Shear buckling of square perforated plates

The behavior of thin square perforated plates under the action of uniform shear deformation is studied experimentally and analytically using finite element analysis. Elastic Shear buckling strength is established as a function of the diameter of a round, centrally located hole in the plate. Post buckling behavior and the behavior of perforated plates with various ring stiffeners are also studied experimentally

Partner notification for sexually transmitted infections in developing countries: a systematic review

<p>Abstract</p> <p>Background</p> <p>The feasibility and acceptability of partner notification (PN) for sexually transmitted infections (STIs) in developing countries was assessed through a comprehensive literature review, to help identify future intervention needs.</p> <p>Methods</p> <p>The Medline, Embase, and Google Scholar databases were searched to identify studies published between January 1995 and December 2007 on STI PN in developing countries. A systematic review of the research extracted information on: (1) willingness of index patients to notify partners; (2) the proportion of partners notified or referred; (3) client-reported barriers in notifying partners; (4) infrastructure barriers in notifying partners; and (5) PN approaches that were evaluated in developing countries.</p> <p>Results</p> <p>Out of 609 screened articles, 39 met our criteria. PN outcome varied widely and was implemented more often for spousal partners than for casual or commercial partners. Reported barriers included sociocultural factors such as stigma, fear of abuse for having an STI, and infrastructural factors related to the limited number of STD clinics, and trained providers and reliable diagnostic methods. Client-oriented counselling was found to be effective in improving partner referral outcomes.</p> <p>Conclusions</p> <p>STD clinics can improve PN with client-oriented counselling, which should help clients to overcome perceived barriers. The authors speculate that well-designed PN interventions to evaluate the impact on STI prevalence and incidence along with cost-effectiveness components will motivate policy makers in developing countries to allocate more resources towards STI management.</p

Pharmacological inhibition of PARP6 triggers multipolar spindle formation and demonstrates therapeutic effects in breast cancer

PARP proteins represent a class of post-translational modification enzymes with diverse cellular functions. Targeting PARPs has proven to be efficacious clinically, but exploration of the therapeutic potential of PARP inhibition has been limited to targeting poly(ADP-ribose) generating PARP, including PARP1/2/3 and tankyrases. The cancer-related functions of mono(ADP-ribose) generating PARP, including PARP6, remain largely uncharacterized. Here, we report a novel therapeutic strategy targeting PARP6 using the first reported PARP6 inhibitors. By screening a collection of PARP compounds for their ability to induce mitotic defects, we uncovered a robust correlation between PARP6 inhibition and induction of multipolar spindle (MPS) formation, which was phenocopied by PARP6 knockdown. Treatment with AZ0108, a PARP6 inhibitor with a favorable pharmacokinetic profile, potently induced the MPS phenotype, leading to apoptosis in a subset of breast cancer cells in vitro and antitumor effects in vivo. In addition, Chk1 was identified as a specific substrate of PARP6 and was further confirmed by enzymatic assays and by mass spectrometry. Furthermore, when modification of Chk1 was inhibited with AZ0108 in breast cancer cells, we observed marked upregulation of p-S345 Chk1 accompanied by defects in mitotic signaling. Together, these results establish proof-of-concept antitumor efficacy through PARP6 inhibition and highlight a novel function of PARP6 in maintaining centrosome integrity via direct ADP-ribosylation of Chk1 and modulation of its activity

Associations between sexual behaviour change in young people and decline in HIV prevalence in Zambia

<p>Abstract</p> <p>Background</p> <p>Evidence suggests that HIV prevalence amongst young Zambians has declined recently, especially in higher-education groups. We studied trends in key sexual behaviour indicators among 15–24 year-olds from 1995 to 2003, including the associations between sexual behaviour change and education.</p> <p>Methods</p> <p>The data stem from a series of three population-based surveys conducted in 1995 (n = 1720), 1999 (n = 1946) and 2003 (n = 2637). Logistic regression and Extended Mantel Haenszel Chi Square for linear trends were used to compare the three surveys.</p> <p>Results</p> <p>Men and lower-education groups reported more than one sexual partner in the year immediately prior to the survey more frequently than did women and higher-education groups (p < 0.01), but these proportions declined regardless of sex and residence. Substantial delays in child-bearing were observed, particularly among higher-education and urban respondents. Condom use at least for casual sexual intercourse increased from 1995 to 2003; the level was highest among urban and higher-education groups. The number of women reporting frequent dry sex using traditional agents fell during the period. Participants from the rural area and those with less education reported more sexual experience than urban and higher-education participants in 2003. The reported number of sexual partners during the year immediately prior to the survey was a factor that reduced the association between HIV and survey times among sexually active young urban men and women.</p> <p>Conclusion</p> <p>High risk behaviours clearly decreased, especially in higher-educated and urban groups, and there is a probable association here with the decline in HIV prevalence in the study population. Fewer sexual partners and condom use were among the core factors involved for both sexes; and for women a further factor was delayed child-bearing.</p