cssi/SciSciGPT-SciSciNet huggingface dataset:
Acidification, stress, and detrital processing: implications for ecosystem function in headwater streams

Environmental influences like acidification promote stress at the ecosystem level that manifests as reduction in metabolic and biogeochemical efficiency. Headwater streams along a chronic acidity gradient were assessed to explore how stress alters microbial abundance and activity and their influence on ecosystem structure and function. Streams draining deciduous forests were investigated during autumn when channels were filled by leaf litter. Whole-system measures of respiration were coupled to estimates of fungal biomass in leaf biofilms to generate an ecosystem-level measure of metabolic efficiency (qCO2E, g CO2–C g C−1 d−1). Stable isotope releases of nitrate nitrogen (15N–NO3) were performed to address nitrate uptake ( $${\text{U}}_{{{\text{NO}}_{ 3} }}$$ ) across streams. Fungal stocks decreased across five streams as pH declined (6.98–5.34). Whole-system respiration decreased fivefold with increasing acidity, while qCO2E did not respond consistently to acidification, but was correlated with stream temperature. Across streams, concentrations of nitrogen (N) were low and $${\text{U}}_{{{\text{NO}}_{ 3} }}$$ related to nutrient availability and not to stream acidity. Results illustrate that acidification alters ecosystem processes through influences on microbial abundance and metabolic activity, while scarce N availability and low $${\text{U}}_{{{\text{NO}}_{ 3} }}$$ characterized biogeochemical behavior during autumnal periods of maximal detrital stocks.
Newly-discovered enzymes that function in metabolite damage-control.

Enzymes of unknown function are estimated to make up around 25% of the sequenced proteome. In the past decade, over 20 conserved families have been shown to function in the metabolism of ‘damaged’ or abnormal metabolites that are wasteful and often toxic. These newly discovered damage-control enzymes either repair or inactivate the offending metabolites, or pre-empt their formation in the first place. Comparative genomics has been of prime importance in predicting the functions of damage-control enzymes and in guiding the biochemical and genetic tests required to validate these functions.
Bore-Lining Slot Antennas for 7T Body MRI

Magnetic Resonance Imaging (MRI) has become indispensable in numerous areas in medicine and biomedical research. Last year, 7 Tesla (T) MRI became cleared by the Food and Drug Administration (FDA) for head and extremity regions promising improved visualization of small structures and subtle pathologies. In recent years, numerous coil structures have been proposed to improve 7T imaging. These designs rely on narrow conducting elements that are positioned close to the body and rely on the transverse radiofrequency (RF) magnetic fields produced primarily (though not entirely) by the positioning of discrete conductors oriented parallel to the main magnetic field (B0). These designs unfortunately, do not allow efficient excitation in the body with satisfactorily low local Specific Absorption Rate (SAR). Here, we mitigate these challenges using two main themes: 1) by introducing slot antennas which create distribute current patterns on the surface of the conductors and 2) by introducing lifted coil designs placed adjacent to the magnet bore ("bore-lining"). The design minimally affects patient comfort and exhibits improvement in B1+ homogeneity, B1+ efficiency and SAR reduction compared to traditional dipole-like array setups.
Short Message Service Surveying With Homeless Youth: Findings From a 30-Day Study of Sleeping Arrangements and Well-Being

Little is known about the location and consistency of sleeping arrangements among youth experiencing homelessness (YEH) and how this is linked to their well-being. This study addresses this gap usi...
Engraftment of NOD/SCID mice with human neuroblastoma xenograft with IMR-32: Experimental in vivo model for immunotherapy in human neuroblastoma

5469 Neuroblastoma, a primitive neuroectodermal tumor, is characterized by metastatic disease at diagnosis and a poor prognosis despite myeloablative autologous stem cell transplantation (Matthay et al, N Engl J Med 341:1165, 1999). NOD/SCID mice provide an excellent murine xenograft model for the study of tumor immunology (Hudson et al, Leukemia 12:2029, 1998, Robin et al, J Exp Med 189:1601, 1999). In this study we sought to characterize tumor associated antigens (TAA) of the human neuroblastoma line, IMR-32, to establish a xenograft with IMR-32 and determine cell dose and time to tumor development in a NOD/SCID mouse for the study of novel immunotherapies. IMR-32, was characterized using reverse transcription PCR analysis for expression of specific TAAs including GAGE1, MAGE3 and N-MYC. The random oligo(dT) primer was used for the first strand cDNA synthesis by AMV retrotranscriptase (Roche). The primer pairs used in the amplification PCR were 5’GTGGACATACTCAGTGGC3’ and 5’CGAAACTCTGACTCGGAG3’ for N-MYC, 5’AGACGCTACGTA-GAGCC3’ and CCATCAGGACCATCTTCA for GAGE1, 5’GGAGTCCTCATAGGATTGGCTCC and GAAGCCGGCCCAGGCTCGGTGA for MAGE3, respectively. The annealing temperatures were 60°C for MAGE3 and N-MYC, 55°C for GAGE1. The PCR programs were 1min at 94°C, 35 cycles of 1 min at 94°, 1 min at annealing temperature for each gene, 1.5 min at 72°C, plus 7 min final extention at 72°C. To determine cell dose needed to achieve human neuroblastoma tumor engraftment, IMR-32 cells were injected subcutaneously into the left flank of adult NOD/SCID mice (4-6 months old). Groups of animals (n=5) received either matrigel only (control), 1x10 6 cells ( dose 1) or 1x10 7 cells (dose 2). The mice were monitored for evidence of tumor engraftment, rate of tumor growth and survival. Tumor size was determined at its greatest circumference by measurement with calipers. IMR-32 expressed GAGE1 and N-MYC amplified genes but was negative for MAGE3. There was no growth in 0/5 animals in the control group, 4/5 animals at dose level 1 and 5/5 animals at dose level 2. A two-way analysis of variance comparing the doses of tumor cells confirmed that the dose of IMR-32 had a significant impact on size and time to tumor engraftment (p
Overweight and obesity among U.S. adults with and without disability, 1999–2012

Abstract Objective Examine the relationship between disability and overweight/obesity among U.S. adults. Methods Study sample (N = 30,363) came from the National Health and Nutrition Examination Survey 1999–2012 waves. Disability was classified into five domains using standardized indices. Any disability was defined as having any difficulty in performing at least one of the activities in any of the five disability domains. Logistic regressions were conducted to estimate the association between disability and overweight/obesity, adjusted by individual characteristics and multiyear complex sampling design. Results Over a quarter (25.99%) of U.S. adults 20 years and older reported having any disability. The overweight/obesity rates across all disability domains were substantially higher than their nondisabled counterparts. The rate of overweight and obesity combined (BMI ≥ 25 kg/m 2 ), obesity (BMI ≥ 30 kg/m 2 ), grade 2 and 3 obesity combined (BMI ≥ 35 kg/m 2 ), and grade 3 obesity (BMI ≥ 40 kg/m 2 ) among people with any disability were 1.14 (73.54% versus 64.50%), 1.38 (41.37% versus 29.99%), 1.71 (19.81% versus 11.60%), and 1.94 (8.60% versus 4.43%) times the corresponding rate among people without disability, respectively. Compared with their nondisabled counterparts, the adjusted odds of overweight and obesity combined, obesity, grade 2 and 3 obesity combined, and grade 3 obesity were 24% (95% confidence interval [CI]: 14%–36%), 32% (95% CI: 22%–44%), 49% (95% CI: 35%–64%), and 55% (95% CI: 27%–89%) higher among people with any disability, respectively. Conclusion People with disabilities have substantially higher risk of obesity compared to their nondisabled peers.
Challenges, pride, and connection: A qualitative exploration of advice transgender youth have for other transgender youth

Transgender youth experience a variety of risk and resilience factors that impact their wellbeing. However, the research on these factors rarely includes the personal perspectives or authority of t...
Conceptions of scientific progress in scientific practice: an empirical study

The aim of this paper is to contribute to the debate over the nature of scientific progress in philosophy of science by taking a quantitative, corpus-based approach. By employing the methods of data science and corpus linguistics, the following philosophical accounts of scientific progress are tested empirically: the semantic account of scientific progress (i.e., scientific progress in terms of truth), the epistemic account of scientific progress (i.e., scientific progress in terms of knowledge), and the noetic account of scientific progress (i.e., scientific progress in terms of understanding). Overall, the results of this quantitative, corpus-based study lend some empirical support to the epistemic and the noetic accounts over the semantic account of scientific progress, for they suggest that practicing scientists use the terms ‘knowledge’ and ‘understanding’ significantly more often than the term ‘truth’ when they talk about the aims or goals of scientific research in their published works. But the results do not favor the epistemic account over the noetic account, or vice versa, for they reveal no significant differences between the frequency with which practicing scientists use the terms ‘knowledge’ and ‘understanding’ when they talk about the aims or goals of scientific research in their published works.
Comparison of disposal options for Tundra orbits in terms of delta-V cost and long-term collision risk

Abstract Tundra orbits are inclined, moderately eccentric orbits with a 24-h period. These orbits undergo large excursions in eccentricity due to luni-solar gravity perturbations. For inclinations above 50°, eccentricity can grow to a value that causes perigee to reach the Earth's atmosphere, resulting in vehicle re-entry. In the current study, a range of potential disposal options for Tundra orbits were compared. Disposal options considered include moving to a disposal orbit near the Tundra mission orbit, lowering apogee just below GEO, and moving to near-circular orbits below and above GEO. Comparison metrics include delta-V cost (a measure of maneuver effort) and long-term collision risk. For the eccentric disposal orbit options, initial inclination and right ascension of ascending node (RAAN) were parametrically varied. For the near-circular disposal orbit options, initial argument of perigee and RAAN were parametrically varied. Study results indicate that a near-Tundra disposal orbit option appears to be the favorable selection since it has much lower delta-V cost than the other options and still has the second lowest overall collision risk, well below the threshold of 0.001 that is cited in U.S. standards on debris mitigation and space safety. In terms of orbital sustainability, for all RAAN values there are inclination values that enable re-entry within 200 years.
Predictive utility of the Minnesota Multiphasic Personality Inventory-2-RF (MMPI-2-RF) in differentiating psychogenic nonepileptic seizures and epileptic seizures in male veterans.

Abstract Objective While psychogenic nonepileptic seizures (PNES) and epileptic seizures (ES) often present similarly, they are etiologically distinct, and correct diagnosis is essential for ensuring appropriate treatment and improving outcomes. The Minnesota Multiphasic Personality Inventory-2-RF (MMPI-2-RF) may assist in differential diagnosis, but prior investigations have been limited by disproportionately female samples, inconsistent accounting for profile invalidity, and limited intra-scale variability from dichotomizing variables. The current investigation addressed these gaps by assessing diagnostic utility of the MMPI-2-RF in differentiating PNES and ES in a male sample of veterans while conservatively accounting for profile invalidity and using a statistical approach that allows for consideration of continuous independent variables to better appreciate intra-scale variance. Method One hundred and forty-four veterans completed the MMPI-2-RF and were diagnosed with PNES (57.6%) or ES (42.4%) by a board-certified neurologist following continuous video-EEG monitoring. Participants with validity scores falling in the definitely or likely invalid ranges were excluded to ensure construct validity among clinical/substantive scales. Independent samples t-tests assessed differences in MMPI-2-RF variables by diagnostic groups. Hierarchical stepwise logistical regressions assessed predictive utility of MMPI-2-RF indices. A clinical calculator was derived from regression findings to help with diagnostic prediction. Results Males with PNES endorsed significantly higher scores on F-r, FBS-r, RBS, RC1, RC7, HPC, and NUC (medium to large effect sizes). The regression block that contained validity, restructured clinical (RC1), and substantive scales (GIC, SUI) had a hit rate of 75.69%, which was an improvement from the baseline model hit rate of 57.64%. Higher endorsement on RC1 and lower reporting on GIC significantly predicted PNES diagnosis for males. Conclusions Minnesota Multiphasic Personality Inventory-2-RF improved diagnostic accuracy of PNES versus ES among male veterans, and RC1 (somatic complaints) emerged as a significant predictor for males with PNES, in line with hypotheses. Several clinical/substantive scales assisted with differential diagnosis after careful accounting for profile validity. Future studies can validate findings among males outside of veteran samples.
ICER controls HIV-1 infection and replication in elite controllers

ABSTRACT A rare subset of HIV-infected individuals, termed elite controllers (ECs), can maintain long-term control over HIV replication in the absence of antiretroviral therapy (ART). To elucidate the biological mechanism of resistance to HIV replication at the molecular and cellular levels, we performed RNA sequencing and identified alternative splicing variants from ECs, HIV-infected individuals undergoing ART, ART-naive HIV-infected individuals, and healthy controls. Differential gene expression patterns that are specific to ECs and may influence HIV resistance were identified, including alternative RNA splicing and exon usage variants of the CREM/ICER gene (cAMP-responsive element modulator/inducible cAMP early repressors). The knockout and knockdown of specific ICER exons that were found to be upregulated in ECs resulted in significantly increased HIV infection in CD4+ T cell line and primary CD4+ T cells. Overexpression of ICER isoforms decreased HIV infection in primary CD4+ T cells. Furthermore, ICER regulated HIV-1 LTR promoter activity in a Tat-dependent manner. Together, these results suggest that ICER is an HIV host factor that may contribute to HIV resistance of ECs. These findings will help elucidate the mechanisms of HIV control by ECs and may yield a new approach for treatment of HIV.
Therapeutic approaches and outcomes in patients with larynx or hypopharynx high-grade neuroendocrine carcinoma: A single-center retrospective analysis

Background High-grade neuroendocrine carcinoma of the larynx (HG-NECL) is rare and aggressive with limited data regarding response to systemic therapy. We evaluated clinicopathological features, therapeutic approaches, and outcomes in patients with laryngeal or hypopharyngeal HG-NECL. Methods Data were retrospectively collected through 1997-2020. Median disease-free (mDFS), progression-free (mPFS), and overall survival (mOS) were estimated using the Kaplan-Meier method. Results Fifteen patients were identified; most had locoregional (N = 7) or metastatic disease (N = 5). The main curative-intent treatment was chemoradiation concurrent with platinum-based chemotherapy; the rate of complete response was 78%. Most patients (80%) developed recurrence; the mDFS was 13.1 months. For the first-line palliative therapy, the ORR and mPFS were 50% and 3.1 months, respectively. For all patients, the mOS was 17.8 months, and 8.6 months for metastatic disease. Conclusion Laryngeal HG-NEC is associated with high relapse rates and dismal prognosis for those with recurrent/metastatic disease. Novel therapeutic strategies are needed.
Two-phase flow pressure drop in superhydrophobic channels

Abstract Superhydrophobic surfaces have been shown to reduce drag in single-phase channel flow; however, little work has been done to characterize their drag-reducing ability found in two-phase flows. Adiabatic, air-water mixtures were used to explore the influence of hydrophobicity on two-phase flows and the hydrodynamics which might be present in flow condensation environments. Pressure drop measurements in a rectangular channel with one superhydrophobic wall (cross-section approximately 0.37 × 10 mm) and three transparent hydrophilic walls were obtained. Data for air/water mixtures with superficial Reynolds numbers ranging from 22–215 and 55–220, respectively, were obtained for superhydrophobic surfaces with three different cavity fractions. Agreement between experimentally obtained two-phase pressure drop data and correlations in the literature for conventional smooth control surfaces was better than 20 percent, which is within the accuracy of the correlations. The data reveal a reduction in the pressure drop for two-phase flow in a channel with a single superhydrophobic wall compared to a control scenario. The observed reduction is approximately 10 percent greater than the reduction that is observed for single-phase flow (relative to a classical channel).
In-source collision induced dissociation of inorganic explosives for mass spectrometric signature detection and chemical imaging

The trace detection, bulk quantification, and chemical imaging of inorganic explosives and components was demonstrated utilizing in-source collision induced dissociation (CID) coupled with laser desorption/ionization mass spectrometry (LDI-MS). The incorporation of in-source CID provided direct control over the extent of adduct and cluster fragmentation as well as organic noise reduction for the enhanced detection of both the elemental and molecular ion signatures of fuel-oxidizer mixtures and other inorganic components of explosive devices. Investigation of oxidizer molecular anions, specifically, nitrates, chlorates, and perchlorates, identified that the optimal in-source CID existed at the transition between fragmentation of the ionic salt bonds and molecular anion bonds. The chemical imaging of oxidizer particles from latent fingerprints was demonstrated, including both cation and anion components in positive and negative mode mass spectrometry, respectively. This investigation demonstrated LDI-MS with in-source CID as a versatile tool for security fields, as well as environmental monitoring and nuclear safeguards, facilitating the detection of elemental and molecular inorganic compounds at nanogram levels.
Serial concatenated single differential space-time coding with soft decision feedback channel estimation

In this article, we present serial concatenated single differential space-time block coding (SDST), with channel estimation based on soft decision feedback. Two schemes with soft decision feedback extracted from different positions of the serial structure, such as the output of inner decoder and outer decoder, are proposed and thoroughly studied. Improved system performance is demonstrated and compared via simulations. Our theoretical analysis and simulation results lead to the conclusion that different allocation of the same error correcting potential gives rise to different system performance and speed of convergence.
Arachidonate and docosahexaenoate added to infant formula influence fatty acid composition and subsequent eicosanoid production in neonatal pigs.

As natural components of human milk, arachidonic and docosahexaenoic acids play important roles in neonatal development ; thus, addition of these fatty acids to infant formula has been suggested. This study examined the effects of supplementation of infant formula with microbial sources of either arachidonate or docosahexaenoate or both on accretion of these fatty acids in phospholipids and subsequent modulation of eicosanoid production in neonatal pig lung. One-day-old piglets received for 25 d one of four diets (n = 5) : 1) standard diet containing a fat blend similar to that of conventional infant formula, 2) diet containing 0.9 g/100 g of total fatty acids as arachidonate, 3) diet containing 0.7 g/100 g as docosahexaenoate, or 4) a diet containing both 1.0 g/100 g as arachidonate and 0.8 g/100 g as docosahexaenoate. Arachidonate supplementation resulted in 30-60% significantly greater arachidonate in lung phosphatidylethanolamine and phosphatidylcholine. In phosphatidylinositol, however, arachidonate was resistant to dietary manipulation. Accretion of docosahexaenoate in all three phospholipid classes was 2.6- to 4.7-fold greater in docosahexaenoate-supplemented groups than in the standard group. Inclusion of arachidonate in the diet augmented both prostacyclin and thromboxane production by 25 to 35%. Docosahexaenoate supplementation resulted in the least eicosanoid production among the treatments, and significant suppression was observed for thromboxane when supplementation with both fatty acids was compared with supplementation with arachidonate alone. Thus, dietary arachidonic acid and docosahexaenoic acid at concentrations only slightly greater than those found in human milk tended to exercise opposing effects on lung eicosanoid production.
Identification of General Linear Mechanical Systems

Previous work in identification theory has been concerned with the general first order time derivative form. Linear mechanical systems, a large and important class, naturally have a second order form. This paper utilizes this additional structural information for the purpose of identification. A realization is obtained from input-output data, and then knowledge of the system input, output, and inertia matrices is used to determine a set of linear equations whereby we identify the remaining unknown system matrices. Necessary and sufficient conditions on the number, type and placement of sensors and actuators are given which guarantee identifiability, and less stringent conditions are given which guarantee generic identifiability. Both a priori identifiability and a posteriori identifiability are considered, i.e. identifiability being insured prior to obtaining data, and identifiability being assured with a given data set.
Chapter 21: Quantitative fluorescence lifetime imaging in cells as a tool to design computational models of ran-regulated reaction networks.

Abstract The understanding of cell function often requires that complex intracellular pathways are considered in quantitative terms. The access to precise measurement of activities in live cells is increasingly provided by the advances in fluorescence lifetime imaging microscopy (FLIM) of Forster (or fluorescence) resonance energy transfer (FRET)‐based molecular biosensors. We discuss how quantitative in vivo imaging can be combined with in vitro biochemical characterization to develop computational systems models simulating the behavior of biochemical networks. We describe the application of such approach in computational modeling of the Ran GTPase function in mitotic spindle assembly. The RanGTP concentration gradient surrounding mitotic chromosomes induces the formation of a gradient of spindle assembly factors (SAFs) activated by RanGTP‐induced release from inhibitory complexes of SAFs with importin β. To visualize the gradient of activated SAFs in live cells, we used FLIM to detect the signal of a FRET‐based biosensor that reports its RanGTP‐induced liberation from importin β. We review the technical aspects of FRET measurements by FLIM and discuss the step‐wise design of systems models aided by quantitative imaging. As evidenced by the example of mitotic Ran gradient studies, the computational simulations are a powerful tool to test new hypotheses on biological function.
The adenovirus E3-14.7K protein and the E3-10.4K/14.5K complex of proteins, which independently inhibit tumor necrosis factor (TNF)-induced apoptosis, also independently inhibit TNF-induced release of arachidonic acid.

Tumor necrosis factor (TNF) is an inflammatory cytokine that inhibits the replication of many viruses in cultured cells. We have reported that adenovirus (Ad) infection of TNF-resistant mouse cells renders them susceptible to lysis by TNF and that two sets of proteins encoded by the E3 transcription unit block TNF cytolysis. The E3 protein sets are named E3-14.7K (14,700 kDa) and E3-10.4K/14.5K (a complex of two proteins of 10,400 and 14,500 kDa). TNF activation of the 85-kDa cytosolic phospholipase A2 (cPLA2) is thought to be essential for TNF cytolysis (i.e.,TNF-induced apoptosis). Here we provide evidence that cPLA2 is important in the response of Ad-infected cells to TNF and that the mechanism by which E3-14.7K and E3-10.4K/14.5K inhibit TNF cytolysis is by inhibiting TNF activation of cPLA2. cPLA2 cleaves arachidonic acid (AA) specifically from membrane phospholipids; therefore, cPLA2 activity was measured by the release of 3H-AA from cells prelabeled with 3H-AA. Uninfected cells or cells infected with wild-type Ad were not lysed and did not release 3H-AA in response to TNF. In contrast, TNF treatment induced cytolysis and 3H-AA release in uninfected cells sensitized to TNF by treatment with cycloheximide and also in infected cells sensitized to TNF by expression of E1A. In C127 cells, in which either E3-14.7K or E3-10.4K/14.5K inhibits TNF cytolysis, either set of proteins inhibited TNF-induced release of 3H-AA. In C3HA cells, in which E3-14.7K but not E3-10.4K/14.5K prevents TNF cytolysis, E3-14.7K but not E3-10.4K/14.5K prevented TNF-induced release of 3H-AA. When five virus mutants with lesions in E3-14.7K were examined, there was a perfect correlation between a mutant's ability to inhibit both TNF-induced cytolysis and release of 3H-AA. E3-14.7K expressed in two stably transfected C127 cell lines prevented both TNF-cycloheximide-induced cytolysis and release of 3H-AA. The E3 proteins also prevented TNF-induced cytolysis and release of 3H-AA in mouse L929 cells, which are spontaneously sensitive to TNF. TNF cytolysis was blocked by dexamethasone, an inhibitor of PLA2 activity, and by nordihydroquaiaretic acid, which inhibits the metabolism of AA to the leukotrienes. Indomethacin, which blocks the formation of prostaglandins from AA, did not inhibit TNF cytolysis. The leukotrienes and prostaglandins are amplifiers of the inflammatory response. We propose that E3-14.7K and E3-10.4K/14.5K function independently in Ad infection to inhibit both cytolysis and inflammation induced by TNF.
Alpha-sarcin causes a specific cut in 28 S rRNA when microinjected into Xenopus oocytes.

Abstract The toxin alpha-sarcin specifically cuts 28 S rRNA at a single position 393 nucleotides from its 3' end in isolated rat liver polysomes, provided the ribosomes are pretreated with EDTA or puromycin (Endo, Y. & Wool, I. G. (1982) J. Biol. Chem. 257, 9054-9060). In addition, alpha-sarcin behaves as a purine-specific RNase on deproteinized RNA, cleaving on the 3' side of purines in both single- and double-stranded RNA (Endo, Y., Huber, P. W., and Wool, I. G. (1983) J. Biol. Chem. 258, 2662-2667). Since alpha-sarcin does not readily enter tissue culture cells, we have injected it into Xenopus oocytes in order to determine whether the toxin cleaves after all purines or if it specifically makes a single cut in 28 S rRNA in intact cells. We report here that in oocytes alpha-sarcin specifically cuts 28 S rRNA 377 nucleotides from its 3' end, even when used at concentrations that would degrade deproteinized RNA. alpha-Sarcin does not behave as a general nuclease when injected into Xenopus oocytes nor does it operate by another means such as initiating proteolytic digestion of endogenous oocyte proteins. We demonstrate that injected alpha-sarcin causes a rapid decline in oocyte protein synthesis for soluble cytoplasmic proteins, similar in effect to injection of cycloheximide or puromycin.
Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft-versus-host disease prophylaxis regimens on outcome

Data for 595 patients with severe aplastic anemia receiving HLA-identical sibling bone marrow transplants were analyzed to determine the effect of pretransplant conditioning and graft-versus-host disease (GVHD) prophylaxis on outcome. Transplants were performed between 1980 and 1987 and reported to the International Bone Marrow Transplant Registry. Three conditioning regimens (cyclophosphamide alone, cyclophosphamide plus limited field radiation, and cyclophosphamide plus total body radiation) were studied; none was associated with superior long-term survival. Three GVHD prophylaxis regimens (methotrexate, cyclosporine, and methotrexate plus cyclosporine) were studied. Recipients of cyclosporine with or without methotrexate had a significantly higher probability of 5-year survival (69%, 95% confidence interval 63% to 74%) than patients receiving methotrexate only (56%, 49% to 62%, P less than .003). Higher survival with cyclosporine resulted from decreased risks of interstitial pneumonia (P less than .0002) and chronic GVHD (P less than .005). Additional risk factors adversely associated with survival included infection pretransplant (P less than .004), use of parous or transfused female donors (P less than .005), older patient age (P less than .005), and 20 or more pretransplant transfusions (P less than .006). These data may prove useful in planning randomized clinical trials and in identifying patients at high-risk of treatment failure.
Origin of Modern Humans: Interpreting the Molecular Evidence

Patterns of genetic diversity within our species imply that we descended from a small number of ancestors, of the order of several thousands. While early genetic evidence suggested major population expansions in our past, recent data from the nuclear genome are ambiguous. Keywords: modern human origins; DNA sequence evolution; ancient demography; coalescent theory
Assessing the efficacy of The American Fertility Society's classification of endometriosis: application of a dose-response methodology.

In order to promote uniform reporting of endometriosis, The American Fertility Society (AFS) recently proposed a classification in which severity was categorized on the basis of both location and extent of disease. The results of this study indicate that the AFS scale poorly specifies the relation between severity of disease and pregnancy outcome after therapy, because of the arbitrary point scores assigned to each classification category, and the arbitrary cutoff points chosen to divide patients into severity groupings. A nonparametric monotonic estimator, which generates a dose-response relationship between AFS score (dose) and pregnancy following treatment (response) is shown to improve the discriminatory power of the AFS scale; however, in order to obtain the full benefit of the detail provided by the AFS classification, it is recommended that the current arbitrary individual-category weights be replaced by empirically derived weights.
Estradiol and estriol suppress CYP1A expression in rainbow trout primary hepatocytes.

Abstract Hepatic levels of the pollutant inducible enzyme, CYP1A, are strongly suppressed in spawning female fish, a phenomenon attributed to high plasma levels of the female sex steroid hormone, estradiol. To evaluate the contribution of estrogen metabolites to estradiol-mediated CYP1A regulation, we treated primary hepatocytes isolated from juvenile rainbow trout ( Oncorhynchus mykiss ) with vehicle, 17β-estradiol, or the estrogen metabolite, estriol, alone and in combination with each other and with the potent CYP1A inducer, benzo[ a ]pyrene (B[ a ]P). We found dose-dependent suppression of B[ a ]P-induced CYP1A activity by both steroids relative to controls. At 10 −7 M doses, estradiol and estriol suppressed B[ a ]P-induced CYP1A activity by 3- and 2-fold, respectively. Although not statistically significant, mean basal CYP1A activity levels were 15- and 13-fold lower in estradiol and estriol treated hepatocytes, respectively, relative to vehicle treated controls. Combining doses of estradiol and estriol failed to produce synergistic suppression of either basal or B[ a ]P-induced CYP1A activity relative to treatment with either steroid alone. The observed suppression is well below the often strong suppression observed in spawning female fish. We conclude that factors in addition to estradiol and estriol are likely involved in producing sexual dimorphism in CYP1A expression observed in spawning fish.
Adsorption of Poly(styrenesulfonate) to the Air Surface of Water by Neutron Reflectivity

The adsorption of the strong polyelectrolyte poly(styrenesulfonate) (PSS) to the air surface of dilute aqueous solutions was investigated as a function of molecular weight and salt concentration. Detailed segment profiles of the deuterated polymer were determined by neutron reflection. Surface activity was also examined through surface tension measurements. In general, the segment profiles are composed of a thin layer (10-20 A thick) of high concentration at the air surface, followed by a distinct second layer of much lower segment concentration that extends to larger depths into the liquid. The high segment density at the air surface is due to a strong surface attraction, arising from the low surface energy of the PSS backbone relative to the surface tension of water. At low salt concentration, the profiles tend toward a single dense layer, suggesting that the chains lie nearly flat at the interface in that limit. The adsorbed amount increases with salt concentration, with a stronger dependence for higher molecular weight chains. The adsorbed amounts at the air/water interface are higher than reported previously for PSS adsorbed onto neutral solid surfaces, consistent with the fact that the air-liquid interface provides a stronger surface attraction. While the trends of adsorbed amount with salt concentration and molecular weight are in good agreement with numerical self-consistent-field lattice calculations, the measured bilayer profiles are rather different from the smoothly decaying theoretical profiles. The surface tensions of the PSS solutions are significantly lowered relative to those of pure salt solutions. Combining the reflectivity and surface tension measurements, an approximately linear relationship is established between the surface pressure and the PSS adsorbed amount.
A mischief of mice

In this issue of Blood, Shavit and colleagues take advantage of major differences in von Willebrand factor gene (VWF) expression between inbred mouse strains to identify both a VWF locus alteration (Mvwf5) and 2 unlinked modifier gene loci (Mvwf6-7) that regulate plasma VWF levels.1
The Role of the Prokineticin 2 Pathway in Human Reproduction: Evidence from the Study of Human and Murine Gene Mutations

A widely dispersed network of hypothalamic GnRH neurons controls the reproductive axis in mammals. Genetic investigation of the human disease model of isolated GnRH deficiency has revealed several key genes crucial for GnRH neuronal ontogeny and GnRH secretion. Among these genes, prokineticin 2 (PROK2), and PROK2 receptor (PROKR2) have recently emerged as critical regulators of reproduction in both mice and humans. Both prok2- and prokr2-deficient mice recapitulate the human Kallmann syndrome phenotype. Additionally, PROK2 and PROKR2 mutations are seen in humans with Kallmann syndrome, thus implicating this pathway in GnRH neuronal migration. However, PROK2/PROKR2 mutations are also seen in normosmic GnRH deficiency, suggesting a role for the prokineticin signaling system in GnRH biology that is beyond neuronal migration. This observation is particularly surprising because mature GnRH neurons do not express PROKR2. Moreover, mutations in both PROK2 and PROKR2 are predominantly detected in the heterozygous state with incomplete penetrance or variable expressivity frequently seen within and across pedigrees. In some of these pedigrees, a "second hit" or oligogenicity has been documented. Besides reproduction, a pleiotropic physiological role for PROK2 is now recognized, including regulation of pain perception, circadian rhythms, hematopoiesis, and immune response. Therefore, further detailed clinical studies of patients with PROK2/PROKR2 mutations will help to map the broader biological role of the PROK2/PROKR2 pathway and identify other interacting genes/proteins that mediate its molecular effects in humans.
Diffusible ligand all-trans-retinal activates opsin via a palmitoylation-dependent mechanism.

In rhodopsin's function as a photoreceptor, 11-cis-retinal is covalently bound to Lys296via a protonated Schiff base. 11-cis/all-transphotoisomerization and relaxation through intermediates lead to the metarhodopsin II photoproduct, which couples to transducin (Gt). Here we have analyzed a different signaling state that arises from noncovalent binding of all-trans-retinal (atr) to the aporeceptor opsin and enhances the very low opsin activity by several orders of magnitude. Like with metarhodopsin II, coupling of Gt to opsin-atr is sensitive to competition by synthetic peptides from the COOH termini of both Gtα and Gtγ. However, atr does not compete with 11-cis-retinal incorporation into the Lys296 binding site and formation of the light-sensitive pigment. Blue light illumination fails to photorevert opsin-atr to the ground state. Thus noncovalently boundatr has no access to the light-dependent binding site and reaction pathway. Moreover, in contrast to light-dependent signaling, removal of the palmitoyl anchors at Cys322 and Cys323 in the rhodopsin COOH terminus impairs the atr-stimulated activity. Repalmitoylation by autoacylation with palmitoyl-coenzyme A restores most of the original activity. We hypothesize that the palmitoyl moieties are part of a second binding pocket for the chromophore, mediating hydrophobic interactions that can activate a large part of the catalytic receptor/G-protein interface.
Glutathione S-transferases catalyzed conjugation of 1,4-disubstituted butanes with glutathione in vitro.

Abstract Rat liver glutathione S-transferases catalyzed the conjugation of 1,4-diiodobutane with glutathione in vitro . The reaction followed saturation kinetics and was dependent on the concentration of the enzyme, substrate and glutathione in the incubation media. S-Benzylglutathione inhibited the enzymatic conversion of 1,4-diiodobutane to product. The cyclic sulfonium compound, γ-glutamyl-β-(S-tetrahydrothiophenium) alanyl-glycine was identified as the product of this conjugation reaction. This product was stable under physiological conditions in presence of rat liver cytosol but rapidly and quantitatively decomposed at pH ≤ 12 to give tetrahydrothiophene.
Noradrenaline and neuropeptide Y innervation of the rat hypothalamus are differentially affected by 6-hydroxydopamine

Abstract The neuropeptide Y (NPY) innervation of the hypothalamus is thought to arise largely from noradrenaline (NA) neurons of the medullary tegmentum in the rat. This view was tested in this study by analyzing the effects of intraventricular injections of 6-hydroxydopamine (6-OHDA) on hypothalamic NA and NPY innervation. 6-OHDA markedly depletes or eliminates the NA innervation of the hypothalamus, as demonstrated by dopamine-β-hydroxylase immunohistochemistry, but does not affect the NPY innervation of the hypothalamus. These results indicate that the hypothalamic NPY innervation arises in large part from intrinsic NPY-producing neurons rather than from medullary neurons in which NA and NPY coexist.
Transthyretin Cardiac Amyloidoses in Older North Americans

The amyloidoses are a group of hereditary or acquired disorders caused by the extracellular deposition of insoluble protein fibrils that impair tissue structure and function. All amyloidoses result from protein misfolding, a common mechanism for disorders in older persons, including Alzheimer's disease and Parkinson's disease. Abnormalities in the protein transthyretin (TTR), a serum transporter of thyroxine and retinol, is the most common cause of cardiac amyloidoses in elderly adults. Mutations in TTR can result in familial amyloidotic cardiomyopathy, and wild-type TTR can result in senile cardiac amyloidosis. These underdiagnosed disorders are much more common than previously thought. The resulting restrictive cardiomyopathy can cause congestive heart failure, arrhythmias, and advanced conduction system disease. Although historically difficult to make, the diagnosis of TTR cardiac amyloidosis has become easier in recent years with advances in cardiac imaging and more widespread use of genetic analysis. Although therapy has largely involved supportive medical care, avoidance of potentially toxic agents, and rarely organ transplantation, the near future brings the possibility of targeted pharmacotherapies designed to prevent TTR misfolding and amyloid deposition. Because these disease-modifying agents are designed to prevent disease progression, it has become increasingly important that older persons with TTR amyloidosis be expeditiously identified and considered for enrollment in clinical registries and trials.
Aging, Diabetes, and the Public Health System in the United States

Diabetes (diagnosed or undiagnosed) affects 10.9 million US adults aged 65 years and older. Almost 8 in 10 have some form of dysglycemia, according to tests for fasting glucose or hemoglobin A1c. Among this age group, diagnosed diabetes is projected to reach 26.7 million by 2050, or 55% of all diabetes cases. In 2007, older adults accounted for $64.8 billion (56%) of direct diabetes medical costs, $41.1 billion for institutional care alone. Complications, comorbid conditions, and geriatric syndromes affect diabetes care, and medical guidelines for treating older adults with diabetes are limited. Broad public health programs help, but effective, targeted interventions and expanded surveillance and research and better policies are needed to address the rapidly growing diabetes burden among older adults.
Global properties of relativistic heavy-ion collisions proved by PHENIX

We report recent experimental results of elliptic flows ( v 2 ), event-by-event fluctuations and Bose-Einstein correlations (HBT) of identified hadrons measured by PHENIX detector at low transverse momentum ( p T ∼ 2 GeV/c ) and mid-rapidity ( | η | 0.35 ) region. We focus on results observed in Au+Au collision at S N N = 200 GeV , but results from Au+Au at 63 GeV and Cu+Cu at 63 and 200 GeV are also reported. These observables give us detailed insights into the properties of the space-time evolution such as the order of the phase transition and the collective dynamics of the hot-and-dense matter.
A body composition model for predicting beef animal growth

Abstract Two beef animal growth computer simulations were compared as to the effects of altering feed energy density. Steers of varying initial degrees of fatness were evaluated. The BEEF-NC114 model used NRC regression equations to predict growth while the BEEF-S156 model used physiological age and body components. Otherwise, the models were essentially identical. On average, the predictions of both models were reasonably close to each other. However, the BEEF-S156 model was more sensitive to extreme conditions of high or low nutrition.
Statistics for Next Generation Sequencing – Meeting Report

The boom of next generation sequencing (NGS) technology and its applications to a wide range of biomedical fields has brought about many computational and statistical challenges. The NHGRI funded small conference “Statistical Analysis for NGS” was held September 26th–27th 2011 in Birmingham, AL, USA, to discuss these statistical challenges and strategies to tackle them. Below, we detail the major themes of the conference.
Are ceramic and metal implant abutments performance similar

Top of pageAbstract Data sources Medline, The Cochrane Library, bibliographies of identified studies and hand searching of the journals, Schweizer Monatsschrift fur Zahnmedizin (Acta Medicinae Dentium Helvetica) and Deutsche Zahnarztliche Zeitschrift and Implantologie. Study selection Randomised-controlled clinical trials, prospective and retrospective studies providing information on ceramic and metal abutments with a mean follow-up time of at least 3 years were included. Patients had to have been examined clinically at the follow-up visit. Data extraction and synthesis Assessment of the identified studies and data abstraction were performed independently by three reviewers. Failure rates were analysed using standard and random-effects Poisson regression models to obtain summary estimates of 5-year survival proportions. Results A total of 29 studies providing information on the clinical performance of the implant abutments were included in the analysis. The estimated 5-year survival rate of ceramic abutments was 99.1% [95% confidence interval (CI): 93.8-99.9%] and 97.4% (95% CI: 96-98.3%) for metal abutments. The estimated cumulative incidence of technical complications after 5 years was 6.9% (95% CI: 3.5-13.4%) for ceramic abutments and 15.9% (95% CI: 11.6-21.5%) for metal abutments. Abutment screw loosening was the most frequent technical problem, occurring at an estimated cumulative incidence after 5 years of 5.1% (95% CI: 3.3-7.7%). All-ceramic crowns supported by ceramic abutments exhibited similar annual fracture rates as metal-ceramic crowns supported by metal abutments. The cumulative incidence of biological complications after 5 years was estimated at 5.2% (95% CI: 0.4-52%) for ceramic and 7.7% (95% CI: 4.7-12.5%) for metal abutments. Aesthetic complications tended to be more frequent at metal abutments. Conclusions The 5-year survival rates estimated from annual failure rates appeared to be similar for ceramic and metal abutments. The information included in this review did not provide evidence of differences for the technical and biological outcomes of ceramic and metal abutments. However, the information for ceramic abutments was limited in the number of studies and abutments analysed as well as the accrued follow-up time. Standardised methods for the analysis of abutment strength are needed.
Studies of the polarity of the tri-n-butyltin radical

Abstract A satisfactory Hammett correlation was observed for the radical reduction of substituted benzyl halides by tri-n-butyltin hydride. The magnitude of the positive ϱ value comparable to that observed for other nucleophilic radicals.
Effect of pressure on liquid-liquid immiscibility of high temperature aqueous solution mixtures of uranyl sulfate and sulfuric acid, 280–450°C, 75–1800 bars

Abstract With rising temperature, aqueous uranyl sulfate and uranyl sulfate-sulfuric acid solutions are very unusual in forming two liquid phases at temperatures above 285°C. In this study the temperatures of immiscibility are shown to be raised by as much as 135°C through the application of hydrostatic pressures up to 1800 bars. This range of pressure extended by a factor of six that of an earlier investigation. An optical cell for use to 500°C and 2000 bars is described, and allowed visual determination of the appearances of immiscibility. The rise in temperature of two liquid phase appearance with increase in hydrostatic pressure was found to be 0·075°C/bar near 300°C, where the initial condition is the boundary of immiscibility in equilibrium with vapor. Upon addition of sulfuric acid the temperature of appearance of immiscibility at vapor saturation is raised, and at these higher initial temperatures the increase in temperature of immiscibility with increase in hydrostatic pressure rises to a value near 0·12°C/bar at 360°C. The present results further confirm a straight line relationship of temperature of immiscibility vs pressure, and support the earlier suggestion of an approximate correlation of the slope with the change in temperature with hydrostatic pressure for pure water either at constant density or constant product of dielectric constant times absolute temperature.