune kidney diseases for which few effective treatments exist. Chronic inflammatory circuits in renal glomerular and tubular cells lead to tissue damage in AGN. These cells are targeted by the cytokine IL-17, which has recently been shown to be a central driver of the pathogenesis of AGN. However, surprisingly little is known about the regulation of pathogenic IL-17 signaling in the kidney. Here, using a well characterized mouse model of AGN, we show that IL-17 signaling in renal tubular epithelial cells (RTECs) is necessary for AGN development. We also show that Regnase-1, an RNA binding protein with endoribonuclease activity, is a negative regulator of IL-17 signaling in RTECs. Accordingly, mice with a selective Regnase-1 deficiency in RTECs exhibited exacerbated kidney dysfunction in AGN. Mechanistically, Regnase-1 inhibits IL-17-driven expression of the transcription factor IκBζ and consequently its downstream gene targets including Il6 and Lcn2. Moreover, deletion of Regnase-1 in human RTECs reduced inflammatory gene expression in an IκBζ-dependent manner. Overall, these data identify an IL-17-driven inflammatory circuit in RTECs during AGN that is constrained by Regnase-1.