Miracle-dz/UniFAR-FTUs huggingface dataset:
The Coming of Age of Phosphoproteomics—from Large Data Sets to Inference of Protein Functions*

Protein phosphorylation is one of the most common post-translational modifications used in signal transduction to control cell growth, proliferation, and survival in response to both intracellular and extracellular stimuli. This modification is finely coordinated by a network of kinases and phosphatases that recognize unique sequence motifs and/or mediate their functions through scaffold and adaptor proteins. Detailed information on the nature of kinase substrates and site-specific phosphoregulation is required in order for one to better understand their pathophysiological roles. Recent advances in affinity chromatography and mass spectrometry (MS) sensitivity have enabled the large-scale identification and profiling of protein phosphorylation, but appropriate follow-up experiments are required in order to ascertain the functional significance of identified phosphorylation sites. In this review, we present meaningful technical details for MS-based phosphoproteomic analyses and describe important considerations for the selection of model systems and the functional characterization of identified phosphorylation sites.
Proliferating cell nuclear antigen and p53 expression as prognostic factors in T1‐2MO prostatic adenocarcinoma

The expression of proliferating cell nuclear antigen and p53 protein was analysed by immunocytochemical methods (PC10, CMI antisera) in 139 patients with T1‐2MO prostatic adenocarcinomas followed‐up for > 12 years. p53 protein was expressed in 21 (15%) tumours (15%), the fraction of positive nuclei being very low (mean SE, 1% ± 0.7%). Accumulation of p53 protein in epithelial cells was independent of tumour stage and Gleason score, and had no effect on prognosis. In 4 cases, p53 protein was expressed only in stromal cells. The fraction of PCNA‐positive nuclei (evaluable in 116 cases) was higher in T2 than in T1 tumours (p < 0.001); furthermore, high Gleason score was positively correlated with PCNA positivity (p < 0.001). A finding of over 5% of PCNA‐positive nuclei predicted progression in T and M categories and were a sign of poor outcome. The fraction of PCNA‐positive stromal‐cell nuclei was related to T‐category with a borderline significance (p = 0.06). In a multi‐variate analysis of the prognostic factors, independent predictors of survival included Gleason score (p < 0.001), fraction of PCNA‐positive nuclei (p = 0.013), observation before therapy (p = 0.05), and T‐category (p = 0.07) in that order of significance. The results suggest that overexpression of p53 protein is of marginal prognostic value in local prostatic adenocarcinomas, whereas direct measurement of cell proliferation by PCNA immunolabelling provides important prognostic information in T1‐2MO tumours, in addition to the Gleason score.
Measuring the Incidence, Causes, and Repercussions of Protocol Amendments

Drug development companies frequently amend finalized clinical trial protocols. Yet the incidence, causes, and impact of protocol amendments have never been quantified. Tufts Center for the Study of Drug Development (Tufts CSDD) conducted a study, in collaboration with 17 large and midsized pharmaceutical and biotechnology companies, examining more than 3,400 clinical trial protocols across development phases and therapeutic areas. Data on protocol characteristics, the number of amendments, the nature and incidence of changes per amendment, the causes of amendments, and the time and cost to implement amendments were among those analyzed. Tufts CSDD found that more than 40% of protocols were amended prior to the first subject/first visit, and one third of amendments were avoidable. Each amended protocol had an average of 2.3 amendments resulting in 4 months of incremental time to implement. Protocol amendments translate into significant unplanned expense and delays for research sponsors and unexpected burden for investigative sites. These findings underscore the substantial impact of protocol amendments on drug development efficiency and present an opportunity to realize substantial cycle time and cost savings.
Thinking big with small stories in narrative and identity analysis

Narrative research is frequently described as a rich and diverse enterprise, yet the kinds of narrative data that it bases itself on present a striking consensus: they are autobiographical in kind (i.e., about non-shared, personal experience, single past events). In this paper, I put forth a case for under-represented narrative data which I collectively call (following Bamberg 2004a, b; also Georgakopoulou & Bamberg, 2005) “small stories” (partly literally, partly metaphorically). My aim is to flesh small stories out, to urge for the sort of systematic research that will establish connections between their interactional features and their sites of engagement and finally to consider the implications of their inclusion in narrative research for identity analysis (as the main agenda of much of narrative research). I will thus propose small stories research as a “new” narrative turn that can provide a needed meeting point for narrative analysis and narrative inquiry.
Effects of angiotensin II receptor blockers on diabetic nephropathy

Impaired kidney function increases the risk of cardiovascular morbidity and mortality. Coexistence of hypertension and type 2 diabetes increases the risk of kidney damage, hypertension being an independent risk factor for kidney disease progression. Angiotensin II, through its inflammatory, proliferative, and thrombotic effects, adversely affects renal perfusion and increases oxidative stress, thus playing a pivotal role in kidney disease progression. Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors improve markers of kidney disease and slow kidney disease progression in diabetic and nondiabetic patients; this kidney protection may be in addition to their antihypertensive activity in those with advanced proteinuric nephropathy. Key beneficial effects of ARBs and ACE inhibitors throughout the kidney disease continuum are primarily explained by blood pressure lowering effects and partially by their direct blockade of angiotensin II. Recent studies have shown that telmisartan, an ARB with high lipophilicity and the longest half-life compared with other ARBs, provides benefits on markers of cardiovascular risk, that is, microalbuminuria and slowing of early-stage nephropathy.
Evaluating the Effectiveness of e-Learning

E-learning is a growing trend among many higher educational institutions. Learners and teaching professionals are attracted by the many benefits of e-learning, such as the flexibility of learning anywhere, at any time and at an individualized pace. The question of the effectiveness of e-learning should be reviewed before adopting e-learning on a large scale. This paper presents a study to evaluate the effectiveness of e-learning, relative to the performance of conventional learning, for a software engineering course. In particular, we compare assessment scores of the cyber group and the conventional group. Our study indicates that e-learning is as effective as the conventional mode of learning.
Marcação imunoistoquímica da expressão astrocitária de proteína glial fibrilar ácida e de vimentina no sistema nervoso central de cães com cinomose

Considering that many aspects involved in the pathogenesis of the central nervous system (CNS) demyelinating diseases are still poorly understood and that astrocytes seem to mediate such processes, this study analyzed the participation of astrocytes in the demyelinating processes of CNS by using immunohistochemical staining of two astrocytic proteins--glial fibrillary acidic protein (GFAP) and vimentin (VIM)--comparing samples of cerebellum and brainstem from eight dogs with canine distemper and from two healthy dogs, from different breeds and ages varying from 1 to 4 years old. Histological sections were submitted to the avidin-biotin-peroxidase indirect method of immunohistochemical staining (ABC) and the astrocytic reactivity, observed in light microscopy, was quantified in a computer system for image analysis. It was possible to notice, on most of the sections from sick animals, degenerative lesions that indicate demyelination. The immunostaining for GFAP and VIM was more intense on animals with canine distemper, specially around the ventricules and near degenerated sites. There was no significant difference between the immunostaining (GFAP and VIM) of animals with canine distemper with and without inflammatory infiltrate of the cerebellar white matter. The increased immunoreactivity of astrocytes for GFAP and the VIM reexpression in injured areas indicate the astrocytic involvement on nervous tissue response to the demyelinating lesions induced by the canine distemper virus (CDV) in the CNS.
Looking in the wrong place? The search for an ideal migraine preventative

The cause of migraine headache is still unknown, although triggers for it are often apparent. There are, in consequence, no reliable migraine headache preventative drugs that act through an influence on known causal pathways. This review discusses the pathophysiology of migraine, the link between migraine triggers and the consequent headache and the putative mode of action of different classes of migraine drugs in the light of a number of pathophysiological models. It advances the idea that migraine triggers produce headache because they increase cortical excitability and discharge, which in turn reduces the inhibitory drive of the descending pain control system, selectively for trigeminovascular sensation. Supporting evidence for such a mechanism is presented and suggestions made as to the modes and sites of action of future improved migraine preventative agents. Drug Dev Res 68:376–388, 2007. © 2007 Wiley‐Liss, Inc.
Initiation School Amongst the Southern Ndebele People of South Africa: Depreciating Tradition or Appreciating Treasure?

ABSTRACT The concept “initiation school” refers to a type of school that was initially established as a secret rite, which, in a symbolic sense, serves as the teenager's “transit education” or “passport” to adulthood. Currently, in South Africa, many opinions are voiced against initiation, mainly because it prevents children from attending formal school for up to ten weeks to attend the initiation schools, and, a rising number of youngsters lose their lives as a direct result of the unprofessional circumcisions that are executed. The matter has become so serious that a new Bill to monitor registration and control of initiation schools was approved in Parliament in 2003. Despite this controversy and the control measures that have been put in place, initiation schools still forms the backbone of traditional education. This research aimed to determine what the initiation schools of the Southern Ndebele people of South Africa entails and what value the Southern Ndebele people attach to this type of traditional education. The study revealed that their initiation, when viewed against the work of Arnold van Gennep (1909, 1969) consists of three significant phases, i.e., the phase of severance, separation and isolation, the phase of thresholding, restoration, preparation and entrance and the phase of inclusion, absorption and incorporation. The study also revealed that initiation, as it is performed today, is consistent with community values and, to a large extent, serves to contribute to the education of the young people of the Southern Ndebele Tribe in that it supports and assists the parents with the difficult task of disciplining their children and transferring the norms and values of the Southern Ndebele, such as respect for others, the observation of their traditions, caring for and affirmation of their cultural identity and the stabilization and perpetuation of their cultural temperospatialtiy.
Optimization of nutrient levels in the medium increases the efficiency of callus induction and plant regeneration in recalcitrant indian barley (Hordeum vulgare L.) in vitro

SummaryThe present study reports that a revised nutrient concentration in the basal medium improved shoot bud induction and subsequent plant regeneration in barley (Hordeum vulgare L. var. BL-2). Cultures were raised from immature embryos on MSB5 medium supplemented with picloram. Concentrations of five nutrients were varied. The effect of these nutrients was investigated on (1) induction, (2) induction and subculture, and (3) induction, subculture and regeneration stages. The basal MSB5 medium was not optimal for each phase of barley culture. Decreased ammonium nitrate, increased potassium dihydrogen phosphate, sodium molybdate, cobalt chloride, and addition of glycine enhanced shoot bud induction and plant regeneration. The different media that were optimal for immature embryo culture were: MSB5 medium supplemented with 20.70 μM picloram, 10.30 mM NH4NO3, 6.25 mM KH2PO4, 2.06 μM Na2MoO4, 0.55 μM CoCl2, and 26.64 μM glycine (for induction); MSB5 medium supplemented with 12.47 μM picloram, 10.30 mM NH4NO3, and 0.55 μM CoCl2 (for subculture); and MSB5 medium supplemented with 0.2 μM picloram and 10.3 mM NH4NO3 (for regeneration). Primary cultures required 6wk (without transfer) for morphogenic callus formation. Callus required 4wk of subculture and another 4wk on regeneration medium for optimal plant regeneration. The revised medium could also promote regeneration of the recalcitrant barley genotype RD-2552. Histological analysis showed that the major pathway of differentiation was through shoot bud formation.
Autoimmunity: Genetic, Immunologic, Virologic, and Clinical Aspects

This book, the product of 40 different contributors from eight countries, is divided into four major parts. The first is devoted to genetic aspects: the major histocompatibility complex and disease, the genetics of autoimmune disease in animals, and the genetic regulation in autoimmune thyroiditis. Part 2 discusses concepts of pathogenesis, self-recognition and tolerance, suppressor T-cell dysfunction, lymphoid malignant neoplasms, thymic hormones, and the biology of immune complexes. Part 3 studies the influence of viral infection on the immune response. The last part consists of nine clinically related chapters that deal with immunodeficiency, aging, and receptor autoimmunity, with three whole chapters given to systemic lupus erythematosus, rheumatoid arthritis, and neurologic disease. The book concludes on a positive theme with a chapter on the possible beneficial role of certain autoimmune phenomenons. Each chapter is an extensively referenced review that could stand on its own in a medical journal, and each can serve
Pleuropneumonia-Like Organisms in the Etiology of Turkey Sinusitis and Chronic Respiratory Disease of Chickens

Abstract Several types of evidence suggest that the causative agents of turkey sinusitis and chronic respiratory disease of chickens might belong to the pleuropneumonia group of microorganisms. Their sensitivity to antibiotics, their morphology and staining reactions, the chronic nature of the lesions with which they are associated, the joint lesions in chick embryos produced by certain strains—these characteristics are consistent with the known properties of certain members of the pleuropneumonia group. Nelson (1936a, b, 1939) who described the coccobacillary bodies associated with a coryza of slow onset in chickens, raised the question of the relationship of the agents which he cultivated in tissue culture and other media to members of the pleuropneumonia group. Van Herick and Eaton (1945) reported the isolation of a pleuropneumonia-like organism which they believed occurred as a contaminant in chick embryos used in their laboratory. Strains of the agent of chronic respiratory disease of chickens and .
Demographic characteristics and opportunistic diseases associated with attrition during preparation for antiretroviral therapy in primary health centres in Kibera, Kenya

Using routine data from HIV‐positive adult patients eligible for antiretroviral therapy (ART), we report on routinely collected demographic characteristics and opportunistic diseases associated with pre‐ART attrition (deaths and loss to follow‐up). Among 2471 ART eligible patients, enrolled between January 2005 and November 2008, 446(18%) were lost to attrition pre‐ART. Adjusted risk factors significantly associated with pre‐ART attrition included age <35 years (Odds Ratio, OR 1.4, 95% Confidence Interval, CI 1.1–1.8), severe malnutrition (OR 1.5, 95% CI 1.1–2.0), active pulmonary tuberculosis (OR 1.6, 95% CI 1.1–2.4), severe bacterial infections including severe bacterial pneumonia (OR 1.9, 95% CI 1.2–2.8) and prolonged unexplained fever (>1 month), (OR 2.6, 95% CI 1.3–5.2). This study highlights a number of clinical markers associated with pre‐ART attrition that could serve as ‘pointers’ or screening tools to identify patients who merit fast‐tracking onto ART and/or closer clinical attention and follow‐up.
Impact of Folic Acid Fortification in the United States: Markedly Diminished High Maternal Serum Alpha-Fetoprotein Values

OBJECTIVE: Folic acid fortification of breads and grains was implemented in the United States in 1998 in an attempt to reduce the incidence of neural tube defects. Outcome data from birth registries have shown a 20% drop—less than originally predicted. In this study, we ascertain if the impact of folic acid fortification is better seen at the time of midtrimester prenatal diagnosis by looking at incidence of high maternal serum alpha-fetoprotein (MSAFP) values. METHODS: Data regarding MSAFP levels in 61,119 patients undergoing maternal serum screening at a large commercial laboratory were categorized by multiples of the median (MoM). The data were compared between 2 groups: before mandatory supplementation in the United States in 1997 and after mandatory supplementation in 2000. High MSAFP values were further categorized as high (2.75–4.00 MoM) or very high (more than 4.00 MoM). Data were analyzed by χ2 analysis. RESULTS: Comparative data showed a 32% decrease of patients with MoM greater than 2.75 + (2.5% −1.7%). Further categorizations revealed similar decreases. CONCLUSION: The introduction of folic acid fortification has produced a profound decrease in the number of high MSAFP values, reflective of a decreased incidence of neural tube defects. Our results help to validate the decision to fortify food with folic acid, which represents a highly successful public health policy for primary prevention of birth defects. LEVEL OF EVIDENCE: II-2
Testing for 22q11 microdeletion in 146 fetuses with nuchal translucency above the 99th percentile and a normal karyotype

The aim of this study was to examine the value of testing for a 22q11 microdeletion in fetuses with nuchal translucency (NT) above the 99th percentile (>3.5 mm). A 22q11 microdeletion results in the development of 22q11 deletion syndrome, a spectrum of disorders also known as DiGeorge/Velocardiofacial syndrome. A total of 146 pregnancies met the inclusion criteria of NT >3.5 mm between 11+2 and 13+6 weeks’ gestation, no structural malformation and normal karyotype. Chorionic villi samples were tested with either multiplex ligation‐dependent probe amplification (MLPA) or fluorescent in situ hybridization (FISH) analysis for 22q11 microdeletion. None were diagnosed with the microdeletion. The estimated prevalence of 22q11 microdeletion in these otherwise normal fetuses with increased NT is below 2.7%.
RAPID RADIATION DOSE ASSESSMENT FOR RADIOLOGICAL PUBLIC HEALTH EMERGENCIES: ROLES OF NIAID and BARDA

A large-scale radiological incident would result in an immediate critical need to assess the radiation doses received by thousands of individuals to allow for prompt triage and appropriate medical treatment. Measuring absorbed doses of ionizing radiation will require a system architecture or a system of platforms that contains diverse, integrated diagnostic and dosimetric tools that are accurate and precise. For large-scale incidents, rapidity and ease of screening are essential. The National Institute of Allergy and Infectious Diseases of the National Institutes of Health is the focal point within the Department of Health and Human Services (HHS) for basic research and development of medical countermeasures for radiation injuries. The Biomedical Advanced Research and Development Authority within the HHS Office of the Assistant Secretary for Preparedness and Response coordinates and administers programs for the advanced development and acquisition of emergency medical countermeasures for the Strategic National Stockpile. Using a combination of funding mechanisms, including funds authorized by the Project BioShield Act of 2004 and those authorized by the Pandemic and All-Hazards Preparedness Act of 2006, HHS is enhancing the nation's preparedness by supporting the radiation dose assessment capabilities that will ensure effective and appropriate use of medical countermeasures in the aftermath of a radiological or nuclear incident.
Measurements on the lumbosacral junction in normal dogs and those with cauda equine compression

Comparative measurements on lateral plain radiographs of the lumbosacral junction in neutral position, in flexion, and in extension, were made of 41 clinically and radiographically normal dogs (21 German shepherd dogs [GSDs], 12 Bernese mountain dogs, eight labrador retrievers) and 58 GSDs with clinical signs of cauda equina compression due to malformation and, or, malarticulation. The comparison of these measurements between sexes, between normal and affected GSDs and between normal GSDs and the two other breeds of dogs showed several statistically significant results. One was that the affected GSDs showed a reduced flexion ability at this junction compared to the normal ones. However, no difference was observed in the degree of sub-luxation of the sacrum between normal and affected GSDs. It was concluded that plain radiographs of the lumbosacral junction in flexion could help in determining a reduced flexion ability, which could be a characteristic of the GSD with cauda equina compression.
Severe physical violence among intimate partners: a risk factor for vaginal bleeding during gestation in less privileged women?

Objectives. To evaluate the role of severe physical violence within intimate partners on the occurrence of vaginal bleeding during gestation in less privileged women. Design. Health service survey. Setting. Three large public maternities in the city of Rio de Janeiro, Brazil. Sample. Five hundred and twenty‐eight women who gave birth to full‐term newborn infants were selected at random among the births that took place during the six months of fieldwork. Methods. Information on vaginal bleeding during gestation was obtained from medical records, pre‐natal cards, and by means of a questionnaire addressed to the women giving birth. To collect severe physical violence data, use was made of the Portuguese version of the instrument Revised Conflict Tactics Scales, formally adapted for use in Brazil. Main outcome measures. Vaginal bleeding during gestation. Results. After accounting for socio‐economic, demographic, reproductive, and pregnant women's life‐style variables, women who had been victims of two or more acts of severe physical violence were 2.74 (95% CI: 1.37–5.48) times more liable to present with vaginal bleeding during pregnancy than those who did not. Conclusion. Our findings suggest that physical violence increases the risk of vaginal bleeding in pregnancy. This result should encourage studies on whether intervention in violent relationships can reduce the risk of vaginal bleeding and other pregnancy complications.