Miracle-dz/UniFAR-FTUs huggingface dataset:
Ten Good Reasons for the Use of the Tellurium-Centered Anderson–Evans Polyoxotungstate in Protein Crystallography

Conspectus Protein crystallography represents at present the most productive and most widely used method to obtain structural information on target proteins and protein–ligand complexes within the atomic resolution range. The knowledge obtained in this way is essential for understanding the biology, chemistry, and biochemistry of proteins and their functions but also for the development of compounds of high pharmacological and medicinal interest. Here, we address the very central problem in protein crystallography: the unpredictability of the crystallization process. Obtaining protein crystals that diffract to high resolutions represents the essential step to perform any structural study by X-ray crystallography; however, this method still depends basically on trial and error making it a very time- and resource-consuming process. The use of additives is an established process to enable or improve the crystallization of proteins in order to obtain high quality crystals. Therefore, a more universal additive addressing a wider range of proteins is desirable as it would represent a huge advance in protein crystallography and at the same time drastically impact multiple research fields. This in turn could add an overall benefit for the entire society as it profits from the faster development of novel or improved drugs and from a deeper understanding of biological, biochemical, and pharmacological phenomena. With this aim in view, we have tested several compounds belonging to the emerging class of polyoxometalates (POMs) for their suitability as crystallization additives and revealed that the tellurium-centered Anderson–Evans polyoxotungstate [TeW6O24]6– (TEW) was the most suitable POM-archetype. After its first successful application as a crystallization additive, we repeatedly reported on TEW’s positive effects on the crystallization behavior of proteins with a particular focus on the protein–TEW interactions. As electrostatic interactions are the main force for TEW binding to proteins, TEW with its highly negative charge addresses in principle all proteins possessing positively charged patches. Furthermore, due to its high structural and chemical diversity, TEW exhibits major advantages over some commonly used crystallization additives. Therefore, we summarized all features of TEW, which are beneficial for protein crystallization, and present ten good reasons to promote the use of TEW in protein crystallography as a powerful additive. Our results demonstrate that TEW is a compound that is, in many respects, predestined as a crystallization additive. We assume that many crystallographers and especially researchers, who are not experts in this field but willing to crystallize their structurally unknown target protein, could benefit from the use of TEW as it is able to promote both the crystallization process itself and the subsequent structure elucidation by providing valuable anomalous signals, which are helpful for the phasing step.
Quantitative evaluation of the lengths of homobifunctional protein cross‐linking reagents used as molecular rulers

Homobifunctional chemical cross‐linking reagents are important tools for functional and structural characterization of proteins. Accurate measures of the lengths of these molecules currently are not available, despite their widespread use. Stochastic dynamics calculations now provide quantitative measures of the lengths, and length dispersions, of 32 widely used molecular rulers. Significant differences from published data have been found.
Effects of chronic methylphenidate in adolescence on later methylphenidate self-administration in rhesus monkeys

Many children diagnosed with attention deficit hyperactivity disorder are treated with methylphenidate (MPH), despite limited information on later vulnerability to drug abuse. A previous study in adolescent monkeys treated with MPH for 1 year did not indicate differences in acquisition to cocaine reinforcement compared with controls. The present study extended this characterization to include MPH self-administration. Adolescent male rhesus monkeys treated previously with a sustained-release formulation of MPH (beginning at ∼30 months old) and control monkeys (n=8/group) were used. All had previous experience of self-administering cocaine under a fixed-ratio 30 schedule of reinforcement. Responding was maintained by food (1.0-g banana-flavored pellets) and MPH (saline, 0.001–0.1 mg/kg/injection) was substituted for food for at least five consecutive sessions. MPH functioned as a reinforcer in all monkeys; there were no differences between groups in MPH self-administration. These findings extend earlier research with cocaine reinforcement showing that MPH treatment in adolescent monkeys does not increase future reinforcing effects of stimulant drugs.
Animal models for exploring the pharmacokinetics of breast cancer therapies

Introduction: Despite massive expenditures in research and development to cure breast cancer, few agents that pass preclinical trials demonstrate efficacy in humans. Although this endeavor relies on murine models to screen for efficacy before progressing to clinical trials, historically there has been little focus on the validation of these models, even in the era of targeted therapy where understanding the genetic signatures of tumors under study is critical. Areas covered: This review includes the transgenic, xenograft, and syngeneic murine breast cancer models, the ectopic, orthotopic and intravenous methods of cell implantation, and the ethics of animal experimentation. It also includes the latest data on tumor gene expression and the issues to consider when exploring the pharmacokinetics and efficacy of breast cancer therapies. Expert opinion: Breast cancer drug development is expensive and inefficient without a consensus preclinical murine model. Investigators must approach the choice of murine model with the same sophistication that is applied to the choice of in vitro assays to improve efficiency. Understanding the limitations of each model available, including the nuances of tumor gene signatures, is critical for investigators exploring the phamacokinetics and efficacy of breast cancer therapies, especially in the context of gene profiling and individualized targeted therapy.
Kartierung von quantitativen Resistenzloci gegen die Blatt- und Spelzenbräune (Septoria nodorum Berk.) bei Weizen (Triticum aestivum L.) mittels molekularer Marker

Die Verbesserung der quantitativen Resistenz gegen Pilzkrankheiten gehort zu den wichtigsten Zielen in der Weizenzuchtung. Die Nachkommenschaften zweier Weizen-kreuzungen wurden mittels molekularer Marker auf quantitative Merkmalsloci (QTL), welche fur eine Resistenz gegen Blatt- und Spelzenbraune (Septoria nodorum) verantwortlich sind, analysiert. Fur die Kreuzung 'Piko'×'Euris' konnten zwei QTL fur Blattresistenz auf den Chromosomen 1BS und 5DL detektiert werden, sowie zwei QTL auf 1BS und 3DS fur die Kreuzung 'Apollo'×'G18/90'. Die Einordnung der QTL auf 1BS in eine Resistenzgenfamilie, fur die Ethylen als Signalmolekul fungiert, wurde diskutiert. Die kartierten QTL bilden eine Grundlage fur die Entwicklung molekularer Marker, die als effektives Instrument zur Verbesserung der quantitativen Resistenz gegen Blatt- und Spelzenbraune im Rahmen einer markergestutzten Selektion in Weizenzuchtungsprogrammen eingesetzt werden konnen.
Oligomerization of SLC4A11 protein and the severity of FECD and CHED2 corneal dystrophies caused by SLC4A11 mutations

Mutations in the SLC4A11 gene, which encodes a plasma membrane borate transporter, cause recessive congenital hereditary endothelial corneal dystrophy type 2 (CHED2), corneal dystrophy and perceptive deafness (Harboyan syndrome), and dominant late‐onset Fuchs endothelial corneal dystrophy (FECD). We analyzed missense SLC4A11 mutations identified in FECD and CHED2 patients and expressed in transfected HEK 293 cells. Chemical cross‐linking and migration in nondenaturing gels showed that SLC4A11 exists as a dimer. Furthermore, co‐immunoprecipitation of epitope‐tagged proteins revealed heteromeric interactions between wild‐type (WT) and mutant SLC4A11 proteins. When expressed alone, FECD‐ and CHED2‐causing mutant SLC4A11 proteins are primarily retained intracellularly. Co‐expression with WT SLC4A11 partially rescued the cell surface trafficking of CHED2 mutants, but not FECD mutants. CHED2 alleles of SLC4A11 did not affect cell surface processing of WT SLC4A11. In contrast, FECD mutants reduced WT cell surface processing efficiency, consistent with dominant inheritance of FECD. The reduction in movement of WT protein to the cell surface caused by FECD SLC4A11 helps to explain the dominant inheritance of this disorder. Similarly, the failure of CHED2 mutant SLC4A11 to affect the processing of WT protein, explains the lack of symptoms found in CHED2 carriers and the recessive inheritance of the disorder. Hum Mutat 33:419–428, 2012. © 2011 Wiley Periodicals, Inc.
A Compact 57–67 GHz Bidirectional LNAPA in 65-nm CMOS Technology

The letter reports a 57-67 GHz bidirectional low-noise amplifier power amplifier (LNAPA) design. To eliminate the use of T/R switches, the bidirectional matching networks are introduced to connect LNA and PA core circuits in parallel and satisfy the isolation requirements with full consideration of input/output matching of the LNA and PA. Thus, the operation modes are simply selected by gate biasing of the LNA and PA core circuits. Fabricated in a commercial 65-nm CMOS technology, the Rx mode features peak gain of 21.5 dB with gain of > 17 dB over 57-67 GHz, NF of 6.7 dB with PDC of 39.6 mW, while Tx mode achieves peak gain of 24.5 dB with gain of > 17 dB over 57-65 GHz, PSAT of 8.4 dBm, PAE of 8.7% with PDC of 71.1 mW. The reverse isolation in both modes is better than 43 dB. The circuit occupies a compact size of 0.22 mm2.
Protocol for the Development of a Behavioral Family Lifestyle Intervention Supported by Mobile Health to Improve Weight Self-Management in Children With Asthma and Obesity

Background Asthma is the most common chronic childhood illness and is a leading cause of emergency department visits in the United States. Obesity increases the risk of poor health outcomes, reduced quality of life, and increased health care expenditures among youth with asthma. Weight loss is crucial for improving asthma outcomes in children with obesity. Our study team developed the Childhood Health and Asthma Management Program (CHAMP), a 16-session behavioral family lifestyle intervention (BFI) for school-age children with asthma and obesity and evaluated CHAMP in a randomized controlled trial compared with attention control. There were medium effect sizes favoring CHAMP for changes in body mass index z-scores, asthma control, and lung function among completers (ie, those who attended ≥9 of 16 sessions). Despite high rates of satisfaction reported by families, attendance and trial attrition were suboptimal, which raised concerns regarding the feasibility of CHAMP. Qualitative feedback from participants indicated 3 areas for refinement: (1) a less burdensome intervention modality, (2) a more individually tailored intervention experience, and (3) that interventionists can better answer health-related questions. Objective We propose to improve upon our pilot intervention by developing the Mobile Childhood Health and Asthma Management Program (mCHAMP), a nurse-delivered BFI, delivered to individual families, and supported by a mobile health (mHealth) app. This study aims to (1) identify structural components of mCHAMP and (2) develop and test the usability of our mCHAMP app. Methods Participants will be recruited from an outpatient pediatric pulmonary clinic. We will identify the structural components of mCHAMP by conducting a needs assessment with parents of children with asthma and obesity. Subsequently, we will develop and test our mCHAMP app using an iterative process that includes usability testing with target users and pediatric nurses. Results This study was funded in 2018; 13 parents of children with asthma and obesity participated in the needs assessment. Preliminary themes from focus groups and individual meetings included barriers to engaging in health-promoting behaviors, perceived relationships between asthma and obesity, facilitators to behavior change, and intervention preferences. Participatory design sessions and usability testing are expected to conclude in late 2019. Conclusions Outcomes from this study are expected to include an mHealth app designed with direct participation from the target audience and usability data from stakeholders as well as potential end users. International Registered Report Identifier (IRRID) DERR1-10.2196/13549
Upregulation of low-density lipoprotein receptor after exposure to transforming growth factor-β2 in tenon's capsule fibroblasts from patients with glaucoma.

PURPOSE The aim of this study was to investigate the dynamic alteration of a low-density lipoprotein receptor (LDLr) and its binding and uptake of LDL after exposure to transforming growth factor-β(2) (TGF-β(2)) in Tenon's capsule fibroblasts from glaucoma patients. METHODS Tenon's capsule fibroblasts obtained from patients who had undergone selective glaucoma surgery were cultured and stimulated with different concentrations (0.1-10 ng/mL) of TGF-β(2) for 1, 3, 5, and 7 days. Expression of LDLr mRNA was detected with relative quantification real-time reverse transcription-polymerase chain reaction, and expression of the corresponding protein was demonstrated with western blot. The extent of binding and uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI)-labeled LDL by GTFs was also checked. RESULTS After exposure to TGF-β(2), LDLr was upregulated at the mRNA and protein levels in a concentration-dependent and/or time-dependent manner with a peak at a concentration of 5 ng/mL TGF-β(2). Binding and uptake of LDL were time dependent, reaching saturation at the first 6 h. CONCLUSIONS This study shows that LDLr has a dose- and/or time-effect relationship with TGF-β(2) in Tenon's capsule fibroblasts from glaucoma patients. The results suggest that LDLr may play an important role in wound healing and scar formation in the activated Tenon's capsule fibroblasts from patients with glaucoma.
Management of chronic pediatric uveitis

Purpose of review The diagnosis and management of chronic pediatric uveitis can be particularly challenging, with an estimated 25-33% of childhood uveitis cases resulting in severe, life-long visual disability. This paper reviews the recent literature on the management of chronic pediatric uveitis. Recent findings This review highlights recent advances in the diagnosis and medical and surgical management of pediatric uveitis. Several systemic diseases associated with chronic uveitis in children are highlighted, including juvenile idiopathic arthritis, sarcoidosis and Behçet's disease. The treatment of primary ocular diseases associated with chronic pediatric uveitis such as intermediate uveitis and Fuchs' heterochromic iridocyclitis is discussed. The management of infectious causes of pediatric uveitis is not covered in this review. Summary Knowledge of the ocular complications of chronic pediatric uveitis can help to customize efficacious therapeutic regimens for each patient, maximize the visual potential and minimize complications of these diseases. In addition a close relation should be fostered between pediatricians, pediatric rheumatologists and ophthalmologists to effectively monitor these patients who have multiple medical, surgical and refractive needs. Finally, surgical intervention must be appropriately timed with expert perioperative management of immunosuppressive medications with pediatric concerns in mind.
The Effect of Etanercept on Cardiac Transplant Recipients: A Study of TNF&agr; Antagonism and Cardiac Allograft Hypertrophy

Cardiac allograft hypertrophy is associated with persistent expression of cardiac tumor necrosis factor (TNF)-&agr;. We investigated whether TNF&agr; antagonism would impact allograft hypertrophy. EFECT (EFfect of Etanercept on Cardiac Transplantation) was a randomized, controlled, double-blind trial evaluating the effect of etanercept versus placebo treatment immediately posttransplant. The primary end-point was change in left ventricular (LV) mass after 6 months. Secondary endpoints included degree of collagen deposition at 6 months and incidence of adverse events. Forty-nine patients were randomized to either etanercept or placebo. LV mass increased significantly in both arms at 6 months, with a smaller increase in the etanercept group (19% vs. 33%, P=ns). Myocardial collagen content increased in the placebo, but not the etanercept, group (+39.8%, P<0.08 vs. −7.0%, P=NS). Allograft hypertrophy develops posttransplant with a corresponding increase in extracellular matrix. Etanercept appeared to decrease LV hypertrophy by decreasing extracellular matrix deposition.
An Intelligent Method for Selecting and Recommending Best Players to Help Build Sports Team

Selection of Players for sports within finite budget is complex task which can be viewed as constrained multi objective optimization and multiple criteria decision making problem. To solve this problem we are proposing a system for providing an interactive sports game to a plurality of participants wherein each participant wishes to form a sports team made up of actual players with the recommendation of team to player and vice versa. General Terms Data Mining, Information Retrieval, Performance, Task, Algorithm, strategy, Academy, Self management
Microfluctuations in accommodation: an update on their characteristics and possible role

Following the recognition, some 80 years ago, that the accommodation of the eye is not stable but fluctuates over a range of about ±0.5 D, mainly at frequencies of up to a few Hz, there has been a continuing interest in the characteristics of these microfluctuations (MFs) and their possible role in the control of accommodation. This paper reviews relevant work carried out since 1988, when we previously reviewed the same topic (Charman WN, Heron G. Fluctuations in accommodation: a review. Ophthalmic Physiol Opt 1988; 8: 153–164).
Investigating the relationship between bad smells and bugs in software systems

Bad smell is a design choice that can degrade different aspects of the source code quality of a software, such as comprehensibility and changeability. Researchers believe that the occurrence of bad smells can lead to the introduction of bugs during maintenance activities. However, there are few studies concerning the impacts of bad smells. Thus, in order to provide more experimental evidence about the impacts of bad smells on software development and maintenance, we conducted an experimental study aiming at investigating the relationship between the occurrence of bad smells and the occurrence of bugs. In this study we evaluated five open-source systems from the Apache community. The results show that classes with bad smells are slightly more related to the occurrence of bugs than classes without bad smells.
A Fund-Constrained Investment Scheme for Profit Maximization in Cloud Computing

Cloud computing is becoming more and more popular and has received considerable attention recently. As a new kind of Information Technology (IT) commercial model, understanding the economics of cloud computing becomes critically important. From the cloud service providers’ perspective, profit maximization is the top issue for them. Because a multi-server system is devoted to serving one type of service requests and application, service providers should build multiple multi-server systems to satisfy the market requirements of different application domains. Because available funding for a service provider is generally limited, it cannot afford to invest in all application domains. Hence, how to select appropriate application domains for investment and allocate funding such that the total profit is maximized are important issues for service providers. To address this problem, a fund-constrained profit maximization model is proposed. However, the exact solution of this optimization model is very difficult to formulate due to its complexity. Hence, this paper presents a heuristic strategy to search for a high quality solution. In our strategy, the optimization problem is solved in four stages, and the solution is optimized gradually. Through the proposed heuristic investment strategy, an appropriate investment scheme can be developed that synthesizes the market requirement, the fund constraint, the service level agreement, and so forth. A series of numerical calculations is executed to assess the performance of the proposed strategy. Then, six other investment strategies are compared to our strategy. Our results show that the investment scheme designed using our strategy can produce much more profit than these six other strategies.
A Singular Field Method for the Solution of Maxwell's Equations in Polyhedral Domains

It is well known that in the case of a regular domain the solution of the time-harmonic Maxwell's equations allows a discretization by means of nodal finite elements: this is achieved by solving a regularized problem similar to the vector Helmholtz equation. The present paper deals with the same problem in the case of a nonconvex polyhedron. It is shown that a nodal finite element method does not approximate in general the solution to Maxwell's equations, but actually the solution to a neighboring variational problem involving a different function space. Indeed, the solution to Maxwell's equations presents singularities near the edges and corners of the domain that cannot be approximated by Lagrange finite elements.A new method is proposed involving the decomposition of the solution field into a regular part that can be treated numerically by nodal finite elements and a singular part that has to be taken into account explicitly. This singular field method is presented in various situations such as electri.
Modélisation du comportement thermomécanique d'un alliage à mémoire de forme à base de fer type Fe-Mn-Si

Il est bien connu que les alliages a memoire de forme (AMF) sont consideres comme une classe particuliere de materiaux qui peuvent retrouver une forme prealablement definie par simple chauffage. Cette propriete remarquable, appelee effet memoire de forme, peut etre exploitee dans la conception d'applications originales afin de trouver les solutions interessantes aux problemes rencontres dans divers champs industriels. Dans notre travail, nous proposons une loi constitutive tridimensionnelle thermomecanique adaptee aux alliages a memoire de forme a base de fer. Elle tient compte de l'effet de la transformation martensitique et des mecanismes de glissement plastique et leurs interactions. La formulation adoptee est basee sur une description micromecanique simplifiee. La comparaison entre les forces motrices et les forces critiques d'activation des mecanismes mis en jeu nous ont permis de determiner le type de comportement induit pour un niveau de chargement donne. Nous avons adopte le schema implicite d'integration de Newton-Raphson pour la resolution de ce systeme. Les resultats obtenus pour des chargements thermomecaniques sont compares a ceux obtenus experimentalement.