123 research outputs found

    Blast Shock Wave Mitigation Using the Hydraulic Energy Redirection and Release Technology

    Get PDF
    A hydraulic energy redirection and release technology has been developed for mitigating the effects of blast shock waves on protected objects. The technology employs a liquid-filled plastic tubing as a blast overpressure transformer to transfer kinetic energy of blast shock waves into hydraulic energy in the plastic tubings. The hydraulic energy is redirected through the plastic tubings to the openings at the lower ends, and then is quickly released with the liquid flowing out through the openings. The samples of the specifically designed body armor in which the liquid-filled plastic tubings were installed vertically as the outer layer of the body armor were tested. The blast test results demonstrated that blast overpressure behind the body armor samples was remarkably reduced by 97% in 0.2 msec after the liquid flowed out of its appropriate volume through the openings. The results also suggested that a volumetric liquid surge might be created when kinetic energy of blast shock wave was transferred into hydraulic energy to cause a rapid physical movement or displacement of the liquid. The volumetric liquid surge has a strong destructive power, and can cause a noncontact, remote injury in humans (such as blast-induced traumatic brain injury and post-traumatic stress disorder) if it is created in cardiovascular system. The hydraulic energy redirection and release technology can successfully mitigate blast shock waves from the outer surface of the body armor. It should be further explored as an innovative approach to effectively protect against blast threats to civilian and military personnel

    Decrease of miR-146b-5p in Monocytes during Obesity Is Associated with Loss of the Anti-Inflammatory but Not Insulin Signaling Action of Adiponectin

    Get PDF
    Background: Low adiponectin, a well-recognized antidiabetic adipokine, has been associated with obesity-related inflammation, oxidative stress and insulin resistance. Globular adiponectin is an important regulator of the interleukin-1 receptor-associated kinase (IRAK)/NFkB pathway in monocytes of obese subjects. It protects against inflammation and oxidative stress by inducing IRAK3. microRNA (miR)-146b-5p inhibits NFkB-mediated inflammation by targeted repression of IRAK1 and TNF receptor-associated factor-6 (TRAF6). Therefore, we measured the expression of miR-146b-5p in monocytes of obese subjects. Because it was low we determined the involvement of this miR in the anti-inflammatory, antioxidative and insulin signaling action of globular adiponectin. Methods: miR-146b-5p expression in monocytes of obese subjects was determined by qRT-PCR. The effect of miR-146b-5p silencing on molecular markers of inflammation, oxidative stress and insulin signaling and the association with globular adiponectin was assessed in human THP-1 monocytes. Results: miR-146b-5p was downregulated in monocytes of obese persons. Low globular adiponectin decreased miR-146b-5p and IRAK3 in THP-1 monocytes, associated with increased mitochondrial reactive oxygen species (ROS). Intracellular ROS and insulin receptor substrate-1 (IRS1) protein were unchanged. Silencing of miR-146b-5p with an antisense inhibitor resulted in increased expression of IRAK1 and TRAF6 leading to more NFkB p65 DNA binding activity and TNFa. As

    Catalytic and Non-Catalytic Roles for the Mono-ADP-Ribosyltransferase Arr in the Mycobacterial DNA Damage Response

    Get PDF
    Recent evidence indicates that the mycobacterial response to DNA double strand breaks (DSBs) differs substantially from previously characterized bacteria. These differences include the use of three DSB repair pathways (HR, NHEJ, SSA), and the CarD pathway, which integrates DNA damage with transcription. Here we identify a role for the mono-ADP-ribosyltransferase Arr in the mycobacterial DNA damage response. Arr is transcriptionally induced following DNA damage and cellular stress. Although Arr is not required for induction of a core set of DNA repair genes, Arr is necessary for suppression of a set of ribosomal protein genes and rRNA during DNA damage, placing Arr in a similar pathway as CarD. Surprisingly, the catalytic activity of Arr is not required for this function, as catalytically inactive Arr was still able to suppress ribosomal protein and rRNA expression during DNA damage. In contrast, Arr substrate binding and catalytic activities were required for regulation of a small subset of other DNA damage responsive genes, indicating that Arr has both catalytic and noncatalytic roles in the DNA damage response. Our findings establish an endogenous cellular function for a mono-ADP-ribosyltransferase apart from its role in mediating Rifampin resistance

    A Transcript Cleavage Factor of Mycobacterium tuberculosis Important for Its Survival

    Get PDF
    After initiation of transcription, a number of proteins participate during elongation and termination modifying the properties of the RNA polymerase (RNAP). Gre factors are one such group conserved across bacteria. They regulate transcription by projecting their N-terminal coiled-coil domain into the active center of RNAP through the secondary channel and stimulating hydrolysis of the newly synthesized RNA in backtracked elongation complexes. Rv1080c is a putative gre factor (MtbGre) in the genome of Mycobacterium tuberculosis. The protein enhanced the efficiency of promoter clearance by lowering abortive transcription and also rescued arrested and paused elongation complexes on the GC rich mycobacterial template. Although MtbGre is similar in domain organization and shares key residues for catalysis and RNAP interaction with the Gre factors of Escherichia coli, it could not complement an E. coli gre deficient strain. Moreover, MtbGre failed to rescue E. coli RNAP stalled elongation complexes, indicating the importance of specific protein-protein interactions for transcript cleavage. Decrease in the level of MtbGre reduced the bacterial survival by several fold indicating its essential role in mycobacteria. Another Gre homolog, Rv3788 was not functional in transcript cleavage activity indicating that a single Gre is sufficient for efficient transcription of the M. tuberculosis genome

    Small Molecule Control of Virulence Gene Expression in Francisella tularensis

    Get PDF
    In Francisella tularensis, the SspA protein family members MglA and SspA form a complex that associates with RNA polymerase (RNAP) to positively control the expression of virulence genes critical for the intramacrophage growth and survival of the organism. Although the association of the MglA-SspA complex with RNAP is evidently central to its role in controlling gene expression, the molecular details of how MglA and SspA exert their effects are not known. Here we show that in the live vaccine strain of F. tularensis (LVS), the MglA-SspA complex works in concert with a putative DNA-binding protein we have called PigR, together with the alarmone guanosine tetraphosphate (ppGpp), to regulate the expression of target genes. In particular, we present evidence that MglA, SspA, PigR and ppGpp regulate expression of the same set of genes, and show that mglA, sspA, pigR and ppGpp null mutants exhibit similar intramacrophage growth defects and are strongly attenuated for virulence in mice. We show further that PigR interacts directly with the MglA-SspA complex, suggesting that the central role of the MglA and SspA proteins in the control of virulence gene expression is to serve as a target for a transcription activator. Finally, we present evidence that ppGpp exerts its effects by promoting the interaction between PigR and the RNAP-associated MglA-SspA complex. Through its responsiveness to ppGpp, the contact between PigR and the MglA-SspA complex allows the integration of nutritional cues into the regulatory network governing virulence gene expression

    The First Stars

    Get PDF
    The first stars to form in the Universe -- the so-called Population III stars -- bring an end to the cosmological Dark Ages, and exert an important influence on the formation of subsequent generations of stars and on the assembly of the first galaxies. Developing an understanding of how and when the first Population III stars formed and what their properties were is an important goal of modern astrophysical research. In this review, I discuss our current understanding of the physical processes involved in the formation of Population III stars. I show how we can identify the mass scale of the first dark matter halos to host Population III star formation, and discuss how gas undergoes gravitational collapse within these halos, eventually reaching protostellar densities. I highlight some of the most important physical processes occurring during this collapse, and indicate the areas where our current understanding remains incomplete. Finally, I discuss in some detail the behaviour of the gas after the formation of the first Population III protostar. I discuss both the conventional picture, where the gas does not undergo further fragmentation and the final stellar mass is set by the interplay between protostellar accretion and protostellar feedback, and also the recently advanced picture in which the gas does fragment and where dynamical interactions between fragments have an important influence on the final distribution of stellar masses.Comment: 72 pages, 4 figures. Book chapter to appear in "The First Galaxies - Theoretical Predictions and Observational Clues", 2012 by Springer, eds. V. Bromm, B. Mobasher, T. Wiklin

    A comprehensive overview of radioguided surgery using gamma detection probe technology

    Get PDF
    The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

    Did smokefree legislation in England reduce exposure to secondhand smoke among nonsmoking adults? Cotinine analysis from the Health Survey for England.

    Get PDF
    Background: On 1 July 2007, smokefree legislation was implemented in England, which made virtually all enclosed public places and workplaces smokefree. Objectives: We examined trends in and predictors of secondhand smoke exposure among nonsmoking adults to determine whether exposure changed after the introduction of smokefree legislation and whether these changes varied by socioeconomic status (SES) and by household smoking status. Methods: We analyzed salivary cotinine data from the Health Survey for England that were collected in 7 of 11 annual surveys undertaken between 1998 and 2008. We conducted multivariate regression analyses to examine secondhand smoke exposure as measured by the proportion of nonsmokers with undetectable levels of cotinine and by geometric mean cotinine. Results: Secondhand smoke exposure was higher among those exposed at home and among lower-SES groups. Exposure declined markedly from 1998 to 2008 (the proportion of participants with undetectable cotinine was 2.9 times higher in the last 6 months of 2008 compared with the first 6 months of 1998 and geometric mean cotinine declined by 80%). We observed a significant fall in exposure after legislation was introduced—the odds of having undetectable cotinine were 1.5 times higher [95% confidence interval (CI): 1.3, 1.8] and geometric mean cotinine fell by 27% (95% CI: 17%, 36%) after adjusting for the prelegislative trend and potential confounders. Significant reductions were not, however, seen in those living in lower-social class households or homes where smoking occurs inside on most days. Conclusions: We found that the impact of England’s smokefree legislation on secondhand smoke exposure was above and beyond the underlying long-term decline in secondhand smoke exposure and demonstrates the positive effect of the legislation. Nevertheless, some population subgroups appear not to have benefitted significantly from the legislation. This finding suggests that these groups should receive more support to reduce their exposure

    Match-Play and Performance Test Responses of Soccer Goalkeepers: A Review of Current Literature.

    Get PDF
    Goalkeepers are typically the last defensive line for soccer teams aiming to minimise goals being conceded, with match rules permitting ball handling within a specific area. Goalkeepers are also involved in initiating some offensive plays, and typically remain in close proximity to the goal line while covering ~ 50% of the match distances of outfield players; hence, the competitive and training demands of goalkeepers are unique to their specialised position. Indeed, isolated performance tests differentiate goalkeepers from outfield players in multiple variables. With a view to informing future research, this review summarised currently available literature reporting goalkeeper responses to: (1) match play (movement and skilled/technical demands) and (2) isolated performance assessments (strength, power, speed, aerobic capacity, joint range of motion). Literature searching and screening processes yielded 26 eligible records and highlighted that goalkeepers covered ~ 4-6 km on match day whilst spending ~ 98% of time at low-movement intensities. The most decisive moments are the 2-10 saves·match-1 performed, which often involve explosive actions (e.g. dives, jumps). Whilst no between-half performance decrements have been observed in professional goalkeepers, possible transient changes over shorter match epochs remain unclear. Isolated performance tests confirm divergent profiles between goalkeepers and outfield players (i.e. superior jump performance, reduced [Formula: see text]2max values, slower sprint times), and the training of soccer goalkeepers is typically completed separately from outfield positions with a focus primarily on technical or explosive drills performed within confined spaces. Additional work is needed to examine the physiological responses to goalkeeper-specific training and match activities to determine the efficacy of current preparatory strategies
    corecore