Miracle-dz/UniFAR-FTUs huggingface dataset:
The limits of functional reorganization in multiple sclerosis

Investigating the brain at rest using functional MRI is a popular new method to investigate brain function in physiologic and pathologic conditions. Avoiding traditional task-based restrictions, it enables the researcher to investigate the entire brain with minimal burden and has therefore flourished recently, leading to the discovery of several consistent networks1 that are active in the healthy brain performing no task (i.e., at rest). One of these is the so-called default-mode network (DMN), which encompasses the medial prefrontal, anterior cingulate, posterior cingulate/precuneus, and lateral parietal cortices. The DMN was initially identified since it is frequently deactivated when performing active cognitive tasks, leading to the hypothesis that this network is involved in cognitive postprocessing at rest; supporting this idea is the finding that it is completely quiet in coma.2 Most current resting state studies focus on this network and have yielded a plethora of studies in a wide spectrum of neurologic diseases, like Alzheimer disease (AD), whereas multiple sclerosis (MS) has been notably absent until now. Resting state studies alone cannot answer all questions regarding task-based functions. Combining resting state with task-based paradigms therefore allows for an optimal assessment of function in several disease states. Normal deactivation of regions of the DMN during tasks is, for example, present3 in early mild cognitive impairment (MCI) stages, combined with …
Improved common-mode feedback based on LCMFB techniques

A novel class AB Differential Difference Amplifier (DDA) for use in continuous-time common-mode feedback circuits is proposed. It is based on using resistive Local Common-Mode Feedback (LCMFB) to enhance gain-bandwidth product (GBW) and dynamic operation of the common-mode feedback loop, without requiring extra static power consumption or supply voltage requirements. Simulation results for a 0.5 μm CMOS process show an increase in open loop DC gain (ADC) of 15.3 dB and also in GBW by a factor of 5.5. Additionally, measurement results for a test chip prototype fabricated in the same process validate the proposal.
Genome-wide association studies: promises and pitfalls.

1 Department of Neurology, Singapore General Hospital, Singapore 2 National Neuroscience Institute, Singapore 3 Duke-NUS Graduate Medical School, Singapore Address for Correspondence: Dr Eng-King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169608. Email: gnrtek@sgh.com. sg Genetic testing is an important means to confi rm the diagnosis of an inheritable disease.1 For this to be feasible, genes that are associated with the disease need to be identifi ed. Hunting for the genes that cause or are associated with a particular disease is a challenging task. Traditionally, mapping causative genes or “genetic susceptibility loci” involves intensive linkage analysis in many families containing clusters of the disease of interest. Genetic association study helps to unravel gene variants that shows an association with a defi ned disease trait.2-4 This association study is usually done using a casecontrol methodology. However, an association does not necessarily equate to a causative effect of the gene variant. Furthermore, the relation between genetic variants and disease status depends on many confounding factors, such as the pattern of physical proximity of the gene variants (linkage disequilibrium) (also described as the non-random association of alleles at two or more loci) in the population; the type of cases and controls; ethnic differences; and selection bias in recruiting the subjects. This “non-rocket science” approach has yielded many observations that by and large could not be consistently replicated. With technological advances and the completion of the Human Genome Project, it has become easier to search for genetic associations of common diseases. In recent years, genome-wide association studies (GWAS), sometimes referred to as whole genome association (WGA) studies, have generated considerable interest among investigators in genetic epidemiology.2,5 The fundamental approach in GWAS is nothing new, as this is essentially a genetic association study, albeit with a much more intricate, and arguably more reliable, approach. Earlier genetic association studies frequently involved the analysis of a single or a few gene variants of selected candidate genes of interest.2-4 However, with an estimated 30,000 genes in the human genome, and possibly million of both common and rare gene variants, it may be unrealistic to expect investigators to strike a “jackpot” and uncover susceptibility or causative genes easily. In GWAS, the analysis involves examining variants across the wholegenome (i.e. the entire DNA sequence) for genetic variations that may associate with certain traits or diseases. Modern chip technology can allow the interrogation of up to 1 million single nucleotide variants (SNPs) at one go.
Reductive dechlorination of high concentrations of tetrachloroethene to ethene by an anaerobic enrichment culture in the absence of methanogenesis

Tetrachloroethene, also known as perchloroethylene (PCE), is a common groundwater contaminant throughout the United States. The incomplete reductive dechlorination of PCE--resulting in accumulations of trichloroethene, dichloroethene isomers, and/or vinyl chloride--has been observed by many investigators in a wide variety of methanogenic environments. Previous mixed-culture studies have demonstrated that complete dechlorination to ethene is possible, although the final dechlorination step from vinyl chloride to ethene is rate limiting, with significant levels of vinyl chloride typically persisting. In this study, anaerobic methanol-PCE enrichment cultures which proved capable of dechlorinating high concentrations PCE to ethene were developed. Added concentrations of PCE as high as 550 microM (91-mg/liter nominal concentration; approximately 55-mg/liter actual aqueous concentration) were routinely dechlorinated to 80% ethene and 20% vinyl chloride within 2 days at 35 degrees C. The methanol level used was approximately twice that needed for complete dechlorination of PCE to ethene. The observed transformations occurred in the absence of methanogenesis, which was apparently inhibited by the high concentrations of PCE. When incubation was allowed to proceed for as long as 4 days, virtually complete conversion of PCE to ethene resulted, with less than 1% persisting as vinyl chloride. An electron balance demonstrated that methanol consumption was completely accounted for by dechlorination (31%) and acetate production (69%). The high volumetric rates of PCE dechlorination (up to 275 mumol/liter/day) and the relatively large fraction (ca. one-third) of the supplied electron donor used for dechlorination suggest that reductive dechlorination could be exploited for bioremediation of PCE-contaminated sites.
Biodiversity losses and conservation responses in the Anthropocene

Biodiversity is essential to human well-being, but people have been reducing biodiversity throughout human history. Loss of species and degradation of ecosystems are likely to further accelerate in the coming years. Our understanding of this crisis is now clear, and world leaders have pledged to avert it. Nonetheless, global goals to reduce the rate of biodiversity loss have mostly not been achieved. However, many examples of conservation success show that losses can be halted and even reversed. Building on these lessons to turn the tide of biodiversity loss will require bold and innovative action to transform historical relationships between human populations and nature.
Global Entrepreneurship and Market-Driven Management

Global entrepreneurship defines the orientation of the firms in the direction of growing interdependence and integration. On the contrary international entrepreneurship is just a combination of innovative, proactive, and risk seeking behaviour that crosses national borders and is intended to create value in organizations. In global markets, the strategic leverage of the firms moves from goods to knowledge. Information systems and inter-firm collaboration become fundamental ways to access to knowledge and to exploit its potential. Market-driven organizations possess superior capabilities in anticipating and exploiting trends and market changes as well as competitors' moves. Firms, in order to be successful, must combine market-driven management with an entrepreneurial attitude.
Weight gain with risperidone among patients with mental retardation: effect of calorie restriction.

BACKGROUND The atypical antipsychotics cause weight gain, which is poorly understood in terms of its mechanism and treatment. A usual recommendation for treatment of antipsychotic-induced weight gain includes calorie restriction and exercise. The authors describe their recent clinical experience with calorie restriction in adults with mental retardation treated with risperidone. METHOD A retrospective chart review was performed on the records of 50 adult patients with mental retardation treated with risperidone while residing at a habilitation center. We assessed dose and duration of risperidone treatment, weight, changes in calorie intake, and frequency of aggressive behavior. RESULTS Of the 50 patients, 39 had adequate data for analysis. Thirty-seven of the 39 patients gained weight with a mean of 18.8 lb (8.3 kg) over about 2 years. Twenty of the 37 patients were calorie restricted. Three of the 20 calorie-restricted patients lost weight at a rate of 0.2 lb (0.1 kg) per month. The other 17 calorie-restricted patients and the 17 patients who were not calorie restricted continued to gain weight at a rate of 0.8 lb (0.4 kg) per month over about another 2 years of treatment. The amount of weight gain was not dose related. Calorie restriction led to no deterioration in behavior. CONCLUSION The current investigation lends support to data that note weight gain with risperidone in adults with mental retardation. It suggests that calorie restriction does not lead to weight loss or behavioral deterioration and that weight gain is not dose related.
Dynamin and endocytosis.

I. Introduction THE transport of proteins, hormones, and nutrients to different locations within a cell is an essential process for many of the functions of eukaryotic cells. It is of particular importance in complex multicellular organisms to enable the cells to communicate with one another. The pathways for transport of materials into and out of cells utilize a variety of large membrane compartments within the cell, which communicate with each other and with the external environment via smaller membrane carriers called transport vesicles, The movement of the transport vesicles between compartments or to the plasma membrane is called membrane or vesicle trafficking. This is a highly ordered and directed process and takes a variety of different forms that are unique for a particular cellular function. Like intercellular communication, intracellular transport pathways are multidirectional in nature, primarily being composed of trafficking between intracellular structures, the exocytptic (secretory) pathway.
Quantification of reaching during stroke rehabilitation using unique upper extremity kinematic model

Quantification of rehabilitation progress is necessary for accurately assessing clinical treatments. A three-dimensional (3D) biomechanical model of the upper extremity was developed for quantification of stroke rehabilitation. The model was designed to accurately track the 3D orientation of the trunk, shoulder, elbow and wrist. This study explains the application of the upper extremity model. Strict validation of the model confirmed the system's accuracy and resolution. The model was applied to eight hemiparetic stroke patients with spasticity, while completing a set of reaching tasks. The model successfully detected statistical differences in elbow range of motion and angular velocity between the nonparetic (unaffected) and paretic (affected) arms. Both simple and complex biomechanical indices for assessment were developed. This model may aid in the assessment and planning of stroke rehabilitation, and help to decrease recovery time.
Histochemical identification of primordial germ cells in human embryos by PAS reaction.

It is known as a common finding in vertebrates that certain cells originating in the entoderm which . are destined to give rise to the gamates, or the primordial germ cells (PGCs), manifest themselves in tissues other than the developing gonad at a certain early stage of development. Witschi (1948)' was the first to give a fairly detailed, convincing account of the above-described sequence of events in human embryos. Namely, morphologically definitely recognizable PGCs appear in an area posteriosuperior to the yolk sac at about the end of the third week of intrauterine life of a human embryo and migrate thence to the primitive gonadal fold (genital ridge) during about the fifth week via the mesentery, and the investigator suggested amoeboidism as a means for migration of PGCs, based on the observation of pseudopods possessed by some of these cells. Meanwhile, PGCs even in routine hematoxylin and eosin preparations are strikingly different from their somatocytic neighbors and, therefore, can be recognized without much difficulty as they are remarkably large cells (20 p in diameter) with pale cytoplasm and contain large spherical nuclei. However, the routine histologic technique essentially has its limit in identifying these particular cells and, recently, histochemical methods have been introduced for the identification of PGCs by demonstration of alkaline phosphatase activity in their cell membranes and of intracytoplasmic glycogen. The periodic acid-Schiff (PAS) reaction is employed for the latter. Increasingly accurate information on the behavior and distribution of PGCs has been obtained through investigations with these histochemical techniques (McKay et al., 19532) ; and Pinkerton et al., 19618)).
Gait measurement system to develop control model of intelligently controllable ankle-foot orthosis

We have developed intelligently controllable ankle-foot orthoses (i-AFO). In a previous report, we discovered that the rotational velocities of planter flexion in the initial phase of gait correlate with the walking speeds of a patient suffering from flaccid paralysis in his ankles. This fact has a potential to be used as a control model of the i-AFO. In order to confirm this fact for more numbers of subjects, we conducted gait experiments for healthy subjects. We developed a new measurement system that can realize (1) the phase detection of gait, (2) measurement of ankle angle, (3) that of step length, and (4) that of stride width, simultaneously. Experimental results show that periods of initial contact to foot flat doesn't correlate with walking speeds. Additionally, the rotational velocities of planter flexion of foot in the initial phase of gait depend on the walking speeds.
Activation of MKK6, an upstream activator of p38, in Alzheimer's disease

Mitogen‐activated protein kinase (MAPK) p38 has been implicated in the pathogenesis of Alzheimer's disease, but the upstream cascade leading to p38 activation has not been elucidated in the disease. In the present study, we focused on mitogen‐activated protein kinase kinase 6 (MKK6), one of the upstream activators of p38 MAPK. We found that MKK6 was not only increased but also specifically associated with granular structures in the susceptible neurons in the hippocampus and cortex of Alzheimer's disease patients, but was only weakly diffuse in the cytoplasm in neurons in control cases. Immunoblot analysis demonstrated a significant increase of MKK6 level in Alzheimer's disease compared with age‐matched controls. In this regard, in hippocampal and cortical regions of individuals with Alzheimer's disease, the activated phospho‐MKK6 was localized exclusively in association with pathological alterations including neurofibrillary tangles, senile plaques, neuropil threads and granular structures, overlapping with activated p38 MAPK suggesting both a functional and mechanic link. By immunoblot analysis, phospho‐MKK6 is also significantly increased in AD compared with control cases. Together, these findings lend further credence to the notion that the p38 MAPK pathway is dysregulated in Alzheimer's disease and also indicates an active role for this pathway in disease pathogenesis.
Variable Selection in Time Series Forecasting Using Random Forests

Time series forecasting using machine learning algorithms has gained popularity recently. Random forest is a machine learning algorithm implemented in time series forecasting; however, most of its forecasting properties have remained unexplored. Here we focus on assessing the performance of random forests in one-step forecasting using two large datasets of short time series with the aim to suggest an optimal set of predictor variables. Furthermore, we compare its performance to benchmarking methods. The first dataset is composed by 16,000 simulated time series from a variety of Autoregressive Fractionally Integrated Moving Average (ARFIMA) models. The second dataset consists of 135 mean annual temperature time series. The highest predictive performance of RF is observed when using a low number of recent lagged predictor variables. This outcome could be useful in relevant future applications, with the prospect to achieve higher predictive accuracy.
Gene isolation by complementation in Candida albicans and applications to physical and genetic mapping

We have isolated three genes, ARG57, SER57, and LYS1, on the basis of their function in Candida albicans. A C. albicans transformation vector containing the C. albicans URA3 gene, a Candida ARS sequence, and a portion of the Saccharomyces cerevisiae 2 microns circle containing the replication origin was constructed. Clones from genomic libraries in this vector were isolated by direct complementation of the auxotrophies in strain 1006 (arg57 ser57 lys1 ura3 MPA1). Transformants typically contain two to four plasmids in a mixed tandem multimer. A scheme to resolve mixed multimers into monomers in vivo by transformation of S. cerevisiae with Candida transformant DNA selecting Ura+ transformants was devised. Monomeric plasmids were then isolated by transformation of Escherichia coli with the S. cerevisiae transformant DNA. These were retested by transformation of strain 1006 to identify the specific plasmid that complemented the auxotrophy. The chromosomal locations of the genes were determined by hybridization to C. albicans chromosomes separated on contour-clamped homogenous electric field gels. We used these locations to assess the stability of individual C. albicans chromosomes in parasexual genetic analysis. The Lys(+)-complementing clone was shown to be LYS1 by complementation of S. cerevisiae lys1 mutants. These cloned genes help to align the Candida physical and genetic maps and provide additional markers for the transformation system.
Significance of diagnostic parameters in [(13)c]octanoic Acid gastric emptying breath tests*.

Abstract Two novel characteristic parameters, the latency time (t (lat)) and the ascension time (t (asc)), are proposed for evaluation of non-invasive [(13)C]octanoic acid breath tests for assessment of the gastric emptying of solids. In breath tests performed in control subjects (n = 30) and diabetic patients (n = 100), the usefulness of these parameters was compared to conventional parameters, i.e., gastric half emptying-time t (1/2,b )) and lag phase (t (lag,b )). The proposed parameters were only loosely correlated (controls, r = 0.199; diabetics, 0.616). A strong correlation was found between the conventional parameters (controls, r = 0.891; diabetics, r = 0.962). Based on the conventional method, 36 patients were suspicious of delayed gastric emptying including 24 patients which exhibited a simultaneous delay in both parameters. Using the new parameters, a total of 46 patients were suspicious of delayed gastric emptying with 15 and 20 having isolated delay in t (lat) and t (asc), respectively. We conclude that the novel parameters may be more appropriate for examination of the different phases of gastric emptying and for evaluation of gastric emptying disturbances in diabetic patients than the parameters conventionally used for this purpose.
Multicycle Mechanical Performance of Titanium and Stainless Steel Transpedicular Spine Implants

Study Design. This was a prospective in vitro study comparing titanium alloy and stainless steel alloy in transpedicular spine implants from two different manufacturers. Objective. To compare the multicycle mechanical performance of these two alloys, used in each of two different implant designs. Summary of Background Data. Transpedicular spine implants primarily have been manufactured from stainless steel, but titanium alloy offers imaging advantages. However, the notch sensitivity of titanium alloy has caused concern regarding how implants made from this material will compare in stiffness and fatigue life with implants made from stainless steel. Methods. Twenty‐four implants (two alloys, two designs, six implants per group) were mounted in machined polyethylene wafers and repetitively loaded (up to 1 million cycles) from 80 N to 800 N using a 5‐Hertz sinusoidal waveform. Load and displacement data were automatically and periodically sampled throughout the entire test. Results. Implant stiffness increased with cycle load number, reached a steady state, then declined just before fatigue failure. Stiffness varied less in titanium transpedicular spine implants than in their stainless counterparts. All stainless steel implant types were stiffer (steady‐state value, P < 0.0001) than their titanium alloy counterparts. One titanium implant design failed with fewer (P < 0.05) load cycles than its stainless steel counterpart, whereas a stainless steel implant of another design failed with fewer (P = 0.002) load cycles than its titanium counterpart. Overall, fatigue life, i.e., the total number of load cycles until failure, was related to implant type (P < 0.0001), but not to implant material. Conclusions. A transpedicular spine implant's fatigue lifetime depends on both the design and the material and cannot be judged on material alone. Stainless steel implants are stiffer than titanium alloy implants of equal design and size; however, for those designs in which the fatigue life of the titanium alloy version is superior, enlargement of the implant's components can compensate for titanium's lower modulus of elasticity and result in an implant equally stiff as its stainless steel counterpart. Such an implant made from titanium alloy would then be clinically preferable because of titanium's previously reported imaging advantages.