cssi/SciSciGPT-SciSciNet huggingface dataset:
Beyond the Window: Patient Characteristics and Geographic Locations Associated with Late Prenatal Care in Women Eligible for 17-P Preterm Birth Prevention.

To reduce the risk of recurrence, women with a history of spontaneous preterm birth (PTB) are recommended to receive 17-hydroxyprogesterone caproate (17-P) injections starting by the 20th week of pregnancy. In women eligible for 17-P, we aimed to identify patient factors and geospatial locations associated with increased risk of presentation beyond 20 weeks gestation. We conducted a secondary analysis of a retrospective cohort study including all women meeting criteria for 17-P within a single academic medical center over a 2-year period. We compared early ( 21 weeks) presenters via demographics, social history, and index pregnancy outcomes using standard and Bayesian statistical models. Geospatial mapping was performed to determine residential areas with high risk for late presentation. Geocoded address data was available for 351 women in whom the mean gestational age at first visit was 14.9 weeks, and 63 of whom were late presenters (17.9%). Younger maternal age, current smoking, and lack of health insurance were predictors of late presentation with greater than 95% probability. Hispanic ethnicity and black race were associated with higher odds of late presentation with 87 and 69% probability, respectively. The area with the latest gestational age at presentation was located within central Durham City and to the northeast. Our study identified patient-level risk factors and geographic locations associated with presentation beyond the recommend window for 17-P initiation. These findings suggest an urgent need for intervention to improve early prenatal care initiation and a target location where such interventions will be most impactful.
Is What Glitters Really Gold? A Quasi-Experimental Study of First-Year Seminars and College Student Success

First-year seminars are frequently designed to help students adjust to and succeed in college. Although considerable literature has explored this topic, many previous studies may have notable problems with self-selection, since students who choose to participate are likely more motivated academically than those who do not. Therefore, this study used quasi-experimental analyses within a large, longitudinal, multi-institutional dataset to explore the link between seminar participation and several student success outcomes. Overall, the use of propensity score analyses substantially alters the results, such that first-year seminars are positively associated with first-year college satisfaction, but they have no effect on fourth-year satisfaction, college grades, retention, or four-year graduation within the full sample. This lack of impact is largely consistent regardless of whether the seminar is designed to engage students in academic inquiry or to promote orientation and academic success. Additional analyses observed some differential effects of first-year seminars by race/ethnicity, ACT score, and sex; the most consistent finding is that first-year seminars appear to promote the college grades and college satisfaction of Black students. Implications for future research and practice are discussed.
European Service Module - Structural Test Article (E-STA) Building Block Test Approach and Model Correlation Observations

The Orion European Service Module—Structural Test Article (E-STA) underwent sine vibration testing in 2016 using the Mechanical Vibration Facility (MVF) multi-axis shaker system at NASA Glenn Research Center’s (GRC) Plum Brook Station (PBS) Space Power Facility (SPF). The main objective was to verify the structural integrity of the European Service Module (ESM) under sine sweep dynamic qualification vibration testing. A secondary objective was to perform a fixed-base modal survey, while E-STA was still mounted to MVF, in order to achieve a test correlate the finite element model (FEM). To facilitate the E-STA system level correlation effort, a building block test approach was implemented. Modal tests were performed on two major subassemblies, the crew module/launch abort structure (CM/LAS) and the crew module adapter (CMA) mass simulators. These subassembly FEMs were individually correlated and then integrated into the E-STA FEM prior to the start of the E-STA sine vibration test. This paper summarizes the modal testing and model correlation efforts of both of these subassemblies and how the building block approach assisted in the overall correlation of the E-STA FEM. This paper will also cover modeling practices that should be avoided, recommended instrumentation positioning on complex structures, and the importance of the FEM geometrically matching CAD in sufficient detail in order to adequately replicate internal load paths. The goal of this paper is to inform the reader of the hard earned lessons learned and pitfalls to avoid when applying a building block test approach.
First-Pass Success Intubations Using Video Laryngoscopy Versus Direct Laryngoscopy: A Retrospective Prehospital Ambulance Service Study.

Abstract Objective In emergency medicine, endotracheal intubation is the gold standard for airway management. First-pass intubation success is beneficial because it secures the patient airway more quickly and avoids complications associated with repeated attempts, such as bleeding and swelling of soft tissue. The key to first-pass success is the ability to visualize the laryngeal inlet. Visualization can be accomplished using traditional direct laryngoscopy or video laryngoscopy. The purpose of our study was to compare the rate of successful first-pass endotracheal intubations using a video laryngoscope with that using a direct visualization laryngoscope in a prehospital emergency setting. Methods We retrospectively reviewed data that had been prospectively collected in our emergency department regarding patients who underwent endotracheal intubation performed by personnel from a single local ambulance service from January 1, 2014, through December 31, 2015. Results One hundred eighty-one patients were intubated using video laryngoscopy and 115 using direct visualization laryngoscopy. The first-pass endotracheal intubation success rate using video laryngoscopy was 12.6% higher than with direct laryngoscopy. Conclusion This retrospective study shows that video laryngoscopy had a higher first-pass success rate than direct laryngoscopy. This is promising because decreasing failure rates provide better patient outcomes.
Who's Buried in Custer's Grave?

On 10 October 1877, the year after the Battle of the Little Bighorn, General George A. Custer's coffin was transported from a temporary grave in Poughkeepsie, NY, by steamer and cortege to permanent interment in the U.S. Military Academy's Post Cemetery. The ceremony included the appropriate military and funerary rituals. There were, nevertheless, reasons to believe that Custer's skeleton may not have been in the coffin—thus, he may have missed his own funeral. Custer's remains, or part of them, may have been overlooked during the exhumation and left on the battle-field, only to be recovered around 1940. These bones, as well as those of another individual, were unceremoniously buried in a grave which is now marked “Two Unknown U.S. Soldiers” in the National Cemetery adjacent to the Little Bighorn Battlefield in Montana. That cemetery, perhaps appropriately enough, is named the Custer National Cemetery. This paper presents information concerning Custer's original interment on the Little Bighorn Battlefield, his supposed disinterment, and the osteological evidence that his remains, or at least part of them, were left on the Little Bighorn Battlefield.
Are reports of reduced field efficacy of diphacinone and chlorophacinone in California ground squirrels (Otospermophilus beecheyi) due to elevated rodenticide metabolism

Abstract Anticoagulant rodenticides are commonly used by agricultural producers to control California ground squirrels, Otospermophilus beecheyi, in a variety of crops. With this widespread use, producers are reporting reductions in the efficacy of diphacinone and chlorophacinone for ground squirrel control. Reductions in efficacy have been shown to be related to increased metabolism of compounds to non-toxic metabolites. This study examined liver metabolism of diphacinone and chlorophacinone using microsome isolations from squirrels captured in areas that had never used anticoagulants and areas with a history of prior use. Only male squirrels from anticoagulant exposed areas had a significant reduction in metabolic activity when compared to males from unexposed locations. Based on these data, the cause of the decreased anticoagulant rodenticide efficacy in ground squirrels does not seem to be related to anticoagulant rodenticide metabolism, but may be a result of other physiological (i.e. genetic resistance) or behavioral (bait avoidance) factors.
The Indigenous Inheritance: Critical Antecedents and State Building in Latin America and Southeast Asia

In comparative-historical analysis, countries are always different places before critical junctures set them on divergent pathways. By comparing the legacies of politicized ethnic diversity for the construction of state infrastructural power in Latin America and Southeast Asia, we elaborate the methodological and substantive importance of these “critical antecedents.” The critical antecedent in each region was the inheritance at independence of a sharp indigenous cleavage. This indigenous inheritance shaped threat perceptions and state-society coalitions in both regions in similarly powerful path-dependent ways—yet in intriguingly divergent directions. A salient indigenous cleavage hindered but did not preclude state building in nineteenth-century Peru, while fostering but not predestining state building in post–World War II Malaysia. Divergent levels of postcolonial state infrastructural power thus exhibit deep if indirect foundations in the identity cleavages inherited from preindependence eras. This cross-region comparative exploration highlights the analytical leverage gained from systematically incorporating preexisting cross-case differences into critical juncture accounts.
Risk assessment: extrapolation to individual risk.

Environmentally related disease is, in principle, preventable. Therefore, public health policies must be developed to minimize the risk from hazardous exposures which may be associated with some environmentally related diseases. An effort must be made to determine what the hazards of specific chemicals might be and how the hazards of one chemical compare with those of another. A variety of environmentally related factors are major determinants for human health: lifestyle (nutrition, smoking, etc.), exposure to infectious agents, and exposure to multiple chemicals and physical factors. However, it is extremely difficult to determine the health risk of low-level exposure to individual environmental pollutants and the impact that current preventive measures make on human health. For example, although a chemical exposure may theoretically cause some effect, in practice, at very low concentrations, many competing elements come into play, and the isolated contribution of individual chemicals to adverse health effects may appear to be of no consequence. Thus, the relationship between human health and environmental pollutants is extremely complex. Further, this relationship becomes even more complicated when considering its health significance on an individual level.
Dosage Adjustment of Irinotecan in Patients with UGT1A1 Polymorphisms: A Review of Current Literature

Objective: To review available literature regarding pharmacogenomics (PGx) effects on the metabolism of irinotecan by the UGT1A1 gene and the resulting dose adjustments based on PGx genetic variant. Summary: Irinotecan is a chemotherapy agent commonly used in treatment of various cancers such as metastatic colorectal cancer (mCRC) and others. The extent of decreased function of UGT1A1 varies based on genotype so irinotecan dose adjustments may be needed. Those with UGT1A1 homozygous *28/*28 genotype may experience 70% reduction in activity, while heterozygous genotypes with *1/*28 may only experience 30% loss. UGT1A1*6 variants may also play a role in decreased function. The incidence of *28 and *6 alleles varies among ethnic populations resulting in the need for dosage adjustments to avoid toxicities. Conclusion: These findings add to a growing body of literature that suggest patients with UGT1A1 *28 or *6 variant alleles benefit from lower doses of irinotecan. However, due to the heterogeneity of currently available studies, more evidence that investigates various regimens in different patient populations is needed to determine the most appropriate dosing strategies. Although other factors, as well as efficacy considerations will likely influence clinical decision making, genotype may be an important factor when determining dose. Review Article
Are criminals strategic? Offender responses to drug sentencing cutoffs

Abstract In many US states, punishment severity for drug offenses increases discontinuously at established quantity limits. Theory predicts that these laws create bunching of offenders at these limits and dominated regions beyond, where it ex-ante appears irrational to locate. These policies provide a novel setting to test for deterrence along a different margin that typically considered in the literature and generate new evidence on the extent to which offenders respond to incentives. Using arrest reports from 28 states and leveraging variation from quantity cutoff changes through time, I find evidence of strategic bunching by offenders in response to cutoff policies.
A simulation-optimization framework for post-disaster allocation ofmental health resources

Abstract. Extreme events, such as natural or human-caused disasters, cause mental health stress in affected communities. While the severity of these outcomes varies based on socioeconomic standing, age group, and degree of exposure, disaster planners can mitigate potential stress-induced mental health outcomes by assessing the capacity and scalability of early, intermediate, and long-term treatment interventions by social workers and psychologists. However, local and state authorities are typically underfunded, understaffed, and have ongoing health and social service obligations that constrain mitigation and response activities. In this research, a resource assignment framework is developed as a coupled-state transition and linear optimization model that assists planners in optimally allocating constrained resources and satisfying mental health recovery priorities post-disaster. The resource assignment framework integrates the impact of a simulated disaster on mental health, mental health provider capacities, and the Center for Disease Control and Prevention's (CDC) Social Vulnerability Index (SVI) to identify vulnerable populations needing additional assistance post-disaster. In this study, we optimally distribute mental health clinicians to treat the affected population based upon rulesets that simulate decision-maker priorities, such as economic and social vulnerability criteria. Finally, the resource assignment framework maps the mental health recovery of the disaster-affected populations over time, providing agencies a means to prepare for and respond to future disasters given existing resource constraints. These capabilities hold the potential to support decision-makers in minimizing long-term mental health impacts of disasters on communities through improved preparation and response activities.
Pearls and Pitfalls of Imaging of the Developing Pediatric Skeleton: Differentiating Normal and Pathology With MRI

Developmental changes occurring in the pediatric skeleton throughout childhood cause imaging appearances that may be confused with pathology. Knowledge of the typical pattern of red to yellow bone marrow conversion and areas of normal developmental irregular ossification is essential for radiologists interpreting musculoskeletal imaging in children to avoid mistaking normal findings for disease. Here we review the normal conversion of hematopoietic to yellow marrow on pediatric MRI and illustrate how MRI can distinguish the normal areas of irregular ossification from various pathology that can occur at and around growth centers in the developing skeleton.
Gluconobacter oxydans Knockout Collection Finds Improved Rare Earth Element Extraction

Abstract Rare earth elements (REE) are critical components of our technological society and essential for renewable energy technologies. Traditional thermochemical processes to extract REE from mineral ores or recycled materials are costly and environmentally harmful1, and thus more sustainable extraction methods require exploration. Bioleaching offers a promising alternative to conventional REE extraction2–4, and is already used to extract 5% of the world’s gold, and ≈ 15% of the world’s copper supply5,6. However, the performance of REE bioleaching lags far behind thermochemical processes2,7–9. Despite this, to the best of our knowledge no genetic engineering strategies have yet been used to enhance REE bioleaching, and little is known of the genetics that confer this capability. Here we build a whole genome knockout collection for Gluconobacter oxydans B58, one of the most promising organisms for REE bioleaching10, and use it to comprehensively characterize the genomics of REE bioleaching. In total, we find 304 genes that notably alter production of G. oxydans’ acidic biolixiviant, including 165 that hold up under statistical comparison with wild-type. The two most impactful groups of genes involved in REE bioleaching have opposing influences on acid production and REE bioleaching. Disruption of genes underlying synthesis of the cofactor pyrroloquinoline quinone (PQQ) and the PQQ-dependent membrane-bound glucose dehydrogenase all but eliminates bioleaching. In contrast, disruption of the phosphate-specific transport system accelerates acid production and enhances bioleaching. We identified 6 disruption mutants, that increase bioleaching by at least 11%. Most significantly, disruption of pstC, encoding part of the phosphate-specific transporter, pstSCAB, enhances bioleaching by 18%. Taken together, these results give a comprehensive roadmap for engineering multiple sites in the genome of G. oxydans to further increase its bioleaching efficiency.
Factor VIIIa A2 subunit residues 558-565 represent a factor IXa interactive site.

Factor VIIIa is a non-covalent heterotrimer of A1, A2, and A3-C1-C2 subunits. Previously, we speculated that the central portion of the A2 subunit, in and around the activated protein C-sensitive bond at Arg562-Gly (Fay, P. J., Smudzin, T.M., and Walker, F.J. (1991) J. Biol. Chem. 266, 20139-20145), is important for macromolecular interactions within the factor Xase enzyme complex. A peptide corresponding to factor VIII residues 558-565, SVDQRGNQ and designated FVIII558-565, was chemically synthesized and inhibited factor Xa generation in a purified system with an apparent KI of 105 microM. Tryptic cleavage of FVIII558-565 eliminated its inhibitory activity, whereas a scrambled sequence version of the peptide possessed < 30% the inhibitory activity of the native version. Overlapping peptides FVIII556-564 and FVIII561-569 were also inhibitory and confirmed the importance of residues in and around the scissile bond for functional factor Xase. Kinetic analysis revealed that peptide-mediated inhibition was non-competitive with respect to factor X. However, increasing factor IXa concentration overcame the observed inhibition. Furthermore, the peptide inhibited the factor IXa-dependent enhancement of factor VIIIa reconstituted from isolated A1/A3-C1-C2 dimer plus A2 subunit. Isolated factor VIII heavy chain (contiguous A1-A2 domains) was cleaved at Arg336 by an equimolar concentration of factor IXa in a reaction that was phospholipid-independent. No proteolysis of the isolated A1 subunit was observed in a similar reaction. These results indicate that the A2 subunit sequence delineated by residues 558-565 contributes to the interaction of cofactor with protease and that this interaction is essential for intrinsic factor Xase activity. Furthermore, that this peptide blocks both factor Xase activity and the capacity of factor IXa to stabilize the labile factor VIIIa heterotrimer suggest that this latter property is of physiologic significance.
Does plant immunity play a critical role during initiation of the legume-rhizobium symbiosis?

Plants are exposed to many different microbes in their habitat. These microbes may be benign or pathogenic, but in some cases they are beneficial. The rhizosphere provides an especially rich palette for colonization by beneficial (associative and symbiotic) microorganisms, which raises the question as to how roots can distinguish such ‘friends’ from possible ‘foes’ (i.e., pathogens). Plants possess an innate immunity system that can recognize pathogens, through an arsenal of protein receptors. These receptors include receptor-like kinases (RLK) and receptor-like proteins (RLP) located at the plasma membrane, as well as intracellular receptors (so called NBS-LRR proteins or R proteins) that recognize molecules released by microbes into the plant cell. The key rhizobial, symbiotic signaling molecule (called Nod factor) is perceived by the host legume plant using LysM-domain containing RLKs. Perception of the symbiotic Nod factor triggers signaling cascades leading to bacterial infection and accommodation of the symbiont in a newly formed root organ, the nodule, resulting in a nitrogen-fixing root nodule symbiosis (RNS). The net result of this symbiosis is the intracellular colonization of the plant with thousands of bacteria; a process that seems to occur in spite of the immune ability of plants to prevent pathogen infection. In this review, we discuss the potential of the invading rhizobial symbiont to actively avoid this innate immunity response, as well as specific examples of where the plant immune response may modulate rhizobial infection and host range.
Studies of antigenicity of human ovarian tissue.

Abstract Normal human ovarian extracts, after homogenization and isonation in physiologic saline, were found to contain specific antigens. These antigens are not serum proteins. They stimulated production of specific antibodies in rabbits. Ouchterlony double gel diffusion revealed two precipitation lines. One component was identical with that found in the human breast, Fallopian tube, and tubular fluid but not in the uterus. Little or no cross-reactivity occurred between ovaries from rabbits, cows, swine, dogs, frogs, turtles, guinea pigs, rats, and monkeys. Immunoelectrophoresis revealed that this antigen's mobility corresponded to that of a β-globulin.
The World's Rim: Great Mysteries of the North American Indians

Reviewed Medium: book Authors: Hartley Burr Alexander Year: 1999 Pages: 261 Publisher: Dover Publications Inc Prices: $8.95 US
The meaning of the interface: a functional and holistic evaluation of a meeting software system

Abstract A method for conducting apreliminary evaluation of a meeting software system is described and illustrated. The method assesses the degree of match between designer and user perspectives of a system by first defining and then evaluating the system in terms of its (1) interface, (2) functionality, and (3) holistic attributes. Applying the method, we were able to identify some preliminary strengths and weaknesses of a specific meeting software system. The application of this method illustrates how general principles developed by Card, Moran, and Newell [4], Silver [41], and other can be applied in a specific situation to assess the match between designer and user views of new meeting software technologies.
Influence of Bile Acid Replacement on Cyclosporine Absorption in a Patient With Jejunoileal Bypass

Jejunoileal bypass reportedly inhibits the absorption of cyclosporine. In patients with malabsorption syndromes, bile acid replacement has been given to enhance the absorption of cyclosporine. A candidate for heart transplantation with New York Heart Association class IV heart failure and a jejunoileal bypass received cyclosporine alone and with concomitant ursodiol administration to determine whether therapeutic cyclosporine plasma concentrations would be attainable after heart transplantation. There were no differences in peak concentration, time to peak, area under the serum concentration versus time curve, or bioavailability of oral cyclosporine when administered alone or with ursodiol. Plasma cyclosporine concentrations were consistent with those in the general population.
Air Quality of American Homes

In a survey of particulate fallout in homes it was found that there is a relation between pollution inside and outside a home. The level inside the home also depends on the location of the home (urban, suburban, or rural). Bathrooms and kitchens show heavier particle fallout than living rooms or bedrooms.
Unraveling the mystery of spinosad resistance in insects

Spinosad is a new and highly promising insecticide, derived from the bacteria Saccharopolyspora spinosa, with efficacy against a wide range of insects. The mechanism of action of spinosad appears to be unique, with a primary site of attack being the nicotinic acetylcholine receptor (nAChR) and a secondary site of attack being γ-aminobutyric acid (GABA) receptors. Neural nAChRs are composed of five subunits, with a minimum of 2 αs. Each subunit possesses a large N-terminal extracellular domain that includes the acetylcholine (ACh) binding site and four transmembrane domains (M1-4) with M2 contributing most of the amino acids that line the ion channel. Spinosad resistance has been selected for and characterized in several insect species. Generally, resistance is monofactorial, recessive and cannot be overcome by insecticide synergists. Spinosad resistance in the house fly maps to chromosome 1 and three nAChR subunit genes (α5, α6, and β3) are predicted to exist on chromosome 1 based on Drosophila/Musca homology maps. However, cloning and sequencing of Mdα5, Mdα6, and Mdβ3 from susceptible and spinosad resistant strains of house fly found no differences that could be associated with resistance. Unraveling the mystery of spinosad resistance in house flies will require further study.
Short-acting barbiturate sedation: effect on arterial pH and PaCO2 in children

One hundred and fifteen unpremedicated children, induced with thiamylal, a short-acting thiobarbiturate, administered rectally (25 mg·kg-1 body wt) or intravenously (6 mg·kg-1) had arterial pH of 7.36 ± 0.03 and PaCO2 of 40 · 4 mmHg. In 22 children over two years of age, the use of fentanyl (1.2 · 0.7 μg·kg-1) in addition to the thiamylal did not change blood gas data compared to those children over two years receiving only barbiturates (pH 7.36 vs 7.36, PaCO2 41 vs 40 mmHg). Children with cyanotic congenital heart disease showed similar pH andPaCO2 to acyanotic childrenfollowing administration of the short-acting barbiturate. Thiobarbiturates, given in a titrated fashion under direct observation, have clinically small effects on arterial pH and PaCO2 in paediatric patients.
Providing integrated toolkit-level support for ambiguity in recognition-based interfaces

Interfaces based on recognition technologies are used extensively in both the commercial and research worlds. But recognizers are still error-prone, and this results in human performance problems, brittle dialogues, and other barriers to acceptance and utility of recognition systems. Interface techniques specialized to recognition systems can help reduce the burden of recognition errors, but building these interfaces depends on knowledge about the ambiguity inherent in recognition. We have extended a user interface toolkit in order to model and to provide structured support for ambiguity at the input event level. This makes it possible to build re-usable interface components for resolving ambiguity and dealing with recognition errors. These interfaces can help to reduce the negative effects of recognition errors. By providing these components at a toolkit level, we make it easier for application writers to provide good support for error handling. Further, with this robust support, we are able to explore new types of interfaces for resolving a more varied range of ambiguity.
Putative bitter-taste receptor from porcine tongues.

DASTOLI and I reported earlier that we had found a sugar-complexing protein fraction in homogenates of bovine tongue epithelium1. Because the interaction of this fraction with sugars resembled in several respects the interactions of taste receptors in vivo, we suggested that it contained the chemoreceptor molecule for sweet-tasting compounds. The active component was subsequently purified and was characterized as a cationic protein of high molecular weight2.
Surgical implications of single coronary artery. A review and two case reports.

S ingle coronary artery is a rare anomaly which usually is of no clinical significance.4 In cardiac operations, however, the recognition of this anomaly may be of crucial importance. The present study describes the anatomic variants of single coronary artery, with emphasis on surgical implications. The literature is summarized since the publication of Smith’s collective review in 19.50, and two case reports are added.
Mini-sphenoidal electrodes in the investigation of seizures

A technique to record from the mesiobasal temporal region is described which can be performed as part of the routine EEG recording. The mini-sphenoidal electrodes were tolerated by all of the patients and were found to be fast, reliable and applicable to outpatient recordings. A small population of patients was studied which demonstrated that the electrodes added useful information not supplied by traditional scalp electrodes in the evaluation of patients with seizure disorders. The electrodes provided information comparable to traditional sphenoidal electrodes, although decreased in amplitude.
RNase II is important for A-site mRNA cleavage during ribosome pausing

In Escherichia coli, translational arrest can elicit cleavage of codons within the ribosomal A site. This A-site mRNA cleavage is independent of RelE, and has been proposed to be an endonucleolytic activity of the ribosome. Here, we show that the 3'-->5' exonuclease RNase II plays an important role in RelE-independent A-site cleavage. Instead of A-site cleavage, translational pausing in DeltaRNase II cells produces transcripts that are truncated +12 and +28 nucleotides downstream of the A-site codon. Deletions of the genes encoding polynucleotide phosphorylase (PNPase) and RNase R had little effect on A-site cleavage. However, PNPase overexpression restored A-site cleavage activity to DeltaRNase II cells. Purified RNase II and PNPase were both unable to directly catalyse A-site cleavage in vitro. Instead, these exonucleases degraded ribosome-bound mRNA to positions +18 and +24 nucleotides downstream of the ribosomal A site respectively. Finally, a stable structural barrier to exoribonuclease activity inhibited A-site cleavage when introduced immediately downstream of paused ribosomes. These results demonstrate that 3'-->5' exonuclease activity is an important prerequisite for efficient A-site cleavage. We propose that RNase II degrades mRNA to the downstream border of paused ribosomes, facilitating cleavage of the A-site codon by an unknown RNase.
Development of peptide antagonists that target estrogen receptor-cofactor interactions.

We have developed a series of high-affinity peptide antagonists that inhibit the transcriptional activity of both subtypes of the human estrogen receptor (ERα and ERβ). We believe that it will be possible to develop these peptides, or corresponding peptidomimetic derivatives, into pharmaceuticals for use in the treatment of breast cancer and other estrogenopathies. It is anticipated that drugs of this type could be used in combination with classical antiestrogens, such as tamoxifen, to achieve a complete blockage of ER-transcriptional activity. Although ER has been the primary target of our studies to date, it is likely that the insights gained from this work will apply to other nuclear receptors and transcription factors.
The Interglobular Domain of Cartilage Aggrecan Is Cleaved by Hemorrhagic Metalloproteinase HT-d (Atrolysin C) at the Matrix Metalloproteinase and Aggrecanase Sites

Two primary cleavage sites have been identified within the interglobular domain of the cartilage aggrecan core protein: one is between amino acid residues Asn 341 and Phe342, where many matrix metalloproteinases (MMP) have been shown to cleave; and the other is between amino acid residues Glu373 and Ala374. Although cleavage at the Glu373-Ala374 site is believed to play a critical role in cartilage aggrecan degradation in arthritic diseases, the enzyme responsible for cleavage at this site, "aggrecanase," has not been identified. Members of the ADAM (a disintegrin and metalloproteinase) family of proteins, which shows structural homology to the snake venom hemorrhagic metalloproteinases (reprolysins), have recently been demonstrated to be expressed in articular chondrocytes. Because many ADAM family members have a putative proteinase function, this raises the possibility that aggrecanase may be a member of this family of proteases. To examine whether reprolysins have the ability to cleave aggrecan at either the aggrecanase site or the MMP site, the snake venom hemorrhagic toxin metalloproteinase HT-d (atrolysin C) was tested for its ability to cleave bovine aggrecan monomer. Cleavage was monitored using the BC-3 antibody, which recognizes aggrecan fragments with the new NH2 terminus ARGSV generated by cleavage at the aggrecanase site, and with the AF-28 antibody, which recognizes aggrecan fragments with the new NH2 terminus FFGVG generated by cleavage at the MMP site. Cleavage at both the aggrecanase and MMP sites occurred in a concentration-dependent manner with 100 nM atrolysin C or greater. AF-28-reactive fragments were generated by 30 min of incubation, and levels were maximal by 8 h; BC-3-reactive fragments were detected at 2 h and continued to increase through 48 h, thus suggesting that atrolysin C can cleave at the MMP and aggrecanase sites. NH2-terminal aggrecan fragments generated by cleavage at the aggrecanase site were also detected using antisera recognizing the new COOH terminus, NITEGE, formed by cleavage at the Glu373-Ala374 bond, indicating that cleavage at this site does not require prior cleavage at the MMP site. These data provide the first demonstration that a reprolysin can cleave the core protein of aggrecan and the first example of a specific protease that can cleave at the aggrecanase site independent of cleavage at the MMP cleavage site.
Peptide ligand structure influences the exchange of 2-microglobulin by cell surface K b

Abstract We have studied the interactions which occur between the peptide ligand and β 2 -microglobulin ( β 2 m) components of the class I MHC complex by analysing the process of β 2 m exchange. We have previously shown that the rate of β 2 m exchange on a cell-surface class I MHC complex varies with the peptide ligand to which it is bound. It remains unclear, however, whether the ability of peptide ligand to alter β 2 m/heavy-chain association is related to peptide affinity, peptide structure, or both. In this article, we examine the effects of variations in peptide ligand structure on the rate of β 2 m exchange by cell surface K b complexes. Using a panel of alanine substituted variants of the MCMV peptide (YPHFMPTNL), we show that single amino acid changes in peptide sequence can have dramatic effects on the rates of β 2 m exchange. The observed changes in β 2 m exchange rates are directly due to modification of the peptide ligand structure as they do not reflect changes in peptide affinity. These findings suggest that peptide ligand structure can induce conformational changes in the K b heavy chain which alter the rates of cell surface β 2 m exchange, and provide further evidence for peptide-dependent fluidity of the class I heavy chain.
Distribution Of Traction Forces Associated With Shape Changes In Migrating Amoeboid Cells

Amoeboid motility results from the cyclic repetition of a repertoire of shape changes leading to periodic oscillations of cell area (motility cycle). This study aimed to identify the dominant shape changes and their association to the regulated activity and localization of molecular motors. For this purpose, we applied Principal Component Analysis (PCA) to time-lapse measurements of cell shape, traction forces and fluorescence from the F-actin-binding protein limEΔcoil-GFP in migrating Dictyostelium cells. This method provides the most significant cell shape changes of the motility cycle, together with maps of the traction forces and F-actin distribution associated with each shape change mode. It also sorts these modes according to their contribution to the variance of the cell area oscillations observed during the motility cycle. Using wild-type cells (wt) as reference, we investigated myosin II activity by studying myosin II null cells (mhcA-) and essential light chain null cells (mlcE-). The results revealed that wt, mlcE- and mhcA- cells implement similar shape changes during their motility cycle, although they are implemented at a slower pace in myosin mutants. The repertoire of shape changes is surprisingly reduced as only three modes are enough to represent 67% of the variance in cell area in wt, mlcE- and mhcA- cells. The three principal shape modes are dilation/elongation, a half-moon shape and bulging of the front/back. The second of these modes represents sideways protrusion/retraction, is associated to lateral asymmetries in the cell traction forces / F-actin distribution, and is significantly less important in mhcA- cells. These results indicate that the mechanical cycle of traction stresses and cell shape remains similar but is slowed down when myosin function is lost, probably due to a reduced control on the spatial organization of the traction stresses.
Comparing students' feedback about clinical instruction with their performances.

Validation of students' feedback as a measure of teaching effectiveness has been problematic for courses teaching clinical skills. This is true in part because establishing a valid and reliable method of assessing students' mastery of clinical skills has been a stumbling block. Reported here is the
Searching for targets of viral microRNAs.

The identification of targets of virally encoded microRNAs is essential to understanding their role in the viral life cycle. A new study reports the successful use of a microarray-based approach to identify a key target of a microRNA encoded by Kaposi's sarcoma–associated herpesvirus, with implications for microRNA target identification in other contexts as well.
Endurance and resistance exercise induce muscle fiber type specific responses in androgen binding capacity

This study examined the effects of different exercise training programs on androgen receptor content and receptor affinity to dihydrotestosterone in fast glycolytic (FG) and slow oxidative (SO) skeletal muscle fibers in rats. Twenty-four male Sprague-Dawley rats were equally divided into three groups: control, endurance exercise trained and resistance exercise trained. After the exercise programs were completed, the extensor digitorum longus (EDL), predominantly a FG muscle, and the soleus, predominantly a SO muscle, were isolated, weighted and both androgen receptor content and affinity to dihydrotestosterone were determined. Resistance training evoked a significant (P < 0.05) hypertrophic response in the soleus but not the EDL. Endurance training was not associated with any significant hypertrophy in either the soleus or the EDL. Neither the endurance nor the resistance training program resulted in changes in androgen receptor affinity to dihydrotestosterone. However, alterations in androgen receptor content were noted. The endurance training program resulted in a significant increase in androgen receptor content in the soleus, but no significant difference in the EDL. The resistance training program elicited a significant decrease in androgen receptor content in the soleus, and a significant increase in the EDL. These results indicate that different exercise stimuli induce changes in androgen receptor content that are specific to skeletal muscle fiber type.
Effectiveness of nasal irrigation for chronic rhinosinusitis and fatigue in patients with Gulf War illness: protocol for a randomized controlled trial.

Abstract Introduction Gulf War Illness (GWI) affects 1 in 7 returned Persian Gulf War veterans. Quality-of-life impact is large; there is no cure. Chronic sinus symptoms and fatigue are common. Nasal irrigation with saline (NI-S) or xylitol (NI-X) improve sinus symptoms and fatigue in the general population. This trial will assess the effect of NI-S and NI-X on sinus and fatigue symptoms, economic outcomes and pro-inflammatory milieu among participants with GWI. Methods 75 participants (age 35 to 65 years, 25 in each of three arms) with GWI will be recruited from the Veteran's Administration and the community. They will use routine care for sinus symptoms and fatigue and be randomized to continued usual care alone or additional therapy with NI-S or NI-X. Participants will be able to adjust specific elements of the NI procedure. The primary outcome (Sinonasal Outcome Test, SNOT-20) and other self-reported assessments will occur at baseline, 8 and 26 weeks; lab assessment of pro-inflammatory cellular and cytokine profiles will occur at baseline and 26 weeks. Other outcomes will include fatigue-specific and overall health-related quality of life, pro-inflammatory cellular and cytokine profiles, cost-effectiveness and participant satisfaction. Results Baseline demographic and clinical data from the first 10 participants show effective participant recruitment, enrollment, randomization, retention and data collection. Conclusion Early study conduct suggests that our participant-oriented approach will yield high rates of participant adherence and data capture, facilitating robust analysis. Results of this study will clarify the value of NI for chronic sinus symptoms and fatigue among patients with GWI. Clinical trial registration clinicaltrials.gov identifier NCT01700725 .
SOLUBILITY AND ABSORBABILITY IN ENDODONTICS: NEED FOR CLARIFICATION OF TERMINOLOGY.

Accuracy in terminology is extremely im­ portant in every facet of human endeavor. Inaccurate definitions have been a stum­ bling block to progress in an important phase of dentistry— endodontics. In the United States the final filling for root canals almost always consists of materials which are referred to as non­ absorbable, nonresorbable or insoluble. Much endodontic treatment in Europe is performed with a soluble or, as it is often called, a resorbable paste as the final filling material. This article will attempt to show that the terms, resorbable, absorbable and sol­ uble, and the negatives of these terms, are used incorrectly and inaccurately. This loose terminology hinders progress. TYPES OF SEALERS
Frustration and production in purelines of chickens and their reciprocal crosses

Abstract Frustration, fear and production traits were measured in four populations of White Plymouth Rock pullets that were maintained singly in wire cages. The populations consisted of two purelines and their reciprocal crosses. Significant differences were found between the purelines for frustration, as measured by head flicking. Means for the cross-line pullets were similar to that of the parental line with lower value, and significantly different from the parental line with the higher value. Highly significant differences were found among lines for fear, with the average of the reciprocal cross means being the same as the mid-parent average of the purelines. Within population, phenotypic correlations showed no relationship between frustration and fear. Also there was no evidence, under our husbandry conditions, that frustration and fear were associated with either body weight, age at first egg or egg production.
A Cyber-Physical Systems architecture for Industry 4.0-based manufacturing systems

Abstract Recent advances in manufacturing industry has paved way for a systematical deployment of Cyber-Physical Systems (CPS), within which information from all related perspectives is closely monitored and synchronized between the physical factory floor and the cyber computational space. Moreover, by utilizing advanced information analytics, networked machines will be able to perform more efficiently, collaboratively and resiliently. Such trend is transforming manufacturing industry to the next generation, namely Industry 4.0. At this early development phase, there is an urgent need for a clear definition of CPS. In this paper, a unified 5-level architecture is proposed as a guideline for implementation of CPS.
Time course for changes in aerobic capacity and body composition in overweight men and women in response to long-term exercise: the Midwest Exercise Trial (MET)

OBJECTIVE: To determine the time course for changes in aerobic capacity, body weight (BW), and composition in overweight adults in response to a supervised exercise trial with a targeted energy expenditure of 2000 kcal week−1. DESIGN: The Midwest Exercise Trial (MET) was a randomized, controlled, 16-month verified, supervised exercise trial. Aerobic exercise progressed to 45 min day−1, 5 days week−1 over 6-months and was then maintained for 10 months. Controls maintained their normal physical activity and all participants maintained ad libitum diets. SUBJECTS: A total of 131 participants were randomized to exercise or control groups and 74 completed the intervention and all laboratory testing. MEASUREMENTS: At baseline and months 4, 9, 12, and 16, aerobic capacity (VO2max) was measured by indirect calorimetry, BW by digital scale, and fat weight and fat-free weight by hydrostatic weighing. RESULTS: Aerobic capacity (ml kg−1 min−1) increased (P<0.05) from baseline (39.2±5.2, mean±s.d.) to 9 months (48.8±4.3) in exercising men as well as women (32.8±4.2–39.6±5.5) with no significant changes occurring at 12 or 16 months. From baseline to 9 months BW (94.0±12.6–88.7±9.7 kg) and fat weight (26.8±6.8–21.8±4.5 kg) significantly decreased in exercising men with no changes occurring at 12 or 16 months. There were no changes in fat-free weight across the 16 months for exercising men or for BW or composition in exercising women. Further, there were no significant changes for the control men for aerobic capacity, BW, or body composition across 16 months. Women in the control group showed significant increases in weight of 2.9±5.5 kg and fat weight of 2.1±4.8 kg at 16 months only. CONCLUSIONS: We recommend that investigations that use exercise without diet as the stimulus for weight loss have at least a 9-month duration to provide sufficient time for the full effects to be realized, should such effects be present.