Miracle-dz/UniFAR-FTUs huggingface dataset:
Current application of mass spectrometry to combinatorial chemistry.

During the past decade, combinatorial chemistry has become an integral component of nearly all drug discovery efforts (1-4). Mass spectrometry (MS) has played a key role in the advancement of combinatorial chemistry efforts: in reaction monitoring and optimization of library synthesis, in the purification of libraries synthesized in a parallel format, and in the assessment of library compound quality, as well as in screening for bioaffinity or pharmaceutical properties of the above. A number of useful books or book chapters (5-8) and review articles (9-18) have been published recently on the application of mass spectrometry to combinatorial chemistry. A few words about the scope of this review article. As nearly all of the pharmaceutical industry now synthesizes and screens single pure entities generated in a parallel format as opposed to combinatorial mixtures (19), this review will deal primarily with parallel synthesis applications. Classical combinatorial libraries made with one-bead-one-compound or split synthesis methods are not reviewed here as efforts in this area are only minimally continued at present. For the interested reader, good recent reviews can be found encompassing the mixture library analysis by MS (5-16, 18). Further, as the vast majority of combinatorial libraries currently being synthesized are small organic molecules (20), this review will not include efforts in peptide and oligonucleotide library synthesis. Relevant references on the analysis of oligomer libraries can be found in reviews (5-16, 18). Small-molecule libraries synthesized in the parallel format may be those directed toward either lead discovery or lead optimization and may be synthesized either on a solid support or in solution. The large numbers of discrete compounds generated require analysis and, most frequently purification. This review will focus upon how mass spectrometry assists in those efforts. High-performance liquid chromatography (HPLC) is an important tool in the analysis and purification of discrete library compounds, often coupled with mass spectrometry (LC/MS). For the interested reader, a good review (21) of HPLC, including equipment, columns, and detectors, is available by LaCourse. A list of abbreviations used in this review may be found at the end of the article.
EFFICIENCY OF PHARMACEUTICAL CONSUMPTION IN TURKEY: BENCHMARKING WITH OECD BY DEA

After 1980s, consumers begin to focus more health-conscious behaviours and attitudes including the concept of consuming pharmaceutical products. Pharmaceutical consumption attitude is a natural outcome of this trend. In this research, it is aimed to analyze Turkey’s benchmarking position among OECD countries in terms of pharmaceutical consumption efficiency. 15 OECD countries’ 5 years (2008-2012) analyzed by DEA-Malmquist TFP with the output-oriented and variable returns to scale methods. TC index shows that Turkey had created more pharmaceutical consumption and longer life expectancy by using same amount of number of physicians, number of pharmacists, total public and private health insurance expenditures and number of doctor consultations. By the way, Turkey had embraced efficiency growth with the rate of 0.4 percent. However, total efficiency level of Turkey got damaged by reason of its administrative limitations.
Development and Testing of a Multidimensional iPhone Pain Assessment Application for Adolescents with Cancer

Background Pain is one of the most common and distressing symptoms reported by adolescents with cancer. Despite advancements in pain assessment and management research, pain due to cancer and/or its treatments continues to be poorly managed. Our research group has developed a native iPhone application (app) called Pain Squad to tackle the problem of poorly managed pain in the adolescent with cancer group. The app functions as an electronic pain diary and is unique in its ability to collect data on pain intensity, duration, location, and the impact pain has on an adolescent’s life (ie, relationships, school work, sleep, mood). It also evaluates medications and other physical and psychological pain management strategies used. Users are prompted twice daily at configurable times to complete 20 questions characterizing their pain and the app transmits results to a database for aggregate reporting through a Web interface. Each diary entry represents a pain case filed by an adolescent with cancer and a reward system (ie, moving up through law-enforcement team ranks, built-in videotaped acknowledgements from fictitious officers) encourages consistent use of the diary. Objective Our objective was to design, develop, and test the usability, feasibility, compliance, and satisfaction of a game-based smartphone pain assessment tool for adolescents with cancer. Methods We used both low- and high-fidelity qualitative usability testing with qualitative semi-structured, audio-taped interviews and iterative cycles to design and refine the iPhone based Pain Squad app. Qualitative thematic analysis of interviews using constant comparative methodology captured emergent themes related to app usability. Content validity was assessed using question importance-rating surveys completed by participants. Compliance and satisfaction data were collected following a 2-week feasibility trial where users were alarmed to record their pain twice daily on the app. Results Thematic analysis of usability interviews showed the app to be appealing overall to adolescents. Analyses of both low- and high-fidelity testing resulted in minor revisions to the app to refine the theme and improve its usability. Adolescents resoundingly endorsed the game-based nature of the app and its virtual reward system. The importance of app pain diary questions was established by content validity analysis. Compliance with the app, assessed during feasibility testing, was high (mean 81%, SD 22%) and adolescents from this phase of the study found the app likeable, easy to use, and not bothersome to complete. Conclusions A multifaceted usability approach demonstrated how the Pain Squad app could be made more appealing to children and adolescents with cancer. The game-based nature and built-in reward system of the app was appealing to adolescents and may have resulted in the high compliance rates and satisfaction ratings observed during clinical feasibility testing.
Associations between distinct pre‐mRNA splicing components and the cell nucleus.

SC‐35 is a non‐snRNP spliceosome component that is specifically recognized by the anti‐spliceosome monoclonal antibody alpha SC‐35. In this paper we provide direct evidence that SC‐35 is an essential splicing factor and we examine the immunolocalization of SC‐35 by confocal laser scanning microscopy and by electron microscopy. We have found that the speckled staining pattern observed by fluorescence microscopy corresponds to structures previously designated as interchromatin granules and perichromatin fibrils. Although snRNP antigens are also concentrated in these nuclear regions, we show that the two types of spliceosome components are localized through different molecular interactions: The distribution of SC‐35 was not affected by treatment with DNase I or RNase A, or when the cells were heat shocked. In contrast, snRNP antigens become diffusely distributed after RNase A digestion or heat shock. Examination of cells at different stages of mitosis revealed that the SC‐35 speckled staining pattern is lost during prophase and speckles containing SC‐35 begin to reform in the cytoplasm of anaphase cells. In contrast, snRNP antigens do not associate with speckled regions until late in telophase. These studies reveal a dynamic pattern of assembly and disassembly of the splicing factor SC‐35 into discrete nuclear structures that colocalize with interchromatin granules and perichromatin fibrils. These subnuclear regions may therefore be nuclear organelles involved in the assembly of spliceosomes, or splicing itself.
A physically-based behavioral snapback model

This paper presents an accurate and robust model for snapback in ESD clamps. Impact ionization, which triggers snapback, takes time to occur; our model introduces a behavioral time-dependent low resistance on-state current that, like real devices, smoothly and continuously turns on and off, thereby eliminating convergence issues during simulation.
Implications of Minimizing Trauma During Conventional Cochlear Implantation

Objective: To describe the relationship between implantation-associated trauma and postoperative speech perception scores among adult and pediatric patients undergoing cochlear implantation using conventional length electrodes and minimally traumatic surgical techniques. Study Design: Retrospective chart review (2002-2010). Setting: Tertiary academic referral center. Patients: All subjects with significant preoperative low-frequency hearing (≤70 dB HL at 250 Hz) who underwent cochlear implantation with a newer generation implant electrode (Nucleus Contour Advance, Advanced Bionics HR90K [1J and Helix], and Med El Sonata standard H array) were reviewed. Intervention(s): Preimplant and postimplant audiometric thresholds and speech recognition scores were recorded using the electronic medical record. Main Outcome Measure(s): Postimplantation pure tone threshold shifts were used as a surrogate measure for extent of intracochlear injury and correlated with postoperative speech perception scores. Results: Between 2002 and 2010, 703 cochlear implant (CI) operations were performed. Data from 126 implants were included in the analysis. The mean preoperative low-frequency pure-tone average was 55.4 dB HL. Hearing preservation was observed in 55% of patients. Patients with hearing preservation were found to have significantly higher postoperative speech perception performance in the CI-only condition than those who lost all residual hearing. Conclusion: Conservation of acoustic hearing after conventional length cochlear implantation is unpredictable but remains a realistic goal. The combination of improved technology and refined surgical technique may allow for conservation of some residual hearing in more than 50% of patients. Germane to the conventional length CI recipient with substantial hearing loss, minimizing trauma allows for improved speech perception in the electric condition. These findings support the use of minimally traumatic techniques in all CI recipients, even those destined for electric-only stimulation.
Outage Analysis of Practical FSO/RF Hybrid System With Adaptive Combining

Hybrid free-space optical (FSO)/radio-frequency (RF) systems have emerged as a promising solution for high-data-rate wireless transmission. We present and analyze a transmission scheme for the hybrid FSO/RF communication system based on adaptive combining. Specifically, only FSO link is active as long as the instantaneous signal-to-noise ratio (SNR) at the FSO receiver is above a certain threshold level. When it falls below this threshold level, the RF link is activated along with the FSO link and the signals from the two links are combined at the receiver using a dual-branch maximal ratio combiner. Novel analytical expression for the cumulative distribution function (CDF) of the received SNR for the proposed hybrid system is obtained. This CDF expression is used to study the system outage performance. Numerical examples are presented to compare the outage performance of the proposed hybrid FSO/RF system with that of the FSO-only and RF-only systems.
Obstinate thrombosis during percutaneous coronary intervention in a case with heparin‐induced thrombocytopenia with thrombosis syndrome successfully treated by argatroban anticoagulant therapy

We describe a case of massive coronary thrombus after the coronary stenting due to heparin‐induced thrombocytopenia with thrombosis syndrome (HITTS). Only argatroban was able to resolve the thrombus. This is the first case in which argatroban successfully treated massive thrombus during percutaneous coronary intervention in a patient with HITTS. Cathet Cardiovasc Intervent 2003;59:351–354. © 2003 Wiley‐Liss, Inc.
Joint L 1 and Total Variation Regularization for Magnetic Detection Electrical Impedance Tomography

─ Magnetic detection electrical impedance tomography (MDEIT) is an imaging modality that aims to compute the cross-sectional distribution of the conductivity of a volume from the magnetic flux density surrounding the object. Owing to the Biot-Savart law, the MDEIT inverse problem is inherently ill-conditioned making image reconstruction highly susceptible to the effects of noise and numerical errors. Appropriate priors or penalties are needed to facilitate reconstruction and to restrict the search space to a specific solution set. The images have the sparsity property and sharp variations. Consequently, this paper presents an approach involving a combination of the L and total variation norm penalties, the former to suppress spurious background signals and enforce sparsity and the latter to preserve local smoothness and piecewise constancy in the MDEIT reconstructed images. The primal dual-interior point method (PD-IPM) for minimizing the joint L–TV penalty was used in the paper. The method was validated by using MDEIT simulated data and experimental data in comparison with the performances of the L, L and total variation norm penalty-based approaches. The results show that the joint L–TV regularized algorithm preserves sparsity property, local smoothness and piecewise constancy, leading to improvements in the localization of the reconstructed images in MDEIT. Index Terms ─ Inverse problem, joint regularization, L norm, magnetic detection electrical impedance tomography, total variation.
Leishmania pifanoi Pathogenesis: Selective Lack of a Local Cutaneous Response in the Absence of Circulating Antibody

ABSTRACT Recently, a role for B cells in the pathogenesis associated with infection by Leishmania (Leishmania mexicana complex and L. donovani) has been established. In the case of L. mexicana complex parasites (L. mexicana, L. pifanoi, and L. amazonensis), a critical role for immunoglobulin G-mediated mechanisms for the amastigote stage in the host is evident; however, the immunological mechanisms involved remain to be established. In vitro analysis of the kinetics of parasite uptake by macrophages failed to indicate a major effect of antibody opsonization. Given the importance of CD4+ T cells in the development of disease caused by these parasites, the possibility that the lack of pathogenesis was due to the lack of development of an immune response at the local site (draining lymph node and/or cutaneous site) was explored. Interestingly, the level of CD4+-T-cell activation (proliferation and cytokine) in draining lymph nodes from mice lacking circulating antibody (resistant) was found to be comparable to that in nodes from wild-type mice (susceptible) at 2, 5, and 10 weeks postinfection. However, antibody-deficient animals had markedly reduced numbers of monocytes and lymphocytes recruited or retained at the site of cutaneous infection in comparison to wild-type mice, indicating a selective impairment in the local cutaneous immune response. In vitro antigen presentation studies employing tissue-derived (opsonized) amastigotes demonstrated that L. pifanoi-infected FcR−/− macrophages, in contrast to comparably infected wild-type cells, failed to activate Leishmania antigen-specific T lymphocytes. These data, taken together, suggest that one possible mechanism for the role of antibody in pathogenesis may be to mediate parasite uptake and regulate the immune response at the local cutaneous site of infection.
A best practice framework for training UK construction site managers

Training has long been recognised as one of the fundamental processes to assist the UK construction industry meet the increasing the demand for adequately trained and qualified construction site managers. However, inadequate commitment by organisations to training, coupled with the recognised fragmentation of the industry perpetuates major hurdles to achieving this objective. Whilst the site manager's role has evolved over the years through changes within the industry, their training at the industry level continue to be provided along the established mode offered by the Chartered Institute of Building's Certificate and Diploma Site Management training (CIOB C/DSM) and the National/Scottish Vocational Qualifications Site Supervision and Site Management (NVQ/SVQ SS/SM) training schemes. This have led critics to argue that the difficulties of meeting the industry's need for trained site managers are associated with inadequacies within the training provisions offered by these schemes. This research was undertaken in recognition for the need for a critical appraisal of their training provisions with a view for improvements. It was developed on the concepts of training best practice which advocates improving the training provisions concurrent with change through the process of re-learning the whole training process. The effectiveness of the training provisions offered by the training schemes and the impact of variables on the site managers' training needs were critically investigated. 'Gaps' within the training provisions were identified, approaches to bridge these 'gaps' were investigated and proposed for improvement. The substantial contribution of the research is the expansion of the knowledge of the factors that impinge on the effective provisions for training site managers. The research findings propounds the conviction that the current training provisions needs to be expanded to be more effective and this can be achieved with the best practice framework for training site managers identified by the research.
Microbe‐induced cytoplasmic incompatibility as a mechanism for introducing transgenes into arthropod populations

Many arthropods are infected with maternally transmitted, intracellular bacteria of the genus Wolbachia. These infections often produce ‘cytoplasmic incompatibility’ (CI)—reduced egg‐hatch frequencies when uninfected females mate with infected males or when males and females carrying different Wolbachia strains mate. Because infected females often enjoy a fitness advantage—they are effectively immune to any effects from males carrying the same Wolbachia strain—Wolbachia and associated cytoplasmic elements can spread rapidly through natural populations. Wolbachia might therefore drive transgenes associated with disease control or pest abatement into populations. In this paper, simple mathematical analyses are presented of three alternative strategies for ‘CI drive’. The analyses reveal which parameters must be estimated in order to predict population dynamics, and they demonstrate stringent requirements for initially driving and/or maintaining transgenes in target populations.
Regulation of bacterial oxidative stress genes.

INTRODUCTION: REACTIVE OXYGEN AND ITS BIOLOGICAL EFFECTS . 3 16 Active Oxygen . 3 16 Molecular and Cellular Damage by Oxygen Radicals . 317 RESPONSES TO OXIDATIVE STRESS: PHySIOLOGy. 317 Hydrogen Peroxide Response. 318 Superoxide Response . 318 Stationary Phase/Starvation Proteins . 319 OXIDATIVE STRESS REGULONS . 320 H202 Response: The oxyR Regulon . 320 Superoxide Response: The soxRS Regulon . 320 Stationary Phase/Starvation: The katF Regulon . 323 soxQ: Redox Stress and Antibiotic Resistance . 324 CONTROL MECHANISMS . 324 Gene A ctivation by the OxyR Protein . 325 SoxR and SoxS: Two Proteins in Positive Control . 326 KatF: An A lternative Sigma Factor? 328 soxQlcfxB and marA: Genes in a Complex Regulatory Locus. 328 EVOLUTIONARY CONSIDERATIONS . 329 The Role of Responses to Oxidative Stress . 329 Integration of Cellular Responses . 329 Positive Control . 331 Generality of Oxidative Stress Responses . 331 OVERVIEW. 332
The growth speed of microtubules with XMAP215-coated beads coupled to their ends is increased by tensile force

The generation of pulling and pushing forces is one of the important functions of microtubules, which are dynamic and polarized structures. The ends of dynamic microtubules are able to form relatively stable links to cellular structures, so that when a microtubule grows it can exert a pushing force and when it shrinks it can exert a pulling force. Microtubule growth and shrinkage are tightly regulated by microtubule-associated proteins (MAPs) that bind to microtubule ends. Given their localization, MAPs may be exposed to compressive and tensile forces. The effect of such forces on MAP function, however, is poorly understood. Here we show that beads coated with the microtubule polymerizing protein XMAP215, the Xenopus homolog of Dis1 and chTOG, are able to link stably to the plus ends of microtubules, even when the ends are growing or shrinking; at growing ends, the beads increase the polymerization rate. Using optical tweezers, we found that tensile force further increased the microtubule polymerization rate. These results show that physical forces can regulate the activity of MAPs. Furthermore, our results show that XMAP215 can be used as a handle to sense and mechanically manipulate the dynamics of the microtubule tip.
The International Cotton Genome Initiative workshop I, at PAG XIII

The International Cotton Genome Initiative (ICGI) Workshop I was held at Plant and Animal Genomes (PAG) XIII on Sunday 16 January 2005. ICGI has held two biennial meetings at which the membership has had the opportunity for scientific exchange, the first at Nanjing, China, in 2002, the second at Hyderabad, India, in 2004, and the next will be held in 2006 (host country to be selected). The ICGI workshop at PAG XIII offered the unique opportunity to interact and draw upon the resources of the wider genomics community. As the first official PAG-ICGI workshop, and as a fledging organization, it was considered appropriate to review the origins of ICGI and what its future should be. In this process, we wanted to draw upon the experience of other crops with regard to how they have established and maintained their cooperation and how they have gone about establishing their goals. We also wanted to draw upon the current activities of ICGI to evaluate its role in international exchanges. From its beginnings, ICGI recognized the need to be inclusive and has encompassed activities from germplasm resources to the delivery of information and materials to the user community. The following six topics were discussed: (1) why and how ICGI came about; (2) international models of cooperation in other crops; (3) how other crops have established their genomic activities; (4) the role ICGI has played in international interactions; (5) the role ICGI has played in interactions with the private sector; and (6) what is the role and scope to which ICGI should strive? The complete presentations will be posted on the ICGI website; http://icgi.tamu. edu. ‘The International Cotton Genome Initiative (ICGI): how did we get here and why? ’ was presented by Curt L. Brubaker, from the Centre for Plant Biodiversity Research, CSIRO Plant Industry, Canberra, Australia. In February 2000, a small group of cotton scientists met in Canberra, Australia, to discuss why molecular markers were not being used effectively in cotton breeding. It was agreed that the limited application of molecular markers in cotton breeding was symptomatic of a broader issue. Cotton genomics, in general, had lagged behind other crops. The impressive gains achieved in Arabidopsis, rice, wheat and mammalian genomics demonstrated that the practical and analytical tools were at hand to progress cotton