Traffic to the inner membrane of the nuclear envelope

Past research has yielded valuable insight into the mechanisms that regulate the nuclear transport of soluble molecules like transcription factors and mRNA. Much less is known about the mechanisms responsible for the transportation of membrane proteins to the inner membrane of the nuclear envelope. The key question is: does the facilitated transport of integral inner membrane proteins exist in the same way as it does for soluble proteins and, if so, what is it used for? Herein, we provide an overview of the current knowledge on traffic to the inner nuclear membrane, and make a case that: (a) known sorting signals and molecular mechanisms in membrane protein biogenesis, membrane protein traffic and nuclear transport are also relevant with respect to INM traffic; and (b) the interplay of the effects of these signals and molecular mechanisms is what determines the rates of traffic to the INM

Representase Visi Surat Kabar dalam Foto Jurnalistik

Dewasa ini foto jurnalistik sebagai salah satu unsur penting dalam kegiatan jurnalistik modern, telah berkembang sangat pesat, apalagi sejak ditemukannya kamera digital yang menawarkan beraneka macam kemudahan. Fotografi jurnalistik semakin besar peranannya menjadi penyampai informasi kepada khalayak secara cepat dan akurat. Pada dasarnya semua foto yang dimuat di media massa diistilahkan sebagai foto jurnalistik, termasuk foto-foto peristiwa yang tampil di media online seperti internet. Artinya semua produk foto yang mempunyai nilai berita bisa disebut sebagai foto jurnalistik. Dalam konteks ini, fotografi jurnalistik tidak berdiri sendiri sebagai sebuah gambar, melainkan acapkali menjadi suatu kesatuan dengan berita. Keduanya saling mempengaruhi dan dipengaruhi, sehingga media massa cetak akan terasa hambar jika salah satunya tidak ada. Media massa cetak hanya akan menjadi lembaran-lembaran mati yang membosankan jika hadir tanpa foto atau gambar (Wijaya, 2011:21). Foto jurnalistik juga dapat dikatakan sebagai metode berkomunikasi melalui fotografi sehingga foto jurnalistik menjadi sebuah berita ataupun informasi yang dibutuhkan masyarakat baik lokal, regional, nasional maupun pada tingkat Internasional. Foto jurnalistik merupakan hasil jerih payah seorang fotografer jurnalistik (kerap juga disebut pewarta foto, foto jurnalis atau wartawan foto) yang dianggap dapat mengekspresikan sudut pandang sang fotografer namun pesan komunikasinya memiliki arti yang jauh lebih luas dari pada hanya sekedar arti dari sudut pandang sang fotografer. Foto jurnalistik merupakan salah satu produk jurnalistik yang dihasilkan oleh wartawan selain tulisan yang berbau berita (straight news atau hard news, berita bertafsir, berita kedalaman (depth reports) maupun non berita (artikel, feature, tajuk rencana, pojok, karikatur dan surat pembaca). Sebagai produk dalam pemberitaan, tentunya foto jurnalistik memiliki peran penting dalam media cetak maupun cyber media (internet). Penggunaan foto jurnalistik dalam surat kabar dan majalah mulai berkembang pada tahun 1930 an. Perkembangannya sangat cepat sehingga pada gilirannya teknologi foto dapat mendorong perkembangan media jurnalistik. Foto jurnalistik kemudian tumbuh menjadi suatu konsep dalam sistem komunikasi yang disebut dengan komunikasi foto (Photographic Communication). Bahkan komunikasi foto kini telah menempati kunci model dalam proses komunikasi massa. Sebagai suatu lambang yang berdimensi visual, foto dan gambar mendeskripsikan sesuatu pesan yang tidak secara eksplisit tertuang dalam komunikasi kata, baik lisan maupun tulisan (Muhtadi, 1999:101). Foto jurnalistik itu sendiri secara harfiah merupakan karya visual dari jurnalisme yang memilki nilai berita atau pesan yang layak untuk diketahui khalayak banyak dan disebarluaskan melalui media massa. Pertimbangan dari kelayakan sebuah foto jurnalistik meliputi unsur visi, informatif, kehangatan, faktual, relevan, misi termasuk juga di dalamnya mengenai angle atau sudut pengambilan gambar. Selain itu, salah satu prasyarat mutlak dari nilai sebuah foto jurnalistik adalah orisinalitas dan bukan hasil rekayasa termasuk rekayasa koputer grafis. Namun begitu, untuk kepentingan cover sebuah majalah atau media internet, pemakaian komputer grafis terhadap foto bisa ditolelir dan menjadi pertimbangan tersendiri dengan tujuan estetika untuk menarik pembaca

Quelling Cabin Noise in Turboprop Aircraft via Active Control

Cabin noise in turboprop aircraft causes passenger discomfort, airframe fatigue, and employee scheduling constraints due to OSHA standards for exposure to high levels of noise. The noise levels in the cabins of turboprop aircraft are typically 10 to 30 decibels louder than commercial jet noise levels. However. unlike jet noise the turboprop noise spectrum is dominated by a few low frequency tones. Active structural acoustic control is a method in which the control inputs (used to reduce interior noise) are applied directly to a vibrating structural acoustic system. The control concept modeled in this work is the application of in-plane force inputs to piezoceramic patches bonded to the wall of a vibrating cylinder. The goal is to determine the force inputs and locations for the piezoceramic actuators so that: (1) the interior noise is effectively damped; (2) the level of vibration of the cylinder shell is not increased; and (3) the power requirements needed to drive the actuators are not excessive. Computational experiments for data taken from a computer generated model and from a laboratory test article at NASA Langley Research Center are provided

A Generalization of the Convex Kakeya Problem

Given a set of line segments in the plane, not necessarily finite, what is a convex region of smallest area that contains a translate of each input segment? This question can be seen as a generalization of Kakeya's problem of finding a convex region of smallest area such that a needle can be rotated through 360 degrees within this region. We show that there is always an optimal region that is a triangle, and we give an optimal \Theta(n log n)-time algorithm to compute such a triangle for a given set of n segments. We also show that, if the goal is to minimize the perimeter of the region instead of its area, then placing the segments with their midpoint at the origin and taking their convex hull results in an optimal solution. Finally, we show that for any compact convex figure G, the smallest enclosing disk of G is a smallest-perimeter region containing a translate of every rotated copy of G.Comment: 14 pages, 9 figure

Abortion Safety and Use with Normally Prescribed Mifepristone in Canada.

BACKGROUND: In the United States, mifepristone is available for medical abortion (for use with misoprostol) only with Risk Evaluation and Mitigation Strategy (REMS) restrictions, despite an absence of evidence to support such restrictions. Mifepristone has been available in Canada with a normal prescription since November 2017. METHODS: Using population-based administrative data from Ontario, Canada, we examined abortion use, safety, and effectiveness using an interrupted time-series analysis comparing trends in incidence before mifepristone was available (January 2012 through December 2016) with trends after its availability without restrictions (November 7, 2017, through March 15, 2020). RESULTS: A total of 195,183 abortions were performed before mifepristone was available and 84,032 after its availability without restrictions. After the availability of mifepristone with a normal prescription, the abortion rate continued to decline, although more slowly than was expected on the basis of trends before mifepristone had been available (adjusted risk difference in time-series analysis, 1.2 per 1000 female residents between 15 and 49 years of age; 95% confidence interval [CI], 1.1 to 1.4), whereas the percentage of abortions provided as medical procedures increased from 2.2% to 31.4% (adjusted risk difference, 28.8 percentage points; 95% CI, 28.0 to 29.7). There were no material changes between the period before mifepristone was available and the nonrestricted period in the incidence of severe adverse events (0.03% vs. 0.04%; adjusted risk difference, 0.01 percentage points; 95% CI, -0.06 to 0.03), complications (0.74% vs. 0.69%; adjusted risk difference, 0.06 percentage points; 95% CI, -0.07 to 0.18), or ectopic pregnancy detected after abortion (0.15% vs. 0.22%; adjusted risk difference, -0.03 percentage points; 95% CI, -0.19 to 0.09). There was a small increase in ongoing intrauterine pregnancy continuing to delivery (adjusted risk difference, 0.08 percentage points; 95% CI, 0.04 to 0.10). CONCLUSIONS: After mifepristone became available as a normal prescription, the abortion rate remained relatively stable, the proportion of abortions provided by medication increased rapidly, and adverse events and complications remained stable, as compared with the period when mifepristone was unavailable. (Funded by the Canadian Institutes of Health Research and the Women's Health Research Institute.)

Implementing Kanyini GAP, a pragmatic randomised controlled trial in Australia: Findings from a qualitative study

© 2015 Liu et al. Background: Pragmatic randomised controlled trials (PRCTs) aim to assess intervention effectiveness by accounting for 'real life' implementation challenges in routine practice. The methodological challenges of PRCT implementation, particularly in primary care, are not well understood. The Kanyini Guidelines Adherence to Polypill study (Kanyini GAP) was a recent primary care PRCT involving multiple private general practices, Indigenous community controlled health services and private community pharmacies. Through the experiences of Kanyini GAP participants, and using data from study materials, this paper identifies the critical enablers and barriers to implementing a PRCT across diverse practice settings and makes recommendations for future PRCT implementation. Methods: Qualitative data from 94 semi-structured interviews (47 healthcare providers (pharmacists, general practitioners, Aboriginal health workers; 47 patients) conducted for the process evaluation of Kanyini GAP was used. Data coded to 'trial impact', 'research motivation' and 'real world' were explored and triangulated with data extracted from study materials (e.g. Emails, memoranda of understanding and financial statements). Results: PRCT implementation was facilitated by an extensive process of relationship building at the trial outset including building on existing relationships between core investigators and service providers. Health providers' and participants' altruism, increased professional satisfaction, collaboration, research capacity and opportunities for improved patient care enabled implementation. Inadequate research infrastructure, excessive administrative demands, insufficient numbers of adequately trained staff and the potential financial impact on private practice were considered implementation barriers. These were largely related to this being the first experience of trial involvement for many sites. The significant costs of addressing these barriers drew study resources from the task of achieving recruitment targets. Conclusions: Conducting PRCTs is crucial to generating credible evidence of intervention effectiveness in routine practice. PRCT implementation needs to account for the particular challenges of implementing collaborative research across diverse stakeholder organisations. Reliance on goodwill to participate is crucial at the outset. However, participation costs, particularly for organisations with little or no research experience, can be substantial and should be factored into PRCT funding models. Investment in a pool to fund infrastructure in the form of primary health research networks will offset some of these costs, enabling future studies to be implemented more cost-effectively. Trial registration:ACTRN12608000583334

Active Nuclear Import of Membrane Proteins Revisited

It is poorly understood how membrane proteins destined for the inner nuclear membrane pass the crowded environment of the Nuclear Pore Complex (NPC). For the Saccharomyces cerevisiae proteins Src1/Heh1 and Heh2, a transport mechanism was proposed where the transmembrane domains diffuse through the membrane while the extralumenal domains encoding a nuclear localization signal (NLS) and intrinsically disordered linker (L) are accompanied by transport factors and travel through the NPC. Here, we validate the proposed mechanism and explore and discuss alternative interpretations of the data. First, to disprove an interpretation where the membrane proteins become membrane embedded only after nuclear import, we present biochemical and localization data to support that the previously used, as well as newly designed reporter proteins are membrane-embedded irrespective of the presence of the sorting signals, the specific transmembrane domain (multipass or tail anchored), independent of GET, and also under conditions that the proteins are trapped in the NPC. Second, using the recently established size limit for passive diffusion of membrane proteins in yeast, and using an improved assay, we confirm active import of polytopic membrane protein with extralumenal soluble domains larger than those that can pass by diffusion on similar timescales. This reinforces that NLS-L dependent active transport is distinct from passive diffusion. Thirdly, we revisit the proposed route through the center of the NPC and conclude that the previously used trapping assay is, unfortunately, poorly suited to address the route through the NPC, and the route thus remains unresolved. Apart from the uncertainty about the route through the NPC, the data confirm active, transport factor dependent, nuclear transport of membrane-embedded mono- and polytopic membrane proteins in baker's yeast

ОСОБЛИВОСТІ ПРОЯВІВ БОЙОВИХ СТРЕСОВИХ РОЗЛАДІВ У ПОРАНЕНИХ ВІЙСЬКОВОСЛУЖБОВЦІВ ЗБРОЙНИХ СИЛ УКРАЇНИ – УЧАСНИКІВ БОЙОВИХ ДІЙ

Early diagnosis of negative mental states, post-stress states allows detecting early and severe manifestations of combat mental trauma and its consequences in wounded servicemen of the Armed Forces of Ukraine, and also allows developing individual tactics and methods of prevention and recovery of each examined serviceman. The lack of a unified, scientifically sound comprehensive approach to the organization of effective measures of medical, psychological and social rehabilitation, the urgent need to improve the quality of life, medical care, social protection and medical and psychological assistance to servicemen, led to the urgency of the study. Disorders among servicemen of the Armed Forces of Ukraine – participants in hostilities. In the course of work it is revealed that participation in the armed conflict, the received wound is a powerful stress factor leading to various functional disturbances of the body, including psychological. When studying such changes in servicemen who were injured, a significant part of them showed signs of post-traumatic stress response. Accordingly, this category of patients needs both medical and psychological rehabilitation.Рання діагностика негативних психічних і постстресових станів дозволяє на ранніх етапах виявити у поранених військовослужбовців Збройних сил України ранні та тяжкі прояви бойової психічної травми та її наслідки, а також розробити індивідуальну тактику і способи профілактики та відновлення кожного обстеженого військовослужбовця. Відсутність у державі єдиного, науково обґрунтованого комплексного підходу до організації проведення ефективних заходів медичної, психологічної та соціальної реабілітації, гостра потреба у підвищенні якості життя, медичного обслуговування, соціального захисту та медико-психологічної допомоги військовослужбовцям зумовили актуальність дослідження, метою якого стало вивчення особливостей проявів бойових стресових розладів серед військовослужбовців Збройних сил України – учасників бойових дій. У процесі роботи виявлено, що участь у збройному конфлікті, отримане поранення є потужним стресовим фактором, що призводить до різнопланових функціональних порушень організму, в тому числі й психологічних. При вивченні таких змін у значної частини військовослужбовців, які отримали поранення, виявлено ознаки посттравматичної стресової реакції. Відповідно дана категорія пацієнтів потребує як медичної, так і психологічної реабілітації

Data-driven quality improvement program to prevent hospitalisation and improve care of people living with coronary heart disease: Protocol for a process evaluation

Background: Practice-level quality improvement initiatives using rapidly advancing technology offers a multidimensional approach to reduce cardiovascular disease burden. For the “QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with heart disease” (QUEL) cluster randomised controlled trial, a 12-month quality improvement intervention was designed for primary care practices to use data and implement progressive changes using “Plan, Do, Study, Act” cycles within their practices with training in a series of interactive workshops. This protocol aims to describe the systematic methods to conduct a process evaluation of the data-driven intervention within the QUEL study. Methods: A mixed-method approach will be used to conduct the evaluation. Quantitative data collected throughout the intervention period, via surveys and intervention materials, will be used to (1) identify the key elements of the intervention and how, for whom and in what context it was effective; (2) determine if the intervention is delivered as intended; and (3) describe practice engagement, commitment and capacity associated with various intervention components. Qualitative data, collected via semi-structured interviews and open-ended questions, will be used to gather in-depth understanding of the (1) satisfaction, utility, barriers and enablers; (2) acceptability, uptake and feasibility, and (3) effect of the COVID-19 pandemic on the implementation of the intervention. Conclusion: Findings from the evaluation will provide new knowledge on the implementation of a complex, multi-component intervention at practice-level using their own electronic patient data to enhance secondary prevention of cardiovascular disease. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134

Abortion Safety and Use with Normally Prescribed Mifepristone in Canada.

BACKGROUND: In the United States, mifepristone is available for medical abortion (for use with misoprostol) only with Risk Evaluation and Mitigation Strategy (REMS) restrictions, despite an absence of evidence to support such restrictions. Mifepristone has been available in Canada with a normal prescription since November 2017. METHODS: Using population-based administrative data from Ontario, Canada, we examined abortion use, safety, and effectiveness using an interrupted time-series analysis comparing trends in incidence before mifepristone was available (January 2012 through December 2016) with trends after its availability without restrictions (November 7, 2017, through March 15, 2020). RESULTS: A total of 195,183 abortions were performed before mifepristone was available and 84,032 after its availability without restrictions. After the availability of mifepristone with a normal prescription, the abortion rate continued to decline, although more slowly than was expected on the basis of trends before mifepristone had been available (adjusted risk difference in time-series analysis, 1.2 per 1000 female residents between 15 and 49 years of age; 95% confidence interval [CI], 1.1 to 1.4), whereas the percentage of abortions provided as medical procedures increased from 2.2% to 31.4% (adjusted risk difference, 28.8 percentage points; 95% CI, 28.0 to 29.7). There were no material changes between the period before mifepristone was available and the nonrestricted period in the incidence of severe adverse events (0.03% vs. 0.04%; adjusted risk difference, 0.01 percentage points; 95% CI, -0.06 to 0.03), complications (0.74% vs. 0.69%; adjusted risk difference, 0.06 percentage points; 95% CI, -0.07 to 0.18), or ectopic pregnancy detected after abortion (0.15% vs. 0.22%; adjusted risk difference, -0.03 percentage points; 95% CI, -0.19 to 0.09). There was a small increase in ongoing intrauterine pregnancy continuing to delivery (adjusted risk difference, 0.08 percentage points; 95% CI, 0.04 to 0.10). CONCLUSIONS: After mifepristone became available as a normal prescription, the abortion rate remained relatively stable, the proportion of abortions provided by medication increased rapidly, and adverse events and complications remained stable, as compared with the period when mifepristone was unavailable. (Funded by the Canadian Institutes of Health Research and the Women's Health Research Institute.)