The Bossler coupling

Mechanical characteristics of flexible drive shaft couplin

Application of Face-Gear Drives in Helicopter Transmissions

The use of face gears in helicopter transmissions was explored. A light-weight, split torque transmission design utilizing face gears was described. Face-gear design and geometry were investigated. Topics included tooth generation, limiting inner and outer radii, tooth contact analysis, contact ratio, gear eccentricity, and structural stiffness. Design charts were developed to determine minimum and maximum face-gear inner and outer radii. Analytical study of transmission error showed face-gear drives were relatively insensitive to gear misalignment, but tooth contact was affected by misalignment. A method of localizing bearing contact to compensate for misalignment was explored. The proper choice of shaft support stiffness enabled good load sharing in the split torque transmission design. Face-gear experimental studies were also included and the feasibility of face gears in high-speed, high-load applications such as helicopter transmissions was demonstrated

Investigation of the Afterglow Mode with the Caprice ECRIS for the GSI Heavy-Ion-Synchrotron operation

The Caprice-type ECRIS of the High Charge State Injector (HLI) of GSI predominantly has been operated in DC mode so far to deliver high duty cycle beams for the experimental area of the LINAC (UNILAC). The increasing demand of the Heavy Ion Synchrotron (SIS) for high intensities of heavy ion beams at very low duty cycle favours the application of the afterglow mode by pulsed operation of the ECRIS in these cases. Experiments with O, Ar, Xe and mainly with Pb were performed at the new ECR injector setup (EIS) which is a copy of the HLI injection beam line. Different RF pulse lengths and repetition rates were compared to optimise the respective afterglow intensities. For Pb two different types of ovens were investigated and modifications of the extraction system were applied. Thus peak intensities in the afterglow for 208Pb27+ of up to 200 emA could be obtained. Stable operation for time periods of several days could be achieved at reduced intensity level. Operational experiences are reported under the aspect of adaptation to SIS injection

Face-gear drives: Design, analysis, and testing for helicopter transmission applications

The use of face-gears in helicopter transmissions was explored. A light-weight, split-torque transmission design utilizing face-gears is described. Face-gear design and geometry were investigated. Topics included tooth generation, limiting inner and outer radii, tooth contact analysis, contact ratio, gear eccentricity, grinding, and structural stiffness. Design charts were developed to determine minimum and maximum face-gear inner and outer radii. An analytical study showed that the face-gear drive is relatively insensitive to gear misalignment with respect to transmission errors, but the tooth contact is affected by misalignment. A method of localizing the bearing contact to permit operation with misalignment was explored. Two new methods for grinding of the face-gear tooth surfaces were also investigated. The proper choice of shaft stiffness enabled good load sharing in the split-torque transmission design. Face-gear experimental studies were also conducted. These tests demonstrated the feasibility of face-gears in high-speed, high-load applications such as helicopter transmissions

Examining Perceptions of Online Harassment among Constables in England and Wales

The ubiquity of the Internet and computer technology has enabled individuals to engage in bullying, threats, and harassing communications online. Limited research has found that local line officers may not view these offenses as serious compared to real world crimes despite their negative physical and emotional impact on victims. The perceptions of officers can produce poor interactions with victims during calls for service, particularly victim blaming, which can reduce citizens’ confidence in police agencies generally. However, local law enforcement agencies are increasingly mandated to respond to these cases, calling to question how their views may impact the community. This study examined the attitudinal and demographic factors associated with the negative views of online harassment and bullying within a sample of 1,348 constables from 34 local agencies across England and Wales. The study found that constables with negative views toward cybercrimes and worked in agencies with inconsistent messaging related to online crimes were more likely to view online harassment as less serious and believe that these offenses could be avoided by victims. The implications of this study for local police staff and command are discussed in detail

Repression of human papillomavirus oncogene expression under hypoxia is mediated by PI3K/mTORC2/AKT signaling

Oncogenic HPV types are major human carcinogens. Under hypoxia, HPV-positive cancer cells can repress the viral E6/E7 oncogenes and induce a reversible growth arrest. This response could contribute to therapy resistance, immune evasion, and tumor recurrence upon reoxygenation. Here, we uncover evidence that HPV oncogene repression is mediated by hypoxia-induced activation of canonical PI3K/mTORC2/AKT signaling. AKT-dependent downregulation of E6/E7 is only observed under hypoxia and occurs, at least in part, at the transcriptional level. Quantitative proteome analyses identify additional factors as candidates to be involved in AKT-dependent E6/E7 repression and/or hypoxic PI3K/mTORC2/AKT activation. These results connect PI3K/mTORC2/AKT signaling with HPV oncogene regulation, providing new mechanistic insights into the cross talk between oncogenic HPVs and their host cells.Hypoxia is linked to therapeutic resistance and poor clinical prognosis for many tumor entities, including human papillomavirus (HPV)-positive cancers. Notably, HPV-positive cancer cells can induce a dormant state under hypoxia, characterized by a reversible growth arrest and strong repression of viral E6/E7 oncogene expression, which could contribute to therapy resistance, immune evasion and tumor recurrence. The present work aimed to gain mechanistic insights into the pathway(s) underlying HPV oncogene repression under hypoxia. We show that E6/E7 downregulation is mediated by hypoxia-induced stimulation of AKT signaling. Ablating AKT function in hypoxic HPV-positive cancer cells by using chemical inhibitors efficiently counteracts E6/E7 repression. Isoform-specific activation or downregulation of AKT1 and AKT2 reveals that both AKT isoforms contribute to hypoxic E6/E7 repression and act in a functionally redundant manner. Hypoxic AKT activation and consecutive E6/E7 repression is dependent on the activities of the canonical upstream AKT regulators phosphoinositide 3-kinase (PI3K) and mechanistic target of rapamycin (mTOR) complex 2 (mTORC2). Hypoxic downregulation of E6/E7 occurs, at least in part, at the transcriptional level. Modulation of E6/E7 expression by the PI3K/mTORC2/AKT cascade is hypoxia specific and not observed in normoxic HPV-positive cancer cells. Quantitative proteome analyses identify additional factors as candidates to be involved in hypoxia-induced activation of the PI3K/mTORC2/AKT signaling cascade and in the AKT-dependent repression of the E6/E7 oncogenes under hypoxia. Collectively, these data uncover a functional key role of the PI3K/mTORC2/AKT signaling cascade for viral oncogene repression in hypoxic HPV-positive cancer cells and provide new insights into the poorly understood cross talk between oncogenic HPVs and their host cells under hypoxia

Ocular lesions in hereditary hemorrhagic telangiectasia: genetics and clinical characteristics

Background: The aim of our study is to study the association between eye lesions in Hereditary Hemorrhagic Telangiectasia (HHT) and other signs of the disease, as well as to characterize its genetics. Methods: A cross-sectional study was conducted of a cohort of 206 patients studied in the HHT Unit of Hospital de Sierrallana, a reference centre for Spanish patients with HHT. Odds ratios for several symptoms or characteristics of HHT and ocular lesions were estimated using logistic regression adjusting for age and sex. Results: The ocular involvement was associated with being a carrier of a mutation for the ENG gene, that is, suffering from a type 1 HHT involvement (OR = 2.09; 95% CI [1.17–3.72]). p = 0.012). In contrast, patients with ocular lesions have less frequently mutated ACVRL1/ALK1 gene (OR = 0.52; 95% CI [0.30–3.88], p = 0.022). Conclusions: In conclusion, half of the patients with HHT in our study have ocular involvement. These eye lesions are associated with mutations in the ENG gene and ACVRL1/ALK1 gene. Thus, the ENG gene increases the risk of ocular lesions, while being a carrier of the mutated ACVRL1/ALK1 gene decreases said risk

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts