cssi/SciSciGPT-SciSciNet huggingface dataset:
Effect of age on diastolic left ventricular filling at rest and during inotropic stimulation and acute systemic hypertension: Experimental studies in conscious beagles

"Pharmacologic" stress testing with inotropic stimulation is useful in the detection of coronary artery disease when ventricular dysfunction is provoked. However, abnormal diastolic filling may be masked or mimicked because of the influence of aging, heart rate, and loading conditions. We evaluated age effects on left ventricular filling at rest in young (n = 5) and old (n = 6) purebred beagles that were free of occlusive coronary disease and left ventricular hypertrophy, and we also evaluated age-related differences in left ventricular filling velocities in response to dobutamine and phenylephrine. Pulsed Doppler echocardiography of left ventricular filling velocities was performed at baseline and then after the administration of dobutamine (10 to 20 micrograms/kg/min) infusion. Repeat baseline recordings were obtained and then phenylephrine was administered intravenously in doses of 5 to 25 micrograms/kg/min until systolic arterial pressure increased by at least 30 mm Hg above baseline. At baseline, Doppler echocardiography revealed that there were no significant differences in the early (E) velocity or velocity time interval (VTI), and atrial (A) velocity or the A/E velocity ratio between the young and old groups. However, the A VTI and the A/(A + E) VTI ratio were significantly increased in the old group. With dobutamine administration, the E velocity did not significantly increase from baseline in either group. The E VTI, A velocity and A VTI increased significantly in both groups, but the increases were not different between groups. With phenylephrine infusion there was a significant decrease in the E VTI in the old group but neither the A/E velocity or the A/(A + E) VTI ratio significantly changed from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
Robotic Pets in Human Lives: Implications for the Human–Animal Bond and for Human Relationships with Personified Technologies

Robotic “pets” are being marketed as social companions and are used in the emerging field of robot-assisted activities, including robot-assisted therapy (RAA). However, the limits to and potential of robotic analogues of living animals as social and therapeutic partners remain unclear. Do children and adults view robotic pets as “animal-like,”“machine-like,” or some combination of both? How do social behaviors differ toward a robotic versus living dog? To address these issues, we synthesized data from three studies of the robotic dog AIBO: (1) a content analysis of 6,438 Internet postings by 182 adult AIBO owners; (2) observations and interviews with 80 preschoolers during play periods with AIBO and with a stuffed dog; and (3) observations and interviews with 72 children, aged 7–15 years, who played with AIBO and a living dog. Overall, the studies revealed that “hybrid” cognitions and behaviors about AIBO emerged: the robotic dog was treated as a technological artifact that also embodied attributes of living animals, such as having mental states, being a social other, and having moral standing (although this latter finding remained difficult to interpret). Implications for use of robotic pets as companions and in interventions or therapy are explored.
Destination buffering for low-bandwidth audio transmissions using redundancy-based error control

Digital audio is becoming increasingly prevalent with the advent of software for Internet telephony and real-time audio playback for World Wide Web browsers. Since audio quality depends on timely delivery of the packet stream, protocol mechanisms must address the control of delays and packet losses in an integrated fashion. Two critical mechanisms for high-quality audio delivery are the receiver buffering strategy and error control. Buffering at the audio receiver is required for continuous playback in the presence of network delay variations (jitter), and a number of algorithms have been proposed. Timely recovery of packet loss protects audio quality against network errors. Recent work has suggested the effectiveness of an approach that sends multiple copies of the audio data in consecutive packets so that small burst losses in the network are overcome. Packet-level traces of Internet audioconferencing software were collected over a network path including LANs and a 28.8 kbits/s dial-up connection. Using these traces in simulations, receiver buffering strategies for controlling packet jitter and for supporting redundancy-based error control are examined. The study determines that jitter control algorithms will not generally provide adequate buffering when the requirements of error control are included. This observation leads to a proposed modification for one popular jitter control algorithm, and the performance trade-offs are explored.
Direct and EM-based map sequence estimation with unknown time-varying channels

We address sequence estimation when the intersymbol interference (ISI) communication channel is unknown and time varying. We employ a maximum a posteriori (MAP) approach, in which the unknown channel parameters are assigned a distribution and integrated out. For several channel models of interest we describe both the exact MAP estimator and Viterbi algorithm based implementations. We also present EM algorithms for solving these MAP sequence estimation problems, and we contrast these EM solutions with direct MAP algorithms.
Successful collaborative model for trauma skills training of surgical and emergency medicine residents in a laboratory setting.

Objectives To determine whether interdepartmental educational and technical resources could be combined to successfully train surgery and emergency medicine residents in common diagnostic and therapeutic trauma skills outside the traditional hospital setting. Design Curriculum improvement survey. Setting Surgical Skills Laboratory, Temple University School of Medicine, Philadelphia, Pennsylvania. Participants A total of 35 surgery residents (PGY 1 to 5) and 26 emergency medicine residents (PGY 1 to 3). Methods Emergency medicine attendings used human volunteers to train surgery residents in Focused Assessment with Sonography in Trauma (FAST). Trauma surgery attendings used a porcine model to teach emergency medicine residents tracheostomy, peripheral venous cutdown, diagnostic peritoneal lavage, tube thoracostomy, and bilateral thoracotomy. Upon completion of the courses, all residents were surveyed using a 5-point Likert scale to assess this teaching model. Results The percentage of residents reporting an improvement in knowledge levels after the course increased significantly (p Conclusions Interdepartmental collaboration between the Department of Surgery and Department of Emergency Medicine offered a unique training relationship that was a positive educational experience for all residents.
Differences between Gay and Lesbian Cohabiting Couples

Partners from gay and lesbian couples were compared on variables from four domains relevant to close relationships (individual differences, relationship beliefs/attitudes, conflict resolution, and social support); change in relationship quality over time; relationship dissolution; and the correlates of relationship satisfaction and relationship dissolution. Participants completed mailed surveys at least once over 14 assessments, n= 80 gay couples and 53 lesbian couples at the first time assessment with additional couples recruited at later assessments. Although few type-of-couple differences were significant, partners from lesbian couples reported more positive beliefs/attitudes about relationships, as well as more positive relationship satisfaction.
Chronology of neurological manifestations of prenatally diagnosed open neural tube defects

Objective: To evaluate the incidence and chronology of sonographic markers of neurological compromise in prenatally diagnosed neural tube defects. Methods: We reviewed our ultrasound database from 1988 to 1999 to identify all cases of prenatally diagnosed neural tube defects. All patients received an initial detailed targeted ultrasound evaluation with subsequent evaluations every 4-6 weeks. Cases involving multiple congenital anomalies, aneuploidy, or inadequate follow-up were excluded. Specific ultrasound markers assessed included the presence of ventriculomegaly (> 10 mm) and clubfoot. Results: Forty-seven cases of neural tube defects were identified over the study interval. After exclusions, 42 cases were available for evaluation. The overall incidence of ventriculomegaly and clubfoot in the study cohort was 86% and 38%, respectively. In the 33 patients with initial ultrasound examination performed at < 24 weeks' gestation, 76% (25/33) had evidence of ventriculomegaly and 30% (10/33) and clubfoot. Onl...
Extraction and inhibition of enzymatic activity of botulinum neurotoxins/A1, /A2, and /A3 by a panel of monoclonal anti-BoNT/A antibodies

Botulinum neurotoxins (BoNTs) are extremely potent toxins that are capable of causing death or respiratory failure leading to long-term intensive care. Treatment includes serotype-specific antitoxins, which must be administered early in the course of the intoxication. Rapidly determining human exposure to BoNT is an important public health goal. In previous work, our laboratory focused on developing Endopep-MS, a mass spectrometry-based endopeptidase method for detecting and differentiating BoNT/A–G serotypes in buffer and BoNT/A, /B, /E, and /F in clinical samples. We have previously reported the effectiveness of antibody-capture to purify and concentrate BoNTs from complex matrices, such as clinical samples. Because some antibodies inhibit or neutralize the activity of BoNT, the choice of antibody with which to extract the toxin is critical. In this work, we evaluated a panel of 16 anti-BoNT/A monoclonal antibodies (mAbs) for their ability to inhibit the in vitro activity of BoNT/A1, /A2, and /A3 complex as well as the recombinant LC of A1. We also evaluated the same antibody panel for the ability to extract BoNT/A1, /A2, and /A3. Among the mAbs, there were significant differences in extraction efficiency, ability to extract BoNT/A subtypes, and inhibitory effect on BoNT catalytic activity. The mAbs binding the C-terminal portion of the BoNT/A heavy chain had optimal properties for use in the Endopep-MS assay.
Structures of two novel crystal forms of Naja naja naja phospholipase A2 lacking Ca2+ reveal trimeric packing.

Abstract Three crystal forms of Naja naja naja phospholipase A 2 were discovered through random crystallization screening, including two heretofore uncharacterized forms. The crystallization conditions for both of these novel crystal forms are Ca 2+ -free whereas previously reported conditions include Ca 2+ . One of the new crystal forms has a cubic lattice in the space group P 2 1 3 ( a = b = c =69.24 A), the other has an orthorhombic lattice in the space group P 2 1 2 1 2 1 ( a =67.22 A, b =73.48 A, c =87.52 A) and a previously characterized crystal belong to the tetragonal space group P 4 3 2 1 2 ( a = b =88.6 A, c =107.4 A). The structure from the cubic crystal form has been determined to 1.8 A and refined to an R -factor of 17% while the structure from the orthorhombic form has been determined to 2.65 A and has been refined to an R -factor of 21%. The determination of the cubic structure extends the resolution to which structures of this molecule have been determined from 2.3 A to 1.8 A. The two newly determined structures, in combination with the previously determined structure, generate an informative structural ensemble from which structural changes due to Ca 2+ , which is required for catalysis, and the effect of crystal contacts on side-chain conformations and oligomeric association can be inferred. Both of the newly determined structures reveal a trimeric oligomer as observed in the tetragonal structure; this appears to be a unique feature of the Naja naja naja enzyme.
Numerical calculation of diffraction coefficients of generic conducting and dielectric wedges using FDTD

Classical theories such as the uniform geometrical theory of diffraction (UTD) utilize analytical expressions for diffraction coefficient for canonical problems such as the infinite perfectly conducting wedge. We present a numerical approach to this problem using the finite-difference time-domain (FDTD) method. We present results for the diffraction coefficient of the two-dimensional (2-D) infinite perfect electrical conductor (PEC) wedge, the 2-D infinite lossless dielectric wedge, and the 2-D infinite lossy dielectric wedge for incident TM and TE polarization and a 90/spl deg/ wedge angle. We compare our FDTD results in the far-field region for the infinite PEC wedge to the well-known analytical solutions obtained using the UTD. There is very good agreement between the FDTD and UTD results. The power of this approach using FDTD goes well beyond the simple problems dealt with in this paper. It can, in principle, be extended to calculate the diffraction coefficients for a variety of shape and material discontinuities, even in three dimensions.
Sensitivity and specificity of glycated hemoglobin as a diagnostic test for diabetes and prediabetes in Arabs.

Context: Glycated hemoglobin (A1C) has been recommended by the American Diabetes Association for the diagnosis of diabetes and prediabetes. The diagnostic utility of A1C has not been evaluated in Arabs, a population at increased risk for developing diabetes. Objective: Our objective was to examine the sensitivity and specificity of A1C for the diagnosis of diabetes and prediabetes in Arabs. Design & Setting: In this cross-sectional study, glucose tolerance was classified by the American Diabetes Association diagnostic criteria specified for A1C, fasting plasma glucose, and 75-g oral glucose tolerance test. Participants: A population-based representative sample of 482 randomly selected adult Arabs without known diabetes was studied. Main Outcome Measures: Sensitivity, specificity, and area under the receiver operating characteristic curve of A1C diagnostic cutpoints for diabetes and prediabetes were calculated. κ Coefficients were used to test for agreement between A1C categorization and glucose-based diag...
Efficacy of a Symptom-Triggered Practice Guideline for Managing Alcohol Withdrawal Syndrome in an Academic Medical Center

This paper describes our experience with an evidence-based Adult Alcohol Withdrawal Syndrome Practice Guideline in an academic medical center. Combined data from two pilot studies demonstrate the efficacy of this approach for hospitalized patients. One hundred-six guideline-managed patients (pilot) were compared with 82 non-guideline managed patients (control). Pilot patients received significantly less benzodiazepine and significantly more clonidine. Significantly more pilot (34%) than control patients (11%) required no drug therapy to manage or prevent AWS symptoms. Adverse events were similar between groups. Control patients required significantly more sitters. These data suggest that hospitalized patients at risk for AWS can be effectively managed with a standardized, symptom-triggered approach.
Cancer compass: examining personal health record usage among breast cancer survivors

As personal health records (PHRs) become more common, they have the potential to become a critical tool for breast cancer survivors. Our research has identified a hierarchy of needs that could be addressed, in part, through PHR capabilities. While breast cancer survivors are expected to receive many benefits from using PHRs, little is known about how people will use and adopt this technology. In order to gain a better understanding of the potential uses and pitfalls for PHRs, we will give 80 breast cancer survivors mobile PHR systems and monitor their usage over the course of two months. We will investigate the motivational factors that lead to PHR adoption and the correlations between system usage, self-efficacy and locus of control. Our goal is to understand if PHRs have the potential to successfully engage breast cancer survivors with their daily health practices.
Prolonged dopamine administration and thyroid hormone economy in normal and critically ill subjects.

A 48-h dopamine (DA) infusion (5-7.5 microgram/kg . min) given to six healthy euthyroid males resulted in a suppression of thyroidal iodine release and serum TSH by 44 +/- 3% (P less than 0.01), serum T3 by 9 +/- 2% (P less than 0.01), and serum T4 by 5 +/- 1% (P less than 0.05) below baseline levels, without a significant change in serum rT3 levels. In critically ill patients receiving DA (2-21 microgram/kg . min) for treatment of shock, serum TSH values and T4 production rates were decreased 60% and 56%, respectively, below the respective levels observed in non-DA-treated patients (P less than 0.01). Serial serum samples collected before and during DA therapy revealed a decrease of 52% in TSH (P less than 0.005) and 30% in T4 (P less than 0.05). The finding of a normal serum TSH value during DA theray in a critically ill patient with primary hypothyroidism emphasized the inhibitory potential of DA on TSH secretion. These findings indicate that the prolonged administration of pharmcological doses of DA significantly reduced serum TSH levels and thyroid hormone secretion in normal and critically ill patients, most likely by a direct inhibition of pituitary TSH with a secondary effect on thyroid gland secretion. Therefore, DA therapy probably prolongs and aggravates the low T4 state in critical illness.
Visualized related topics (VRT) system for health information retrieval

To help bridge the gap between consumer user's vocabulary and controlled vocabulary used to index health information, in this demo we implemented a Visualized Related Topics (VRT) browser system. The VRT was integrated into the "MeshMed" [2] system to support health information retrieval. The key technology behind the VRT browser is to select MeSH terms, which represent the related topics or subjects, from the top relevant documents. We rank these MeSH terms using the traditional Term Frequency-Inverse Document Frequency (TF-IDF) algorithm. The VRT browser displays a graphic representation of these MeSH terms by creating a visual where the selected MeSH terms stem from the centered user query. The design goal is provide users an overview of the key topics of the search results. In addition, VRT browser may also help users form better queries. Using the VRT browser we will be studying how to effectively assist in consumer users with their health information seeking.
The Persuasive Effects of Metaphor: A Meta-Analysis

Empirical investigations of metaphor's persuasive effects have produced mixed results. In an effort to integrate the literature, we present a review and meta-analytic summary of existing studies. Six explanations for the potential suasory advantage of metaphor over literal language were reviewed: (a) pleasure or relief, (b) communicator credibility, (c) reduced counterarguments, (d) resource-matching, (e) stimulated elaboration, and (f) superior organization. Next, a meta-analysis was conducted and the impact of seven moderator variables was tested. The overall effect for the metaphor-literal comparison for attitude change was r = .07, which supported the claim that metaphors enhance persuasion. The effect rose to r = .42 under optimal conditions, when a single, nonextended metaphor was novel, had a familiar target, and was used early in a message. Metaphor appeared to exert a small effect on perceptions of source dynamism (r = .06), but showed no demonstrable impact on competence (r =−.01) or character (r =−.02). Of the six theories considered, the superior organization explanation of metaphor's persuasive impact was most supported by the results.
Folate Deficiency in Rats Fed Diets Containing Free Amino Acids or Intact Proteins

Development of folate deficiency (FD) was evaluated in weanling rats fed diets containing mixtures of free amino acids or of vitamin-free casein and gelatin as sources of dietary nitrogen. FD could be produced in 21 d with amino acid diets that promoted maximum growth rate, were completely devoid of folate and contained 1% succinylsulfathiazole. Growth retardation and blood dyscrasia associated with FD could not be demonstrated in rats fed diets containing casein and gelatin as nitrogen sources because the vitamin-free casein contained low but measurable levels of folate. The most effective protocol to produce experimental FD in rats is to feed a folate-free diet that otherwise supports maximum growth in young animals. Additional modifications such as use of methotrexate or amino acid-imbalanced or protein-deficient diets are unnecessary.
Layer-Structured Copper Antimony Chalcogenides (CuSbSexS2–x): Stable Electrode Materials for Supercapacitors

The ever-growing need for energy generation and storage applications demands development of materials with high performance and long-term stability. A sizable number of chalcogenide-based materials have been investigated for supercapacitor applications. Layer-structured chalcogenides are advantageous in terms of providing large surface area with good ionic conductivity and ability to host a variety of atoms or ions between the layers. CuSbS2 is a ternary layered chalcogenide material that is composed of earth abundant and less-toxic elements. For the first time, we have developed a simple colloidal method for the synthesis of CuSbSexS2–x mesocrystals over the whole composition range (0 ≤ x ≤ 2) by substitution of S with Se. Our approach yields mesocrystals with belt-like morphology for all the compositions. X-ray diffraction results show that substitution of sulfur with selenium in CuSbS2 enables tuning the width of the interlayer gap between the layers. To investigate the suitability of CuSbSexS2–x mesoc...
Arrival times of P waves and upper mantle structure

ABSTRACT Residuals of arrival times of P waves, as given in the International Seismological Summary for Kiruna, Sweden, Reykjavik, Iceland, and Scoresbysund, Greenland, were studied in order to detect upper mantle anomalies. The Kiruna arrivals were systematically too early, with a mean residual of −1.4 seconds, while the mean Reykjavik residual was +1.3 seconds. The difference in mean residual was 2.7 seconds with a standard error of about 0.5 second. The mean residual at Scoresbysund was −0.4 second. It is assumed that there is a depth D below which the mantle is homogeneous. The difference in mean residuals at the stations is assumed to be caused by different wave velocities at depths less than D in the vicinities of the stations. If it is assumed that the P -wave velocity in the upper mantle is constant down to a depth D below each station, this depth can be computed. This velocity is known from other data to be 8.36 km/sec below Kiruna and 7.4 km./sec. below Reykjavik. If only earthquakes at distances from 20° to 39° were used, D is determined to be 246 ± 36 km. (standard error). Earthquakes at distances 40° to 59° give D = 177 ± 25 km., at distances 60° to 79° give D = 234 ± 14 km., and at distances 80° to 99° give D = 281 ± 20 km. The most probable value of D is thus about 240 km. below the earth9s surface, with a standard error of about 40 km. In the vicinity of Scoresbysund the upper mantle velocity is found to be about 8.0 km./sec., using the same assumption.
Two Photon Intravital Microscopy Reveals CD4+ T Cells Making Cognate Interactions With Tissue Dendritic Cells In Skin Graft-Versus-Host-Disease

Graft-versus-host disease (GVHD) limits the broader application of allogeneic hematopoietic stem cell transplantation. In prior studies we defined roles for both host and donor-derived antigen presenting cells (APCs) in the activation of alloreactive donor T cells and promotion of GVHD. While initial T cell activation in GVHD occurs predominantly in secondary lymphoid organs (SLO), we have consistently observed MHCII+ donor-derived tissue APCs (t-APCs), including tissue dendritic cells (t-DCs) in histopathologic GVHD lesions, frequently adjacent to infiltrating T cells. We hypothesize that productive interactions occur between donor APCs and T cells in situ in GVHD target tissues, which propagate disease locally. We could not use knockout or APC depletion approaches to study T cell: t-APCs interactions as they impact APCs systemically and might therefore affect T cell stimulation in SLO. We therefore utilized two-photon intravital microscopy to analyze interactions between fluorescent donor CD4+ T cells and t-DCs in skin. 129 (H-2b) hosts were irradiated and reconstituted with B6 (H-2b) CD11c-YFP transgenic (Tg) Bone Marrow (BM) with B6 RFP Tg CD4 cells and nonfluorescent B6 CD8 cells. We imaged ear skin in GVHD mice 4 weeks later. In general CD4 cells co-localized with DCs. We observed CD4+ T cells that were highly motile and only in transient contact with DCs and others that made stable contact with DCs. To determine how much TCR: MHCII interactions drive sustained CD4+ T cell: DC interactions and arrest CD4+ T cell motility, mice were imaged and then injected with an MHCII blocking antibody (Ab; Y3P) with continued imaging of the same regions. After injection, T cell mean speed significantly increased and the proportion of T cells in stable contact with DCs decreased, indicating that transient disruption of TCR: MHCII is sufficient to restore motility to some T cells. In a second approach to assess the specificity of CD4+ T cell: t-DC interactions we transplanted 129 mice with B6 RFP+ CD4 cells, nonfluorescent CD8 cells and a mix of CD11c-YFP MHCII-/- and RFP wt BM or a mix of CD11c-YFP wt and RFP Tg MHCII-/- BM. We are currently comparing the motility of CD4 cells that make contact with MHCII+ as compared to MHCII- DCs, with the prediction that contact times will be shorter with the latter. Our data suggest that CD4+ T cells make cognate interactions with t-DCs in skin and we hypothesize that these interactions promote GVHD locally. Because the graft-versus-leukemia effect occurs primarily in bone marrow and secondary lymphoid tissues, targeting of tissue-infiltrating APCs could represent a unique strategy to ameliorate GVHD while preserving GVL. Disclosures: No relevant conflicts of interest to declare.
Molecular biologic aspects of human prostatic carcinoma

Adenocarcinoma of the prostate is the most common noncutaneous malignancy in American men, yet relatively little is known about the molecular mechanisms involved in its initiation and progression. This review surveys the current state of knowledge of selected molecular biological aspects of human prostate cancer. It focuses on four classes of genes implicated in the growth control and cellular differentiation of human prostatic carcinoma: tumor suppressor genes, oncogenes, growth factor genes, and growth factor receptor genes. The relation of changes in structure or expression or both of these genes to pathologic or clinical endpoints is discussed.
Structure and Management of an Engineering Senior Design Course

The design of products and processes is an important area in engineering. Students in engineering schools learn fundamental principles in their courses but often lack an opportunity to apply these methods to real-world problems until their senior year. This article describes important elements that should be incorporated into a senior capstone design course. It includes a description of the general principles used in engineering design and a discussion of why students often have difficulty with application and revert to trial and error methods. The structure of a properly designed capstone course is dissected and its individual components are evaluated. Major components include assessing resources, identifying projects, establishing teams, understanding requirements, developing conceptual designs, creating detailed designs, building prototypes, testing performance, and final presentations. In addition to the course design, team management and effective mentoring are critical to success. This article includes suggested guidelines and tips for effective design team leadership, attention to detail, investment of time, and managing project scope. Furthermore, the importance of understanding business culture, displaying professionalism, and considerations of different types of senior projects is discussed. Through a well-designed course and proper mentoring, students will learn to apply their engineering skills and gain basic business knowledge that will prepare them for entry-level positions in industry.
Energy Conversion Methods

Most of the energy released in fission or fusion appears as kinetic energy of a few high-speed particles. As these pass through matter, they slow down by multiple collisions and impart thermal energy to the medium. This chapter discusses the means by which this energy is transferred to a cooling agent and transported to devices that convert mechanical energy into electrical energy. The principal modes by which fission energy is transferred in a reactor are conduction and convection. The radial temperature in a fuel pellet is approximately parabolic. The rate of heat transfer from fuel surface to coolant by convection is directly proportional to the temperature difference. The allowed power level of a reactor is governed by the temperatures at local “hot spots.” Coolant flow along channels extracts thermal energy and delivers it to an external circuit consisting of a heat exchanger (PWR), a steam turbine that drives an electrical generator, a steam condenser, and various pumps.
Dopamine agonist therapy induces significant recovery of HPA axis function in prolactinomas independent of tumor size: a large single center experience

Our objective was to compare prevalence and rates of recovery of hypothalamic–pituitary–adrenal axis dysfunction in prolactinoma patients before and after dopamine agonist therapy with nonfunctioning pituitary adenoma patients pre-transsphenoidal and post-transsphenoidal surgery. We retrospectively compared hypothalamic–pituitary–adrenal axis function in patients with prolactinomas naive to dopamine agonist therapy with a cohort of nonfunctioning pituitary adenoma patients matched for gender and tumor size by classification (n = 57; 30 male/27 female; 27 microadenoma/30 macroadenoma). Patients with <52 weeks follow up, previous medical therapy, surgery, or radiation therapy were excluded. At baseline, there was no difference between groups for age, mean tumor size, or prevalence of adrenal insufficiency. Recovery from baseline adrenal insufficiency was demonstrated in patients with microprolactinomas and macroprolactinomas at a 52 week follow up (p = 0.003 and p = 0.004). These rates were similar to nonfunctioning pituitary adenoma patients after surgery. We show, in a large uniform study, that adrenal insufficiency significantly recovered after dopamine agonist treatment, independent of tumor size and gender in patients with prolactinomas naive to therapy.
The Ontology of Biological and Clinical Statistics (OBCS) for standardized and reproducible statistical analysis

Statistics play a critical role in biological and clinical research. However, most reports of scientific results in the published literature make it difficult for the reader to reproduce the statistical analyses performed in achieving those results because they provide inadequate documentation of the statistical tests and algorithms applied. The Ontology of Biological and Clinical Statistics (OBCS) is put forward here as a step towards solving this problem. The terms in OBCS including ‘data collection’, ‘data transformation in statistics’, ‘data visualization’, ‘statistical data analysis’, and ‘drawing a conclusion based on data’, cover the major types of statistical processes used in basic biological research and clinical outcome studies. OBCS is aligned with the Basic Formal Ontology (BFO) and extends the Ontology of Biomedical Investigations (OBI), an OBO (Open Biological and Biomedical Ontologies) Foundry ontology supported by over 20 research communities. Currently, OBCS comprehends 878 terms, representing 20 BFO classes, 403 OBI classes, 229 OBCS specific classes, and 122 classes imported from ten other OBO ontologies. We discuss two examples illustrating how the ontology is being applied. In the first (biological) use case, we describe how OBCS was applied to represent the high throughput microarray data analysis of immunological transcriptional profiles in human subjects vaccinated with an influenza vaccine. In the second (clinical outcomes) use case, we applied OBCS to represent the processing of electronic health care data to determine the associations between hospital staffing levels and patient mortality. Our case studies were designed to show how OBCS can be used for the consistent representation of statistical analysis pipelines under two different research paradigms. Other ongoing projects using OBCS for statistical data processing are also discussed. The OBCS source code and documentation are available at: https://github.com/obcs/obcs . The Ontology of Biological and Clinical Statistics (OBCS) is a community-based open source ontology in the domain of biological and clinical statistics. OBCS is a timely ontology that represents statistics-related terms and their relations in a rigorous fashion, facilitates standard data analysis and integration, and supports reproducible biological and clinical research.
Prefabrication of the Superstructure

Prefabrication of the bridge superstructure is the most important aspect of the accelerated bridge construction (ABC) method. This chapter discusses the prefabrication of the superstructure. A list of successful projects completed in recent years in different states is presented. Other issues covered in this chapter include a wider use of the P3 system and the use of a high-friction deck surface to prevent rusting of rebars.
Apnea of Prematurity: Current Practices and Future Directions

Apnea of prematurity (AOP) is a developmental disorder affecting most infants born at less than 34 weeks’ gestational age. AOP is one of the most common diagnoses in the NICU, contributing substantially to prolonged hospitalization. Despite its frequent occurrence in premature neonates born at less than 37 weeks’ gestation, there is no common consensus on its definition, monitoring practices, and clinical relevance, leading to significant variation in practice. It is also not clear how and if repeated apneas, bradycardias, and hypoxemia are indeed detrimental to the developing neonate. This article reviews the definitions of AOP and the current standard of care for AOP, which includes positioning, positive pressure ventilation, and methylxanthine therapy. We also explore some novel therapies, as well as address controversies in initiating treatment, length of treatment, and guidelines for discharge.
Characterization and detection of a novel idaeovirus infecting blackcurrant

A novel virus was discovered in a blackcurrant accession (Ribes nigrum L.) at the USDA genebank in Oregon, USA. The genome consists of two positive-sense, single-stranded RNAs with the first encoding a 197 kDa multifunctional protein with methyl transferase, helicase and RNA-dependent RNA polymerase enzymatic motifs. The second molecule encodes two putative proteins; the 39 kDa movement and 30 kDa coat proteins. Both RNAs have conserved sequences and structures at the 5′ and 3′ termini. The genome organization, sequence and phylogenetic analyses indicate that the virus is a putative new member of the genus Idaeovirus, as it consistently groups with privet leaf blotch-associated virus and raspberry bushy dwarf virus. A duplex RT-PCR assay was developed for rapid detection of both genomic RNAs simultaneously. The work presented in this communication will assure the health status of blackcurrant plants in mother blocks, nurseries and production fields alike.
The thermodynamic basis of glucose-stimulated insulin release: a model of the core mechanism.

A model for glucose sensing by pancreatic β-cells is developed and compared with the available experimental data. The model brings together mathematical representations for the activities of the glucose sensor, glucokinase, and oxidative phosphorylation. Glucokinase produces glucose 6-phosphate (G-6-P) in an irreversible reaction that determines glycolytic flux. The primary products of glycolysis are NADH and pyruvate. The NADH is reoxidized and the reducing equivalents transferred to oxidative phosphorylation by the glycerol phosphate shuttle, and some of the pyruvate is oxidized by pyruvate dehydrogenase and enters the citric acid cycle. These reactions are irreversible and result in a glucose concentration–dependent reduction of the intramitochondrial NAD pool. This increases the electrochemical energy coupled to ATP synthesis and thereby the cellular energy state ([ATP]/[ADP][Pi]). ATP and Pi are 10–100 times greater than ADP, so the increase in energy state is primarily through decrease in ADP. The decrease in ADP is considered responsible for altering ion channel conductance and releasing insulin. Applied to the reported glucose concentration–dependent release of insulin by perifused islet preparations (Doliba et al. 2012), the model predicts that the dependence of insulin release on ADP is strongly cooperative with a threshold of about 30 μmol/L and a negative Hill coefficient near −5.5. The predicted cellular energy state, ADP, creatine phosphate/creatine ratio, and cytochrome c reduction, including their dependence on glucose concentration, are consistent with experimental data. The ability of the model to predict behavior consistent with experiment is an invaluable resource for understanding glucose sensing and planning experiments.
Impact of Climate Changes on Human Health in India

The impact of climate change has been considerably enough to threaten human health both directly and indirectly through increasing temperatures, rising sea levels, water and food supply impacts, extreme weather events like floods, droughts, earthquakes, etc., susceptible shelter and population migration. Direct effect of environmental circumstances may ease the diffusion of vector-borne diseases, water-borne diseases, cardiovascular diseases, respiratory allergies and malnutrition, etc. Indirect effects of climate change such as mental health problems and involuntary migration are also important. Children, the elderly and communities are living in poverty among the most susceptible of the damaging effects due to climate change. Environmental consequences climate change, such as extreme heat wave, rising sea-levels, changes in precipitation resulting in cyclones, earthquake, flooding and droughts, intense hurricanes and degraded air quality, affect directly and indirectly the physical, social and psychological health of humans. For instance, changes in precipitations are creating changes in the availability and quality of water, as well as resulting in extreme weather events such as intense hurricanes and flooding. Seeing the cumulative trend of impact of climate change on human health, implementation of alleviation measures like consolidation health systems and service delivery mechanisms through early monitoring, disease investigation, vector and disease control, and health insurance to counter the same becomes authoritative. Investment in research and development, health risk calculation studies, susceptibility mapping studies, formation of baseline circumstances, scenario modeling and acceptance of clean expansion mechanisms, etc. are the need of the hour. Economics would play a major role in combating the potential threat. Countries with good GDP would be able to introduce the best available tools of intervention and can fill up the lacunae in health system.
What is the role of microRNA-301A expression as a diagnostic and predictive marker of biochemical recurrence for prostate cancer?

19Background: Prostate specific antigen (PSA) screening for prostate cancer (PCa) remains controversial, due to its association with an increase in overdiagnosis of clinically insignificant PCa, and overtreatment. Hence, the need for more specific biomarkers to detect PCa and determine its prognosis. MicroRNA expression has previously been demonstrated as a biomarker to detect several malignancies. Studies suggest that microRNA-301a (miR-301a) inhibits the pro-apoptotic function of RUNX3, a transcription factor, and consequently activates ROCK1-mediated survival signaling in PCa. This study establishes the role of miR-301a as a reliable biomarker that can distinguish between patients with benign prostate hyperplasia (BPH) and PCa, and predict biochemical recurrence (BCR) after definitive treatment of PCa. Methods: Serum samples and tissue from prostate biopsies were collected from patients with an elevated PSA prospectively. The expression of miR- 301a was measured via reverse transcriptase-polymerase cha...
Drug treatment of elderly patients with acute myocardial infarction: practical recommendations.

Aspirin (acetylsalicylic acid) should be administered to patients on day 1 of an acute myocardial infarction (MI) and continued indefinitely. Early intravenous β-blockade should be used during acute MI. β-blockers should be continued indefinitely. Angiotensin-converting enzyme (ACE) inhibitors should be used in patients with acute MI with ST-segment elevation in two or more anterior precordial leads. ACE inhibitors should be used during and after acute MI in patients with chronic heart failure (CHF) or with a left ventricular ejection fraction ≤40%. There are no class I indications for using calcium channel antagonists during and after acute MI. Intravenous heparin should be used in patients with acute MI undergoing coronary revascularisation and in patients at high risk for systemic embolisation. Enoxaparin should be used in patients with non-Q-wave MI. Thrombolytic therapy should be considered in patients with acute MI with ST-segment elevation in contiguous leads of a 12-lead electrocardiogram or with left bundle branch block. Platelet glycoprotein IIb/IIIa inhibitors should be administered intravenously as an adjunct to heparin and aspirin in patients with non-Q-wave MI. Intravenous nitroglycerin should be used: (i) for the first 24 to 48 hours in patients with acute MI and CHF, large anterior MI, persistent ischaemia or hypertension; and (ii) continued beyond 48 hours in patients with recurrent angina pectoris or persistent pulmonary congestion. Long-acting nitrates should be given after MI, along with β-blockers, to patients with angina pectoris. There are no class I indications for using intravenous magnesium during acute MI. The routine use of antiarrhythmic drugs other than β-blockers during and after acute MI is not recommended.
Cell Cycle Regulators and Lineage-Specific Therapeutic Targets for Cushing Disease.

Cell cycle proteins are critical to pituitary development, but their contribution to lineage-specific tumorigenesis has not been well elucidated. Emerging evidence from in vitro human tumor analysis and transgenic mouse models indicates that G1/S-related cell cycle proteins, particularly cyclin E, p27, Rb, and E2F1, drive molecular mechanisms that underlie corticotroph-specific differentiation and development of Cushing disease. The aim of this review is to summarize the literature and discuss the complex role of cell cycle regulation in Cushing disease, with a focus on identifying potential targets for therapeutic intervention in patients with these tumors.
Enzymatic Synthesis of Virazole by Purine Nucleoside Phosphorylase of Enterobacter aerogenes

A potent antiviral agent, Virazole (1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide), was synthesized from inosine and 1,2,4-triazole-3-carboxamide (TCA) by a two step reaction with purified purine nucleoside phosphorylase (PNPase) of Enterobacter aerogenes AJ 11125. The first step involves the production of ribose-1-phosphate (R-1-P) through the phosphorolysis of inosine. The second step involves the production of Virazole through the transribosyl reaction of R-1-P and TCA. The R-1-P produced from inosine was isolated by ion-exchange chromatography and used as a substrate for Virazole synthesis without crystallization. TCA (10 mm) was transformed to Virazole with a 75% yield (molar basis) in the presence of 50mm R-1-P. Enzymatically synthesized Virazole was isolated from a large scale reaction mixture and identified by physicochemical means. The Km values of PNPase for TCA and hypoxanthine were 167mm and 5.6 mm, respectively.
Design of biodegradable nanoparticles to modulate phenotypes of antigen-presenting cells for antigen-specific treatment of autoimmune disease

Abstract Current therapeutic options for autoimmune diseases, such as multiple sclerosis (MS), often require lifelong treatment with immunosuppressive drugs, yet strategies for antigen-specific immunomodulation are emerging. Biodegradable particles loaded with disease-specific antigen, either alone or with immunomodulators, have been reported to ameliorate disease. Herein, we hypothesized that the carrier could impact polarization of the immune cells that associate with particles and the subsequent disease progression. Single injection of three polymeric carriers, 50:50 poly (DL-lactide-co-glycolide) (PLG) with two molecular weights (Low, High) and poly (DL-lactide) (PLA), loaded with the disease-specific antigen, proteolipid protein (PLP139-151), were investigated for the ability to attenuate clinical scores in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. At a low particle dose, mice treated with PLA-based particles had significantly lower clinical scores at the chronic stage of the disease over 200 days post immunization, while neither PLG-based particles nor OVA control particles reduced the clinical scores. Compared to PLG-based particles, PLA-based particles were largely associated with Kupffer cells and liver sinusoidal endothelial cells, which had a reduced co-stimulatory molecule expression that correlated with a reduction of CD4+ T-cell populations in the central nervous system. Delivery of PLA-based particles encapsulated with higher levels of PLP139-151 at a reduced dose were able to completely ameliorate EAE over 200 days along with inhibition of Th1 and Th17 polarization. Collectively, our study demonstrates that the carrier properties and antigen loading determine phenotypes of immune cells in the peripheral organs, influencing the amelioration of both acute and chronic stages of autoimmunity.
22 – Flowering Plants

Publisher Summary Several characteristics of angiosperms are believed to have played a role in their rapid diversification and ability to outcompete other groups. One of the most often cited is a pollination syndrome intimately associated with insects. The reticulate sculpture of many Early Cretaceous grains suggests that this association was well established by the Barremian, although some fossil grains with uncertain affinities also possess reticulate sculpture. In addition to entomophily, stigmatic compatibility has also been suggested as a contributing factor to the increased speciation rates among the early flowering plants. Another selective advantage often cited in early angiosperms is the shorter reproductive cycle and rapid seedling growth, which certainly provided the opportunity to outcompete many gymnosperms and to exploit new habitats.