Miracle-dz/UniFAR-FTUs huggingface dataset:
Identical phosphatase mechanisms achieved through distinct modes of binding phosphoprotein substrate

Two-component signal transduction systems are widespread in prokaryotes and control numerous cellular processes. Extensive investigation of sensor kinase and response regulator proteins from many two-component systems has established conserved sequence, structural, and mechanistic features within each family. In contrast, the phosphatases which catalyze hydrolysis of the response regulator phosphoryl group to terminate signal transduction are poorly understood. Here we present structural and functional characterization of a representative of the CheC/CheX/FliY phosphatase family. The X-ray crystal structure of Borrelia burgdorferi CheX complexed with its CheY3 substrate and the phosphoryl analogue reveals a binding orientation between a response regulator and an auxiliary protein different from that shared by every previously characterized example. The surface of CheY3 containing the phosphoryl group interacts directly with a long helix of CheX which bears the conserved (E - X2 - N) motif. Conserved CheX residues Glu96 and Asn99, separated by a single helical turn, insert into the CheY3 active site. Structural and functional data indicate that CheX Asn99 and CheY3 Thr81 orient a water molecule for hydrolytic attack. The catalytic residues of the CheX·CheY3 complex are virtually superimposable on those of the Escherichia coli CheZ phosphatase complexed with CheY, even though the active site helices of CheX and CheZ are oriented nearly perpendicular to one other. Thus, evolution has found two structural solutions to achieve the same catalytic mechanism through different helical spacing and side chain lengths of the conserved acid/amide residues in CheX and CheZ.
The changes of lumbar muscle flexion-relaxation phenomenon due to antero-posteriorly slanted ground surfaces

Abstract Uneven ground surface is a common occupational injury risk factor in industries such as agriculture, fishing, transportation and construction. Studies have shown that antero-posteriorly slanted ground surfaces could reduce spinal stability and increase the risk of falling. In this study, the influence of antero-posteriorly slanted ground surfaces on lumbar flexion-relaxation responses was investigated. Fourteen healthy participants performed sagittally symmetric and asymmetric trunk bending motions on one flat and two antero-posteriorly slanted surfaces (−15° (uphill facing) and 15° (downhill facing)), while lumbar muscle electromyography and trunk kinematics were recorded. Results showed that standing on a downhill facing slanted surface delays the onset of lumbar muscle flexion-relaxation phenomenon (FRP), while standing on an uphill facing ground causes lumbar muscle FRP to occur earlier. In addition, compared to symmetric bending, when performing asymmetric bending, FRP occurred earlier on the contralateral side of lumbar muscles and significantly smaller maximum lumbar flexion and trunk inclination angles were observed. Practitioner Summary: Uneven ground surface is a common risk factor among a number of industries. In this study, we investigated the influence of antero-posteriorly slanted ground surface on trunk biomechanics during trunk bending. Results showed the slanted surface alters the lumbar tissue load-sharing mechanism in both sagittally symmetric and asymmetric bending.
Celastrol and Attenuation of Tumor Growth in Systemic Malignancies: A Clinical Perspective

Wang et al. [2012] have provided interesting data in their recent article. Interestingly, celastrol exerts significant anti-neoplastic effects in other systemic malignancies. For instance, celastrol inhibits tumor growth in breast malignancies. It acts by attenuating NF-kB-mediated MMP-9 expression in the cancerous cells (Kim et al., 2011). This markedly attenuates tumor invasiveness as well as metastasis. IkBa degradation is also decreased resulting in further decrease in tumor growth. Proliferation is thus inhibited by modulation of a mitochondrial dependent caspase pathway. Bax levels are typically up-regulated (Yang et al., 2011). On the other hand, Bcl-2 levels are downregulated. Increased PARP cleavage accompanies these changes and further augments tumor growth inhibition. Besides these effects, celastrol also modulates the estrogen receptor a thus further inhibiting tumor growth. It attenuates estrogen receptor a transcription (Jang et al., 2011). Similar effects have been seen in non-small cell lung carcinomas. It mediates this effect by activation of FasL mediated apoptosis. At the same time, it also induces mitochondrial mediated apoptosis in the cancerous cells. Mitochondrial membrane potential is attenuated markedly. Simultaneously, it decreases Bcl-2 expression while increasing Bax expression within the tumor cells (Mou et al., 2011). Caspase-3 cleavage is also augmented resulting in further enhancement of apoptosis. These effects are time dependent. Celastrol also inhibits Hsp90 and thereby accentuates the radio sensitivity of pulmonary malignancies (Lee et al., 2011). As a result increased p53 expression is also seen. Similar effects are seen in bladder malignancies. It mediates its anti-neoplastic effects in these tumors by inducing ROS. It also causes down-regulation of miR-27a. As a result, there is increased ROS mediated induction of ZBTB4 and ZBTB10 (Chadalapaka et al., 2012). As a result, intra-tumoral apoptosis is markedly accentuated. Celastrol also causes down-regulation of survivin in the cancerous cells thus further inhibiting growth. Cyclin D1 expression is also decreased. miR-20a/17-5p is also down-regulated by celastrol resulting in increased tumor attenuation. Besides its attenuating affect on the above tumors celastrol also attenuates tumor growth in other malignancies such as melanomas and hepatocellular carcinomas. It is clearly evident from the above examples that celastrol has significant growth inhibiting effects in systemic tumors. Further, research is needed to fully explore its anti-neoplastic effects in other systemic malignancies and also further assess and evaluate its safety in humans.
Requirement of Multiple Basic Helix-Loop-Helix Genes for Retinal Neuronal Subtype Specification*

Retinal precursor cells give rise to six types of neurons and one type of glial cell during development, and this process is controlled by multiple basic helix-loop-helix (bHLH) genes. However, the precise mechanism for specification of retinal neuronal subtypes, particularly horizontal neurons and photoreceptors, remains to be determined. Here, we examined retinas with three different combinations of triple bHLH gene mutations. In retinas lacking the bHLH genes Ngn2, Math3, and NeuroD, horizontal neurons as well as other neurons such as bipolar cells were severely decreased in number. In the retina lacking the bHLH genes Mash1, Ngn2, and Math3, horizontal and other neurons were severely decreased, whereas ganglion cells were increased. In the retina lacking the bHLH genes Mash1, Math3, and NeuroD, photoreceptors were severely decreased, whereas ganglion cells were increased. In all cases, glial cells were increased. The increase and decrease of these cells were the result of cell fate changes and cell death and seem to be partly attributable to the remaining bHLH gene expression, which also changes because of triple bHLH gene mutations. These results indicate that multiple bHLH genes cross-regulate each other, cooperatively specify neuronal subtypes, and regulate neuronal survival in the developing retina.
LEVELS OF VIRUS-SPECIFIC CD4 T CELLS CORRELATE WITH CYTOMEGALOVIRUS CONTROL AND PREDICT VIRUS-INDUCED DISEASE AFTER RENAL TRANSPLANTATION1

Background. Immunosuppressive treatment in transplant patients frequently causes infectious complications with cytomegalovirus (CMV). The extent of CMV replication can be followed by a number of diagnostic methods. There is, however, no simple diagnostic tool to assess the quality of the cellular antiviral immune response of an individual patient. This would be of particular importance for therapy decisions, as patients with detectable virus load do not necessarily develop CMV-related disease. Using a rapid whole blood assay, the frequencies of CMV-reactive CD4 and CD8 T cells were followed after renal transplantation to characterize their relative contribution in the containment of CMV infection. Methods. T cells from transplant patients and healthy control persons were stimulated with CMV antigen in vitro. Based on specific cellular activation and induction of intracellular cytokines, the frequency of CMV-reactive CD4 and CD8 T cells was determined using flow cytometry. Viral load was quantified using the “hybrid-capture” assay. Results. The absence of CMV complications in long-term transplant recipients is reflected by stable virus-specific T-cell frequencies, which do not differ from healthy CMV-positive controls. In contrast, during the first months after transplantation, clinical symptoms are preceded by a decrease in CMV-reactive CD4 T-cell frequencies and an increase in CMV load. Conclusions. The individual immune response and CMV replication are critically balanced and can be characterized by assessing both viral load and antiviral T cells. Our experimental design allows the identification of patients with sufficient, insufficient, or absent T-cell activity and can serve as diagnostic tool to facilitate decisions on antiviral therapy.
Understanding Patients’ Perception and Experience in Improving Quality Healthcare with one of the Leading Public Hospitals in Erbil, Iraq

This public hospital survey aims to assess patients’ satisfaction with health care services at one of the largest public institutions in Erbil-Kurdistan the semiautonomous region of Iraq. The study identifies factors in determining patients’ perceptions and experiences in order to improve quality healthcare within public health facilities in this province. Patient’s sample was simple random sample of all eligible patients applying HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) survey instrument. As per National Research Corporation, HCAHPS is backed by leading hospital associations and is actively supported by foremost healthcare and consumer organizations. Data from 180 patients were collected over a period of 3 months, by medical and pharmacy students through direct interview of patients for the purpose of reliability and consistency of the assessment. The study shows there were some factors in hospital care causing dissatisfaction among a number of patients. Those factors resulting dissatisfaction were courtesy and respect, poor sanitation, attitude of the providers, availability of medicines, and level of noise at night, communication and in providing vital information, as well as hygiene. The findings would assist in the implementation of quality health care and improvement of public health services. Keywords: Patient satisfaction, quality improvement, healthcare quality
The relationship of intracellular pathways of iron metabolism to cellular iron overload and the iron storage diseases. Cell sap and cytocavitary network pathways in relation to lysosomal storage and turnover of iron macromolecules.

THIS PAPER IS CONCERNED with the intracellular metabolism and transport of iron. Particular emphasis is given to iron macromolecular components, including ferritin and hemosiderin, and their relation to iron overload at the cellular level. Recently there have been a number of reports which have clarified many aspects of intracellular metabolism and transport of iron. Two groups of studies in particular have been most helpful: first, biochemical investigations utilizing apoferritin and ferritin as markers in the study of mechanisms controlling protein synthesis 1,2 and, second, combined ultrastructural and functional studies defining the subcellular localization and compartmentalization of ferritin and hemosiderin.38 When these studies are reviewed in the light of what is known about the relationship between the metabolism of the cell membrane and iron, it is possible to develop a rational concept to explain the manner in which iron is stored in the cell and to clarify the mechanism of cellular iron overload in iron storage diseases and in other disease states.8 Cell membrane metabolism in health and disease is intimately related to iron metabolism and iron overload. For example, iron can be taken up by or released from the cell by a variety of mechanisms, all of which involve membranes. These include phagocytosis, pinocytosis and membrane transport systems. Moreover, iron compounds form
Essays In the Airline Industry

In 2008, most U.S. airlines implemented checked baggage fee policies to generate additional revenue to help with their financial distress caused by abnormally high fuel prices. Since this time, the fees have provided a steady revenue stream and often are the difference between a profit and a loss. Recently, some literature in the operations management field has postulated that altering consumer behavior in a manner that is beneficial to both the firm and customers is an additional purpose of these fees. In Essay 1, we empirically investigate the airline perspective of this hypothesis by considering the operational impact of airline baggage fees as measured by the airlines’ departure delays. We do so by using primarily data collected by the Bureau of Transportation Statistics for the time periods immediately before and after fees for one and two checked bags were imposed by most U.S. airlines in 2008, and using a Tobit regression model to assess the impact of the fees on departure time performance. According to the 2013 North America Airline Satisfaction Study by J.D. Power & Associates, the baggage fees are still a source of passenger dissatisfaction. In Essay 2, we empirically investigate the customer perspective of the above hypothesis by considering the benefits provided by the service of checking bags. Thus, we examine airline service attributes that affect customer choice itinerary, and how checking or not checking bags influence these relationships, by employing discrete choice models estimated on stated-preference survey data.
Benchmarking Audit Committee Effectiveness in the UK

This paper adopts the benchmarking approach to study audit committee effectiveness in the UK. Using FRRP sample spanning a decade from 1990 to 2000, this paper investigates factors leading to the violation of accounting and financial reporting standards by UK firms. Our binary logit regression suggest the following results: First, smaller boards provide better incentive for monitoring; Second, consistent with previous studies, board and committee independence enhances reduce the likelihood of financial reporting problems; Third, contrary to popular suggestions, director share ownership might cause non-compliance with standards; Forth, outside directorships seem to enable non-executive directors to gain monitoring experience more quickly and is conductive to better financial reporting; Fifth, financial literacy and audit committee meeting frequency all reduce the probability of standard violations in financial reporting.
Managing knowledge sharing in distributed innovation from the perspective of developers: empirical study of open source software projects in China

ABSTRACT Knowledge sharing is the key factor that influences the performance of open source software (OSS) projects, which are the representative cases of distributed innovation. This paper aims to explore the mechanism of knowledge sharing in OSS projects from the perspective of developers in China. A quantitative method with the analysis of 403 valid questionnaires is adopted. A series of hypotheses about how distributed innovation (independent variables) influences knowledge sharing (mediating variable) and then affects the performance of OSS projects (dependent variable) are tested and approved. On the one side, we argue that developers will actively affect knowledge sharing in terms of participative motivation, social network and organisational culture. On the other hand, users may also affect the knowledge sharing when considering innovation willingness and capacity. It is interesting to find that social network is the most important factor in Chinese cases. It is strongly recommended to strengthen the collaboration between software companies and OSS communities.
Development of a retroviral vector for inducible expression of transforming growth factor beta 1

A retroviral vector system for the expression of exogenous genes under the control of an inducible promoter was developed. By utilizing this system, the cDNA for human transforming growth factor beta 1 (TGF-beta 1) was inserted into a retroviral vector under the control of an internal mouse metallothionein promoter and introduced via infection into normal rat kidney fibroblasts (NRK-49F) and epithelial cells (NRK-52E), Chinese hamster ovary cells (CHO), and the human monocytic cell line U937. Control of TGF-beta 1 expression, achieved by Cd2+ induction of vector-encoded TGF-beta 1 mRNA, was cell line specific and resulted in a concomitant increase in neutralizable TGF-beta 1 production by the cells. Autocrine stimulation of vector-containing cells by vector-encoded TGF-beta 1 was detected by an increase in soft-agar colony formation of NRK-49F infectants compared with that of the control cells. In addition, the use of a second internal promoter in a retroviral vector of similar design allowed isolation of stable infectants from a cell line (CHO) in which the viral long terminal repeat does not function efficiently.
The Acquisition of Conditioned Suppression as a Function of Interstimulus Interval Duration

The effect of interstimulus interval (ISI) variation on the acquisition of a classically conditioned emotional response was investigated using a one-trial conditioning procedure. The optimum ISI was found to be 10 s with a bidirectional gradient for conditioned suppression at ISI above and below 10 s. Control groups demonstrated that conditioning was not a function of either pseudoconditioning, sensitization or stimulus novelty.
Magnetoencephalographic analysis of roland discharges in benign childhood epilepsy

We report the detailed analysis of the generator and propagation of rolandic discharges in benign childhood epilepsy with centrotemporal spikes by means of 37‐channel magnetoencephalography with neuromagnetic three‐dimensional dipole localization. Equivalent current dipoles of prominent negative sharp waves of rolandic discharges appeared as tangential dipoles in the rolandic region, positive poles being situated anteriorly. These equivalent current dipoles showed a relatively limited localization and regular directions compared with other components. Equivalent current dipoles of preceding small positive waves, positive waves following negative sharp waves, and negative slow waves appeared in the vicinity of negative sharp waves. Equivalent current dipoles of rolandic discharges were located around the generator of somatosensory evoked magnetic fields stimulated at the lower lip. These findings suggest that rolandic discharges are generated through basically a mechanism similar to that for the middle‐latency components of somatosensory evoked responses.
Millimeter-wave wireless backhauling for 5G small cells: Star versus mesh topologies

MmWave wireless communication, operating in the 10–300 GHz band, appears to be a promising candidate for the next generation of cellular systems by which multiple gigabit-per-second data rates can be supported. It is a promising technology for future cellular systems, especially in mobile backhauling for the new small-cell evolution. In this paper, MmWave backhauling is considered in two different topologies; a star topology and a mesh topology. The two topologies are compared from the point of view of the system throughput. Different scenarios are considered including the Line Of Sight (LOS) and the Non Line Of Sight (NLOS) connections.
Diabetes area participation analysis: a review of companies and targets described in the 2008 – 2010 patent literature

Importance of the field: Type 2 diabetes is a chronic disease characterized by the development of insulin resistance, impaired pancreatic β-cell function and, ultimately, hyperglycemia. The disease is highly associated with obesity and it is thought that the inappropriate deposition of lipid in tissues such as liver and muscle contributes to a reduction in insulin sensitivity which, in turn, places a burden on the β-cell to secrete more insulin to achieve normoglycemia. Over an extended period of time, this can result in β-cell failure and diminished glycemic control. When poorly managed, type 2 diabetes increases the risk of developing both microvascular and macrovascular complications, including retinopathy, nephropathy and coronary artery disease. The number of Americans with diabetes has approached 24 million in 2007 and the prevalence of the disease is projected to increase with the sedentary lifestyles and high caloric diets that are common today. First-line treatment for the disease involves lifestyle modifications and, if unsuccessful, pharmacotherapy to control symptoms. Anti-diabetic drugs belonging to several mechanistic classes are available (e.g., insulin secretagogues, insulin sensitizers, insulin mimetics and DPP IV inhibitors); however, many of these drugs lose their effectiveness over time, are not well-tolerated in some patients or may have suboptimal risk:benefit ratios. The search for new anti-diabetic drugs has continued to attract considerable interest from both academia and the pharmaceutical industry. Areas covered in this review: An analysis of 2008 – 2010 patent applications claiming diabetes as an indication has been undertaken. What the reader will gain: An understanding of: i) the pharmaceutical companies that have filed patent applications in the anti-diabetes area during 2008 – 2010; ii) the different pharmacological targets under investigation and the patent activity around such targets; iii) some of the targets in the research portfolios of selected companies; iv) chemical structures of compounds that modulate emerging targets and v) the pharmacological rationale underlying several targets with the largest patent counts. Take home message: Type 2 diabetes is a complex disease with many potential points of intervention for pharmacotherapy. A majority of anti-diabetic patent applications claim chemical matter for just eight targets which include five enzymes, a GPCR, a family of nuclear hormone receptors and a class of sodium-dependent glucose co-transporters (11β-HSD1, DGAT1, DPP IV, glucokinase, GPR119, PPAR-α, -δ, -γ, SGLT1 and SGLT2, and stearoyl-CoA desaturase 1 (SCD1)). The major pharmaceutical companies are all pursuing some combination of these top eight targets. Several companies stand out for the breadth of new targets under investigation (e.g., F. Hoffmann-La Roche, Merck & Co., Pfizer, Takeda Pharmaceuticals, Sanofi-Aventis).