Miracle-dz/UniFAR-FTUs huggingface dataset:
The genetic structure of admixed populations.

A method for simultaneously estimating the admixture proportions of a hybrid population and Wright's fixation index, FST, for that hybrid is presented. It is shown that the variance of admixture estimates can be partitioned into two components: (1) due to sample size, and (2) due to evolutionary variance (i.e., genetic drift). A chi-square test used to detect heterogeneity of admixture estimates from different alleles, or loci, can now be corrected for both sources of random errors. Hence, its value for the detection of natural selection from heterogeneous admixture estimates is improved. The estimation and testing procedures described above are independent of the dynamics of the admixture process. However, when the admixture dynamics can be specified, FST can be predicted from genetic principles. Two admixture models are considered here, gene flow and intermixture. These models are of value because they lead to very different predictions regarding the accumulation of genes from the parental populations and the accumulation of variance due to genetic drift. When there is not evidence for natural selection, and it is appropriate to apply these models to data, the variance effective size (Ne) of the hybrid population can be estimated. Applications are made to three human populations: two of these are Afro-American populations and one is a Yanomamö Indian village. Natural selection could not be detected using the chi-square test in any of these populations. However, estimates of effective population sizes do lead to a richer description of the genetic structure of these populations.
Eradication of Staphylococcus aureus Catheter-Related Biofilm Infections Using ML:8 and Citrox

ABSTRACT Staphylococci are a leading cause of catheter-related infections (CRIs) due to biofilm formation. CRIs are typically managed by either device removal or systemic antibiotics, often in combination with catheter lock solutions (CLSs). CLSs provide high concentrations of the antimicrobial agent at the site of infection. However, the most effective CLSs against staphylococcal biofilm-associated infections have yet to be determined. The purpose of this study was to evaluate the efficacy and suitability of two newly described antimicrobial agents, ML:8 and Citrox, as CLSs against Staphylococcus aureus biofilms. ML:8 (1% [vol/vol]) and Citrox (1% [vol/vol]), containing caprylic acid and flavonoids, respectively, were used to treat S. aureus biofilms grown in vitro using newly described static and flow biofilm assays. Both agents reduced biofilm viability >97% after 24 h of treatment. Using a rat model of CRI, ML:8 was shown to inactivate early-stage S. aureus biofilms in vivo, while Citrox inactivated established, mature in vivo biofilms. Cytotoxicity and hemolytic activity of ML:8 and Citrox were equivalent to those of other commercially available CLSs. Neither ML:8 nor Citrox induced a cytokine response in human whole blood, and exposure of S. aureus to either agent for 90 days was not associated with any increase in resistance. Taken together, these data reveal the therapeutic potential of these agents for the treatment of S. aureus catheter-related biofilm infections.
Faster Algorithms for Multivariate Interpolation With Multiplicities and Simultaneous Polynomial Approximations

The interpolation step in the Guruswami-Sudan algorithm is a bivariate interpolation problem with multiplicities commonly solved in the literature using either structured linear algebra or basis reduction of polynomial lattices. This problem has been extended to three or more variables; for this generalization, all fast algorithms proposed so far rely on the lattice approach. In this paper, we reduce this multivariate interpolation problem to a problem of simultaneous polynomial approximations, which we solve using fast structured linear algebra. This improves the best known complexity bounds for the interpolation step of the list-decoding of Reed-Solomon codes, Parvaresh-Vardy codes, and folded Reed-Solomon codes. In particular, for Reed-Solomon list-decoding with re-encoding, our approach has complexity O~(ℓω-1m2(n - k)), where ℓ, m, n, and k are the list size, the multiplicity, the number of sample points, and the dimension of the code, and ω is the exponent of linear algebra; this accelerates the previously fastest known algorithm by a factor of ℓ/m.
Study examining attitudes of staff, patients and relatives to witnessed resuscitation in adult intensive care units.

BACKGROUND Witnessed resuscitation is widely accepted in paediatric practice and is becoming more common in adult emergency departments, but information on this topic is sparse. METHODS We gave a questionnaire to 50 intensive care medical and nursing staff and 55 patients and next of kin before elective postoperative admission to the intensive care unit to examine staff opinion about witnessed resuscitation, patient and relatives' demand for witnessed resuscitation, and their perception of the benefits. RESULTS We found that 56% of doctors and 66% of nurses favoured giving relatives the option to stay. If relatives requested to be present, 70% of doctors and 82% of nurses would allow this if the relatives were escorted. The role of the escort was felt to explain, prevent interference, and to provide emotional support. We found that 29% of patients and 47% of relatives wanted to be together during resuscitation, the commonest reasons being to provide support and to see that everything was done. We found that 95% of patients and 91% of relatives felt their views should be formally sought before ICU admission. CONCLUSIONS Intensive care staff support witnessed resuscitation. Many intensive care personnel have experienced witnessed resuscitation and the majority felt that relatives gained benefit. Almost all agree that the views of both patient and relatives should be sought formally before admission to intensive care.
Anti-ganglioside antibodies induced in chickens by an alum-adsorbed anti-idiotype antibody targeting NeuGcGM3

Racotumomab is a murine anti-idiotype cancer vaccine targeting NeuGcGM3 on melanoma, breast, and lung cancer. In order to characterize the immunogenicity of alum-adsorbed racotumomab in a non-clinical setting, Leghorn chickens were immunized in dose levels ranging from 25 μg to 1600 μg. Racotumomab was administered subcutaneously in the birds' neck with three identical boosters and serum samples were collected before, during and after the immunization schedule. A strong antibody response was obtained across the evaluated dose range, confirming the immunogenicity of racotumomab even at dose levels as low as 25 μg. As previously observed when using Freund's adjuvant, alum-adsorbed racotumomab induced an idiotype-specific response in all the immunized birds and ganglioside-specific antibodies in 60–100% of the animals. In contrast to the rapid induction anti-idiotype response, detection of ganglioside-specific antibodies in responsive animals may require repeated boosting. Kinetics of anti-NeuGcGM3 antibody titers showed a slight decline 2 weeks after each booster, arguing in favor of repeated immunizations in order to maintain antibody titer. Interestingly, the intensity of the anti-NeuGcGM3 response paralleled that of anti-mucin antibodies and anti-tumor antibodies, suggesting that the in vitro detection of anti-ganglioside antibodies might be a surrogate for an in vivo activity of racotumomab. Taken together, these results suggest that Leghorn chicken immunization might become the means to test the biological activity of racotumomab intended for clinical use.
Biological Effect Monitoring in Peripheral Blood Lymphocytes from Subjects Occupationally Exposed to Antineoplastic Drugs: Assessment of Micronuclei Frequency

Biological Effect Monitoring in Peripheral Blood Lymphocytes from Subjects Occupationally Exposed to Antineoplastic Drugs: Assessment of Micronuclei Frequency: Milena VILLARINI, et al. Department of Medical‐Surgical Specialties and Public Health (Section of Public Health), University of Perugia, Italy—
Prognostic Value of Serum Albumin Changes Over Time in Elderly Adults Undergoing Hemodialysis

The French–Swiss cohort Association R egionale des N ephrologues OSt eodystrophie (ARNOS) included information on 2,179 individuals undergoing hemodialysis followed at 6-month intervals from July 2005 to January 2009. The present analysis excluded individuals younger than 75, those with type 1 diabetes mellitus, and those with missing values. SAlb was standardized according to dialysis center. SAlb variations were modeled using individual linear regression models according to time. Body mass index (BMI) and BMI percentage change per year are associated with survival in elderly adults undergoing hemodialysis. These two covariates were therefore used in the models to assess the effect of SAlb on survival independent of BMI. The survival analysis used frailty Cox models with random effects on categories of age and dialysis vintage, a special case of stratified Cox model more adapted to strata of small sample sizes, and included the covariates baseline SAlb, SAlb rate of change, sex, diabetes mellitus, baseline BMI, BMI percentage change, cardiac insufficiency, interdialytic weight gain, and C-reactive protein (CRP).
CCG-1423: a small-molecule inhibitor of RhoA transcriptional signaling

Lysophosphatidic acid receptors stimulate a Gα12/13/RhoA-dependent gene transcription program involving the serum response factor (SRF) and its coactivator and oncogene, megakaryoblastic leukemia 1 (MKL1). Inhibitors of this pathway could serve as useful biological probes and potential cancer therapeutic agents. Through a transcription-based high-throughput serum response element-luciferase screening assay, we identified two small-molecule inhibitors of this pathway. Mechanistic studies on the more potent CCG-1423 show that it acts downstream of Rho because it blocks SRE.L-driven transcription stimulated by Gα12Q231L, Gα13Q226L, RhoA-G14V, and RhoC-G14V. The ability of CCG-1423 to block transcription activated by MKL1, but not that induced by SRF-VP16 or GAL4-VP16, suggests a mechanism targeting MKL/SRF-dependent transcriptional activation that does not involve alterations in DNA binding. Consistent with its role as a Rho/SRF pathway inhibitor, CCG-1423 displays activity in several in vitro cancer cell functional assays. CCG-1423 potently (<1 μmol/L) inhibits lysophosphatidic acid–induced DNA synthesis in PC-3 prostate cancer cells, and whereas it inhibits the growth of RhoC-overexpressing melanoma lines (A375M2 and SK-Mel-147) at nanomolar concentrations, it is less active on related lines (A375 and SK-Mel-28) that express lower levels of Rho. Similarly, CCG-1423 selectively stimulates apoptosis of the metastasis-prone, RhoC-overexpressing melanoma cell line (A375M2) compared with the parental cell line (A375). CCG-1423 inhibited Rho-dependent invasion by PC-3 prostate cancer cells, whereas it did not affect the Gαi-dependent invasion by the SKOV-3 ovarian cancer cell line. Thus, based on its profile, CCG-1423 is a promising lead compound for the development of novel pharmacologic tools to disrupt transcriptional responses of the Rho pathway in cancer. [Mol Cancer Ther 2007;6(8):2249–60]
Loop fusion and temporal common subexpression elimination in window-based loops

This paper describes a system for compiling codes written in a conventional high-level language to recon gurable FPGA-based hardware. SA-C is a singleassignment language, and its compiler performs a variety of optimizations, some conventional and some specialized, before generating data ow graphs. The data ow graphs are then compiled to VHDL. Three novel compiler optimizations are described here, all based on loops with windowing behavior. Loop fusion with windows requires a unique approach to producer-consumer fusion. Temporal Common Subexpression Elimination identi es expressions that recompute values that were computed in previous iterations, and replaces them with registers. Window narrowing reduces window sizes after other optimizations have been applied. Finally, the performance e ects of these optimizations on a four-loop sequence
FAULT-TOLERANT ARCHITECTURES FOR SPACE AND AVIONICS APPLICATIONS

Over the past half century, computing systems have experienced over three orders of magnitude improvement in average time to failure and over seven orders of magnitude improvement in work accomplished between outages. This paper surveys, compares and contrasts the architectural techniques used to improve system reliability in space and avionics applications. The generic techniques are instantiated by actual system examples taken from the space and avionics domains. The paper concludes by observing trends and projecting future developments.
Enhanced high‐altitude polar cap plasma and magnetic field values in response to the interplanetary magnetic cloud that caused the great storm of 31 March 2001: A case study for a new magnetospheric index

[1] The magnetospheric electron number density and the magnetic field strength near 8 R E over the polar cap increased dramatically after the arrival of an interplanetary magnetic cloud on 31 March 2001. These parameters were determined with high accuracy from the plasma resonances stimulated by the Radio Plasma Imager (RPI) on Imager for Magnetopause-to-Aurora Global Exploration (IMAGE) near apogee during both quiet (30 March 2001) and disturbed (31 March 2001) days. The quiet day and disturbed day values were each compared with magnetospheric magnetic field and electron density models; good agreement was found with the former but not the latter. The magnetospheric response was also expressed in terms of the ratio of the electron plasma frequency f pe to the electron cyclotron frequency f ce , which is proportional to the ratio of the electron gyroradius to the Debye radius. Simultaneous Wind measurements of the solar wind magnetic field strength, speed, and plasma density were used to calculate the solar wind quasi-invariant QI. This index is equivalent to the ratio of the solar wind magnetic pressure to the solar wind ram pressure or to the inverse of the magnetic Mach number squared. These nondimensional quantities, QI and f pe /f ce , have fundamental meanings in the solar wind MHD regime and in the relation between electric and magnetic forces on electrons in the magnetosphere, respectively. During the large 31 March 2001 storm, IMAGE was at the right place at the right time so as to enable comparisons between RPI f pe /f ce and Wind QI determinations. Both QI and f pe /f ce formed maxima during 6-hour observing intervals during this storm that were found to be highly correlated (87%) with a magnetospheric time lag of about 3 hours for f pe /f ce . These results, based on a detailed case study of this important event, suggest that the plasma parameter f pe /f ce may serve as a useful magnetospheric index.
Hierarchical Module Classification in Mixed-initiative Conversational Agent System

Our operational context is a task-oriented dialog system where no single module satisfactorily addresses the range of conversational queries from humans. Such systems must be equipped with a range of technologies to address semantic, factual, task-oriented, open domain conversations using rule-based, semantic-web, traditional machine learning and deep learning. This raises two key challenges. First, the modules need to be managed and selected appropriately. Second, the complexity of troubleshooting on such systems is high. We address these challenges with a mixed-initiative model that controls conversational logic through hierarchical classification. We also developed an interface to increase interpretability for operators and to aggregate module performance.
Mercury in Active‐Layer Tundra Soils of Alaska: Concentrations, Pools, Origins, and Spatial Distribution

Tundra soils serve as major sources of mercury (Hg) input to the Arctic Ocean via river runoff and coastal erosion; yet little information is available on tundra soil Hg concentrations, pool sizes, origins, and dynamics. We present a detailed investigation of Hg in the active layer (upper ~100 cm subject to seasonal thaw) of tundra soils across 11 sites in Alaska. Soil Hg concentrations in organic horizons (151 ± 7 μg/kg) were in the upper range of temperate soil organic horizons, and concentrations in mineral horizons (98 ± 6 μg/kg) were much higher than in temperate soils. Soil Hg concentrations declined from inland to coastal sites, in contrast to a hypothesized northward increase expected because of proximity to coastal atmospheric mercury depletion events. Principle component analyses and elemental ratios results show that exogenic sources dominated over geogenic sources—in A‐horizons (66 ± 4%) and mineral B‐horizons (51 ± 1%). 14C age‐dating suggested recent origins of Hg in surface soils but showed that mineral soils (more than 7,300 years old) must have accumulated atmospheric inputs across millennia leading to high soil concentrations and pools. We estimated a total Northern Hemisphere active‐layer tundra soil Hg pool of 184 Gg (range of 136 to 274 Gg), suggesting a globally important Hg storage pool. Tundra soils are subject to seasonal thaw and freeze dynamics, thereby providing large inputs to rivers, lakes, and the Arctic Ocean. Understanding processes that mobilize Hg from tundra soils will be critical to understanding future Arctic wildlife and human Hg exposures.
Observational Constraints on Past Attributable Warming and Predictions of Future Global Warming

This paper investigates the impact of aerosol forcing uncertainty on the robustness of estimates of the twentieth-century warming attributable to anthropogenic greenhouse gas emissions. Attribution analyses on three coupled climate models with very different sensitivities and aerosol forcing are carried out. The Third Hadley Centre Coupled Ocean–Atmosphere GCM (HadCM3), Parallel Climate Model (PCM), and GFDL R30 models all provide good simulations of twentieth-century global mean temperature changes when they include both anthropogenic and natural forcings. Such good agreement could result from a fortuitous cancellation of errors, for example, by balancing too much (or too little) greenhouse warming by too much (or too little) aerosol cooling. Despite a very large uncertainty for estimates of the possible range of sulfate aerosol forcing obtained from measurement campaigns, results show that the spatial and temporal nature of observed twentiethcentury temperature change constrains the component of past warming attributable to anthropogenic greenhouse gases to be significantly greater (at the 5% level) than the observed warming over the twentieth century. The cooling effects of aerosols are detected in all three models. Both spatial and temporal aspects of observed temperature change are responsible for constraining the relative roles of greenhouse warming and sulfate cooling over the twentieth century. This is because there are distinctive temporal structures in differential warming rates between the hemispheres, between land and ocean, and between mid- and low latitudes. As a result, consistent estimates of warming attributable to greenhouse gas emissions are obtained from all three models, and predictions are relatively robust to the use of more or less sensitive models. The transient climate response follo wing a1 % yr 1 increase in CO2 is estimated to lie between 2.2 and 4 K century 1 (5–95 percentiles).
The spectrum of WRN mutations in Werner syndrome patients

The International Registry of Werner syndrome (www.wernersyndrome.org) has been providing molecular diagnosis of the Werner syndrome (WS) for the past decade. The present communication summarizes, from among 99 WS subjects, the spectrum of 50 distinct mutations discovered by our group and by others since the WRN gene (also called RECQL2 or REQ3) was first cloned in 1996; 25 of these have not previously been published. All WRN mutations reported thus far have resulted in the elimination of the nuclear localization signal at the C‐terminus of the protein, precluding functional interactions in the nucleus; thus, all could be classified as null mutations. We now report two new mutations in the N‐terminus that result in instability of the WRN protein. Clinical data confirm that the most penetrant phenotype is bilateral ocular cataracts. Other cardinal signs were seen in more than 95% of the cases. The median age of death, previously reported to be in the range of 46–48 years, is 54 years. Lymphoblastoid cell lines (LCLs) have been cryopreserved from the majority of our index cases, including material from nuclear pedigrees. These, as well as inducible and complemented hTERT (catalytic subunit of human telomerase) immortalized skin fibroblast cell lines are available to qualified investigators. Hum Mutat 27(6), 558–567, 2006. Published 2006 Wiley‐Liss, Inc.
The bystander effect and social control behavior: the effect of the presence of others on people's reactions to norm violations

Observers of deviant social behavior sometimes communicate disapproval directly or indirectly to the perpetrator of a deviant act. This reaction has been termed ‘social control’. Three field studies were conducted to explore the influence of the number of bystander-observers on the likelihood of social control. We predicted that the presence of others would inhibit people’s tendency to communicate their disapproval to the deviant but only if personal implication was low. In the first study, we measured participants’ perceptions of two fictive situations, one in which a deviant draws graffiti in an elevator of a shopping center and one in which a deviant litters in a small neighborhood park by throwing a plastic bottle in the bushes. As expected, participants considered both behaviors to be equally counternormative but felt personally more implicated by the littering behavior in the park. In Studies 2 and 3, the two situations were enacted with confederates of the experimenter. Nao¨ve bystanders served as participants, and social control was the primary dependent variable. Consistent with our hypothesis, we found evidence for a bystander effect in the low personal implication situation (‘graffiti in the elevator’) but not in the high personal implication situation (‘littering in park’). These results make clear that perceived personal implication moderates the extent to which people are inhibited by the presence of others when they decide whether they should exert social control or not. Copyright # 2002 John Wiley & Sons, Ltd. It is generally agreed that social norms are powerful determinants of human behavior (Asch, 1951; Cialdini, Kallgren, & Reno, 1991; Newcomb, 1961; Schachter & Singer, 1962; Schwartz, 1977; Sherif, 1936; Sherif, Harvey, White, Hood, & Sherif, 1961). Social norms are specific to particular groups, as each group creates its own standards for what attitudes or behaviors are acceptable and desirable. What is considered normative in one group may be seen as being a counternormative (deviant) behavior in another group. For example, in France it is considered polite to fill up a guest’s wine glass when it is still half full. A host who lets his or her guests empty their wine glasses is considered inattentive. In Germany, on the other hand, it is expected that hosts pour more wine only when the guest’s wine glass is empty. Filling up a wine glass that is still half full would be considered