bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cysteines and N-Glycosylation Sites Conserved among All Alphaherpesviruses Regulate Membrane Fusion in Herpes Simplex Virus 1 Infection
Authors: Rider Paul J. F. , Naderi Misagh , Bergeron Scott , Chouljenko Vladimir N. , Brylinski Michal , Kousoulas Konstantin G. 
Published: August 2017

ABSTRACT
Neurotropism is a defining characteristic of alphaherpesvirus pathogenicity. Glycoprotein K (gK) is a conserved virion glycoprotein of all alphaherpesviruses that is not found in other herpesvirus subfamilies. The extracellular amino terminus of gK has been shown to be important to the ability of the prototypic alphaherpesvirus herpes simplex virus 1 (HSV-1) to enter neurons via axonal termini. Here, we determined the role of the two conserved N-linked glycosylation (N48 and N58) sites of gK in virus-induced cell fusion and replication. We found that N-linked glycosylation is important to the regulation of HSV-1-induced membrane fusion since mutating N58 to alanine (N58A) caused extensive virus-induced cell fusion. Due to the known contributions of N-linked glycosylation to protein processing and correct disulfide bond formation, we investigated whether the conserved extracellular cysteine residues within the amino terminus of gK contributed to the regulation of HSV-1-induced membrane fusion. We found that mutation of C37 and C114 residues led to a gK-null phenotype characterized by very small plaque formation and drastic reduction in infectious virus production, while mutation of C82 and C243 caused extensive virus-induced cell fusion. Comparison of N-linked glycosylation and cysteine mutant replication kinetics identified disparate effects on infectious virion egress from infected cells. Specifically, cysteine mutations caused defects in the accumulation of infectious virus in both the cellular and supernatant fractions, while glycosylation site mutants did not adversely affect virion egress from infected cells. These results demonstrate a critical role for the N glycosylation sites and cysteines for the structure and function of the amino terminus of gK.

IMPORTANCE
We have previously identified important entry and neurotropic determinants in the amino terminus of HSV-1 glycoprotein K (gK). Alphaherpesvirus-mediated membrane fusion is a complex and highly regulated process that is not clearly understood. gK and UL20, which are highly conserved across all alphaherpesviruses, play important roles in the regulation of HSV-1 fusion in the context of infection. A greater understanding of mechanisms governing alphaherpesvirus membrane fusion is expected to inform the rational design of therapeutic and prevention strategies to combat herpesviral infection and pathogenesis. This work adds to the growing reports regarding the importance of gK to alphaherpesvirus pathogenesis and details important structural features of gK that are involved in gK-mediated regulation of virus-induced membrane fusion.
Cost-effectiveness of age-related macular degeneration study supplements in the UK: combined trial and real-world outcomes data
Authors: Lee Aaron Y , Butt Thomas , Chew Emily , Agron Elvira , Clemons Traci E , Egan Catherine A , Lee Cecilia S , Tufail Adnan 
Published: August 2017

AimsTo evaluate the cost-effectiveness of Age-Related Eye Disease Study (AREDS) 1 & 2 supplements in patients with either bilateral intermediate age-related macular degeneration, AREDS category 3, or unilateral neovascular age-related macular degeneration AMD (nAMD), AREDS category 4.MethodsA patient-level health state transition model based on levels of visual acuity in the better-seeing eye was constructed to simulate the costs and consequences of patients taking AREDS vitamin supplements. Setting: UK National Health Service (NHS). The model was populated with data from AREDS and real-world outcomes and resource use from a prospective multicentre national nAMD database study containing 92 976 ranibizumab treatment episodes.InterventionsTwo treatment approaches were compared: immediate intervention with AREDS supplements or no supplements. Main outcome measures: quality-adjusted life years (QALYs) and healthcare costs were accrued for each strategy, and incremental costs and QALYs were calculated for the lifetime of the patient. One-way and probabilistic sensitivity analyses were employed to test the uncertainty of the model.ResultsFor AREDS category 3, the incremental cost-effectiveness ratio was £30 197. For AREDS category 4 compared with no intervention, AREDS supplements are more effective (10.59 vs 10.43 QALYs) and less costly (£52 074 vs 54 900) over the lifetime of the patient.ConclusionsThe recommendation to publicly fund AREDS supplements to category 3 patients would depend on the healthcare system willingness to pay. In contrast, initiating AREDS supplements in AREDS category 4 patients is both cost saving and more effective than no supplement use and should therefore be considered in public health policy.
Systematic review of pharmacological therapies for the management of ischaemic pain in patients with non-reconstructable critical limb ischaemia
Authors: Laoire Áine Ní , Murtagh Fliss E M 
Published: August 2017

BackgroundCritical limb ischaemia (CLI) is a severe manifestation of peripheral arterial disease, characterised by chronic ischaemic rest pain, ulcers or gangrene. Management of ischaemic pain is challenging in patients with no options for revascularisation and optimal pharmacological therapies have not been established.ObjectivesTo identify and evaluate the effectiveness of pharmacological therapies to treat ischaemic pain secondary to non-reconstructable CLI.MethodsThis systematic review was reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Comprehensive searches of three electronic databases, a PubMed-related articles link search, grey literature search and hand-searches of the bibliographies of relevant papers and textbooks were performed. Studies recruiting adult patients with CLI of any aetiology were eligible for inclusion. Surgical and revascularisation procedures, and all invasive interventions were excluded.ResultsOf 792 studies, six met full inclusion criteria. These studies researched the use of intravenous lidocaine, intravenous ketamine, oral gabapentin and the combination of transdermal buprenorphine and epidural morphine/ropivacaine infusion. All studies showed an improvement in severity of ischaemic pain in CLI but with varying side effect profiles and quality. The extracted studies showed substantial heterogeneity and therefore a meta-analysis was not performed.ConclusionThe pharmacological management of pain secondary to non-reconstructable CLI is a challenging review topic. No recommendations of pharmacological agents can be made following this review but a number of novel approaches to manage pain in this cohort have shown positive results and require further investigation.
Non-battle injury among repatriated UK armed forces since cessation of combat operations: a prospective observational study
Authors: Toman Emma , Beaven A , Naumann D N , Myatt R W , Parker P J , Kay A R 
Published: August 2017

AimTo describe the mechanisms, burden of injury, inpatient management and rehabilitation requirements of wounded military personnel at the UK Role 4 (R4) facility within the first 12 months following cessation of combat operations in Afghanistan.MethodsAll aeromedical evacuations were recorded prospectively between October 2014 and October 2015. Demographic, logistical and clinical data were derived manually from referring medical unit and patient movement requests in addition to host nation and R4 medical records.ResultsNinety-five patients were repatriated to R4 following traumatic injury: 98.9% (n=94) were male, and median age was 27 years (IQR 25–36 years). The most common mechanisms of injury (MOIs) were sports 26.3% (n=25), falls <2 m 11.6% (n=11) and road traffic collisions 9.8% (n=9). The most common anatomical regions of injury were isolated lower limb 24.1% (n=22), isolated hand 20.0% (n=19) and polytrauma 14.7% (n=14). Median Injury Severity Score was 4 (IQR 4–9), mean 8 (range 1–41). Eleven patients (11.6%) were discharged to rehabilitation units, of whom 7 (63.6%) required neurorehabilitation.ConclusionAlthough service personnel sustain civilian-type injuries, the specific rehabilitation goals and shift in the acute rehabilitation requirements for military personnel must be considered in the absence of enduring combat operations. It is notable that permanent medical downgrading secondary to trauma still occurs outside of warfare. The colocation of civilian major trauma services and R4 has ensured a mutually beneficial partnership that contributes to institutional memory and improves the coordination of patient pathways. The importance of relevant resource allocation, training, support and logistical considerations remain, even during the current scale of military activity overseas.
Long-term prognosis for neck-shoulder pain and disorders: a 14-year follow-up study
Authors: Jakobsen Emma Lise Thorlund , Biering Karin , Kærgaard Anette , Dalbøge Annett , Andersen Johan Hviid 
Published: August 2017

ObjectivesThe long-term prognosis for neck-shoulder pain and disorders and the impact of shoulder exposure among former sewing machine operators were investigated in a 14-year follow-up study.MethodsInformation on neck-shoulder pain and disorders was collected by questionnaire and clinical examination at baseline in 243 female sewing machine operators and by questionnaire 14 years later. During follow-up, information on comorbidity and job exposures was obtained from registers and by linking register-based D-ISCO 88 codes with a job exposure matrix. Logistic regression analyses were performed to examine associations between neck-shoulder pain and disorders at baseline and neck-shoulder pain and physical functioning at follow-up.ResultsWe found an association between neck-shoulder disorders at baseline and neck-shoulder pain at follow-up (OR 5.9;95% CI 1.9 to 17.7), and between neck-shoulder pain at baseline and neck-shoulder pain at follow-up (OR 8.2;95% CI 3.5 to 19.2). Associations between neck-shoulder disorders and pain at baseline and limited physical functioning at follow-up had ORs of 5.0 (95% CI 1.5 to 16.1) and 2.2 (95% CI 1.1 to 4.6), respectively. In women still working in 2008, the association between neck-shoulder pain in 1994 and in 2008 seemed to be stronger for those in jobs with high job shoulder exposure.ConclusionsThe results suggest a long-term adverse prognosis for neck-shoulder pain. High job shoulder exposure can worsen this prognosis for those who continue working. This knowledge could influence the counselling given to similar workers and emphasises the need to prevent neck-shoulder pain.
Optimal Control of PEVs with a Charging Aggregator Considering Regulation Service Provisioning
Authors: Cui Tiansong , Chen Shuang , Wang Yanzhi , Nazarian Shahin , Pedram Massoud 
Published: August 2017

Plug-in electric vehicles (PEVs) are considered the key to reducing fossil fuel consumption and an important part of the smart grid. The plug-in electric vehicle-to-grid (V2G) technology in the smart grid infrastructure enables energy flow from PEV batteries to the power grid so that the grid stability is enhanced and the peak power demand is shaped. PEV owners will also benefit from V2G technology, as they will be able to reduce energy cost through proper PEV charging and discharging scheduling. Moreover, power regulation service (RS) reserves have been playing an increasingly important role in modern power markets. It has been shown that by providing RS reserves, the power grid achieves a better match between energy supply and demand in presence of volatile and intermittent renewable energy generation. This article starts with the problem of PEV charging under dynamic energy pricing, properly taking into account the degradation of battery state-of-health (SoH) during V2G operations as well as RS provisioning. An overall optimization throughout the whole parking period is proposed for the PEV and an adaptive control framework is presented to dynamically update the optimal charging/discharging decision at each hour to mitigate the effect of RS tracking error.
As more and more PEVs are being plugged into the power grid, the control or management issue of PEV charging arises, since mass unregulated charging processes of PEVs may result in degradation of power quality and damage utility equipments and customer appliances. To solve this problem, this article also presents an SoH-aware charging aggregator design, which decides the control sequences of a group of PEVs. An energy storage system is used in the charging aggregator to do a peak power shaving, and future parking PEVs are properly taken care of. Experimental results show that the proposed optimal charging algorithm minimizes the combination of electricity cost and battery aging cost in the RS provisioning power market. Experimental results also show that the introduction of charging aggregator can significantly reduce the peak power consumption caused by simultaneous PEV charging.
Animation of Fingerspelled Words and Number Signs of the Sinhala Sign Language
Authors: Punchimudiyanse Malinda , Meegama Ravinda Gayan Narendra 
Published: August 2017

Sign language is the primary communication medium of the aurally handicapped community. Often, a sign gesture is mapped to a word or a phrase in a spoken language and named as a conversational sign. A fingerspelling sign is a special sign derived to show a single character that matches a character in the alphabet of a given language. This enables the deaf community to express words that do not have a conversational sign, such as a name, using a letter-by-letter technique. Sinhala Sign Language (SSL) uses a phonetic pronunciation mechanism to decode such words due to the presence of one or more modifiers after a consonant. Expressing numbers also have a similar notation, and it is broken down into parts before interpretation in sign gestures.
This article presents the variations implemented to make the 3D avatar-based interpreter system look similar to an actual fingerspelled SSL by a human interpreter. To accomplish the task, a phonetic English-based 3D avatar animation system is developed with Blender animation software. The conversion of Sinhala Unicode text to phonetic English and numbers written in digits to sign gestures is done with a Visual Basic.NET (VB.NET) application. The presented application has 61 SSL fingerspelling signs and 40 SSL number signs. It is capable of interpreting any word written using the modern Sinhala alphabet without conversational signs and interprets the numbers that go up to the billions. This is a helpful tool in teaching SSL fingerspelling and number signs of SSL to deaf children.
Scaling Reliably
Authors: Trinder Phil , Chechina Natalia , Papaspyrou Nikolaos , Sagonas Konstantinos , Thompson Simon , Adams Stephen , Aronis Stavros , Baker Robert , Bihari Eva , Boudeville Olivier , Cesarini Francesco , Stefano Maurizio Di , Eriksson Sverker , fördős Viktória , Ghaffari Amir , Giantsios Aggelos , Green Rickard , Hoch Csaba , Klaftenegger David , Li Huiqing , Lundin Kenneth , Mackenzie Kenneth , Roukounaki Katerina , Tsiouris Yiannis , Winblad Kjell 
Published: August 2017

Distributed actor languages are an effective means of constructing scalable reliable systems, and the Erlang programming language has a well-established and influential model. While the Erlang model conceptually provides reliable scalability, it has some inherent scalability limits and these force developers to depart from the model at scale. This article establishes the scalability limits of Erlang systems and reports the work of the EU RELEASE project to improve the scalability and understandability of the Erlang reliable distributed actor model.
We systematically study the scalability limits of Erlang and then address the issues at the virtual machine, language, and tool levels. More specifically: (1) We have evolved the Erlang virtual machine so that it can work effectively in large-scale single-host multicore and NUMA architectures. We have made important changes and architectural improvements to the widely used Erlang/OTP release. (2) We have designed and implemented Scalable Distributed (SD) Erlang libraries to address language-level scalability issues and provided and validated a set of semantics for the new language constructs. (3) To make large Erlang systems easier to deploy, monitor, and debug, we have developed and made open source releases of five complementary tools, some specific to SD Erlang.
Throughout the article we use two case studies to investigate the capabilities of our new technologies and tools: a distributed hash table based Orbit calculation and Ant Colony Optimisation (ACO). Chaos Monkey experiments show that two versions of ACO survive random process failure and hence that SD Erlang preserves the Erlang reliability model. While we report measurements on a range of NUMA and cluster architectures, the key scalability experiments are conducted on the Athos cluster with 256 hosts (6,144 cores). Even for programs with no global recovery data to maintain, SD Erlang partitions the network to reduce network traffic and hence improves performance of the Orbit and ACO benchmarks above 80 hosts. ACO measurements show that maintaining global recovery data dramatically limits scalability; however, scalability is recovered by partitioning the recovery data. We exceed the established scalability limits of distributed Erlang, and do not reach the limits of SD Erlang for these benchmarks at this scale (256 hosts, 6,144 cores).
B-cell Receptor Signaling Regulates Metabolism in Chronic Lymphocytic Leukemia
Authors: Vangapandu Hima V. , Havranek Ondrej , Ayres Mary L. , Kaipparettu Benny Abraham , Balakrishnan Kumudha , Wierda William G. , Keating Michael J. , Davis R. Eric , Stellrecht Christine M. , Gandhi Varsha 
Published: August 2017

AbstractPeripheral blood chronic lymphocytic leukemia (CLL) cells are quiescent but have active transcription and translation processes, suggesting that these lymphocytes are metabolically active. Based on this premise, the metabolic phenotype of CLL lymphocytes was investigated by evaluating the two intracellular ATP-generating pathways. Metabolic flux was assessed by measuring glycolysis as extracellular acidification rate (ECAR) and mitochondrial oxidative phosphorylation as oxygen consumption rate (OCR) and then correlated with prognostic factors. Further, the impact of B-cell receptor signaling (BCR) on metabolism was determined by genetic ablation and pharmacological inhibitors. Compared with proliferative B-cell lines, metabolic fluxes of oxygen and lactate were low in CLL cells. ECAR was consistently low, but OCR varied considerably in human patient samples (n = 45). Higher OCR was associated with poor prognostic factors such as ZAP 70 positivity, unmutated IGHV, high β2M levels, and higher Rai stage. Consistent with the association of ZAP 70 and IGHV unmutated status with active BCR signaling, genetic ablation of BCR mitigated OCR in malignant B cells. Similarly, knocking out PI3Kδ, a critical component of the BCR pathway, decreased OCR and ECAR. In concert, PI3K pathway inhibitors dramatically reduced OCR and ECAR. In harmony with a decline in metabolic activity, the ribonucleotide pools in CLL cells were reduced with duvelisib treatment. Collectively, these data demonstrate that CLL metabolism, especially OCR, is linked to prognostic factors and is curbed by BCR and PI3K pathway inhibition.Implications: This study identifies a relationship between oxidative phosphorylation in CLL and prognostic factors providing a rationale to therapeutically target these processes. Mol Cancer Res; 15(12); 1692–703. ©2017 AACR.
Association Between Acidosis Soon After Reperfusion and Contrast‐Induced Nephropathy in Patients With a First‐Time ST‐Segment Elevation Myocardial Infarction
Authors: Gohbara Masaomi , Hayakawa Azusa , Akazawa Yusuke , Furihata Shuta , Kondo Ai , Fukushima Yusuke , Tomari Sakie , Endo Tsutomu , Kimura Kazuo , Tamura Kouichi 
Published: August 2017

Background

Contrast‐induced nephropathy (
CIN
) is associated with poor outcomes in patients with acute myocardial infarction. However, the predictors of
CIN
have yet to be fully elucidated.

Methods and Results

The study included 273 consecutive patients with a first‐time
ST
‐segment elevation myocardial infarction who underwent reperfusion within 12 hours of symptom onset. The exclusion criteria were hemodialysis, mechanical ventilation, or previous coronary artery bypass grafting. All patients underwent arterial blood gas analysis soon after reperfusion.
CIN
was defined as an increase of 0.5 mg/dL in serum creatinine or a 25% increase from baseline between 48 and 72 hours after contrast medium exposure. Acidosis was defined as an arterial blood
pH
<7.35.
CIN
was observed in 35 patients (12.8%). Multivariable logistic regression analysis with forward stepwise algorithm revealed a significant association between
CIN
and the following: reperfusion time, the prevalence of hypertension, peak creatine kinase‐
MB
, high‐sensitivity C‐reactive protein on admission, and the incidence of acidosis (
P
<0.05). Multivariable logistic regression analysis revealed that the incidence of acidosis was associated with
CIN
when adjusted for age, male sex, body mass index, amount of contrast medium used, estimated glomerular filtration rate on admission, glucose level on admission, high‐sensitivity C‐reactive protein on admission, and left ventricular ejection fraction (
P
<0.05). Moreover, the incidence of acidosis was associated with
CIN
when adjusted for the Mehran
CIN
risk score (odds ratio: 2.229,
P
=0.049).

Conclusions

The incidence of acidosis soon after reperfusion was associated with
CIN
in patients with a first‐time
ST
‐segment elevation myocardial infarction.
Is the Study of Religions in the Eastern Europe still behind the Iron Curtain? Response to Gregory Alles, Barbara Krawcowicz and Stefan Ragaz
Authors: Bubík Tomáš 
Published: August 2017

Abstract
The text is a response to the review articles of Gregory Alles, Barbara Krawcowicz and Stefan Ragaz reviewing the book Studying Religions with the Iron Curtain Closed and Open: The Academic Study of Religion in Eastern Europe (Brill 2015). It discusses the book’s title, the relationship of religious studies to theology, and the relationship of current religious studies to scientific atheism.