bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative Evolutionary Pathways for Drug-Resistant Small Colony Variant Mutants in
Staphylococcus aureus
Authors: Cao Sha , Huseby Douglas L. , Brandis Gerrit , Hughes Diarmaid 
Published: June 2017

ABSTRACT

Staphylococcus aureus
is known to generate small colony variants (SCVs) that are resistant to aminoglycoside antibiotics and can cause persistent and recurrent infections. The SCV phenotype is unstable, and compensatory mutations lead to restored growth, usually with loss of resistance. However, the evolution of improved growth, by mechanisms that avoid loss of antibiotic resistance, is very poorly understood. By selection with serial passaging, we isolated and characterized different classes of extragenic suppressor mutations that compensate for the slow growth of small colony variants. Compensation occurs by two distinct bypass mechanisms: (i) translational suppression of the initial SCV mutation by mutant tRNAs, ribosomal protein S5, or release factor 2 and (ii) mutations that cause the constitutive activation of the SrrAB global transcriptional regulation system. Although compensation by translational suppression increases growth rate, it also reduces antibiotic susceptibility, thus restoring a pseudo-wild-type phenotype. In contrast, an evolutionary pathway that compensates for the SCV phenotype by activation of SrrAB increases growth rate without loss of antibiotic resistance. RNA sequence analysis revealed that mutations activating the SrrAB pathway cause upregulation of genes involved in peptide transport and in the fermentation pathways of pyruvate to generate ATP and NAD
+
, thus explaining the increased growth. By increasing the growth rate of SCVs without the loss of aminoglycoside resistance, compensatory evolution via the SrrAB activation pathway represents a threat to effective antibiotic therapy of staphylococcal infections.

IMPORTANCE
Small colony variants (SCVs) of
Staphylococcus aureus
are a significant clinical problem, causing persistent and antibiotic-resistant infections. However, SCVs are unstable and can rapidly evolve growth-compensated mutants. Previous data suggested that growth compensation only occurred with the loss of antibiotic resistance. We have used selection with serial passaging to uncover four distinct pathways of growth compensation accessible to SCVs. Three of these paths (reversion, intragenic suppression, and translational suppression) increase growth at the expense of losing antibiotic resistance. The fourth path activates an alternative transcriptional program and allows the bacteria to produce the extra ATP required to support faster growth, without losing antibiotic resistance. The importance of this work is that it shows that drug-resistant SCVs can evolve faster growth without losing antibiotic resistance.
POEMS syndrome: a rare cause of exudative ascites and chronic peripheral neuropathy
Authors: Al-Mayoof Omar , AL Sughaiyer Hana , Abuomar Wuroud , Khan Maria 
Published: June 2017

POEMS syndrome (Peripheral neuropathy, Organomegaly, Endocrinopathy, M protein, Skin changes) is a rare plasma cell disorder with multisystem involvementA 40-year-old man with a chronic history of unexplained peripheral neuropathy , presented with exudative ascites.He was found to have an incidental osteolytic lesion of the sacrum proven to be a plasmacytoma. Immunoelectrophoresis for monoclonal protein was negative.In addition, the patient was found to have hepatosplenomegaly, erectile dysfunction, hyperprolactinaemia and hypothyroidism.The patient, was given steroid along with lenalidomide, and showed a good clinical response.
Rapid Detection of the mt3243A > G Mutation Using Urine Sediment in Elderly Chinese Type 2 Diabetic Patients
Authors: Zhang Yinan , Du Xiujuan , Geng Xinqian , Chu Chen , Lu Huijuan , Shen Yixie , Chen Ruihua , Fang Pingyan , Feng Yanmei , Zhang Xiaojie , Chen Yan , Zhou Yanping , Wang Congrong , Jia Weiping 
Published: June 2017

Objective. In this study, we aimed to identify mt3243A > G mutation carriers in a group of Chinese elderly type 2 diabetic patients by a rapid and noninvasive diagnostic system. Methods. DNA was extracted from blood, saliva, and urine sediment samples. The mutation screening and quantitation of heteroplasmy were performed by high-resolution melting (HRM) curve and pyrosequencing, respectively. Patients with mt3243A > G mutation underwent a detailed audiometric, ophthalmologic, neurological, and cardiac examination. Results. Two patients (2/1041) carrying the mt3243A > G mutation were detected among all type 2 diabetic patients. In patient 1, the heteroplasmy was 0.8%, 2.8%, and 14.7% in peripheral blood leukocytes, saliva, and urine sediment, respectively. In patient 2, the heteroplasmy was 5.3%, 8.4%, and 37.7% in peripheral blood leukocytes, saliva, and urine sediment, respectively. Both of the two patients showed hearing impairment. Abnormal ophthalmologic conditions and hyperintensity on T2-weighted magnetic resonance images were showed in patient 1. Conclusion. The occurrence of mt3243 A > G mutation was 0.2% in Chinese elderly type 2 diabetic patients. Moreover, detection of mt3243 A > G mutation in urine sediment with high-resolution melting (HRM) curve and pyrosequencing is feasible in molecular genetic diagnosis.
The association between apolipoprotein A1-C3-A5 gene cluster promoter polymorphisms and risk of ischemic stroke in the northern Chinese Han population
Authors: Wang Yanzhe , Liu Fang , Li Lei , Deng Shumin , He Zhiyi 
Published: June 2017

Objective Given its effects on lipid metabolism, the apolipoprotein A1-C3-A5 ( APOA1-C3-A5) gene cluster is thought to play an important role in ischemic stroke pathogenesis. Here, we evaluated whether the APOA1-C3-A5 cluster is associated with ischemic stroke in the northern Chinese Han population. Methods This case–control study analyzed 812 patients with ischemic stroke and 844 healthy controls with regard to four APOA1-C3-A5 cluster promoter single nucleotide polymorphisms (SNPs), rs670, rs2854116, rs2854117, and rs662799, using the SNaPshot Multiplex sequencing assay. Potential associations among ischemic stroke, genotyping, and allele frequencies were assessed. Results APOA1 rs670 CT/TT genotypes, APOA5 rs662799 AG/GG genotypes, and the APOC3 rs2854116 CC genotype were associated with an increased risk of ischemic stroke according to multivariate logistic analysis after adjusting for confounding factors. A significantly increased risk for ischemic stroke was also identified among high-risk haplotypes (C-C-T-A and T-T-C-A) for rs670–rs2854116–rs2854117–rs662799. Conclusion This study showed that rs670, rs2854116, and rs662799 SNPs of the APOA1-C3-A5 cluster are associated with ischemic stroke in the northern Chinese Han population.
Barriers and facilitators of participation in intervention research by mental health occupational therapists
Authors: Birken Mary , Couch Elyse , Morley Mary 
Published: June 2017

Statement of context Occupational therapists in clinical practice are required to deliver interventions within clinical trials to demonstrate the effectiveness of occupational therapy interventions. Challenges to participation in intervention research by occupational therapists working in community mental health have been identified and require further investigation. Critical reflection on practice A cross-sectional online survey of occupational therapists working in mental health was used, and obtained a 50% ( n = 144) response rate. Limited time, large generic caseloads, and lack of skills and experience in research were identified barriers to participation in occupational therapy intervention research. Occupational therapists had limited dedicated time to carry out occupational therapy interventions and outcome measurement was limited. Implications for practice Occupational therapy roles need to be regained in adult community mental health alongside routine outcome measurement. This will enable occupational therapy interventions to contribute to community mental health services and support participation in clinical trials of occupational therapy interventions.
Quality dementia care: Prerequisites and relational ethics among multicultural healthcare providers
Authors: Sellevold Gerd Sylvi , Egede-Nissen Veslemøy , Jakobsen Rita , Sørlie Venke 
Published: June 2017

Background: Many nursing homes appear as multicultural workplaces where the majority of healthcare providers have an ethnic minority background. This environment creates challenges linked to communication, interaction and cultural differences. Furthermore, the healthcare providers have varied experiences and understanding of what quality care of patients with dementia involves. Purpose: The aim of this study is to illuminate multi-ethnic healthcare providers’ lived experiences of their own working relationship, and its importance to quality care for people with dementia. Research design: The study is part of a greater participatory action research project: ‘Hospice values in the care for persons with dementia’. The data material consists of extensive notes from seminars, project meetings and dialogue-based teaching. The text material was subjected to phenomenological-hermeneutical interpretation. Participants and research context: Participants in the project were healthcare providers working in a nursing home unit. The participants came from 15 different countries, had different formal qualifications, varied backgrounds and ethnic origins. Ethical considerations: The study is approved by the Norwegian Regional Ethics Committee and the Norwegian Social Science Data Services. Findings: The results show that good working relationships, characterized by understanding each other’s vulnerability and willingness to learn from each other through shared experiences, are prerequisites for quality care. The healthcare providers further described ethical challenges as uncertainty and different understandings. Discussion: The results are discussed in the light of Lögstrup’s relational philosophy of ethics and the concepts of vulnerability, ethic responsibility, trust and openness of speech. Conclusion: The prerequisite for quality care for persons with dementia in a multicultural working environment is to create arenas for open discussions between the healthcare providers. Leadership is of great importance.
Acute Testosterone Deficiency Alters Adipose Tissue Fatty Acid Storage
Authors: Santosa Sylvia , Bush Nikki C , Jensen Michael D 
Published: June 2017

AbstractContextAlthough the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood.ObjectiveWe examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms.DesignThis was a prospective, randomized trial.SettingMayo Clinic Clinical Research Unit.Patients or ParticipantsThirty-two male volunteers ages 18 to 50 participated in these studies.InterventionsVolunteers were randomized to receive (1) no treatment (control), (2) injections (7.5 mg) of Lupron®, or (3) Lupron and testosterone (L+T) replacement for 49 days, resulting in 4 weeks of sex steroid suppression in the Lupron group.Main Outcome MeasuresWe measured body composition, fat cell size, adipose tissue meal FA and direct free FA storage, lipoprotein lipase (LPL), acyl coenzyme A synthetase (ACS), diacylglycerol acyltransferase activities, and CD36 content.ResultsCompared with control and L+T groups, acute testosterone deficiency resulted in greater femoral adipose tissue meal FA storage rates, fasting and fed LPL activity, and ACS activity.ConclusionsThese results suggest that in men, testosterone plays a tonic role in restraining FA storage in femoral adipose tissue via suppression of LPL and ACS activities. FA storage mechanisms in men appear sensitive to short-term changes in testosterone concentrations.
Branch-and-Price-and-Cut for the Active-Passive Vehicle-Routing Problem
Authors: Tilk Christian , Bianchessi Nicola , Drexl Michael , Irnich Stefan , Meisel Frank 
Published: June 2017

This paper presents a branch-and-price-and-cut algorithm for the exact solution of the active-passive vehicle-routing problem (APVRP). The APVRP covers a range of logistics applications where pickup-and-delivery requests necessitate a joint operation of active vehicles (e.g., trucks) and passive vehicles (e.g., loading devices such as containers or swap bodies). The objective is to minimize a weighted sum of the total distance traveled, the total completion time of the routes, and the number of unserved requests. To this end, the problem supports a flexible coupling and decoupling of active and passive vehicles at customer locations. Accordingly, the operations of the vehicles have to be synchronized carefully in the planning. The contribution of the paper is twofold: First, we present an exact branch-and-price-and-cut algorithm for this class of routing problems with synchronization constraints. To our knowledge, this algorithm is the first such approach that considers explicitly the temporal interdependencies between active and passive vehicles. The algorithm is based on a nontrivial network representation that models the logical relationships between the different transport tasks necessary to fulfill a request as well as the synchronization of the movements of active and passive vehicles. Second, we contribute to the development of branch-and-price methods in general, in that we solve, for the first time, an ng-path relaxation of a pricing problem with linear vertex costs by means of a bidirectional labeling algorithm. Computational experiments show that the proposed algorithm delivers improved bounds and solutions for a number of APVRP benchmark instances. It is able to solve instances with up to 76 tasks, four active, and eight passive vehicles to optimality within two hours of CPU time. The online appendix is available at https://doi.org/10.1287/trsc.2016.0730 .
Computational methods in preformulation study for pharmaceutical solid dosage forms of therapeutic proteins
Authors: Majee Sutapa Biswas , Biswas Gopa Roy 
Published: June 2017

AbstractDesign and delivery of protein-based biopharmaceuticals needs detailed planning and strict monitoring of intermediate processing steps, storage conditions and container-closure system to ensure a stable, elegant and biopharmaceutically acceptable dosage form. Selection of manufacturing process variables and conditions along with packaging specifications can be achieved through properly designed preformulation study protocol for the formulation. Thermodynamic stability and biological activity of therapeutic proteins depend on folding–unfolding and three-dimensional packing dynamics of amino acid network in the protein molecule. Lack of favourable environment may cause protein aggregation with loss in activity and even fatal immunological reaction. Although lyophilization can enhance the stability of protein-based formulations in the solid state, it can induce protein unfolding leading to thermodynamic instability. Formulation stabilizers such as preservatives can also result in aggregation of therapeutic proteins. Modern instrumental techniques in conjunction with computational tools enable rapid and accurate prediction of amino acid sequence, thermodynamic parameters associated with protein folding and detection of aggregation “hot-spots.” Globular proteins pose a challenge during investigations on their aggregation propensity. Biobetter therapeutic monoclonal antibodies with enhanced stability, solubility and reduced immunogenic potential can be designed through mutation of aggregation-prone zones. The objective of the present review article is to focus on the various analytical methods and computational approaches used in the study of thermodynamic stability and aggregation tendency of therapeutic proteins, with an aim to develop optimal and marketable formulation. Knowledge of protein dynamics through application of computational tools will provide the essential inputs and relevant information for successful and meaningful completion of preformulation studies on solid dosage forms of therapeutic proteins.
Simple Expression Domains Are Regulated by Discrete CRMs During Drosophila Oogenesis
Authors: Revaitis Nicole T , Marmion Robert A , Farhat Maira , Ekiz Vesile , Wang Wei , Yakoby Nir 
Published: June 2017

Abstract
Eggshell patterning has been extensively studied in Drosophila melanogaster. However, the cis-regulatory modules (CRMs), which control spatiotemporal expression of these patterns, are vastly unexplored. The FlyLight collection contains &gt;7000 intergenic and intronic DNA fragments that, if containing CRMs, can drive the transcription factor GAL4. We cross-listed the 84 genes known to be expressed during D. melanogaster oogenesis with the ∼1200 listed genes of the FlyLight collection, and found 22 common genes that are represented by 281 FlyLight fly lines. Of these lines, 54 show expression patterns during oogenesis when crossed to an UAS-GFP reporter. Of the 54 lines, 16 recapitulate the full or partial pattern of the associated gene pattern. Interestingly, while the average DNA fragment size is ∼3 kb in length, the vast majority of fragments show one type of spatiotemporal pattern in oogenesis. Mapping the distribution of all 54 lines, we found a significant enrichment of CRMs in the first intron of the associated genes’ model. In addition, we demonstrate the use of different anteriorly active FlyLight lines as tools to disrupt eggshell patterning in a targeted manner. Our screen provides further evidence that complex gene patterns are assembled combinatorially by different CRMs controlling the expression of genes in simple domains.
Speaker Identification in Whisper
Authors: Foulkes Paul , Smith India , Sóskuthy Márton 
Published: June 2017

Sociophonetic methods and findings have value in application to real-life issues, including providing expert forensic evidence in legal cases. Forensic cases often involve voices which differ markedly from those typically encountered in laboratory or field studies. We assess the ability of people to identify familiar voices produced in whisper, a commonly used form of disguise. Members of a pre-existing social network were recorded speaking normally and in whisper. Speakers found it difficult to maintain whisper beyond 30 seconds. They and other members of the group listened to extracts that were (i) short and whispered, (ii) long and whispered, and (iii) short and normal (non-whispered). Foils were also included. Performance was well above chance, and improved significantly in conditions (ii) and (iii). Differences were found across listeners and voices. The study emphasises how important is it not to overgeneralise from experimental data to a witness’s ability under forensic conditions.********************************************************************Identificação de falante a partir de fala sussurradaResumo: Os métodos e achados sociofonéticos são valiosos para aplicação a questões da vida real, como no fornecimento de evidência forense pericial em casos legais. Os casos forenses envolvem vozes que se diferem marcadamente daquelas tipicamente encontradas em laboratório ou estudos de campo. Avaliamos a habilidade de pessoas de identificar vozes familiares produzidas de forma sussurrada, uma estratégia de disfarce comumente utilizada. Membros de uma rede social pré-existente foram gravados falando normalmente e de forma sussurrada. Os falantes consideraram difícil manter o sussurro por mais do que 30 segundos. Esses falantes e outros membros do grupo ouviram trechos que foram (i) curtos e sussurrados; (ii) longos e sussurrados e (iii) curtos e normais (não sussurrados). Distratores foram incluídos. A performance foi bem acima do acaso e melhorou significativamente nas condições (ii) e (iii). Diferenças foram encontradas entre falantes e vozes. O estudo enfatiza o quanto é importante não supergeneralizar a partir de dados experimentais quanto à habilidade da testemunha sob condições forenses.Palavras-chave: Sociofonética; Fonética Forense; Sussurro
О 4-квазипланарных отображениях полукватернионных многообразий
Authors: Kurbatova Irina 
Published: June 2017

Ранее мы ввели в рассмотрение понятие полукватернионной структуры на пространстве аффинной связности, порожденной парой почти комплексных структур, коммутирующих друг с другом. Мы также исследовали 4-квазипланарные отображения пространств аффинной связности с полукватернионными структурами при различных условиях дифференциального характера. В настоящей статье продолжается изучение 4-квазипланарных отображений полукватернионных келеровых пространств. Строятся геометрические объекты, инвариантные относительно рассматриваемых отображений. Выделен класс полукватернионных келеровых пространств (4-квзиплоские), допускающих 4-квазипланарное отображение на плоское пространство. Получен их тензорный признак. Доказано, что любое 4-квазиплоское полукватернионное келерово пространтво допускает нетривиальные 4-квазипланарные отображения (это аналог теоремы Бельтрами в теории геодезических отображений римановых пространств). Показано, что 4-квазиплоское полукватернионное келерово пространство представляет собой прямое произведение двух келеровых пространств постоянной голоморфной кривизны.
How to use Voluntary, Self-Regulatory and Alernative Environmental Compliance Tools: Some Lessons Learnt
Authors: Nel Johan N , Wessels Jan-Albert 
Published: June 2017

A number of alternative environmental enforcement tools are available that may be used to enhance the environmental enforcement effort in South Africa. Current debate focuses on which tools work effectively and the reasons for their success. The debate is however dominated by issues concerning policy challenges, such as the adoption of alternative tools and necessary arrangements to ensure these tools contribute to overall environmental enforcement performance. In order to contribute to the debate and stimulate further debate, this article offers a typology of alternative enforcement tool categories, lists the generally argued benefits and disadvantages of both command and control approaches and alternative enforcement tools, offers framework conditions for the successful adoption and use of some of the enforcement tools, and explores empirical and other evidence to determine whether environmental management systems are adequately able to drive sustained and consistent legal compliance. A South African case study is also presented to illustrate the manner in which a combination of alternative enforcement tools may be integrated with command and control tools to ensure consistent and sustained legal compliance.
Uso de la descomposición TOEPLITZ en la estratificación de matrices
Authors: Gómez Plata Adrián Ricardo 
Published: June 2017

Las matrices Normales N son una subvariedad estratificada en forma de estrella de R^[(2n)^2]; se prefiere para propósitos prácticos, tener en forma concreta como es la estratificación de algunas matrices. Se presentará aquí algunos teoremas que permiten decantar una estratificación de las matrices Normales hecha por medio de la descomposición de Toeplitz y que conlleva a realizar el cálculo de valores propios usando el método Hermitiano de Lanczos o el método de Arnoldo según Huthanen [4].