Miracle-dz/UniFAR-FTUs huggingface dataset:
Activated Rac1 GTPase Translocates Protein Phosphatase 5 to the Cell Membrane and Stimulates Phosphatase Activity in Vitro*

Physiological studies of ion channel regulation have implicated the Ser/Thr protein phosphatase 5 (PP5) as an effector of Rac1 GTPase signaling, but direct biochemical evidence for PP5 regulation by Rac1 is lacking. In this study we used immunoprecipitation, in vitro binding, cellular fractionation, and immunofluorescence techniques to show that the tetratricopeptide repeat domain of PP5 interacts specifically and directly with active Rac1. Consequently, activation of Rac1 promoted PP5 translocation to the plasma membrane in intact cells and stimulated PP5 phosphatase activity in vitro. In contrast, neither constitutively active RhoA-V14 nor dominant negative Rac1N17, which preferentially binds GDP and retains an inactive conformation, bound PP5 or stimulated its activity. In addition, Rac1N17 and Rac1(PBRM), a mutant lacking the C-terminal polybasic region required for Rac1 association with the membrane, both failed to cause membrane translocation of PP5. Mutation of predicted contact residues in the PP5 tetratricopeptide repeat domain or within Rac1 also disrupted co-immunoprecipitation of Rac1-PP5 complexes and membrane translocation of PP5. Specific binding of PP5 to activated Rac1 provides a direct mechanism by which PP5 can be stimulated and recruited to participate in Rac1-mediated signaling pathways.
Actinomycin‐D plus 5‐(3,3‐dimethyl‐ 1‐triazeno)‐ imidazole‐4‐carboxamine (DTIC) with or without intravenous corynebacterium parvum in metastatic malignant melanoma

Chemotherapy and chemoimmunotherapy of Stage IV B malignant melanoma were compared in 88 patients. Chemotherapy consisted of DTIC 250 mg/M2 of the body surface area daily X five days and actinomycin‐D 2 mg/M2 on day 1 repeated every 3–4 weeks. Chemoimmunotherapy consisted of the same regimen plus C. parvum 2 mg/M2I.V. daily for 14 days before every third cycle of chemotherapy, plus 2 mg/M2 I.V. daily on days 7 and 14 of each 21–28 day chemotherapy cycle. There was 32 evaluable chemotherapy and 33 evaluable chemoimmunotherapy patients and the groups were well balanced for clinical and pathologic as well as prognostic variables. The complete and partial remission rates, remission and survival durations, and hematologic and gastrointestinal toxicities were different in the two randomized groups being 6 and 3%, 9 and 9%, 7.6 and 12 months, 8.8 and 6.0 months, 20 and 16%, and 62 and 70%, respectively for these parameters. This difference was not statistically significant. Therefore, it can be concluded that the results of chemotherapy with actinomycin‐D plus DTIC were not substantially different from those reported using DTIC alone, and that we cannot recommend the addition of actinomycin‐D to DTIC for palliative management in these patients. Furthermore, C. parvum immunotherapy did not add to chemotherapy in terms of remission rate, remission duration, or survival for patients with Stage IV B malignant melanoma.
Lymphocyte Activation Gene-3 (LAG-3) Expression and IFN-γ Production Are Variably Coregulated in Different Human T Lymphocyte Subpopulations

We evaluated the relationship between cytokine profile and the expression of the lymphocyte activation gene-3 (LAG-3) in both T cell clones and polyclonal T cell lines; LAG-3 is a CD4-like protein whose expression is reportedly restricted to Th1/0 cells and dependent upon IFN-γ. We found that, while LAG-3 was expressed only by CD4+ T cell clones producing IFN-γ, most CD8+ clones producing IL-4 but not IFN-γ (i.e., with a T cytotoxic-2-like profile) were LAG-3+. The intensity of LAG-3 expression by CD8+ clones correlated with the amount of released IFN-γ, suggesting that this cytokine is not required for expression but rather for the up-regulation of LAG-3. Flow cytometric analyses of polyclonal T cell lines confirmed that LAG-3 could be expressed by both CD4+ and CD8+ cells that did not contain cytoplasmic IFN-γ. In these cell lines, large proportions of CD4+ and CD8+ cells coexpressed LAG-3 and CD30, a putative marker of Th2-like cells. Overall, our data do not support the earlier suggestion that LAG-3 and CD30 are selective markers of T cells with type-1 and type-2 cytokine profiles, respectively.
Performance Evaluation of Indian Information Technology-enabled Services (ITeS) Industry: An Application of Two-Stage Data Envelopment Analysis

This study aims to evaluate the performance of Indian ITeS industry during 2000-01 to 2014-15 by using a two-stage empirical method. In the first stage, performance is evaluated in terms of technical efficiency by using data envelopment analysis (DEA). In the second stage, the determinants of the technical efficiency score are assessed by using random-effects tobit model. For this purpose, data is collated from the Centre for Monitoring Indian Economy (CMIE) Prowess database. In DEA, overall, managerial and scale efficiency scores are evaluated. Pareto-Koopmans technical efficiency is evaluated to take care of the presence of non-radial input and/or output slacks. The DEA results reveal that managerial inefficiency is the major contributor to the overall technical inefficiency as compared to the inefficient scale of production. Moreover, the Indian ITeS industry is found to be dominated by the firms exhibiting decreasing returns to scale for most of the study period. The findings of the second-stage regression show that firm-size, Market concentration, net exports and profit rate have positive and statistically significant impact on efficiency. The empirical results also reveal that Public limited and non-group firms are more efficient than their private and group counterparts, respectively. Finally, the regression results indicate that 2008’s US sub-prime crisis has negative and statistically significant impact on the performance of Indian ITeS industry. Keywords : Indian ITeS industry; Data envelopment analysis; Pareto-Koopmans technical efficiency; Input-specific Efficiency; Two-stage analysis; Random-effects Tobit model .
Early progression of disease in HIV-infected infants with thymus dysfunction.

BACKGROUND Infants with congenital thymic deficiency (the DiGeorge syndrome) have immunodeficiency and a characteristic pattern of low CD4+ and CD8+ T-lymphocyte counts and low CD5+ B-lymphocyte counts. Because the thymus is essential for the generation of CD4+ cells, we sought evidence of thymus dysfunction in infants infected perinatally with the human immunodeficiency virus (HIV). METHODS We studied the immunophenotypes of 59 infants with maternally transmitted HIV, 5 infants with the DiGeorge syndrome, and 168 infants exposed to HIV but not infected. The criteria for a presumed thymic defect were reductions in both the CD4+ and CD8+ T-cell subgroups during the first six months of life that were confirmed in a subgroup of infants by low counts of CD4+CD45RA+ and CD4+CD45RO+ T cells and CD5+ B cells. RESULTS Of the 59 HIV-infected infants, 17 had immunophenotypes similar to those of infants with the DiGeorge syndrome. The risks of the acquired immunodeficiency syndrome (AIDS) by the ages of 12 and 24 months were 75 percent and 92 percent in these 17 infants, as compared with 14 and 34 percent in the other 42 infants (P<0.001). Nine of the HIV-infected infants with the DiGeorge-like immunophenotype (53 percent) died within six months of the progression to AIDS, as compared with only three of the other infants (7 percent, P=0.006). CONCLUSIONS In some infants infected perinatally with HIV, a pattern of lymphocyte depletion develops that resembles the pattern in congenital thymic deficiency. Since HIV disease progresses rapidly in such infants, they may be candidates for early antiviral therapy and attempts at immune reconstitution.
Deciphering Transcriptional Regulatory Mechanisms Associated with Hemicellulose Degradation in Neurospora crassa

ABSTRACT Hemicellulose, the second most abundant plant biomass fraction after cellulose, is widely viewed as a potential substrate for the production of liquid fuels and other value-added materials. Degradation of hemicellulose by filamentous fungi requires production of many different enzymes, which are induced by biopolymers or its derivatives and regulated mainly at the transcriptional level through transcription factors (TFs). Neurospora crassa, a model filamentous fungus, expresses and secretes enzymes required for plant cell wall deconstruction. To better understand genes specifically associated with degradation of hemicellulose, we applied secretome and transcriptome analysis to N. crassa grown on beechwood xylan. We identified 34 secreted proteins and 353 genes with elevated transcription on xylan. The xylanolytic phenotype of strains with deletions in genes identified from the secretome and transcriptome analysis of the wild type was assessed, revealing functions for known and unknown proteins associated with hemicellulose degradation. By evaluating phenotypes of strains containing deletions of predicted TF genes in N. crassa, we identified a TF (XLR-1; xylan degradation regulator 1) essential for hemicellulose degradation that is an ortholog to XlnR/XYR1 in Aspergillus and Trichoderma species, respectively, a major transcriptional regulator of genes encoding both cellulases and hemicellulases. Deletion of xlr-1 in N. crassa abolished growth on xylan and xylose, but growth on cellulose and cellulolytic activity were only slightly affected. To determine the regulatory mechanisms for hemicellulose degradation, we explored the transcriptional regulon of XLR-1 under xylose, xylanolytic, and cellulolytic conditions. XLR-1 regulated only some predicted hemicellulase genes in N. crassa and was required for a full induction of several cellulase genes. Hemicellulase gene expression was induced by a combination of release from carbon catabolite repression (CCR) and induction. This systematic analysis illustrates the similarities and differences in regulation of hemicellulose degradation among filamentous fungi.
Exploring the ‘criminology of place’ in Chicago: a multi-level analysis of the spatial variation in violent crime across micro-places and neighborhoods

OF THE DISSERTATION . ii ACKNOWLEDGEMENTS . iv TABLE OF CONTENTS . v LIST OF TABLES . ix LIST OF ILLUSTRATIONS . xi CHAPTER 1 INTRODUCTION . 1 Micro-Places and Criminal Opportunity . 4 Neighborhoods and Social Disorganization. 8 Theoretical Integration . 12 The Study . 15 Research Question One . 16 Research Question Two . 17 Research Question Three . 19 CHAPTER 2 MICRO-PLACES AND CRIME . 21 Micro-Places and Spatial Aggregation . 22 The Distribution of Crime at Micro-Places . 25 Cross-Sectional . 25 Longitudinal. 30 Opportunity Theories . 36 Rational Choice . 37 Routine Activities . 39 Crime Pattern Theory . 42 Broken Windows Theory. 45 Understanding the Distribution of Crime Opportunities at Micro-Places . 48 Facilities. 48 Site Features . 50
A Property Rights Approach to Understanding Human Displacement from Protected Areas: the Case of Marine Protected Areas

Abstract: The physical, economic, and sociocultural displacement of local peoples from protected areas generates intense discussion among scholars and policy makers. To foster greater precision and clarity in these discussions, we used a conceptual framework from the political economy literature to examine different forms of human displacement from protected areas. Using marine protected areas (MPAs) to ground our analysis, we characterized the 5 types of property rights that are reallocated (lost, secured, and gained) through the establishment of protected areas. All forms of MPA “displacement” involve reallocation of property rights, but the specific types and bundles of rights lost, secured, and gained dramatically shape the magnitude, extent, and equity of MPA impacts—positive and negative—on governance, economic well‐being, health, education, social capital, and culture. The impacts of reallocating rights to MPA resources vary within and among social groups, inducing changes in society, in patterns of resource use, and in the environment. To create more environmentally sustainable and socially just conservation practice, a critical next step in conservation social science research is to document and explain variation in the social impacts of protected areas.
Toxic shock syndrome-associated staphylococcal and streptococcal pyrogenic toxins are potent inducers of tumor necrosis factor production

Toxic shock syndrome-associated staphylococcal and streptococcal exotoxins were tested for an ability to induce the production of tumor necrosis factor (TNF). Staphylococcal enterotoxins B and C1, along with streptococcal pyrogenic exotoxin A, all induced TNF production in a dose-dependent manner, with production peaking on the average at 3 days but continuing over the 6 days tested. This time course of exotoxin-induced TNF production contrasts with the 1-day peak-2-day duration observed with endotoxin as the stimulus and may be significant to development of toxic shock syndrome.
The blend justifies the means: the relationships between lecturer use of online content in-class, student age, and student self-stated understanding, with students’ use of online content out-of-class in a blended commerce course

With the increasing adoption of blended (flipped/ hybrid) learning year-by-year this century in higher education, the need for research on the learner experience in blended learning courses is an essential emerging body of literature, but it is one particularly under-represented in Asia. Furthermore, the assumptions emergent from a largely Western milieu investigating mostly Western students in Western University settings need to be tested in an Asian context. Therefore, the purpose of this paper is to understand whether relationships exist between three hitherto well-researched factors - lecturer use of online content in teaching, the students’ ages and students’ understanding of content – and the participation online of working adult students enrolled in a Higher Education Blended course, but crucially one in a Singaporean Higher Education setting. The methodology employs a survey of students (n=1,047) analyzed using the Pearson Chi-Square test of independence. The findings show relationships between all three and student online participation and challenges previously held views that students in high teacher-dependency cultures like Singapore find blended and online learning inferior to traditional modes.
Thalamic connections of the primary motor cortex (M1) of owl monkeys

To determine the relative contributions of transthalamic cerebellar and pallidal projections to the primary motor cortex (M1) of owl monkeys, we examined the thalamic labeling resulting from injections of fluorescent tracers and wheatgerm agglutinin/horseradish peroxidase conjugate (WGA‐HRP) into regions of M1 identified by intracortical microstimulation. Injections were placed in the major somatotopic divisions of M1 (the hindlimb, trunk, forelimb, and face representations) and in the caudal and rostral M1 subareas. In most cases, we injected several differentiable tracers into different parts of M1. Our results indicate that the strongest connections of M1 are with subdivisions of the ventral lateral thalamus (VL); other connections are mainly with intralaminar nuclei (the central lateral, paracentral, and center median nuclei) and the reticular nucleus. Most projections are reciprocal and topographically organized. M1 is strongly connected with the principal (VLp), medial (VLx), and anterior (VLa) subdivisions of the VL complex but has at most weak connections with the dorsal division (VLd). Each of the major somatotopic divisions of M1 is connected with an anteroposteriorly elongated territory within the VL complex. The connections are somatotopically organized such that the M1 hindlimb representation is connected with a band of cells in the lateral and anterior portions of the VL complex (spanning VLa and VLp), whereas the trunk, forelimb, and face representations are connected with successively more medially and posteriorly situated cell bands (spanning VLa, VLp, and VLx). There is some degree of overlap between the somatotopic territories within VL, although the absence of double‐labeled cells in cases with injections of adjacent somatotopic divisions of M1 suggests that individual thalamic neurons project to single somatotopic regions.
Association of the CYP3A4*1B 5´-Flanking Region Polymorphism With Cyclosporine Pharmacokinetics in Healthy Subjects

To determine the relationship between CYP3A4*1B polymorphism and cyclosporine pharmacokinetic parameters among healthy volunteers, the oral cyclosporine pharmacokinetic study was performed in 14 healthy subjects. Blood cyclosporine concentrations were measured by a high performance liquid chromatography. Concentration–time data were analyzed by a non-compartmental method using WinNonLin, and the blood samples were genotyped for the CYP3A4*1B 5´-promotor region using the polymerase chain reaction and a restriction digest. Each cyclosporine pharmacokinetic parameter was compared using the one-way ANOVA test according to his or her CYP3A4*1B genotype. There were four (4) homozygous A/A (wild-type), four (4) homozygous G/G (variant) and six (6) heterozygous A/G genotypes for CYP3A4*1B in these 14 healthy volunteers. The mean AUC/D (ng.hr/mL/mg) of CsA were 21.5 ± 6.0 (A/A), 11.7 ± 3.2 (G/G) and 19.2 ± 2.3 (A/G), P = 0.0103 and the mean CL/F (L/hr) were 49.4 ± 13.9 (A/A), 83.5 ± 16.0 (G/G), and 52.5 ± 5.6 (A/G), P = 0.0024. All other parameters were not significantly different among the three genotypes.
Microbial Fe(III) oxide reduction potential in Chocolate Pots hot spring, Yellowstone National Park

Chocolate Pots hot springs (CP) is a unique, circumneutral pH, iron‐rich, geothermal feature in Yellowstone National Park. Prior research at CP has focused on photosynthetically driven Fe(II) oxidation as a model for mineralization of microbial mats and deposition of Archean banded iron formations. However, geochemical and stable Fe isotopic data have suggested that dissimilatory microbial iron reduction (DIR) may be active within CP deposits. In this study, the potential for microbial reduction of native CP Fe(III) oxides was investigated, using a combination of cultivation dependent and independent approaches, to assess the potential involvement of DIR in Fe redox cycling and associated stable Fe isotope fractionation in the CP hot springs. Endogenous microbial communities were able to reduce native CP Fe(III) oxides, as documented by most probable number enumerations and enrichment culture studies. Enrichment cultures demonstrated sustained DIR driven by oxidation of acetate, lactate, and H2. Inhibitor studies and molecular analyses indicate that sulfate reduction did not contribute to observed rates of DIR in the enrichment cultures through abiotic reaction pathways. Enrichment cultures produced isotopically light Fe(II) during DIR relative to the bulk solid‐phase Fe(III) oxides. Pyrosequencing of 16S rRNA genes from enrichment cultures showed dominant sequences closely affiliated with Geobacter metallireducens, a mesophilic Fe(III) oxide reducer. Shotgun metagenomic analysis of enrichment cultures confirmed the presence of a dominant G. metallireducens‐like population and other less dominant populations from the phylum Ignavibacteriae, which appear to be capable of DIR. Gene (protein) searches revealed the presence of heat‐shock proteins that may be involved in increased thermotolerance in the organisms present in the enrichments as well as porin–cytochrome complexes previously shown to be involved in extracellular electron transport. This analysis offers the first detailed insight into how DIR may impact the Fe geochemistry and isotope composition of a Fe‐rich, circumneutral pH geothermal environment.
Perceptions and attitudes of clinical staff towards telemedicine acceptance in Saudi Arabia

Regardless of promised benefits of telemedicine and its potential technical superiority, its adoption is often cited as a failed project and the lack of understanding potential user acceptance is one of the most pervasive reasons leading to this failure. More than 40% of Information and Communications Technology (ICT) adoption projects have failed for this reason and any ICT system would not be effective if its potential user were averse to utilising its adoption. To the best of our knowledge, no comprehensive scientific study has investigated the perceptions and attitudes of clinical staff towards telemedicine acceptance and use in the Kingdom of Saudi Arabia (KSA) healthcare system at a national level. The objective of this novel research lies in addressing this gap and is conducted in collaboration with the Saudi Ministry of Health (MOH). The Unified Theory of Acceptance and Use of Technology (UTAUT) is used to underpin this research and a questionnaire to support the objective of this research was conducted in KSA to collect data from a random sample of different categories of clinical staff in KSA. The survey of 1,523 returned questionnaires were selected and the findings of this study show that 67.6% of clinical staff on average expect or extremely expect high performance from using telemedicine in KSA. Also 62.6% of clinical staff agree or extremely agree that the use of telemedicine in KSA will be compatible with culture and society. On the other hand, 38.0% of clinical staff agree or extremely agree that the use of telemedicine will not be compatible with their job role. Furthermore 40.6% of participants stated that using telemedicine would not be easy for clinical staff and 37.4% of them indicated that it will waste a lot of time and require a lot of technical and non-clinical administrative time to complete
Molecular characterization of adult mouse subventricular zone progenitor cells during the onset of differentiation

Adult mouse subventricular zone (SVZ) neural progenitor cells (NPCs) retain the capacity to generate multiple lineages in vitro and in vivo. Thus far, the mechanisms involved in the regulation of these cells have not been well elucidated. We have carried out RNA profiling of adult SVZ cell cultures undergoing differentiation, to identify pathways that regulate progenitor cell proliferation and to define a set of transcripts that can be used as molecular tools in the drug discovery process. We carried out a stepwise stratification of the results to identify transcripts specifically enriched in NPCs and validated some of these using comparative literature analysis, quantitative polymerase chain reaction and immunological techniques. The results show a set of transcription factors, secreted molecules and plasma membrane markers that are differentially regulated during differentiation. Pathway analysis highlights alterations in insulin growth factor, Wnt and transforming growth factor β signalling cascades. Further characterization of these components could provide greater insight into the mechanisms involved in the regulation of neurogenesis in the adult brain.
Tuberculosis Vaccines: Review of Current Development Trends andFuture Challenges

Despite plaguing humans for thousands of years, tuberculosis remains a widespread and lethal public health problem throughout the world today. The recent rise of multi-drug-resistant tuberculosis (MDR-TB) perpetuates the public health threat while presenting a potential bioterrorism agent. The BCG vaccine is the only available prevention against TB, yet it elicits inconsistent protection when given to infants, fails to provide consistent protection in adults against pulmonary disease, and is unsafe for use in immunocompromised patients. A new crop of TB vaccine candidates has entered into clinical trials, with a second generation following shortly. These new TB vaccines are hoped to provide a safe, efficacious replacement, or addition to, the nearly century-old BCG and provide protection against TB disease beyond childhood. This review details the status of the most promising TB vaccine candidates in development, as one of these candidates may play a key role in defending against an ominous health threat.