6,825 research outputs found
Seismic responses of civil structures under magnetorheological-device direct control
This paper presents an efficient control strategy for magnetorheological (MR) dampers embedded in building structures to mitigate quake-induced vibrations. In this work, MR dampers are used as semi-active devices, taking the advantages of the fail-safe operation and low power requirement. By using a static hysteresis model for the MR damper, a suitable controller is proposed here for direct control of the supply currents of the MR dampers using feedback linearization. The dampers are configured in a differential mode to counteract the force-offset problem from the use of a single damper. The effectiveness of the proposed technique is verified in simulation by using a ten-storey building model subject to quake-like excitations
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The HIV Genomic Incidence Assay Meets False Recency Rate and Mean Duration of Recency Infection Performance Standards.
HIV incidence is a primary metric for epidemic surveillance and prevention efficacy assessment. HIV incidence assay performance is evaluated via false recency rate (FRR) and mean duration of recent infection (MDRI). We conducted a meta-analysis of 438 incident and 305 chronic specimens' HIV envelope genes from a diverse global cohort. The genome similarity index (GSI) accurately characterized infection stage across diverse host and viral factors. All except one chronic specimen had GSIs below 0.67, yielding a FRR of 0.33 [0-0.98] %. We modeled the incidence assay biomarker dynamics with a logistic link function assuming individual variabilities in a Beta distribution. The GSI probability density function peaked close to 1 in early infection and 0 around two years post infection, yielding MDRI of 420 [361, 467] days. We tested the assay by newly sequencing 744 envelope genes from 59 specimens of 21 subjects who followed from HIV negative status. Both standardized residuals and Anderson-Darling tests showed that the test dataset was statistically consistent with the model biomarker dynamics. This is the first reported incidence assay meeting the optimal FRR and MDRI performance standards. Signatures of HIV gene diversification can allow precise cross-sectional surveillance with a desirable temporal range of incidence detection
Daily HIV pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine reduced Streptococcus and increased Erysipelotrichaceae in rectal microbiota.
Daily PrEP is highly effective at preventing HIV-1 acquisition, but risks of long-term tenofovir disoproxil fumarate plus emtricitabine (TDF-FTC) include renal decline and bone mineral density decrease in addition to initial gastrointestinal side effects. We investigated the impact of TDF-FTC on the enteric microbiome using rectal swabs collected from healthy MSM before PrEP initiation and after 48 to 72 weeks of adherent PrEP use. The V4 region of the 16S ribosomal RNA gene sequencing showed that Streptococcus was significantly reduced from 12.0% to 1.2% (p = 0.036) and Erysipelotrichaceae family was significantly increased from 0.79% to 3.3% (p = 0.028) after 48-72 weeks of daily PrEP. Catenibacterium mitsuokai, Holdemanella biformis and Turicibacter sanguinis were increased within the Erysipelotrichaceae family and Streptococcus agalactiae, Streptococcus oralis, Streptococcus mitis were reduced. These changes were not associated with host factors including PrEP duration, age, race, tenofovir diphosphate blood level, any drug use and drug abuse, suggesting that the observed microbiome shifts were likely induced by daily PrEP use. Long-term PrEP resulted in increases of Catenibacterium mitsuokai and Holdemanella biformis, which have been associated with gut microbiome dysbiosis. Our observations can aid in characterizing PrEP's side effects, which is likely to improve PrEP adherence, and thus HIV-1 prevention
Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Circuit computation requires precision in the timing, extent, and synchrony of principal cell (PC) firing that is largely enforced by parvalbumin-expressing, fast-spiking interneurons (PVFSIs). To reliably coordinate network activity, PVFSIs exhibit specialized synaptic and membrane properties that promote efficient afferent recruitment such as expression of high-conductance, rapidly gating, GluA4-containing AMPA receptors (AMPARs). We found that PVFSIs upregulate GluA4 during the second postnatal week coincident with increases in the AMPAR clustering proteins NPTX2 and NPTXR. Moreover, GluA4 is dramatically reduced in NPTX2(-/-)/NPTXR(-/-) mice with consequent reductions in PVFSI AMPAR function. Early postnatal NPTX2(-/-)/NPTXR(-/-) mice exhibit delayed circuit maturation with a prolonged critical period permissive for giant depolarizing potentials. Juvenile NPTX2(-/-)/NPTXR(-/-) mice display reduced feedforward inhibition yielding a circuit deficient in rhythmogenesis and prone to epileptiform discharges. Our findings demonstrate an essential role for NPTXs in controlling network dynamics highlighting potential therapeutic targets for disorders with inhibition/excitation imbalances such as schizophrenia.Work supported by a PRAT fellowship to M.S.W., an NICHD intramural award to C.J.M., NIDCD intramural
research program funding to R.S.P., an NIMH intramural award to H.A.C., NIH grants (PAR-02-059, NS 039156)
to P.F.W., and an NIH grant (EY022730) to M.T.
Alternative metrics for characterizing longer-term clinical outcomes in difficult-to-treat depression: II. Sensitivity to treatment effects
Chlamydia and Vaginitis in Sexually Active Females: Classical Identification Methods for Effective Control
Laboratory diagnosis of Chlamydia and vaginitis in sexually active females has been limited by unavailability of a sequential method/rapid technique for simple diagnosis. Six hundred (600) adult females from hotel/brothel, Sexually Transmitted Infections (STIs) Clinic, Obstetrics/Gynaecology Clinic, Family Planning Clinic and Healthy controls were investigated for Chlamydia, Candida, trichomoniasis and bacterial vaginosis (BV). This was done using microscopy: wet mount, stained vaginal secretion and stained smear after culture. Results showed that there were 72% infections in the female groups. The brothel and STI group had infection in the range (70-86%). Chlamydial infection was highest in the STI group while Candida infection was highest in the healthy (control) females. Bacterial vaginosis was distributed in all groups. As p-value increased, f-value increased indicating constant co-infection of Candida and BV in Chlamydia positive females. Microscopy by direct detection from sample and stained smear after culture were in the range: 56-86%. Direct microscopy for BV was 78.5% and stained smear after culture, 57.1%. Sensitivity and specificity of the techniques showed that detection of Chlamydia was less sensitive by direct microscopy of sample but sensitivity and specificity of stained smear after culture were high. Immunoassay (32.2%) was also less sensitive. Sensitivity and specificity of wet mount microscopy for Candida, Trichomoniasis and BV were in the range 62.5 – 80% and 62.5-97.8% respectively. Wet mount has high sensitivity and specificity for detecting agents of vaginitis and may be useful for routine use and for diagnosis where disease is absent, thus, making identification more cost effective
The biosocial event : responding to innovation in the life sciences
Innovation in the life sciences calls for reflection on how sociologies separate and relate life processes and social processes. To this end we introduce the concept of the ‘biosocial event’. Some life processes and social processes have more mutual relevance than others. Some of these relationships are more negotiable than others. We show that levels of relevance and negotiability are not static but can change within existing relationships. Such changes, or biosocial events, lie at the heart of much unplanned biosocial novelty and much deliberate innovation. We illustrate and explore the concept through two examples – meningitis infection and epidemic, and the use of sonic ‘teen deterrents’ in urban settings. We then consider its value in developing sociological practice oriented to critically constructive engagement with innovation in the life sciences
Risk-Driven Design Processes: Balancing Efficiency with Resilience in Product Design
Current design methods and approaches focus on increasing the efficiency of the product design system by, for example, eliminating waste and focusing on value creation. However, continuing failures in the development of complex, large scale products and systems point towards weaknesses in the existing approaches. We argue that product development organizations are hindered by the many uncertainties that are inherent in the process. Common management heuristics ignore uncertainty and thus overly simplify the decision making process. Creating transparency regarding uncertainties and the associated risks (i.e. effect of uncertainties on design objectives) is not seen as an explicit priority. Consequently organizations are unable to balance risk and return in their development choices. Product development processes do not emphasize reduction of risks, particularly those risks that are apparent early in the process. In addition, the resilience of the PD system, i.e. its ability to deliver on-target results under uncertainty, is not deliberately designed to match the level of residual uncertainty. This chapter introduces the notion of Risk-Driven Design and its four principles of 1. Creating transparency regarding design risks; 2. Risk-driven decision making; 3. Minimizing uncertainty; and 4. Creating resilience.Massachusetts Institute of Technology. Lean Advancement InitiativeCenter for Clean Water and Clean Energy at MIT and KFUP
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