cssi/SciSciGPT-SciSciNet huggingface dataset:
Incorporation of functional human immunodeficiency virus type 1 integrase into virions independent of the Gag-Pol precursor protein.

Retroviral integrase (IN) is expressed and incorporated into virions as part of the Gag-Pol polyprotein precursor. IN catalyzes integration of the proviral DNA into host cell chromosomes during the early stages of the virus life cycle, and as a component of Gag-Pol, it is involved in virion morphogenesis during late stages. It is unknown whether the scheme, conserved among retroviruses, for expressing and incorporating IN as a component of the Gag-Pol precursor protein is necessary for its function in the infected cell after viral entry. We have developed human immunodeficiency virus (HIV) virion-associated accessory proteins (Vpr and Vpx) as vehicles to deliver both foreign and viral proteins into the virus particle by their expression in trans as heterologous fusion proteins (X. Wu, et al., J. Virol. 69:3389-3398, 1995; X. Wu, et al., J. Virol. 70:3378-3384, 1996; X. Wu, et al., EMBO J. 16:5113-5122, 1977). To analyze IN function independent of its expression as a part of Gag-Pol, we expressed and incorporated IN into HIV type 1 (HIV-1) virions in trans as a fusion partner of Vpr (Vpr-IN). Our results demonstrate that the Vpr-IN fusion protein is efficiently incorporated into virions and then processed by the viral protease to liberate the IN protein. Virus derived from IN-minus provirus is noninfectious. However, this defect is overcome by trans complementation with the Vpr-IN fusion protein. Moreover, complemented virions are able to replicate through a complete cycle of infection, including formation of the provirus (integration). These results show, for the first time, that full IN function can be provided in trans, independent of its expression and incorporation into virions as a component of Gag-Pol. This finding also indicates that the IN domain of Gag-Pol is not required for the formation of infectious virions when IN is provided in trans. The ability to incorporate functional IN into retroviral particles in trans will provide unique opportunities to explore the function of this critical enzyme in a biologically relevant context, i.e., in infected cells as part of the nucleoprotein/preintegration complex.
Clinical trial methodology in stroke.

On March 6 and 7, 1989, 28 researchers with expertise in cerebrovascular disease, clinical trial methodology, and biostatistics met at the Priory of Corsendonk, Belgium, to exchange views on the problems in design of clinical trials in stroke. Trials in ischemic or hemorrhagic stroke were addressed as were those in stroke prevention. The presentations are summarized below
Increased Prevalence of G1P[4] Genotype among Children with Rotavirus-Associated Gastroenteritis in Metropolitan Detroit

The G and P genotypes of rotavirus stool isolates from 100 children were determined by reverse transcription-PCR and nucleotide sequencing. G1P[4] was the most prevalent genotype(41%), followed by G1P[8] (16%) and G4P[4] (14%). The G genoypes detected were G1 (73%), G4 (17.4%), G9 (6.3%), and G2 (2.8%). The P genotypes were P[4] (71%) and P[8] (29%). Coinfection with more than one G genotype occurred in 12 patients, and coinfection with more than one P genotype occurred in 11 patients.
Comparative usability testing of conventional and single incision laparoscopic surgery devices

Objective:The objective was to perform competitive usability testing to assess the user experience of conventional laparoscopic and laparoendoscopic single-site surgery (LESS) devices.Background:Recent advancements in single-incision instrumentation have created more interest in and usage of LESS. However, neither LESS nor its novel multichannel access devices have been thoroughly studied.Method:Using a simulation test bed and standardized laparoscopic surgery task, the user experience of three commercially available LESS devices was compared to conventional laparoscopic ports based on time on task, errors, task success, and perceived ease of use.Results:There were no significant differences between devices for time on task, errors, or task success (p > .05). For all devices, there were significantly more recoverable than unrecoverable errors, and errors occurred more frequently during the second phase of the task when the dominant hand was more active (p < .0001). Conventional laparoscopy was rated as ea...
System-level thermal modeling and co-simulation with hybrid power system for future all electric ship

This paper presents an approach to performing thermal-electrical coupled co-simulation of hybrid power system and cooling system of future all-electric Navy ships. The goal is to study the transient interactions between the electrical and the thermal sub-systems. The approach utilizes an existing Solid Oxide Fuel Cell (SOFC) / Gas Turbine (GT) hybrid electrical power model and the ship cooling system model developed on the Virtual Test Bed (VTB) platform at University of South Carolina. The integrated system simulation approach merges the thermal modeling capacity with the electrical modeling capacity in the same platform. The paper first briefly discusses the dynamic SOFC / GT hybrid engine system combined with propulsion plant model. It then describes ship cooling system model and the interactions between the electrical and the thermal sub-systems. A simple application scenario has been implemented and analyzed to illustrate the simulation. Dynamic responses of coupled thermal-electrical systems are explored under a step change of the service load to reveal important system interactions.
End-to-end delay assurances in multihop wireless local area networks

Emerging wireless local area network (WLAN) technologies support high data rates over relatively short distances. To achieve high data rate communication from larger distances, multihop wireless connections between mobile users and wireless Internet gateways may be necessary. In this paper, we address the challenges in providing a wide range of diverse delay assurances to end-to-end applications in a multihop WLAN. Due to node mobility and distributed medium access, multihop communication experiences substantial delay variations. The paper proposes a delay assurance mechanism based on consistent class-based service differentiation and end-to-end class selection. With simulations, the solution demonstrates remarkable enhancements in delay assurances as compared with the best effort service of IEEE 802.11 in both stationary and mobile scenarios.
Advocating for the woman with breast cancer

Health care workers and breast cancer survivors have an important role to play as advocates for breast cancer patients. At the most basic level, advocates must ensure that the patient has access to medical care. In addition they must help to ensure that the quality of care is optimal, enhancing the likelihood of survival, rehabilitation, and psychological adaptation. This article describes important advocacy issues for women with breast cancer, including informational needs, patient-physician communication, choice of primary surgical treatment, reconstructive surgery, adjuvant therapy, psychosocial issues, and employment and insurance problems.
The Anticancer Drug Edelfosine Is a Potent Inhibitor of Neovascularization In Vivo

Edelfosine is an alkyl-lysophospholipid that acts as an anticancer agent in vivo. To test the hypothesis that part of its antineoplastic activity may be due to its ability to inhibit the neovascularization on which the progressive growth of all tumors depends, we evaluated edelfosine in vitro and in vivo for antiangiogenic activity. Edelfosine acted directly on cultured capillary endothelial cells, inhibiting their migration toward the angiogenic factor, basic fibroblastic growth factor (bFGF), at doses of 8–200 nM. When given systemically to rats (20 mg/kg IP twice daily), edelfosine was well tolerated and antiangiogenic. The majority of treated animals became unable to mount a corneal neovascular response to a pellet releasing bFGF, whereas vigorous vessel ingrowth was seen in untreated controls.
Datalink streaming in wireless sensor networks

Datalink layer framing in wireless sensor networks usually faces a trade-off between large frame sizes for high channel bandwidth utilization and small frame sizes for effective error recovery. Given the high error rates of intermote communications, TinyOS opts in favor of small frame sizes at the cost of extremely low channel bandwidth utilization. In this paper, we describe Seda: a streaming datalink layer that resolves the above dilemma by decoupling framing from error recovery. Seda treats the packets from the upper layer as a continuous stream of bytes. It breaks the data stream into blocks, and retransmits erroneous blocks only (as opposed to the entire erroneous frame). Consequently, the frame-error-rate (FER), the main factor that bounds the frame size in the current design, becomes irrelevant to error recovery. A frame can therefore be sufficiently large in great favor of high utilization of the wireless channel bandwidth, without compromising the effectiveness of error recovery. Meanwhile, the size of each block is configured according to the error characteristics of the wireless channel to optimize the performance of error recovery. Seda has been implemented as a new datalink layer in the TinyOS, and evaluated through both simulations and experiments in a testbed of 48 MicaZ motes. Our results show that, by increasing the TinyOS frame size from the default 29 bytes to 100 bytes (limited by the buffer space at MicaZ firmware), Seda improves the throughput around 25% under typical wireless channel conditions. Seda also reduces the retransmission traffic volume by more than 50%, compared to a framebased retransmission scheme. Our analysis also exposes that future sensor motes should be equipped with radios with more packet buffer space on the radio firmware to achieve optimal utilization of the channel capacity.
Mobility Enhancement of Peripheral PMOSFET Using e-SiGe Source and Drain in Sub-50nm DRAM

The mobility enhanced pMOS transistors have been successfully implemented into sub-50nm DRAM for the first time. The uni-axial strained channels were embodied by filling the recessed source / drain with epitaxial SiGe film. Mobility boosting and reduced external resistance enabled pMOS transistors to increase saturation current by 20%, and retarded boron diffusion reduced DIBL by 17mV/V compared to control process without degradation of DRAM cell data retention time characteristics. The local variation of threshold voltage is suppressed to the same level of control process. The hot electron induced punch-through (HEIP) degradation can be controlled to negligible degree.
Antimicrobial activity and a comparison of published pharmacodynamics of gemifloxacin and eight fluoroquinolones against Streptococcus pneumoniae.

Abstract Gemifloxacin was evaluated for its in vitro activity and was compared with eight fluoroquinolones. Pharmacodynamic comparisons were made based on published pharmacokinetic information. Gemifloxacin demonstrated excellent in vitro activity (minimum inhibitory concentration necessary to inhibit 90% of the strains tested, MIC 90 =0.03mg/L (range 0.0019–0.03mg/L)) against 199 strains of Streptococcus pneumoniae . Its activity was not influenced by penicillin or ciprofloxacin non-susceptibility. Gemifloxacin demonstrated excellent pharmacodynamic parameters, with a C max /MIC 90 of 67 (where C max is the peak serum level) and an AUC/MIC 90 of 297 (where AUC is the area under the curve). Compared with the other eight fluoroquinolones tested, gemifloxacin demonstrated the best in vitro activity and C max /MIC 90 .
Nicotinic agonists, phorbol esters, and growth factors activate two extracellular signal-regulated kinases, ERK1 and ERK2, in bovine chromaffin cells.

: Treatment of bovine chromaffin cells with nicotinic agonists, phorbol esters, and growth factors increases protein kinase activity toward microtubule-associated protein-2 and myelin basic protein (MBP) in vitro. To characterize the kinases that are activated by these agents, we separated chromaffin cell proteins by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels into which MBP had been incorporated, allowed the proteins to renature, and then assayed MBP kinase activity by incubating the gels with [γ-32P]ATP. Chromaffin cells contain a family of kinases that phosphorylate MBP in vitro. Two of these kinases, of Mr 46,000 and 42,000 (PK46 and PK42), were activated by treatment of the cells with dimethylphenylpiperazinium (DMPP), phorbol 12,13-dibutyrate (PDBu), or insulin-like growth factor I (IGF-I). Activation of PK46 and PK42 by DMPP was dependent on extracellular Ca2+, whereas the effects of PDBu and IGF-I were Ca2+ independent. Down-regulation of protein kinase C by incubation of the cells with PDBu abolished the activation of PK46 and PK42 by DMPP, PDBu, and IGF-I. Staurosporine, a protein kinase C inhibitor, prevented the activation of PK46 and PK42 by DMPP and PDBu but did not block the activation of these kinases by IGF-I. Immunoblotting experiments with antiphosphotyrosine (anti-PTyr) antibodies demonstrated that agents that increased the kinase activities of PK46 and PK42 also increased the apparent PTyr content of Mr 46,000 and 42,000 proteins. PK46 and PK42 comigrated with proteins that reacted with antibodies against extracellular signal-regulated kinases (ERKs). Thus, PK46 and PK42 appear to be the bovine homologues of ERK1 and ERK2. These kinases are regulated by multiple pathways and may play a role in the mechanism by which a variety of agonists regulate chromaffin cell function.
Spermatogenesis and apparent fertility in a eunuchoid male in the eleventh year of androgen therapy.

THE purpose of this paper is to report several unusual occurrences in a male eunuchoid, at present in his twelfth year of androgen therapy. This patient is discussed for three reasons: the time intervals involved; the eventual achievement of normal testis size and histologic structure; and the presumptive demonstration of fertility and parenthood. A summary of the findings in this patient follows in the text. Plum (1) in 1943 reported the production of spermatogenesis in a eunuchoid male, as evidenced by semen examination. He treated this patient for four years with chorionic gonadotropin, pregnant mare's serum hormone, and testosterone propionate. Heller and coworkers (2) shortly thereafter used chorionic gonadotropin supplemented by anterior hypophyseal gonadotropin for brief periods and found evidence of spermatogenesis in the testicular biopsy specimen. Kinsell (3) reported in 1948 the appearance of spermatogenesis in a male with panhypopituitarism who was treated with testosterone pellets, and whose ...
On the role of locality in learning stress patterns

This paper presents a previously unnoticed universal property of stress patterns in the world's languages: they are, for small neighbourhoods, neighbourhood-distinct. Neighbourhood-distinctness is a locality condition defined in automata-theoretic terms. This universal is established by examining stress patterns contained in two typological studies. Strikingly, many logically possible – but unattested – patterns do not have this property. Not only does neighbourhood-distinctness unite the attested patterns in a non-trivial way, it also naturally provides an inductive principle allowing learners to generalise from limited data. A learning algorithm is presented which generalises by failing to distinguish same-neighbourhood environments perceived in the learner's linguistic input – hence learning neighbourhood-distinct patterns – as well as almost every stress pattern in the typology. In this way, this work lends support to the idea that properties of the learner can explain certain properties of the attested typology, an idea not straightforwardly available in optimality-theoretic and Principle and Parameter frameworks.
Effect of concrete slab on the behavior of fire exposed subframe assemblies with bolted double angle connections

Abstract This paper presents the development of a three-dimensional nonlinear finite element model for evaluating the system-level transient fire response of double angle connections that are part of a sub framed assembly. The behavior of two subframe assemblies, with double angle connections, exposed to different fire scenarios were modeled using a commercially available finite element software ANSYS. The finite element model accounts for material and geometrical nonlinearities, degradation of constitutive material properties with temperature and non-linear contact interactions. The model is validated by comparing predicted thermal and structural response parameters of connection assemblies with measured data from fire tests on subframe assemblies with and without the concrete slab. The validated model is applied to study the effect of decay rate, loading type, presence of the concrete slab and degree of axial restraint on the fire performance of double angle connection assemblies. Results from the parametric studies indicate that decay rate, loading type and axial restraint have significant influence on the transient fire performance of subframe assembly. Further, presence of the concrete slab significantly enhances the rigidity of the connection assembly and mitigates local instabilities, such as local and lateral torsional buckling, that arise in beams and this improves the performance of connections.
Avian Navigation, Geomagnetic Field Sensitivity, and Biogenic Magnetite

How birds manage to find their way around in the world has long been a source of fascination. These animals range widely when foraging for food, sometimes traveling 100 km or more from their nest or roost. Moreover, many species of birds fly long distances between breeding grounds and wintering areas, returning with extraordinary precision to specific locales year after year. Distances traveled during such migrations typically average between 1000 and 6000 km each way between breeding and wintering grounds. Several species of birds travel close to 30,000 km annually between arctic breeding grounds and wintering areas in or near the antarctic. It would seem that birds, as well as other animals which forage and migrate over large distances, must possess navigational abilities of a fair degree of sophistication. Indeed, given the essential importance to such animals of an accurate and fail-safe navigational system, one might not be surprised to find that evolution has been opportunistic in exploiting available environmental sources of navigationally useful information.
Diverse Abnormalities of the c-erbAβ Thyroid Hormone Receptor Gene in Generalized Thyroid Hormone Resistance

The syndrome of generalized thyroid hormone resistance (GTHR) was first described in 1967 in a kindred, G, with elevated free thyroid hormones and absence of the typical clinical features of hyperthyroidism (1). The proband, a 6-year-old girl, demonstrated stippled epiphyses, dysmorphic features (bird-like facies, pigeon breast, and winged scapulae) and deaf-mutism. The syndrome was transmitted as a recessive trait and affected members were the product of a consanguineous union. As children, affected members had intelligence quotients within the ranges normally seen in hearingimpaired individuals (1,2). Although minimal delay of bone age was observed in affected members, final adult height was above the parental mean. Interestingly, affected members showed a paradoxical increase of serum TSH in response to the administration of suppressive doses of T3 (3) and no significant effect of antithyroid drugs on the level of TSH (2). This constellation of clinical findings in the original kindred--stippled epiphyses, somatic abnormalities, and deafmutism--has never been reported in other kindreds with GTHR. However, less severe hearing defects, learning disabilities and growth retardation are not uncommon.
Stress weakens prefrontal networks: molecular insults to higher cognition

A variety of cognitive disorders are worsened by stress exposure and involve dysfunction of the newly evolved prefrontal cortex (PFC). Exposure to acute, uncontrollable stress increases catecholamine release in PFC, reducing neuronal firing and impairing cognitive abilities. High levels of noradrenergic α1-adrenoceptor and dopaminergic D1 receptor stimulation activate feedforward calcium-protein kinase C and cyclic AMP-protein kinase A signaling, which open potassium channels to weaken synaptic efficacy in spines. In contrast, high levels of catecholamines strengthen the primary sensory cortices, amygdala and striatum, rapidly flipping the brain from reflective to reflexive control of behavior. These mechanisms are exaggerated by chronic stress exposure, where architectural changes lead to persistent loss of PFC function. Understanding these mechanisms has led to the successful translation of prazosin and guanfacine for treating stress-related disorders. Dysregulation of stress signaling pathways by genetic insults likely contributes to PFC deficits in schizophrenia, while age-related insults initiate interacting vicious cycles that increase vulnerability to Alzheimer's degeneration.
Solvation dynamics in Ni+ (H2O)n clusters probed with infrared spectroscopy.

Infrared photodissociation spectroscopy is reported for mass-selected Ni+(H2O)n complexes in the O−H stretching region up to cluster sizes of n = 25. These clusters fragment by the loss of one or more intact water molecules, and their excitation spectra show distinct bands in the region of the symmetric and asymmetric stretches of water. The first evidence for hydrogen bonding, indicated by a broad band strongly red-shifted from the free OH region, appears at the cluster size of n = 4. At larger cluster sizes, additional red-shifted structure evolves over a broader wavelength range in the hydrogen-bonding region. In the free OH region, the symmetric stretch gradually diminishes in intensity, while the asymmetric stretch develops into a closely spaced doublet near 3700 cm-1. The data indicate that essentially all of the water molecules are in a hydrogen-bonded network by the size of n = 10. However, there is no evidence for the formation of clathrate structures seen recently via IR spectroscopy of protonat...
Increasing the Rate of Return in Mail Surveys

This article illustrates a simple experimental approach, used in increasing the rate of return in mail surveys.
Light-triggered doxorubicin release quantified by spatial frequency domain imaging and diffuse optical spectroscopy

Chemo efficacy depends on the drug concentration at the target sites. Here we show quantification of the drug concentration of recently developed porphyrin-phospholipid (PoP)-liposome encapsulated Dox using diffuse optical methods.
Identification of cell surface receptors for the novel adipokine CTRP3

C1q TNF Related Protein 3 (CTRP3) is a member of a family of secreted proteins that exert a multitude of biological effects throughout the body. Our initial work shows promise in the development of...
Associations with rhizosphere bacteria can confer an adaptive advantage to plants

Host-associated microbiomes influence host health. However, it is unclear whether genotypic variations in host organisms influence the microbiome in ways that have adaptive consequences for the host. Here, we show that wild accessions of Arabidopsis thaliana differ in their ability to associate with the root-associated bacterium Pseudomonas fluorescens, with consequences for plant fitness. In a screen of 196 naturally occurring Arabidopsis accessions we identified lines that actively suppress Pseudomonas growth under gnotobiotic conditions. We planted accessions that support disparate levels of fluorescent Pseudomonads in natural soils; 16S ribosomal RNA sequencing revealed that accession-specific differences in the microbial communities were largely limited to a subset of Pseudomonadaceae species. These accession-specific differences in Pseudomonas growth resulted in enhanced or impaired fitness that depended on the host's ability to support Pseudomonas growth, the specific Pseudomonas strains present in the soil and the nature of the stress. We suggest that small host-mediated changes in a microbiome can have large effects on host health.
Introduction and overview of hematopoietic growth factors.

Blood cell development is regulated by a variety of hematopoietic growth factors that mediate the growth, maturation, and activation of hematopoietic cell elements. Several of these factors have been isolated and are now being produced by means of recombinant DNA techniques in quantities sufficient for study and clinical use. Three factors in particular have recently received considerable attention in the clinical arena: recombinant human granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), and erythropoietin (EPO). Although both may prove to be clinically useful, G-CSF and GM-CSF have distinct and different biological characteristics. The regulatory action of G-CSF is apparently lineage-specific for the proliferation and maturation of neutrophil granulocytes. GM-CSF is less restricted in its actions, affecting all granulocytes, especially eosinophil granulocytes. It also stimulates the proliferation and activation of monocyte-macrophages and induces these cells to produce a number of cytokines. EPO mediates the growth of erythroid progenitors into mature erythrocytes. The CSFs and EPO have many potential clinical applications, including enhancing myeloid effector cell production and function, rendering malignant cells more susceptible to killing by cycle-specific agents, and correcting the anemia of end-stage renal disease.
Quantitative Experimental Analysis of the Influence of Quasi-Specific Sites on Kinetics of DNA Scanning by the Zinc-Finger Protein Egr-1

For gene regulation, transcription factors must bind to specific DNA sites in cis-regulatory elements of genes. However, chromosomal DNA contains numerous sites that are similar to the target sequences recognized by transcription factors. The influence of such ‘quasi-specific’ sites on functions of the transcription factors is not well understood to date by experimental means. In this work, using fluorescence methods, we have investigated the influence of quasi-specific DNA sites on the efficiency of target location by the DNA-binding domain of the inducible transcription factor Egr-1, which recognizes 9 base pairs via 3 zinc fingers. By stopped-flow assays, we measured the kinetics of Egr-1's association with a target site on 143 base-pair DNA in the presence of various competitor DNA including nonspecific and quasi-specific sites. The presence of quasi-specific sites on competitor DNA significantly decelerated the target association by the Egr-1 protein. The impact of the quasi-specific sites depended strongly on their affinity, concentration, and the degree of their binding to the protein. To quantitatively describe the kinetic impact of the quasi-specific sites, we derived an analytical form of the apparent kinetic rate constant for the target association and used it for fitting to the experimental data. Our kinetic data with calf thymus DNA as competitor suggested that there are millions of high-affinity quasi-specific sites for Egr-1 among 3-billion base pairs of the genomic DNA. This study quantitatively demonstrates that naturally abundant quasi-specific sites on DNA can considerably impede the target search processes of sequence-specific DNA-binding proteins.This work was supported by Grant R01-GM107590 from National Institutes of Health (to J.I.).
Starvation (Transition into the Postabsorptive Phase)

: Insulin and glucagon are usually released in an inverse fashion. With low carbohydrate, high protein diets, both insulin and glucagon secretion may increase. The metabolic phase following a meal varies as a function of the fuel ingested. Exquisitely sensitive physiologic mechanisms respond to small changes in the blood glucose concentration. The immediate postabsorptive phase of starvation is associated with decreasing hepatic glycogen reserves.
The Law of Diminishing Returns and the Generalized CES Production Function

There are two troubling and largely unrecognized implications of the generalized CES production function when there are increasing returns to scale and the elasticity of substitution (𝜎) exceeds one: (1) under these conditions the CES production function is always inconsistent with the law of diminishing marginal returns to either labor or capital and (2) the marginal product of labor (capital) always approaches infinity as labor (capital) approaches infinity. To avoid these two implications one must restrict the parameter values of the CES production function to either not allow for increasing returns to scale or to require that σ
Evaluation of a commercially available radioimmunoassay and enzyme immunoassay for the analysis of progesterone and estradiol and the comparison of two extraction efficiency methods

The measurement of progesterone (P4) and estradiol (E2) is essential for monitoring reproductive cycles and can aid in diagnosing the cause of poor reproductive performance in dairy cattle. Readily available, reproducible, accurate, non-radioactive assays are needed for the assessment of P4 and E2 in bovine serum. The gold standard for hormone assessment, radioimmunoassay (RIA), was compared with enzyme-linked immunoassay (EIA). Serum collected from various points in the estrous cycle was extracted with radiolabeled P4 (ie, 3H-P4; HE) and without 3H-P4 (CE) before being used in the assay. For the assessment of P4, there is a great degree of correlation between the RIA and EIA (adjusted R-square = 0.95; Pearson correlation coefficient (PCC) = 0.98, P < 0.001). A difference between the RIA and EIA methods was not detected for E2 concentrations (P = 0.16), but the correlation between techniques was poor (adjusted R-squared = 0.73; PCC = 0.87, P = 0.002). There was no difference in the serum extraction efficiency as measured with 3H-P4 as opposed to without (P = 0.94). The two methods for the measurement of serum extraction efficiency were highly correlated (adjusted R-square = 0.83; PCC = 0.92, P < 0.001). The concordance correlation coefficient (CCC) showed an excellent agreement between RIA and EIA for P4 determination (0.89) and between HE and CE methods (0.90). Although the 95% limits of agreement of the Bland-Altman plots encompassed 89% (8/9) and 92% (12/13) of the differences between methods for P4 quantification and extraction respectively, the CCC indicated an excellent agreement among them. The CCC between RIA and EIA for E2 quantification was 0.68 which corresponds with a fair agreement; however, the 95% limits of agreement of the Bland-Altman plot encompassed 100% (9/9) of differences between methods. The EIA and CE methods are comparable alternatives to the RIA and HE methods, respectively and can be used to quantify P4 and E2 for bovine serum.
The Gastroenterology Fellowship Match: A Decade Later

Following a period of uncertainty and disorganization, the gastroenterology (GI) national leadership decided to reinstitute the fellowship match (the Match) under the auspices of the National Residency Matching Program (NRMP) in 2006. Although it has now been a decade since the rebirth of the Match, there have been limited data published regarding progress made. In this piece, we discuss reasons for the original collapse of the GI Match, including most notably a perceived oversupply of GI physicians and a poor job market. We discuss the negative impacts the absence of the Match had on programs and on applicants, as well as the impetus to reorganize the Match under the NRMP. We then utilize data published annually by the NRMP to demonstrate that in the decade since its rebirth, the GI Match has been remarkably successful in terms of attracting the participation of applicants and programs. We show that previous misguided concerns of an oversupply of GI physicians were not realized, and that GI fellowship positions remain highly competitive for internal medicine applicants. Finally, we discuss possible implications of recent changes in the healthcare landscape on the GI Match.
Success of labor induction for pre-eclampsia at preterm and term gestational ages

Determine the impact of gestational age (GA) on vaginal delivery following induction of labor (IOL) for pre-eclampsia, and evaluate factors that influence successful induction. Population-based retrospective cohort of 1 034 552 live births in Ohio (2006–2012). The rate of vaginal delivery in women with pre-eclampsia who underwent induction was calculated with 95% confidence intervals, stratified by week of GA at birth. Factors associated with the decision to undergo IOL, and success of IOL were evaluated, and multivariable logistic regression estimated the strength of association. 18 296 (71.3%) of the patients who underwent IOL had a vaginal delivery. The majority achieved vaginal delivery at both preterm (66% at 23–36 weeks) and term GAs (72%). Factors most strongly associated with vaginal delivery following IOL for pre-eclampsia included prior vaginal delivery and young maternal age. The majority of women with pre-eclampsia who undergo IOL achieve vaginal birth, even at early GAs.
Managing Insomnia Symptoms Among Adolescents With Anxiety Disorders

ABSTRACTInsomnia is extremely common among adolescents with anxiety disorders, is associated with significant functional impairment, and may serve to maintain anxiety in this population. Despite th...
Chromosome 19 microRNAs exert antiviral activity independent from type III interferon signaling

Introduction Cultured primary human trophoblasts (PHT), derived from term placentas, are relatively resistant to infection by diverse viruses. The resistance can be conferred to non-trophoblastic cells by pre-exposing them to medium that was conditioned by PHT cells. This antiviral effect is mediated, at least in part, by microRNAs (miRNA) expressed from the chromosome 19 microRNA cluster (C19MC). Recently we showed that PHT cells and cells pre-exposed to PHT medium are also resistant to infection by Zika virus (ZIKV), an effect mediated by the constitutive release of the type III interferons (IFN) IFN lambda-1 and IFN lambda-2 in trophoblastic medium. We hypothesized that trophoblastic C19MC miRNA are active against ZIKV, and assessed the interaction of this pathway with IFN lambda-1 - mediated resistance.
Giant among dwarfs: Meganannus lewisi, gen. n. and sp. n., a new genus and species of minute litter bugs from Costa Rica (Hemiptera: Schizopteridae).

The Neotropical biodiversity of the cryptic and tiny minute litter bugs in the family Schizopteridae—although thought to be the best documented tropical fauna of Schizopteridae—is still poorly known. Sixteen species of Schizopteridae have been described from Costa Rica, 13 of which during the past few years, and the last new genus of Schizopteridae from that country was described more than half a century ago. We here describe and document a new monotypic genus of Schizopteridae from Costa Rica, Meganannus n. gen. The new genus belongs to the “Ogeriinae” + Schizopterinae lineage of Schizopteridae and stands out among other litter bugs by the large body size, among other features. We provide habitus photographs and document morphological details using scanning electron, confocal, and light compound microscopic images. A map and measurements are also produced. An illustrated identification key to genus groups and/or genera of Neotropical Schizopteridae including this new genus is presented.
Analysis of Multistate Autoregressive Models

In this paper, we consider the inference problem for a wide class of time-series models, referred to as multistate autoregressive models. The time series that we consider are composed of multiple epochs, each modeled by an autoregressive process. The number of epochs is unknown, and the transitions of states follow a Markov process of an unknown order. We propose an inference strategy that enables reliable and efficient offline analysis of this class of time series. The inference is carried out through a three-step approach: detecting the structural changes of the time series using a recently proposed multiwindow algorithm, identifying each segment as a state and selecting the most appropriate number of states, and estimating the Markov source based upon the symbolic sequence obtained from previous steps. We provide theoretical results and algorithms in order to facilitate the inference procedure described above. We demonstrate the accuracy, efficiency, and wide applicability of the proposed algorithms via an array of experiments using synthetic and real-world data.
The role of adult hippocampal neurogenesis in brain health and disease

Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by a number of environmental and cell-intrinsic factors to adapt to environmental changes. Accumulating evidence suggests that adult-born neurons may play distinct physiological roles in hippocampus-dependent functions, such as memory encoding and mood regulation. In addition, several brain diseases, such as neurological diseases and mood disorders, have deleterious effects on adult hippocampal neurogenesis, and some symptoms of those diseases can be partially explained by the dysregulation of adult hippocampal neurogenesis. Here we review a possible link between the physiological functions of adult-born neurons and their roles in pathological conditions.
Surgical treatment of endocarditis: current status.

Infective endocarditis can be described by confidence in its diagnosis (Duke criteria), by its causative microorganisms, its infectious activity, its location, its affecting a native or prosthetic valve, its pathologic characteristics, and its cardiac and extracardiac complications. Although the treatment of endocarditis has improved, endocarditis remains a serious disease.1
A Viral Enterotoxin

Acute infectious gastroenteritis is a major cause of infant morbidity in developed countries and of infant mortality in developing areas of the world. Rotavirus is recognized as the most important etiologic agent of infantile gastroenteritis, and studies of rotavirus serve as models to understand the complex interactions between enteric viruses and the multifunctional cells of the gastrointestinal tract. Understanding such interactions is significant for microbial pathogenesis because most (>80%) infections are initiated at mucosal surfaces. Rotaviruses are pathogens that infect the mature ente-rocytes of the villi in the intestine and infection appears to be limited to these highly differentiated cells in immunologically competent hosts. In such hosts, infections are generally acute yet diarrheal disease can be severe and life-threatening. Disease generally is resolved within 2–5 days after infection if affected hosts receive adequate rehydration. In immunocompromised hosts, virus infections persist, virus can be detected extraintestinally and virus excretion may be detected for extended periods of time (many months).
Thrombin-like venom enzymes: structure and function.

While thrombin itself has an ever-growing number of reported biochemical and biological actions, the term thrombin-like enzyme usually connotes only one of these actions—the ability to induce the clotting of fibrinogen. The phylogenetic and developmental distance between mammalian thrombin and the thrombin-like enzymes of snake venoms provides opportunities for comparative studies on the structural requirements for their highly specific coagulant actions on fibrinogen.
Behavioral Deficiencies in Protein-Deprived Monkeys

It is a well documented fact that large numbers of people in the world, predominantly children in underdeveloped countries, suffer from protein-calorie malnutrition (Behar, L968; Coursin, 1965). Some of the major investigations conducted with human beings suggest that malnutrition experienced early in life may produce a permanent alteration of the phenotypic expression of the normal intellectual and social development of the child (Cravioto and Robles, 1963, 1965; Stoch and Smythe, 1963). Studies concerning severe protein-calorie malnutrition reveal profound behavioral deficiencies in children who suffer such a nutritional deficit before they are six months of age (Brockman and Ricciuti, 1971; Pollitt, 1972). Cravioto and Robles (1965) have reported deficiencies in adaptive behavior, interpersonal social abilities, language acquisition, and motor skills. It is apparent, then, that children with a history of protein-calorie malnutrition exhibit deficits in a variety of developmental tasks when compared to adequately nourished children.
Mechanism for basal expression of rat mitochondrial branched-chain-2-oxo- acid dehydrogenase

The rat branched-chain-2-oxo-acid dehydrogenase (BCOD) kinase mRNA is transcribed from a TATA-less promoter that has GC-rich sequences and two putative Sp1 binding sites near the transcription start site. We demonstrated previously that the 5' region of the kinase gene, base pairs -128 to +264, contained promoter activity when assayed using luciferase as a reporter (Huang and Chuang (1996) Biochem. J. 313, 603-609). To define DNA elements required for efficient expression of the kinase gene, nested deletion constructs of the above promoter region fused with a luciferase reporter gene were transfected into cultured H4IIE (hepatoma) and NRK-52E (kidney) cells. The results showed that the region between nucleotides -58 and +21 was indispensable for the kinase basal promoter activity. Methylation-interference and mutagenesis-promoter assays identified nucleotides -50 to -40 (ACAACTCCCA) as cis-acting DNA sequences that are required for nuclear protein binding and efficient promoter activity. Gel-supershift analysis with anti-Sp1 antibody suggested that the nuclear protein capable of binding to the -58 oligonucleotide (bp -58 to -34) was immunologically related to the Sp1 protein. The -58 oligonucleotide formed a DNA-protein complex with recombinant Sp1 protein with an affinity approximately ten-fold lower than that of the consensus Sp1 oligonucleotide. Co-transfection of the Sp1 expression plasmid and the -58 promoter construct into Drosophila Schneider cells revealed that Sp1 contributed to the kinase basal promoter activity by binding to the non-consensus site in the -58 region. Deletion of two consensus Sp1 binding sites (bases -150 to -140 and bases +29 to +38) in the kinase gene did not affect the basal promoter activity. Therefore binding of Sp1 or Sp1-like proteins to the above single non-consensus Sp1 sequence in the -58 region plays a major role of transactivating basal expression of the BCOD kinase.
The Construction and Assessment of an Experimental Test of Auditory Perception

The assessment of visual perception has become a very common means of studying those behaviors felt to be associated with neurological impairment. Visual perception is only one behavior that may be interfered with due to CNS impairment. The question of the relationship of auditory perceptual behaviors to visual perceptual function and neurological impairment frequently goes unanswered. The data from this study show that auditory and visual perception are abstract human behaviors. Auditory perception is a global complex set of behaviors that can be differentiated for assessment. The receptive language model and the Experimental Test of Auditory Perception (TAP) have shown an ability to differentiate neurologically impaired from normal (matched control) subjects.
Immunotherapy for Neuroblastoma

Abstract Current therapeutic approaches for high-risk neuroblastoma include dose-intensive chemotherapy, surgical and radiotherapeutic interventions that are associated with long- and short-term toxicities. Immunotherapy utilizes mechanisms of action that are not cross-reactive with other antitumor modalities and reduce exposure to cytotoxic agents, improving both the survival and quality of life in patients treated for high-risk neuroblastoma. In this chapter, we review antineuroblastoma immunotherapy strategies in clinical use and preclinical development. These include monoclonal antibodies and cytokines, immunoconjugates, chemoimmunotherapy, radioimmunotherapy, adoptive cell therapies, and cancer vaccines.
Impact of phantom-based partial volume corrections on in vivo dosimetry of theranostic molecularly targeted radionuclide therapy in patient-derived xenograft murine models

136 Objectives: The development of molecularly targeted radionuclide therapy (MTRT) agents requires characterization of pharmacokinetic behavior in vivo and subsequent estimation of tumor dosimetry. Theranostic pharmaceuticals, which can be used for both diagnosis and therapy, can be used as surrogates to describe agent biodistribution and estimate tumor dosimetry. However, PET imaging innately suffers from partial volume effects that can impede image accuracy. This study establishes a methodology utilizing 3D printed “hot spheres” phantom (‘diagnostic’) to produce a recovery coefficient (RC) correction model and evaluates the dosimetric impact (‘radiotherapeutic’) on a small cohort of subjects bearing flank tumors. Methods: A phantom with 12 spheres (diameters ranging from 1.05 - 12.4 mm) was developed using a computer-aided design software and then 3D printed with a proprietary photopolymer. The phantom was filled with a DI-water based solution containing an activity concentration of I-124 comparable to tumor concentrations observed in previous work and imaged on a microPET/CT scanner. CT-based regions of interest were drawn and mean activity concentrations were measured on the overlaid PET images for calculation of RCs for each volume. Thereafter, tumor uptake and retention of [I-124]-CLR1404 was evaluated in 3 patient-derived xenograft (PDX) flank models (n=12 mice) via in vivo PET/CT imaging at five-time points over the course of six days post-injection. Following the last scan, tumors were resected, and activity concentration was measured with gamma counting. For dosimetry, tumor uptake was decay corrected to represent [I-131]-CLR1404 and absorbed dose was calculated using the OLINDA sphere model for PV-corrected (PVC) and non-corrected (NC) pharmacokinetics. Results: Uptake and selectivity of [I-124]-CLR1404 was confirmed in all PDX models via the microPET/CT imaging with a range of 1.7 to 4.6 %ID/g. Prior to correcting for PV effects, the PET-based quantification was underestimating uptake by an average of 49% relative to ex vivo measurements. Applying the PVC to the PET-based measurements reduced this difference to an average of 9%. When the PVC pharmacokinetics were used in the dosimetry, the percent increases in the estimated integral absorbed doses (Gy/MBq) ranged between 51% and 135% (mean 85%). Larger increases in integral absorbed dose were observed at lower tumor volumes. Conclusion: Preliminary results suggest that I-124 PV effects cause an underestimation of the quantitative PET-based uptake and determination of integral absorbed dose in preclinical theranostic studies. The phantom-based RC correction model presented in this study provides a method of achieving more quantitatively accurate PET-based dosimetry in the rapidly growing field of theranostics and MTRT.
A parametric resonance based capacitive ultrasonic transducer for wireless power transfer in air

Capacitive ultrasonic transducers have been in use for many years for various applications such as medical imaging, wireless power, sensing, and nondestructive testing. Typically, capacitive transducers require a DC bias or electret in order to operate efficiently and with high sensitivity. This makes them less desirable for applications such as wireless power transfer or energy harvesting, where a passive piezoelectric transducer may be preferred. Recently, it was shown that the requirement of a DC bias can be overcome by driving the capacitive transducer into parametric resonance using ultrasound (Surappa et al., Appl. Phys. Lett. 111(4), 043503). In this work, we present the operation of the first ever biasless, chargeless capacitive parametric ultrasonic transducer (CPUT) in air and demonstrate the utility of such a system for acoustic power transfer and sensing. Experiments performed in air show that the CPUT has an open-circuit sensitivity of more than 100 mV/Pa and is able to recover 31 µW at a distance of 10 cm from a 50 kHz ultrasonic source in the absence of a DC bias.