Miracle-dz/UniFAR-FTUs huggingface dataset:
Diffusion tensor imaging in male premutation carriers of the fragile X mental retardation gene

Older male premutation carriers of the FMR1 gene are associated with the risk of developing a late‐onset neurodegenerative disorder, fragile X–associated tremor/ataxia syndrome. Although previous postmortem and in vivo magnetic resonance imaging studies have indicated white matter pathology, the regional selectivity of abnormalities, as well as their relationship with molecular variables of the FMR1 gene, has not been investigated. In this study, we used diffusion tensor imaging to study male premutation carriers with and without fragile X–associated tremor/ataxia syndrome and healthy sex‐matched controls. We performed a tract of interest analysis for fractional anisotropy and axial and radial diffusivities of major white matter tracts in the cerebellar–brain stem and limbic systems. Compared with healthy controls, patients with fragile X–associated tremor/ataxia syndrome showed significant reductions of fractional anisotropy in multiple white matter tracts, including the middle cerebellar peduncle, superior cerebellar peduncle, cerebral peduncle, and the fornix and stria terminalis. Significant reduction of fractional anisotropy in these tracts was confirmed by voxel‐wise analysis using tract‐based spatial statistics. Analysis of axial and radial diffusivities showed significant elevation of these measures in middle cerebellar peduncle, even among premutation carriers without fragile X–associated tremor/ataxia syndrome. Furthermore, regression analyses demonstrated a clear inverted U‐shaped relationship between CGG‐repeat size and axial and radial diffusivities in middle cerebellar peduncle. These results provide new evidence from diffusion tensor imaging for white matter abnormalities in the cerebellar–brain stem and limbic systems among individuals with the fragile X premutation and suggest the involvement of molecular mechanisms related to the FMR1 gene in their white matter pathology. © 2011 Movement Disorder Society
Scalable Overlay Multicast Tree Construction for QoS-Constrained Media Streaming

Overlay networks have become popular in recent times for content distribution and end-system multicasting of media streams. In the latter case, the motivation is based on the lack of widespread deployment of IP multicast and the ability to perform end-host processing. However, constructing routes between various end-hosts, so that data can be streamed from content publishers to many thousands of subscribers, each having their own QoS constraints, is still a challenging problem. First, any routes between end-hosts using trees built on top of overlay networks can increase stress on the underlying physical network, due to multiple instances of the same data traversing a given physical link. Second, because overlay routes between end-hosts may traverse physical network links more than once, they increase the end-to-end latency compared to IP-level routing. Third, algorithms for constructing efficient, large-scale trees that reduce link stress and latency are typically more complex. This paper therefore compares various methods to construct multicast trees between end-systems, that vary in terms of implementation costs and their ability to support per-subscriber QoS constraints. We describe several algorithms that make trade-offs between algorithmic complexity, physical link stress and latency. While no algorithm is best in all three cases we show how it is possible to efficiently build trees for several thousand subscribers with latencies within a factor of two of the optimal, and link stresses comparable to, or better than, existing technologies.
Clinical application of self-expanding metallic stent in the management of acute left-sided colorectal malignant obstruction.

AIM To summarize our experience with the application of self-expanding metallic stent (SEMS) in the management of acute left-sided colorectal malignant obstruction. METHODS A retrospective chart review of all patients undergoing placement of SEMS between April 2000 and January 2004 was performed. RESULTS Insertion of SEMS was attempted in 26 patients under fluoroscopic guidance with occasional endoscopic assistance. The sites of lesions were located in splenic flexure of two patients, left colon of seven patients, sigmoid colon of eight patients and rectum of nine patients. The intended uses of SEMS were for palliation in 7 patients and as a bridge to elective surgery in 19 patients. In the latter group, placement of SEMS allowed for preoperative systemic and bowel preparation and the following one-stage anastomosis. Successful stent placement was achieved in 22 (85%) of the 26 patients. The clinical bowel obstruction resolved 24 hours after successful stent placement in 21 (95%) patients. Three SEMS-related minor complications occurred, two stents migrated and one caused anal pain. CONCLUSION SEMS represents an effective and safe tool in the management of acute malignant colorectal obstruction. As a bridge to surgery, SEMS can provide time for systematic support and bowel preparation and obviate the need for fecal diversion or on-table lavage. As a palliative measure, SEMS can eliminate the need for emergent colostomy.
Altered Spermidine/SpermineN 1-Acetyltransferase Activity as a Mechanism of Cellular Resistance to Bis(ethyl)polyamine Analogues*

To develop a model system to investigate mechanisms of antiproliferative action of bis(ethyl)polyamine analogues, intermittent analogue treatments followed by recovery periods in drug-free medium were used to select anN 1,N 12-bis(ethyl)spermine-resistant derivative of the Chinese hamster ovary cell line C55.7. The resulting C55.7Res line was at least 10-fold resistant toN 1,N 12-bis(ethyl)spermine andN 1,N 11-bis(ethyl)norspermine. The stability of the resistance in the absence of selection pressure was ≥9 months, indicating that a heritable genotypic change was responsible for the resistance phenotype. Polyamine transport alterations and multi-drug resistance were eliminated as causes of the resistance. Spermidine/spermineN 1-acetyltransferase (SSAT) activity and regulation were altered in C55.7Res cells as basal activity was decreased, and no activity induction resulted from exposure to analogue concentrations, which caused 300-fold enzyme induction in parental cells. SSAT mRNA levels in the absence and presence of analogue were unchanged, but no SSAT protein was detected in C55.7Res cells. A point mutation, which results in the change leucine156 (a fully conserved residue) to phenylalanine, was identified in the C55.7Res SSAT cDNA. Expression of wtSSAT activity in C55.7Res cells restored sensitivity to bis(ethyl)polyamines. These results provided definitive evidence that SSAT activity is a critical target of the cytotoxic action of these analogues.
Efficacy of ivermectin oral liquid for horses.

I vermectin has become a popular equine anthelmintic because of its high efficacy, broad spectrum of action, and wide margin of safety (1). Ivermectin is effective against all parasitic stages of Gasterophilus spp. (2), benzimidazole-resistant small strongyles (3), Dictyocaulus spp. (4), and the microfilariae of Onchocerca cervicalis (5). Although the efficacy of ivermectin against adults of Parascaris equorum is 95 to 100%, its efficacy against immature stages of this parasite has been suggested by some veterinary practitioners to be much lower. Ivermectin is significantly more effective against immature Parascaris larvae when given orally rather than by injection (6). Ivermectin is highly effective against adult ovaproducing nematode parasites. Within 7-14 days after treatment, fecal ova counts are usually near zero. A 9007 or greater reduction in eggs per gram (epg) is maintained for at least 63 days after treatment. Numbers of parasite ova usually increase slowly between 13 and 26 weeks following treatment (7). A new liquid formulation of ivermectin was developed to permit administration of ivermectin to horses by either nasogastric intubation or by oral drench. The objective of this study was to determine the acceptability and efficacy of ivermectin oral liquid (L-640, 471-242-F; MSD Agvet, Rahway, New Jersey, USA), for horses, administered as an oral drench or by nasogastric intubation at a dose of 1 mL/50 kg (200 ug/kg of body weight). The efficacy of the oral liquid formulation was also compared to ivermectin paste (Eqvalan, MSD Agvet, Rahway, New Jersey). The investigation was carried out on 40 adult and 60 yearling horses on two farms in Alberta and began in February 1986. Of the 60 Standardbred horses on farm A, there were 58 yearlings and two two-year-olds. The yearlings on this farm had been dewormed in November, three months prior to the start of the trial. The 40 horses on the second farm (B) included 38 grade saddle horses, aged 3 to 24 years, and two yearlings. None of the mares was pregnant or lactating. The horses on farm B had not been treated with an
Apo B/apo A-I ratio and cardiovascular risk prediction.

Apolipoproteins are proteins associated with lipids in lipoprotein particles. They play important roles in lipoprotein metabolism, such as transport of these hydrophobic molecules in plasma aqueous medium, binding to specific receptors in cell surface to correctly direct lipids to target organs and body tissues, and activation or inhibition of enzymes involved in lipid metabolism
Dysfunction of the islet lysosomal system conveys impairment of glucose-induced insulin release in the diabetic GK rat.

Accumulated evidence links an important signal involved in glucose-stimulated insulin release to the activation of the islet lysosomal glycogenolytic enzyme acid glucan-1,4-alpha-glucosidase. We have analyzed the function of the lysosomal system/lysosomal enzyme activities in pancreatic islets of young (6-8 weeks), spontaneously diabetic, GK (Goto-Kakizaki) rats and Wistar control rats in relation to glucose-induced insulin release. The insulin secretory response to glucose was markedly impaired in the GK rat, but was restored by the adenylate cyclase activator forskolin. Islet activities of classical lysosomal enzymes, e.g. acid phosphatase, N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, and cathepsin D, were reduced by 20-35% in the GK rat compared with those in Wistar controls. In contrast, the activities of the lysosomal alpha-glucosidehydrolases, i.e. acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase, were increased by 40-50%. Neutral alpha-glucosidase (endoplasmic reticulum) was unaffected. Comparative analysis of liver tissue showed that lysosomal enzyme activities were of the same magnitude in GK and Wistar rats. Notably, in Wistar rats, the activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase were approximately 15-fold higher in islets than in liver. Other lysosomal enzymes did not display such a difference. Normalization of glycemia in GK rats by phlorizin administered for 9 days did not influence either the lysosomal alpha-glucosidehydrolase activities or other lysosomal enzyme activities in GK islets. Finally, the pseudotetrasaccharide acarbose, which accumulates in the lysosomal system, inhibited acid glucan-1,4-alpha-glucosidase activity in parallel with its inhibitory action on glucose-induced insulin release in intact Wistar islets, whereas no effect was recorded for either parameter in intact GK islets. In contrast, acarbose inhibited the enzyme activity equally in islet homogenates from both GK and Wistar rats, showing that the catalytic activity of the enzyme itself in disrupted cells was unaffected. We propose that dysfunction of the islet lysosomal/vacuolar system is an important defect impairing the transduction mechanisms for glucose-induced insulin release in the GK rat.
Deletion of A44L, A46R and C12L Vaccinia Virus Genes from the MVA Genome Improved the Vector Immunogenicity by Modifying the Innate Immune Response Generating Enhanced and Optimized Specific T-Cell Responses

MVA is an attenuated vector that still retains immunomodulatory genes. We have previously reported its optimization after deleting the C12L gene, coding for the IL-18 binding-protein. Here, we analyzed the immunogenicity of MVA vectors harboring the simultaneous deletion of A44L, related to steroid synthesis and A46R, a TLR-signaling inhibitor (MVAΔA44L-A46R); or also including a deletion of C12L (MVAΔC12L/ΔA44L-A46R). The absence of biological activities of the deleted genes in the MVA vectors was demonstrated. Adaptive T-cell responses against VACV epitopes, evaluated in spleen and draining lymph-nodes of C57Bl/6 mice at acute/memory phases, were of higher magnitude in those animals that received deleted MVAs compared to MVAwt. MVAΔC12L/ΔA44L-A46R generated cellular specific memory responses of higher quality characterized by bifunctionality (CD107a/b+/IFN-γ+) and proliferation capacity. Deletion of selected genes from MVA generated innate immune responses with higher levels of determining cytokines related to T-cell response generation, such as IL-12, IFN-γ, as well as IL-1β and IFN-β. This study describes for the first time that simultaneous deletion of the A44L, A46R and C12L genes from MVA improved its immunogenicity by enhancing the host adaptive and innate immune responses, suggesting that this approach comprises an appropriate strategy to increase the MVA vaccine potential.
Relationship between alkaline phosphatase levels, osteopontin expression, and mineralization in differentiating MC3T3‐E1 osteoblasts

We are using viral oncogene probes to study the pathways by which osteoblast‐specific gene expression is induced in ascorbic acid‐treated MC3T3‐E1 cells. The 12S product of the adenovirus E1A gene binds directly to key cellular regulators and, as a result, represses tissue specific gene expression and blocks differentiation in a wide variety of cell types. The main cellular targets of the E1A 12S product are the pRB family and p300/CBP family. The p300 family appears to be the primary target for E1A‐mediated repression of tissue‐specific gene expression in a variety of cell types. We have generated MC3T3‐E1 cell lines that stably express either the wild‐type 12S product or a mutant that targets p300/CBP, but not the pRB family. Using these constructs to dissect osteoblast differentiation, we found that targeting of p300/CBP appears to be sufficient to repress alkaline phosphatase expression, although a low but functional level of expression can be maintained if the pRB family is not targeted as well. Induction of alkaline phosphatase expression and activity can be dissociated from expression of late‐stage markers such as osteocalcin and osteopontin. Surprisingly, cell lines exhibiting severe repression of alkaline phosphatase activity differentiate to a mineral‐secreting phenotype much like normal MC3T3‐E1 cells. Osteopontin induction is dependent on at least a minimal level of alkaline phosphatase activity, although it is not dependent on induction of alkaline phosphatase at the RNA level. If alkaline phosphatase is supplied exogenously, osteopontin expression can be induced in conditions in which endogenous alkaline phosphatase is severely repressed. J. Cell. Biochem. 68:269–280, 1998. © 1998 Wiley‐Liss, Inc.
Prevalence of vitamin D deficiency in post renal transplant patients

Aim: Deficiency of Vitamin D is prevalent in the general population, especially in Chronic Kidney Disease (CKD) patients. The exact prevalence of Vitamin D deficiency is unknown in post renal transplant recipients. The classical and non-classical effects of vitamin D deficiency are complicated by the use of steroids and calcineurin inhibitors (CNIs) in the renal transplant population. The aim of this study is to document the prevalence of Vitamin D deficiency in the post renal transplant population. Materials and Methods: A total of 51 renal transplant recipients under follow-up at Indraprastha Apollo Hospital, between June 2009 and March 2011, were enrolled in this study. Parathormone (PTH), 25(OH)-vitaminD3, calcium, and phosphate levels were determined in all the patients. The patients were then classified into different groups based on the severity of the Vitamin D deficiency, time since transplantation, and level of graft function. Results: Overall, four patients (8%) were vitamin D sufficient, 17 patients (33%) insufficient, 26 patients (51%) mildly deficient, and four (8%) severely deficient. The degree of deficiency did not differ with reference to the time since transplant or level of graft function. Sixty-nine percent had high PTH level, 22% were normal, and 9% had a low parathyroid hormone level. There was an inverse correlation between Vitamin D deficiency and serum PTH level. Conclusion: In this study, there was a high prevalence of vitamin D deficiency in renal transplant recipients. This did not get corrected, despite nutritional improvement or normalization of the glomerular filtration rate (GFR) post transplantation. Therefore, the study emphasizes routine evaluation and proper supplementation of Vitamin D in all post renal transplant patients.
Exploring the Intended and Unintended Consequences of High-Stakes Teacher Evaluation on Schools, Teachers, and Students

Background/Context The stakes are getting higher for teachers daily as more and more states adopt hiring, firing, and tenure-granting policies based on teacher evaluations. Even more concerning is the limited discussion about whether or not high-stakes teacher evaluation can meet the intended outcome of improved student achievement, and at what cost. These high-stakes decisions are based on the rationale that firing ineffective teachers (as primarily measured by observation data and value-added scores) will improve student achievement. This premise is challenged by various variables and assumptions (e.g., reliability, validity, percentage fired, and turnover) that, if not met, could result in a number of possible unintended consequences. Focus of Study This paper examines the history of high-stakes teacher evaluation and the ways in which teacher evaluation data are being used in today's schools to make human capital decisions. The intended consequences and unintended consequences are explored in great detail. Research Design This paper is an analytic essay. Conclusions/Recommendations There is no evidence that high-stakes teacher evaluation can produce a more effective teacher workforce and improve student achievement. Even if basic requirements and assumptions are met (e.g., highly reliable and valid measures, retention of effective teachers, and highly effective hires), gains in student achievement may be short lived, insignificant, or practically meaningless. The possible unintended consequences could result in worse, rather than better, student achievement outcomes and increase the gap in opportunity to learn for students attending the most and least affluent schools.
An exploration of teachers’ voice problems and their possible solution

The vocal demands on teachers in UK classrooms are explored in this mixed methods research which notes how little voice support teachers receive. The study draws on information from a range of fields: literature on voice problems, voice science, actor training, and the perspectives of teachers themselves. First-hand evidence collected through a survey questionnaire and individual interviews gives information of teachers ' voice problems. The study provides also an exploration of how voice quality is influenced by psychophysical use as defined in the Alexander Technique. The Technique was discovered by F.M. Alexander (1869-1955) and is well-known in the preparation of actors for performance. There are different understandings of what Alexander taught; what I set out in this study is the particular basis he passed on which influences my own use and voice. Detailed exploration taking place in a biomechanical laboratory replicated general vocal demand. Considerable quantitative data emerged with results showing that it is feasible to measure voice quality and other changes occurring when the teacher follows a procedure of the Technique to adjust their stance. The research aims to contribute towards knowledge of the teacher's voice, to inform provision for UK teachers, and to demonstrate further research is warranted.
Automated design of a three-dimensional fishbone antenna using parallel genetic algorithm and NEC

A new antenna configuration, named the three-dimensional fishbone antenna (3DFA), as an improvement of the conventional fishbone antenna, is presented in this letter. It consists of dipoles that may be of nonuniform lengths with unequal spacing and are allowed to tilt in haphazard directions. To achieve a high endfire gain and good impedance match, the structural parameters of the 3DFA are optimized in an automated design, making use of the genetic algorithm (GA) in conjunction with numerical electromagnetic codes (NEC) and cluster parallel computation. The design results are presented and discussed. A prototype of such designed 3DFA has been fabricated and tested. The measured radiation pattern and the return loss of the antenna are compared with the computational results, and a good agreement is observed. Another such designed 3DFA has achieved an endfire gain up to 16.72 dBi, which surpass the maximum gain of a conventional Yagi-Uda antenna with the same number of elements by 87%.
Activating NK‐cell receptors co‐stimulate CD4+CD28− T cells in patients with rheumatoid arthritis

Effector T‐cell responses can be modulated by competing positive or negative signals transduced by NK‐cell receptors (NKR). In the CD4+ T‐cell population, the expression of NKR is primarily found in the CD4+CD28− T‐cell subset, also known as CD28null T cells. These T cells are frequently found in rheumatoid arthritis (RA) and other inflammatory disorders, suggesting that signaling through NKR may play a role in the autoimmune reaction. Here we aimed to dissect the phenotype and function of NKR‐expressing CD4+CD28− T cells in patients with RA. By analyzing a broad array of NKR on CD4+CD28− T cells we found a significant expression of the co‐activating receptors 2B4 (CD244), DNAM‐1 (CD226), and CRACC. Pair‐wise ligations of 2B4 with DNAM‐1 and/or NKG2D lead to increased effector functions of primary CD4+CD28− T cells to suboptimal levels of anti‐CD3 stimulation. Using multi‐parameter flow cytometry, we demonstrate that such co‐ligation led to an increased magnitude in overall responsiveness without changing qualitative aspects of the response. Altogether these results demonstrate a pattern of additive effects in NKR‐mediated functional modulation of CD4+CD28− T cells in RA. This may have consequences for the inflammatory responses imposed by these cells, thus influencing disease manifestations.