Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancing GABA Signaling during Middle Adulthood Prevents Age-Dependent GABAergic Interneuron Decline and Learning and Memory Deficits in ApoE4 Mice

Apolipoprotein E4 (apoE4) is the major genetic risk factor for Alzheimer's disease (AD). However, the underlying mechanisms are still poorly understood. We previously reported that female apoE4 knock-in (KI) mice had an age-dependent decline in hilar GABAergic interneurons that correlated with the extent of learning and memory deficits, as determined by Morris water maze (MWM), in aged mice. Enhancing GABA signaling by treating aged apoE4-KI mice with the GABAA receptor potentiator pentobarbital (PB) for 4 weeks before and during MWM rescued the learning and memory deficits. Here, we report that withdrawal of PB treatment for 2 weeks before MWM abolished the rescue in aged apoE4-KI mice, suggesting the importance of continuously enhancing GABA signaling in the rescue. However, treating apoE4-KI mice during middle adulthood (9–11 months of age) with PB for 6 weeks prevented age-dependent hilar GABAergic interneuron decline and learning and memory deficits, when examined at 16 month of age. These data imply that increasing inhibitory tone after substantial GABAergic interneuron loss may be an effective symptomatic, but not a disease-modifying, treatment for AD related to apoE4, whereas a similar intervention before substantial interneuron loss could be a disease-modifying therapeutic. SIGNIFICANCE STATEMENT We previously reported that female apoE4-KI mice had an age-dependent decline in hilar GABAergic interneurons that correlated with the extent of cognitive deficits in aged mice. The current study demonstrates that enhancing GABA signaling by treating aged apoE4-KI mice with a GABAA receptor potentiator pentobarbital (PB) before and during behavioral tests rescued the cognitive deficits; but withdrawal of PB treatment for 2 weeks before the tests abolished the rescue, suggesting the importance of continuously enhancing GABA signaling. However, treating apoE4-KI mice during middle adulthood with PB for a short period of time prevented age-dependent hilar GABAergic interneuron decline and cognitive deficits late in life, suggesting early intervention by enhancing GABA signaling as a potential strategy to prevent AD related to apoE4.
TOA Estimation and Data Association for Through-Wall Tracking of Moving Targets

Through-wall tracking of moving targets is of great interest for rescue, surveillance, and security operations. For its realization, the handheld ultrawideband radars with small antenna array provide a practical solution. The radar signal processing, which is hidden behind the estimation of the final target tracks, represents a complex process with several processing phases. In this paper, all phases for through wall tracking are outlined whereas the attention is devoted to the estimation of the correct input data for the localization phase. This is done by applying a new approach that combines the time of arrival (TOA) estimation and the data-association into a single step. The properties of the proposed algorithm are illustrated by processing of real radar signals. Here, the obtained results confirm that the proposed algorithm has provided good, stable, and robust TOA estimation including deghosting task solution.
Nanoscaffold based stem cell regeneration therapy: recent advancement and future potential

Importance of the field: Over the past years, extensive research has been directed towards tissue engineering using conventional scaffolds. In-depth studies in this field have led to the realization that in vivo cells interact with the extracellular matrix, composed of nanofibers at sub-micron scale, which not only provides the mechanical support to the cells but also plays a key role in regulation of cellular behavior. This has led to the development of nanofibrous scaffold (NFS) technology which in combination with stem cells is emerging as an important tool in the development of tissue engineering and regenerative medicine. Areas covered in this review: This review summarizes the three methods of nanofibrous scaffold preparation and provides a state-of-the-art update on the recent advancement in the use of nanoscaffolds in stem cell regeneration therapy. What the reader will gain: The review gives the reader an insight on nanoscaffold based therapy methods, such as how these scaffolds can potentially be designed and used in successful development of stem cell based therapies. Take home message: NFS technology when coupled with stem cells and exploited in the right way has a strong potential of being used in stem cell based regenerative medicine.
Data-driven anomaly detection in cyber-physical production systems

Abstract Due to global competition and increasing product complexity, the complexity of production systems has grown significantly in recent years. This places an increasing burden on automation developers, systems engineers and plant constructors. Intelligent assistance systems and smart automation systems are a possible solution to face this complexity: The machines, i.e. the software and assistance systems, take over tasks that were previously carried out manually by experts. At the heart of this concept are intelligent anomaly detection approaches based on models of the system behaviors. Intelligent assistance systems learn these models automatically: Based on data, these systems extract most necessary knowledge about the diagnosis task. This paper outlines this data-driven approach to plant analysis using several use cases from industry.
Objective Assessment of Laparoscopic Skills

Background. Assessment of surgical performance is often accomplished with traditional methods that often provide only subjective data. Trainees who perform well on a simulator in a controlled environment may not perform well in a real operating room environment with distractions. This project uses the ideas of dual-task methodology and applies them to the assessment of performance of laparoscopic surgical skills. The level of performance on distracting secondary tasks while trying to perform a primary task becomes an indirect but objective measure of the surgical skill of the trainee. Methods. Nine surgery residents and 6 experienced laparoscopic surgeons performed 3 primary tasks on a laparoscopic virtual reality simulator (camera position, grasping, and cholecystectomy) while being distracted by 3 secondary tasks (counting beeps, selective responses, and mental arithmetic). Completion time and error rates were recorded for each combination of tasks. Results. When performed separately, time to completion and error rates for primary and secondary tasks were similar for learners and experts. When performing the tasks simultaneously, learners had more errors than experts. Error rates increased for learners when distracting tasks became more difficult or required more attention. Expert surgeons maintained consistent error rates despite the increasing difficulty of task combinations. Conclusions. The use of dual-task methodology may help trainers to identify which surgical trainees require more preparation before entering the real operating room environment. Expert surgeons are capable of maintaining performance levels on a primary task in the face of distractions that may occur in the operating room.
Development of preceding vehicle recognition algorithm for lead vehicle of autonomous platooning system based on multi sensor fusion and digital map

We have been developing an autonomous platooning system of heavy trucks aimed at enhancing its energy efficiency by shortening headway distance between trucks. In this paper, we focused on developing a forward environment perception method for fully automated lead vehicle of the autonomous platooning system. To percept the forward environment of autonomous platooning system, it is important to robustly detect obstacles from distance. Additionally, it is also important to recognize which lane the detected obstacles exist. In this research, the obstacles are detected robustly and precisely based on multi-sensor fusion scheme between LIDAR and RADAR. Moreover, the lanes, where the obstacles exist, are recognized by using digital map based on lane marker detection.
Parsing engineering and empirical robustness

Robustness has been traditionally stressed as a general desirable property of any computational model and system. The human NL interpretation device exhibits this property as the ability to deal with odd sentences. However, the difficulties in a theoretical explanation of robustness within the linguistic modelling suggested the adoption of an empirical notion. In this paper, we propose an empirical definition of robustness based on the notion of performance. Furthermore, a framework for controlling the parser robustness in the design phase is presented. The control is achieved via the adoption of two principles: the modularisation, typical of the software engineering practice, and the availability of domain adaptable components. The methodology has been adopted for the production of CHAOS, a pool of syntactic modules, which has been used in real applications. This pool of modules enables a large validation of the notion of empirical robustness, on the one side, and of the design methodology, on the other side, over different corpora and two different languages (English and Italian).
Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-gamma secretion in specific allergen-stimulated T cell cultures.

The mechanisms of bee venom immunotherapy (VIT) are largely unknown. The aim of this study was to follow the changes of T cell cytokine secretion during the course of VIT. Ten bee venom-allergic patients with a history of severe systemic reactions, positive skin tests, and bee venom (BV)-specific serum IgE Abs were treated as follows: on the first day, a cumulative dose of 111 micrograms, starting with 0.1 microgram, was administered s.c. under intensive care conditions. Further injections of 100 micrograms BV were given on day 7, day 21, and thereafter at intervals of 4 wk. Blood samples were obtained just before the initiation of VIT, after the last injection on the same day, and before the subsequent BV injections on days 7, 21, and 50 of VIT. Peripheral blood mononuclear cells (PBMC) were stimulated with phospholipase A (PLA), the major BV allergen, or with a control Ag tetanus toxoid (TT). Cytokine secretion was measured 24 h after restimulation of the cultures with solid-phase bound OKT3 F(ab')2 mAbs after 7 days of culture. In PLA-stimulated cultures, VIT resulted in decreased IL-4 and IL-5 and increased IFN-gamma secretion. In TT-stimulated cultures, we observed similar levels of cytokines before and during VIT. We conclude that ultra-rush VIT changes allergen-specific T cell reactivity.
Segmentation and Shape Extraction of 3D Boundary Meshes

In this report we present the state of the art on segmentation, or partitioning techniques used on boundary meshes. Recently, these have become a part of many mesh and object manipulation algorithms in computer graphics. We formulation the segmentation problem as an optimization problem and identify two primarily distinct types of mesh segmentation, namelyparts segmentation and patch segmentation. We classify previous segmentation solutions according to the different segmentation goals, the optimization criteria and features used, and the various algorithmic techniques employed. We also present generic algorithms for the major techniques of segmentation.
Analysis of Keystone Enzyme in Agar Hydrolysis Provides Insight into the Degradation (of a Polysaccharide from) Red Seaweeds*

Background: The catalytic mechanism and substrate recognition required for cleavage of the α-linkage in agarose are unclear. Results: Structural analysis of a family 117 glycoside hydrolase details substrate recognition and supports an inverting mechanism. Conclusion: GH117 enzymes use substrate distortion and an unusual general acid for catalysis. Significance: Microbes may utilize alternate strategies to catalyze the degradation of polysaccharides with unique structural characteristics. Agars are abundant polysaccharides from marine red algae, and their chemical structure consists of alternating d-galactose and 3,6-anhydro-l-galactose residues, the latter of which are presumed to make the polymer recalcitrant to degradation by most terrestrial bacteria. Here we study a family 117 glycoside hydrolase (BpGH117) encoded within a recently discovered locus from the human gut bacterium Bacteroides plebeius. Consistent with this locus being involved in agarocolloid degradation, we show that BpGH117 is an exo-acting 3,6-anhydro-α-(1,3)-l-galactosidase that removes the 3,6-anhydrogalactose from the non-reducing end of neoagaro-oligosaccharides. A Michaelis complex of BpGH117 with neoagarobiose reveals the distortion of the constrained 3,6-anhydro-l-galactose into a conformation that favors catalysis. Furthermore, this complex, supported by analysis of site-directed mutants, provides evidence for an organization of the active site and positioning of the catalytic residues that are consistent with an inverting mechanism of catalysis and suggests that a histidine residue acts as the general acid. This latter feature differs from the vast majority of glycoside hydrolases, which use a carboxylic acid, highlighting the alternative strategies that enzymes may utilize in catalyzing the cleavage of glycosidic bonds.
Consumption pattern, biochemical composition and nutritional value of fermented pearl millet gruels in Burkina Faso

Ben-kida and ben-saalga are popular pearl-millet-based fermented gruels in Burkina Faso. A survey of 318 households in Ouagadougou (Burkina Faso) showed that they are often used as complementary food for young children. Pearl millet and gruels, sampled in 48 production units, were analysed for proximate composition, factors reducing nutrient bioavailability (phytate, insoluble fibres and iron-binding phenolic compounds), α-galactosides, sugars, total lactic acid and d-lactic acid, zinc and iron contents. The effects of processing of pearl millet into fermented gruel are discussed. Both positive effects (e.g. a decrease in factors reducing nutrient bioavailability or α-galactosides) and undesirable effects (e.g. considerable lipid, protein, iron and zinc losses) were observed. Lactic acid was produced during processing and d(−)-lactate was detected in all samples. The gruels had very low energy density, even after addition of sugar, and low lipid, protein and mineral contents, well below recommendations for complementary foods.
Controlled comparison of a new sublingual lormetazepam formulation and i.v. diazepam in outpatient minor oral surgery.

In a randomized, double-blind, parallel groups study, 40 patients undergoing surgical removal of impacted 3rd molar teeth received either sublingual lormetazepam 2.5 mg (n = 20) in a new cellulose wafer formulation followed at 35 min by i.v. saline; or sublingual placebo followed at 35 min by i.v. diazepam 10 mg (Diazemuls). Rapid onset of sedation was seen after sublingual lormetazepam, while the course and duration of postoperative sedation, measured using standard psychometric tests, was similar following both treatments. Surgeons' ratings indicated that sublingual lormetazepam was comparable to i.v. diazepam but patients' ratings indicated greater satisfaction with and preference for i.v. diazepam. Significant anterograde amnesia was found following both treatments. Both treatments were tolerated well, with no significant cardiovascular complications. These results indicate that sublingual lormetazepam may have a role in anaesthesia as a premedicant and for conscious sedation.
Prototyping new concepts beyond 4G – The Fraunhofer Open5GCore

Abstract The 5th Generation of mobile networks (5G) is expected to be rolled out by 2020. New and revolutionary applications are already being envisioned, real-time control of machines, the Tactile Internet for wireless, Industry 4.0, the Internet of Things and self-driving cars, among others. To make this possible important enhancements and improvements in today's existing telecommunication technologies form an end-to-end perspective are required. Early testing and fast prototyping of new approaches and solutions will help to shape the evolving technologies. One of the technical enablers for 5G are two concepts based on the softwarisation and virtualisation of the core network, known as Software Defined Networking (SDN) and Network Function Virtualisation, NFV. Fraunhofer FOKUS has set up the Open5GCore testing environment to start shaping, together with its partners, the nascent 5G technologies by addressing these topics together with other relevant technological developments. After a short motivation, the architecture of the open5GCore is presented, followed by a functional description of supported features.
Steady-state levels and bone marrow toxicity of etoposide in children and infants: does etoposide require age-dependent dose calculation?

PURPOSE Most pediatric treatment protocols specify dose calculations for cytostatic drugs based on body-surface area (BSA). However, for children less than 1 year of age, calculation guidelines vary. Normally, reduced dosages are recommended with calculations based on body weight (BW). However, the optimal dose for infants should take age-dependent and drug-specific pharmacokinetic parameters into account. PATIENTS AND METHODS The current investigation focused on the effects of different dose-reduction rules on the steady-state levels (Css) of etoposide and related bone marrow toxicity. One hundred seventy three treatment courses in 78 children on a 96-hour continuous infusion schedule were monitored for Css (determined by high-performance liquid chromatography [HPLC]), and 100 courses were documented in detail with regard to dose calculation (125 mg/m2, 4.17/kg, or 2/3 x 4.17/kg) and toxicity. RESULTS Dose calculation on the basis of BSA led to Css of 4.9 +/- 1.2 micrograms/mL, which on the basis of BW was 3.5 +/- 1.1 micrograms/mL and 1.95 +/- 0.6 micrograms/mL (2/3.kg-dose), respectively. However, conversion of the latter levels to those expected with the regular square-meter-dose, resulted in values of 4.7 +/- 1.4 micrograms/mL and 4.2 +/- 1.2 micrograms/mL (/125 mg/m2). Lower etoposide Css levels resulted in less pronounced thrombocyte and WBC nadirs in the respective groups. The dose-calculation rules for infants, therefore, decreased both dose-intensity and related toxicity. Etoposide clearance rates related to BW (0.8 +/- 0.3 mL/min/kg) or BW (19 +/- 6 mL/min/m2) did not show any differences between children and infants, even in the age range of 3 to 12 months. CONCLUSION In the case of etoposide, special dose-calculation guidelines for infants are not substantiated by age-dependent pharmacokinetics or tolerance.
Loss of SIRT3 Provides Growth Advantage for B Cell Malignancies*

B cell malignancies comprise a diverse group of cancers that proliferate in lymph nodes, bone marrow, and peripheral blood. SIRT3 (sirtuin 3) is the major deacetylase within the mitochondrial matrix that promotes aerobic metabolism and controls reactive oxygen species (ROS) by deacetylating and activating isocitrate dehydrogenase 2 (IDH2) and superoxide dismutase 2 (SOD2). There is controversy as to whether SIRT3 acts as an oncogene or a tumor suppressor, and here we investigated its role in B cell malignancies. In mantle cell lymphoma patient samples, we found that lower SIRT3 protein expression was associated with worse overall survival. Further, SIRT3 protein expression was reduced in chronic lymphocytic leukemia primary samples and malignant B cell lines compared to primary B cells from healthy donors. This lower level of expression correlated with hyperacetylation of IDH2 and SOD2 mitochondrial proteins, lowered enzymatic activities, and higher ROS levels. Overexpression of SIRT3 decreased proliferation and diminished the Warburg-like phenotype in SIRT3-deficient cell lines, and this effect is largely dependent on deacetylation of IDH2 and SOD2. Lastly, depletion of SIRT3 from malignant B cell lines resulted in greater susceptibility to treatment with an ROS scavenger but did not result in greater sensitivity to inhibition of the hypoxia-inducible factor-1α pathway, suggesting that loss of SIRT3 increases proliferation via ROS-dependent but hypoxia-inducible factor-1α-independent mechanisms. Our study suggests that SIRT3 acts as a tumor suppressor in B cell malignancies, and activating the SIRT3 pathway might represent a novel therapeutic approach for treating B cell malignancies.
Methodology development for predicting subcellular localization and other attributes of proteins

Facing the explosion of newly generated protein sequences in the postgenomic age, we are challenged to develop computational methods for the fast and accurate identification of their subcellular localization and other attributes. This review summarizes recent methodology developments, with a focus on artificial neural networks, the statistical learning and support vector machine, the fuzzy logic-based algorithm and the evidence-theory-based algorithm, as well as the ensemble classifier approach. Meanwhile, an outline of the use of different descriptors for protein samples is given. In addition, a series of web servers established recently based on various ensemble classifiers are also briefly introduced.
Visual Human Intent Analysis Survey

Abstract : Visual Human Intent Analysis (VHIA) is a growing field of research devoted to algorithms that categorize human behavior through input of visual image sequences. In VHIA, it is difficult to make an implementation framework that is robust enough to handle the many non-deterministic ways of human physical actions. This paper will survey several techniques currently used in VHIA including non-traditional artificial intelligence techniques, visual languages, statistical algorithms, and others. It will give the reader the background and understanding of how open this domain is to new algorithms; improving on the overall research in VHIA or similarly related problems.
Microfabrication of Capillary System Using a Perfusion Cell Chamber

Nowadays, the biological tissue realized in vitro at experimental level, is characterised by thickness to the order of a few millimetres. This is related to the limitation of the diffusive transport of oxygen, nutrients and metabolic by-products. These results are incompatible with the realization of tissue which has relevant thickness or which requires a high vascularisation level (e.g. liver, heart, lungs). The attempts to create a vascular bed, integrated on bioartificial tissue, still remains in preliminary phases. The aim of the present study is to realize in vitro microvascular structures for tissue engineering applications. We designed and realized a culture chamber that allows the seeding, the development and the perfusion of cellular microvessels. The strategy adopted consist of the use of cylindrical polymeric scaffolds, onto which cells of the connective tissue (murine fibroblasts) can adhere and proliferate.