cssi/SciSciGPT-SciSciNet huggingface dataset:
EUS--predicting the future?

Abstract QUESTION: What endosonographic findings are predictive of long term survival in patients with esophageal carcinoma? DESIGN: Retrospective review. SETTING: University in the United States (University of Pennsylvania, Philadelphia, PA). PATIENTS: Two hundred three consecutive patients with biopsy-proven esophageal/gastroesophageal junction carcinoma over a 66-month period. DATA: Medical records for each patient were reviewed for patient demographics, endoscopic ultrasonography (EUS) stage, patient’s treatment, and survival outcome. Patient survival was tracked from hospital records, social security death records, or primary physician records. INTERVENTION: Two endoscopists performed all of the endosonographic staging. All of the patients were classified according to American Joint Committee on Cancer staging criteria, and celiac lymphadenopathy was determined. Patient treatment was categorized as 1) surgery alone, 2) surgery plus adjuvant therapy, 3) chemotherapy with or without radiation therapy, 4) photodynamic therapy, 5) palliative treatment, and 6) strategy unknown. The most common chemotherapy regiment was 5-fluorouracil and cisplatin. MAIN OUTCOME: The primary outcome was median survival. This was defined as the time from the date of EUS staging to the date of death. PATIENT DATA: In this study 203 patients were enrolled and the mean age was 65 yr. The mean follow-up was 35.4 months. There was a male predominance (85%), and the majority of the patients had esophageal adenocarcinoma (72.9% adenocarcinoma, 27.1% squamous cell carcinoma). Of the cases, patient treatment was recorded in 92% and survival was determined in 96.5%. MAIN RESPONSE: The overall survival irrespective of tumor stage and treatment was 17.8 months. Median survival was determined according to each of the tumor and node stages and the presence or absence of celiac lymphadenopathy using the Kaplan-Meier survival curve. Lower-staged tumors (T stages 0 and 1) were found to have a longer mean survival (T0 median survival > 26.7 months vs T4 median survival p = 0.0005) when compared by the log rank test. In this analysis there was no difference in survival when comparing T2 stage with any other stage. With the log rank test, the presence of malignant-appearing lymphadenopathy (stage N1) was associated with a statistically significant difference in median survival (13.5 months vs >25 months) ( p vs 23.8 months) ( p = 0.0049). With multivariate analysis, only the N stage was predictive of survival. CONCLUSION: EUS staging can accurately predict survival of patients with esophageal cancer. The presence of regional nodal involvement is an independent predictor of survival irrespective of T stage, celiac lymphadenopathy, and treatment received. FUNDING: None noted.
Identification of Rotavirus VP6-Specific CD4+ T Cell Epitopes in a G1P[8] Human Rotavirus-Infected Rhesus Macaque

A non-human primate model was used to evaluate its potential for identification of rotavirus viral protein 6 (VP6) CD4+ T cell epitopes. Four juvenile rhesus macaques were inoculated with a mixed inoculum (G1P[8] and G9P[8]) of human rotaviruses. Infection accompanied by G1P[8] shedding was achieved in the two macaques that had no rotavirus immunoglobulin A (IgA) in plasma. To measure the interferon gamma (IFN-γ) and tumor necrosis factor (TNF) anti-viral cytokines produced by peripheral CD4+ cells that recognize VP6 epitopes, whole blood cells from one infected macaque were stimulated in vitro with VP6 peptides. Stimulation with peptide pools derived from the simian rotavirus VP6(161-395) region revealed reactivity of CD4+ T cells with the VP6(281-331) domain. A VP6(301-315) region was identified as the epitope responsible for IFN-γ production while a broader VP6(293-327) domain was linked to TNF production. These results suggest that human rotavirus-infected macaques can be used for identification of additional epitopes and domains to address specific questions related to the development of pediatric vaccines.
Properties of Rocks and Minerals – Seismic Properties of Rocks and Minerals, and Structure of the Earth

We examine the role of mineral physics as the interpretive link between seismological observations of the structure of the Earth’s interior and its dynamics and evolution. We focus mostly on Earth’s mantle because the problem of determining the chemical and thermal state is particularly rich and because substantial progress has been made in the last decade, although we also discuss the core. With Earth structure as an organizing principle, we review those aspects of the physical properties and behavior of mantle minerals and assemblages that are most important for interpreting seismological observations and to relating those observations to the thermal and chemical state and evolution of the interior. A discussion of the one-dimensional elastic structure of the mantle emphasizes the origin of high gradient zones and discontinuities. We continue with a discussion of lateral variations in seismic structure and their interpretation in terms of lateral variations in temperature, composition, and phase. A discussion of anisotropy highlights the many important advances that have been made, particularly in our knowledge of the full elastic constant tensor of minerals, and also the formidable difficulties remaining, including a need for a better understanding of deformation mechanisms. We end with that part of Earth’s seismic structure that is currently least amenable to interpretation, the anelastic part, indicating important developments in our understanding of the relevant material properties, and the gaps in our knowledge that remain.
Payoff-based communication adaptation based on network service availability

Interactive applications will continue to push the limits of available network bandwidths, processing speeds, and other computing resources. These applications present challenges concerning the specification of service requirements for their multiple types of data transfer and the online management of service quality. We present a cooperative solution in which a configurable communication layer is used to adapt communication in response to both application requirements and network resource availability. Adaptation decisions are based on: (1) payoff functions which capture the requirements of the application in a functional form, and (2) service availability curves which represent network resource availability. Experimentation with representative multimedia applications demonstrates the benefit of using such payoff based adaptation.
Properties of a cell-bound homogeneous murine IgM anti-dextran--V. Effects of density of cell-bound IgM on immunological activities.

Abstract O-stearoyl dextran coated sheep erythrocytes (OSD-E) were sensitized with increasing amounts of MOPC 104E IgM to give IgM-OSD-E in antigen excess, in equivalence and in antibody excess. These zones were defined operationally by susceptibility of the cells to complement-mediated lysis, and by the number of free Fab regions on the cell-bound IgM. The free Hab regions were measured by ability to (a) bind soluble dextran and (b) to react with and participate in complement-mediated lysis of bystander OSD-E. In antigen excess, complement-mediated lysis is proportional to cell-bound IgM and there are few free Fab regions. In the equivalence zone, complement-mediated lysis reaches a plateau, while the number of free Fab regions becomes significant. Throughout the zone of antihody excess, complement-mediated lysis diminishes while the number of free Fab region increase exponentially. Blocking these free Fab regions with soluble dextran prevents reactions with bystander OSD-E. he rate of reaction of IgM-OSD-E, in antibody excess, with bystander OSD-E is proportional to reaction temperature and the extent of reaction is proportional to cell concentration.
Performances of innocence and deviance in Disney cosplaying

Disney cosplayers are uniquely positioned in relationship to the characters they perform because of Disney's reliance on innocence as a narrative trope and character element. Their cosplaying transmutes normative innocence via performative fan practice.
Moisture control in retrofit commercial roof insulations

Commercial buildings built prior to the current period of soaring energy costs have typically been underinsulated and increasingly expensive to operate. Current methods for installing retrofit insulation in these buildings may have limitations due to severe climates or high interior humidity conditions. These factors can lead to condensation at the roof deck. The ability to predict when problems will occur depends largely on the understanding of the heat and mass transfer mechanisms and the coupling between them. Experimental and analytical models have been developed to permit the evaluation of retrofit roof insulation systems in terms of their potential for condensation. This method is now being used to evaluate various commercial roof insulation systems. Some preliminary results demonstrating the transient predictions and measured values available from this procedure are displayed. Good agreement between the experimental and analytical models is shown. Refinements and improvements in the procedure are suggested.
Factors Affecting the Time to Burst in Exploding Wires

Studies of Al, Cu, Ag, Au, Pd, and Pb wires are being conducted using a condenser bank of 11.4 kj maximum storage capacity. The order of increasing times to burst, which is not the same as the order of decreasing first-pulse energies, is Pb < Al < Au < Ag < Cu ≈ Pd. Resu lts with numerous sets of Al samples of constant length but cross sections varying by a factor of about 25 show a linear relationship between the cross-sectional area A and the time to burst, at constant initial voltage. This linearity is shown to be consistent with a theoretical relationship, previously derived, which emphasizes the hydrodynamic energy per unit length and the radial expansion.
Lipid Metabolism and Prebiotic Synthesis of Lipids

This chapter discusses fatty acid breakdown, synthesis membrane biosynthesis, and possible prebiotic pathways for the synthesis of lipids. Degradation of fatty acid occurs through the process of fatty acid breakdown that occurs in blocks of two-carbon atoms; oxidation of saturated fatty acids occurs in the mitochondria in eukaryotes; and fatty acid oxidation yields large amounts of adenosine triphosphate. First step in fatty acid synthesis is catalyzed by acetyl-coenzyme A carboxylase. Seven reactions are catalyzed by the fatty acid ligase. This chapter discusses synthesis of phospholipids, which explains that phospholipids are amphipathic compounds. Phosphatidic acid reacts with CTP to yield CDP-diacylglycerol, which, in bacteria, is converted to phosphatidylserine, phosphatidylglycerol, or diphosphatidylglycerol. Prebiotic synthesis of lipids explains that strenuous conditions have been used by organic chemists to synthesize fatty acid chains; saturated hydrocarbons can be synthesized under mild conditions with the help of iron sulfide; a prebiotic pathway that resembles the biosynthetic pathway; and the final step in lipid synthesis could be driven by dehydration. Saturated hydrocarbons can be synthesized under considerably milder conditions with the help of iron sulfide catalysts, which must have been abundant in the prebiotic world. The final step in lipid synthesis could be driven by dehydration. David Deamer has demonstrated that lipids can be made by heating to dryness mixtures of fatty acids, glycerol, and inorganic phosphate at 65°C.
Protein kinase C isoforms in human neutrophil cytoplasts

Granule-poor human neutrophil cytoplasts, prepared without heat or cytochalasin B treatment so as to preserve both motile function and activatable respira- tory burst oxidase, were investigated for their content of several isoforms of protein kinase C (P1(C). Immunoblot- ting with isoform-specific rabbit antibodies (Abs) to PKC revealed that both the a-specifIc and the i3(I and II)- specific Abs recognized a protein band of 78 kd comigrat- ing with PKC from rat brain cytosol. The 'y-specific anti- serum did not detect any protein of this molecular mass. The cytoplast 13-PKC band was more readily detected than the cytoplast a-PKC band. Antibodies to 131- or 13-Il- specific PKC sequences showed the /311 subtype to be the predominant form of f3-PKC, although some /31 was also found. The identity of the 78-kd cytoplast bands as PKC was established by the fact that phorbol ester treatment of intact cytoplasts induced translocation of the bands from cytosol to membrane fractions. However, whereas PKC specific activity was similar in cytoplast lysates and brain cytosol, immunoreactivity of cytoplast a- and /3- PKC bands was considerably less than that of rat brain. Hydroxylapatite chromatography of partially purified cytoplast PKC revealed two major peaks of PKC activity precisely coeluting with brain a- and 13-PKC and display- ing comparable enzymatic activities despite the relatively weak immunoreactivity of cytoplast a- and 13-PKC. To our knowledge, this is the first demonstration that human neutrophil-derived cytoplasts contain a, /31, and /311 forms of PKC and that each isoform translocates from cytosol to membrane upon exposure to phorbol ester at concentrations that induce superoxide production. In ad- dition, our evidence raises the possibility that cytoplasts may also possess other isoforms of PKC that we are un- able to detect with our a, /3, and y antibodies. Finally, the granule-poor cytoplasts seem a particularly useful prepa- ration in which to examine the role of individual PKC isoforms in neutrophil activation. J. Leukoc. Biol. 51: 84-92; 1992.
Selective termination for fetal anomaly/genetic disorder in twin pregnancy at 32+ menstrual weeks. Report of four cases.

Objectives: To conduct a pilot study of 4 cases of selective termination of a single abnormal fetus in a dichorionic, diamniotic twin pregnancy advanced to 32 or more menstrual week
A Multiwire Proportional Chamber for Imaging Thermal, Epicadmium, and Fast Neutrons

The 25 cm × 25 cm chamber described images thermal and epicadmium neutron beams using two boron-coated conversion screens, and fast neutrons using a single polyethylene converter. Sample images and quantitative attenuation and resolution data are presented. Measurements of neutron attenuation in lucite patterns give good agreement with expected values for thermal, epicadmium, and fast (Pu-Be) beams. The measured mean free paths were 0.30, 0.81, and 5.8 cm, respectively. Thermal neutron resolution (0.2 cm) depends upon ?-particle range, but resolution for fast neutrons (0.4 cm) appears to be limited by chamber thickness (to approximately one-half of the chamber thickness). Measurements involving digital image storage and manipulation are also described and illustrated.
Multi-scale Computational Models of Pro-angiogenic Treatments in Peripheral Arterial Disease

The induction of angiogenesis is a promising therapeutic strategy for the amelioration of peripheral arterial disease (PAD). This occlusive disease results in muscle ischemia, and neovascularization is a route to increasing the perfusion in the tissue. The vascular endothelial growth factor (VEGF) family of potent pro-angiogenic cytokines is a potential therapeutic agent, increasing VEGF-receptor signaling on tissue vasculature. To investigate the effects of possible therapies on the VEGF concentrations and gradients within the tissue, we consider three such strategies: VEGF gene therapy (e.g. by adeno-associated virus); VEGF cell-based therapy (injected myoblasts that overexpress VEGF); and chronic exercise (which upregulates VEGF receptor expression). The multi-scale computational model used to investigate these strategies is an integration of several components: an anatomical description of the muscle geometry and cell types; microvascular blood flow; tissue oxygen distribution; VEGF secretion from muscle fibers; VEGF transport through interstitial space; and VEGF-receptor binding on microvascular endothelial cells. Exercise training, which results in increased VEGF secretion in hypoxic tissue and increased VEGF receptor expression, exhibits increases in both VEGF concentration and VEGF gradients, and is predicted to be more effective than the other, VEGF-only treatments.
Transmission of the locoweed endophyte to the next generation of plants

Abstract Locoweed species of the legume genera Astragalus and Oxytropis (Fabaceae) contain the toxic alkaloid swainsonine, and poison livestock in semi-arid regions throughout the world. Recently, the endophyte Undifilum oxytropis (previously characterized as Embellisia spp.) was found in species of Astragalus and Oxytropis , and was shown to produce swainsonine. A survey of major locoweed species was conducted throughout the western U.S. in 2005 to verify the presence of the endophyte and swainsonine. Seed from these plants was collected to verify the transmission of the endophyte to progeny. In study 1, seed from each parent plant from which the endophyte could be cultured was germinated and seedlings were grown for 4–6 months and then harvested. The presence and quantity of the endophyte was determined by real-time PCR, and swainsonine concentration by LC/MS. The endophyte was transmitted to nearly all of the progeny, however, it was extremely low ( −1 , and swainsonine concentration ranged from 0.21 % to 0.79 %. In study 2, seeds were taken from parent plants in the original 2005 survey from which the endophyte could not be cultured, though its presence was detected by PCR. The seeds were germinated and seedlings were grown for 4 months. The endophyte was detected by PCR in 94 % of the progeny, but the amounts were very low ( −1 ) and swainsonine was not detected in any of the samples. It appears that U. oxytropis has near perfect (approaching 100 %) vertical transmission to the next generation of seedlings. However, a small proportion of the progeny had low endophyte/low or no swainsonine, and this characteristic was inherited in the next generation.
Transient tactile allodynia following intrathecal puncture in mouse: Contributions of Toll-like receptor signaling

Studies of spinal drug action in mice often involve percutaneous intrathecal drug administration delivered in a lightly anesthetized animal. A successful lumbar intrathecal (IT) needle stick of a lightly anesthetized (isoflurane) mouse evokes a tail flick, which is an indication of local spinal nerve stimulation. Immediately upon arousal, a hind paw tactile allodynia, as measured with von Frey hairs (pre 1.55±0.11 g vs. injected 0.66±0.08 g) lasts 3-4 h. In a similarly anesthetized mouse without the needle stick, a 1-h allodynia was noted. In studies on spinal Toll-like receptor (TLR) signaling, we observed that following intrathecal puncture and mechanical stimulation of the nerve roots mice deficient in TLR down-stream signaling (Myd88(-/-)/Trif(lps2)), displayed only the transient (1-h) allodynia otherwise observed following isoflurane alone. These data suggest that the extended period of hyperalgesia observed with needle penetration of the dura and mechanical stimulation of the nerve roots requires signaling through the MyD88/TRIF pathways and supports the intrinsic role of Toll-like receptors in the allodynia secondary to the minor nerve activation occurring during the intradural puncture.
Linkage of prostate cancer susceptibility loci to chromosome 1.

Three prostate cancer susceptibility genes have been reported to be linked to different regions on chromosome 1: HPC1 at 1q24–25, PCAP at 1q42–43, and CAPB at 1p36. Replication studies analyzing each of these regions have yielded inconsistent results. To evaluate linkage across this chromosome systematically, we performed multipoint linkage analyses with 50 microsatellite markers spanning chromosome 1 in 159 hereditary prostate cancer families (HPC), including 79 families analyzed in the original report describing HPC1 linkage. The highest lod scores for the complete dataset of 159 families were observed at 1q24–25 at which the parametric lod score assuming heterogeneity (hlod) was 2.54 (P=0.0006) with an allele sharing lod of 2.34 (P=0.001) at marker D1S413, although only weak evidence was observed in the 80 families not previously analyzed for this region (hlod=0.44, P=0.14, and allele sharing lod=0.67, P=0.08). In the complete data set, the evidence for linkage across this region was very broad, with allele sharing lod scores greater than 0.5 extending approximately 100 cM from 1p13 to 1q32, possibly indicating the presence of multiple susceptibility genes. Elsewhere on chromosome 1, some evidence of linkage was observed at 1q42–43, with a peak allele sharing lod of 0.56 (P=0.11) and hlod of 0.24 (P=0.25) at D1S235. For analysis of the CAPB locus at 1p36, we focused on six HPC families in our collection with a history of primary brain cancer; four of these families had positive linkage results at 1p36, with a peak allele sharing lod of 0.61 (P=0.09) and hlod of 0.39 (P=0.16) at D1S407 in all six families. These results are consistent with the heterogeneous nature of hereditary prostate cancer, and the existence of multiple loci on chromosome 1 for this disease.
The Effect of Selected Nonmusical Factors on Adjudicators’ Ratings of High School Solo Vocal Performances

The purpose of this study was to examine the effect of differentiated performance attire and stage deportment on adjudicators’ ratings of high school solo vocal performances. High school choral students (n = 153) and undergraduate (n = 97) and graduate music majors (n = 32) served as adjudicators (N = 282). Adjudicators rated recorded solo vocal performances displayed in audio-only and four audiovisual presentation conditions with differentiated combinations of performance attire and stage deportment. Performance quality ratings were affected significantly by soloists’ performance attire and stage deportment and adjudicators’ academic level. Significant two-way interactions were identified: adjudicator gender by academic level for comparisons of performance ratings assigned in four of the five presentation conditions and adjudicator gender by academic level when differentiated attire was isolated from presentation conditions. Adjudicators assigned significantly higher ratings to performances presented in ...
Effect of Acute Prior Exercise on Glycemic and Insulinemic Indices

Background: Acute exercise is associated with increased insulin sensitivity characterized by increased insulin-induced glucose transport for periods of up to 48h after the bout of exercise. This suggests that the glycemic response to a meal may be altered by prior exercise.Objective: We tested the hypothesis that the glycemic and insulinemic responses to a test food consumed following exercise would be lower than when consumed without prior exercise.Design: Four lean males (age: 27 ± 4 y) and 4 females (age: 23 ± 3 y) completed 3 experimental conditions in random order: ExCHO—Subjects exercised on a cycle ergometer at 70% VO2peak with a net energy cost of 400 kcal, which was followed by consumption of a high carbohydrate (CHO) energy bar; NoExCHO—Same as ExCHO except subjects sat quietly rather than exercised; and NoExGlc—Same as NoExCHO except subjects consumed a 50 g glucose (glc) drink as the reference CHO for GI and insulinemic index (II) determination. For each condition, following exercise or rest, ...
Lipid and Lipoprotein Metabolism in Chronic Kidney Disease

The risk of cardiovascular events and mortality increases as renal function declines although the relative risk of mortality contributed by the standard Framingham risk factors are altered or replaced. Low-density lipoprotein (LDL) cholesterol does not predict mortality but low high-density lipoprotein (HDL) cholesterol and triglycerides remain risk factors. The lipoproteins within each class are shifted to smaller, more dense isoforms. The accumulation of apolipoprotein B−containing lipoproteins, including lipoprotein(a) results primarily from decreased clearance rather than from increased synthesis. Lipoprotein(a) levels are also associated with cardiovascular outcome among dialysis patients. Decreased clearance of very low-density lipoprotein and intermediate-density lipoprotein is a result of decreased lipoprotein lipase, structural alterations in the lipoproteins rendering them poorer substrates, and a decrease in receptor number for these proteins. HDL levels are decreased as a result of an increased fractional catabolic rate both among obese patients with normal renal function and among dialysis patients, but the mechanisms responsible for increased HDL fractional catabolic rate may differ. In patients with advanced kidney disease, HDL fails to mature normally as a result of decreased lecithin cholesterol ester transfer protein, leaving cholesterol ester−poor, triglyceride-rich HDL3 and pre-β HDL. HDL in patients with chronic kidney disease is a less effective antioxidative agent than is HDL from normal subjects because of a decrease in paroxonase activity, allowing the accumulation of oxidized LDL.
Infrared spectra of activated acyl groups in deuterium oxide solution.

Abstract The principal infrared absorption bands of a number of carbonyl-containing compounds of biological significance in deuterium oxide solution are reported. Within a given class of compounds there appears to be some relationship between carbonyl frequency and “energy-rich” nature and/or reactivity toward nucleophilic reagents. No such relationship exists among compounds of widely different chemical structure, and it is suggested that this lack of correlation may be due to a differing relative importance of inductive and resonance effects in affecting carbonyl absorption frequency and reactivity. The markedly lower absorption frequency of carbonyl compounds in deuterium oxide, compared to nonpolar solvents or the vapor state, is attributed to hydrogen bonding of the carbonyl group to the solvent, which, as a form of general acid catalysis, may also increase the susceptibility of carbonyl groups to nucleophilic attack in aqueous solution.
Human papillomavirus (HPV) vaccine: a position statement of the Society for Adolescent Medicine.

Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide causing genital warts and nearly all cases of cervical cancer. On June 8 2006 the Food and Drug Administration approved a three-dose HPV vaccine for use in females 9 to 26 years of age. The vaccine has been shown to be safe and effective in preventing infection with HPV types 16 and 18 (which cause approximately 70% of cervical cancers) as well as types 6 and 11 (which cause > 90% of genital warts). As a prophylactic vaccine it is most effective when administered before the onset of sexual activity. Although this is the first vaccine designated as pregnancy category B vaccination is not recommended during pregnancy. (excerpt)
Semantic interference and associative facilitation from words presented in rapid serial visual presentation

Semantic interference in picture naming is readily obtained when categorically related distractor words are displayed with picture targets; however, this is not typically the case when both primes and targets are words. Researchers have argued that to obtain semantic interference for word primes and targets, the prime must be shown for a sufficient duration, prime processing must be made difficult, and participants must attend to the primes. In this article, we used a novel procedure for prime presentation to investigate semantic interference in word naming. Primes were presented as the last word of a rapid serial visual presentation stream, with the target following 600-1,200 msec later. Semantic interference was observed for categorically related targets, whereas facilitation was found for associatively related targets.
Scaled carbon-ionogel supercapacitors for electronic circuits

Capacitors are ubiquitous in signal processing circuits. Dielectric capacitors based on metal-oxide-semiconductor (MOS) and metal-insulator-metal (MIM) designs are currently the industry standard for on-chip charge storage. By comparison, electric double-layer capacitors (EDLC), or supercapacitors, offer capacitances that are orders of magnitude higher than dielectric capacitors. In this paper we present some early work in fabricating solid-state, on-chip EDLC.
Assay of the immune inhibitor in classic haemophilia: application of virus-antibody reaction kinetics.

Summary The kinetics of virus neutralization by antibody are shown to apply to factor-VIII neutralization by the immune antibody of haemophilic patients. The analysis established for virus neutralization has been used as a model for designing a general system for inhibitor assay based on mixtures in which antigen is present in excess, rather than with antibody in excess, as has been the case with systems previously proposed. The new system permits conversion of inhibitor potency results from other systems based on the use of different mixtures of factor VIII and inhibitor as long as factor VIII is in excess and as long as constant physical conditions of time and temperature of incubation are applied. It also takes account of the fact that some antibodies reveal a‘residual resistant fraction’ of antigen with which they cannot react. The procedure for converting assay data into‘Oxford units’ is described.
Inactivation of Murine Usp1 Results in Genomic Instability and a Fanconi Anemia Phenotype

Fanconi anemia (FA) is a human genetic disease characterized by chromosome instability, cancer predisposition, and cellular hypersensitivity to DNA crosslinking agents. The FA pathway regulates the repair of DNA crosslinks. A critical step in this pathway is the monoubiquitination and deubiquitination of FANCD2. Deubiquitination of FANCD2 is mediated by the ubiquitin protease, USP1. Here, we demonstrate that targeted deletion of mouse Usp1 results in elevated perinatal lethality, male infertility, crosslinker hypersensitivity, and an FA phenotype. Usp1(-/-) mouse embryonic fibroblasts had heightened levels of monoubiquitinated Fancd2 in chromatin. Usp1(-/-) cells exhibited impaired Fancd2 foci assembly and a defect in homologous recombination repair. Double knockout of Usp1 and Fancd2 resulted in a more severe phenotype than either single knockout. Our results indicate that mouse Usp1 functions downstream in the FA pathway. Deubiquitination is a critical event required for Fancd2 nuclear foci assembly, release from chromatin, and function in DNA repair.
Hemoptysis in rheumatic heart disease

Abstract 1. 1. Fifty cases of rheumatic heart disease in which hemoptysis occurred are analyzed. This complication is encountered in at least 10 per cent of all adults with rheumatic heart disease who are admitted to a general hospital. In our series, the average age at the onset of hemoptysis was 33.4 years. 2. 2. The symptoms most commonly associated with hemoptysis were palpitation, pain in the chest, and dyspnea. 3. 3. The associated anatomic, pathologic, and physiologic abnormalities, in the order of their frequency, were 3.1. (a) Mitral stenosis, in all but one case. 3.2. (b) Pulmonary infarction, in twenty-three cases. 3.3. (c) Multiple valve involvement, in twenty-two case 3.4. (d) Chronic auricular fibrillation, in twenty cases. Paroxysmal arrhythmia, in five cases. 3.5. (e) Marked cardiac enlargement, in nineteen eases. 3.6. (f) Active rheumatic infection, in twelve cases. 3.7. (g) Congestive failure, in eight cases. 3.8. (h) At autopsy Easily recognizable pulmonary vascular sclerosis in six cases. Right auricular thrombi in three cases. 4. 4. The prognosis and the mechanism of hemoptysis are discussed. 5. 5. It is noteworthy that only eight patients had congestive failure prior to, or at the time of, the initial hemoptysis, and that nine had hearts of normal size. Pulmonary infarction is the most likely cause when there is congestive failure and may be excluded when the heart is of normal size. The combination of pulmonary infarction, a heart of normal size, and progressive cardiac enlargement following hemoptysis may indicate a severe grade of pulmonary arteriosclerosis. 6. 6. The occurrence of hemoptysis in a case of rheumatic heart disease may help in distinguishing between an Austin-Flint murmur and the murmur of aortic regurgitation, or in the diagnosis of mitral stenosis, in certain cases. 7. 7. When hemoptysis occurs in rheumatic heart disease, only occasionally is it caused by something other than the heart disease.
Measurement of PLL phase error caused by power supply noise

The measurement of the accumulated phase error of phase-locked loops (PLLs) in microprocessor systems is discussed. A system which creates controlled power supply noise and measures the PLL response is described. Examples of the use of this technique are shown for a PLL used in a 400 MHz microprocessor.
Hepatic N-acetyltransferases: Selective inactivation in vivo by a carcinogenic N-arylhydroxamic acid

Abstract N -Hydroxy-2-acetamidofluorene ( N -OH-AAF), a carcinogenic N -arylhydroxamic acid, is a selective and irreversible inhibitor of arylamine N -acetyltransferase (NAT) activity in vitro . The present study demonstrates that intraperitoneal administration of ( N -OH-AAF) to hamsters caused an irreversible reduction of the hepatic transacetylase activity that catalyzes the transfer of the acetyl group from NOH-AAF to 4-aminoazobenzene (AAB), but did not affect the acetyl coenzyme A (CoASAc) dependent NAT that is responsible for acetylation of p-aminobenzoic acid (PABA). A 40% loss of N -OHAAF:AAB transacetylase activity occurred 4 hr after administration of 50 mg/kg of N -OH-AAF. To determine whether biotransformation of N -OH-AAF is a factor in determining its ability to inactivate N -OH-AAF:AAF transacetylase activity in vivo , the enzyme-inducing agent phenobarbital and the esterase/acylamidase inhibitor bis( p -nitrophenyl)phosphate (BNPP) were administered to the animals prior to the administration of N -OH-AAF. The loss of N -OH-AAF:AAB transacetylase activity was prevented by treatment of the animals with either phenobarbital or with BNPP. The ability of the esterase/acylamidase inhibitor, BNPP, to prevent the N -OH-AAF-mediated loss of transacetylase activity indicates that, in contrast to the inactivation process in vitro , esterase-catalyzed deacetylation of N -OH-AAF may be required for transacetylase inactivation in vivo . It is proposed that in vivo the endogenous acetyl donor, CoASAc, acetylates the enzyme and prevents the deacetylation of N -OHAAF by NAT, thereby impeding the N -OH-AAF-mediated inactivation process, but facilitating enzyme inactivation by N -hydroxy-2-aminofluorene. The latter proposal was supported by the demonstration that CoASAc inhibited the in vitro inactivation of N -OH-AAF:AAB transacetylase activity by N -OHAAF.
DNS of Oscillatory Boundary Layer Over a Closely Packed Layer of Sediment Particles

Lack of accurate criteria for onset of incipient motion and sediment pickup function remain two of the biggest hurdles in developing better predictive models for sediment transport. To study pickup and transport of sediment, it is necessary to have a detailed knowledge of the small amplitude oscillatory flow over the sediment layer near the sea bed. Fully resolved direct numerical simulations are performed using fictitious domain approach [1] to investigate the effect of a sinusoidally oscillating flow field over a rough wall made of regular hexagonal pack of spherical particles. The flow arrangement is similar to the experimental data of Keiller et al. [2]. Transitional and turbulent flows at Reδ = 95,150,200 and 400 (based on the Stokes layer thickness, Display Formulaδ=2ν/ω) are explored over a range of non-dimensional sphere sizes. Turbulent flow is characterized in terms of coherent vortex structures, Reynolds stress variation, turbulent kinetic energy budget and PDF distributions. The nature of unsteady hydrodynamic lift forces on sediment grains and their correlation to sweep and burst events is also reported. The dynamics of the oscillatory flow over the sediment bed is used to understand the mechanism of sediment pick-up.Copyright © 2014 by ASME
Age-related changes in brain energetics and phospholipid metabolism

Evidence suggests that mitochondria undergo functional and morphological changes with age. This study aimed to investigate the relationship of brain energy metabolism to healthy aging by assessing tissue specific differences in metabolites observable by phosphorus (31P) MRS. 31P MRSI at 4 Tesla (T) was performed on 34 volunteers, aged 21–84, screened to exclude serious medical and psychiatric diagnoses. Linear mixed effects models were used to analyze the effects of age on phosphorus metabolite concentrations, intracellular magnesium and pH estimates in brain tissue. A significant age associated decrease in brain pH (−0.53% per decade), increase in PCr (1.1% per decade) and decrease in PME (1.7% per decade) were found in total tissue, with PCr effects localized to the gray matter. An increase in beta NTP as a function of age (1% per decade) approached significance (p = 0.052). There were no effects demonstrated with increasing age for intracellular magnesium, PDE or inorganic phosphate. This study reports the effects of healthy aging on brain chemistry in the gray matter versus white matter using 31P MRS measures of high energy phosphates, pH and membrane metabolism. Increased PCr, increased beta NTP (reflecting ATP) and reduced pH may reflect altered energy production with healthy aging. Unlike some previous studies of aging and brain chemistry, this study examined healthy, non-demented and psychiatrically stable older adults and specifically analyzed gray-white matter differences in brain metabolism. Copyright © 2009 John Wiley & Sons, Ltd.
Vagal afferent controls of feeding: a possible role for gastrointestinal BDNF.

Vagal gastrointestinal (GI) afferents do not appear to contribute to long-term controls of feeding, despite downstream connections that could support such a role. This view is largely attributable to a lack of evidence for long-term effects, especially the failure of vagal afferent lesions to produce hyperphagia or obesity. Here, the possibility is evaluated that “side effects” of vagal lesion methods resulting largely from complexities of vagal organization would probably suppress long-term effects. Criteria based on knowledge of vagal organization were utilized to critique and compare vagal lesion methods and to interpret their effects on GI function, feeding and body weight. This analysis suggested that it was premature to eliminate a long-term vagal GI afferent role based on the effects of these lesions and highlighted aspects of vagal organization that must be addressed to reduce the problematic side effects of vagal lesions. The potential of “genetic” lesions that alter vagal sensory development to address these aspects, examination of the feasibility of this approach, and the properties of brain-derived neurotrophic factor (BDNF) that made it an attractive candidate for application of this approach are described. BDNF knockout from GI smooth muscle unexpectedly demonstrated substantial overeating and weight gain associated with increased meal size and frequency. The decay of eating rate during a scheduled meal was also reduced. However, meal-induced c-Fos activation was increased in the dorsal motor nucleus of the vagus, suggesting that the effect on eating rate was due to augmentation of GI reflexes by vagal afferents or other neural systems.
Measles Virus C Protein Impairs Production of Defective Copyback Double-Stranded Viral RNA and Activation of Protein Kinase R

Measles virus (MV) lacking expression of C protein (C(KO)) is a potent activator of the double-stranded RNA (dsRNA)-dependent protein kinase (PKR), whereas the isogenic parental virus expressing C protein is not. Here, we demonstrate that significant amounts of dsRNA accumulate during C(KO) mutant infection but not following parental virus infection. dsRNA accumulated during late stages of infection and localized with virus replication sites containing N and P proteins. PKR autophosphorylation and stress granule formation correlated with the timing of dsRNA appearance. Phospho-PKR localized to dsRNA-containing structures as revealed by immunofluorescence. Production of dsRNA was sensitive to cycloheximide but resistant to actinomycin D, suggesting that dsRNA is a viral product. Quantitative PCR (qPCR) analyses revealed reduced viral RNA synthesis and a steepened transcription gradient in C(KO) virus-infected cells compared to those in parental virus-infected cells. The observed alterations were further reflected in lower viral protein expression levels and reduced C(KO) virus infectious yield. RNA deep sequencing confirmed the viral RNA expression profile differences seen by qPCR between C(KO) mutant and parental viruses. After one subsequent passage of the C(KO) virus, defective interfering RNA (DI-RNA) with a duplex structure was obtained that was not seen with the parental virus. We conclude that in the absence of C protein, the amount of PKR activator RNA, including DI-RNA, is increased, thereby triggering innate immune responses leading to impaired MV growth.
“Boyd V. Deaver - Litigation Strategies” videodisc: an opportunity to improve curriculum and prototype expert systems

Once in a rare while we come across an environment that can illuminate several areas of inquiry. BOYD V. DEAVER: LITIGATION STRATEGIES is such a tool. The major original thesis of the paper is that using AI tools to gather the “audit trails” of case development strategies of experienced attorneys, and bringing them to the attention of law school professors would assist in curriculum assessment and development.The second aspect of the paper is a brief proposal to develop three expert systems and compare them.
Videoconferencing psychotherapy: A systematic review.

Individuals with mental health problems may face barriers to accessing effective psychotherapies. Videoconferencing technology, which allows audio and video information to be shared concurrently across geographical distances, offers an alternative that may improve access. We conducted a systematic literature review of the use of videoconferencing psychotherapy (VCP), designed to address 10 specific questions, including therapeutic types/formats that have been implemented, the populations with which VCP is being used, the number and types of publications related to VCP, and available satisfaction, feasibility, and outcome data related to VCP. After electronic searches and reviews of reference lists, 821 potential articles were identified, and 65 were selected for inclusion. The results indicate that VCP is feasible, has been used in a variety of therapeutic formats and with diverse populations, is generally associated with good user satisfaction, and is found to have similar clinical outcomes to traditional face-to-face psychotherapy. Although the number of articles being published on VCP has increased in recent years, there remains a need for additional large-scale clinical trials to further assess the efficacy and effectiveness of VCP.
Efficient jumpgliding: Theory and design considerations

A dynamic model of a jump glider is presented and correlated with the results obtained with a prototype glider. The glider uses a carbon fiber spring and a main wing that pivots approximately parallel to the airflow during ascent and latches into place for a gliding descent. The robot demonstrates longer traveled distance than an equivalent drag-free ballistic mass. A detailed numerical and a simplified algebraic model are also introduced, which are useful for exploring design tradeoffs and performance. These models suggest ways to improve the traveled distance and indicate that with modest variations in the wing angle of attack during ascent, one can choose from a variety of launch angles to accommodate variations in ground friction without greatly compromising range.
PROGESTERONE AND THE CONTROL OF HUMAN PREGNANCY AND PARTURITION

Almost 80 years ago George Corner and colleagues provided the first evidence that progesterone maintains pregnancy and that it does so, at least in part, by promoting myometrial relaxation. In the 1950s, Arpad Csapo proposed the “progesterone block hypothesis”, which posits that progesterone maintains pregnancy by promoting myometrial relaxation and that its withdrawal initiates a cascade of hormonal interactions that transforms the myometrium to a highly contractile state leading to the onset of labour. Csapo later proposed that contractility of the pregnant myometrium is determined by the balance between relaxation induced by progesterone and contraction induced by a cohort of signals including oestrogens, uterine distention and stimulatory uterotonins such as prostaglandins (PGs) and oxytocin (OT). According to this “seesaw” hypothesis, progesterone promotes myometrial relaxation by directly inducing relaxation and/or by inhibiting the production of, or myometrial responsiveness to, stimulatory uterotonins. These landmark concepts, though derived from studies of experimental animals, form the foundation for current understanding of progesterone's role in the physiology of human pregnancy. Remarkable progress has been made over the last 20–30 years in understanding the signal transduction pathways through which steroid hormones affect target cells. This knowledge has broadened the scope of Csapo's original paradigms and we are now beginning to unravel the specific signaling pathways and molecular interactions by which progesterone affects human myometrium and how its actions are controlled at the functional level. This is important for the development of progestin-based therapeutics for the prevention or suppression of preterm labour and preterm birth. Here we review recent progress in understanding the mechanisms by which progesterone sustains pregnancy and in particular how it promotes myometrial relaxation, how its relaxatory actions are nullified at parturition, and the hormonal interactions that induce progesterone withdrawal to determine the timing of human birth.
The triose-phosphate site of homogeneous reconstituted sn-glycerol-3-phosphate acyltransferase of EScherichia coli

Abstract The sn-glycerol-3-phosphate (glycerol-phosphate) acyltransferase of Escherichia coli was purified to near homogeneity and its activity reconstituted with phospholipids (Green, P.R., Merrill, A.M., Jr. and Bell, R.M. (1981) J. Biol. Chem. 256, 11151–11159). The competency of glycerol-P analogues to serve as inhibitors and as substrates was investigated. Dihydroxyacetone-P, ethyleneglycol-P, 1,3-propanediol-P, 3,4-dihydroxy-butylphosphonate and dl - glyceraldehyde -3-P were inhibitors of the reconstituted purified glycerol-phosphate acyltransferase. The kinetics of inhibition, while formally of the mixed type, most closely resembled that of a simple competitive inhibition with respect to glycerol-3-P. Inorganic phosphate was also found to be a competitive inhibitor. All of the glycerol-3-P analogues except dl - glyceraldehyde -3-P were substrates. Of these, dihydroxyacetone-P proved to be the best substrate. The secondary hydroxyl was not necessary for activity. Glycerol-phosphate acyltransferase catalyzed the hydrolysis of palmitoyl-CoA in the presence of dl -, but not d - glyceraldehyde -3-P . This suggests that the gem diol of l - glyceraldehyde -3-P may be a substrate, and that the acylated adduct may be unstable. The enzyme was inactivated by phenylglyoxal and butanedione, suggesting that arginine may be at or near the active site.