Miracle-dz/UniFAR-FTUs huggingface dataset:
Hsp90 phosphorylation, Wee1 and the cell cycle

Heat Shock Protein 90 (Hsp90) is an essential molecular chaperone in eukaryotic cells, and it maintains the functional conformation of a subset of proteins that are typically key components of multiple regulatory and signaling networks mediating cancer cell proliferation, survival, and metastasis. It is possible to selectively inhibit Hsp90 using natural products such as geldanamycin (GA) or radicicol (RD), which have served as prototypes for development of synthetic Hsp90 inhibitors. These compounds bind within the ADP/ATP-binding site of the Hsp90 N-terminal domain to inhibit its ATPase activity. As numerous N-terminal domain inhibitors are currently undergoing extensive clinical evaluation, it is important to understand the factors that may modulate in vivo susceptibility to these drugs. We recently reported that Wee1Swe1-mediated, cell cycle-dependent, tyrosine phosphorylation of Hsp90 affects GA binding and impacts cancer cell sensitivity to Hsp90 inhibition. This phosphorylation also affects Hsp90 ATPase activity and its ability to chaperone a selected group of clients, comprised primarily of protein kinases. Wee1 regulates the G2/M transition. Here we present additional data demonstrating that tyrosine phosphorylation of Hsp90 by Wee1Swe1 is important for Wee1Swe1 association with Hsp90 and for Wee1Swe1 stability. Yeast expressing non-phosphorylatable yHsp90-Y24F, like swe1∆ yeast, undergo premature nuclear division that is insensitive to G2/M checkpoint arrest. These findings demonstrate the importance of Hsp90 phosphorylation for proper cell cycle regulation.
The Special Constabulary: Historical Context, International Comparisons and Contemporary Themes

Special constables are warranted officers retained within British constabularies. Wearing similar uniforms, carrying the same personal protective equipment and holding identical powers to enforce the criminal law, special constables are to all intents and purposes indistinguishable from their colleagues in the regular police service. However, very little is documented about the experiences and motivations of special constables, the roles they play in contemporary policing or the impact that they have on the police organisation. This book draws together academics and practitioners to provide a valuable insight into historical, international and contemporary themes pertinent to the historical development and contemporary operation of the special constabulary. The book critically considers the origins of the special constabulary and the political, social and economic factors which led to its evolution over time. It compares and contrasts the organisation, functions and status of the special constabulary with other auxiliary forces, notably from the United States. The book also contributes to theoretical understanding of contemporary policing, to debates about the roles and operation of the 'mixed economy' of provision, and informs policy and practice in the United Kingdom and beyond.
Therapeutic plasma exchange in the treatment of myasthenia gravis

Aim: The aim of this study was to analyze the retrospective experience related to the indication, complication and outcome of Therapeutic Plasma Exchange (TPE) in Myasthenia gravis (MG). It is a well known autoimmune disease characterized by antibodies against the acetylcholine receptor (anti-ACHR) on the post synaptic surface of the motor end plate. Plasma exchange is the therapeutic modality well established in MG with a positive recommendation based on strong consensus of class III evidence. Materials and Methods: A total of 35 patients of MG were submitted to a total of 41 cycles and 171 session of TPE. It was performed using a single volume plasma exchange with intermittent cell separator (Hemonetics) by Femoral or central line access and schedule preferably on alternate day interval. Immediate outcome was assessed shortly after each session and overall outcome at discharge. Results: Total of 110 patients of MG who were admitted to our hospital during the study period of two years. 35 (31.8%) patients had TPE performed with mean age of 32 years (M:F = 2:1). The mean number of TPE session was 4.2 (SD±1.2), volume exchange was 2215 ml (SD±435); overall incidence of adverse reaction was 21.7%. All patients had immediate benefits of each TPE cycle. Good acceptance of procedure was observed in 78.3% of patients. Conclusion: TPE may be considered as one of the treatment options especially in developing countries like ours as it is relatively less costly but as effective for myasthenic crisis as other modalities.
High-Performance and Cost-Effective Detector Using Microcolumnar CsI:Tl and SiPM

We are developing a technique to fabricate high spatial resolution and cost-effective photon counting detectors using silicon photomultipliers (SiPMs) and microcolumnar structured scintillator. Photon counting detectors using SiPMs are of much interest to the gamma- and X-ray detector community, but they have limitations at low energy due to their dark noise. In this paper, we report on vapor deposition of CsI:Tl directly onto a SiPM, a technique that improves optical coupling and allows for detection of low energy gamma- and X-rays. It simultaneously addresses related issues of light loss and light spread in the scintillator, thereby improving the performance of the detector. Devices made by this technique may be used for both photon counting and gamma- and X-ray imaging.
Spectrum Sensing for OFDM-Based Cognitive Radio

Abstract-Given the ever growing demand for radio spectrum,cognitive radio has recently emerged as an attractive wireless technology. Since orthogonal frequency division multiplexing (OFDM) is one of the major wideband transmission techniques, detection of OFDM signals in low signal-to-noise-ratio (SNR)scenario is an important research problem. In this paper, it is shown that the cyclic prefix correlation coefficient (CPCC) algorithm, which has been introduced as a simple and computationally efficient spectrum sensing test for OFDM signals, is a special case of the constrained generalized likelihood ratio test(GLRT) in the absence of multipath. As such, the performance of this algorithm degrades in a multipath scenario where OFDM is usually implemented. Moreover, by considering the multipath correlation in the GLRT algorithm and employing the inherent structure of OFDM signals, a simple and low complexity algorithm, called multipath-based constrained-GLRT (MP-based CGLRT)algorithm is obtained. The MP-based C-GLRT algorithm is shown to outperform the CPCC-based algorithm in a rich multipath environment. Further performance improvement can be achieved by simply combining both the CPCC-based and MPbased C-GLRT algorithms.
Comparative analysis of the uptake and expression of plasmid vectors in human ciliary and retinal pigment epithelial cells in vitro

The retinal pigment epithelium is uniquely suited to gene therapy that uses lipid‐mediated DNA transfer due to its high phagocytic activity in situ. We compared the relative efficacy of phagocytosis on the uptake of labeled plasmid vectors by retinal pigment epithelial and ciliary epithelial cells in vitro. Relative levels of endocytosis were then compared with the efficiency of marker transgene expression in these cells. Human retinal pigment epithelial and ciliary epithelial cells from a single donor were isolated and expanded in vitro. Polyplex‐mediated transfections were performed using a rhodamine‐labeled expression vector for green fluorescent protein. Rhodamine‐labeled endosomes were examined by fluorescence microscopy at different time points. Rhodamine labeling and green fluorescent protein expression were analyzed by flow cytometry 48 h after transfection. These gene transfer studies showed that expression of transgenes does occur in both human retinal pigment epithelial and ciliary epithelial cells in vitro. Endocytosis of labeled plasmid vectors occurs at a significantly higher number and density in retinal pigment epithelial cells than in ciliary epithelial cells (P < 0.04). However, the efficiency of marker transgene expression is similar in the two cell types. These studies demonstrate that the higher intrinsic phagocytic activity does not enhance the efficacy of transgene expression in retinal pigment epithelial cells in vitro. Both human retinal pigment epithelial and ciliary epithelial cells are competent recipients for lipid‐mediated gene transfer, and transgene expression occurs at similar levels in both cell types. J. Cell. Biochem. 83: 671–677, 2001. © 2001 Wiley‐Liss, Inc.
Effects of dietary calcium on adipocyte lipid metabolism and body weight regulation in energy‐restricted aP2‐agouti transgenic mice

We have demonstrated previously a regulatory role for intracellular Ca2+ ([Ca2+]i) in adipocyte lipogenesis and lipolysis and have recently reported that 1,25‐(OH)2‐D increases adipocyte [Ca2+]i, which causes increased lipogenesis and decreased lipolysis. We have now tested the hypothesis that suppressing 1,25‐(OH)2‐D by increasing dietary calcium will suppress adipocyte [Ca2+]i, thereby facilitating weight loss by stimulating lipolysis and inhibiting lipogenesis in calorically (Kcal)‐restricted (70% of ad lib) aP2‐agouti transgenic (aP2‐a) mice. Mice (aP2‐a) exhibiting a pattern of obesity gene expression similar to humans were fed a low‐Ca (0.4%)/high‐fat/high‐sucrose diet for six weeks, resulting in a 27% and twofold increase in body weight and total fat pad mass, respectively, with a twofold increase in adipocyte [Ca2+]i (p<0.001). Mice were then either maintained on the same low‐Ca basal diet ad lib or Kcal‐restricted (70% of ad lib) on this diet either unsupplemented (basal) or with 25% or 50% of the protein replaced by non‐fat dry milk (medium or high) dairy or supplemented with CaCO3 to 1.2% Ca for six weeks. Adipocyte [Ca2+]i was unaffected by Kcal restriction but was reduced markedly by all three high Ca diets (290 vs. 130 nM, p<0.001). Body weight was reduced by 11%, 19%, 25%, and 29% by the restricted basal, high‐Ca, medium‐dairy and high‐dairy diets, with corresponding decreases in fat pad mass of 8, 42, 60, and 69% vs. ad lib basal (p<0.001), respectively. The high‐Ca diets caused similar decreases in fatty acid synthase activity 35%‐63%, p<0.001), increases in lipolysis (two‐ to threefold, p<0.001). All three high‐Ca diets increased adipocyte uncoupling protein 2 expression approximately twofold (p<0.02), with a corresponding increase in core temperature (0.48‐0.67°C, p<0.05). Thus, high‐Ca diets suppress adipocyte [Ca2+]i and thereby reduce energy storage and increase thermogenesis during Kcal restriction.
Differences in heart valve procedures between North American and European centers: a report from the Artificial Valve Endocarditis Reduction Trial (AVERT).

BACKGROUND AND AIM OF THE STUDY Differences in heart valve procedures between North American (NA) and European (EU) centers were evaluated in a multicenter trial. METHODS Between July 1998 and January 2000, 807 patients from 12 NA (n = 446) and seven EU centers (n = 361) were randomized to receive either Silzone or conventional valves in the Artificial Valve Endocarditis Reduction Trial (AVERT). Subanalysis was performed to compare demographics, patient risk profile, surgical techniques and perioperative management of patients in NA and EU centers. RESULTS Mean age was significantly younger and body mass index higher in NA. Patients' risk profiles showed significantly higher incidences of previous myocardial infarction, congestive heart failure, angina, prior cardiovascular surgery, and history of smoking in NA. A different distribution of implant position was observed between groups: aortic valve/mitral valve/double valve replacement in 54.0, 35.7 and 10.3% in NA, and 64.5, 27.4 and 8.0% in EU (p <0.01). Concomitant coronary artery bypass grafting was performed in 31.6% of NA patients and 19.4% of EU patients (p <0.001). Timing of surgery showed a higher incidence of urgent procedures in NA centers. Distribution of valve sizes and perioperative complication rate were similar, but length of hospital stay was longer in EU centers. CONCLUSION Surprisingly, surgeons in NA and EU centers are faced by different patient populations requiring mechanical heart valve replacement. NA patients were younger, but required more extensive surgery. Surgical technique and perioperative management appear to differ in NA and EU centers. These differences in reporting heart valve procedures might have been influenced by variable interpretations of definitions and different patient expectations, although a uniform study protocol with consistent definitions was used at all sites.
Phytorestoration using Arbuscular Mycorrhizal Fungi in Association with Desert Plants in Boron-Contaminated Soils

Borax mining at the Rio Tinto boron mine in Boron, California has caused pollution of soil, desertification of local habitats, and loss of biodiversity due to severe boron contamination. I conducted a phytoremediation study to test the effects arbuscular mycorrhizal fungi in association with native plant species. The goal of this study was to evaluate the effect of arbuscular mycorrhizal fungi on desert plants’ ability to tolerate the boron pollution from Rio Tinto soils. I evaluated bush peppergrass (Lepidium fremontii), quail bush (Atriplex lentiformis), desert dandelion (Malacothrix glabrata), white cheesebush (Hymenoclea salsola), and cattle spinach (Atriplex polycarpa) in Rio Tinto soils containing three different levels of boron. Eight replicates of each species grew in each soil type, with half inoculated with arbuscular mycorrhizal fungi. After four weeks of growth in the Rio Tinto soils, I harvested, cleaned, and dried the plants. I measured fresh weights immediately after harvesting and dry weights after forty-eight hours of oven drying to determine biomass accumulation. The results of the study indicate that in general arbuscular mycorrhizal fungi acts as a parasite on plants in order to obtain nutrients rather than a symbiont under high boron conditions, leading to significantly lower survival and biomass accumulation in plants inoculated with arbuscular mycorrhizal fungi compared to those that were not inoculated. The results indicate that the addition of arbuscular mycorrhizal fungi to native plants is not a viable addition for increasing plant survival or biomass accumulation for phytoremediation purposes at the Rio Tinto boron mine.
Aleutian mink disease parvovirus infection of mink peritoneal macrophages and human macrophage cell lines

Aleutian mink disease parvovirus (ADV) mRNAs are found in macrophages in lymph nodes and peritoneal exudate cells from ADV-infected mink. Therefore, we developed an in vitro infection system for ADV by using primary cultures of mink macrophages or macrophage cell lines. In peritoneal macrophage cultures from adult mink, virulent ADV-Utah I strain showed nuclear expression of viral antigens with fluorescein isothiocyanate-labeled ADV-infected mink serum, but delineation of specific viral proteins could not be confirmed by immunoblot analysis. Amplification of ADV DNA and production of replicative-form DNA were observed in mink macrophages by Southern blot analysis; however, virus could not be serially propagated. The human macrophage cell line U937 exhibited clear nuclear expression of viral antigens after infection with ADV-Utah I but not with tissue culture-adapted ADV-G. In U937 cells, ADV-Utah I produced mRNA, replicative-form DNA, virion DNA, and structural and nonstructural proteins; however, virus could not be serially passaged nor could [3H]thymidine-labeled virions be observed by density gradient analysis. These findings indicated that ADV-Utah I infection in U937 cells was not fully permissive and that there is another restricted step between gene amplification and/or viral protein expression and production of infectious virions. Treatment with the macrophage activator phorbol 12-myristate 13-acetate after adsorption of virus reduced the frequency of ADV-positive U937 cells but clearly increased that of human macrophage line THP-1 cells. These results suggested that ADV replication may depend on conditions influenced by the differentiation state of macrophages. U937 cells may be useful as an in vitro model system for the analysis of the immune disorder caused by ADV infection of macrophages.
Post-neurosurgical meningitis: Management of cerebrospinal fluid drainage catheters influences the evolution of infection

Background: In order to better define the pathogenic role of cerebrospinal fluid (CSF) drainage catheters in postoperative patients, we comparatively analyze the clinical course of device and non-device-related meningitis. Methods: This is an observational, partially prospective, study on consecutive adult patients who developed meningitis after undergoing neurosurgical procedures at the Neurosurgery and Neurointensive care Departments, Spedali Civili, Brescia, Italy, between January 1999 and August 2007. Results: All 77 consecutive post-neurosurgical meningitis events in 65 patients were included in the analysis. Most were classified as external ventricular drainage (EVD)-related meningitis (23 cases, group A), external spinal drainage (ESD)-related meningitis (12 cases, group B), and non-device-related post-neurosurgical meningitis (30 cases, group C). Proven meningitis was identified in 78.3%, 91.7% and 56.7% of the events, respectively. ESD-related meningitis had a shorter onset time vs EVD and non-device-associated meningitis (3 days versus 6 and 7 days, respectively). Median antibiotic treatment duration was 20, 17, and 22.5 days in groups A, B, and C, respectively. Overall, 8 patients (34.8%) in group A, 3 (25.0%) in group B, and 3 (10.0%) in group C died. Median time to become afebrile was shorter in group C than in group A (10 days versus 12 days, P = 0.04). Removal of the device later than 48 hours after meningitis onset, as well as implantation of a second device were associated with a slower time of meningitis resolution. Conclusions: Early device removal and avoiding implantation of a second device were associated with short illness duration. Larger studies are warranted to confirm the conclusions of this study.
Stability of the flapping-wing vehicle near hovering under active control by varying flapping frequency

We establish the dynamics relative to flapping angle of the flapping wing vehicle based on the quasi-steady aerodynamics model and Newton-Euler motion equations, and describe the stability analysis method of linearized perturbation equation under active control by varying flapping frequency based on the Routh-Hurwitz stability criterion. To give a demonstration, we design a flapping wing mechanism and analyze its stability under the linear controller. As a typical benchmark, the aerodynamic and kinematic parameters of a hummingbird are used to estimate stability derivatives of the flapping-wing vehicle. The feasible region for the gain selection of our linear controller is finally obtained.
Mass spectrometry-based neurochemical analysis: perspectives for primate research

The analysis of neurochemicals from the brain represents a challenge for current analytical techniques due to a variety of factors, such as compositional complexity, limited amounts of sample and endogenous inferences. Advances in mass spectrometry (MS) provide great opportunities for the sensitive measurement of neurochemicals, offering benefits including simple sample preparation, broad capability for analysis of diverse compounds and rich structural information of analytes. Until recently, however, limited numbers of studies have reported on the analysis of small molecular neurochemicals, such as classical neurotransmitters, in part due to the difficulties in separation of polar molecules by using current chromatography techniques with MS-compatible conditions. By contrast, MS has become an indispensable tool for neuropeptide analysis , offering tremendous potential in the discovery of novel signaling peptides and biomarkers. This review covers recent advances in MS-based neurochemical analysis , including a comparison with related detection techniques, chromatographic separation and neuropeptide discovery. Issues relating to in vivo sample collection and sample preparation are discussed. To provide a wider view of the capability of MS in basic neuroscience and clinical research, we discuss MS-based neurochemical analysis conducted in different animal models and humans. We specifically highlight perspectives for the use of MS for brain functional studies and drug discovery in nonhuman primates.
Physician social networks and variation in prostate cancer treatment in three cities.

OBJECTIVE To examine whether physician social networks are associated with variation in treatment for men with localized prostate cancer. DATA SOURCE 2004-2005 Surveillance, Epidemiology and End Results-Medicare data from three cities. STUDY DESIGN We identified the physicians who care for patients with prostate cancer and created physician networks for each city based on shared patients. Subgroups of urologists were defined as physicians with dense connections with one another via shared patients. PRINCIPAL FINDINGS Subgroups varied widely in their unadjusted rates of prostatectomy and the racial/ethnic and socioeconomic composition of their patients. There was an association between urologist subgroup and receipt of prostatectomy. In city A, four subgroups had significantly lower odds of prostatectomy compared with the subgroup with the highest rates of prostatectomy after adjusting for patient clinical and sociodemographic characteristics. Similarly, in cities B and C, subgroups had significantly lower odds of prostatectomy compared with the baseline. CONCLUSIONS Using claims data to identify physician networks may provide an insight into the observed variation in treatment patterns for men with prostate cancer.
Prevalence of visual and hearing impairment in a Dutch institutionalized population with intellectual disability.

A screening of hearing and visual function was performed using clinical assessment methods in a Dutch institutionalized population of 672 people with mild to profound intellectual disability (ID). Because the studied population was not comparable to the total Dutch population with ID, subgroups were distinguished according to level of ID, age younger and older than 50 years, and the presence or absence of Down's syndrome (DS). The prevalences of both hearing and visual impairment were considerably increased in all subgroups, as compared with the general population. In the least affected group, i.e. those < 50 years with a mild or moderate ID by other causes than DS, the prevalences of hearing and visual impairment were 21% and 4%, respectively (as opposed to 2-7% and 0.2-1.9% in the general Dutch population <50 years, respectively). The prevalence of hearing impairment showed a sharp and highly significant increase in individuals with DS and subjects > or = 50 years. To a lesser extent, young adults with severe or profound ID had an increased risk of hearing impairment. Visual impairment and blindness were specifically highly prevalent in people with severe or profound ID (51% < 50 years of age). Down's syndrome and an age > or = 50 years were also significant risk factors for visual impairment. There was an alarmingly high prevalence of combined sensory impairment, especially in those with severe or profound ID (20%). Although hearing impairment had been diagnosed prior to this screen in 138 people and visual impairment in 65 individuals, a first diagnosis of hearing impairment was made in 128 subjects and of visual impairment in 90 cases. This highlights the tendency for sensory impairments to go unnoticed in people with ID, which is not restricted to those with severe or profound ID. Therefore, the present authors stress the importance of regular screening as outlined in the existing IASSID international consensus statement.