Miracle-dz/UniFAR-FTUs huggingface dataset:
Stability of AML1 (core) site enhancer mutations in T lymphomas induced by attenuated SL3-3 murine leukemia virus mutants

Murine retrovirus SL3-3 is highly T lymphomagenic. Its pathogenic properties are determined by the transcriptional enhancer of the U3 repeat region which shows preferential activity in T cells. Within the U3 repeats, the major determinant of T-cell specificity has been mapped to binding sites for the AML1 transcription factor family (also known as the core binding factor [CBF], polyomavirus enhancer binding protein 2 [PEBP2], and SL3-3 enhancer factor 1 [SEF-1]). SL3-3 viruses with AML1 site mutations have lost a major determinant of T-cell-specific enhancer function but have been found to retain a lymphomagenic potential, although disease induction is slower than for the SL3-3 wild type. To compare the specificities and mechanisms of disease induction of wild-type and mutant viruses, we have examined lymphomas induced by mutant viruses harboring transversions of three consecutive base pairs critical to AML1 site function (B. Hallberg, J. Schmidt, A. Luz, F. S. Pedersen, and T. Grundström. J. Virol. 65:4177-4181, 1991). Our results show that the mutated AML1 sites are genetically stable during lymphomagenesis and that ecotropic provirus numbers in DNA of tumors induced by wild-type and mutant viruses fall within the same range. Moreover, proviruses were found to be integrated at the c-myc locus in similar proportions of wild-type and mutant SL3-3-induced tumors, and the mutated AML1 sites of proviruses at c-myc are unaltered. In some cases, however, including one c-myc-integrated provirus, a single-base pair change was detected in a second, weaker AML1 binding site. By DNA rearrangement analysis of the T-cell receptor beta-locus, tumors induced by the AML1 site mutants are found to be of the T-cell type. Thus, although the AML1 site mutants have weakened T-cell-specific enhancers they are T-lymphomagenic, and wild-type- and mutant-virus-induced tumor DNAs are similar with respect to the number of overall ecotropic and c-myc-integrated clonal proviruses. The SL3-3 wild-type and AML1 site mutant viruses may therefore induce disease by similar mechanisms.
Age-related association of small intestinal mucosal enteropathy with nutritional status in rural Gambian children.

Small bowel enteropathy (assessed by the lactulose (L) : mannitol (M) permeability test) is a major factor in infant growth faltering and malnutrition in The Gambia. However, little is known about its persistence and nutritional effect beyond 2 years of age. This was addressed by two cross-sectional studies of intestinal permeability and nutritional status in 162 residents, aged 2-60 years, living in three villages in rural Gambia. L:M ratio was found to be highest in the youngest children and although there was a significant improvement with age (P<0.0001), values were always greater than the range found in UK counterparts. M recovery (mean value 5.68 (se 0.12) %) was at all times between one-third and one-half of expected UK values and showed no improvement with age. Gut barrier function, assessed by L uptake, improved with age (P<0.001) and fell within the UK normal range beyond age 10 years. Both the L:M permeability ratio and L recovery were significantly associated with height-for-age z-scores and -0.22 respectively, P<0.001), a relationship that persisted throughout childhood and into adulthood. Change in height-for-age z-score between the two visits was also related to the L:M ratio P=0.018). The close within-subject correlation of permeability variabilities between the two visits suggests a long-term persistence of enteropathy within individuals. It appears that the small bowel enteropathy previously described in Gambian infants persists through to adulthood. Although the lesion improves with age, the relationship between attained height and L:M permeability raises the possibility that enteropathy may continue to limit growth throughout childhood and puberty.
The Protective Effect of Melatonin against Fumonisin-Induced Renal Damage in Rats

The present study was designed to investigate the potential protective effect of melatonin against the renal toxicity of fumonisin in female rats. Six groups of animals were used in this study. The first group served as control. The second group was given melatonin only at a dose level of 10 mg/kg. The third group was fed ration contaminated with fumonisin (100 mg/kg diet). The fourth group was fed ration contaminated with fumonisin (200 mg/kg diet). The fifth group was given daily interperitoneal injection (IP) 10 mg/kg melatonin and fed ration contaminated with fumonisin (100 mg/kg diet). The sixth group was given daily interperitoneal injection of 10 mg/kg melatonin and fed ration contaminated with fumonisin (200 mg/kg diet). The rats were treated for 1 month. Histopathological and histochemical changes in the kidney were investigated. In addition, DNA ploidy was measured in the kidney. Fumonisin administration (100 or 200 mg/Kg diet) to unpretreated control rats caused extensive renal damage as evaluated by histopathology, histochemistry, and/or DNA ploidy measurement. No apparent changes following administration of melatonin. Melatonin coadministration to the fumonisin-administered rats reduced kidney damage and the tissues appeared more or less like the normal. The present study indicates that melatonin has a protective effect in fumonisin-induced renal damage.
Fetal alcohol syndrome disorder pilot media intervention in New Jersey.

BACKGROUND The New Jersey Fetal Alcohol Spectrum Disorders Task Force launched the âBe in the kNOwâ multimedia public education campaign in July 2006. The campaign continued until December 2006. OBJECTIVE To report on the pilot media intervention campaign in Essex and Atlantic Counties, New Jersey, with the goal of identifying strategies to help prevent Fetal Alcohol Syndrome Disorder (FASD). METHODS The campaign used various media outlets from July 2006 to December 2006, including billboard posters along New Jersey transit routes serving Atlantic City and Newark, local newspapers and radio public service announcements. Messages were distributed in English and Spanish and were primarily aimed at Essex and Atlantic counties. Printed material was distributed throughout the community. All media materials included an 800 number for the New Jersey Family Health Line. Data was collected from individual callers. RESULTS A total of 49 Fetal Alcohol Syndrome (FAS) related telephone calls were received through the Family Health Line over the six-month period. An increase from the 5-6 FAS calls typically received in a six-month period. Callers were located throughout New Jersey with 24.5% from Essex County, 12.2% from Mercer County, and 12.2% from Bergen County. 69% of callers identified themselves as white, 25% black, and 6% other. 76% of callers were female. Ages ranged from 8 to 50. CONCLUSION The media intervention reached a wide geographic audience, provoking interest beyond the initial target area and expected age ranges. The results, however, point to the difficulty of raising awareness of FASD.
Etude articulatoire et acoustique des fricatives sibilantes

L’objectif de cette these est de decrire de maniere analytique le spectre du bruit de friction en mettant en evidence l’affiliation des pics spectraux aux cavites du conduit vocal, par le biais de la modelisation acoustique et avec l’aide des donnees IRM de 7 langues [30 locuteurs]. Les resultats sont les suivants : 1. La dispersion des sibilantes dans l’espace articulatoire depend du systeme phonologique [contrastes [+/- anterieur], [+/- distribue], ou les deux]. En francais [+/- anterieur], 7 locuteurs], la variation inter-individuelle est importante. 2. Cette variation est due a deux variantes articulatoires du /ʃ/ : (a) plutot apical, comportant une cavite sublinguale, accompagne de protrusion labiale, et semblable au /ʂ/ polonais ; et [b] palatalise, mettant en œuvre le bombement du dos de la langue, comparable au /ɕ/ polonais. L’equivalence acoustique des deux variantes est demontree par une simulation acoustique systematique. 3. En polonais, ou la difference articulatoire est phonemique, /ʂ/ est caracterise par un pic ultra-bas [1,5-1,8 kHz], affilie a la cavite anterieure, d’apres la simulation acoustique a l’aide de fonction d’aire reelles de deux locuteurs. 4. Les donnees articulatoires presentent systematiquement une constriction dentale etroite. D’apres la modelisation acoustique, la protrusion labiale aurait comme effet d’abaisser la frequence d’un formant affilie specifiquement a la cavite labiale. En somme, la presence de deux constrictions etroites linguale et dentale rend possible le controle quasi independant d’au moins deux resonances. Cette specificite garantit aux sibilantes un bruit distinctif qui permet d’expliquer la richesse de leurs inventaires
Inhibition of Clostridium botulinum by antioxidants, phenols, and related compounds

A total of 75 compounds, including antioxidants, preservatives, gallic acid and p-hydroxybenzoic acid esters, hydroquinones, hydroxyquinolines, phenol derivatives, and related compounds, were screened for their antibotulinal activity in prereduced Thiotone-yeast extract-glucose broth. The most effective inhibitors of Clostridium botulinum growth and toxin production were long-chain esters of p-hydroxybenzoic acid and gallic acid, antioxidants, and butylphenol derivatives. The antioxidant nordihydroguaiaretic acid at 100 microgram/ml delayed the growth and toxin production for the entire incubation period (7 days). Other antioxidants, such as butylated hydroxytoluene, butylated hydroxyanisole, and tert-butylhydroquinone were also very effective (at 200 to 400 microgram/ml) for the inhibition of C. botulinum growth and toxin production. Toxin was detected, although no detectable growth was found by daily absorbance measurements, in the prereduced medium containing 50 to 400 microgram of 8-hydroxyquinoline, pentylphenol, tert-pentylphenol, 3,5-ditert-butylphenol, 3,5-ditert-butylcatechol, (2-hydroxydiphenyl)methane, or (4-hydroxydiphenyl)methane per ml.
Neural associations of the substantia innominata in the rat: Afferent connections

The afferent connections of the substantia innominata (SI) in the rat were determined employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA‐L) and the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA‐HRP), in combination with histochemical procedures to characterize the neuropil of the SI and identify cholinergic cells. Both neurochemical and connectional data establish that the SI is organized into a dorsal and a ventral division. Each of these divisions is strongly affiliated with a different region of the amygdala, and, together with its amygdalar affiliate, forms part of one of two largely distinct constellations of interconnected forebrain and brainstem cell groups.
Population pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with type 2 diabetes

Data from five randomized, placebo‐controlled, multiple oral dose studies of empagliflozin in patients with type 2 diabetes mellitus (T2DM; N = 974; 1–100 mg q.d.; ≤12 weeks) were used to develop a population pharmacokinetic (PK) model for empagliflozin. The model consisted of two‐compartmental disposition, lagged first‐order absorption and first‐order elimination, and incorporated appropriate covariates. Population estimates (interindividual variance, CV%) of oral apparent clearance, central and peripheral volumes of distribution, and inter‐compartmental clearance were 9.87 L/h (26.9%), 3.02 L, 60.4 L (30.8%), and 5.16 L/h, respectively. An imposed allometric weight effect was the most influential PK covariate effect, with a maximum effect on exposure of ±30%, using 2.5th and 97.5th percentiles of observed weights, relative to the median observed weight. Sex and race did not lend additional description to PK variability beyond allometric weight effects, other than ∼25% greater oral absorption rate constant for Asian patients. Age, total protein, and smoking/alcohol history did not affect PK parameters. Predictive check plots were consistent with observed data, implying an adequate description of empagliflozin PKs following multiple dosing in patients with T2DM. The lack of marked covariate effects, including weight, suggests that no exposure‐based dose adjustments were required within the study population and dose range.
Computerized, interactive, multimedia cognitive-behavioural program for anxiety and depression in general practice

Background. Cognitive-behavioural therapy (CBT) brings about significant clinical improvement in anxiety and depression, but therapists are in short supply. We report the first phase of a randomized controlled trial of an interactive multimedia program of cognitive-behavioural techniques, Beating the Blues™ (BtB), in the treatment of patients in general practice with anxiety, depression or mixed anxiety/depression. Method. One hundred and sixty-seven adults suffering from anxiety and/or depression and not receiving any form of psychological treatment or counselling were randomly allocated to receive, with or without medication, BtB or treatment as usual (TAU). Measures were taken on five occasions: prior to treatment, 2 months later, and at 1, 3 and 6 months follow-up using the Beck Depression Inventory, Beck Anxiety Inventory and Work and Social Adjustment Scale. Results. Patients who received BtB showed significantly greater improvement in depression and anxiety compared to TAU by the end of treatment (2 months) and to 6 months follow-up. Symptom reduction was paralleled by improvement in work and social adjustment. There were no interactions of BtB with concomitant pharmacotherapy or duration of illness, but evidence, on the Beck Anxiety Inventory only, of interaction with primary care practice. Importantly, there was no interaction between the effects of BtB and baseline severity of depression, from which we conclude that the effects of the computer program are independent of starting level of depression. Conclusions. These results demonstrate that computerized interactive multimedia cognitive-behavioural techniques under minimal clinical supervision can bring about improvements in depression and anxiety, as well as in work and social adjustment, with and without pharmacotherapy and in patients with pre-treatment illness of durations greater or less than 6 months. Thus, our results indicate that wider dissemination of cognitive-behavioural techniques is possible for patients suffering from anxiety and/or depression.
Morphological and immunocytochemical diagnosis of thyroiditis: Comparison between conventional and liquid‐based cytology

The efficacy of thyroid (FNAB) processed by liquid‐based cytology (LBC) in Hashimoto's Thyroiditis (HT) in two reference periods, is evaluated. The morphologic features of 820 cases with both methods and the cyto‐histological comparison are analyzed. The diagnosis of hyperplastic nodules (HN) in HT, its mimickers especially in presence of oxyphilic cells and the role of immunocytochemistry (IHC) are studied.
Kinematic and Kinetic Variations Among Three Depth Jump Conditions in Male NCAA Division III Athletes

Smith, JP, Kernozek, TW, Kline, DE, and Wright, GA. Kinematic and kinetic variations among three depth jump conditions in male NCAA division III athletes. J Strength Cond Res 25(1): 94-102, 2011-Our purpose was to provide an in-depth investigation of 2 commonly used depth jump variants: depth jumping over a hurdle and depth jumping while touching as high as possible using an overhead goal. Fourteen male athletes performed a series of depth jumps from a 45-cm box. Three types of jumping conditions were used. One type of depth jump was a control jump (DJ45-C), performed for maximal height with no external apparatus used to influence the jump. Another type of depth jump was performed over a hurdle (DJ45-H), which was set at an individualized height for each athlete based on their leaping ability. The final type of depth jump was performed for maximal touch height on a Vertec measuring device (DJ45-T). Timing, kinematics, and kinetics of the 3 jumping conditions were compared. The hurdle depth jumping condition demonstrated lower ground contact times and significantly less (p < 0.05) flexion in the hips (41.22 ± 8.10 degrees) and knees (67.47 ± 8.36 degrees) when compared to control (49.26 ± 10.90 degrees of hip flexion and 73.85 ± 10.68 degrees of knee flexion) and target (50.51 ± 9.51 degrees of hip flexion and 75.01 ± 9.97 degrees of knee flexion) conditions. Jumping conditions that used goals (DJ45-H, DJ45-T) produced significantly higher (p < 0.05) vertical velocity of the sacrum at toe-off (3.57 ± .34 m/s and 3.46 ± .36 m/s, respectively) than the control condition (3.32 ± .34 m/s). The hurdle depth jump condition had higher ground reaction forces (875.36 ± 135.66 N) and higher dorsiflexion (566.02 ± 402.45 W) and plantar flexion power (768.84 ± 192.19 W) at the ankle than the Vertec (409.83 ± 387.23 W for dorsiflexion and 622.54 ± 188.95 W for plantar flexion) and control conditions (425.60 ± 380.01 W for dorsiflexion and 643.35 ± 166.70 W for plantar flexion). Few differences were found to exist between the Vertec and control conditions. Hurdle jumping in particular may be superior for the development of short ground contact time (<0.3 s) sport movements requiring brief but powerful lower-extremity power production.
Hepatitis C Virus RNA Replication Occurs on a Detergent-Resistant Membrane That Cofractionates with Caveolin-2

ABSTRACT The mechanism and machinery of hepatitis C virus (HCV) RNA replication are still poorly understood. In this study, we labeled de novo-synthesized viral RNA in situ with bromouridine triphosphate (BrUTP) in Huh7 cells expressing an HCV subgenomic replicon. By immunofluorescence staining using an anti-BrUTP antibody and confocal microscopy, we showed that the newly synthesized HCV RNA was localized to distinct speckle-like structures, which also contain all of the HCV nonstructural (NS) proteins. These speckles are distinct from lipid droplets and are separated from the endoplasmic reticulum (ER), where some HCV NS proteins also reside. Membrane flotation analysis demonstrated that almost all of the NS5A and part of the NS5B proteins and all of the viral RNA were present in membrane fractions which are resistant to treatment with 1% NP-40 at 4°C. They were cofractionated with caveolin-2, a lipid-raft-associated intracellular membrane protein, in the presence or absence of the detergent. In contrast, the ER-resident proteins were detergent soluble. These properties suggest that the membranes on which HCV RNA replication occurs are lipid rafts recruited from the intracellular membranes. The protein synthesis inhibitors cycloheximide and puromycin did not inhibit viral RNA synthesis, indicating that HCV RNA replication does not require continuous protein synthesis. We suggest that HCV RNA synthesis occurs on a lipid raft membrane structure.
Role of continuous subcutaneous insulin infusion in patients with recalcitrant diabetes in South India.

BACKGROUND We aimed to assess the effect of continuous subcutaneous insulin infusion (CSII) therapy in patients with "recalcitrant diabetes" whose glycemia had not been controlled adequately with multiple daily injections of insulin or insulin plus oral hypoglycemic agents. PATIENTS AND METHODS We retrospectively analyzed the medical records of patients with diabetes who were initiated on insulin pump therapy at our center in India between 2002 and 2007. Data analysis included fasting and postprandial blood glucose and glycated hemoglobin (HbA1c) values, insulin requirement, body weight, and the occurrence of hypoglycemia and diabetic ketoacidosis. RESULTS We studied 33 patients with diabetes (type 1 [n = 17] and type 2 [n = 16]) who were on CSII therapy for a mean duration of 3.4 years. A statistically significant reduction in HbA1c was found after initiating CSII (prepump 10.7% vs. postpump 8.3%, P < 0.001). The reduction was greater in type 1 patients (10.6 +/- 2.1 vs. 8.0 +/- 1.6%) than in type 2 patients (11.0 +/- 2.1 vs. 8.8 +/- 1.4%). There was a reduction in frequency of severe hypoglycemia after starting the CSII pump, and there were no instances of diabetic ketoacidosis. CONCLUSIONS Although HbA1c levels did not reach optimal targets, our data indicate that CSII is an effective therapy for patients with diabetes having recalcitrant diabetes who can afford this treatment and whose glycemia is poorly controlled with conventional therapies.
Students' Motivation and Learning and Teachers' Motivational Strategies in English Classrooms in Thailand

This research aimed to investigate second language learners’ motivation and learning of English and the ways in which the teachers supported the students’ motivation and learning in natural classroom settings. Based on Self-Determination Theory (SDT), questionnaires were developed and data were collected from students and their teachers in twelve English language classrooms around Thailand. In addition, each lesson was observed by two observers. The data were triangulated and used to describe the students’ motivation and learning and the teacher’s motivational strategies in each class. The findings showed that most students had a relatively high level of motivation and many reported having internal interests in learning English; however, the level of learning was not assessed to be as high. Furthermore, a few students in almost every class showed a lack of motivation. The teachers were found to employ a variety of motivational strategies, including autonomy-support and controlling styles. While autonomy controlling strategies were commonly used in these classes, autonomy-support strategies were found only in highly motivated and high performing classrooms. The findings from this study suggest the use of strategies that do not only initialize but also nurture students’ internal motivation in order to enhance sustainable learning of English in and outside the classroom; therefore, research on how motivation theories are deployed in teacher education programs should be further undertaken.
Epigenetic biomarkers of T-cells in human glioma

Immune factors are thought to influence glioma risk and outcomes, but immune profiling studies to further our understanding of the immune response are limited by current immunodiagnostic methods. We developed a new assay to capture glioma immune biology based on quantitative methylation specific PCR (qMSP) of two T-cell genes (CD3Z: T-cells, and FOXP3: Tregs). Flow cytometry of T-cells correlated well with the CD3Z demethylation assay (r = 0.93; p < 2.2 × 10−16), demonstrating the validity of the assay. Furthermore, there was a high correlation between qMSP and immunohistochemistry (IHC) in quantifying tumor infiltrating T-cells (r = 0.85; p = 3.4 × 10−11). Applying our qMSP methods to archival whole blood from 65 glioblastoma multiforme (GBM) cases and 94 non-diseased controls, GBM cases had highly statistically significantly lower T-cells (p = 1.7 × 10−9) as well as Tregs (p = 5.2 × 10−11) and a modestly lower ratio of Tregs/T-cells (p = 0.024). Applying the methods to 120 excised glioma tumors, we observed that tumor infiltrating CD3+ T-cells were positively correlated with glioma tumor grade (p = 5.7 × 10−7), and that Tregs were enriched in tumors compared with peripheral blood indicating active chemoattraction of suppressive Tregs into the tumor compartment. Poorer patient survival was correlated with higher levels of tumor infiltrating T-cells (p = 0.01) and Tregs (p = 0.04). DNA methylation based immunodiagnostics represent a new generation of powerful laboratory tools offering many advantages over conventional methods that will facilitate large clinical epidemiologic studies and capitalize on stored archival blood and tissue banks.