cssi/SciSciGPT-SciSciNet huggingface dataset:
The effect of busulfan treatment on endogenous spermatogonial stem cells in immature roosters

ABSTRACT Several methods have been developed for suppression of endogenous spermatogenesis in recipient males before spermatogonial stem cells transfer. Currently the chemical treatment with alkylating agent busulfan is the method of choice in mammals. Still, in different mammalian species wide variability in optimal doses of busulfan has been demonstrated, whereas in birds, the dosage has not yet been optimized. We tested the sterilizing effect of several busulfan doses: 20, 40, and 60 mg/kg of BW as a single or double intraperitonial injections in pubertal-age roosters. It was found that the 20 to 40 mg/kg of BW doses effective in mice did not lead to suppression of spermatogenesis in birds. A single high dose of busulfan (60 mg/kg of BW) resulted in the death of all treated chickens, whereas the same amount of busulfan applied in 2 doses resulted in considerable suppression of spermatogenesis in majority of treated birds. Application of busulfan in several doses also caused less physiological stress than single-dose application.
Quantifying Methane Oxidation from Landfills Using Stable Isotope Analysis of Downwind Plumes

Landfills are major contributors to the atmospheric CH4 budget. A major uncertainty in estimating CH4 flux from landfills is determining the attenuation of CH4 emission by methanotrophic bacteria in the aerobic outer portions of the cover soil. These bacteria intercept the gas as it migrates toward the atmosphere. To estimate cover soil oxidation, we made seasonal measurements of the difference in the δ13C of CH4 within the anoxic zone and CH4 released from landfills and captured downwind at two landfills in the Northeastern United States. Anoxic zone CH4 at the Nashua Landfill averaged −54.6 ± 0.7‰, n = 205, and displayed no significant seasonal pattern. Methane was in excess over ambient air concentrations in the downwind plume ranging from 2.13 to 3.41 ppmv. The δ13C of excess CH4, as determined by mass balance with correction for ambient air CH4, varied from −49.35 to −54.28‰. We used these values to calculate soil CH4 oxidation, which ranged from 0 to 23.6%. Oxidation was greatest in the summer and i...
Dynamic B-spline surface reconstruction: Closing the sensing-and-modeling loop in 3D digitization

In this paper, we present a new B-spline surface reconstruction approach, called dynamic surface reconstruction, aiming to close the sensing-and-modeling loop in 3D digitization. At its core, this approach uses a recursive least squares method, the Kalman filter, to dynamically reconstruct the B-spline surface as the surface data are acquired. That is, the acquired data are dynamically incorporated into the surface model and the updated surface model is then used to dynamically guide further data acquisition. It thus enables a closed-loop shape sensing-and-modeling methodology for 3D digitization. Our technical contribution lies on the exploitation of the recursive nature of the Kalman filter for B-spline surface reconstruction. This enables dynamic parameterization of data points, dynamic determination of next optimal sensing locations, and low-discrepancy based efficient sensing and reconstruction. Experiments demonstrate that such dynamic surface reconstruction leads to more efficient data acquisition and better surface reconstruction.
“Let me tell you the point”: How speakers with aphasia assign prominence to information in narratives

Background: A central purpose of narration is to convey one's point of view about a narrated event. One's expressed evaluation of a narrated event (modalising behaviour) is often differentiated from one's expression of the sequence of events proper (referential behaviour). Modalising and referential language may be dissociated in aphasia, with modalising language relatively preserved. Use of narrative evaluative devices is one way to modalise, transmit significance, or assign prominence to information in narratives. Aims: This study examines the frequency of use, co-occurrence, and distribution of multiple evaluative devices in the personal narratives of speakers with aphasia, as compared to that of narratives produced by demographically similar speakers without aphasia. Methods & Procedures: Participants were 33 demographically matched, English-speaking, middle-aged adults. Of these, 17 had aphasia, and 16 had no neurological disorder. Each group included similar proportions of three demographic subgroup...
Human, Bovine and Porcine Systematic Vascular Input Impedances Are Not Equivalent: Implications for Device Testing and Xenotransplantation in Heart Failure

Background Advanced therapies for heart failure (HF), such as mechanical circulatory support (MCS) devices and xenotransplantation, are usually tested in bovine and porcine models. This approach assumes a priori that animal (patho)physiology will closely match that of humans. Systemic aortic input impedance (Z ART ) is an important physiologic determinant of left ventricular (LV) performance. We tested the hypothesis that Z ART is lower in bovine and porcine than in humans with normal or failing hearts. Methods High-fidelity aortic pressure and flow waveforms were recorded intra-operatively at native and paced heart rates of 100 beats per minute (bpm) in adult human patients with normal LV function ( n = 13) or end-stage HF ( n = 15), and normal calves ( n = 10) and pigs ( n = 18). Fast Fourier transformation was used to calculate Z ART , and arterial resistance and compliance were estimated using a 4-element Windkessel model. Results Humans with HF had greater Z ART than those with normal LV function, characterized by higher resistance (1.16 ± 0.12 vs 1.00 ± 0.10 mm Hg·s/ml, p p p Conclusions Z ART is significantly lower in calves and pigs than in humans with or without HF. This finding has important implications for the pre-clinical testing of MCS devices and xenotransplants, which are usually examined in bovine and porcine models, respectively. Specifically, these therapies may respond differently in humans than animals due to non-equivalence of systemic after-load.
Estimating the Extent of Reduction Needed to Statistically Demonstrate Reduced Non-Point Phosphorus Loading to Lake Erie

Abstract The need to reduce non-point phosphorus contributions to Lake Erie has led to extensive efforts to implement conservation tillage in the Lake Erie basin. Because annual loads are highly variable, statistical approaches will be required to document the success of conservation tillage and other best management practices in reducing loads. Important management issues are how large a reduction will be required, and how long it will take to achieve the needed reduction. In response to these issues, a method is presented for estimating the amount of change needed to establish a statistically significant reduction, based on the standard t-test. Analysis of data from the Sandusky River, a north-central Ohio tributary of Lake Erie, indicates that the necessary change is about 35% of the current loads. When the loads are adjusted for variations in discharge, the necessary change can be reduced to about 20%. Based on projections of the Army Corps of Engineers of adoption rates of conservation tillage, and the associated effects on phosphorus loads, a 35% change would take 25 years or more, but a 20% change would occur by the end of 8 years. The documentation of these changes will require high quality monitoring data, collected before and during the implementation period with the same sampling strategy.
Efficient Bidding for Virtual Machine Instances in Clouds

Combinatorial auctions are efficient mechanisms for allocating Virtual Machine (VM)instances to cloud computing users. Despite the fact that in general these mechanisms lead to higher revenues than the currently employed fixed-price mechanisms, the cloud computing providers do not employ them to allocate their resources. One of the main reasons is the complexity faced by the users when determining the bid (i.e., the bundle of VM instances and the bid value). We address this issue by developing an efficient bidding strategy for the users requesting VM instances. We design new metrics for evaluating bundles of VM instances based on the characteristics of the computing tasks. These metrics allow us to determine the valuation of the requested bundles and to design algorithms for selecting the best bundles to bid for. We perform simulation experiments to evaluate the proposed strategy in a simulated cloud environment.
UO speciation determines uranium toxicity and bioaccumulation in an environmental Pseudomonas sp. isolate

In the present study, experiments were performed to investigate how representative cellulosic breakdown products, when serving as growth substrates under aerobic conditions, affect hexavalent uranyl cation (UO(2) (2+)) toxicity and bioaccumulation within a Pseudomonas sp. isolate (designated isolate A). Isolate A taken from the Cold Test Pit South (CTPS) region of the Idaho National Laboratory (INL), Idaho Falls, ID, USA. The INL houses low-level uranium-contaminated cellulosic material and understanding how this material, and specifically its breakdown products, affect U-bacterial interactions is important for understanding UO(2) (2+) fate and mobility. Toxicity was modeled using a generalized Monod expression. Butyrate, dextrose, ethanol, and lactate served as growth substrates. The potential contribution of bicarbonate species present in high concentrations was also investigated and compared with toxicity and bioaccumulation patterns seen in low-bicarbonate conditions. Isolate A was significantly more sensitive to UO(2) (2+) and accumulated significantly more UO(2) (2+) in low-bicarbonate concentrations. In addition, UO(2) (2+) growth inhibition and bioaccumulation varied depending on the growth substrate. In the presence of high bicarbonate concentrations, sensitivity to UO(2) (2+) inhibition was greatly mitigated, and did not vary between the four substrates tested. The extent of UO(2) (2+) accumulation was also diminished. The observed patterns were related to UO(2) (2+) aqueous complexation, as predicted by MINTEQ (ver. 2.52) (Easton, PA, USA). In the low- bicarbonate medium, the presence of positively charged and unstable UO(2) (2+)-hydroxide complexes explained both the greater sensitivity of isolate A to UO(2) (2+), and the ability of isolate A to accumulate significant amounts of UO(2) (2+). The exclusive presence of negatively charged and stable UO(2) (2+)-carbonate complexes in the high bi-carbonate medium explained the diminished sensitivity of isolate A to UO(2) (2+) toxicity, and limited ability of isolate A to accumulate UO(2) (2+).
Lesion processing by a repair enzyme is severely curtailed by residues needed to prevent aberrant activity on undamaged DNA

DNA base excision repair is essential for maintaining genomic integrity and for active DNA demethylation, a central element of epigenetic regulation. A key player is thymine DNA glycosylase (TDG), which excises thymine from mutagenic G·T mispairs that arise by deamination of 5-methylcytosine (mC). TDG also removes 5-formylcytosine and 5-carboxylcytosine, oxidized forms of mC produced by Tet enzymes. Recent studies show that the glycosylase activity of TDG is essential for active DNA demethylation and for embryonic development. Our understanding of how repair enzymes excise modified bases without acting on undamaged DNA remains incomplete, particularly for mismatch glycosylases such as TDG. We solved a crystal structure of TDG (catalytic domain) bound to a substrate analog and characterized active-site residues by mutagenesis, kinetics, and molecular dynamics simulations. The studies reveal how TDG binds and positions the nucleophile (water) and uncover a previously unrecognized catalytic residue (Thr197). Remarkably, mutation of two active-site residues (Ala145 and His151) causes a dramatic enhancement in G·T glycosylase activity but confers even greater increases in the aberrant removal of thymine from normal A·T base pairs. The strict conservation of these residues may reflect a mechanism used to strike a tolerable balance between the requirement for efficient repair of G·T lesions and the need to minimize aberrant action on undamaged DNA, which can be mutagenic and cytotoxic. Such a compromise in G·T activity can account in part for the relatively weak G·T activity of TDG, a trait that could potentially contribute to the hypermutability of CpG sites in cancer and genetic disease.
Contractile Function and Response to Agonists in Myocytes from Failing Human Heart

Ventricular myocytes from failing human hearts have a similar maximum contraction amplitude in high Ca2+ to those from non-failing heart at low stimulation rates (0.2 Hz, 32 degrees C), but do not exhibit the same positive frequency-interval relationship. At higher stimulation rates (1 Hz) therefore, the amplitude is depressed in cells from failing hearts compared to controls. Slow relaxation is seen in myocytes from failing ventricle at all stimulation rates, and contraction velocity is also slightly reduced. beta-adrenoceptor desensitization is evident, and increases with severity of disease. There is also a post-receptor defect in myocytes from failing heart since responses to forskolin and cyclic AMP analogues are reduced, and this is accompanied by decreased cyclic AMP levels in myocardium from patients in end-stage disease. Pertussis toxin treatment, which inactivates Gi, reverses most of the alterations in the beta-adrenoceptor pathway. The role of the sympathetic system is indicated by the parallels between myocytes from failing human heart and those from the noradrenaline-treated guinea-pig, which show beta-adrenoceptor desensitization, a post-receptor defect and reduced basal cyclic AMP levels. However, relaxation velocities are not slowed in these guinea-pig myocytes, indicating that basal cyclic AMP does not have a tonic role in speeding relaxation.
A molecular basis for Weber's law.

A mathematical model is presented that obeys a strong form of Weber's law – over a range of adapting and stimulus intensities, equal contrast stimuli evoke identical responses. To account for the strong Weber's law, the adaptive stage in the proposed model employs a “delayed” reverse reaction along with a power-law input. It is suggested that this Weber's law mechanism is responsible for a slow, voltage-uncorrelated component of adaptation in the vertebrate photoreceptor. A plausible biochemical mechanism is the G-protein cycle with phosphorylation of photoactivated photopigment (and binding of arrestin to the phosphorylated photopigment) as the adaptive process. In an Appendix, features of the general model and implications of a specific biochemical model are examined by computer simulation.
A microbial link between elevated CO2 and methane emissions that is plant species-specific.

Rising atmospheric CO2 levels alter the physiology of many plant species, but little is known of changes to root dynamics that may impact soil microbial mediation of greenhouse gas emissions from wetlands. We grew co-occurring wetland plant species that included an invasive reed canary grass (Phalaris arundinacea L.) and a native woolgrass (Scirpus cyperinus L.) in a controlled greenhouse facility under ambient (380 ppm) and elevated atmospheric CO2 (700 ppm). We hypothesized that elevated atmospheric CO2 would increase the abundance of both archaeal methanogen and bacterial methanotroph populations through stimulation of plant root and shoot biomass. We found that methane levels emitted from S. cyperinus shoots increased 1.5-fold under elevated CO2, while no changes in methane levels were detected from P. arundincea. The increase in methane emissions was not explained by enhanced root or shoot growth of S. cyperinus. Principal components analysis of the total phospholipid fatty acid (PLFA) recovered from microbial cell membranes revealed that elevated CO2 levels shifted the composition of the microbial community under S. cyperinus, while no changes were detected under P. arundinacea. More detailed analysis of microbial abundance showed no impact of elevated CO2 on a fatty acid indicative of methanotrophic bacteria (18:2ω6c), and no changes were detected in the terminal restriction fragment length polymorphism (T-RFLP) relative abundance profiles of acetate-utilizing archaeal methanogens. Plant carbon depleted in 13C was traced into the PLFAs of soil microorganisms as a measure of the plant contribution to microbial PLFA. The relative contribution of plant-derived carbon to PLFA carbon was larger in S. cyperinus compared with P. arundinacea in four PLFAs (i14:0, i15:0, a15:0, and 18:1ω9t). The δ13C isotopic values indicate that the contribution of plant-derived carbon to microbial lipids could differ in rhizospheres of CO2-responsive plant species, such as S. cyperinus in this study. The results from this study show that the CO2–methane link found in S. cyperinus can occur without a corresponding change in methanogen and methanotroph relative abundances, but PLFA analysis indicated shifts in the community profile of bacteria and fungi that were unique to rhizospheres under elevated CO2.
The observer-based controller design of discrete-time singularly perturbed systems

A class of linear shift-invariant discrete-time singularly perturbed systems with inaccessible states is considered. A design technique is formulated by which the stabilizing controller can be formed through the controllers of the slow and fast subsystems. Sufficient conditions for stability of the closed-loop system under this composite controller are given.
Risk stratification for coronary bypass surgery in patients with left ventricular dysfunction: analysis of the coronary artery bypass grafting patch trial database.

Background—Preoperative characteristics may influence morbidity and mortality in patients undergoing coronary artery bypass grafting (CABG). The CABG Patch Trial was designed to assess the impact of prophylactic insertion of an implantable cardioverter-defibrillator in patients undergoing high-risk CABG. This database was used to investigate the influence of symptomatic congestive heart failure (CHF) and angina on morbidity and mortality in CABG patients with ventricular dysfunction. Methods and Results—Data were analyzed for 900 randomized patients with an ejection fraction ≤35% and an abnormal signal-averaged ECG. Single-variable and stepwise multiple logistic regression analyses were used for mortality and length-of-stay (LOS) data. Severity of CHF and angina was graded by the New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) classifications, respectively. Perioperative mortality was 3.5% in 454 patients without clinical signs of heart failure versus 7.7% in 443 patients with ...
Personal article filing with multiple keywords: why and how

A common PC database, with a dash of Visual Basic code, results in improved office article filing management for faculty trying to control their personal collection of printed journal articles, URLs, and conference handouts. Outlined are the problems inherent in personal storage as well as the features of the suggested database approach that can make collection management more palatable.
Performance capture with physical interaction

This paper introduces a technique for combining performance-based animation with a physical model in order to synthesize complex interactions in an animated scene. The approach is to previsualize interaction of final integrated scene, online, while the performance is being recorded. To accomplish this goal, we propose a framework which unifies kinematic playback of motion capture and dynamic motion synthesis. The proposed method augments a real-time recording of a human actor with dynamics-based response in order to modify motion data based on the conditions of the character. The system unifies kinematic and dynamic aspects of the final motion while allowing user control over the outcome both temporally and spatially across the character's body. Examples of complex interactions interleaved with intelligent response underscore the power of the technique along with multi-person captures in which remote users interact physically in a shared virtual world.
Coplanar waveguide excitation of dielectric resonator antennas

The circuit and radiation properties of a cylindrical dielectric resonator antenna excited by a coplanar waveguide feed are investigated. The coupling between the feed and the radiator was measured as a function of the position, dielectric constant, and height of the cylinder. The radiation patterns and resonant frequencies were also measured. These measured results are found to be in good agreement with theoretical calculations. >
Classifier performance as a function of distributional complexity

Abstract When choosing a classification rule, it is important to take into account the amount of sample data available. This paper examines the performances of classifiers of differing complexities in relation to the complexity of feature-label distributions in the case of small samples. We define the distributional complexity of a feature-label distribution to be the minimal number of hyperplanes necessary to achieve the Bayes classifier if the Bayes classifier is achievable by a finite number of hyperplanes, and infinity otherwise. Our approach is to choose a model and compare classifier efficiencies for various sample sizes and distributional complexities. Simulation results are obtained by generating data based on the model and the distributional complexities. A linear support vector machine (SVM) is considered, along with several nonlinear classifiers. For the most part, we see that there is little improvement when one uses a complex classifier instead of a linear SVM. For higher levels of distributional complexity, the linear classifier degrades, but so do the more complex classifiers owing to insufficient training data. Hence, if one were to obtain a good result with a more complex classifier, it is most likely that the distributional complexity is low and there is no gain over using a linear classifier. Hence, under the model, it is generally impossible to claim that use of the nonlinear classifier is beneficial. In essence, the sample sizes are too small to take advantage of the added complexity. An exception to this observation is the behavior of the three-nearest-neighbor (3NN) classifier in the case of two variables (but not three) when there is very little overlap between the label distributions and the sample size is not too small. With a sample size of 60, the 3NN classifier performs close to the Bayes classifier, even for high levels of distributional complexity. Consequently, if one uses the 3NN classifier with two variables and obtains a low error, then the distributional complexity might be large and, if such is the case, there is a significant gain over using a linear classifier.
Hematopoietic progenitor cell large volume leukapheresis (LVL) on the Fenwal Amicus blood separator.

A technique for large volume leukapheresis (LVL) for hematopoietic progenitor cell (HPC) collection using the Fenwal Amicus is presented. It was compared to standard collections (STD) with regard to CD34+ cell yields and cross-cellular content. Optimal cycle volumes and machine settings were evaluated for LVL procedures. A total of 68 patients underwent 80 HPC collection procedures. Because of differences in CD34+ cell yields associated with peripheral white blood cell counts (WBC), the comparison was divided into groups of 20 with WBC ≤35 × 109/L (≤35 K) and those >35 × 109/L (>35 K). Baseline CD34+ cell counts (peripheral count when patient started HPC collection) were used (median 18–23 cells/μl). Significantly more whole blood (corrected for anticoagulant) was processed with LVL (LVL 20 l vs. STD 13.5 l). For ≤35 K, median CD34+ × 106, WBC × 109, RBC ml, Plt × 1011 yields/collection were 183, 21.2, 14, 0.8, respectively, for STD vs. 307, 22.1, 11, 1.0, respectively, for LVL. For >35 K, median CD34+ × 106, WBC × 109, RBC ml, Plt × 1011 yields/collection were 189, 32.7, 15, 1.4, respectively, for STD vs. 69, 40.8, 21, 1.3, respectively, for LVL. We have described a method of LVL using the Amicus that, in patients with pre-procedure WBC ≤35×109/L, collects more CD34+ cells than a standard procedure with acceptable cross-cellular content. This method is not recommended when pre-procedure WBC counts are >35 × 109/L. J Clin Apheresis 19:103–111, 2004. © 2004 Wiley-Liss, Inc.
A fine-grain, high-throughput architecture using through-wafer optical interconnect

The author present a highly parallel, three-dimensionally interconnected system to process high-throughput stream data such as images. Optical interconnect at wavelengths to which silicon is transparent is used to create the 3D system. Thin film InP/InGaAsP-based emitters and detectors operating at 1.3 microns are bonded to the silicon circuitry, and emit through the silicon wafer to create the vertical optical interconnect. Foundry-fabricated Si circuits are post processed using standard, low cost, high yield microfabrication techniques to integrate the thin film devices with the circuits. In order to meet off-chip I/O requirements, a high-bandwidth, three-dimensional optical network is also being designed. Using through-wafer optical interconnect, a new offset cube topology has been created, and naming and routing schemes have been developed. Its performance is comparable to that of a three-dimensional mesh. A processing architecture has also been defined that minimizes overhead for basic parallel operations. A complete processing node for high-throughput, low-memory applications can be implemented using a fraction of a chip. >
Sexual behavior patterns of methamphetamine-using gay and bisexual men

We assessed the sexual behaviors of 49 gay and bisexual methamphetamine users in New York City and the relationship between their use of the substance and their sexual practices as part of a larger investigation of the behavioral aspects of methamphetamine use. Participants were assessed on their use of methamphetamine and their sexual behaviors in conjunction with use of the substance. Participants reported equivalent rates of unprotected anal insertive and receptive behaviors when comparing their sexual acts while high on methamphetamine, high on other drugs, and sober. In addition, equivalent rates of “extreme” sex acts were found for 10 of the 12 behaviors examined while high on methamphetamine and while sober. While we found few differences in terms of rates of sexual behaviors, our analysis revealed more frequent risky sexual behaviors among HIV positive men when compared with HIV negative men. Our results suggest that methamphetamine attracts a hypersexual risk-taking group of men who engage in unp...
The insulator protein Suppressor of Hairy-wing is an essential transcriptional repressor in the Drosophila ovary.

Suppressor of Hairy-wing [Su(Hw)] is a DNA-binding factor required for gypsy insulator function and female germline development in Drosophila. The insulator function of the gypsy retrotransposon depends on Su(Hw) binding to clustered Su(Hw) binding sites (SBSs) and recruitment of the insulator proteins Centrosomal Protein 190 kD (CP190) and Modifier of mdg4 67.2 kD (Mod67.2). By contrast, the Su(Hw) germline function involves binding to non-clustered SBSs and does not require CP190 or Mod67.2. Here, we identify Su(Hw) target genes, using genome-wide analyses in the ovary to uncover genes with an ovary-bound SBS that are misregulated upon Su(Hw) loss. Most Su(Hw) target genes demonstrate enriched expression in the wild-type CNS. Loss of Su(Hw) leads to increased expression of these CNS-enriched target genes in the ovary and other tissues, suggesting that Su(Hw) is a repressor of neural genes in non-neural tissues. Among the Su(Hw) target genes is RNA-binding protein 9 (Rbp9), a member of the ELAV/Hu gene family. Su(Hw) regulation of Rbp9 appears to be insulator independent, as Rbp9 expression is unchanged in a genetic background that compromises the functions of the CP190 and Mod67.2 insulator proteins, even though both localize to Rbp9 SBSs. Rbp9 misregulation is central to su(Hw)-/- sterility, as Rbp9+/-, su(Hw)-/- females are fertile. Eggs produced by Rbp9+/-, su(Hw)-/- females show patterning defects, revealing a somatic requirement for Su(Hw) in the ovary. Our studies demonstrate that Su(Hw) is a versatile transcriptional regulatory protein with an essential developmental function involving transcriptional repression.
Dynamic-sleep transistor and body bias for active leakage power control of microprocessors

In order to manage the active power consumption of high-performance digital designs, active leakage control techniques are required to provide significant leakage power savings coupled with fast time constants for entering and exiting idle mode. In this paper, dynamic sleep transistors and body bias are used in conjunction with clock gating to control active leakage for a 32-bit integer execution core in 130-nm CMOS technology. Measurements on pMOS sleep transistor reveal that lowest-leakage state is reached in less than 1 /spl mu/s, resulting in 37/spl times/ reduction in leakage power, while reactivation of block is achieved in less than two clock cycles. PMOS body bias reduces leakage power by 2/spl times/ with no performance penalty, and similar reactivation time. Power measurements at 4 GHz, 1.3 V, 75/spl deg/C demonstrate 8% total power reduction using dynamic body bias and 15% power reduction using a pMOS sleep transistor, for a typical activity profile.
A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression

CONTEXT: The efficacy of antidepressant drug treatment in depression is unsatisfactory; 1 in 3 patients does not fully recover even after several treatment trials. Genetic factors and clinical characteristics contribute to the failure of a favorable treatment outcome. OBJECTIVE: To identify genetic and clinical determinants of antidepressant drug treatment outcome in depression. DESIGN: Genomewide pharmacogenetic association study with 2 independent replication samples. SETTING: We performed a genomewide association study in patients from the Munich Antidepressant Response Signature (MARS) project and in pooled DNA from an independent German replication sample. A set of 328 single-nucleotide polymorphisms highly related to outcome in both genomewide association studies was genotyped in a sample of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. PARTICIPANTS: A total of 339 inpatients with a depressive episode (MARS sample), a further 361 inpatients with depression (German replication sample), and 832 outpatients with major depression (STAR*D sample). MAIN OUTCOME MEASURES: We generated a multilocus genetic variable that described the individual number of alleles of the selected single nucleotide polymorphisms associated with beneficial treatment outcome in the MARS sample ("response" alleles) to evaluate additive genetic effects on antidepressant drug treatment outcome. RESULTS: Multilocus analysis revealed a significant contribution of a binary variable that categorized patients as carriers of a high vs low number of response alleles in the prediction of antidepressant drug treatment outcome in both samples (MARS and STAR*D). In addition, we observed that patients with a comorbid anxiety disorder combined with a low number of response alleles showed the least favorable outcome. CONCLUSION: These results demonstrate the importance of multiple genetic factors combined with clinical features in the prediction of antidepressant drug treatment outcome, which underscores the multifactorial nature of this trait.
Fatigue Resistance of Fiberglass Laminates at Thick Material Transitions

A complex test coupon with ply drops, intended to be representative of blade structure, has been developed with the aid of finite element analysis. The complex coupon can be used to evaluate the static and fatigue performance of infused wind turbine blade laminates containing various fabrics, resins, and material transition choices under tension, compression and reversed uniaxial loading conditions. Static and fatigue test results are presented for polyester, vinyl ester and epoxy resins and a toughened vinyl ester, for both plain and complex coupon geometries. The complex coupon damage sequence involves matrix cracking, ply delamination, load redistribution, and finally ±45 o and 0 o ply failure. The coupon performance showed significant sensitivity to the resin, with delamination results correlated to the Modes I and II interlaminar toughness. The static and fatigue damage loads varied approximately inversely with the square root of the number of plies dropped at a single position, with up to 5 mm thickness of dropped unidirectional material. Reversed loading in fatigue reduced lifetimes significantly compared to pure tensile or compression loading. The results of the study can be used to estimate the knockdowns and trade-offs associated with resin type and fabrication options.
RSC1 and RSC2 Are Required for Expression of Mid-Late Sporulation-Specific Genes in Saccharomyces cerevisiae

Rsc1 and Rsc2 are alternative bromodomain-containing subunits of the ATP-dependent RSC chromatin remodeling complex in Saccharomyces cerevisiae. Smk1 is a sporulation-specific mitogen-activated protein kinase homolog that is required for the postmeiotic events of spore formation. In this study we show that RSC1 and RSC2 are haploinsufficient for spore formation in a smk1 hypomorph. Moreover, diploids lacking Rsc1 or Rsc2 show a subset of smk1-like phenotypes. High-copy-number RSC1 plasmids do not suppress rsc2-Δ/rsc2-Δ sporulation defects, and high-copy-number RSC2 plasmids do not suppress rsc1-Δ/rsc1-Δ sporulation defects. Mid-late sporulation-specific genes, which are normally expressed while key steps in spore assembly occur and which include genes that are required for spore wall formation, are not expressed in cells lacking Rsc1 or Rsc2. We speculate that the combined action of Rsc1 and Rsc2 at mid-late promoters is specifically required for the proper expression of this uniquely timed set of genes. Our data suggest that Smk1 and Rsc1/2 define parallel pathways that converge to provide signaling information and the expression of gene products, respectively, that are required for spore morphogenesis.
The force on a lattice defect in an elastic body

It is shown that the force on a lattice defect in an elastic body is, like the force on a disclination in a nematic liquid crystal, a real force which, for equilibrium, must be balanced by an external force applied to the closed surface enclosing the defect.
Bringing the Public Back In: Should Sociologists Consider the Impact of Public Opinion on Public Policy?

The struggle for democracy, central to Western politics for hundreds ofyears, is predicated upon the belief that democratic institutions give citizens considerable power over their government. Whether this belief is correct is a key question in the study of democratic politics. This article argues that this question is neglected by sociologists who examine the determinants of public policy; they neither address theories of democratic responsiveness nor assess the impact of public opinion on public policy. This neglect is problematic for two reasons: there is much evidence that public opinion strongly influences public policy, and there is reason to believe that adding public opinion to sociologists' empirical analyses of policy change would undermine some of their conclusions about the influence of otherfactors. Two ways of responding to these findings are presented. It has been 350 years since the struggle for representative democracy began during the English Revolution. It was then that the Levellers first articulated many ideas still central to democratic thought: that government should be subject to the people; that the rights of citizens should be protected by a written constitution; and that among these rights should be the right to vote, equality before the law, freedom of speech, legal representation, and the right to remain silent during judicial proceedings.'
Wide-bandwidth lasers and modulators for RF photonics

In this paper, the basic principle of operation, design issues, limitations, recent developments and emerging research trends on wide-bandwidth lasers and modulators for radio-frequency photonic applications are reviewed. The topics covered are wide-bandwidth lasers, lumped and traveling-wave electroabsorption modulators, traveling-wave LiNbO/sub 3/, GaAs, and polymer modulators.
The Thermal Structure of the Upper Ocean

Abstract The salient feature of the oceanic thermal structure is a remarkably shallow thermocline, especially in the Tropics and subtropics. What factors determine its depth? Theories for the deep thermohaline circulation provide an answer that depends on oceanic diffusivity, but they deny the surface winds an explicit role. Theories for the shallow ventilated thermocline take into account the influence of the wind explicitly, but only if the thermal structure in the absence of any winds, the thermal structure along the eastern boundary, is given. To complete and marry the existing theories for the oceanic thermal structure, this paper invokes the constraint of a balanced heat budget for the ocean. The oceanic heat gain occurs primarily in the upwelling zones of the Tropics and subtropics and depends strongly on oceanic conditions, specifically the depth of the thermocline. The heat gain is large when the thermocline is shallow but is small when the thermocline is deep. The constraint of a balanced heat b...
The effect of triclosan on the proliferation of peritoneal tissue explants

Abstract. Due to the high frequency of post-surgical infection, antibacterial coated suture material has been developed and is suggested to reduce infection during healing. Triclosan is a common antibacterial that is now being incorporated into suture material. When the sutures are placed in the body, the triclosan is slowly released into the tissue over time. Recent studies show a potential for accumulation in fatty body tissues which would amplify the exposure to triclosan. Since exposure time to the drug plays a significant role in the magnitude of its results, the effects on tissue cultures should be investigated. The purpose of this study was to determine if triclosan inhibits tissue proliferation at supraphysiological doses to find out whether or not further study is required. Rat peritoneal tissue was excised from neonatal rats. It was hypothesized that triclosan would have a significantly negative effect on tissue proliferation. However, the results showed that even at high doses, triclosan had no...
Synthesis and characterization of 7,8,15,16-tetraazaterrylene

A facile three-step synthesis of 7,8,15,16-tetraazaterrylene (TAT) from phenalene-1,3-dione, with potential application in organic electronics, is reported. Single crystal structure analysis shows one-dimensional columnar stacks with an interplanar distance of 3.352 A.
Associations of Welding and Manganese Exposure with Parkinson's Disease: A Systematic Review and Meta-Analysis (P07.127)

Objective: To examine associations of welding and manganese exposure with Parkinson9s disease (PD) using meta-analyses of published data from cohort, case-control and mortality studies. Background Case reports suggest that exposure to high levels of manganese is associated with the development of manganism. It has been suggested that welders might be at higher risk of PD because of their exposure to manganese through inhalation of the fume. However, the association of manganese exposure with PD remains controversial. Design/Methods: Epidemiologic studies related to welding or manganese exposure and PD were identified using a PUBMED search from 1974 to 2011, published reviews, reference lists from articles, and published abstracts. Studies were included if they met the following criteria: (1) cohort, case-control or mortality study with relative risk (RR), odds ratio (OR) or mortality odds ratio (MOR) and 95% CI; (2) studies matched or adjusted for age and sex; (3) valid design and analysis. When participants of one study were a subgroup of participants of a larger study, only results of the larger study were included to assure independence of datasets. Pooled risk estimates and 95% CIs were obtained using a random effects model, and heterogeneity of study effects was evaluated using the Q statistic and I² Index. Results: Fourteen studies (3 cohort, 8 case-control and 3 mortality) met inclusion criteria. The overall pooled RR for the association between welding and PD for all study designs was 0.86 (95% CI: 0.80-0.92; p Conclusions: The findings from this meta-analysis demonstrate an inverse association between welding and PD and are incompatible with the observation that welding or manganese exposure increases the risk of PD. Disclosure: Dr. Mortimer has received personal compensation for activities with Davies, McFarland, and Carroll. Dr. Borenstein has nothing to disclose. Dr. Nelson has received personal compensation for activities with Goldberg and Segalla.
Perceived Risks from Disease and Management Policies: An Expansion and Testing of a Zoonotic Disease Risk Perception Model

Human dimensions information about wildlife disease risk management is an important component in developing successful policies because policy implementation depends on stakeholder involvement and public support. Understanding how stakeholders perceive risks is fundamental to successful disease management, yet a clear systematic theory-based framework is lacking. We expanded and tested a portion of the zoonotic disease risk information seeking and processing (ZDRISP) framework using a tailored design method survey with a sample (n= 4,000) of Michigan deer hunters. Our study revealed respondents perceived risks from wildlife disease management policies, which are influenced by disease risk perceptions and subjective and descriptive norms. These results advance a zoonotic disease risk perception theoretical framework that can be applied to understand stakeholder perceptions of different wildlife diseases having varying levels of prevalence, susceptibility, or severity. Integrating insights about human perce...
NEO212: A NOVEL TEMOZOLOMIDE-PERILLYL ALCOHOL CONJUGATE EXHIBITS SUPERIOR ACTIVITY AGAINST TEMOZOLOMIDE RESISTANT GLIOMAS AND INTRACRANIAL TRIPLE NEGATIVE BREAST CANCER METASTASIS

BACKGROUND: Although the alkylating agent temozolomide (TMZ) has become the standard of care in the treatment of malignant gliomas, its overall efficacy is still limited by development of drug resistance, limited blood brain barrier (BBB) penetrance, and myelotoxicity. Recently, we have synthesized a TMZ analog where the monoterpene perillyl alcohol (POH) is covalently linked to TMZ via an amide bond. This new compound (NEO212) has been tested in two situations: TMZ resistant gliomas and breast cancer intracranial metastasis. METHODS: Glioma cell lines (U251TR, LN229TR2, T98G) determined to be TMZ resistant based on base excision repair (BER) pathway, mismatch repair (MMR) deficiency, or overexpression of O6 methyl-guanine-DNA methyltransferase (MGMT) were evaluated in-vitro. In vivo experiments were performed using intracranial implant of luciferase labeled TMZ resistant cell lines. Triple negative breast cancer lines were tested, and implanted intracranially for in-vivo model. NEO212 was administered in both cases using subcutaneous injection using 10 day treatment, 7 day rest cycles. RESULTS: NEO212, at equimolar concentrations to TMZ, was more cytotoxic to TMZ resistant cells, and did not have significant toxicity on normal astrocytes and brain endothelial cells. NEO212 induced cell death appeared to be independent of the mechanism of DNA repair resistance. In vivo experiments using intracranial implant of luciferase labeled TMZ resistant cell lines demonstrated that NEO212 crossed the BBB, reduced intracranial growth, and increased animal survival significantly compared to TMZ, without significant toxicity (including bone marrow). NEO212 was also effective in TMZ resistant breast cancer lines. In an intracranial mouse tumor model with triple-negative breast cancer, NEO212 revealed considerably greater therapeutic efficacy than TMZ, where a single cycle of treatment (10 days) extended median survival benefit from 6 days (in the case of TMZ) to 28 days, with good tolerance. CONCLUSIONS: NEO212 appears to be a promising well tolerated new agent with similar mechanism of cytotoxicity to TMZ. Its increased potency is most likely multi-factorial: 1) increased DNA damage, involving a broader scope of DNA repair mechanisms. 2) linkage with POH, resulting in longer biological half-life and greater opportunity for placement of cytotoxic DNA lesions. 3) increased lipophilicity, allowing for better penetration of the BBB, and possibly cell membrane. Preliminary results demonstrate that it can safely be administered systemically; more detailed toxicity studies are currently underway. SECONDARY CATEGORY: Tumor Biology.
236 PREDICTORS OF SURVIVAL FOLLOWING SUDDEN CARDIAC ARREST IN OUTPATIENT HEMODIALYSIS CLINICS.

Background Sudden cardiac arrest (SCA) is the single most common cause of death in ESRD, and it is implicated in over 50% of all cardiac deaths in hemodialysis patients. The prognosis for survival following an in-hemodialysis clinic arrest is dismal, with one series reporting a 32% 30-day survival rate and a 15% 1-year survival rate. The purpose of this study was to identify factors that predict survival following an in-clinic arrest in the outpatient hemodialysis population. Methods All patients who suffered in-center SCA in the Gambro Healthcare System in the US from 2002-2005 were identified. Baseline demographic and clinical characteristics at the time of the event were compared between patients who did and patients who did not survive for 6 months after the event. Univariate and multivariate models were constructed to identify predictors of survival. Results 789 patients who suffered from in-clinic SCA were identified; 124 patients (16%) survived 30 days and 85 patients (11%) survived 180 days. Univariable predictors of survival included younger age (62.6 yrs vs 68.6 yrs, p = .0001), female gender (60% vs 53%, p = .02), longer dialysis vintage (4.7 vs 3.3 yrs, p Conclusions This study verifies the abysmal outcome of SCA in a large, nationally representative, and contemporary cohort of hemodialysis patients. This analysis also suggests novel risk associations of advanced age and use of catheter-based dialysis access with outcome. However, few traditional cardiovascular risk factors are associated with survival from SCA. Future studies should focus on prevention or modification of nontraditional risk factors to improve outcomes from SCA.
Ballistic Perforation of Double Reinforced Concrete as a Function of Energy

In an effort to better understand the energy required to breach double-reinforced concrete (DRC) walls it was attempted to estimate by numerical simulations the minimum kinetic energy required to perforate a DRC target. To this end, a parametric numerical study was conducted at the U. S. Army Research Laboratory. Large scale, high-fidelity, three-dimensional numerical simulations were conducted using an Eulerian shock physics code considering both eroding penetration and rigid body penetration. The parametric study investigated right cylindrical steel rods with masses of 500–2000 g and length-to-diameter ratios (L/D) of 1–10 impacting with velocities ranging from 500 to 1500 m/s, and perforating rebar reinforced concrete targets with a range of presented areas. This paper explores the numerical simulation results to consider the kinetic energy of perforation of DRC for the described range of conditions. Experimental results from the literature are compared with the numerical results. An empirical fit to the data is reported.