Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutational Anatomy of an HIV-1 Protease Variant Conferring Cross-resistance to Protease Inhibitors in Clinical Trials

Site-specific substitutions of as few as four amino acids (M46I/L63P/V82T/I84V) of the human immunodeficiency virus type 1 (HIV-1) protease engenders cross-resistance to a panel of protease inhibitors that are either in clinical trials or have recently been approved for HIV therapy (Condra, J. H., Schleif, W. A., Blahy, O. M., Gadryelski, L. J., Graham, D. J., Quintero, J. C., Rhodes, A., Robbins, H. L., Roth, E., Shivaprakash, M., Titus, D., Yang, T., Teppler, H., Squires, K. E., Deutsch, P. J., and Emini, E. A. (1995) Nature374, 569-571). These four substitutions are among the prominent mutations found in primary HIV isolates obtained from patients undergoing therapy with several protease inhibitors. Two of these mutations (V82T/I84V) are located in, while the other two (M46I/L63P) are away from, the binding cleft of the enzyme. The functional role of these mutations has now been delineated in terms of their influence on the binding affinity and catalytic efficiency of the protease. We have found that the double substitutions of M46I and L63P do not affect binding but instead endow the enzyme with a catalytic efficiency significantly exceeding (110-360%) that of the wild-type enzyme. In contrast, the double substitutions of V82T and I84V are detrimental to the ability of the protease to bind and, thereby, to catalyze. When combined, the four amino acid replacements institute in the protease resistance against inhibitors and a significantly higher catalytic activity than one containing only mutations in its active site. The results suggest that in raising drug resistance, these four site-specific mutations of the protease are compensatory in function; those in the active site diminish equilibrium binding (by increasing Ki), and those away from the active site enhance catalysis (by increasing kcat/KM). This conclusion is further supported by energy estimates in that the Gibbs free energies of binding and catalysis for the quadruple mutant are quantitatively dictated by those of the double mutants.
Interest Rates Linkages within the EMS: What Lies Ahead for the Euro

This paper applies multi-equation cointegration methodology to the short-term interest rate series of European Monetary System (EMS) member countries during the period from March 1979 to July 1998. The objective of the paper is to measure the degree to which the interest rates of EMS member countries moved together and whether they exhibited different trends over the period. The behavior of the interest rates provides a test of the EMS' performance in coordinating member country interest rates. The results based on the performance of the EMS yield information about future prospects for the Euro and about the future impacts of the single European currency on member countries. Our results show that interest rates of EMS member countries conformed to a long-term equilibrium relationship between 1979 and 1998. The equilibrium relationship is stronger before the 1992 crisis, and loses its strength after 1992. Based on the lack of coordination of interest rates under the EMS system, the introduction of the Euro will impact the credit markets of ECU members differently and complicate, monetary policy decision-making by the European Central Bank.
Medication adherence and quality of life in pediatric inflammatory bowel disease.

OBJECTIVE To examine the relationship between medication adherence and quality of life (QOL) in adolescent patients with inflammatory bowel disease (IBD) utilizing a multimethod adherence assessment approach. METHODS Medication adherence in 36 adolescents with IBD was assessed via interviews, pill counts, and biological assays. QOL was assessed via patient and parent report. Pediatric gastroenterologists provided disease severity assessments. RESULTS Hierarchical multiple regression analyses revealed that adherence contributed significant variance to patient-reported QOL but not parent-reported QOL. Nonadherence to 6-MP/azathioprine was related to poorer patient-reported physical health QOL. Greater self-reported 5-ASA adherence was related to poorer overall psychological health QOL, and particularly social functioning QOL. CONCLUSIONS Results provide preliminary support for the negative effects of 6-MP/azathioprine nonadherence on QOL and an inverse relationship between 5-ASA adherence and QOL in this population. Adherence burden in patients and the utility of multimethod adherence assessment in research are discussed.
TCP performance improvement with the inclusion of TCP proxy nodes

In this paper we study the performance of TCP in long-delay networks aiming to big data transmission. As it is stated in slow-start phase of the congestion-avoidance algorithm, the congestion window increases by a minimum of one MSS each round-trip time (RTT). We noted that, in fact, the data transmission is inversely related to RTT. Note that in long-delay networks the packet-loss recovery is slower than typical medium-size networks. Thus, so the throughput is lower. We propose the use of a TCP proxy node as a solution to this situation. That is, a node will capture the data package that was sent by the transmitter, copy it and send the acknowledgement package to the client and the original data package to the receiver, this is accomplish because the node is transparent to the transmitter and the receiver. We show that our approach is effective in this scenario by increasing the throughput linearly with the number of proxy nodes.
Construction and characterization of a bispecific diabody for retargeting T cells to human carcinomas

We describe the construction of a recombinant bispecific antibody fragment in the diabody format with specificity for both the well‐established human pancarcinoma associated target antigen EGP2 (epithelial glycoprotein 2, also known as the CO17‐1A antigen or KSA) and the CD3ϵ chain of human TCR/CD3 complex. The murine anti‐EGP2 (MOC31) single chain variable fragment (scFv) and the humanized anti‐CD3 (Ucht1v9) scFv were cast into a diabody format (designated Dia5v9) using a short 5 amino acid Gly‐Ser linker between immunoglobulin heavy‐chain and light‐chain variable domains. Purification of the poly‐histidine tagged Dia5v9 was achieved from extracts of protease deficient Escerichia coli by IMAC chromatography. The Dia5v9 diabody showed strong binding to both EGP2 and CD3 in transfected cells. The in vitro efficacy of Dia5v9 in mediating tumor cell lysis by interleukin‐2 activated human T cells appeared to be similar to that of the hybrid‐hybridoma–derived BsF(ab′)2 Bis1 (anti‐EGP2/anti‐CD3) in a standard 4‐hr 51Cr‐release assay. This small and partially humanized recombinant bispecific antibody fragment may be valuable for T‐cell–based immunotherapeutical treatment protocols, retargeting activated peripheral blood T lymphocytes to lyse various human carcinomas in vivo. Int. J. Cancer 76:232–239, 1998. © 1998 Wiley‐Liss, Inc.
An investigation of students opinions related to the authority of university professors in terms of authority and authoritarianism duality

Otorite, öğrenme-öğretme süreçlerinin temel bir parçasıdır. Eğitim çalışmalarında pedagojik otorite ve gücün otoriter kullanımı arasında genellikle bir ayrım yapılmaktadır. Bu ayrım, otoritenin olumlu ve olumsuz yönleri arasında sürekli devam eden bir gerilimi işaret etmektedir (Harjunen, 2009). Otorite kavramı, eğitim literatüründe sıklıkla güç kavramı ile birlikte kullanılmaktadır. Güç otoritenin içine gömülüdür. Güç kavramı, eleştirel pedagoji çalışmalarında tahakküm ve baskı aracı olarak gücün kötüye kullanılması ile ilişkilendirilerek tartışılmaktadır (Rogers, 2011). Otoriteryanizm ise, “gücün yanlış kullanımı, adil kullanılmaması veya aşırı kullanımı ya da kötüye kullanılması” gibi anlamlarda kullanılmaktadır (Watt, 1982). Bir entelektüel olarak öğretmenin uzmanlık gücünü ve pedagojik otoritesini, gücün otoriter kullanımı ve bu otoritenin sınırları ikileminde tartışan Giroux (1988) ve Freire (2005)’in bu kavramlara ilişkin önermeleri, bu çalışmanın çerçevesini oluşturmaktadır. Giroux’a göre (2004) kamusal eğitim ve yükseköğretim, bireylerin toplumsal vatandaşlık becerilerinin ne anlama geldiği ile demokratik ve kolektif yaşam olanaklarının nasıl genişletilebileceğinin öğrenebileceği sınırlı birkaç alandan birisidir. Böyle bir alanda bireylerin ve toplumun dönüşümünde temel rol oynaması beklenen üniversiteler ve öğretim üyelerinin pedagojik otoritesini eğitim hizmetinden yararlanan öğrencilerin gözünden incelenmesi araştırmaya değer bir konu olarak görülmektedir. Bu çalışmada Türkiye’de bir devlet üniversitesinin eğitim bilimleri enstitüsü kapsamındaki dört farklı öğretim programında öğrenim görmekte olan lisansüstü öğrencilerin görüşleri doğrultusunda, öğretim üyesinin otoritesinin kaynağını ve bunun pratiğe yansımalarının pedagojik otorite ve otoriteryanizm ikileminde ve geriliminde ampirik bulgular ekseninde çözümlenmesi amaçlanmıştır. Bu çerçevede, öğretim üyelerinin öğrenciler ile etkileşimlerinde; kullandıkları yetki türlerinin neler olduğu, öğretim üyesinin yetkisinin/gücünün kaynağının ne olduğu ve öğrencilerin bu yetkiyi/gücü sorgulamalarının mümkün olup olmadığına ilişkin sorulara yanıt aranmıştır. Araştırma, nitel araştırma desenlerinden fenomenolojik desen olarak tasarlanmıştır. Katılımcıların belirlenmesinde ölçüt örnekleme tekniği kullanılmıştır. Veri toplama aracı olarak açık uçlu sorulardan oluşan yarı yapılandırılmış görüşme formu kullanılmıştır. Öğrencilerin tecrübelerine göre öğretim üyesinin otoritesinin kaynağı “üst düzeyde bilgi birikimi, alanına hâkim olma ve çalışmalarının niteliği” olmalı iken, öğrenciler öğretim üyelerinin otoritesinin unvanından ve yasal yetkisinden (not verme gibi) kaynaklandığını ileri sürmüşlerdir. Anahtar Sözcükler: Otorite, Otoriteryanizm, Öğretim üyesinin otoritesi, Yetki, Öğrenci görüşleri
Evaluating Health Promotion—Progress, Problems and solutions

This article addresses various aspects of health promotion evaluation that are under debate. The paper opens by noting the recent growth in research directed toward health promotion and its evaluation. Next the definition of "success" in health promotion is discussed in terms of 1) valued outcomes and valued processes 2) health outcomes 3) health outcomes and health promotion outcomes and 4) measurement of outcomes. The next section describes how best to evaluate "success" by presenting a hierarchy of evaluation stages (problem definition solution generation testing innovations intervention demonstration intervention dissemination and program management). Analysis of ways to assess cause and effect in evaluating outcome considers experimental designs to attribute cause and effect alternatives to experimental designs strategic issues in evaluating community/population interventions community interventions and social movements and building evidence using multiple methods and multiple sources of data. Examination of the evaluation of the process looks at program reach program acceptability and program integrity. The article concludes that the four key challenges to the evaluation of health promotion are 1) using research evidence more systematically while planning activities 2) improving the definition and measurement of outcome 3) adopting an appropriate evaluation intensity and 4) adopting an appropriate evaluation design.
The Neglected “R” in the Risk-Needs-Responsivity Model: A New Approach for Assessing Responsivity to Correctional Interventions

Abstract Prevailing correctional practice holds that offenders should be assigned to interventions on the basis of assessments for risk, needs, and responsivity. Assessments of responsivity, however, typically consist of little more than a checklist of items such as motivation, gender, language, or culture. We introduce a new actuarial approach for assessing responsivity, which focuses on predicting whether individuals will desist after participating in an intervention. We assess responsivity by using multiple classification methods and predictive performance metrics to analyze various approaches for prioritizing individuals for correctional interventions. The results suggest that adding an actuarial responsivity assessment to the existing risk and needs assessments would likely improve treatment assignments and further enhance the effectiveness of an effective intervention. We conclude by discussing the implications of more rigorous responsivity assessments for correctional research, policy, and practice.
Algal light sensing and photoacclimation in aquatic environments.

Anoxygenic photosynthetic prokaryotes arose in ancient oceans ~3.5 billion years ago. The evolution of oxygenic photosynthesis by cyanobacteria followed soon after, enabling eukaryogenesis and the evolution of complex life. The Archaeplastida lineage dates back ~1.5 billion years to the domestication of a cyanobacterium. Eukaryotic algae have subsequently radiated throughout oceanic/freshwater/terrestrial environments, adopting distinctive morphological and developmental strategies for adaptation to diverse light environments. Descendants of the ancestral photosynthetic alga remain challenged by a typical diurnally fluctuating light supply ranging from ~0 to ~2000 μE m-2 s-1 . Such extreme changes in light intensity and variations in light quality have driven the evolution of novel photoreceptors, light-harvesting complexes and photoprotective mechanisms in photosynthetic eukaryotes. This minireview focuses on algal light sensors, highlighting the unexpected roles for linear tetrapyrroles (bilins) in the maintenance of functional chloroplasts in chlorophytes, sister species to streptophyte algae and land plants.
Tissue-Specific Progenitor and Stem Cells Generation of Functional Human Cardiac Progenitor Cells by High-Efficiency Protein Transduction

The reprogramming of fibroblasts to induced pluripotent stem cells raises the possibility that somatic cells could be directly reprogrammed to cardiac progenitor cells (CPCs). The present study aimed to assess highly efficient protein-based approaches to reduce or eliminate the geneticmanipulations to generate CPCs for cardiac regeneration therapy. A combination of QQ-reagent-modified Gata4, Hand2, Mef2c, and Tbx5 and three cytokines rapidly and efficiently reprogrammed human dermal fibroblasts (HDFs) into CPCs. This reprogramming process enriched trimethylated histone H3 lysine 4, monoacetylated histone H3 lysine 9, and Baf60c at the Nkx2.5 cardiac enhancer region by the chromatin immunoprecipitation quantitative polymerase chain reaction assay. Protein-induced CPCs transplanted into rat heartsaftermyocardial infarction improvedcardiac function, and thiswas related todifferentiation into cardiomyocyte-like cells. These findings demonstrate that the highly efficient protein-transduction method can directly reprogram HDFs into CPCs. This protein reprogramming strategy lays the foundation for future refinements both in vitro and in vivo andmight provide a source of CPCs for regenerative approaches. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1415–1424
Human blood group A‐like determinants as marker of the intracellular pools of glycoproteins in secretory and absorbing of A+ rabbit jejunum

Human blood group A antigenicity of glycoproteins is retained on epon‐embedded jejunum sections after glutaraldehyde fixation and osmium treatment. The intracellular location of molecules bearing these determinants was visualized in the four types of epithelial cells of A+ rabbit jejunum sections with immuno‐colloidal gold labeling. The brush border membrane and in particular the glycocalyx of absorbing cells as well as the secretory granules of goblet and Paneth cells were heavily labeled. In enteroendocrine cells, the membrane of secretory granules and not their content was lightly labeled. The differential labeling of secretory or membrane bound glycoproteins is accompanied by different labels of the Golgi complex as expected if labeling of the Golgi saccules was due to the presence of glycoproteins in transit. In all cases the label is primarily concentrated in only half the cisternae on the trans side of the Golgi stacks. In absorbing cells, structures have been revealed in the terminal web that could be related to the brush border membrane and consequently implicated in its biogenesis. The fibrillar material of the glycocalyx appears as highly labeled tangled structures which apparently proceed from densely stained “carrier” vesicles arising from the Golgi apparatus. Vesicles fusing at the lower part of microvilli could result of integration of this material into the lightly labeled vesicles strictly found in the terminal web. These last vesicles could also contain newly synthesized brush border hydrolases.
Kinetics of chlorinated hydrocarbon degradation by Methylosinus trichosporium OB3b and toxicity of trichloroethylene

The kinetics of the degradation of trichloroethylene (TCE) and seven other chlorinated aliphatic hydrocarbons by Methylosinus trichosporium OB3b were studied. All experiments were performed with cells grown under copper stress and thus expressing soluble methane monooxygenase. Compounds that were readily degraded included chloroform, trans-1,2-dichloroethylene, and TCE, with Vmax values of 550, 330, and 290 nmol min-1 mg of cells-1, respectively. 1,1-Dichloroethylene was a very poor substrate. TCE was found to be toxic for the cells, and this phenomenon was studied in detail. Addition of activated carbon decreased the acute toxicity of high levels of TCE by adsorption, and slow desorption enabled the cells to partially degrade TCE. TCE was also toxic by inactivating the cells during its conversion. The degree of inactivation was proportional to the amount of TCE degraded; maximum degradation occurred at a concentration of 2 mumol of TCE mg of cells-1. During conversion of [14C]TCE, various proteins became radiolabeled, including the alpha-subunit of the hydroxylase component of soluble methane monooxygenase. This indicated that TCE-mediated inactivation of cells was caused by nonspecific covalent binding of degradation products to cellular proteins.
Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase

The level of genetic variation of human immunodeficiency virus type 1 (HIV-1), a member of the lentivirus genus of the Retroviridae family, is high relative to that of retroviruses in some other genera. The high error rates of purified HIV-1 reverse transcriptase in cell-free systems suggest an explanation for this high genetic variation. To test whether the in vivo rate of mutation during reverse transcription of HIV-1 is as high as predicted by cell-free studies, and therefore higher than that rates of mutation of retroviruses in other genera, we developed an in vivo assay for detecting forward mutations in HIV-1, using the lacZ alpha peptide gene as a reporter for mutations. This system allows the rates and types of mutations that occur during a single cycle of replication to be studied. We found that the forward mutation rate for HIV-1 was 3.4 x 10(-5) mutations per bp per cycle. Base substitution mutations predominated; G-to-A transition mutations were the most common base substitution. The in vivo mutation rates for HIV-1 are three and seven times higher than those previously reported for two other retroviruses, spleen necrosis virus and bovine leukemia virus, respectively. In contrast, our calculated in vivo mutation rate for HIV-1 is about 20-fold lower than the error rate of purified HIV-1 reverse transcriptase, with the same target sequence. This finding indicates that HIV-1 reverse transcription in vivo is not as error prone as predicted from the fidelity of purified reverse transcriptase in cell-free studies. Our data suggest that the fidelity of purified HIV-1 reverse transcriptase may not accurately reflect the level of genetic variation in a natural infection.
Mechanics of fresh, frozen-thawed and heated porcine liver tissue

Abstract Purpose: For a better understanding of the effects of thermally altered soft tissue, the biothermomechanics of these tissues need to be studied. Without the knowledge of the underlying physical processes and the parameters that can be controlled clinically, thermal treatment of cancerous hepatic tissue or the preservation of liver grafts are based primarily on trial and error. Materials and methods: Thus, this study is concerned with the investigation of the influence of temperature on the rheological properties and the histological properties of porcine liver. Results: Heating previously cooled porcine liver tissue above 40 °C leads to significant, irreversible stiffness changes observed in the amplitude sweep. The increase of the complex shear module of healthy porcine liver from room temperature to 70 °C is approximately 9-fold. Comparing the temperatures −20 °C and 20 °C, no significant difference of the mechanical properties was observed. Furthermore, there is a strong relation between the mechanical and histological properties of the porcine liver. Temperatures above 40 °C destroy the collagen matrix within the liver tissue. This results in the alteration of the biomechanical properties. The time-temperature superposition principle is applied to generate temperature-dependent shift factors that can be described by a two-part exponential function model with an inflection temperature of 45 °C. Conclusions: Tumor ablation techniques such as heating or freezing have a significant influence on the histology of liver tissue. However, only for temperatures above body temperature an influence on the mechanical properties of hepatic tissues was noticeable. Freezing up to −20 °C did not affect the liver mechanics.
TD-LTE network indoor offloading study in a realistic metropolitan scenario

In the wireless broadband network, most traffic are generated from indoor users. Meanwhile the indoor coverage is identified as the major bottleneck especially in dense urban environment with high-rising buildings. In this paper, the TD-LTE network downlink performance of indoor is studied with various network deployment options, including outdoor Macro cell, outdoor Micro cell, indoor distributed antenna system (DAS), indoor Femto cell, and their combinations in a realistic large-scale dense urban scenario. Since a DAS cell consists of several or even tens of access points (AP), the computation load is too high to be accepted when calculating the received signal power and the interference power by traditional widely-used methodology. Thus a new DAS model is proposed to decrease the computation complexity to a reasonable level in the simulation. To have more accurate channel modeling, the real three-dimensional (3D) city map of the investigated area is employed. A 3D ray-tracing tool is used to estimate the large scale propagation occurring between outdoor sites and buildings. The traffic offloading features of Micro, DAS, and Femto cell are evaluated through system simulations.