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The uptake of laser powder bed fusion for polymers has remained limited mainly because the interaction between material properties and process parameters is not well understood. The constraints of experimentally determining the optimal process parameters for new polymers in laser powder bed fusion include high expense, time-consumption, errors, and considerable effort. Hence, the need for using analytical and numerical models as alternatives. This paper starts with a summary on laser powder bed fusion of polymers, reviews the aspects of the process requiring the use of analytical and numerical tools, limitations, and possible improvements of the existing studies on the analytical models, and finally briefly explores approaches for numerical modelling of laser powder bed fusion of polymers. Some of the key aspects of the process that have been identified as being amenable to modelling include powder spreading and deposition of the layers, interaction between the laser beam and powder particles, melting and fusion of the particles, powder bed surface temperature, heat transfer through the powder, cooling phase, and the properties of printed parts. It is suggested in the study that the existing analytical and/or numerical models can be improved by increasing relevant variables (process parameters and material characteristics) used in them.

Cassia abbreviata is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots of C. abbreviata , and showed that six bioactive compounds inhibit HIV-1 infection. In the present study, we demonstrate that the six compounds block HIV-1 entry into cells: oleanolic acid, palmitic acid, taxifolin, piceatannol, guibourtinidol-(4α→8)-epiafzelechin, and a novel compound named as cassiabrevone. We report, for the first time, that guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC 50 of 42.47 µM and 30.96 µM, respectively), as well as that piceatannol interacts with cellular membranes. Piceatannol inhibits HIV-1 infection in a dual-chamber assay mimicking the female genital tract, as well as HSV infection, emphasizing its potential as a microbicide. Structure-activity relationships (SAR) showed that pharmacophoric groups of piceatannol are strictly required to inhibit HIV-1 entry. By a ligand-based in silico study, we speculated that piceatannol and norartocarpetin may have a very similar mechanism of action and efficacy because of the highly comparable pharmacophoric and 3D space, while guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone may display a different mechanism. We finally show that cassiabrevone plays a major role of the crude extract of CA by blocking the binding activity of HIV-1 gp120 and CD4.

Three new ( 1 - 3 ) and 25 known compounds were isolated from the crude extract of Cassia abbreviata . The chemical structures of new compounds were established by extensive spectroscopic analyses including 1D and 2D NMR and HRESIMS. Cassiabrevone ( 1 ) is the first heterodimer of guibourtinidol and planchol A. Compound 2 was a new chalcane, while 3 was a new naphthalene. Cassiabrevone ( 1 ), guibourtinidol-(4α→8)-epiafzelechin ( 4 ), taxifolin ( 8 ), oleanolic acid ( 17 ), piceatannol ( 22 ), and palmitic acid ( 28 ), exhibited potent anti-HIV-1 activity with IC 50 values of 11.89 µM, 15.39 µM, 49.04 µM, 7.95 µM, 3.58 µM, and 15.97 µM, respectively.

Design: The study's design was a cluster-randomized, matched-pairs, parallel trial of a behavior-based sexual assault prevention intervention in the informal settlements., Methods: The participants were primary school girls aged 10-16. Classroom-based interventions for girls and boys were delivered by instructors from the same settlements, at the same time, over six 2-h sessions. The girls' program had components of empowerment, gender relations, and self-defense. The boys' program promotes healthy gender norms. The control arm of the study received a health and hygiene curriculum. The primary outcome was the rate of sexual assault in the prior 12 months at the cluster level (school level). Secondary outcomes included the generalized self-efficacy scale, the distribution of number of times victims were sexually assaulted in the prior period, skills used, disclosure rates, and distribution of perpetrators. Difference-in-differences estimates are reported with bootstrapped confidence intervals., Results: Fourteen schools with 3147 girls from the intervention group and 14 schools with 2539 girls from the control group were included in the analysis. We estimate a 3.7 % decrease, p = 0.03 and 95 % CI = (0.4, 8.0), in risk of sexual assault in the intervention group due to the intervention (initially 7.3 % at baseline). We estimate an increase in mean generalized self-efficacy score of 0.19 (baseline average 3.1, on a 1-4 scale), p = 0.0004 and 95 % CI = (0.08, 0.39)., Interpretation: This innovative intervention that combined parallel training for young adolescent girls and boys in school settings showed significant reduction in the rate of sexual assault among girls in this population.

This study investigated the effects of a gender-based violence (GBV) educational curriculum on improving male attitudes toward women and increasing the likelihood of intervention if witnessing GBV, among adolescent boys in Nairobi, Kenya. In total, 1,543 adolescents participated in this comparison intervention study: 1,250 boys received six 2-hr sessions of the "Your Moment of Truth" (YMOT) intervention, and 293 boys comprised the standard of care (SOC) group. Data on attitudes toward women were collected anonymously at baseline and 9 months after intervention. At follow-up, boys were also asked whether they encountered situations involving GBV and whether they successfully intervened. Compared with baseline, YMOT participants had significantly higher positive attitudes toward women at follow-up, whereas scores for SOC participants declined. At follow-up, the percentage of boys who witnessed GBV was similar for the two groups, except for physical threats, where the intervention group reported witnessing more episodes. The percentage of boys in the intervention group who successfully intervened when witnessing violence was 78% for verbal harassment, 75% for physical threat, and 74% for physical or sexual assault. The percentage of boys in the SOC group who successfully intervened was 38% for verbal harassment, 33% for physical threat, and 26% for physical or sexual assault. Results from the logistic regression demonstrate that more positive attitudes toward women predicted whether boys in the intervention group would intervene successfully when witnessing violence. This standardized 6-week GBV training program is highly effective in improving attitudes toward women and increasing the likelihood of successful intervention when witnessing GBV.

The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared the replication of recombinant virus pairs carrying the full Env (Env viruses) or the Env ectodomain fused to the gp41CT of NL4.3 (EnvEC viruses) (12 subtype C and 10 subtype B pairs) in primary CD4+ T-cells and monocyte-derived-macrophages (MDMs). In CD4+ T-cells, replication was as follows: B-EnvEC = B-Env>C-EnvEC>C-Env, indicating that the gp41CT of subtype C contributes to the low replicative capacity of this subtype. In MDMs, in contrast, replication capacity was comparable for all viruses regardless of subtype and of gp41CT. In CD4+ T-cells, viral entry, viral release and viral gene expression were similar. However, infectivity of free virions and cell-to-cell transmission of C-Env viruses released by CD4+ T-cells was lower, suggestive of lower Env incorporation into virions. Subtype C matrix only minimally rescued viral replication and failed to restore infectivity of free viruses and cell-to-cell transmission. Taken together, these results show that polymorphisms in the gp41CT contribute to viral replication capacity and suggest that the number of Env spikes per virion may vary across subtypes. These findings should be taken into consideration in the design of vaccines., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: Sexual assault is a major cause of injury, unplanned pregnancy, HIV infection, and mental health problems worldwide. In parts of sub-Saharan Africa, sexual assault has reached epidemic proportions. This study evaluated the efficacy of an empowerment and self-defense intervention for adolescent girls to decrease the incidence of sexual assault and harassment in Nairobi's large informal settlements., Methods: A prospective cohort of 1978 adolescents from 4 neighborhoods near Nairobi were taught empowerment, deescalation, and self-defense skills in six 2-hour sessions. The standard-of-care (SOC) group (n = 428) received a life skills class. Self-reported, anonymous survey data were collected at baseline and 10.5 months after intervention., Results: Annual sexual assault rates decreased from 17.9/100 person-years at baseline to 11.1 at follow-up (rate ratio = 1.61; 95% confidence interval [CI], 1.26-1.86; P < .001); there was no significant change in the SOC group (14.3 to 14.0, rate ratio = 1.02; 95% CI, 0.67-1.57, P = .92). Sexual assault disclosure in the intervention group increased from 56% to 75% (P = .006), compared with a constant incidence of disclosure (53%) in the SOC group. The majority (52.3%) of adolescents in the intervention group reported using skills learned to stop an assault., Conclusions: This intervention decreased sexual assault rates among adolescent girls in Kenya. The intervention was also associated with an increase in the disclosure of assaults, thereby enabling survivors to seek care and support and possibly leading to the identification and prosecution of perpetrators. This model should be adaptable to other settings both in Africa and globally., (Copyright © 2014 by the American Academy of Pediatrics.)

Purpose: To determine the effect of a standardized 6-week self-defense program on the incidence of sexual assault in adolescent high school girls in an urban slum in Nairobi, Kenya., Methods: Population-based survey of 522 high school girls in the Korogocho-Kariobangi locations in Nairobi, Kenya, at baseline and 10 months later. Subjects were assigned by school attended to either a "No Means No Worldwide" self-defense course (eight schools; N = 402) or to a life-skills class (two schools; N = 120). Both the intervention and the life-skills classes were taught in the schools by trained instructors. Participants were administered the same survey at baseline and follow-up., Results: A total of 522 girls (mean age, 16.7 ± 1.5 years; range, 14-21 years) completed surveys at baseline, and 489 at 10-month follow-up. At baseline, 24.5% reported sexual assault in the prior year, with the majority (90%) reporting assault by someone known to them (boyfriend, 52%; relative, 17%; neighbor, 15%; teacher or pastor, 6%). In the self-defense intervention group, the incidence of sexual assault decreased from 24.6% at baseline to 9.2% at follow-up (p < .001), in contrast to the control group, in which the incidence remained unchanged (24.2% at baseline and 23.1% at follow-up; p = .10). Over half the girls in the intervention group reported having used the self-defense skills to avert sexual assault in the year after the training. Rates of disclosure increased in the intervention group, but not in controls., Conclusions: A standardized 6-week self-defense program is effective in reducing the incidence of sexual assault in slum-dwelling high school girls in Nairobi, Kenya., (Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Lentiviruses have unusually long envelope (Env) cytoplasmic tails, longer than those of other retroviruses. Whereas the Env ectodomain has received much attention, the gp41 cytoplasmic tail (gp41-CT) is one of the least studied parts of the virus. It displays relatively high conservation compared to the rest of Env. It has been long established that the gp41-CT interacts with the Gag precursor protein to ensure Env incorporation into the virion. The gp41-CT contains distinct motifs and domains that mediate both intensive Env intracellular trafficking and interactions with numerous cellular and viral proteins, optimizing viral infectivity. Although they are not fully understood, a multiplicity of interactions between the gp41-CT and cellular factors have been described over the last decade; these interactions illustrate how Env expression and incorporation into virions is a finely tuned process that has evolved to best exploit the host system with minimized genetic information. This review addresses the structure and topology of the gp41-CT of lentiviruses (mainly HIV and SIV), their domains and believed functions. It also considers the cellular and viral proteins that have been described to interact with the gp41-CT, with a particular focus on subtype-related polymorphisms.

Background: Human Immunodeficiency virus type-1 (HIV) entry into target cells involves binding of the viral envelope (Env) to CD4 and a coreceptor, mainly CCR5 or CXCR4. The only currently licensed HIV entry inhibitor, maraviroc, targets CCR5, and the presence of CXCX4-using strains must be excluded prior to treatment. Co-receptor usage can be assessed by phenotypic assays or through genotypic prediction. Here we compared the performance of a phenotypic Env-Recombinant Viral Assay (RVA) to the two most widely used genotypic prediction algorithms, Geno2Pheno[coreceptor] and webPSSM., Methods: Co-receptor tropism of samples from 73 subtype B and 219 non-B infections was measured phenotypically using a luciferase-tagged, NL4-3-based, RVA targeting Env. In parallel, tropism was inferred genotypically from the corresponding V3-loop sequences using Geno2Pheno[coreceptor] (5-20% FPR) and webPSSM-R5X4. For discordant samples, phenotypic outcome was retested using co-receptor antagonists or the validated Trofile® Enhanced-Sensitivity-Tropism-Assay., Results: The lower detection limit of the RVA was 2.5% and 5% for X4 and R5 minority variants respectively. A phenotype/genotype result was obtained for 210 samples. Overall, concordance of phenotypic results with Geno2Pheno[coreceptor] was 85.2% and concordance with webPSSM was 79.5%. For subtype B, concordance with Geno2pheno[coreceptor] was 94.4% and concordance with webPSSM was 79.6%. High concordance of genotypic tools with phenotypic outcome was seen for subtype C (90% for both tools). Main discordances involved CRF01&#95;AE and CRF02&#95;AG for both algorithms (CRF01&#95;AE: 35.9% discordances with Geno2Pheno[coreceptor] and 28.2% with webPSSM; CRF02&#95;AG: 20.7% for both algorithms). Genotypic prediction overestimated CXCR4-usage for both CRFs. For webPSSM, 40% discordance was observed for subtype A., Conclusions: Phenotypic assays remain the most accurate for most non-B subtypes and new subtype-specific rules should be developed for non-B subtypes, as research studies more and more draw conclusions from genotypically-inferred tropism, and to avoid unnecessarily precluding patients with limited treatment options from receiving maraviroc or other entry inhibitors.

F18(+)Escherichia coli infections causing post-weaning diarrhoea and/or oedema disease are a major cause of economic losses in pig industry. To date, no preventive strategy can protect pigs from F18(+)E. coli infections. One of the most attractive approaches to eliminate F18(+)E. coli infections is the selection for pigs that are resistant to F18(+)E. coli infections. However, this strategy was not believed to be favourable because of reports of genetic association with the stress-susceptibility gene in the Swiss Landrace. To investigate this potential association more thoroughly, 131 randomly selected Belgian hybrid pigs were genotyped for both the F18(+)E. coli resistance alleles (FUT1(A)) and the stress-susceptibility alleles (RYR1(T)) and their association was investigated by determining the linkage disequilibrium. This linkage disequilibrium (LD=-0.0149) is close to zero and does not differ significantly from 0 (likelihood ratio test chi(1)(2)=1.123, P=0.29), demonstrating no association between the FUT1(A) and RYR1(T) alleles. Furthermore, only a small fraction (4.6%) of the Belgian pigs was found to be resistant to F18(+)E. coli infections. Our results suggest that selection for F18(+)E. coli resistant pigs might be an attractive approach to prevent pigs from F18(+)E. coli infections, unlike to what has previously been postulated.