bluuebunny/crossref_metadata_2025_split huggingface dataset:
Möglichkeiten der universitären Einflussnahme auf die globale Preisgestaltung von Medikamenten
Authors: Jaehn Philipp , Inhoffen Johannes , Scheer Jana , Streicher Felix , Gesine Huhn Anna , Lance Christopher 
Published: August 2017

ZusammenfassungMenschen in Ländern des globalen Südens sind einerseits von einem eigenen Spektrum an Krankheiten betroffen, andererseits stellen die Gesundheitskosten im Kontext der vorherrschenden Armut eine erhebliche Belastung dar. In diesen Ländern spielen außerdem auch nicht-übertragbare Krankheiten eine immer größere Rolle. Medikamentenforschung in Deutschland und die Preisgestaltung der Endprodukte rücken daher in einen globalen Kontext. Universitäten haben diesbezüglich aus 2 Gründen eine besondere Verantwortung. Erstens tragen sie zu einem nicht unerheblichen Teil, insbesondere durch geleistete Grundlagenforschung, zur Entwicklung neuer Medikamente bei. Zweitens ist die Universität eine gemeinnützige Institution und hat als solche die Verantwortung, neu erworbenes Wissen an die Öffentlichkeit zurückzugeben. Von der öffentlichen Gemeinschaft mitfinanzierte Innovationen sollten deshalb so verwertet werden, dass finanziell benachteiligte Individuen und Bevölkerungen weltweit Zugang dazu haben. Als ersten konkreten Schritt in diese Richtung fordern wir die Einführung einer global verantwortlichen Lizenzpolitik an deutschen Universitäten. Verschiedene Mechanismen unter dem Sammelbegriff „Equitable Licensing“ bieten eine Grundlage zur Realisierung dieses ambitionierten Vorhabens, wie es bereits von den Universitäten Tübingen, Münster und Freiburg praktiziert wird.
Anatomy of an innovation in IT service
Authors: Ghoshal Sankar , Roy Rahul Kumar 
Published: August 2017

The case study covers aspects of service innovation in the IT services sector. The client Nordics is a global telecommunication major. They have a large and diverse set of IT business applications, most of which is on SAP applications. The subject of the case study is that of SAP Releases, the service of enhancing and creating new business functionalities in the existing business applications. The case is seen from the perspective of the Program Manager of the SAP Release service. This service is delivered by the IT Services major AVON. The case study covers the full lifecycle of the innovation in service, from the identification of the need, conceptualization and creation of the service offering up till pilot execution. The important aspects of innovation in the revenue model and service delivery model are also covered. The case can be analyzed from two perspectives, as a detailed lifecycle of a major innovation in service or as a requirement of dynamic capabilities in the IT service provider organization, to bring about that innovation.
Nasopharyngeal infection byStreptococcus pyogenesrequires superantigen-responsive Vβ-specific T cells
Authors: Zeppa Joseph J. , Kasper Katherine J. , Mohorovic Ivor , Mazzuca Delfina M. , Haeryfar S. M. Mansour , McCormick John K. 
Published: August 2017

SignificanceSuperantigen toxins were defined over 25 years ago for their ability to activate T cells in a T-cell receptor β-chain variable domain-dependent manner. This “Vβ-specific” T-cell activation is the hallmark feature of the superantigen, and although these toxins can mediate dangerous human disease such as toxic shock syndrome, mechanisms that explain why bacteria produce superantigens have remained enigmatic. Herein, we provide evidence thatStreptococcus pyogenesutilizes superantigens to target functional, Vβ-specific T cells to promote a state of colonization providing a mechanism that helps explain why bacteria produce toxins that specifically activate T cells of the adaptive immune system. This work also implicates the superantigen exotoxins as potential vaccine candidates against this globally important, human-specific pathogen.
Lethality of MalE-LacZ hybrid protein shares mechanistic attributes with oxidative component of antibiotic lethality
Authors: Takahashi Noriko , Gruber Charley C. , Yang Jason H. , Liu Xiaobo , Braff Dana , Yashaswini Chittampalli N. , Bhubhanil Sakkarin , Furuta Yoshikazu , Andreescu Silvana , Collins James J. , Walker Graham C. 
Published: August 2017

Significance
Understanding the molecular basis of the lethality of antibiotics and certain other stresses is complicated because cell death can result from direct inhibition of a critical biological process as well as from reactive oxygen species (ROS) generated by events metabolically downstream of the direct interaction of the agent with its target. Prior evidence has indicated that the ROS-dependent component of antibiotic lethality is due in part to lethal DNA problems resulting from the incorporation of oxidized nucleotides into DNA and incomplete DNA repair. Our observations unexpectedly indicate that the predominant mechanism of lethality from a hybrid protein that jams the machinery that translocates proteins across the cytoplasmic membrane shares attributes with the ROS-dependent component of antibiotic lethality.
Utilization of Buprenorphine and Methadone among Opioid users who Inject Drugs
Authors: Tsui Judith I. , Burt Richard , Thiede Hanne , Glick Sara N. 
Published: August 2017

Background There has been a rise in opioid abuse and related injection drug use in the United States, and treatment for opioid use disorders may be underutilized. The study aim was to describe utilization of opioid agonist therapy (OAT), and assess factors associated with utilization of OAT, among persons who inject drugs (PWID) in the Seattle metropolitan area. Methods Data were obtained from the 2015 National HIV Behavioral Surveillance (NHBS) system among PWID in the Seattle area. Persons aged ≥18 years who injected drugs in the past year were recruited using respondent-driven sampling. Local supplemental questions assessed whether participants had received methadone or buprenorphine treatment in the past year. The analysis was restricted to participants who reported use of any opioids in the past year. Analyses compared the demographic, health insurance status, duration of injection drug use, prior history of overdose, prior receipt of hepatitis C virus/human immunodeficiency virus (HCV/HIV) testing (self-report), and screening positive for HCV/HIV via study testing between methadone- or buprenorphine-treated and untreated PWID. Multivariate logistic models were performed to assess adjusted associations with receipt of any OAT. Results The sample included 487 PWID who used opioids in the past year, of whom 27.1% (95% confidence interval [CI]: 23.1–31.1) reported past-year treatment with methadone and 4.7% (95% CI: 2.8–6.6) reported treatment with buprenorphine. There were no significant differences in demographics among participants who did and did not report past-year OAT; however, participants who were treated with methadone were more likely to be insured and have hepatitis C. After adjustment for other covariates, having health insurance was strongly associated with receipt of OAT (adjusted odds ratio [aOR] = 18.6; 95% CI: 2.5–138.7). Conclusions OAT, in particular buprenorphine, has been underutilized by opioid-using PWID in the Seattle area. Health insurance is a critical factor for enabling PWID to utilize OAT treatment for opioid use disorders.
Scaling Theory of Polyelectrolyte Nanogels*
Authors: Qu Li-Jian 
Published: August 2017

Abstract

The present paper develops the scaling theory of polyelectrolyte nanogels in dilute and semidilute solutions. The dependencies of the nanogel dimension on branching topology, charge fraction, subchain length, segment number, solution concentration are obtained. For a single polyelectrolyte nanogel in salt free solution, the nanogel may be swelled by the Coulombic repulsion (the so-called polyelectrolyte regime) or the osmotic counterion pressure (the so-called osmotic regime). Characteristics and boundaries between different regimes of a single polyelectrolyte nanogel are summarized. In dilute solution, the nanogels in polyelectrolyte regime will distribute orderly with the increase of concentration. While the nanogels in osmotic regime will always distribute randomly. Different concentration dependencies of the size of a nanogel in polyelectrolyte regime and in osmotic regime are also explored.
In silico identification of rescue sites by double force scanning
Authors: Tiberti Matteo , Pandini Alessandro , Fraternali Franca , Fornili Arianna 
Published: August 2017

Abstract

Motivation
A deleterious amino acid change in a protein can be compensated by a second-site rescue mutation. These compensatory mechanisms can be mimicked by drugs. In particular, the location of rescue mutations can be used to identify protein regions that can be targeted by small molecules to reactivate a damaged mutant.

Results
We present the first general computational method to detect rescue sites. By mimicking the effect of mutations through the application of forces, the double force scanning (DFS) method identifies the second-site residues that make the protein structure most resilient to the effect of pathogenic mutations. We tested DFS predictions against two datasets containing experimentally validated and putative evolutionary-related rescue sites. A remarkably good agreement was found between predictions and experimental data. Indeed, almost half of the rescue sites in p53 was correctly predicted by DFS, with 65% of remaining sites in contact with DFS predictions. Similar results were found for other proteins in the evolutionary dataset.

Availability and implementation
The DFS code is available under GPL at https://fornililab.github.io/dfs/

Supplementary information
Supplementary data are available at Bioinformatics online.
Decompositions of Grothendieck Polynomials
Authors: Pechenik Oliver , Searles Dominic 
Published: August 2017

AbstractWe investigate the long-standing problem of finding a combinatorial rule for the Schubert structure constants in the $K$-theory of flag varieties (in type $A$). The Grothendieck polynomials of A. Lascoux–M.-P. Schützenberger (1982) serve as polynomial representatives for $K$-theoretic Schubert classes; however no positive rule for their multiplication is known in general. We contribute a new basis for polynomials (in $n$ variables) which we call glide polynomials, and give a positive combinatorial formula for the expansion of a Grothendieck polynomial in this basis. We then provide a positive combinatorial Littlewood–Richardson rule for expanding a product of Grothendieck polynomials in the glide basis. Our techniques easily extend to the $\beta$-Grothendieck polynomials of S. Fomin–A. Kirillov (1994), representing classes in connective $K$-theory, and we state our results in this more general context.
Hyper Suprime-Cam: Camera dewar design
Authors: Komiyama Yutaka , Obuchi Yoshiyuki , Nakaya Hidehiko , Kamata Yukiko , Kawanomoto Satoshi , Utsumi Yousuke , Miyazaki Satoshi , Uraguchi Fumihiro , Furusawa Hisanori , Morokuma Tomoki , Uchida Tomohisa , Miyatake Hironao , Mineo Sogo , Fujimori Hiroki , Aihara Hiroaki , Karoji Hiroshi , Gunn James E , Wang Shiang-Yu 
Published: August 2017

Abstract
This paper describes the detailed design of the CCD dewar and the camera system which is a part of the wide-field imager Hyper Suprime-Cam (HSC) on the 8.2 m Subaru Telescope. On the 1.°5 diameter focal plane (497 mm in physical size), 116 four-side buttable 2 k × 4 k fully depleted CCDs are tiled with 0.3 mm gaps between adjacent chips, which are cooled down to −100°C by two pulse tube coolers with a capability to exhaust 100 W heat at −100°C. The design of the dewar is basically a natural extension of Suprime-Cam, incorporating some improvements such as (1) a detailed CCD positioning strategy to avoid any collision between CCDs while maximizing the filling factor of the focal plane, (2) a spherical washers mechanism adopted for the interface points to avoid any deformation caused by the tilt of the interface surface to be transferred to the focal plane, (3) the employment of a truncated-cone-shaped window, made of synthetic silica, to save the back focal space, and (4) a passive heat transfer mechanism to exhaust efficiently the heat generated from the CCD readout electronics which are accommodated inside the dewar. Extensive simulations using a finite-element analysis (FEA) method are carried out to verify that the design of the dewar is sufficient to satisfy the assigned errors. We also perform verification tests using the actually assembled CCD dewar to supplement the FEA and demonstrate that the design is adequate to ensure an excellent image quality which is key to the HSC. The details of the camera system, including the control computer system, are described as well as the assembling process of the dewar and the process of installation on the telescope.
Exploiting the sequence diversity of TALE-like repeats to vary the strength of dTALE-promoter interactions
Authors: de Lange Orlando , Schandry Niklas , Wunderlich Markus , Berendzen Kenneth Wayne , Lahaye Thomas 
Published: August 2017

Abstract
Designer transcription activator-like effectors (dTALEs) are programmable transcription factors used to regulate user-defined promoters. The TALE DNA-binding domain is a tandem series of amino acid repeats that each bind one DNA base. Each repeat is 33–35 amino acids long. A residue in the center of each repeat is responsible for defining DNA base specificity and is referred to as the base specificying residue (BSR). Other repeat residues are termed non-BSRs and can contribute to TALE DNA affinity in a non-base-specific manner. Previous dTALE engineering efforts have focused on BSRs. Non-BSRs have received less attention, perhaps because there is almost no non-BSR sequence diversity in natural TALEs. However, more sequence diverse, TALE-like proteins are found in diverse bacterial clades. Here, we show that natural non-BSR sequence diversity of TALEs and TALE-likes can be used to modify DNA-binding strength in a new form of dTALE repeat array that we term variable sequence TALEs (VarSeTALEs). We generated VarSeTALE repeat modules through random assembly of repeat sequences from different origins, while holding BSR composition, and thus base preference, constant. We used two different VarSeTALE design approaches combing either whole repeats from different TALE-like sources (inter-repeat VarSeTALEs) or repeat subunits corresponding to secondary structural elements (intra-repeat VarSeTALEs). VarSeTALE proteins were assayed in bacteria, plant protoplasts and leaf tissues. In each case, VarSeTALEs activated or repressed promoters with a range of activities. Our results indicate that natural non-BSR diversity can be used to diversify the binding strengths of dTALE repeat arrays while keeping target sequences constant.
Factors Associated With Health-Related Quality of Life in Patients With Open Fractures
Authors: Sprague Sheila , Petrisor Brad A. , Jeray Kyle J. , McKay Paula , Scott Taryn , Heels-Ansdell Diane , Schemitsch Emil H. , Liew Susan , Guyatt Gordon H. , Walter Stephen D. , Bhandari Mohit ,   on behalf of the FLOW Investigators
Published: August 2017

Objectives:
To analyze FLOW data to identify baseline patient, injury, fracture, and treatment factors associated with lower health-related quality of life (HRQoL) at 12-month postfracture.

Design:
Prognostic study using data from a prospective randomized controlled trial.

Setting:
Thirty-one clinical centers in the United States, Canada, Australia, and India.

Patients/Participants:
One thousand four hundred twenty-seven patients with open fracture from the FLOW trial with complete 12-month Short Form-12 (SF-12) follow-up assessment and no missing data for selected baseline factors.

Intervention:
Not applicable.

Main Outcome Measurement:
Physical Component Score (PCS) and the Mental Component Score (MCS) of the SF-12 at 12-month postfracture.

Results:
One thousand four hundred twenty-seven patients were included in the SF-12 PCS and MCS linear regression models. Smoking, lower preinjury SF-12 PCS and MCS, and work-related injuries were significantly associated with lower SF-12 PCS and MCS at 12-month postfracture. A lower extremity fracture and a wound that was not closed at initial irrigation and debridement were significantly associated with lower 12-month SF-12 PCS but not MCS. Only the adjusted mean difference for lower extremity fractures approached the minimally important difference for the SF-12 PCS.

Conclusions:
We identified a number of statistically significant baseline factors associated with lower HRQoL; however, only the presence of a lower extremity fracture approached clinical significance. More research is needed to quantify the impact of these factors on patients and to determine whether changes to modifiable factors at baseline will lead to clinically significant improvements in HRQoL after open fractures.

Level of Evidence:
Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
MACROANEURYSMS ASSOCIATED WITH CONGENITAL RETINAL MACROVESSELS
Authors: Sebrow Dov B. , Cunha de Souza Eduardo , Belúcio Neto José , Roizenblatt Marina , Zett Lobos Claudio , Paulo Bonomo Pedro , Modi Yasha , Schuman Joel S. , Freund K. Bailey 
Published: August 2017

Purpose:
Congenital retinal macrovessels are large aberrant retinal blood vessels that cross the horizontal raphe and can traverse the central macula. Using multimodal imaging and optical coherence tomography angiography, we describe 2 cases of congenital retinal macrovessel associated with macroaneurysms.

Methods:
Two patients presented for evaluation and were found to have congenital retinal macrovessels associated with macroaneurysms. Color photography, optical coherence tomography, fundus autofluorescence fluorescein angiography, and optical coherence tomography angiography were performed and used to establish the diagnosis and monitor resolution at follow-up visits.

Results:
The first patient presented with central vision loss in the right eye and was noted to have a ruptured macroaneurysm and scattered microaneurysms along the course of a venous macrovessel. After 3 months of observation, the patient's vision improved. The second patient presented for evaluation of a cataract in her left eye and was incidentally found to have an arterial macrovessel in her right eye with an associated macroaneurysm. Both cases demonstrated an intricate capillary network in the central macula best visualized on optical coherence tomography angiography.

Conclusion:
Macroaneurysms can occur on both arterial and venous macrovessels. After rupture of these lesions, hemorrhage and exudation can resolve with observation alone. Macrovessels can also present with microaneurysms. Optical coherence tomography angiography can effectively image the complex capillary network associated with these vascular anomalies.
Outcome of Micropulse Laser Transscleral Cyclophotocoagulation on Pediatric Versus Adult Glaucoma Patients
Authors: Lee Jun Hui , Shi Yuhua , Amoozgar Behzad , Aderman Christopher , De Alba Campomanes Alejandra , Lin Shan , Han Ying 
Published: August 2017

Purpose:
To study and compare the outcome of micropulse transscelral cyclophotocoagulation in pediatric glaucoma patients to that in adult glaucoma patients.

Methods:
Consecutive pediatric and adult patients who received micropulse transscelral cyclophotocoagulation between July 2015 and December 2016 at University of California, San Francisco were retrospectively analyzed. All cases had at least 12 months of follow-up.

Results:
Nine eyes from 9 pediatric patients and 27 eyes from 25 adult patients were included. The sample size in pediatric group is small because MP-TCP was not offered to pediatric patients after unsatisfactory results in initial cases. Preoperatively, the mean intraocular pressure (IOP) was 28.41±8.32 mm Hg in adult patients and 34.28±9.92 mm Hg in pediatric patients. Postoperatively, the mean IOP in adult patients significantly decreased at all follow-up points (P<0.001). In pediatric patients, the mean IOP decreased to 20.44±13.41 mm Hg at 1 month (P=0.021), 23.56±10.10 mm Hg at 3 months (P=0.093), 23.00±8.31 mm Hg (P=0.018) at 6 months, and 27.20±15.68 mm Hg (P=0.15) at 12 months. No significant complications were noted in either group. The success rate in adults was 72.22% versus 22.22% in pediatric patients at 12 months (P=0.02). Seven of 9 pediatric patients required reoperation during the 12 months of follow-up.

Conclusions:
Micropulse transscelral cyclophotocoagulation is a safe procedure for pediatric as well as adult glaucoma patients. Its effect seems to be short lived in pediatric patients and the rate of reoperation was high.
Spontaneous Retinal Venous Pulsation in Unilateral Primary Open-angle Glaucoma With Low Intraocular Pressure
Authors: Lee EunJi , Kim Tae-Woo , Kim Jung-Ah , Kim Ji Ah , Kim Hyunjoong 
Published: August 2017

Purpose:
The aim of this study was to investigate the presence of spontaneous retinal venous pulsation (SVP) in patients with unilateral primary open-angle glaucoma (POAG) and low intraocular pressure (IOP).

Materials and Methods:
The SVP of 93 POAG patients with unilateral glaucoma and untreated IOP of ≤21 mm Hg was assessed using the movie tool of a confocal scanning laser ophthalmoscope (Spectralis HRA; Heidelberg Engineering). The frequency of SVP was compared between the glaucomatous and fellow eyes. Intereye differences in the frequency of SVP were assessed using McNemar test. A linear mixed-effect model was used to determine the factors associated with glaucomatous eyes, taking into account clustering of eyes within subjects.

Results:
Forty-five patients had SVP in both eyes and 15 had SVP in neither eye. Of the remaining 33 patients who showed SVP only in 1 eye, 31 had SVP only in the fellow eye, and 2 had SVP only in the glaucomatous eye. The SVP was significantly less prevalent in glaucomatous eyes (50.5%) than in fellow control eyes (81.7%) (P<0.001). In the linear mixed-effect model, the presence of SVP (P<0.001) and higher untreated IOP (P=0.001) were the significant predictors for glaucoma.

Conclusions:
SVP was less frequently found in glaucomatous eyes than healthy fellow eyes in unilateral POAG patients with low IOP.