Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of p16, p53 and Ki-67 proteins in the progression of epithelial dysplasia of the oral cavity.

BACKGROUND The overexpression of the protein products of genes associated with the cell cycle tumour protein53 (p53), cyclin-dependent kinase inhibitor 2A (p16) and antigen identified by monoclonal antibody Ki-67 (Ki-67) is apparently of great significance. This study evaluated the immunohistochemical expression of these proteins in precancerous lesions and in carcinoma of the oral cavity. MATERIALS AND METHODS The nuclear expression of p53 and Ki-67 and nuclear and/or cytoplasmic expression of p16 protein was examined in 54 biopsy specimens from the oral cavity obtained over a period of 3 years. The samples included 18 cases of normal/hyperplastic mucosa, 25 cases of dysplasia and 11 cases of invasive squamous cell carcinoma. The specimens were grouped into three categories: 1 = no or mild dysplasia, 2 = moderate or severe dysplasia, and 3 = invasive carcinoma. RESULTS p16 was negative in all the group 1 specimens, while both p53 and Ki-67, when present, were limited to the cells of the basal layer. In the group 2 specimens, the number of p16-, p53-, and Ki-67-positive cells increased as the grade of dysplasia progressed. In group 3 (invasive carcinomas), p53 and p16 expression occurred respectively in 81.8% and 54.5% of cases, while Ki-67 was elevated in all the cases. CONCLUSION The expression of the cell-cycle proteins p16 and p53 in the dysplastic epithelium, in association with Ki-67, may represent significant markers to recognize evolution of precancerous disease in the oral cavity and to improve identification of the degree of dysplasia.
Exploring Characteristics and Effects of User Participation in Online Social Q&A Sites

People are seeking more meaningful and customized information than what is obtained by keywords-based queries and document retrieval through a search engine. In this paper, we look at a set of such services, referred to as social Q&A sites. With sites such as Google Answers, and primarily Yahoo! Answers, we attempt to understand various characteristics of user participation and their possible effects on the design and success of the site. We discuss these social Q&A sites by comparing their designs based on user participation and point out the effects and defects of each. We show that active user participation is the core component of these sites. We further analyze rich data collected from more than 55,000 Yahoo! Answers user profiles to understand the nature of user participation, and the quality of this participation. With our analysis we discover that Yahoo! Answers model implicitly encourages users to make an active contribution. An important contribution of the work reported here is the framework with which various factors relating to user participation in social Q&A sites can be studied.
Evolution of Cryoglobulinemia in Direct-Acting Antiviral-Treated Asian Hepatitis C Patients With Sustained Virological Responses: A 4-Year Prospective Cohort Study

Background How cryoglobulinemia evolves after sustained virological response (SVR) following direct-acting antiviral (DAA) treatment in Asian hepatitis C virus (HCV)-infected patients remains elusive. Methods A prospective cohort study was conducted in 422 Taiwanese patients (358 completed DAA therapy and 353 experienced SVRs). Serum cryoglobulins were surveyed at baseline and every 3-6 months posttherapy. Results Of 422, 227 (53.8%) had cryoglobulinemia, 8 (1.89%) had cryoglobulinemic vasculitis. Of 227, 54 (23.8%), 57 (25.1%) and 116 (51.1%) had 1, 2 and 3 cryoglobulins, respectively; those with 3 cryoglobulins had the highest alanine aminotransferase, immunoglobulin G (IgG) and fibrosis-4 index. During a 4-year follow-up, among SVR patients, cryoglobulinemia rates decreased from 56.4% to 15.4%, single cryoglobulin rates increased (21.6% to 63.9%) and 3 cryoglobulin rates decreased (55.7% to 11.1%). Compared with baseline values, among SVR patients with baseline cryoglobulinemia, complement component 4 levels increased, and IgG and IgM levels decreased until 48 weeks posttherapy for those without posttherapy cryoglobulinemia. All 8 cryoglobulinemic vasculitis patients exhibited SVRs; 5 (62.5%) achieved complete clinical response 12 weeks posttherapy, of whom, 2 (40%) experienced clinical relapse 24~48 weeks posttherapy. Baseline IgM levels were associated with posttherapy cryoglobulinemia in SVR patients (cut-off values at 12, 24, 48 weeks and 4 years posttherapy: 130, 105, 118 and 168 mg/dL, respectively). Conclusions Among DAA-treated SVR patients, in 4 years, cryoglobulinemia rates decreased from 56.4% to 15.4%, multiple cryoglobulin rates decreased, cryoglobulinemia signals reversed, 62.5% of cryoglobulinemic vasculitis patients achieved complete clinical response (40% had relapse), and baseline IgM levels indicated posttherapy cryoglobulinemia.
Restoring Adenine Nucleotides in a Brain Slice Model of Cerebral Reperfusion

Tissue adenine nucleotides are depleted during cerebral ischemia, impeding recovery after reperfusion. Although prior studies have attempted to prevent the initial loss of adenylates, the present study tests the hypothesis that stimulating synthesis of adenine nucleotides, through either adenosine kinase or adenine phosphoribosyltransferase, would result in significant cerebroprotection. To study the effects on neurons and glia directly while avoiding the influence of the cerebral vasculature, hippocampal brain slices were used for the model of transient ischemia with reperfusion. The standard brain slice insult of brief exposure to anoxia with aglycemia was modified based on studies which showed that a 30-minute exposure to air with 1 mmol/L glucose produced a stable, moderate reduction in ATP during the insult and that, 2 hours after return to normal conditions, there was moderate depletion of tissue adenine nucleotides and histologic injury. Treatments with 1 mmol/L adenosine, AMP, or adenine were equivalent in partially re-storing adenine nucleotides. Despite this, only adenosine af-forded histologic protection, suggesting a protective role for adenosine receptors. There also was evidence for metabolic cycling among adenine nucleotides, nucleosides, and purines. Adenosine may exert direct cerebroprotective effects on neural tissue as well as indirect effects through the cerebral vasculature.
Detección de polimorfismos en la región codificante del gen receptor de hormona luteinizante mediante análisis de polimorfismo conformacional de cadena simple y secuenciación en bovinos Carora

Con el objeto de caracterizar los polimorfismos nucleotidicos simples (SNP) presentes en una region del exon 11 del gen receptor de hormona luteinizante en bovinos Carora, se analizaron 98 muestras de ADN bovino pertenecientes al banco de ADN del laboratorio de Biotecnologia Agricola de la Escuela Socialista de Agricultura Tropical (ESAT). El ADN se extrajo mediante una metodologia de precipitacion salina. Las secuencias variantes fueron evidenciadas en primera instancia por amplificacion del segmento de interes y analisis de polimorfismo conformacional de cadena simple (PCR-SSCP). Se detectaron cuatro patrones electroforeticos en el fragmento estudiado. Luego, 19 muestras representativas de cada uno de los patrones fueron amplificadas y enviadas a un servicio de secuenciacion capilar estandar (Macrogen, Inc., Corea). Se detectaron dos variantes en el fragmento de ADN evaluado: rs41256848 (1410G > T) detectada previamente y una variante nueva (1337C > T). Se detectaron dos alelos (G y T) y tres genotipos (GG, GT, TT) para la variante rs41256848; y dos ale- los (C y T) y dos genotipos (CC, CT) para la variante nueva. Las frecuencias alelicas para la variante rs41256848 fueron 0,852 – 0,147 para G y T, respectivamente; mientras que para la nueva variante fueron 0,964 – 0,035 para C y T, respectivamente. Las frecuencias genotipicas para rs41256848 fueron 0,7551 – 0,1938 – 0,0510 para GG, GT, TT, respectivamente; para la variante nueva fueron 0,9285 – 0,0071 para CC, CT, respectivamente. La muestra poblacional estudiada no se encuentra en equilibrio de Hardy-Weinberg para la variante rs41256848. Los resultados obtenidos en la presente investigacion demostraron la presencia de polimorfismos en el fragmento de LHR estudiado, en animales Carora.
Dynamics of Ganymede's magnetopause: Intermittent reconnection under steady external conditions: GANYMEDE MAGNETOPAUSE DYNAMICS

[1] Magnetic reconnection at the terrestrial magnetopause is frequently intermittent, leading to the formation of localized reconnected flux bundles referred to as flux transfer events (FTEs). It remains unclear whether the intermittency of the process is intrinsic or arises because of fluctuations of solar wind properties. Here we use Ganymede's magnetosphere, which is embedded in a background of field and plasma whose properties vary imperceptibly over time scales pertinent to plasma flow across the moon's magnetosphere, to demonstrate that reconnection is intrinsically intermittent. We run time-dependent global magnetohydrodynamic (MHD) simulations that describe Ganymede's magnetospheric environment realistically and reproduce plasma and field measurements made on multiple Galileo passes by the moon with considerable fidelity. The simulations reveal that even under steady external conditions, dynamic variations associated with magnetic reconnection on time scales of the order of tens of seconds occur over a large region near the upstream magnetopause. The MHD simulations give direct evidence of magnetic reconnection at the magnetopause and reproduce the amplitude and spatial distribution of observed fluctuations of the magnetic field near boundary crossings. The consistency of data and simulations leads us to conclude that even under steady upstream conditions, upstream reconnection is intermittent. The bursty magnetopause structures at Ganymede and the FTEs identified at planetary magnetospheres (Mercury, Earth, and Jupiter) extend the parameter regime for analysis of intermittent magnetopause reconnection. We find that FTE recurrence times decrease with the scale length of the system.
Injection drug users’ perceived barriers to using self-initiated harm reduction strategies

Introduction and Aims: Increasing the frequency with which injecting drug users (IDUs) engage in self-initiated harm reduction strategies could improve their health, but few investigations have examined IDUs’ perceived barriers to engaging in these behaviors. Method: We interviewed 90 IDUs recruited from needle exchanges to assess: (a) perceived obstacles to their use of two specific harm reduction strategies (i.e., test shots and pre-injection skin cleaning) designed to reduce two unhealthy outcomes (i.e., overdose and bacterial infections, respectively) and (b) their use of other risk-reduction practices. Results: The most frequently cited barrier for both test shots and skin cleaning was being in a rush to inject one's drugs. Other, less commonly cited barriers were strategy-specific (e.g., buying drugs from a known dealer as a reason not to do a test shot; not having access to cleaning supplies as a reason not to clean skin). Regarding other risk reduction practices, participants most frequently reported using new or clean injecting supplies and avoiding sharing needles and injecting supplies. Discussion and Conclusions: Some, but not all, of the barriers generated by participants in our study were similar to those frequently reported in other investigations, perhaps due to differences in the type of sample recruited or in the harm reduction behaviors investigated.
Précis of Democratic Autonomy

Democratic Autonomy's central aim is to characterize how, within democratic institutions, we may reason with one another so as legitimately to settle the ends or aims of our joint, governmental activity. Standard conceptions of policy reasoning, such as cost-benefit and risk-benefit analysis, typically take the ends for granted, as revealed by individuals in market behavior or as settled by "the decision-makers. " The book aims to describe how we, as the decision-makers, can reason about the ends of policy. To discharge this main task, the book had to extend beyond the topic of collective practical reasoning, in two directions. First, it is clear that our ability to reason together about policy matters is highly mediated by an institutional structure that parcels out authority and responsibility in complex and overlapping ways. Hence, any persuasive account of how we reason together, democratically, must be an institutionally rich account. One might take the institutional setting of much democratic reasoning to be simply incompatible with joint reasoning. DA does not take that tack. Rather, it accepts that while the institutional settings within which democratic reasoning goes on especially the constitutionally protected public sphere, the elected legislature employing majority rule, and the administrative agencies do indeed present distinctive challenges to whether we can reason together about the ends of policy, they also provide positive opportunities for an account of joint reasoning that accepts that this reasoning may be institutionally distributed. The second extension of the book's scope concerned the idea of legitimacy. Adequately to assess the conditions under which joint, public reasoning about ends is legitimate, it turned out, required developing a broad account of democratic legitimacy, one specifying the place that reasoning, of any kind, ought to have in democracies. Keeping this question central enabled DA, as I think, to shed new light on our multi-faceted ideal of democracy; and
Higher consumption of green tea may enhance equol production.

BACKGROUND Our previous case-control study revealed that Japanese living in Japan and Koreans living in Korea can be divided into equol producers who have an ability to metabolize daidzein to equol and non-producers, and that the incidence of prostate cancer is higher in the latter group. In the present study, we examined relationships between type of food intake and the capacity for equol production in Japanese subjects. METHODS The subjects were the individuals analyzed for the ability to produce equol in our previous study and newly registered cases. From December 2000 to December 2002, 276 hospitalized patients were interviewed face-to-face and blood samples were collected before breakfast. These included 122 patients with prostate cancer and 154 age-matched controls. RESULTS The frequency of equol producers (0.5 ng/ml or more) among cases and controls was 29% and 45%, respectively (p = 0.004). The consumption of soybeans and green tea were significantly higher in equol producers than in the non-producers (p<0.05). By contrast, the consumption of selenium and fiber was significantly lower in equol producers (p<0.05). CONCLUSIONS Our results suggest that higher consumption of soybean and green tea are strongly related to the establishment of a capacity for equol production.
Lipid Synthetic Transcription Factor SREBP-1a Activates p21WAF1/CIP1, a Universal Cyclin-Dependent Kinase Inhibitor

ABSTRACT Sterol regulatory element-binding proteins (SREBPs) are membrane-bound transcription factors that regulate lipid synthetic genes. In contrast to SREBP-2, which regulates cellular cholesterol level in normal cells, SREBP-1a is highly expressed in actively growing cells and activates entire programs of genes involved in lipid synthesis such as cholesterol, fatty acids, triglycerides, and phospholipids. Previously, the physiological relevance of this potent activity of SREBP-1a has been thought to regulate the supply of membrane lipids in response to cell growth. Here we show that nuclear SREBP-1a and SREBP-2 bind directly to a novel SREBP binding site in the promoter of the p21WAF1/CIP1 gene, the major cyclin-dependent kinase inhibitor, and strongly activate its promoter activity. Only the SREBP-1a isoform consistently causes induction of p21 at both the mRNA and protein levels. Colony formation assays and polyploidy of livers from transgenic mice suggest that activation of p21 by SREBP-1a could inhibit cell growth. Activation of endogenous SREBPs in lipid deprivation conditions was associated with induction of p21 mRNA and protein. Expression of p21 was reduced in SREBP-1 null mice. These data suggest a physiological role of SREBP-1a in p21 regulation. Identification of p21 as a new SREBP target might implicate a new paradigm in the link between lipid synthesis and cell growth.
Specific vulnerability of mouse spinal cord motoneurons to membrane depolarization

Intracellular calcium (Ca2+) concentration determines neuronal dependence on neurotrophic factors (NTFs) and susceptibility to cell death. Ca2+ overload induces neuronal death and the consequences are thought to be a probable cause of motoneuron (MN) degeneration in neurodegenerative diseases. In the present study, we show that membrane depolarization with elevated extracellular potassium (K+) was toxic to cultured embryonic mouse spinal cord MNs even in the presence of NTFs. Membrane depolarization induced an intracellular Ca2+ increase. Depolarization‐induced toxicity and increased intracellular Ca2+ were blocked by treatment with antagonists to some of the voltage‐gated Ca2+ channels (VGCCs), indicating that Ca2+ influx through these channels contributed to the toxic effect of depolarization. Ca2+ activates the calpains, cysteine proteases that degrade a variety of substrates, causing cell death. We investigated the functional involvement of calpain using a calpain inhibitor and calpain gene silencing. Pre‐treatment of MNs with calpeptin (a cell‐permeable calpain inhibitor) rescued MNs survival; calpain RNA interference had the same protective effect, indicating that endogenous calpain contributes to the cell death caused by membrane depolarization. These findings suggest that MNs are especially vulnerable to extracellular K+ concentration, which induces cell death by causing both intracellular Ca2+ increase and calpain activation.
Immunochromatographic Test for Detection of Plasmodium falciparum and Plasmodium vivax in Patients with a Presumptive Clinical Diagnosis of Malaria in Eastern Indonesia

EMILIANA TJITRA, SRI SUPRIANTO, MARY DYER, BART J. CURRIE, AND NICHOLAS M. ANSTEY* Communicable Diseases Research Centre, National Institute of Health Research and Development, and Directorate General of Communicable Disease Control and Environmental Health, Jakarta, Indonesia, and Tropical Medicine and International Health Unit, Menzies School of Health Research, Darwin, Northern Territory, Australia
Dose doubling, relative potency, and dose equivalence of potassium-sparing diuretics affecting blood pressure and serum potassium: systematic review and meta-analyses

Background: Potassium-sparing diuretics (PSDs) are valuable antihypertensives with additional benefits unrelated to control of systolic blood pressure (SBP). However, their key parameters affecting SBP and serum potassium are poorly defined, fostering underutilization. Method: Consequently, we conducted systematic reviews and meta-analyses, yielding 3668 articles and ultimately 84 randomized comparisons. Results: For office SBP, overall placebo-adjusted changes were triamterene –1.9 (low dose only), amiloride –9.9, spironolactone –13.2, and eplerenone –9.2. Differences in antihypertensive effect were due to potency rather than efficacy. Doubling amiloride, eplerenone, and spironolactone doses reduced SBP (95% confidence limits) on average by –2.3 (–3.1, –1.5). Relative antihypertensive potencies were spironolactone>amiloride>eplerenone. Spironolactone had significantly greater antihypertensive potency than amiloride, –4.0 (–7.4, –0.6), and eplerenone, –5.5 (–7.4, –3.6). Dose equivalencies were eplerenone–spironolactone 4.5-to-1 (e.g., eplerenone 125∼spironolactone 25), amiloride–spironolactone 3.3-to-1, and eplerenone–amiloride 1.4-to-1. Increases in serum potassium from amiloride and spironolactone at commonly used doses averaged 0.14–0.29 mEq/l; the dose doubling effect was 0.16 (0.10, 0.22). Spironolactone caused greater hyperkalemia than amiloride across their dose ranges: 0.14, P = 0.043. Seven features make important bias unlikely: a comprehensive literature search, adjustment for covariates, all models explaining 95–100% of the between-study variability, similar dose doubling effects among PSDs, two different methods giving the same potency sequence, similar results from double blind comparisons, and similar results for eplerenone versus spironolactone from analysing direct comparison data (i.e., no meta-regression) for office and 24-h SBP. Conclusion: This synthesis accomplishes for PSDs what has already been achieved for thiazide-type diuretics and other antihypertensives and can guide the application of these underutilized medicines.
Controlling Public Debt without Forgetting Inflation

Consider the problem of a government that wants to control its debt-to-GDP (gross domestic product) ratio, while taking into consideration the evolution of the inflation rate of the country. The uncontrolled inflation rate follows an Ornstein-Uhlenbeck dynamics and affects the growth rate of the debt ratio. The level of the latter can be reduced by the government through fiscal interventions. The government aims at choosing a debt reduction policy which minimises the total expected cost of having debt, plus the total expected cost of interventions on debt ratio. We model such problem as a two-dimensional singular stochastic control problem over an infinite time-horizon. We show that it is optimal for the government to adopt a policy that keeps the debt-to-GDP ratio under an inflation-dependent ceiling. This curve is the free-boundary of an associated fully two-dimensional optimal stopping problem, and it is shown to be the unique solution of a nonlinear integral equation.
Phagosome Formation in Paramecium: Roles of Somatic and Oral Cilia and of Solid Particles as Revealed by Video Microscopy

Abstract The roles of somatic and oral cilia and solid particles during digestive vacuole (DV) formation in Paramecium multimicronucleatum were investigated using video-enhanced and immunofluorescence microscopy. Membrane incorporation into DVs was found to increase linearly with increasing particle concentration. The rate of discoidal vesicle transport to the cytopharynx was not affected by particles, showing that particles are not required for membrane trafficking to the cytopharynx. However, the presence of particles leads to an increased membrane fusion between the cytopharyngeal membrane and the discoidal vesicles. When live cells lost their somatic cilia on the left-ventral side anterior to the oral region due to deciliation, membrane incorporation into newly formed DVs was strongly inhibited. Using video-enhanced microscopy, latex beads were seen to be loaded along the quadrulus on the dorsal surface of the buccal cavity, but few beads were seen next to the dorsal and ventral peniculi. Particle sequestration into a pre-formed nascent digestive vacuole (NDV) was studied in Triton X-100-permeabilized cells whose ciliary beating was reactivated by the addition of Mg-ATP. Both beat frequency and the percentage of cells containing bead-labeled NDV were dependent on the Mg-ATP concentration: the higher the beat frequency, the higher the percentage of cells with a bead-labeled NDV. These results suggest that ciliary beating is probably the only mechanism required for particle accumulation in the NDV, while a coordinated beating of the somatic cilia on the left-ventral side anterior to the oral region as well as the quadrulus moves particles into the NDV. The beating of the peniculi may somehow prevent the backward flow of particles out of the NDV.