Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacological characterization of two specific binding sites for neurohypophyseal hormones in hippocampal synaptic plasma membranes of the rat.

Synaptic plasma membranes containing binding sites for tritiated oxytocin and arginine vasopressin were isolated from rat hippocampus. The binding parameters for oxytocin and vasopressin sites were determined and statistically analysed. The fitted curve for oxytocin binding was compatible with a model where the ligand interacts with two classes of receptors with different capacities and affinities. The sites with low binding capacity had an apparent dissociation constant at equilibrium of 1.8 nM and a maximal binding capacity of 17 fmol/mg protein. By contrast, the Scatchard plot failed to reveal a marked heterogeneity in the population of sites labelled with [3H]vasopressin with an affinity of 1.5 nM and a maximal binding capacity of 39 fmol/mg protein. The specificity of these binding sites, tested in competition experiments, revealed that these neurohypophyseal hormones labelled two distinct populations of sites. One population with a high affinity for vasopressin, oxytocin and vasotocin, the other population with a high affinity for vasopressin and vasotocin and a low affinity for oxytocin. Adenylate cyclase activity was not affected by arginine‐vasopressin or oxytocin. These receptors are compared with previously characterized peripheral receptors.
Descriptive Epidemiology of Amyotrophic Lateral Sclerosis in Japan, 1995-2001

BACKGROUND: This study was conducted to describe the epidemiologic features of amyotrophic lateral sclerosis (ALS) in Japan by examining annual trends in mortality (1995-2001), and to discuss the background factors possibly responsible for the recent variations in the mortality rate. METHODS: Trends in both the age-adjusted and age-specific mortality rates of ALS were examined by using the data obtained from the vital statistics of Japan between 1995 and 2001. RESULTS: There were small increases in the number of ALS deaths (from 1249 to 1400 per year) and the crude mortality rates (from 1.00 to 1.10 per 100,000 population) between 1995 and 2001. The age-adjusted mortality rate of ALS (adjusted using the 1985 model population of Japan) has decreased (from 0.84 per 100,000 population in 1995 to 0.74 in 2001). Age-specific mortality rates have been increasing particularly in the population older than 70 years of age, with the peak in mortality in the 70- to 80-year old age group. CONCLUSIONS: ALS mortality rates increased proportionally more for elderly population during the study period. Further epidemiologic studies will be needed to clarify the possible background factors contributing to the increase in ALS mortality in the elderly.
Concomitant gastrin and ERBB2 gene amplifications at 17q12–q21 in the intestinal type of gastric cancer

Our recent studies using comparative genomic hybridization showed that gain or amplification at the 17q12–q21 region is very common in the intestinal type of gastric cancer. Here, we describe a fluorescence in situ hybridization study with gastrin (GAS)‐specific and ERBB2‐specific probes on ten specimens of gastric carcinoma that, by using comparative genomic hybridization, showed 1) DNA copy number gain or amplification at 17q12–q21, a region known to harbor the GAS and ERBB2 genes (four cases); 2) gain of the entire chromosome 17 (three cases); or 3) normal copy number of chromosome 17 (three cases). GAS and ERBB2 protein expression was studied by Western immunoblotting from gastric cancer cell lines with or without gain at 17q12–q21 as well as a breast cancer cell line with ERBB2 amplification. Our results showed that simultaneous amplification of both GAS and ERBB2 was four‐ to ninefold in the tumors with the 17q12–q21 amplification. Both genes were amplified in the same nuclei, and the hybridization signals were localized to the same region of the nucleus. Overexpression of GAS and ERBB2 was observed by Western immunoblotting only in the gastric cancer cell line with gain at 17q12–q21. The ERBB2 amplification is also a recurrent change in breast cancer. To investigate whether the GAS amplification is unique in gastric cancer, fluorescence in situ hybridization analysis was performed on 40 breast cancer cell lines. The ERBB2 amplification was observed in 11 cell lines, but none of the lines showed the GAS amplification. This indicates that the formation of an amplicon, in which both the GAS and the ERBB2 genes are amplified, might be unique in gastric cancer, especially in its intestinal type, and that simultaneous amplification of both genes is important to the tumorigenesis of intestinal gastric cancer. We demonstrate here for the first time that a gene of a physiological hormone is amplified in tumors that originate from cells that normally secrete the hormone. Genes Chromosomes Cancer 24:24–29, 1999. © 1999 Wiley‐Liss, Inc.
Iron Deprivation Suppresses Hepatocellular Carcinoma Growth in Experimental Studies

Purpose: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death, and iron overload is a significant risk factor in the development of HCC. In this study, we investigated the potential application of depriving iron by a novel iron chelator, thiosemicarbazone-24 (TSC24), in HCC treatment. Experimental Design: Two HCC cell lines and HFE knockout (HFE−/−) mice were used to determine iron chelation efficiency of TSC24. The anticancer effects of TSC24 on HCC were analyzed in vitro and in athymic xenograft mouse models. Results: Treatment with TSC24 significantly decreased the cellular iron concentration in hepatoma cells and the serum iron concentration in HFE−/− mice by blocking iron uptake and interfering with normal regulation of iron levels. Moreover, the viability of HCC cell lines was reduced by TSC24. Confirming the mechanism of the agent, this decrease in viability could be partially rescued by addition of exogenous iron. TSC24 also suppressed tumor growth in athymic mice bearing human HCC xenografts in a concentration-dependent manner, without apparent toxicity in parallel with a decrease in the serum iron level. Further studies revealed that TSC24 efficiently triggered cell-cycle arrest and apoptosis in Hep3B and HepG2 cell lines. Conclusions: TSC24 is a potent iron chelator that suppresses human HCC tumor growth by disrupting iron homeostasis, reducing available iron, and triggering cell-cycle arrest and apoptosis, without apparent host toxicity at effective doses. Thus, TSC24 shows great potential for the treatment of HCC. Clin Cancer Res; 17(24); 7625–33. ©2011 AACR.
Discovering Morphological Paradigms from Plain Text Using a Dirichlet Process Mixture Model

We present an inference algorithm that organizes observed words (tokens) into structured inflectional paradigms (types). It also naturally predicts the spelling of unobserved forms that are missing from these paradigms, and discovers inflectional principles (grammar) that generalize to wholly unobserved words. Our Bayesian generative model of the data explicitly represents tokens, types, inflections, paradigms, and locally conditioned string edits. It assumes that inflected word tokens are generated from an infinite mixture of inflectional paradigms (string tuples). Each paradigm is sampled all at once from a graphical model, whose potential functions are weighted finite-state transducers with language-specific parameters to be learned. These assumptions naturally lead to an elegant empirical Bayes inference procedure that exploits Monte Carlo EM, belief propagation, and dynamic programming. Given 50--100 seed paradigms, adding a 10-million-word corpus reduces prediction error for morphological inflections by up to 10%.
Woody Encroachment Removal from Midwestern Oak Savannas Alters Understory Diversity across Space and Time

Recovering biodiversity is a common goal during restoration; however, for many ecosystems, it is not well understood how restoration influences species diversity across space and time. I examined understory species diversity and composition after woody encroachment removal in a large‐scale savanna restoration experiment in central Iowa, United States. Over a 4‐year time series, restoration had profound effects across space and time, increasing richness at local and site‐level scales. Restoration sites had increased α (within sample) Simpson’s diversity and α and γ (site level) species richness relative to control sites, although γ and β (among sample) Simpson’s diversity, β richness, and α species evenness were not affected. Changes in richness were driven by graminoids at the α and γ scales and woody species (and some evidence for forbs) at the α scale. Interestingly, indicator species analysis revealed that at least some species from all functional groups were promoted by restoration, although no species were significant indicators of pre‐treatment or control sites. Both savanna and nonsavanna species were indicators of restored sites. Restoration promoted exotic species at both scales, although species with spring phenologies were unaffected. Woody encroachment removal may be a means to promote species establishment in savannas; however, in this study, it resulted in establishment and proliferation of native and exotic and savanna and nonsavanna species. Future work might consider reintroduction of key savanna species to supplement those that have established. Work like this demonstrates the utility of restoration experiments for conducting research on large‐ and multiscale processes, such as species diversity.
Angiotensin II Type 1 Receptor Blockers

In the 1970s, a series of observations demonstrated that angiotensin II has deleterious effects on the heart and kidney and that patients with high levels of plasma renin activity are at a higher risk of developing stroke or myocardial infarction than those with low plasma renin activity.1 2 Thereafter, the development of pharmacological probes that block the renin-angiotensin system helped define the contribution of this system to blood pressure control and to the pathogenesis of diseases such as hypertension, congestive heart failure, and chronic renal failure. Thus, the concept of treating hypertension and congestive heart failure by a specific blockade of the renin-angiotensin system was first established with the use of saralasin, a nonselective peptidic antagonist of angiotensin II receptors.3 4 5 6 7 8 9 With saralasin, it became possible to demonstrate that angiotensin II receptor blockade, alone or in combination with salt depletion, lowers blood pressure in hypertensive patients and improves systemic hemodynamics in patients with congestive heart failure.3 4 5 6 7 8 9 10 However, saralasin had many drawbacks. Because it is a peptide, it had to be administered intravenously. This characteristic limited its use to hours or a few days at maximum. In addition, at higher doses, saralasin had some partial agonist, angiotensin II–like effects. The next major breakthrough in the understanding of the renin-angiotensin system was triggered by the development of orally active angiotensin-converting enzyme (ACE) inhibitors.10 11 12 13 14 15 Studies performed with these agents rapidly confirmed and reinforced the seminal clinical observations made with saralasin. ACE inhibitors are now recognized as an important therapeutic step to control blood pressure in hypertensive patients and to reduce morbidity and mortality in patients with congestive heart failure.16 In addition, because of their ability to lower proteinuria, ACE inhibitors have …
VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release

Enhanced formation of reactive oxygen species (ROS), superoxide (O2 ·−), and hydrogen peroxide (H2O2) may result in either apoptosis or other forms of cell death. Here, we studied the mechanisms underlying activation of the apoptotic machinery by ROS. Exposure of permeabilized HepG2 cells to O2 ·− elicited rapid and massive cytochrome c release (CCR), whereas H2O2 failed to induce any release. Both O2 ·− and H2O2 promoted activation of the mitochondrial permeability transition pore by Ca2+, but Ca2+-dependent pore opening was not required for O2 ·−-induced CCR. Furthermore, O2 ·− alone evoked CCR without damage of the inner mitochondrial membrane barrier, as mitochondrial membrane potential was sustained in the presence of extramitochondrial ATP. Strikingly, pretreatment of the cells with drugs or an antibody, which block the voltage-dependent anion channel (VDAC), prevented O2 ·−-induced CCR. Furthermore, VDAC-reconstituted liposomes permeated cytochrome c after O2 ·− exposure, and this release was prevented by VDAC blocker. The proapoptotic protein, Bak, was not detected in HepG2 cells and O2 ·−-induced CCR did not depend on Bax translocation to mitochondria. O2 ·−-induced CCR was followed by caspase activation and execution of apoptosis. Thus, O2 ·− triggers apoptosis via VDAC-dependent permeabilization of the mitochondrial outer membrane without apparent contribution of proapoptotic Bcl-2 family proteins.
Reduced Expression of Osteonectin and Increased Natural Killer Cells May Contribute to the Pathophysiology of Aplastic Anemia

Normal hematopoiesis involves complex interactions between hematopoietic cells and the bone marrow (BM) microenvironment. The exact causes and mechanisms involved in aplastic anemia (AA) are not known. For better understanding of the pathophysiology of AA, we investigated changes in the hematopoietic stem cell (HSC) compartment and the BM microenvironment in patients with AA by immunohistochemical analysis. A total of 10 AA patients and 10 controls were enrolled. Using BM biopsy specimen, we performed immunohistochemistry for osteopontin, osteonectin, osteocalcin, nestin, stromal-derived factor-1 (SDF-1), lymphocytes, macrophage, and HSCs. Numbers of HSCs and T/B lymphocytes were significantly lower in the AA specimens than the controls, and the AA specimens contained more natural killer cells (CD56+ cells) (P<0.01). The 2 groups had similar levels of expression of osteopontin, osteocalcin, nestin, and SDF-1. However, the number of osteonectin+ cells in the AA specimens was significantly lower than in the control specimens (P<0.01). Our findings support the hypothesis that defects in the stromal cells contribute to the pathogenesis of AA by damaging HSC niche. Immune-mediated natural killer cells may also play a role in the pathogenesis of AA.
Quantitative analysis of ultrathin doping layers in semiconductors using high‐angle annular dark field images

It is well known that the high‐angle annular dark field (HAADF) technique in scanning transmission electron microscopy is an incoherent imaging process in the lateral (xy) plane. However, as a consequence of the existence of partial coherence in the z direction, accurate quantitative interpretation of image intensity is difficult. The effects of coherence in the z direction can be reduced by increasing the inner collector angle of the annular detector so that the scattering from atoms in the z direction is essentially incoherent. We thus show that it is feasible to quantify the total As concentration of ultrathin InAsxP1−x layers in InP in a simple but accurate way using a thickness integrated Bloch wave calculation including phonon scattering with a large inner collector angle of the annular detector of around 150 mrad. We compare the As composition derived from this approach with that from the Fresnel method and high resolution imaging. We also show that the non‐linear variation of the HAADF intensity with thickness is consistent with our simpler simulations for such conditions. Therefore, this approach enables us easily and quickly to quantify compositions using HAADF images. The tetragonal distortion due to lattice mismatch is also shown to influence the contrast and has been included in the calculations.
Age Differences in Interhemispheric Interactions: Callosal Structure, Physiological Function, and Behavior

There is a fundamental gap in understanding how brain structural and functional network connectivity are interrelated, how they change with age, and how such changes contribute to older adults’ sensorimotor deficits. Recent neuroimaging approaches including resting state functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) have been used to assess brain functional (fcMRI) and structural (DTI) network connectivity, allowing for more integrative assessments of distributed neural systems than in the past. Declines in corpus callosum size and microstructure with advancing age have been well documented, but their contributions to age deficits in unimanual and bimanual function are not well defined. Our recent work implicates age-related declines in callosal size and integrity as a key contributor to unimanual and bimanual control deficits. Moreover, our data provide evidence for a fundamental shift in the balance of excitatory and inhibitory interhemispheric processes that occurs with age, resulting in age differences in the relationship between functional and structural network connectivity. Training studies suggest that the balance of interhemispheric interactions can be shifted with experience, making this a viable target for future interventions.
Mechanisms of Seasonal – ENSO Interaction

Abstract The mechanisms by which the seasonal cycle in the equatorial Pacific affects ENSO are investigated using the Zebiak and Cane ENSO prediction model. The most dominant seasonal effect is found to be due to the wind divergence field, as determined by the seasonal motion of the ITCZ, through its effect on the atmospheric heating. The next-order seasonal effects are due to the seasonality of the background SST and ocean upwelling velocity, and the corresponding mechanisms are analyzed. It is suggested that the seasonal forcing has a first-order effect on ENSO’s dynamics and that important aspects of the seasonal forcing may be included in idealized delayed oscillator ENSO models by making the model background shift seasonally from stable to unstable states.
Resistance Training Effects on Metabolic Function Among Youth: A Systematic Review.

PURPOSE This systematic review evaluates the relationship between resistance training and metabolic function in youth. METHODS PubMed, Embase, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials. gov were searched for articles that (1): studied children (2); included resistance training (3); were randomized interventions; and (4) reported markers of metabolic function. The selected studies were analyzed using the Cochrane Risk-of-Bias Tool. RESULTS Thirteen articles met inclusion criteria. Mean age ranged from 12.2 to 16.9 years, but most were limited to high school (n = 11) and overweight/obese (n = 12). Sample sizes (n = 22-304), session duration (40-60min), and intervention length (8-52 wks) varied. Exercise frequency was typically 2-3 d/wk. Resistance training was metabolically beneficial compared with control or resistance plus aerobic training in 5 studies overall and 3 out of the 4 studies with the fewest threats to bias (p ≤ .05); each was accompanied by beneficial changes in body composition, but only one study adjusted for change in body composition. CONCLUSIONS Limited evidence suggests that resistance training may positively affect metabolic parameters in youth. Well-controlled resistance training interventions of varying doses are needed to definitively determine whether resistance training can mitigate metabolic dysfunction in youth and whether training benefits on metabolic parameters are independent of body composition changes.
Pastured Poultry Production: An Evaluation of Its Sustainability in Hawaii

Poultry broiler production in Hawaii declined 30 percent in the past 10 years, a reduction and trend largely due to high production costs associated with land, housing, and imported feeds. In addition to high production costs, many former poultry farmers have retired, and new farmers are not taking their place. This publication describes a new and innovative method of raising poultry that capitalizes on Hawaii’s productive pastures. Two experiments were conducted to test the method by raising broilers on pasture, slaughtering the birds to evaluate carcass weights and feed conversion, and marketing the product. The results suggest that the pastured poultry production system offers potential economic opportunities for agricultural entrepreneurs. However, careful management and proper environmental conditions are vital to the profitability of the system. Demand for poultry broiler products is increasing, due in part to marketing efforts by the national poultry industry. To meet the market demand, inshipments of broilers to Hawaii increased 27 percent between 1987 and 1991 and an average of 3.5 percent in each of the past ten years. The supply of locally grown fresh poultry in the market is limited, although there are established niche markets, for example in local grocery supermarkets where imported range-raised chickens are sold for approximately $8.00 for a 4-pound bird, and in “ethnic” markets where locally produced processed or live birds are sold. Considering the strength of current consumer demands for “Island Fresh” food quality and freshness, the potential market in Hawaii for range-raised poultry is large. Also, with the decline of plantation industries (sugarcane and pineapple) in Hawaii, more land is becoming available for other agricultural uses. If land leases for former plantation lands are reasonable, young entrepreneurs with limited financial resources and credit can enter the farming business.
Clinicopathological study of male breast cancer in Nigerians and a review of the literature.

BACKGROUND Breast cancer is rare in men, accounting for approximately 1% of all cases of breast carcinoma. OBJECTIVE To evaluate the incidence, presentation, histopathological types, management and outcome of male patients with breast cancer treated at the University of Benin Teaching Hospital, Benin City, Nigeria. METHODS A 20 year (1987-2006) retrospective study of all male patients with breast cancer was done. Clinic demographic data regarding age, sex, clinical information, treatment and follow up were obtained from request cards and case files. Slides were retrieved from the archives of the Department of Pathology and reviewed. RESULTS Sixteen cases of male breast cancer were encountered. This comprised 18.4% of the breast lesions in males and 2.8% of all breast cancers seen in the Department during the 20 year study period. The ages of patients ranged from 35-90 years with a mean age of 64.4 years. Delay in patient presentation to physician ranged from 14-49 months. Clinically, patients presented mostly with a self-detected lump (87.5%), or ulceration (68.8%), nipple discharge (43.8%) and nipple bleeding (25.0%). Unilaterality was observed in 87.5% of cases were while 12.5% of cases were bilateral (metachronous). Invasive ductal carcinoma (81.25%) was the predominant histological type of cancer. Stage IV disease was most commonly encountered (43.8%). Eleven (68.8%) patients had modified radical mastectomy. Only 31.3% patients came for follow-up, for a median duration of 10 months. CONCLUSION Male breast cancer is rare and patients present late with advanced disease. Education needs to be intensified to increase awareness of the disease.