Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple LRRK2 variants modulate risk of Parkinson disease: a chinese multicenter study

We and others found two polymorphic LRRK2 (leucine‐rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first sequenced the coding regions in young onset and familial PD patients and identified 59 variants. We then examined these variants in 250 patients and 250 control subjects. Among the 17 polymorphic variants, five demonstrated different frequency in cases versus controls and were considered in a larger sample of 1,363 patients and 1,251 control subjects. The relative risk of an individual with both p.G2385R and p.R1628P is about 1.9, and this is reduced to 1.5–1.6 if the individual also carries rs7133914:G>C; p.R1398H or rs7308720:C>A: p.N551K. The risk of a carrier with p.R1628P is largely negated if the individual also carries p.R1398H or p.N551K. In dopaminergic neuronal lines, p.R1398H had significantly lower kinase activity, whereas p.G2385R and p.R1628P showed higher kinase activity than wild type. We provided the first evidence that multiple LRRK2 variants exert an individual effect and together modulate the risk of PD among Chinese. Hum Mutat 31:561–568, 2010. © 2010 Wiley‐Liss, Inc.
Interaction between Visual- and Goal-related Neuronal Signals on the Trajectories of Saccadic Eye Movements

During natural viewing, the trajectories of saccadic eye movements often deviate dramatically from a straight-line path between objects. In human studies, saccades have been shown to deviate toward or away from salient visual distractors depending on visual- and goal-related parameters, but the neurophysiological basis for this is not well understood. Some studies suggest that deviation toward is associated with competition between simultaneously active sites within the intermediate layers of the superior colliculus (SC), a midbrain structure that integrates sensory and goal-related signals for the production of saccades. In contrast, deviation away is hypothesized to reflect a higher-level process, whereby the neural site associated with the distractor isactively suppressed via a form of endogenous, top–down inhibition. We tested this hypothesis by measuring presaccadic distractor-evoked activation of SC visuomotor neurons while monkeys performed a simple task configured specifically to induce a high degree of saccades that deviate away. In the SC, cognitive processes such as top–down expectation are represented as variation in the sustained, low-frequency presaccadic discharge. We reasoned that any inhibition at the distractor-related locus associated with saccade deviation should affect the excitability of the neuron, thereby affecting the discharge rate. We found that, although the task produced robust deviation away, there was no evidence of a relationship between saccade deviation and distractor-evoked activation outside a short perisaccadic window that began no earlier than 22 msec before saccade onset. This indicates that deviation away is not adequately explained by a form of sustained, top–down inhibition at the distractor-related locus in the SC. The results are discussed in relation to the primary sources of inhibition associated with saccadic control.
Personal health records: key adoption issues and implications for management

Electronic Personal Health Records (PHRs) has been perceived as the tool to empower consumers to become active decision-makers of their healthcare instead of leaving the decision to providers. However, there has been the lack of enthusiasm and adoption of PHRs. This paper examines the current healthcare climate and attempts to understand the major challenges associated with PHRs adoption. The paper-based and fragmented healthcare system is no longer appropriate for the digital economy of the 21st century. The integrated health information technology system is the solution to transform clinical practice to consumer centric and information driven. Tools such as PHRs are means to an end that provide better, safer and more affordable healthcare for consumers. However, there has been little research conducted to demonstrate PHR's tangible value, despite the widespread perceived value of these technologies. Although survey data reveals that there is a lack of awareness among the public, consumers are receptive to this concept, especially when a physician recommends it. Key issues in adopting PHRs and strategies for successful implementation of PHRs are discussed.
Visually Grounded Meaning Representations

In this paper we address the problem of grounding distributional representations of lexical meaning. We introduce a new model which uses stacked autoencoders to learn higher-level representations from textual and visual input. The visual modality is encoded via vectors of attributes obtained automatically from images. We create a new large-scale taxonomy of 600 visual attributes representing more than 500 concepts and 700 K images. We use this dataset to train attribute classifiers and integrate their predictions with text-based distributional models of word meaning. We evaluate our model on its ability to simulate word similarity judgments and concept categorization. On both tasks, our model yields a better fit to behavioral data compared to baselines and related models which either rely on a single modality or do not make use of attribute-based input.
Renal tubular sensitivity to atrial natriuretic factor in essential hypertension

Objective To study the tubular site or sites of the natriuretic action of atrial natriuretic factor and the possible differences between healthy subjects and patients with essential hypertension Design Nine healthy volunteers and six patients with essential hypertension were studied on four test days under standard conditions, water loading and hydropenia with mannitol or saline loading. On each test day baseline, atrial natriuretic factor infusion (1 µg/min) and recovery measurements were performed after equilibrium had been reached. The measurements included the atrial natriuretic factor (ANF) plasma levels, blood pressure, glomerular filtration rate (GFR), effective renal plasma flow, urinary osmolality and the (fractional) excretions of (free) water, sodium and potassium Methods Fractional free-water excretion and free-water reabsorption (as a function of osmolar clearance) were calculated during water loading and hydropenia with mannitol or saline loading, respectively, using standard formulae. [125I]-iothalamate and [131I]-hippuran were infused continuously for the measurement of GFR and effective renal plasma flow, respectively Results The plasma ANF concentration rose five- to eightfold during the infusion of ANF, which induced an increase in urinary sodium excretion, a small increase in GFR and a decrease in the effective renal plasma flow. Moreover, ANF induced an increase in fractional free-water excretion and a decrease in fractional free-water reabsorption. These changes did not correlate with changes in GFR. The blood pressure and potassium excretion were not affected. The effects of ANF on the plasma ANF levels, natriuresis and renal haemodynamics did not differ between the normotensives and the essential hypertensives. However, the increase in fractional free-water excretion was significantly greater in the patients with essential hypertension and correlated significantly with blood pressure (r = 0.56, P < 0.05) Conclusions These results indicate that the infusion of ANF at a low dose induces a similar natriuretic response in normotensive subjects and in patients with essential hypertension. This natriuresis is probably the result of both a glomerular and a tubular effect of ANF. Proximal as well as distal tubular sites seem to be involved. In essential hypertension an enhanced proximal as well as an impaired distal tubular action of ANF can be hypothesized
Selective Tumor Targeting by the Hypoxia-Activated Prodrug AQ4N Blocks Tumor Growth and Metastasis in Preclinical Models of Pancreatic Cancer

Purpose: The antitumor activities and pharmacokinetics of the hypoxia-activated cytotoxin AQ4N and its metabolites were assessed in several preclinical models of pancreatic cancers. Experimental Design: The cytotoxic effects of AQ4N prodrug and its bioreduced form, AQ4, were tested against multiple human tumor cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Nude mice bearing s.c. or orthotopically implanted human BxPC-3 or Panc-1 tumor cells were treated with AQ4N. Tumor growth inhibition, time to progression/end point, and liver metastasis were evaluated in treatment versus control groups. Plasma and tumor levels of AQ4N and its metabolites were quantitated by liquid chromatography-tandem mass spectrometry. Results: In contrast to AQ4N, the bioreduced AQ4 metabolite displayed potent cytotoxicity in many human tumor lines, including those derived from human pancreatic adenocarcinomas. Single-agent administration of AQ4N significantly delayed tumor growth, progression, and survival in a manner comparable with gemcitabine in multiple pancreatic tumor models in vivo. Survival increases were accompanied by a reduction in incidence and spread of liver metastasis. Quantitation of AQ4N and its metabolites in tumor-bearing mice showed that the prodrug is rapidly cleared from the circulation by 24 h and neither of the bioreduced metabolites was detected in plasma. In contrast, AQ4N readily penetrated BxPC-3 tumors and the cytotoxic AQ4 metabolite rapidly accumulated in tumor tissues at high levels in a dose-dependent fashion. Conclusion: AQ4N undergoes rapid and selective conversion into the potent antineoplastic metabolite AQ4 in tumors in vivo and provides proof of principle for the use of hypoxia-activated prodrugs in the treatment against pancreatic cancers.
Razones de un distanciamiento político : el Movimiento Indígena ecuatoriano y la Revolución Ciudadana

Despite sharing common initial political concerns, the relationship between the Ecuadorian Indigenous movement –mainly represented by the CONAIE confederation- and the Leftist government of Rafael Correa and his PAIS movement has been characterized by conflicts and disagreements. This is the central contradiction behind this article. The objective of the study is to analytically explore particular reasons behind this conflictive relationship since the establishment of the Correa government from 2007 onwards. Four interconnected thematic fields are emphasized as likely explanations to the disagreement and distance between the indigenous organizations and the government. These programmatic differences are: opposition against resource exploitation, attitudes towards social mobilization, agrarian politics, and lastly, the state policy we label de-sectorization.
Nontuberculous Mycobacterial Disease Mortality in the United States, 1999–2010: A Population-Based Comparative Study

Background Environmental nontuberculous mycobacteria (NTM) are ubiquitous organisms with which humans commonly interact. The epidemiologic characteristics of NTM diseases including mortality rate and its associated factors remain largely unknown. In this study, we explored the geographical area of exposure and mortality and comorbid conditions of affected persons to determine environment, host, and host-pathogen interactive factors. Methods We analyzed mortality related to nontuberculous mycobacterial infections from 1999 through 2010 by examining multiple-cause-of-death data from the National Center for Health Statistics. Among those who died with these diseases, we analyzed age-adjusted mortality rates, trends, associations with demographic variables, and comorbid conditions and correlated this information with similar data for tuberculosis-related mortality during the same time. Measurements and Mean Results From 1999 through 2010, nontuberculous mycobacterial disease was reported as an immediate cause of death in 2,990 people in the United States with a combined overall mean age-adjusted mortality rate of 0.1 per 100,000 person-years. A significant increase in the number of NTM related deaths was seen from 1999 through 2010 (R2 = 0.72, p<0.0001), but it was not significant after adjustment for age. Persons aged 55 years and older, women, those living in Hawaii and Louisiana, and those of non-Hispanic, white ethnicity had higher mortality rates. Compared to tuberculosis-related mortality, chronic obstructive pulmonary disease, bronchiectasis, HIV, interstitial lung diseases, and tobacco use were significantly more common in persons with nontuberculous mycobacteria-related deaths. Conclusions Nontuberculous mycobacteria-related death numbers are rising and are unevenly distributed. The strong association of nontuberculous mycobacterial disease with age suggests that its prevalence will increase as the United States population ages.
Teamwork: what health care has learned from the military.

IN THE MILITARY, chain of command and clearly stated instructions matter a great deal. “We follow orders or people die. It’s that simple,” Jack Nicholson’s COL Jessup famously declared in the 1992 movie A Few Good Men. But it isn’t that simple because a strong sense of team lies at the foundation. Similarly, health care depends on clear instructions—and also relies not just on individuals but also on strong teams. These interprofessional teams are composed of physicians, nurses, physician assistants, pharmacists, technicians, assistants, and many other participants. The performance of each of these contributors is critical to the endeavor’s success. Not all teams are created equal. Teams can work well together or poorly. Some
Vitamin D Is a Good Marker for Disease Activity of Rheumatoid Arthritis Disease

Aim. This study was conducted to find out the optimal vitamin D cutoff point in predicting activity of RA disease. Materials and Methods. One hundred and two rheumatoid arthritis Saudi patients of both genders were recruited in this study. Vitamin D as 25-hydroxy-vitamin D [25(OH)D] was measured and serum level less than 20 ng/mL defined as deficient patient. Disease activity was measured based on the disease activity score index of a 28-joint count (DAS28) using serum erythrocyte sedimentation rate levels. Receiver operating characteristic (ROC) curves were used to determine the optimal vitamin D cutoff points for identifying disease activity. Results. It has been observed that vitamin D levels were lower (P < 0.05) in patients with high disease activity. A significant inverse correlation between serum 25(OH)D levels and DAS28 (r = −0.277, P = 0.014) was shown. ROC curves results showed that vitamin D less than 12.3 ng/mL predicted high disease activity, and vitamin D more than 17.9 ng/mL predicted low disease activity, with good sensitivity and accuracy results regarding vitamin D. Conclusion. Study results concluded that vitamin D is a good predictor of RA disease activity in Saudi patients.
Reevaluation of the Requirement for TIP47 in Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Incorporation

ABSTRACT Incorporation of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins into assembling particles is crucial for virion infectivity. Genetic and biochemical data indicate that the matrix (MA) domain of Gag and the cytoplasmic tail of the transmembrane glycoprotein gp41 play an important role in coordinating Env incorporation; however, the molecular mechanism and possible role of host factors in this process remain to be defined. Recent studies suggested that Env incorporation is mediated by interactions between matrix and tail-interacting protein of 47 kDa (TIP47; also known as perilipin-3 and mannose-6-phosphate receptor-binding protein 1), a member of the perilipin, adipophilin, TIP47 (PAT) family of proteins implicated in protein sorting and lipid droplet biogenesis. We have confirmed by nuclear magnetic resonance spectroscopy titration experiments and surface plasmon resonance that MA binds TIP47. We also reevaluated the role of TIP47 in HIV-1 Env incorporation in HeLa cells and in the Jurkat T-cell line. In HeLa cells, TIP47 overexpression or RNA interference (RNAi)-mediated depletion had no significant effect on HIV-1 Env incorporation, virus release, or particle infectivity. Similarly, depletion of TIP47 in Jurkat cells did not impair HIV-1 Env incorporation, virus release, infectivity, or replication. Our results thus do not support a role for TIP47 in HIV-1 Env incorporation or virion infectivity.
Social Movements, Field Frames, and Industry Emergence: A Cultural-Political Perspective

This article examines how social movements contribute to institutional change and the creation of new industries. We build on current efforts to bridge institutional and social movement perspectives in sociology and develop the concept of field frame to study how industries are shaped by social structures of meanings and resources that underpin and stabilize practices and social organization. Drawing on the case of how non-profit recyclers and the recycling social movement enabled the rise of a for-profit recycling industry, we show that movements can help to transform extant socio-economic practices and enable new kinds of industry development by engaging in efforts that lead to the de-institutionalization of field frames.
Gene expression profile of fibrovascular membranes from patients with proliferative diabetic retinopathy

Background/aims The purpose of this study was to generate a profile of genes expressed in preretinal fibrovascular membranes (FVMs) from patients with proliferative diabetic retinopathy. Methods A PCR-amplified complementary DNA (cDNA) library was constructed using the RNAs isolated from FVMs obtained during vitrectomy. The sequence from the 5′ end was obtained for randomly selected clones and used to generate expressed sequence tags (ESTs). Functional annotation was retrieved from Ensemble database and analysed by FatiGO. The web-based VisANT software was used to identify the molecular networks within the FVMs. Results A total of 2816 ESTs were assembled in 625 non-redundant clusters. Among these, 515 matched the human cDNA database. The 515 clusters were subdivided by functional subsets of genes related to ribosomal activity, oxidative phosphorylation, focal adhesion, cell adhesion and other functions. Querying against the VisANT database yielded 3175 possible physical relationships to other genes/proteins, which included an additional 2480 genes that were not detected in the FVM library. Conclusions The cDNA library constructed from human FVMs will be a valuable source of information. It should facilitate a wide range of studies that can establish the molecular mechanisms underlying the development of FVMs.
Ethnicity, race, and socioeconomic status influence incidence of langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a rare disease, and its etiology is not well understood. Population‐based studies may contribute to etiologic research by defining incidence patterns. This study was designed to evaluate the descriptive epidemiology of disseminated LCH in the United States, using data from population‐based cancer registries.
Chronicle of a death foretold: Plasmodium liver stage parasites decide on the fate of the host cell.

Protozoan parasites of the genus Plasmodium are the causative agents of malaria. Despite more than 100 years of research, the complex life cycle of the parasite still bears many surprises and it is safe to say that understanding the biology of the pathogen will keep scientists busy for many years to come. Malaria research has mainly concentrated on the pathological blood stage of Plasmodium parasites, leaving us with many questions concerning parasite development within the mosquito and during the exo-erythrocytic stage in the vertebrate host. After the discovery of the Plasmodium liver stage in the middle of the last century, it remained understudied for many years but the realization that it represents a promising target for vaccination approaches has brought it back into focus. The last decade saw many new and exciting discoveries concerning the exo-erythrocytic stage and in this review we will discuss the highlights of the latest developments in the field.
Coprime arrays and samplers for space-time adaptive processing

This paper extends the use of coprime arrays and samplers for the case of moving sources. Space-time adaptive processing (STAP) plays an important role in estimating direction-of-arrivals (DOAs) and radial velocities of emitting sources. However, the detection performance is fundamentally limited by the array geometry and the temporal samplers at each sensor. Coprime arrays and coprime samplers offer an enhanced degree of freedom of O(MN) using only O(M + N) physical sensors or samples. In this paper, we propose coprime joint angle-Doppler estimation (coprime JADE), which incorporates both coprime arrays and coprime samplers with the STAP framework. Nonuniform time samples at different sensors can be used to generate a sampled autocorrelation matrix, from which we compute a spatial smoothed matrix. It will be proved that spatial smoothed matrices can be used in the MUSIC algorithm for parameter estimation. With sufficient snapshots, coprime JADE distinguishes O(M1N1M22) independent sources if it corresponds to coprime arrays and coprime samplers with coprime integers (M1;1) and (M2;N2), respectively. It is verified through simulations that coprime JADE resolves the angle-Doppler information better compared to other conventional algorithms.
The Autobiographical Self in Time and Culture

Table of Contents Preface Introduction Chapter 1: Personal stories, family stories Chapter 2: Autobiography in time Chapter 3: The stories we keep Chapter 4: When does our autobiographical self begin? Chapter 5: What are we made of? Stories told and untold Chapter 6: The autobiographical self in prospective
Neurochemical differences in two rat strains exposed to social isolation rearing

Objective: Isolation rearing of rats provides a non-pharmacological method of inducing behavioural changes in rodents that resemble schizophrenia or depression. Nevertheless, results are variable within different strains. We focused on neurochemical changes in several in vivo and post-mortem brain regions of Wistar (W) and Lister Hooded (LH) rats following post-weaning social separation. Methods: Experiments were conducted after 6–8 weeks of isolation. For post-mortem studies, prefrontal cortex (PFC), nucleus accumbens (NAC), hippocampus (Hipp) and striatum (St) were collected by tissue dissection. In vivo experiments were conducted by microdialysis in the PFC. Analyses of dopamine (DA), serotonin (5-HT) levels and relative turnover were performed by using high-performance liquid chromatography. Results: We found significant strain-related differences in biogenic amine content. LH rats were characterised by markedly raised DA, along with its turnover reduction, in all the post-mortem brain regions examined as well as in microdialysis samples, while in W rats 5-HT tissue concentration was lower in PFC and St and higher in NAC and Hipp. Cortical extracellular 5-HT concentrations were increased in group housed and decreased in isolated W animals. Moreover, isolation increased DA concentrations in the PFC of LH rats, and decreased 5-HT in W rats in NAC and Hipp. Lately, 5-HT turnover was also affected by both strain and isolation conditions. Conclusions: This study suggests that W and LH rats have markedly different neurochemical profiles in response to isolation, resulting in altered monoamine levels that vary according to brain area and rat strain. These findings highlight the importance of selecting an appropriate rat strain when considering isolation rearing to model symptoms of schizophrenia and/or depression.