Miracle-dz/UniFAR-FTUs huggingface dataset:
The ARIC-PET amyloid imaging study

Objective: To evaluate differences in amyloid deposition in a community-based cohort without dementia by age, sex, race, education, and APOE ε4 allele status. Methods: Recruited from the longitudinal Atherosclerosis Risk in Communities study, 329 participants without dementia, ages 67–88 years, were imaged using florbetapir PET at 3 US community sites (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi). Standardized uptake value ratios (SUVRs) were calculated; global cortical SUVR >1.2 was evaluated as the primary outcome. Age, race, sex, education level, and number of APOE ε4 alleles were evaluated in multivariable models including vascular risk factors, brain white matter hyperintensity and total intracranial volume, and cognitive status. Results: A total of 141 of the participants (43%) were black. In multivariable models, odds of elevated SUVR was increased in participants with increasing age (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.01–2.65 per 10 years of age) and black race (OR 2.08, 95% CI 1.23–3.51) but did not differ by educational level. Each ε4 allele was associated with increased odds of elevated SUVR (OR 2.65, 95% CI 1.61–4.39). Conclusions: In this community-based cohort without dementia, florbetapir uptake is associated with older age and APOE genotype. Black race was associated with higher SUVR, after adjusting for demographics, vascular risk factors, cognitive status, white matter hyperintensity volume, and APOE genotype, with effect sizes nearing those seen for APOE ε4. Replication of these findings is needed in other cohorts, and reasons for and consequences of these observed differences by race warrant further study.
Voltage‐ and stage‐development uncoupling of Rohon‐Beard neurones during embryonic development of Xenopus tadpoles

1. Electrical coupling of Rohon‐Beard neurones in the spinal cord of Xenopus laevis has been studied from the time of closure of the neural tube (stage 20, 22h after fertilization of the egg) to the free swimming tadpole (stage 49, 12d old). Pairs of cells were examined by impaling both simultaneously with single micro‐electrodes having current‐passing and voltage‐recording capabilities.
Targeting p53-Null Neuroblastomas through RLIP76

The search for p53-independent mechanism of cancer cell killing is highly relevant to pediatric neuroblastomas, where successful therapy is limited by its transformation into p53-mutant and a highly drug-resistant neoplasm. Our studies on the drug-resistant p53-mutant as compared with drug-resistant p53 wild-type neuroblastoma revealed a novel mechanism for resistance to apoptosis: a direct role of p53 in regulating the cellular concentration of proapoptotic alkenals by functioning as a specific and saturable allosteric inhibitor of the alkenal–glutathione conjugate transporter, RLIP76. The RLIP76-p53 complex was showed by both immunoprecipitation analyses of purified proteins and immunofluorescence analysis. Drug transport studies revealed that p53 inhibited both basal and PKCα-stimulated transport of glutathione conjugates of 4HNE (GSHNE) and doxorubicin. Drug resistance was significantly greater for p53-mutant as compared with p53 wild-type neuroblastoma cell lines, but both were susceptible to depletion of RLIP76 by antisense alone. In addition, inhibition of RLIP76 significantly enhanced the cytotoxicity of cisplatin. Taken together, these studies provide powerful evidence for a novel mechanism for drug and apoptosis resistance in p53-mutant neuroblastoma, based on a model of regulation of p53-induced apoptosis by RLIP76, where p53 is a saturable and specific allosteric inhibitor of RLIP76, and p53 loss results in overexpression of RLIP76; thus, in the absence of p53, the drug and glutathione-conjugate transport activities of RLIP76 are enhanced. Most importantly, our findings strongly indicate RLIP76 as a novel target for therapy of drug-resistant and p53-mutant neuroblastoma. Cancer Prev Res; 4(6); 879–89. ©2011 AACR.
Baseline sensitivity to three triazole fungicides in Pyrenophora tritici-repentis

Pyrenophora tritici-repentis (anamorph: Drechslera tritici-repentis) causes yellow spot of wheat. The disease can be responsible for yield losses of 30–50% and, when severe, requires management with fungicide. Forty-five single conidium isolates collected from the northern wheatbelt of Western Australia were tested for sensitivity to three triazole fungicides in culture. At 0.2 mg/mL epoxiconazole and 0.4 mg/mL propiconazole and tebuconazole, the mean relative diameter of cultures was close to 50%, indicating that epoxiconazole had about twice the in vitro activity of propiconazole or tebuconazole. Isolates exhibited a significant fungicide rate interaction such that some isolates differed in response to propiconazole compared with epoxiconazole or tebuconazole. Sensitivity among 32 isolates collected from commercial wheat crops over the period 2001–03 was not significantly different from sensitivity among 13 isolates collected in 1986–87 when fungicide use was minimal. The observed EC50 values (concentration of fungicide required to cause 50% inhibition of growth of isolates) provide a basis to monitor potential changes in sensitivity to azole fungicides.
DNA Demethylase Is a Processive Enzyme*

DNA methylation patterns are generated during development by a sequence of methylation and demethylation events. We have recently demonstrated that mammals bear a bona fidedemethylase enzyme that removes methyl groups from methylated cytosines. A general genome wide demethylation occurs early in development and in differentiating cell lines. This manuscript tests the hypothesis that the demethylase enzyme is a processive enzyme. Using bisulfite mapping, this report demonstrates that demethylase is a processive enzyme and that the rate-limiting step in demethylation is the initiation of demethylation. Initiation of demethylation is determined by the properties of the sequence. Once initiated, demethylation progresses processively. We suggest that these data provide a molecular explanation for global hypomethylation.
Mechanisms of Platelet Dysfunction and Response to DDAVP in Patients with Congenital Platelet Function Defects

Summary To examine the impact of the underlying defective platelet mechanism on the response to 1-desamino-8-D-arginine vasopressin (DDAVP, Desmopressin), we studied the effect of intravenous infusion of 0.3 μg/kg of DDAVP in a randomized double blind placebo-controlled trial with cross-over in 18 carefully characterized patients with congenital platelet defects (CPD) and BT ≥9 min. Eleven patients had normal dense granule stores and normal thromboxane A2 (TxA2) production (Group I), 3 patients had normal granule stores but impaired TxA2 production (Group II), and 4 had δ-storage pool deficiency (Group III). DDAVP shortened BT at 50 min (DDAVP 14.6 ± 2.2 vs placebo 19.6 ± 2.3 min; n = 18; mean ± SE; p = 0.003) and 4h (17.0 ± 2.2 vs 19.6 ±2.1 min, p = 0.055), and raised plasma FVIIIC and von Willebrand factor (vWF). At 50 min DDAVP shortened BT by ≥5 min in 8 of 11 Group I patients (mean 9.7 ± 1.3 vs 16.3 ± 2.8 min; p <0.008), 1 of 3 Group II patients (11.9 ± 3.9 vs 17.7 ± 6.6; p = NS) and none of Group III patients (mean 30 min both arms). Ten patients (Group I or II) were managed successfully during surgical procedures with DDAVP alone. We conclude that DDAVP shortens BT in majority of CPD patients with normal dense granule stores and suggest that BT response may be dependent on the underlying platelet defect. DDAVP is a useful modality in management of selected patients, particularly those with normal dense granule stores.
Effect of Concentrate Feeding Level on Production of Holstein Cows Grazing Winter Annuals

Abstract A replicated randomized block trial was conducted to determine the response of Holstein cows rotationally grazing annual ryegrass-Crimson clover pasture to supplemental concentrate. Within each of 2 yr, 16 Holstein cows were assigned to one of four blocks by energy-corrected milk yield, days in milk, and parity. Treatments included one of four levels of concentrate based on the following grain to milk ratios: 0 kg concentrate or 1 kg for each 7, 5, or 3 kg of energy-corrected milk. Average chemical composition (DM basis) of pasture during each grazing season was 22.5% DM, 18.5% CP, and 21.5% ADF in 1996 and 23.5% DM, 14.6% CP, and 25.2% ADF in 1997. Concentrate DMI averaged 0, 4.4, 6.2, and 8.3 kg/d for 0, 1:7, 1:5, and 1:3 treatments in 1996, respectively. Yield of milk and components increased linearly as the amount of concentrate fed increased. A quadratic response was observed for yield of milk fat and protein as yield of these components increased up to 1:5 and then reached a plateau. Concentrate DMI in 1997 averaged 0, 4.4, 6.1, and 10.5 kg/d for 0, 1:7, 1:5, and 1:3 treatments, respectively. Yields of milk and milk protein, lactose, and solids-not-fat increased linearly as the amount of concentrate fed increased. Regression analysis predicted that pasture alone would support milk yields of 20.4 kg and that the increase in milk yield diminished with each increase in amount of concentrate fed. These data indicate that the amount of concentrate fed when high quality annual ryegrass-crimson clover pasture is readily available can be limited to 1 kg for each 4.5 kg of energy-corrected milk to optimize income over concentrate cost.
Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum)

Extracts of St John's wort (Hypericum perforatum) are widely used in the treatment of depression, often as an over‐the‐counter drug. In contrast to its frequent use, knowledge about the pharmacokinetics of ingredients and drug interactions of St John's wort is poor. We studied the interaction between hypericum extract LI160 and digoxin.
Feeling safe in school

Abstract This paper advances the hypothesis that for a child to feel safe and to learn at school certain psychological conditions must be met. These conditions are described using concepts derived from psychoanalytic research and include; a background of SAFETY and a feeling of WELL BEING derived from a healthy ego with perceptual skills appropriate to the task, a HOLDING environment of adults who can respond appropriately to the child's developmental needs, an environment that provides CONTAINMENT and helps children process negativity in relationships, processes that help children regulate affect, value relationships, and leam to mentalise, in a SECURE ATTACHMENT experience, and finally, supports that encourage children to function as responsible members of a community organized as an OPEN SOCIAL SYSTEM.
The FEAR Before MEN: Networks of Mitotic Exit

Variations in the normal regulation of the mitotic cell cycle can lead to such global cellular changes as differential development or malignant transformation. Studies on the control of mitosis are particularly important to discover the details of the basic mechanisms responsible for normal cell division, as well as to learn about strategies employed by cancerous cells to indefinitely proliferate. The past years have brought noteworthy progress in elucidating the molecular pathways that regulate crucial events during mitosis such as: chromosome condensation, formation of the mitotic spindle, chromosome segregation, cytokinesis, and disassembly of the mitotic spindle. Key Words: Mitosis, FEAR, MEN
Mutation analysis of PIK3CA and PIK3CB in esophageal cancer and Barrett's esophagus

Mutation of PIK3CA, the gene coding for the p110α catalytic subunit of phosphoinositide 3‐kinase (PI3K), has been reported in a limited range of human tumors. We now report that PIK3CA is also mutated in esophageal tumors. Single‐strand conformational polymorphism (SSCP) and denaturing high‐performance liquid chromatography (DHPLC) were used to screen all 20 exons of PIK3CA in 101 samples from 95 individuals with esophageal cancer and/or Barrett's esophagus. Somatic mutation of PIK3CA was detected in 4 of 35 (11.8%) of esophageal squamous cell carcinomas (SCC) and 3 of 50 (6%) adenocarcinomas. No mutations were detected in any of 17 samples of Barrett's esophagus. For PIK3CB, we screened exons 11 and 22, which code for the regions corresponding to the exon 9 and 20 mutational ‘hotspots’ of PIK3CA. No somatic changes were detected in PIK3CB This study extends previous observations in other tumor types by demonstrating the presence of somatic PIK3CA mutations in both SCC and adenocarcinoma of the esophagus, thus implicating the PI3K pathway in the initiation and/or progression of esophageal cancers. © 2005 Wiley‐Liss, Inc.
Science, Values, and the Priority of Evidence

: It is now commonly held that values play a role in scientific judgment, but many arguments for that conclusion are limited. First, many arguments do not show that values are, strictly speaking, indispensable. The role of values could in principle be filled by a random or arbitrary decision. Second, many arguments concern scientific theories and concepts which have obvious practical consequences, thus suggesting or at least leaving open the possibility that abstruse sciences without such a connection could be value-free. Third, many arguments concern the role values play in inferring from evidence, thus taking evidence as given. This paper argues that these limitations do not hold in general. There are values involved in every scientific judgment. They cannot even conceivably be replaced by a coin toss, they arise as much for exotic as for practical sciences, and they are at issue as much for observation as for explicit inference.
Rôle du motif SDN dans l'inhibition et l'activité des β-lactamases des mycobactéries

Mycobacterium tuberculosis et Mycobacterium abscessus produisent les β-lactamases BlaC et BlaMab qui contribuent a la resistance intrinseque de ces bacteries aux β-lactamines. Notre objectif est de caracteriser l’inhibition de ces β-lactamases par l’avibactam et le clavulanate pour contribuer au developpement de nouveaux traitements. Nous avons determine le profil de substrat et d’inhibition de BlaMab ainsi que sa structure cristalline, revelant trois differences majeures avec BlaC. BlaMab a une activite superieure a celle de BlaC pour toutes les β-lactamines sauf la cefoxitine qui est utilisee pour les infections dues a M. abscessus. BlaC est inhibee irreversiblement par le clavulanate et inefficacement par l’avibactam alors que BlaMab presente le comportement inverse impliquant une hydrolyse du clavulanate et une inhibition tres rapide par l’avibactam. La structure de BlaMab differe de celle de BlaC principalement par le remplacement du motif conserve SDN par SDG. L’introduction de SDG dans BlaMab et de SDN dans BlaC a montre que cette difference determine le profil d’inhibition des β-lactamases. Une seule mutation peut donc entrainer l’emergence d’une resistance aux combinaisons d’une β-lactamine avec le clavulanate ou l’avibactam mais pas avec les deux inhibiteurs. L’avibactam et le clavulanate offrent donc des alternatives therapeutiques en cas de resistance a l’un des inhibiteurs. Nous nous sommes egalement interesses aux β-lactamines partenaires du clavulanate, pour le traitement de la tuberculose et montrer que la structure des carbapenemes pouvait etre optimisee pour ameliorer l’inactivation des cibles et diminuer l’hydrolyse par BlaC.
Los entornos sociales y su relación con el conflicto y la violencia escolar en las ciudades de Armenia y Manizales, Colombia

Este articulo se propone describir como los entornos sociales (familiares, barriales y escolares) estan asociados a la problematica de la violencia escolar en las instituciones educativas publicas de las ciudades de Manizales y Armenia. Con un enfoque cuantitativo, de diseno transversal y alcance descriptivo, se aplicaron 500 encuestas a estudiantes de grados sexto a once y 30 a docentes y coordinadores. Los resultados muestran que los entornos sociales residenciales y escolares tienen variaciones notables en las dos capitales. En Manizales los entornos vecinales representan una mayor exposicion a la venta y consumo de sustancias psico-activas, barras o pandillas futboleras y a personal armado; en Armenia, sus entornos escolares presencian y tienen mayor influencia las dinamicas violentas o adictivas.
EVALUATING SIGN RESTRICTIONS

Sign restrictions identify the responses to structural shocks only weakly, i.e there is more than one impulse response compatible with the identifying assumption. This paper assesses to what extent imposing sign restrictions can recover the impulse responses generated from a DSGE model. I abstr act entirely from estimation uncertainty and focus solely on the problems stemming from weak identification. To this end, two DSGE models are specified and the implied VAR representation of a certain set of observables is backed out. Hence, all parameter matrices including the covariance matrix of VAR innovations are treated as known. The main findings are as follows. First, weak identification arising from sign restrictions is an important issue since the range of all impulse responses consistent with theory is typically very wide. Second, for the sign restriction method to be informative a large number of sign restrictions must be imposed. This implies that minimal restrictions are likely to come to inconclusive findings. Third the amount of sign restrictions necessary to achieve sufficient informativeness may co nflict with the desire of some researchers to specify robust sign restrictions.
Effect of Non-starch Polysaccharides and Resistant Starch on Mucin Secretion and Endogenous Amino Acid Losses in Pigs

Generally, dietary fibre (DF) includes lignin, non-starch polysaccharides (NSP) and resistant starch (RS). In monogastric species, low levels of dietary fibre in the diet are associated with various diseases and high levels reduce nutrient digestibilities. In this study, the effects of different types and levels of NSP (soluble: β-glucan, insoluble cellulose) and resistant starch on mucin secretion and endogenous nitrogen and amino acid losses in pigs were investigated. A total of 25 five-week-old weaner pigs (9.5 kg±1.5 kg), were randomly allocated to each of five experimental diets. Different levels of purified barley β-glucan (BG) extract (5 or 10% of Glucagel ® β-glucan, providing 4 or 8% of BG in the diet), and resistant starch (RS) (8.3 or 16.6% of Hi-Maize TM , providing 5 or 10% RS in the diet) were substituted for wheat starch in a purified diet in which enzymatically-hydrolysed casein was the sole source of protein. The diets were fed for 21 days. No statistically significant difference between treatments (p>0.05) was observed for growth performance and organs weights. No difference in ileal starch digestibility was observed between pigs on the cellulose or β-glucan diets. However, as the level of resistant starch in the diet increased the ileal starch digestibility decreased (p<0.05). The inclusion of resistant starch in the diet (5 or 10%) did not increase mucin production when compared with the cellulose-only diet. However, as the level of beta-glucan in the diet increased, both crude mucin in the digesta dry matter and per kg dry matter intake increased (p<0.05). Pigs fed the diet containing 8% of beta-glucan had higher endogenous loss flow than those fed the diets including 5 or 10% of resistant starch or 4% of β-glucan. In conclusion, dietary inclusion of resistant starch increased the level of starch reaching the large intestine without any effect on mucin secretion, or endogenous nitrogen or amino acid losses content in the small intestine. The addition of β-glucan to a diet containing cellulose increases both mucin secretion and endogenous amino acid and nitrogen losses in the small intestine. (Asian-Aust. J. Anim. Sci. 2005. Vol 18, No. 11 : 1634-1641)
A Multivariate Framework for Variable Selection and Identification of Biomarkers in High-Dimensional Omics Data

In this thesis, we address the identification of biomarkers in high-dimensional omics data. The identification of valid biomarkers is especially relevant for personalized medicine that depends on accurate prediction rules. Moreover, biomarkers elucidate the provenance of disease, or molecular changes related to disease. From a statistical point of view the identification of biomarkers is best cast as variable selection. In particular, we refer to variables as the molecular attributes under investigation, e.g. genes, genetic variation, or metabolites; and we refer to observations as the specific samples whose attributes we investigate, e.g. patients and controls. Variable selection in high-dimensional omics data is a complicated challenge due to the characteristic structure of omics data. For one, omics data is high-dimensional, comprising cellular information in unprecedented details. Moreover, there is an intricate correlation structure among the variables due to e.g internal cellular regulation, or external, latent factors. Variable selection for uncorrelated data is well established. In contrast, there is no consensus on how to approach variable selection under correlation. Here, we introduce a multivariate framework for variable selection that explicitly accounts for the correlation among markers. In particular, we present two novel quantities for variable importance: the correlation-adjusted t (CAT) score for classification, and the correlation-adjusted (marginal) correlation (CAR) score for regression. The CAT score is defined as the Mahalanobis-decorrelated t-score vector, and the CAR score as the Mahalanobis-decorrelated correlation between the predictor variables and the outcome. We derive the CAT and CAR score from a predictive point of view in linear discriminant analysis and regression; both quantities assess the weight of a decorrelated and standardized variable on the prediction rule. Furthermore, we discuss properties of both scores and relations to established quantities. Above all, the CAT score decomposes Hotellingâ€TMs T 2 and the CAR score the proportion of variance explained. Notably, the decomposition of total variance into explained and unexplained variance in the linear model can be rewritten in terms of CAR scores. To render our approach applicable on high-dimensional omics data we devise an efficient algorithm for shrinkage estimates of the CAT and CAR score. Subsequently, we conduct extensive simulation studies to investigate the performance of our novel approaches in ranking and prediction under correlation. Here, CAT and CAR scores consistently improve over marginal approaches in terms of more true positives selected and a lower model error. Finally, we illustrate the application of CAT and CAR score on real omics data. In particular, we analyze genomics, transcriptomics, and metabolomics data. We ascertain that CAT and CAR score are competitive or outperform state of the art techniques in terms of true positives detected and prediction error.
Defining Macropinocytosis

Macropinocytosis represents a distinct pathway of endocytosis in mammalian cells. This actin‐driven endocytic process is not directly co‐ordinated by the presence of cargo but can be induced upon activation of growth factor signalling pathways. The capacity to dissect the contribution of macropinocytosis to cellular processes has been hampered by a lack of unique molecular markers and defining features. While aspects of macropinosome formation and maturation are common to those shared by the other endocytic pathways, a number of key differences have recently begun to emerge and will be discussed in this study. It is now well established that macropinocytosis significantly contributes to antigen presentation by the immune system and is exploited by a range of pathogens for cellular invasion and avoidance of immune surveillance.