3,928 research outputs found
Complexity for Modules Over the Classical Lie Superalgebra gl(m|n)
Let be a
classical Lie superalgebra and be the category of finite
dimensional -supermodules which are completely reducible over the
reductive Lie algebra . In an earlier paper the authors
demonstrated that for any module in the rate of growth of the
minimal projective resolution (i.e., the complexity of ) is bounded by the
dimension of . In this paper we compute the complexity
of the simple modules and the Kac modules for the Lie superalgebra
. In both cases we show that the complexity is related to
the atypicality of the block containing the module.Comment: 32 page
The X-43A Six Degree of Freedom Monte Carlo Analysis
This report provides an overview of the Hyper-X research vehicle Monte Carlo analysis conducted with the six-degree-of-freedom simulation. The methodology and model uncertainties used for the Monte Carlo analysis are presented as permitted. In addition, the process used to select hardware validation test cases from the Monte Carlo data is described. The preflight Monte Carlo analysis indicated that the X-43A control system was robust to the preflight uncertainties and provided the Hyper-X project an important indication that the vehicle would likely be successful in accomplishing the mission objectives. The X-43A inflight performance is compared to the preflight Monte Carlo predictions and shown to exceed the Monte Carlo bounds in several instances. Possible modeling shortfalls are presented that may account for these discrepancies. The flight control laws and guidance algorithms were robust enough as a result of the preflight Monte Carlo analysis that the unexpected in-flight performance did not have undue consequences. Modeling and Monte Carlo analysis lessons learned are presented
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Antibiotic Stewardship Implementation and Antibiotic Use at Hospitals With and Without On-site Infectious Disease Specialists.
BackgroundMany US hospitals lack infectious disease (ID) specialists, which may hinder antibiotic stewardship efforts. We sought to compare patient-level antibiotic exposure at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist, defined as an ID physician and/or ID pharmacist.MethodsThis retrospective VHA cohort included all acute-care patient admissions during 2016. A mandatory survey was used to identify hospitals' antibiotic stewardship processes and their access to an on-site ID specialist. Antibiotic use was quantified as days of therapy per days present and categorized based on National Healthcare Safety Network definitions. A negative binomial regression model with risk adjustment was used to determine the association between presence of an on-site ID specialist and antibiotic use at the level of patient admissions.ResultsEighteen of 122 (14.8%) hospitals lacked an on-site ID specialist; there were 525 451 (95.8%) admissions at ID hospitals and 23 007 (4.2%) at non-ID sites. In the adjusted analysis, presence of an ID specialist was associated with lower total inpatient antibacterial use (odds ratio, 0.92; 95% confidence interval, .85-.99). Presence of an ID specialist was also associated with lower use of broad-spectrum antibacterials (0.61; .54-.70) and higher narrow-spectrum β-lactam use (1.43; 1.22-1.67). Total antibacterial exposure (inpatient plus postdischarge) was lower among patients at ID versus non-ID sites (0.92; .86-.99).ConclusionsPatients at hospitals with an ID specialist received antibiotics in a way more consistent with stewardship principles. The presence of an ID specialist may be important to effective antibiotic stewardship
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Antibiotic stewardship implementation and patient-level antibiotic use at hospitals with and without on-site Infectious Disease specialists.
Many US hospitals lack Infectious Disease (ID) specialists, which may hinder antibiotic stewardship efforts. We sought to compare patient-level antibiotic exposure at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist, defined as an ID physician and/or ID pharmacist. This retrospective VHA cohort included all acute-care patient-admissions during 2016. A mandatory survey was used to identify hospitals' antibiotic stewardship processes and their access to an on-site ID specialist. Antibiotic use was quantified as days of therapy (DOT) per days-present and categorized based on National Healthcare Safety Network definitions. A negative binomial regression model with risk adjustment was used to determine the association between presence of an on-site ID specialist and antibiotic use at the level of patient-admissions. Eighteen of 122 (14.8%) hospitals lacked an on-site ID specialist; there were 525,451 (95.8%) admissions at ID hospitals and 23,007 (4.2%) at non-ID sites. In the adjusted analysis, presence of an ID specialist was associated with lower total inpatient antibacterial use [OR 0.92, (95% CI, 0.85-0.99)]. Presence of an ID specialist was also associated with lower use of broad-spectrum antibacterials [OR 0.61 (95% CI, 0.54-0.70)] and higher narrow-spectrum beta-lactam use [OR 1.43 (95% CI, 1.22-1.67)]. Total antibacterial exposure (inpatient plus post-discharge) was lower among patients at ID versus non-ID sites [OR 0.92 (95% CI, 0.86-0.99)]. Patients at hospitals with an ID specialist received antibiotics in a way more consistent with stewardship principles. The presence of an ID specialist may be important to effective antibiotic stewardship
Sexed up: theorizing the sexualization of culture
This paper reviews and examines emerging academic approaches to the study of ‘sexualized culture’; an examination made necessary by contemporary preoccupations with sexual values, practices and identities, the emergence of new forms of sexual experience and the apparent breakdown of rules, categories and regulations designed to keep the obscene at bay. The paper maps out some key themes and preoccupations in recent academic writing on sex and sexuality, especially those relating to the contemporary or emerging characteristics of sexual discourse. The key issues of pornographication and democratization, taste formations, postmodern sex and intimacy, and sexual citizenship are explored in detail. </p
Laboratory Focus on Improving the Culture of Biosafety: Statewide Risk Assessment of Clinical Laboratories That Process Specimens for Microbiologic Analysis
The Wisconsin State Laboratory of Hygiene challenged Wisconsin laboratories to examine their biosafety practices and improve their culture of biosafety. One hundred three clinical and public health laboratories completed a questionnaire-based, microbiology-focused biosafety risk assessment. Greater than 96% of the respondents performed activities related to specimen processing, direct microscopic examination, and rapid nonmolecular testing, while approximately 60% performed culture interpretation. Although they are important to the assessment of risk, data specific to patient occupation, symptoms, and travel history were often unavailable to the laboratory and, therefore, less contributory to a microbiology-focused biosafety risk assessment than information on the specimen source and test requisition. Over 88% of the respondents complied with more than three-quarters of the mitigation control measures listed in the survey. Facility assessment revealed that subsets of laboratories that claim biosafety level 1, 2, or 3 status did not possess all of the biosafety elements considered minimally standard for their respective classifications. Many laboratories reported being able to quickly correct the minor deficiencies identified. Task assessment identified deficiencies that trended higher within the general (not microbiology-specific) laboratory for core activities, such as packaging and shipping, direct microscopic examination, and culture modalities solely involving screens for organism growth. For traditional microbiology departments, opportunities for improvement in the cultivation and management of highly infectious agents, such as acid-fast bacilli and systemic fungi, were revealed. These results derived from a survey of a large cohort of small- and large-scale laboratories suggest the necessity for continued microbiology-based understanding of biosafety practices, vigilance toward biosafety, and enforcement of biosafety practices throughout the laboratory setting
A Diverse Array of Cancer-Associated MTOR Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity
Genes encoding components of the PI3K–AKT–mTOR signaling axis are frequently mutated in cancer, but few mutations have been characterized in MTOR, the gene encoding the mTOR kinase. Using publicly available tumor genome sequencing data, we generated a comprehensive catalog of mTOR pathway mutations in cancer, identifying 33 MTOR mutations that confer pathway hyperactivation. The mutations cluster in six distinct regions in the C-terminal half of mTOR and occur in multiple cancer types, with one cluster particularly prominent in kidney cancer. The activating mutations do not affect mTOR complex assembly, but a subset reduces binding to the mTOR inhibitor DEPTOR. mTOR complex 1 (mTORC1) signaling in cells expressing various activating mutations remains sensitive to pharmacologic mTOR inhibition, but is partially resistant to nutrient deprivation. Finally, cancer cell lines with hyperactivating MTOR mutations display heightened sensitivity to rapamycin both in culture and in vivo xenografts, suggesting that such mutations confer mTOR pathway dependency.
Significance: We report that a diverse set of cancer-associated MTOR mutations confer increased mTORC1/2 pathway activity and that cells harboring these mutations are highly sensitive to rapamycin in culture and in vivo. These findings are clinically relevant as the MTOR mutations characterized herein may serve as biomarkers for predicting tumor responses to mTOR inhibitors.Starr Cancer ConsortiumDavid H. Koch Institute for Integrative Cancer Research at MITAlexander and Margaret Stewart TrustNational Institutes of Health (U.S.) (Grant CA103866)National Institutes of Health (U.S.) (Grant CA129105)National Institutes of Health (U.S.) (Grant AI07389
Predicting the redshift 2 Halpha luminosity function using [OIII] emission line galaxies
Upcoming space-based surveys such as Euclid and WFIRST-AFTA plan to measure
Baryonic Acoustic Oscillations (BAOs) in order to study dark energy. These
surveys will use IR slitless grism spectroscopy to measure redshifts of a large
number of galaxies over a significant redshift range. In this paper, we use the
WFC3 Infrared Spectroscopic Parallel Survey (WISP) to estimate the expected
number of Halpha (Ha) emitters observable by these future surveys. WISP is an
ongoing HST slitless spectroscopic survey, covering the 0.8-1.65micron
wavelength range and allowing the detection of Ha emitters up to z~1.5 and
[OIII] emitters to z~2.3. We derive the Ha-[OIII] bivariate line luminosity
function for WISP galaxies at z~1 using a maximum likelihood estimator that
properly accounts for uncertainties in line luminosity measurement, and
demonstrate how it can be used to derive the Ha luminosity function from
exclusively fitting [OIII] data. Using the z~2 [OIII] line luminosity function,
and assuming that the relation between Ha and [OIII] luminosity does not change
significantly over the redshift range, we predict the Ha number counts at z~2 -
the upper end of the redshift range of interest for the future surveys. For the
redshift range 0.7<z<2, we expect ~3000 galaxies/deg^2 for a flux limit of
3x10^{-16} ergs/s/cm^2 (the proposed depth of Euclid galaxy redshift survey)
and ~20,000 galaxies/deg^2 for a flux limit of ~10^{-16} ergs/s/cm^2 (the
baseline depth of WFIRST galaxy redshift survey).Comment: Minor revisions to match accepted ApJ versio
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Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques.
Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing costimulatory and cytokine-dependent Tfh help to B cells. However, the question remains as to whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced antienvelope (anti-Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein 10 (IP-10)-adjuvanted HIV-1 DNA prime followed by a monophosphoryl lipid A and QS-21 (MPLA+QS-21)-adjuvanted Env protein boost (DIP-10 PALFQ) in macaques, we observed higher anti-Env serum IgG titers with greater cross-clade reactivity, specificity for V1V2, and effector functions than in macaques primed with DNA lacking IP-10 and boosted with MPLA-plus-alum-adjuvanted Env protein (DPALFA) The DIP-10 PALFQ vaccine regimen elicited higher anti-Env IgG1 and lower IgG4 antibody levels in serum, showing for the first time that adjuvants can dramatically impact the IgG subclass profile in macaques. The DIP-10 PALFQ regimen also increased vaginal and rectal IgA antibodies to a greater extent. Within lymph nodes, we observed augmented GC B cell responses and the promotion of Th1 gene expression profiles in GC Tfh cells. The frequency of GC Tfh cells correlated with both the magnitude and avidity of anti-Env serum IgG. Together, these data suggest that adjuvant-induced stimulation of Th1-Tfh cells is an effective strategy for enhancing the magnitude and quality of anti-Env antibody responses.IMPORTANCE The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transiently. Poor antibody durability hampers efforts to develop an effective HIV-1 vaccine. This study was designed to identify the specific elements involved in the immunological mechanism necessary to produce robust HIV-1-specific antibodies in rhesus macaques. By clearly defining immune-mediated pathways that improve the magnitude and functionality of the anti-HIV-1 antibody response, we will have the foundation necessary for the rational development of an HIV-1 vaccine
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