Miracle-dz/UniFAR-FTUs huggingface dataset:
Early Golgi Abnormalities and Neurodegeneration upon Loss of Presynaptic Proteins Munc18-1, Syntaxin-1, or SNAP-25

The loss of presynaptic proteins Munc18-1, syntaxin-1, or SNAP-25 is known to produce cell death, but the underlying features have not been compared experimentally. Here, we investigated these features in cultured mouse CNS and DRG neurons. Side-by-side comparisons confirmed massive cell death, before synaptogenesis, within 1–4 DIV upon loss of t-SNAREs (syntaxin-1, SNAP-25) or Munc18-1, but not v-SNAREs (synaptobrevins/VAMP1/2/3 using tetanus neurotoxin (TeNT), also in TI-VAMP/VAMP7 knock-out (KO) neurons). A condensed cis-Golgi was the first abnormality observed upon Munc18-1 or SNAP-25 loss within 3 DIV. This phenotype was distinct from the Golgi fragmentation observed in apoptosis. Cell death was too rapid after syntaxin-1 loss to study Golgi abnormalities. Syntaxin-1 and Munc18-1 depend on each other for normal cellular levels. We observed that endogenous syntaxin-1 accumulates at the Golgi of Munc18-1 KO neurons. However, expression of a non-neuronal Munc18 isoform that does not bind syntaxin-1, Munc18-3, in Munc18-1 KO neurons prevented cell death and restored normal cis-Golgi morphology, but not synaptic transmission or syntaxin-1 targeting. Finally, we observed that DRG neurons are the only Munc18-1 KO neurons that do not degenerate in vivo or in vitro. In these neurons, cis-Golgi abnormalities were less severe, with no changes in Golgi shape. Together, these data demonstrate that cell death upon Munc18-1, syntaxin-1, or SNAP-25 loss occurs via a degenerative pathway unrelated to the known synapse function of these proteins and involving early cis-Golgi abnormalities, distinct from apoptosis. SIGNIFICANCE STATEMENT This study provides new insights in a neurodegeneration pathway triggered by the absence of specific proteins involved in synaptic transmission (syntaxin-1, Munc18-1, SNAP-25), whereas other proteins involved in the same molecular process (synaptobrevins, Munc13–1/2) do not cause degeneration. Massive cell death occurs in cultured neurons upon depleting syntaxin-1, Munc18-1, and/or SNAP-25, well before synapse formation. This study characterizes several relevant cellular phenotypes, especially early cis-Golgi abnormalities, distinct from abnormalities observed during apoptosis, and rules out several other phenotypes as causal (defects in syntaxin-1 targeting and synaptic transmission). As proteins, such as syntaxin-1, Munc18-1, or SNAP-25, modulate α-synuclein neuropathy and/or are dysregulated in Alzheimer's disease, understanding this type of neurodegeneration may provide new links between synaptic defects and neurodegeneration in humans.
Increased T-bet+ cytotoxic effectors and type I interferon-mediated processes in chronic graft-versus-host disease of the oral mucosa.

Although chronic graft-versus-host disease (cGVHD) is a major long-term complication of allogeneic hematopoietic stem cell transplantation, little is known of its pathogenesis. We have systematically examined oral mucosa among cGVHD patients and determined that the clinical severity of oral cGVHD was correlated with apoptotic epithelial cells, often found adjacent to infiltrating effector-memory T cells expressing markers of cytotoxicity and type I cytokine polarization. Accumulation of T-bet(+) T-cell effectors was associated with both increased proliferation and the expression of the type I chemokine receptor CXCR3. Concurrently, in both infiltrating cells and keratinocytes, we observed increased expression of the CXCR3 ligand MIG (CXCL9) and interleukin-15 (IL-15), type I interferon (IFN)-inducible factors that support the migration, type I differentiation, and expansion of alloreactive effectors. In severely affected mucosa, we observed high levels of MxA, a protein specifically induced by type I IFN, and signal transducer and activator of transcription 1 (STAT1) phosphorylation, a critical step in the IFN-signaling pathway, along with increased numbers of plasmacytoid dendritic cells. These data challenge the current paradigm of cGVHD as a type II cytokine-driven disorder and support the model that oral cGVHD results from type I IFN-driven immigration, proliferation, and differentiation of T-bet(+) type I T effectors. The clinical trials are registered at http://www.clinicaltrials. gov as NCT00331968.
Modelling individual routines and spatio-temporal trajectories in human mobility

Human mobility modelling is of fundamental importance in a wide range of applications, such as the developing of protocols for mobile ad hoc networks or for what-if analysis and simulation in urban ecosystems. Current generative models generally fail in accurately reproducing the individuals' recurrent daily schedules and at the same time in accounting for the possibility that individuals may break the routine and modify their habits during periods of unpredictability of variable duration. In this article we present DITRAS (DIary-based TRAjectory Simulator), a framework to simulate the spatio-temporal patterns of human mobility in a realistic way. DITRAS operates in two steps: the generation of a mobility diary and the translation of the mobility diary into a mobility trajectory. The mobility diary is constructed by a Markov model which captures the tendency of individuals to follow or break their routine. The mobility trajectory is produced by a model based on the concept of preferential exploration and preferential return. We compare DITRAS with real mobility data and synthetic data produced by other spatio-temporal mobility models and show that it reproduces the statistical properties of real trajectories in an accurate way.
Antiangiogenic drugs and advanced proliferative diabetic retinopathy

Advanced diabetic retinopathy with vitreous hemorrhage or tractional retinal detachment (TDR) is an important cause of severe visual loss in patients with proliferative diabetic retinopathy (PDR), frequently representing an indication for pars plana vitrectomy in diabetic patients. In these cases, surgery is not free from complications such as intraoperative vitreous hemorrhage and retinal rupture. Also, during the postoperative period, these patients may suffer untoward events such as intraocular rebleeding and neovascular glaucoma. Antiangiogenic drugs have been extensively used for the treatment of chorioretinal vascular disorders. The intravitreal use of bevacizumab, ranibizumab and pegaptanib has shown positive effects on diabetic retinopathy. The inhibition of vascular endothelial growth factor (VEGF) by these drugs can induce regression of diabetic neovascular retinopathy and combat exudative phenomena, thus being useful for the preoperative management of these patients. In the present article we review the use of antiangiogenic drugs as adjuvants in pars plana vitrectomy for the treatment of complications of diabetic retinopathy.
Multiparadigm communications in Java for grid computing

In this article, we argue that the rapid development of Java technology now makes it possible to support, in a single object-oriented framework, the different communication and coordination structures that arise in scientific applications. We outline how this integrated approach can be achieved, reviewing in the process the state-of-the-art in communication paradigms within Java. We also present recent evaluation results indicating that this integrated approach can be achieved without compromising on performance.
University of Groningen Stability analysis of piezoelectric beams

Piezoelectric materials are used in many engineering application. When modeling piezoelectric materials the standard assumption is that the electromagnetic field which is used to actuate the piezoelectric material is quasi static. In this paper we show that although the assumption of a quasi static electrical field is valid when one is interested in simulating a piezoelectric material, this assumption renders the system non stabilizable in terms of control. We also show that this issue is caused by the assumption of a quasi static electrical field and therefore can be avoided by modeling a dynamical electrical field.
Comparative Visualization for Wave-based and Geometric Acoustics

We present a comparative visualization of the acoustic simulation results obtained by two different approaches that were combined into a single simulation algorithm. The first method solves the wave equation on a volume grid based on finite elements. The second method, phonon tracing, is a geometric approach that we have previously developed for interactive simulation, visualization and modeling of room acoustics. Geometric approaches of this kind are more efficient than FEM in the high and medium frequency range. For low frequencies they fail to represent diffraction, which on the other hand can be simulated properly by means of FEM. When combining both methods we need to calibrate them properly and estimate in which frequency range they provide comparable results. For this purpose we use an acoustic metric called gain and display the resulting error. Furthermore we visualize interference patterns, since these depend not only on diffraction, but also exhibit phase-dependent amplification and neutralization effects
Methods for the Detection of Subterranean Methane Leakage

The development of small unmanned aircraft systems (sUAS) has led to a plethora of industry applications. One such application for a sUAS is detecting subterranean methane leakage. The rapid detection of methane will streamline work in industries such as construction and utilities. However, prior to flying a sUAS, the optimal way to detect methane must be determined so that unknown levels of subterranean methane leakage can be detected accurately and efficiently. In this thesis, two methods were used in conjunction to optimize a sUAS method for methane detection. The primary objective was to use hyperspectral data to locate the optimal wavelengths for methane detection for use on a sUAS. This was accomplished in two parts. The first part of the study was a simulated pipeline experiment where a copper pipe and mass flow controller were used to mimic a natural pipeline leak close to the surface. The methane-stressed and healthy vegetation were measured daily using a handheld spectrometer alongside two other forms of stressed vegetation. The analysis of the data showed potentially important variation at a two band combination of wavelengths. The second part of the study used the measured hyperspectral data as targets for a combination of atmospheric models developed using
Practical and theoretical advances in predicting the function of a protein by its phylogenetic distribution

The gap between the amount of genome information released by genome sequencing projects and our knowledge about the proteins' functions is rapidly increasing. To fill this gap, various ‘genomic-context’ methods have been proposed that exploit sequenced genomes to predict the functions of the encoded proteins. One class of methods, phylogenetic profiling, predicts protein function by correlating the phylogenetic distribution of genes with that of other genes or phenotypic characteristics. The functions of a number of proteins, including ones of medical relevance, have thus been predicted and subsequently confirmed experimentally. Additionally, various approaches to measure the similarity of phylogenetic profiles and to account for the phylogenetic bias in the data have been proposed. We review the successful applications of phylogenetic profiling and analyse the performance of various profile similarity measures with a set of one microsporidial and 25 fungal genomes. In the fungi, phylogenetic profiling yields high-confidence predictions for the highest and only the highest scoring gene pairs illustrating both the power and the limitations of the approach. Both practical examples and theoretical considerations suggest that in order to get a reliable and specific picture of a protein's function, results from phylogenetic profiling have to be combined with other sources of evidence.
Micromagnetic selection of aptamers in microfluidic channels

Aptamers are nucleic acid molecules that have been selected in vitro to bind to their molecular targets with high affinity and specificity. Typically, the systematic evolution of ligands by exponential enrichment (SELEX) process is used for the isolation of specific, high-affinity aptamers. SELEX, however, is an iterative process requiring multiple rounds of selection and amplification that demand significant time and labor. Here, we describe an aptamer discovery system that is rapid, highly efficient, automatable, and applicable to a wide range of targets, based on the integration of magnetic bead-based SELEX process with microfluidics technology. Our microfluidic SELEX (M-SELEX) method exploits a number of unique phenomena that occur at the microscale and implements a design that enables it to manipulate small numbers of beads precisely and isolate high-affinity aptamers rapidly. As a model to demonstrate the efficiency of the M-SELEX process, we describe here the isolation of DNA aptamers that tightly bind to the light chain of recombinant Botulinum neurotoxin type A (with low-nanomolar dissociation constant) after a single round of selection.
Route to Chaos in the Fluidic Pinball

The fluidic pinball has been recently proposed as an attractive and effective flow configuration for exploring machine learning fluid flow control. In this contribution, we focus on the route to chaos in this system without actuation, as the Reynolds number is smoothly increased. It was found to be of the Newhouse-Ruelle-Takens kind, with a secondary pitchfork bifurcation that breaks the symmetry of the mean flow field on the route to quasi-periodicity.
Construction of Weight Gain Charts in a Low-Risk Obstetric Belgian Population

Aim: To generate reference charts for weight gain during pregnancy for the different BMI categories (underweight, normal weight, overweight, obesity), based on recent data in a homogeneous, Caucasian, low-risk obstetric population. Methods: Weight gain and prepregnancy BMI were retrospectively gathered from 605 pregnant Belgian women with accurately dateable, uncomplicated singleton pregnancies. Percentile curves for the different BMI categories were constructed using the linear mixed model, based on absolute weight gain. The effect of parity on weight gain was examined. Results: Overall mean weight gain was 14.8 kg (±4.7). Weight gain differed significantly between underweight (15.4 ± 4.1 kg) and obese patients (12.0 ± 5.9 kg), between patients with normal weight (15.1 ± 4.5 kg) and overweight patients (13.7 ± 5.3 kg), and between normal-weight and obese patients. Parity had a statistical, but no clinically significant, influence on amount and evolution of weight gain. Conclusion: By using strict inclusion criteria, BMI-category-specific reference charts were generated representing, in terms of outcome, the optimal weight gain during pregnancy rather than the mean observed weight gain. This enables the weight charts to be used as a clinical tool during the counseling of pregnant women.
Writing-Based Learning Analytics for Education

Computer-driven analytics are becoming increasingly essential to various disciplines. Written language in particular has received a great deal of attention, and many tools now exist to gather information about compositions. This research has resulted in Internet search programs, translators, and computerized narrators. However, analytics have yet to be rigorously applied to the field of academic writing. Within this specialized area, there are many prospects for how analytics may be applied. These details, however, first require definitions of analytics and writing analytics in particular, consideration on how they may be used, and the tools available for their collection and implementation.
Catalytic Improvement and Evolution of Atrazine Chlorohydrolase

ABSTRACT The atrazine chlorohydrolase AtzA has evolved within the past 50 years to catalyze the hydrolytic dechlorination of the herbicide atrazine. It is of wide research interest for two reasons: first, catalytic improvement of the enzyme would facilitate its application in bioremediation, and second, because of its recent evolution, it presents a rare opportunity to examine the early stages in the acquisition of new catalytic activities. Using a structural model of the AtzA-atrazine complex, a region of the substrate-binding pocket was targeted for combinatorial randomization. Identification of improved variants through this process informed the construction of a variant AtzA enzyme with 20-fold improvement in its kcat/Km value compared with that of the wild-type enzyme. The reduction in Km observed in the AtzA variants has allowed the full kinetic profile for the AtzA-catalyzed dechlorination of atrazine to be determined for the first time, revealing the hitherto-unreported substrate cooperativity in AtzA. Since substrate cooperativity is common among deaminases, which are the closest structural homologs of AtzA, it is possible that this phenomenon is a remnant of the catalytic activity of the evolutionary progenitor of AtzA. A catalytic mechanism that suggests a plausible mechanistic route for the evolution of dechlorinase activity in AtzA from an ancestral deaminase is proposed.
[Antagonistic effect of 3'-daidzein sulfonate sodium on prostatic hyperplasia in mice].

OBJECTIVE To study the antagonistic effect of 3'-daidzein sulfonate sodium (DSS) on benign prostatic hyperplasia (BPH) and its possible mechanism. METHODS Forty healthy mice were randomly divided into five groups: a normal control group without any treatment, a model group of BPH treated by subcutaneous injection of testosterone propionate, a positive control group with the BPH procedure treated by Qianliekang, a 20 mg/(kg x d) DSS group with the BPH procedure and a 40 mg/(kg x d) DSS group with the BPH procedure. After 12 days of the above treatments, the mice were sacrificed for measurement of the prostate glandular wet weight, the index of prostate gland (PI), the morphological changes of prostate gland by light microscopy and the contents of testosterone and estradiol in the serum. RESULTS The prostate wet weight and PI decreased dose-dependently after DSS treatment for 12 days compared with the BPH model group (P < 0.05 or P < 0.01). The hyperplastic epithelioglandular papilla waned and even disappeared in the DSS treated groups under the light microscope, the epithelial cells became cubical or flat. The effect of DSS at 40 mg/(kg x d) was similar to that of the positive anti-BPH drug Qianliekang. DSS reduced the serum testosterone, estradiol contents and the T/E2 ratio (P < 0.05 or P < 0.01). CONCLUSION DSS has significant antagonistic effect on BPH induced by testosterone propionate in mice, which may involve its regulatory action on the sex hormone balance.
[Effects of training on static and dynamic balance in elderly subjects who have had a fall or not].

OBJECTIVE To evaluate the effects of a physical training program on static and dynamic balance during single and dual task conditions in elderly subjects who have had a fall or not. PATIENTS Two groups, comprising a total of 33 elderly subjects, were trained: 16 who had a fall were 69.2 +/- 5.0 years old and 17 who had not had a fall were 67.3 +/- 3.8 years. METHODS All subjects underwent an unipedal test with eyes open and eyes closed, followed by gait assessment during single and dual motor task conditions, before and after a physical training program. RESULTS All subjects showed a significant decrease, by six times for subjects who had fallen and four times by those who had not, in the number of touch-downs in the unipedal test with eyes open (P < 0.05), and by 2.5 and 2 times, respectively, with eyes closed (P < 0.05) after the training program. All subjects showed a significant increase in speed (P < 0.05), cadence (P < 0.05) and stride length (P < 0.05) and a significant decrease in the single support time (P < 0.05) and stride time (P < 0.05) in gait assessment during single and dual task conditions after the training program. During the training program, no subjects fell. CONCLUSION The physical training program improved static balance and quality of gait in elderly subjects who had had a fall and those who had not, which could contribute to minimizing and/or retarding the effects of aging and maintaining physical independence.
Accounting for Style in Machine Translation

A significant part of the meaning of any text lies in the author's style. Different choices of words and syntactic structure convey different nuances in meaning, which must be carried through in any translation if it is to be considered faithful. Up to now, machine translation systems have been unable to do this. Subtleties of style are simply lost to current MT systems. The goal of the present research is to develop a method to provide MT systems with the ability to understand and preserve the intent of an author's stylistic characteristics. Unilingual natural language understanding systems could also benefit from an appreciation of these aspects of meaning. However, in translation, style plays an additional role, for here one must also deal with the generation of appropriate target-language style. Consideration of style in translation involves two complementary, but sometimes conflicting, aims: • The translation must preserve, as much as possible, the author's stylistic intent— the information conveyed through the manner of presentation. • But it must have a style that is appropriate and natural to the target language. The study of comparative stylistics is, in fact, guided by the recognition that languages differ in their stylistic approaches: each has its own characteristic stylistic preferences. The stylistic differences between French and English are exemplified by the predominance of the pronominal verb in French. This contrast allows us to recognize the greater preference of English for the passive voice: (1) (a) Le jambon se mange froid. (b) Ham is eaten cold.
Sleep Problems of Adolescents: A Detailed Survey

We investigated the sleep problems and sleep habits of adolescents at three public primary schools and two high schools. Our study included 428 Turkish school children (244 girls and 184 boys). We used a questionnaire to determine the time they went to sleep at night; waking time in the morning; incidence of nightmares, snoring, daytime sleepiness, and intrafamilial physical trauma; concentration difficulty in class; and school success. The students were divided into age-related groups (group 1 = 11 to 13 years of age; group 2 = 14 to 15 years; group 3 = 16 to 18 years). The time they went to sleep was mostly between 10 and 11 p.m. in groups 1 and 2, and 11 to 12 p.m. in group 3. Difficulty in falling asleep was reported by 16.8 to 19.6% of the students in the three groups. Difficulty in waking up in the morning was reported by 12.7% of group 1, 16.0% of group 2, and 16.8% of group 3. Snoring was present in 12.1% of females and 22.0% of males. The occurrence of one nightmare in the preceding 3 months was reported by 11.3% of the students; 17.9% of the students reported having nightmares several times. Daytime sleepiness was present in 65.1%, and concentration difficulty was present in 56.8% of the students. We conclude that difficulty in falling asleep, snoring, and daytime sleepiness may be seen in adolescents who are in both primary and high schools. Watching inappropriate programs and movies on television and intrafamilial physical trauma may cause nightmares and sleeping problems in these adolescents. Students and families should be educated about the importance of sleep in academic performance. Countries’ public health policies should address sleep problems and related educational activities.