Miracle-dz/UniFAR-FTUs huggingface dataset:
Wnt-1-inducing factor-1: a novel G/C box-binding transcription factor regulating the expression of Wnt-1 during neuroectodermal differentiation

The Wnt-1 proto-oncogene is essential for proper development of the midbrain and is expressed in a spatially and temporally restricted manner during central nervous system development in mice. In vitro, the gene is specifically transcribed during the retinoic acid (RA)-induced neuroectodermal differentiation of the P19 line of embryonal carcinoma cells. The P19 cells differentiate into neurons, astrocytes, and fibroblast-like cells when treated with RA. Treatment of the cells with dimethyl sulfoxide leads to differentiation along mesodermal lineages, including skeletal and cardiac muscle. We have used the P19 cell line to study the Wnt-1 promoter and identify and characterize the transcription factor(s) that regulates the differentiation-specific transcription of Wnt-1 in RA-treated P19 cultures. Transient-transfection assays have revealed that a 230-bp region comprising positions -278 to -47 of the 5' upstream Wnt-1 sequence was sufficient to direct RA-specific transcription. This promoter fragment was shown to contain a binding site for a nuclear factor that was not detected in undifferentiated P19 stem cells or their dimethyl sulfoxide-treated derivatives but was induced in differentiating RA-treated cells. This factor was termed Wnt-1-inducing factor-1 (WiF-1). DNase I footprinting analysis has identified the G/C-rich WiF-1 binding site, and UV cross-linking studies have shown that WiF-1 is a protein with an M(r) of 65,000. WiF-1 binding activity was also detected in postpubertal mouse testis, the only tissue that expresses Wnt-1 in adults. Site-directed mutations that inhibited WiF-1 binding to the Wnt-1 promoter concomitantly abolished the activity of the promoter in RA-treated P19 cells. The active WiF-1 protein was purified by DNA affinity chromatography. Our data suggest that WiF-1 is a novel G/C box-binding transcription factor and support a physiological role for WiF-1 in the developmentally regulated expression of Wnt-1.
Oral Plasmablastic Lymphomas in AIDS Patients Are Associated With Human Herpesvirus 8

Human herpes virus type 8 (HHV8) has been strongly associated with Kaposi sarcoma, primary effusion lymphoma (PEL), and Castleman's disease. To our knowledge, infection by this virus has not been strongly associated with other hematopathologic malignancies. We examined five oral cavity lymphomas from men with AIDS for HHV8 and HIV-1 by reverse transcriptase in situ polymerase chain reaction, as well as for Epstein-Barr virus (EBV) (EBER-1, -2) using in situ hybridization and HHV8 protein with immunohistochemistry. Four of these tumors were plasmablastic lymphomas; the final case was diffuse large B-cell lymphoma. Most of the neoplastic cells in these five lymphomas contained HHV8 RNA and protein. Further, the four plasmablastic lymphoma cases had tumor cells that contained EBV. HIV-1 RNA was not detected in the tumor cells but was noted in surrounding benign T cells. In comparison, HHV8 RNA was not detected in any of the five oral cavity lymphomas from people who did not have acquired immunosuppression nor in five lymphomas from AIDS patients that were located at a site other than the oral cavity. It is concluded that oral cavity lymphomas from people with AIDS are strongly associated with infection by HHV8 and EBV. Given the poor prognosis of oral cavity lymphomas in immunocompromised patients, therapy directed against the HHV8 and EBV infection may be of therapeutic value.
Treatment intensity and childhood apraxia of speech.

BACKGROUND Intensive treatment has been repeatedly recommended for the treatment of speech deficits in childhood apraxia of speech (CAS). However, differences in treatment outcomes as a function of treatment intensity have not been systematically studied in this population. AIM To investigate the effects of treatment intensity on outcome measures related to articulation, functional communication and speech intelligibility for children with CAS undergoing individual motor speech intervention. METHODS & PROCEDURES A total of 37 children (32-54 months of age) with CAS received 1×/week (lower intensity) or 2×/week (higher intensity) individual motor speech treatment for 10 weeks. Assessments were carried out before and after a 10-week treatment block to study the effects of variations in treatment intensity on the outcome measures. OUTCOMES & RESULTS The results indicated that only higher intensity treatment (2×/week) led to significantly better outcomes for articulation and functional communication compared with 1×/week (lower intensity) intervention. Further, neither lower nor higher intensity treatment yielded a significant change for speech intelligibility at the word or sentence level. In general, effect sizes for the higher intensity treatment groups were larger for most variables compared with the lower intensity treatment group. CONCLUSIONS & IMPLICATIONS Overall, the results of the current study may allow for modification of service delivery and facilitate the development of an evidence-based care pathway for children with CAS.
Highly Efficient In Vivo Agonist-Induced Internalization of sst2 Receptors in Somatostatin Target Tissues

The successful peptide receptor imaging of tumors, as exemplified for somatostatin receptors, is based on the overexpression of peptide receptors in selected tumors and the high-affinity binding to these tumors of agonist radioligands that are subsequently internalized into the tumor cells in which they accumulate. Although in vitro studies have shown ample evidence that the ligand–receptor complex is internalized, in vivo evidence of agonist-induced internalization of peptide receptors, such as somatostatin receptors, is missing. Methods: Rats subcutaneously transplanted with the somatostatin receptor subtype 2 (sst2)–expressing AR42J tumor cells were treated with intravenous injections of various doses of the sst2 agonist [Tyr3, Thr8]-octreotide (TATE) or of the sst2 antagonist 1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″,-tetraacetic acid (DOTA)-Bass and were sacrificed at various times ranging from 2.5 min to 24 h after injection. The tumors and pancreas were then removed from each animal. All tissue samples were processed for sst2 immunohistochemistry using sst2-specific antibodies. Results: Compared with the sst2 receptors in untreated animals, which localized at the plasma membrane in pancreatic and AR42J tumor cells, the sst2 receptors in treated animals are detected intracellularly after an intravenous injection of the agonist TATE. Internalization is fast, as the receptors are already internalizing 2.5 min after TATE injection. The process is extremely efficient, as most of the cell surface receptors internalize into the cell and are found in endosomelike structures after TATE injection. The internalization is most likely reversible, because 24 h after injection the receptors are again found at the cell surface. The process is also agonist-dependent, because internalization is seen with high-affinity sst2 agonists but not with high-affinity sst2 antagonists. The same internalization properties are seen in pancreatic and AR42J tumor cells. They can further be confirmed in vitro in human embryonic kidney–sst2 cells, with an immunofluorescence microscopy–based sst2 internalization assay. Conclusion: These animal data strongly indicate that the process of in vivo sst2 internalization after agonist stimulation is fast, extremely efficient, and fully functional under in vivo conditions in neoplastic and physiologic sst2 target tissues. This molecular process is, therefore, likely to be responsible for the high and long-lasting uptake of sst2 radioligands seen in vivo in sst2-expressing tumors.
PD-1 and PD-L1 as emerging therapeutic targets in gastric cancer: current evidence

Gastric adenocarcinoma is a leading cause of global cancer-related morbidity and mortality, and new therapeutic approaches are needed. Despite the improved outcomes with monoclonal antibodies targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor receptor 2, durable responses are uncommon. Targeting immune checkpoints including PD-1, PD-L1 and CTLA-4 have led to improved survival across several tumor types, frequently characterized by prolonged benefit in responding patients. Tumoral and lymphocyte-derived immunohistochemical staining for PD-1, PD-L1, and tumor mutational burden have shown potential as predictive response biomarkers in several tumor types. Optimal incorporation of immune-mediated therapies into gastric cancer (GC) is an area of intense ongoing investigation and benefit has been demonstrated in smaller studies of advanced patients. Important questions of biomarker selection, roles for molecular characterization, optimal combinatorial approaches, and therapeutic sequencing remain. In this study, current data are reviewed for immune checkpoint inhibitors in GC, and putative biomarkers, ongoing trials, and future considerations are discussed.
Resveratrol induces apoptosis in pancreatic cancer cells

Background Pancreatic cancer is one of the most lethal human cancers with a very low survival rate of 5 years. Conventional cancer treatments including surgery, radiation, chemotherapy or combinations of these show little effect on this disease. Several proteins have been proved critical to the development and the progression of pancreatic cancer. The aim of this study was to investigate the effect of resveratrol on apoptosis in pancreatic cancer cells. Methods Several pancreatic cancer cell lines were screened by resveratrol, and its toxicity was tested by normal pancreatic cells. Western blotting was then performed to analyze the molecular mechanism of resveratrol induced apoptosis of pancreatic cancer cell lines. Results In the screened pancreatic cancer cell lines, capan‐2 and colo357 showed high sensitivity to resveratrol induced apoptosis. Resveratrol exhibited insignificant toxicity to normal pancreatic cells. In resveratrol sensitive cells, capan‐2 and colo357, the activation of caspase‐3 was detected and showed significant caspase‐3 activation upon resveratrol treatment; p53 and p21 were also detected up‐regulated upon resveratrol treatment. Conclusion Resveratrol provides a promising anti‐tumor stratagy to fight against pancreatic cancer. Chin Med J 2011;124(11):1695–1699
Studies on zona hardening in rat oocytes that are matured in vitro in a serum‐free medium

The present study confirms that zonae pellucidae of rat oocytes became resistant to chymotrypsin digestion (zona hardening) after undergoing in vitro maturation (IVM) in a serum‐free medium. However, zona hardening and did not occur when empty zonae without oocytes were cultured in the same IVM conditions, suggesting that oocyte‐derived factor(s) is responsible for zona hardening in oocytes matured in the serum‐free medium. Zona hardening occurred primarily after dictyate oocytes were cultured for 6–8 hours in the IVM medium without serum. Zona hardening could be prevented or alleviated if oocytes were cultured in the IVM medium containing bovine foetal calf serum, a soybean trypsin inhibitor, or β‐mercaptoethanol, and in vitro fertilization rates for such oocytes were normal. Possible mechanisms of the phenomenon of zona hardening in oocytes matured in serum‐free conditions are discussed in relation to its possible relevance to the cortical reaction and the physiological block to polyspermy.
Carriage of Haemophilus influenzae type b in children after widespread vaccination with conjugate Haemophilus influenzae type b vaccines

Rates of invasive Haemophilus influenzae type b (Hib) disease in children decreased very rapidly after licensure of Hib conjugate vaccines. A role for a vaccine-related reduction in nasopharyngeal carriage of Hib has been suggested. We studied oropharyngeal carriage of Hib and vaccination rates in a population of 2− to 5-year-old children in metropolitan Atlanta. Among 584 children 75% were vaccinated with an Hib conjugate vaccine, 17% had not been vaccinated and 8% had no vaccination records available. Forty-one percent of the children were colonized with H. influenzae. One child was colonized with Hib. Hib carriage (0.17%; upper 95% confidence interval boundary, 0.97%) was substantially lower than the estimates of Hib carriage from prior studies of children who had not received Hib conjugate vaccines. Our data are consistent with a decline in Hib carriage induced by widespread use of conjugate Hib vaccines, which may have contributed to the decline of Hib disease in United States children.
Sequential Estrogen and Progestogen Therapy: Assessment of Progestational Effects on the Postmenopausal Endometrium

Healthy postmenopausal women were randomly assigned to groups receiving 28-day treatment cycles of estradiol (E2) valerate (2 mg, days 1-21) combined with medroxyprogesterone acetate (10 mg, days 12-21) (N=18), 17 β-estradiol (1.5 mg, days 1-24) combined with desogestrel (150 µg, days 13-24) (N=20), or placebo (N=18). The progestational effects on the endometrium were assessed by histology, uterine bleeding pattern, and biochemical markers of secretion measured in endometrial tissue (E2 and isocitrate dehydrogenase) and serum (placental protein 14). After 2 years of therapy, 24 women in the hormone groups had secretory endometrium and 13 had atrophic endometrium; in the placebo group, the results were one and 15, respectively. Withdrawal bleeding generally started between days 9-12 after the addition of progestogen in the E2-medroxyprogesterone acetate group, and between days 14-17 in the E2- desogestrel group. All three biochemical markers of secretion were increased in each of the hormone-treated groups compared with the placebo group (P<.01-.001). Serum placental protein 14 was twice as high in the secretory as in the atrophic phase (P<.01). Isocitrate dehydrogenase, but not E2 dehydrogenase, was also higher in the secretory phase (P<.05). Only serum placental protein 14 was significantly related to the uterine bleeding pattern (P<.01). We conclude that serum placental protein 14 reflects both endometrial histology and bleeding pattern and may be a useful marker of progestational effects on the endometrium. The markers of secretion measured in endometrial tissue are not as reliable for endometrial histology or bleeding pattern.
Do Asian renal transplant patients need another mycophenolate mofetil dose compared with Caucasian or African American patients?

Mycophenolate mofetil (MMF) is used to prevent acute rejection following solid organ transplantation in transplant centers all over the world. Patients from different ethnic backgrounds are treated with this drug, for which therapeutic drug monitoring (TDM) has not become the standard of practice in most centers. Whether or not some ethnic groups require a different MMF dose has been a topic of debate in recent years. In this review, it is shown that Asian patients, compared with Caucasian patients, with a comparable MMF dose reach higher mycophenolic acid (MPA) exposure. Also clinical experience points toward more adverse events in case of treatment with 1 g MMF bid in Asian patients, and therefore, for this ethnic group, a lower maintenance dose seems justified. In contrast, African American patients reach similar drug concentrations as Caucasians patients receiving the same MMF dose, but due to immunological reasons, they require a higher MMF dose to reach comparable acute rejection incidences. When TDM is performed, clinicians can correct the dose and compensate for interethnic differences in drug exposure. Otherwise, it is important to choose the right dose. This optimal dose is 20–46% lower in Asian transplant recipients than in Caucasian or African American patients.
Empirical Investigation of the Environmental Kuznets Curve Hypothesis for Nitrous Oxide Emissions for Mongolia

A comprehensive set of econometric methods were employed on annual data for 1981-2012 to investigate the environmental Kuznets curve (EKC) hypothesis for nitrous oxide (NOx) emissions for Mongolia; the short- and long-run relationships between NOx emissions, income, exports, urbanization, and growth in the different sectors of the economy; and their consequent Granger causal relationships. A highly significant and robust long-run U-shaped relationship between NOx emissions and income was found; thereby, discrediting the existence of the environmental EKC. Furthermore, exports, urbanization, and growth in the industrial and services sectors were found to decrease - while growth in the agricultural sector was found to increase - NOx emissions. Finally, the findings have also exhibited significant short- and long-run Granger causal relationships amongst the variables; thereby, leading to policy recommendations which are briefly discussed.
Chicago transit authority train noise exposure

ABSTRACT To characterize noise exposure of riders on Chicago Transit Authority (CTA) trains, we measured noise levels twice on each segment of 7 of the 8 CTA train lines, which are named after colors, yielding 48 time-series measurements. We found the Blue Line has the highest noise levels compared to other train lines, with mean 76.9 dBA; and that the maximum noise level, 88.9 dBA occurred in the tunnel between the Chicago and Grand stations. Train segments involving travel through a tunnel had significantly higher noise levels than segments with travel on elevated and ground level tracks. While 8-hr doses inside the passenger cars were not estimated to exceed occupational exposure limits, train operators ride in a separate cab with operational windows and may therefore have higher noise exposures than riders. Despite the low risk of hearing loss for riders on CTA trains, in part because transit noise accounts for a small part of total daily noise exposure, 1-min average noise levels exceeded 85 dBA at times. This confirms anecdotal observations of discomfort due to noise levels, and indicates a need for noise management, particularly in tunnels.
Comparison of a commercial ELISA with the modified agglutination test for detection of Toxoplasma infection in the domestic pig

The modified agglutination test (MAT) and a commercially available enzyme-linked immunosorbent assay (ELISA) were compared for detection of antibodies to Toxoplasma gondii in naturally-infected market-aged pigs. Infected pigs were obtained from commercial slaughter facilities and from farms where infection had previously been detected. Infection was confirmed by bioassay in cats. For 70 bioassay positive pigs, 60 were positive by MAT (85.7% sensitivity) and 62 were positive by ELISA (88.6% sensitivity). Of 204 bioassay negative samples 193 were negative by MAT (94.6% specificity) and 200 were negative by ELISA (98.0% specificity). Good correlation was seen between MAT and ELISA results. The results suggest that the ELISA may be a good tool for epidemiological studies of Toxoplasma infection on pig farms. # 2004 Elsevier B.V. All rights reserved.
Epidemiology of Infection with Epstein-Barr Virus Types 1 and 2: Lessons from the Study of a T-Cell-Immunocompromised Hemophilic Cohort

ABSTRACT In apparent contrast to earlier work on Epstein-Barr virus (EBV) carriage in the general Caucasian population, in vitro virus isolations from human immunodeficiency virus (HIV)-positive male homosexual cohorts have shown frequent examples of multiple EBV infection and an overall prevalence of type 2 EBV strains exceeding 30%. Here we ask to what extent these findings might hold true in another T-cell-immunocompromised cohort, HIV-positive hemophilic patients. Resident EBV strains were rescued within lymphoblastoid cell lines derived from the blood and throat washings of 39 such individuals, using the same in vitro protocols of virus isolation as for the homosexual cohort. A mean of 19 independent cell lines was made per patient, and in each case the resident virus was characterized by PCR-based viral genomic analysis and by immunoblotting to reveal the viral “EBNAprint. ” By these criteria a significant proportion (14 of 39) of the hemophilic cohort carried more than one EBV strain, suggesting that T-cell impairment does indeed sensitize virus carriers to reinfection with new strains of exogenously transmitted virus. However, the overall incidence of type 2 EBV infection was 10%, which is close to that observed in the earlier work with healthy carriers and substantially lower than that seen in HIV-positive homosexuals. We infer that type 2 EBV is relatively rare in the general Caucasian population but has become endemic in the homosexual community.
TWO Advances in Dyslexia Genetics d New Insights Into the Role of Brain Asymmetries

Dyslexia is a common condition affecting up to 10% school-aged children. There is strong evidence that genetics plays an important role in dyslexia and is expected to be complex in nature. Few specific susceptibility factors have been identified so far, but their functional characterization has provided novel insights into the biology of dyslexia. In particular, they point to an unexpected role of candidate genes for dyslexia in the biology of cilia, cellular organelles required in many processes including the establishment of leftright asymmetries early in development. This observation has brought back into the spotlight the old idea of a link between dyslexia and handedness. Yet much of the genetics contributing to dyslexia remains unexplained. The lack of biological markers, clear diagnostic criteria, and homogeneous assessment strategies are just some of the factors preventing the collection of the cohorts powered enough for large-scale genetic studies. While the technology and methods to generate and handle large-scale data have reached unprecedented potential, the main challenge remains in establishing universal guidelines to collect suitable phenotype information across independent studies. These difficulties reflect the complex nature of dyslexia which is highly heterogeneous and often co-occurs with other neurodevelopmental disorders.
A Class of Wide-Band Linear-Phase FIR Differentiators Using a Two-Rate Approach and the Frequency-Response Masking Technique

This paper introduces a class of wide-band linear-phase finite-length impulse response (FIR) differentiators. It is based on two-rate and frequency-response masking techniques. It is shown how to use these techniques to obtain all four types of linear-phase FIR differentiators. Design examples demonstrate that differentiators in this class can achieve substantial savings in arithmetic complexity in comparison with conventional direct-form linear-phase FIR differentiators. The savings achievable depend on the bandwidth and increase with increasing bandwidth beyond the break-even points which are in the neighborhood of 90% (80%) of the whole bandwidth for Type II and III (Type I and IV) differentiators. The price to pay for the savings is a moderate increase in the delay and number of delay elements. Further, in terms of structural arithmetic operations, the proposed filters are comparable to filters based on piecewise-polynomial impulse responses. The advantage of the proposed filters is that they can be implemented using non-recursive structures as opposed to the polynomial-based filters which are implemented with recursive structures.