Miracle-dz/UniFAR-FTUs huggingface dataset:
Current Insights into Molecular Mechanisms of Alzheimer Disease and Their Implications for Therapeutic Approaches

During the last 10 years, a lot of progress has been made in unraveling the pathogenic cascade leading to Alzheimer disease (AD). According to the most widely accepted hypothesis, production and aggregation of the amyloid β (Aβ) peptide plays a key role in AD, and thus therapeutic interference with these processes is the subject of intense research. However, some important aspects of the disease mechanism are not yet fully understood. There is no consensus as yet on whether the disease acts through a loss- (LOF) or a gain-of-function (GOF) mechanism. While for many years, an increased production of Aβ42 was considered to be the prime culprit for the initiation of the disease process, and accordingly Aβ42 is elevated by AD-related presenilin(PS) mutations, recent data strongly suggest that PS mutations also lead to a LOF of PS towards a plethora of its substrates including amyloid precursor protein. How this PS LOF, especially decreased Aβ40 secretion due to mutant PS, impacts on the disease pathogenesis is yet to be elucidated. Secondly, vascular abnormalities – frequently observed to co-occur with AD – might also play a critical role in the initiation and aggravation of AD pathology given that the elimination of Aβ through a vascular route is an important brain Aβ clearance mechanism and its failure leads to formation of vascular amyloidosis and dense-core plaques. In this review, we will first focus on the important issue of a LOF versus a GOF mechanism for AD due to mutant PS, as well as on the possible role of vascular damage and reduced perfusion in AD. Special emphasis will be given to some of the AD mouse models that have helped to gain insights into the disease mechanism. Secondly, considering these mechanistic insights, we will discuss some therapeutic strategies which are currently in clinical or preclinical trials for AD.
Medication Overuse Headache: Predictors and Rates of Relapse in Migraine Patients With Low Medical Needs. A 1-Year Prospective Study

The aim of this study was to evaluate the rates and predictors of relapse, after successful drug withdrawal, in migraine patients with medication overuse headache (MOH) and low medical needs. The study population, study design, inclusion criteria and short-term effectiveness of the medication withdrawal strategies have been described elsewhere (Rossi et al., Cephalalgia 2006; 26:1097). Relapsers were defined as those patients fulfilling, at follow-up, the new International Classification of Headache Disorders, 2nd edn, appendix criteria for MOH. Complete datasets were available for 83 patients. At 1 year's follow up, the relapse rate was 20.5±. Univariate analysis showed that patients who relapsed had a longer duration of migraine with more than eight headache days/month, a longer duration of drug overuse, had tried a greater number of preventive treatments in the past, had a lower reduction of headache frequency after withdrawal, and had previously consulted a greater number of specialists. Binary logistic regression analysis was performed, and three variables emerged as significant predictors of relapse: duration of migraine with more than eight headache days/month [odds ratio (OR) 1.57, P = 0.01], a higher frequency of migraine after drug withdrawal (OR 1.48, P = 0.04) and a greater number of previous preventive treatments (OR 1.54, P = 0.01). In patients with migraine plus MOH and low medical needs, relapse seems to depend on a greater severity of baseline migraine.
256-Channel Neural Recording Microsystem with On-Chip 3D Electrodes

A 16times16-channel 3.5times4. 5mm2 neural recording interface is fabricated in 0.35mum CMOS and is integrated with on-chip 3D Au and Pt microelectrodes. Each channel dissipates 15muW with an input-referred noise of 7muV over 5kHz bandwidth. A switched-capacitor delta read-out data-compression circuit trades recording accuracy for the output data rate. In-vitro experimental results validate the circuit design and the on-chip 3D electrode bonding technology
Platelet-Rich Fibrin With 1.2% Rosuvastatin for Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Controlled Clinical Trial.

BACKGROUND Regenerative periodontal therapy encompasses use of various bioactive agents that are not only inflammomodulatory but also osteoclast-inhibitory or, rather, osteostimulative. Hypolipidemic statin drugs, particularly rosuvastatin (RSV), are known to be associated with alveolar bone formation and periodontal improvements. Platelet analogs such as platelet-rich fibrin (PRF), being rich sources of growth factors, have also come into widespread periodontal regenerative use. The aim of this study is to evaluate and compare efficacy of open flap debridement (OFD) with or without PRF or PRF + 1.2% RSV gel in treatment of intrabony defects (IBDs) in patients with chronic periodontitis (CP). METHODS Ninety individuals with a total of 90 IBDs were randomly assigned to one of three treatment groups: 1) OFD alone; 2) OFD + PRF; and 3) OFD + PRF + 1.2% RSV gel placement. Measurements recorded at baseline and 9 months after surgery were: 1) plaque index (PI); 2) modified sulcus bleeding index (mSBI); 3) probing depth (PD); 4) clinical attachment level (CAL); and 5) IBD depth. RESULTS Significant PI and mSBI reductions were observed in all three groups. PRF placement significantly enhanced improvements in periodontal parameters compared with OFD alone. Addition of 1.2% RSV gel to PRF resulted in significantly greater CAL gain and PD and IBD depth reductions over 9 months compared with other groups. CONCLUSION OFD with RSV (1.2%) and PRF results in significantly greater periodontal benefits compared with OFD alone or with PRF.
Costs, Demand, and Producer Price Changes

Abstract Using business survey data, we estimate an ordered probit model to explain the occurrence of producer price increases and decreases in the French manufacturing industry. Our results show that changes in intermediate input prices are the main driver of producer price changes. Changes in firms' labor costs, their production level, or the producer price index of their industry contribute less to the occurrence of price changes. Moreover, when they face a change in their costs, firms adjust their prices upward more often and more rapidly than they do it downward, especially when the shock is perceived as permanent.
Phylogenetic classification of short environmental DNA fragments

Metagenomics is providing striking insights into the ecology of microbial communities. The recently developed massively parallel 454 pyrosequencing technique gives the opportunity to rapidly obtain metagenomic sequences at a low cost and without cloning bias. However, the phylogenetic analysis of the short reads produced represents a significant computational challenge. The phylogenetic algorithm CARMA for predicting the source organisms of environmental 454 reads is described. The algorithm searches for conserved Pfam domain and protein families in the unassembled reads of a sample. These gene fragments (environmental gene tags, EGTs), are classified into a higher-order taxonomy based on the reconstruction of a phylogenetic tree of each matching Pfam family. The method exhibits high accuracy for a wide range of taxonomic groups, and EGTs as short as 27 amino acids can be phylogenetically classified up to the rank of genus. The algorithm was applied in a comparative study of three aquatic microbial samples obtained by 454 pyrosequencing. Profound differences in the taxonomic composition of these samples could be clearly revealed.
Meta-Analyses of Developing Brain Function in High-Risk and Emerged Bipolar Disorder

Objectives: Identifying early markers of brain function among those at high risk (HR) for pediatric bipolar disorder (PBD) could serve as a screening measure when children and adolescents present with subsyndromal clinical symptoms prior to the conversion to bipolar disorder. Studies on the offspring of patients with bipolar disorder who are genetically at HR have each been limited in establishing a biomarker, while an analytic review in summarizing the findings offers an improvised opportunity toward that goal. Methods: An activation likelihood estimation (ALE) meta-analysis of mixed cognitive and emotional activities using the GingerALE software from the BrainMap Project was completed. The meta-analysis of all fMRI studies contained a total of 29 reports and included PBD, HR, and typically developing (TD) groups. Results: The HR group showed significantly greater activation relative to the TD group in the right DLPFC–insular–parietal–cerebellar regions. Similarly, the HR group exhibited greater activity in the right DLPFC and insula as well as the left cerebellum compared to patients with PBD. Patients with PBD, relative to TD, showed greater activation in regions of the right amygdala, parahippocampal gyrus, medial PFC, left ventral striatum, and cerebellum and lower activation in the right VLPFC and the DLPFC. Conclusion: The HR population showed increased activity, presumably indicating greater compensatory deployment, in relation to both the TD and the PBD, in the key cognition and emotion-processing regions, such as the DLPFC, insula, and parietal cortex. In contrast, patients with PBD, relative to HR and TD, showed decreased activity, which could indicate a decreased effort in multiple PFC regions in addition to widespread subcortical abnormalities, which are suggestive of a more entrenched disease process.
A Longitudinal Examination of First Term Attrition and Reenlistment among FY1999 Enlisted Accessions

Abstract : The U.S. Army Research Institute for the Behavioral and Social Sciences (ARI) developed Project First Term as a multi-year, longitudinal investigation of Soldier attrition and reenlistment among the cohort of recruits who joined the Army in Fiscal Year 1999. This effort allowed the evaluation of models of attrition and reenlistment intentions based on information contained in personnel records and collected from Soldiers who were surveyed as they entered the service, completed training segments, conducted duty assignments, and left the service. These models explored reasons for attrition and reenlistment intentions, and suggested management strategies that might be employed to reduce attrition. This report provides a comprehensive description of Project First Term methodology and analyses, and documents those results that are most relevant to the management of first term attrition. The focus of the analysis was on attrition that occurred during four major phases of a Soldier's first term (48 months) of service, specifically: Basic Combat Training (BCT), Advanced Individual Training (AIT), One-Station Unit Training (OSUT), and In-Unit. The authors devote a separate chapter of the report to examining attrition occurring in each of these phases (Chapters 4-7). In Chapter 2 they define how attrition was coded for the analyses conducted in each chapter as well as how the samples examined in these chapters were defined. In Chapter 3 they open their examination of attrition with a general look at attrition across all 48 months of service. Chapter 8 presents the results of modeling reenlistment.
Music-induced mood improves retention in visuomotor adaptation

Learning to adapt motor outputs in response to changes in sensory feedback, or sensorimotor adaptation, is crucial to rehabilitation following injury or disease. Adapted movements are often forgotten when the sensory distortion is removed, creating a barrier to long-term rehabilitation. Binary success-error feedback and pictorial reinforcement have been shown to improve retention of adapted motor outputs. In one previous study, positively valenced music improved adaptation rate but had no effects on retention. Pleasurable music has been found to improve performance on spatial intelligence and cognitive tasks, possibly because of its moodand arousal-enhancing qualities, and has been found to have similar neural properties as reward. In Experiment 1, participants who listened to music that induced a positive or negative mood increased retention of movements adapted to a visual feedback distortion in comparison to silence. In Experiment 2, the combination of reward feedback in adaptation and music that induced a positive mood decreased retention, possibly because the rewarding properties of the music which were present during training (no visuomotor distortion) overrode the rewarding properties of the reinforcement when it were no longer present. These experiments provide evidence for a novel method of improving retention in sensorimotor adaptation.
A comparison of anaerobic power between black and white adolescent males

Oversize materials (e.g., maps, drawings, charts) are re­ produced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. These are also available as one exposure on a standard 35mm slide or as a 17" x 23" black and w hite photographic p rin t for an additional charge.
Feature Subset Selection for Software Cost Modelling and Estimation

Feature selection has been recently used in the area of software engineering for improving the accuracy and robustness of software cost models. The idea behind selecting the most informative subset of features from a pool of available cost drivers stems from the hypothesis that reducing the dimensionality of datasets will significantly minimise the complexity and time required to reach to an estimation using a particular modelling technique. This work investigates the appropriateness of attributes, obtained from empirical project databases and aims to reduce the cost drivers used while preserving performance. Finding suitable subset selections that may cater improved predictions may be considered as a pre-processing step of a particular technique employed for cost estimation (filter or wrapper) or an internal (embedded) step to minimise the fitting error. This paper compares nine relatively popular feature selection methods and uses the empirical values of selected attributes recorded in the ISBSG and Desharnais datasets to estimate software development effort.
Interference mitigation utilizing antenna mutual coupling

In this paper, we show interference can be removed almost perfectly under some conditions in multi-user MIMO if antenna mutual coupling is properly utilized. We analyze the capacity region of a Gaussian multiple access channel (MAC), where each transmitter has a single antenna and the receiver can measure the electric field in a given spherical volume with additive noise. The additive noise in the sphere is assumed to be spatially correlated based on the fluctuation-dissipation theorem in thermodynamics. As a result, the interference can be almost perfectly removed under some conditions.
A General Framework for Density Based Time Series Clustering Exploiting a Novel Admissible Pruning Strategy

Time Series Clustering is an important subroutine in many higher-level data mining analyses, including data editing for classifiers, summarization, and outlier detection. It is well known that for similarity search the superiority of Dynamic Time Warping (DTW) over Euclidean distance gradually diminishes as we consider ever larger datasets. However, as we shall show, the same is not true for clustering. Clustering time series under DTW remains a computationally expensive operation. In this work, we address this issue in two ways. We propose a novel pruning strategy that exploits both the upper and lower bounds to prune off a very large fraction of the expensive distance calculations. This pruning strategy is admissible and gives us provably identical results to the brute force algorithm, but is at least an order of magnitude faster. For datasets where even this level of speedup is inadequate, we show that we can use a simple heuristic to order the unavoidable calculations in a most-useful-first ordering, thus casting the clustering into an anytime framework. We demonstrate the utility of our ideas with both single and multidimensional case studies in the domains of astronomy, speech physiology, medicine and entomology. In addition, we show the generality of our clustering framework to other domains by efficiently obtaining semantically significant clusters in protein sequences using the Edit Distance, the discrete data analogue of DTW.
A method to preserve sputum for delayed examination

Examination of sputum cell counts is limited by the need to process samples within hours of expectoration. The validity and repeatability of a method to preserve sputum for delayed processing and examination were investigated in this study. Portions of selected sputum from 39 subjects were dispersed with dithiothreitol (routine method), or were fixed in a dithiothreitol-formaldehyde mixture for 48–72 h before dispersal with trypsin (preservation method). Total and differential cell counts using the two methods were compared; within-method repeatability of the preservation method was also examined. The intraclass correlation coefficient (ICC) for total cell counts and percentage of eosinophils, neutrophils and macrophages in sputum processed by the two methods was 0.89, 0.86, 0.91 and 0.90, respectively. Within-method repeatability (ICC) of the preservation method for the same cellular indices was 0.99, 0.94, 0.97 and 0.97, respectively. The interobserver repeatability for eosinophils, neutrophils and macrophages was 0.96, 0.97 and 0.97 using the preservation method, and 0.96, 0.99 and 0.99 using the routine method, respectively. This method of sputum preservation and dispersal is valid, reliable and convenient, and may be used for delayed processing and examination.
Regression Models for Disease Prevalence with Diagnostic Tests on Pools of Serum Samples

Summary. Whether the aim is to diagnose individuals or estimate prevalence, many epidemiological studies have demonstrated the successful use of tests on pooled sera. These tests detect whether at least one sample in the pool is positive. Although originally designed to reduce diagnostic costs, testing pools also lowers false positive and negative rates in low prevalence settings and yields more precise prevalence estimates. Current methods are aimed at estimating the average population risk from diagnostic tests on pools. In this article, we extend the original class of risk estimators to adjust for covariates recorded on individual pool members. Maximum likelihood theory provides a flexible estimation method that handles different covariate values in the pool, different pool sizes, and errors in test results. In special cases, software for generalized linear models can be used. Pool design has a strong impact on precision and cost efficiency, with covariate‐homogeneous pools carrying the largest amount of information. We perform joint pool and sample size calculations using information from individual contributors to the pool and show that a good design can severely reduce cost and yet increase precision. The methods are illustrated using data from a Kenyan surveillance study of HIV. Compared to individual testing, age‐homogeneous, optimal‐sized pools of average size seven reduce cost to 44% of the original price with virtually no loss in precision.
Ruminal lipid balance and intestinal digestion by dairy cows fed calcium salts of rapeseed oil fatty acids or rapeseed oil.

The effects of supplemental calcium salts of rapeseed oil fatty acids (FA) and rapeseed oil on ruminal metabolism and apparent digestibility of lipids in the small intestine were studied using three multiparous Holstein x Friesian cows in a 3 x 3 Latin square design. Cows fitted with ruminal, duodenal, and ileal cannulas were fed restricted amounts of a control diet (C) containing 65% corn silage and 35% concentrate mix or diet C with supplemental calcium salts of rapeseed oil FA (S) or diet C supplemented with rapeseed oil (O). Fatty acid contents were 1.9, 8.4, and 7.6% for diets C, S, and O, respectively. The average flow of total FA to the duodenum was lower than the intake for supplemented treatments, suggesting catabolism of FA by ruminal microbes. Fatty acid flows at the duodenum were higher (P < .10) for diets supplemented with fat than for diet C, except for C18: 3(n-3) and straight-chain and branched-chain C15 and C17. Fat treatment affected total and individual FA flow to the ileum, except C14:0 and C18:2(n-6) and excreted amount of individual FA, except C14:0, C16:0, and total C18:1. In our trial, the addition of fat, regardless of origin, affected small intestinal digestibilities of C14:0 and C18:2(n-6) and did not affect changes in the amount of FA in the hindgut.
Mossy fiber-evoked subthreshold responses induce timing-dependent plasticity at hippocampal CA3 recurrent synapses

Significance Dentate mossy fibers represent the main conduit for information transfer from the cerebral cortex to the hippocampus, a structure essential for learning and memory. It is generally accepted that the information conveyed by mossy fibers must take the form of powerful all-or-none digital signals, known as action potentials, to ensure the formation of stable memory traces; however, experiments in behaving rodents have revealed that mossy fibers might not generate sufficient numbers of action potentials in hippocampal cells to support memory function. Here we show that analog signals elicited by mossy fiber activity, which are weaker but much more frequent than action potentials, can compensate for the paucity of digital signaling and effectively control hippocampal circuits important for memory. Dentate granule cells exhibit exceptionally low levels of activity and rarely elicit action potentials in targeted CA3 pyramidal cells. It is thus unclear how such weak input from the granule cells sustains adequate levels of synaptic plasticity in the targeted CA3 network. We report that subthreshold potentials evoked by mossy fibers are sufficient to induce synaptic plasticity between CA3 pyramidal cells, thereby complementing the sparse action potential discharge. Repetitive pairing of a CA3–CA3 recurrent synaptic response with a subsequent subthreshold mossy fiber response induced long-term potentiation at CA3 recurrent synapses in rat hippocampus in vitro. Reversing the timing of the inputs induced long-term depression. The underlying mechanism depends on a passively conducted giant excitatory postsynaptic potential evoked by a mossy fiber that enhances NMDA receptor-mediated current at active CA3 recurrent synapses by relieving magnesium block. The resulting NMDA spike generates a supralinear depolarization that contributes to synaptic plasticity in hippocampal neuronal ensembles implicated in memory.