Protection against Chlamydia Promoted by a Subunit Vaccine (CTH1) Compared with a Primary Intranasal Infection in a Mouse Genital Challenge Model

Background: The chlamydial proteins CT443 (OmcB) and CT521 (rl16) have previously been identified as human B and/or T cell targets during a chlamydial infection in humans. Here we compare the protective effector mechanism promoted by a fusion protein composed of CT521 and CT443 (CTH1) with a primary intranasal Chlamydia muridarum infection known to provide high levels of protection against a genital chlamydial challenge. Methodology/Principal Findings: The fusion protein CTH1, adjuvanted with a strong Th1 inducing cationic adjuvant (CAF01), significantly reduced the bacterial shedding compared to a control group in both a C. trachomatis Serovar D and C. muridarum challenge model. The CTH1/CAF01 vaccine was found to induce polyfunctional T cells consisting of TNFa/IL-2 and TNFa/IL-2/IFN-c positive cells and high titers of CTH1 specific IgG2a and IgG1. By depletion experiments the protection in the C. muridarum challenge model was demonstrated to be mediated solely by CD4 + T cells. In comparison, an intranasal infection with C. muridarum induced a T cell response that consisted predominantly of TNFa/IFN-c co-expressing effector CD4 + T cells and an antibody response consisting of C. muridarum specific IgG1, IgG2a but also IgA. This response was associated with a high level of protection against challenge—a protection that was only partially dependent on CD4 + T cells. Furthermore, whereas the antibody response induced by intranasal infection was strongly reactive against the native antigens displayed in the chlamydial elementary body, only low levels of antibodies against this preparation were foun

The effects of 52 weeks of soccer or resistance training on body composition and muscle function in +65-year-old healthy males:A randomized controlled trial

The effects of 52 weeks of soccer or resistance training were investigated in untrained elderly men. The subjects aged 68.1±2.1 yrs were randomised into a soccer (SG; n = 9), a resistance (RG; n = 9) and a control group (CG; n = 8). The subjects in SG and RG, respectively, trained 1.7±0.3 and 1.8±0.3 times weekly on average during the intervention period. Muscle function and body composition were determined before and after 16 and 52 weeks of the intervention period. In SG, BMI was reduced by 1.5% and 3.0% (p<0.05) after 16 and 52 weeks, respectively, unchanged in RG and 2% higher (p<0.05) in CG after 52 weeks of the intervention period. In SG, the response to a glucose tolerance test was 16% lower (p<0.05) after 16 wks, but not after 52 wks, compared to before the intervention period, and unchanged in RG and CG. In SG, superoxide dismutase-2 expression was 59% higher (p<0.05) after 52 wks compared to before the intervention period, and unchanged in RG and CG. In RG, upper body lean mass was 3 and 2% higher (p<0.05) after 16 and 52 wks, respectively, compared to before the intervention period, and unchanged in SG and CG. In RG, Akt-2 expression increased by 28% (p<0.01) and follistatin expression decreased by 38% (p<0.05) during the 52-wk intervention period, and was unchanged in SG and CG. Thus, long-term soccer training reduces BMI and improves anti-oxidative capacity, while long-term resistance training impacts muscle protein enzyme expression and increases lean body mass in elderly men. Trial Registration: ClinicalTrials.gov: NCT01530035

Lasting effects of workplace strength training for neck/shoulder/arm pain among laboratory technicians:Natural experiment with 3-year follow-up

Objectives. This study investigated long-term effects and implementation processes of workplace strength training for musculoskeletal disorders. Methods. 333 and 140 laboratory technicians from private and public sector companies, respectively, replied to a 3-year follow-up questionnaire subsequent to a 1-year randomized controlled trial (RCT) with high-intensity strength training for prevention and treatment of neck, shoulder, and arm pain. Being a natural experiment, the two participating companies implemented and modified the initial training program in different ways during the subsequent 2 years after the RCT. Results. At 3-year follow-up the pain reduction in neck, shoulder, elbow, and wrist achieved during the first year was largely maintained at both companies. However, the private sector company was rated significantly better than the public sector company in (1) training adherence, (2) training culture, that is, relatively more employees trained at the workplace and with colleagues, (3) self-reported health changes, and (4) prevention of neck and wrist pain development among initially pain-free employees. Conclusions. This natural experiment shows that strength training can be implemented successfully at different companies during working hours on a long-term basis with lasting effects on pain in neck, shoulder, and arm

Wireless Sensor Network for Advanced Energy Management Solutions

Eaton has developed an advanced energy management solution that has been deployed to several Industries of the Future (IoF) sites. This demonstrated energy savings and reduced unscheduled downtime through an improved means for performing predictive diagnostics and energy efficiency estimation. Eaton has developed a suite of online, continuous, and inferential algorithms that utilize motor current signature analysis (MCSA) and motor power signature analysis (MPSA) techniques to detect and predict the health condition and energy usage condition of motors and their connect loads. Eaton has also developed a hardware and software platform that provided a means to develop and test these advanced algorithms in the field. Results from lab validation and field trials have demonstrated that the developed advanced algorithms are able to detect motor and load inefficiency and performance degradation. Eaton investigated the performance of Wireless Sensor Networks (WSN) within various industrial facilities to understand concerns about topology and environmental conditions that have precluded broad adoption by the industry to date. A Wireless Link Assessment System (WLAS), was used to validate wireless performance under a variety of conditions. Results demonstrated that wireless networks can provide adequate performance in most facilities when properly specified and deployed. Customers from various IoF expressed interest in applying wireless more broadly for selected applications, but continue to prefer utilizing existing, wired field bus networks for most sensor based applications that will tie into their existing Computerized Motor Maintenance Systems (CMMS). As a result, wireless technology was de-emphasized within the project, and a greater focus placed on energy efficiency/predictive diagnostics. Commercially available wireless networks were only utilized in field test sites to facilitate collection of motor wellness information, and no wireless sensor network products were developed under this project. As an outgrowth of this program, Eaton developed a patented energy-optimizing drive control technology that is complementary to a traditional variable frequency drives (VFD) to enable significant energy savings for motors with variable torque applications, such as fans, pumps, and compressors. This technology provides an estimated energy saving of 2%-10% depending on the loading condition, in addition to the savings obtained from a traditional VFD. The combination of a VFD with the enhanced energy-optimizing controls will provide significant energy savings (10% to 70% depending on the load and duty cycle) for motors that are presently connected with across the line starters. It will also provide a more favorable return on investment (ROI), thus encouraging industries to adopt VFDs for more motors within their facilities. The patented technology is based on nonintrusive algorithms that estimate the instantaneous operating efficiency and motor speed and provide active energy-optimizing control of a motor, using only existing voltage and current sensors. This technology is currently being commercialized by Eaton’s Industrial Controls Division in their next generation motor control products. Due to the common nonintrusive and inferential nature of various algorithms, this same product can also include motor and equipment condition monitoring features, providing the facility owner additional information to improve process uptime and the associated energy savings. Calculations estimated potential energy savings of 261,397GWh/Yr ($15.7B/yr), through retrofitting energy-optimizing VFDs into existing facilities, and incorporating the solution into building equipment sold by original equipment manufacturers (OEMs) and installed by mechanical and electrical contractors. Utilizing MCSA and MPSA for predictive maintenance (PM) of motors and connected equipment reduces process downtime cost and the cost of wasted energy associated with shutting down and restarting the processes. Estimated savings vary depending on the industry segment and equipment criticality per facility/process. Average downtime for an industrial facility is 4-12 hours with a cost/hr of$7500/hr, with large, critical processes reaching $50-100k/hr. Specific downtime costs are not included in this report because of customer confidentiality, but projected savings across the Industries of the Future (IoF) are still expected to be comparable to the original program estimates. Two generations of customer field deployments and evaluation have been completed during the course of this project. Results from these customer sites have been used for identifying the scope and improving the developed energy and wellness algorithms. The field deployments have confirmed that the hardware for sensing and sampling motor currents and voltages are reliable and able to provide an adequate signal-to-noise ratio from the electrical noise present on the motor signals

Effects of 3 months of full-court and half-court street basketball training on health profile in untrained men

Purpose: The aim of the present study was to investigate whether street basketball organized as 3 v 3 on either a half court (HC) with 1 basket or a full court (FC) with 2 baskets could improve fitness and health profiles of untrained men after 3 months of supervised training. Methods: Thirty-five untrained men (aged 20–42 years) completed the pre- and post-intervention testing (FC: n = 13, HC: n = 12, CO (control): n = 10). The training attendance was 2.0 ± 0.4 and 1.9 ± 0.3 times per week in FC and HC, respectively. Mean heart rate (HR) was 83.8 ± 6.0 percent of maximal heart rate (%HRmax) and 84.5 ± 2.9 %HRmax in FC and HC, respectively. Results: The 3 months of street basketball training on an FC with 2 baskets increased maximal oxygen uptake (2.4 mL/min/kg (95% confidence interval (CI): 1.0–3.9)), time to exhaustion (47 s (95%CI: 26–67)), lean body mass (0.8 kg (95%CI: 0.1–1.5)), and bone mineral density (0.021 g/cm2 (95%CI: 0.011–0.031)), whereas mean arterial pressure (–5.6 mmHg (95%CI: –7.5 to 3.7)), body fat percentage (–1.6%, (95%CI: –2.5 to –0.7)), heart rate (–18 bpm (95%CI: –24 to –12)), and blood lactate (median: –1.4 mmol/L (interquartile range: –1.5 to –0.6)) during submaximal running were lowered. The changes were less pronounced after the training period when playing on an HC with 1 basket, but increases in maximal oxygen uptake (1.6 mL/min/kg (95%CI: –0.1 to 3.3)), time to exhaustion (28 s (95%CI: 9–47)), lean body mass (1.3 kg (95%CI: 0.3–2.4)), and lower body fat percentage (–0.9% (95%CI: –1.9 to –0.1)) were observed in this group. Conclusion: Three months of 3 v 3 street basketball training improved fitness and led to broad-spectrum improvements in variables related to overall health profile, with the most marked effects observed when playing on an FC with 2 baskets. Keywords: Blood pressure, Body composition, Cardiovascular fitness, Maximal oxygen uptake, Muscoloskeletal fitness, Physical demands, Small-sided games, Team spor

Distinct patterns of blood-stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections

International audienceBACKGROUND: In endemic regions naturally acquired immunity against Plasmodium falciparum develops as a function of age and exposure to parasite infections and is known to be mediated by IgG. The targets of protective antibodies remain to be fully defined. Several immunoepidemiological studies have indicated an association of cytophilic anti-parasite IgG with protection against malaria. It has been hypothesized that the initial antibody responses against parasite antigens upon first few Plasmodium falciparum infections is dominated by non-protective IgG2/IgG4 and IgM antibodies, which then gradually develop into protective response dominated by cytophilic IgG1 and IgG3 antibodies. METHODS: Naturally occurring IgG antibodies against P. falciparum blood-stage antigens were analysed from plasma samples collected from four groups of individuals differing in age and level of exposure to P. falciparum infections. Western Blot profiling of blood-stage parasite antigens displaying reactivity with individual plasma samples in terms of their subclass specificities was conducted. Parasite antigens detected by IgG were grouped based on their apparent molecular sizes resolved by SDS-PAGE as high molecular weight (≥ 70 kDa) or low molecular weight (< 70 kDa). The number of discernable low molecular weight parasite antigens detected by different IgG subclass antibodies from each plasma sample was recorded. Using Wilcoxons rank sum test these reactivities were compared amongst groups of individuals with different levels of exposure to P. falciparum infections. RESULTS: IgG4 and IgM antibodies in plasma samples from all groups detected very few parasite antigens. IgG2 antibodies from all groups detected a common pattern of high molecular weight parasite antigens. Cytophilic IgG subclasses in plasma samples from individuals with higher levels of exposure to P. falciparum infections distinctly detected higher numbers of low molecular weight parasite antigens. CONCLUSIONS: In the present study, there was no evidence for switching of antibody responses from non-cytophilic to cytophilic subclasses against blood-stage parasite antigens as a likely mechanism for induction of protective immunity against malaria

A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children.

BACKGROUND: GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. METHODS: Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. RESULTS: A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). CONCLUSIONS: GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role

Enhancing Biomolecule Analysis and 2DMS Experiments by Implementation of (Activated Ion) 193 nm UVPD on a FT-ICR Mass Spectrometer

Ultraviolet photodissociation is a fast, photon-mediated fragmentation method that yields high sequence coverage and informative cleavages of biomolecules. In this work, 193 nm UVPD was coupled with a 12 Tesla FT-ICR mass spectrometer and 10.6 μm infrared multi-photon dissociation to provide gentle slow-heating of UV-irradiated ions. No internal instrument hardware modifications were required. Adjusting the timing of laser pulses to the ion motion within the ICR cell provided consistent fragmentation yield shot-to-shot and may also be used to monitor ion positions within the ICR cell. Single-pulse UVPD of the native-like 5+ charge state of ubiquitin resulted in 86.6% cleavage coverage. Additionally, IR activation post UVPD doubled the overall fragmentation yield and boosted the intensity of UVPD-specific x-type fragments up to 4-fold. This increased yield effect was also observed for the 6+ charge state of ubiquitin, albeit less pronounced. This indicates that gentle slow-heating serves to sever tethered fragments originating from non-covalently linked compact structures and makes activation post UVPD an attractive option to boost fragmentation efficiency for top-down studies. Lastly, UVPD was implemented and optimized as a fragmentation method for 2DMS, a data-independent acquisition method. UVPD-2DMS was demonstrated to be a viable method using BSA digest peptides as a model system