Miracle-dz/UniFAR-FTUs huggingface dataset:
Adapting mass spectrometry-based platforms for clinical proteomics applications: The capillary electrophoresis coupled mass spectrometry paradigm

Single biomarker detection is common in clinical laboratories due to the currently available method spectrum. For various diseases, however, no specific single biomarker could be identified. A strategy to overcome this diagnostic void is to shift from single analyte detection to multiplexed biomarker profiling. Mass spectrometric methods were employed for biomarker discovery in body fluids. The enormous complexity of biofluidic proteome compartments implies upstream fractionation. For this reason, mass spectrometry (MS) was coupled to two-dimensional gel electrophoresis, liquid chromatography, surface-enhanced laser desorption/ionization, or capillary electrophoresis (CE). Differences in performance and operating characteristics make them differentially suited for routine laboratory applications. Progress in the field of clinical proteomics relies not only on the use of an adequate technological platform, but also on a fast and efficient proteomic workflow including standardized sample preparation, proteomic data processing, statistical validation of biomarker selection, and sample classification. Based on CE-MS analysis, we describe how proteomic technology can be implemented in a clinical laboratory environment. In the last part of this review, we give an overview of CE-MS-based clinical studies and present information on identity and biological significance of the identified peptide biomarkers providing evidence of disease-induced changes in proteolytic processing and posttranslational modification.
Analysis of petrol and diesel vapour and vehicle engine exhaust gases using selected ion flow tube mass spectrometry.

We have used selected ion flow tube mass spectrometry (SIFT-MS) to analyse the vapours emitted by petrol and diesel fuels and the exhaust gases from petrol (spark ignition) and diesel (compression ignition) engine vehicles fitted with catalytic converters. Only those components of these media that have significant vapour pressures at ambient temperatures were analysed and thus particulates were obviously not detected. These media have been analysed using the full scope of SIFT-MS, i.e., with the three available precursor ions H3O+, NO+ and O2+. The combination of the H3O+ and NO+ analyses is seen to be essential to distinguish between different product ions at the same mass-to-charge ratio (m/z) especially in identifying aldehydes in the exhaust gases. The O2+ precursor ions are used to detect and quantify the large amount of nitric oxide present in the exhaust gases from both engine types. The petrol and diesel vapours consist almost exclusively of aliphatic alkanes, alkenes and alkynes (and dienes) and aromatic hydrocarbons. Some of these compounds appear in the exhaust gases together with several aldehydes, viz. formaldehyde, acetaldehyde, pentanal, pentenal (acrolein), butenal, and also methanol and ethanol. Acetone, nitric oxide and ammonia are also present, acetone and nitric oxide being much more abundant in the diesel exhaust gas than in the petrol exhaust gas. These data were obtained from samples collected into pre-evacuated stainless steel vessels. Trapping of the volatile compounds from the gas samples is not required and analysis was completed a few minutes later. All the above compounds are detected simultaneously, which demonstrates the value of SIFT-MS in this area of research.
Sparse Haptic Proxy: Touch Feedback in Virtual Environments Using a General Passive Prop

We propose a class of passive haptics that we call Sparse Haptic Proxy: a set of geometric primitives that simulate touch feedback in elaborate virtual reality scenes. Unlike previous passive haptics that replicate the virtual environment in physical space, a Sparse Haptic Proxy simulates a scene's detailed geometry by redirecting the user's hand to a matching primitive of the proxy. To bridge the divergence of the scene from the proxy, we augment an existing Haptic Retargeting technique with an on-the-fly target remapping: We predict users' intentions during interaction in the virtual space by analyzing their gaze and hand motions, and consequently redirect their hand to a matching part of the proxy. We conducted three user studies on haptic retargeting technique and implemented a system from three main results: 1) The maximum angle participants found acceptable for retargeting their hand is 40°, with an average rating of 4.6 out of 5. 2) Tracking participants' eye gaze reliably predicts their touch intentions (97.5%), even while simultaneously manipulating the user's hand-eye coordination for retargeting. 3) Participants preferred minimized retargeting distances over better-matching surfaces of our Sparse Haptic Proxy when receiving haptic feedback for single-finger touch input. We demonstrate our system with two virtual scenes: a flight cockpit and a room quest game. While their scene geometries differ substantially, both use the same sparse haptic proxy to provide haptic feedback to the user during task completion.
Activation and Inhibition of Anaplastic Lymphoma Kinase Receptor Tyrosine Kinase by Monoclonal Antibodies and Absence of Agonist Activity of Pleiotrophin*

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is transiently expressed in specific regions of the central and peripheral nervous systems, suggesting a role in its normal development and function. The nature of the cognate ligands of ALK in vertebrate is still a matter of debate. We produced a panel of monoclonal antibodies (mAbs) directed against the extracellular domain of the human receptor. Two major species of ALK (220 and 140 kDa) were identified in transfected cells, and the use of our mAbs established that the 140-kDa species results from a cleavage of the 220-kDa form. Two mAbs, in the nm range, induced the differentiation of PC12 cells transiently transfected with ALK. In human embryonic kidney 293 cells stably expressing ALK, these two mAbs strongly activated the receptor and subsequently the mitogen-activated protein kinase pathway. We further showed for the first time that activation of ALK also resulted in a specific activation of STAT3. In contrast, other mAbs presented the characteristics of blocking antibodies. Finally, in these cell systems, a mitogenic form of pleiotrophin, a proposed ligand of ALK, failed to activate this receptor. Thus, in the absence of clearly established ligand(s) in vertebrates, the availability of mAbs allowing the activation or the inhibition of the receptor will be essential for a better understanding of the biological roles of ALK.
Range-based cooperative localization with single landmark

We consider the problem of range-based cooperative localization for multiple agents in a GPS-denied environment. For the minimal reference purpose, there exists only one single landmark whose global position is known to a subset of agents. All agents which are equipped with Ultra Wideband (UWB) radars are able to measure the relative distance between themselves and their communicating neighbours. We propose two approaches for the purpose of cooperative localization. We first design a covariance intersection (CI) based estimator which needs the information exchange among the agents to enhance their localization precision and show that the estimate is stable under mild conditions. We also design an alternative approach based on estimate consensus which differs from CI approach that primarily focuses on covariance fusion. Simulation results show the effectiveness of both the proposed approaches.
Thalamocortical oscillations in a genetic model of absence seizures

We used field potential recordings in an in vitro thalamocortical slice preparation to compare the rhythmic oscillations generated by reciprocally connected networks of the thalamus and cerebral cortex obtained from epileptic (> 160 days old) WAG/Rij and age‐matched, nonepileptic control (NEC) rats. To increase neuronal excitability, and thus to elicit spontaneous field potential activity in vitro, we applied medium containing: (i) zero [Mg2+]; (ii) high [K+] (8.25 mm); or (iii) low concentrations of the K+ channel blocker 4‐aminopyridine (4AP, 0.5–1 µm). Of these procedures, only the last was effective in triggering oscillatory activity that depended on the type of tissue. Thus, during 4AP application: (i) sequences of fast (intraburst frequency 9.5–16.1 Hz) and slower (5–8.9 Hz) field potential oscillations (FPOs) were recorded in WAG/Rij slices (n = 23), but (ii) only fast FPOs were seen in NEC slices (n = 7). Slower FPOs in WAG/Rij slices reflected a larger degree of thalamocortical synchronization than fast FPOs, and disappeared after surgical separation of cortex and thalamus (n = 5); under these conditions fast FPOs continued to occur in thalamus only. In addition, fast and slower FPOs disappeared in all areas of the WAG/Rij slice during thalamic application of the excitatory amino acid receptor antagonist kynurenic acid (n = 3), while fast FPOs continued to occur in thalamus when kynurenic acid was applied to the cortex (n = 4). Bath application of the N‐methyl‐d‐aspartic acid (NMDA) receptor antagonist 3,3‐(2‐carboxypiperazine‐4‐yl)‐propyl‐1‐phosphonate (CPP) abolished slower FPOs in WAG/Rij cortex and thalamus (n = 6) without infuencing fast FPOs recorded in WAG/Rij (n = 6) or NEC slices (n = 4). Moreover, cortical application of CPP (n = 6) abated slower FPOs although they persisted following CPP application to the thalamus (n = 7). Our data demonstrate that highly synchronized, slower FPOs can occur during 4AP application in WAG/Rij but not in NEC slices. This activity, which may represent an in vitro hallmark of thalamocortical epileptogenicity, requires the function of reciprocally connected thalamic and cortical networks and depends on cortical NMDA receptor‐mediated mechanisms.
A digitally tunable stabilization technique for transimpedance amplifiers in optical wireless and visible light communication links

A digitally controllable stabilization technique for bandwidth-enhanced shunt-feedback (SFB) transimpedance amplifiers (TIA) with active Gm-feedback is proposed. The Gm-feedback programmability uses a switchable tail current network to digitally control the global TIA phase margin and correct for any instability resulting from device modeling imperfections, unconsidered layout parasitics or PVT variations. The proposed technique is demonstrated using a dual-stage TIA implemented in 0.35 μm CMOS technology. The TIA consumes 10.9 mA from a 3.3 V DC voltage supply, with 600 μA additional current from the phase margin correcting circuits, to achieve around 25 degrees phase margin control range. The TIA was tested as a part of a fully integrated optical receiver in a 2.7-m link visible light communication (VLC) setup. The phase margin control bits allowed bit-error-rate (BER) improvement by three orders of magnitude (<; 10-10) at 1.8 Gb/s.
Control frame for synchronous stability of interconnected power systems in deregulated environments

Power system restructuring brings about new challenges to power system stability, especially the transient stability (TS) and small-signal stability (SS) of interconnected large-scale power systems under large and cascaded disturbances. This is because of the need to yield more economic benefits in deregulated environments. In order to improve interconnected power system TS and SS in deregulated environments, the development of an effective global control frame is very important. In this paper a preliminary study on the issue is presented. First, nonlinear robust adaptive control (RAC) is applied to excitation system utilizing local measurements. Then, RAC for the supplementary control of HVDC transmission and FACTS device (e.g. TCSC) using the WAMS signal of system center of inertia (COI) dynamics is presented. The computer test results are shown to be very positive. Based on the results, an overall control frame is suggested for enhancing TS and SS of interconnected power systems. Future work in realizing the new control frame is also discussed
Deep Learning for Semantic Composition

Learning representation to model the meaning of text has been a core problem in NLP. The last several years have seen extensive interests on distributional approaches, in which text spans of different granularities are encoded as vectors of numerical values. If properly learned, such representation has showed to achieve the state-of-the-art performance on a wide range of NLP problems. In this tutorial, we will cover the fundamentals and the state-of-the-art research on neural network-based modeling for semantic composition, which aims to learn distributed representation for different granularities of text, e.g., phrases, sentences, or even documents, from their sub-component meaning representation, e.g., word embedding.
Predictability of Extreme Returns in the Turkish Stock Market

ABSTRACT In this paper, we show that extreme returns can predict future returns in the Turkish stock market. We find that extreme return (high MAX) generating stocks show a lower performance in the next month in this market. More explicitly, there is a strong negative relationship between the firm’s maximum (MAX) daily returns over the previous month and its succeeding stock returns. Our results are robust in both firm-level cross-sectional, and portfolio-level analysis.
Responses of Heterodera glycines and Meloidogyne incognita to exogenously applied neuromodulators

Abstract Biogenic amines regulate important behaviours in nematodes and are associated with pharyngeal activity in plant-parasitic nematodes. A robust behavioural assay based upon nematode body movements was developed to expand the study of these and other neuroregulators in plant-parasitic nematodes. Dopamine, octopamine and serotonin each had significant but differing effects on the behaviour of soybean cyst nematode Heterodera glycines and root-knot nematode Meloidogyne incognita juveniles. Body movement frequency was increased twofold in H.glycines by 5 mM dopamine (P = 0.0001), but decreased by 50 mM dopamine in H. glycines (88%) and M. incognita (53%) (P < 0.0001). Movement frequency in both species was increased by 50–70% (P < 0.0001) by 50 mM octopamine, and 5 mM octopamine increased M. incognita movement frequency more than twofold (P < 0.0001). Movement frequency in each species was reduced by more than 90% by 5 mM serotonin (P < 0.0001). While amplitude of body movement in H. glycines was unaffected by any amine, it was significantly reduced in M.incognita by all amines (P < 0.0006). Stylet pulsing frequencies in either species were unaffected by dopamine or octopamine, but 5 mM serotonin stimulated pulsing in H. glycines by nearly 13-fold (P < 0.0001) and in M. incognita by more than 14-fold (P < 0.0001). The invertebrate neuropeptide FLRFamide (N-Phe-Leu-Arg-Phe) increased M. incognita body movement frequency 45% (P = 0.02) at 1 mM but did not affect stylet activity. Finally, H. glycines egg hatch was completely suppressed by 50 mM serotonin, and partially suppressed by 50 mM dopamine (75%; P < 0.0001) and 50 mM octopamine (55%; P < 0.0001).
Homologies of the transversospinalis muscles in the anterior presacral region of Sauria (crown Diapsida)

Homologies of muscles of the m. transversospinalis group in the dorsal and cervical regions in Sauria are established based on detailed dissections and published accounts of lepidosaurs, crocodylians, and birds. Attachments and directions of tendons comprising this muscle group are fairly conserved among the saurian clades, enabling rather robust inferences on muscle homologies. The innervation pattern indicates that mm. ascendentes are the most lateral muscles of the m. transversospinalis group in Aves, and are inferred to be homologous with the crocodylian m. tendinoarticularis based on their topological similarities. It is suggested here that the lepidosaurian articulo‐parietalis part of m. longissimus cervico‐capitis actually belongs to the m. transversospinalis group because its tendons of origin are shared with those of m. semispinalis. The avian m. complexus and the lateral part of the crocodylian m. transversospinalis capitis have origins and insertions similar to this lepidosaurian muscle, and are proposed to be homologous with the latter. In some birds, m. longus colli dorsalis, pars profunda continues directly into the anterior cervical region as m. splenius accessorius, suggesting a serially homologous relationship. Similarly, m. splenius anticus continues anteriorly from m. longus colli dorsalis, pars cranialis, and both of these muscles lie dorsal to m. splenius accessorius. Therefore, the currently used nomenclature that regards m. splenius accessorius as a part of m. longus colli dorsalis, pars cranialis and that regards m. splenius anticus as a part of the former muscle does not accurately reflect the serial homologies among these muscles and may not be justified. © 2004 Wiley‐Liss, Inc.
Gene expression changes in human cells after exposure to mobile phone microwaves

Possible biological effects of mobile phone microwaves were investigated in vitro. In this study, which was part of the 5FP EU project REFLEX (Risk Evaluation of Potential Environmental Hazards From Low‐Energy Electromagnetic Field Exposure Using Sensitive in vitro Methods), six human cell types, immortalized cell lines and primary cells, were exposed to 900 and 1800 MHz. RNA was isolated from exposed and sham‐exposed cells and labeled for transcriptome analysis on whole‐genome cDNA arrays. The results were evaluated statistically using bioinformatics techniques and examined for biological relevance with the help of different databases. NB69 neuroblastoma cells, T lymphocytes, and CHME5 microglial cells did not show significant changes in gene expression. In EA.hy926 endothelial cells, U937 lymphoblastoma cells, and HL‐60 leukemia cells we found between 12 and 34 up‐ or down‐regulated genes. Analysis of the affected gene families does not point towards a stress response. However, following microwave exposure, some but not all human cells might react with an increase in expression of genes encoding ribosomal proteins and therefore up‐regulating the cellular metabolism.
Amphibian oocyte nuclei expressing lamin A with the progeria mutation E145K exhibit an increased elastic modulus

Mutations in the human lamin A gene (LMNA) cause a wide range of diseases (laminopathies). Among these is the Hutchinson-Gilford progeria syndrome (HGPS), a rare premature aging disease. Most HGPS patients carry a silent point mutation, which activates a cryptic splice site resulting in the expression of a permanently isoprenylated and truncated lamin AΔ50/progerin. Another type of mutant lamin A namely, E145K-lamin A, also causes HGPS. E145K-lamin A induces profound changes in the nuclear architecture of patient cells as well as after expression in cultured cells. The E145K mutation is located in the α-helical central domain of lamin A, which is involved in lamin filament assembly. In vitro analyses of purified E145K-lamin A have revealed severe assembly defects into higher order lamin structures, which indicates an abnormal lateral association of protofilaments. To analyze how the altered assembly observed in vitro might influence the mechanics of a nuclear lamina formed by E145K-lamin A, mutant and wild type lamin A were ectopically expressed in amphibian oocytes. Both types form a lamina consisting of multi-layered sheets of filaments at the inner side of the nuclear envelope. The mechanical properties of isolated nuclei were measured by atomic force microscopy (AFM). From the resulting force curves, the stiffness of the lamina was estimated. The thickness of the resulting lamin A layer was then measured by TEM. The two parameters allowed us to estimate the elastic modulus (Young's modulus) of the lamina. Lamin A sheets made from E145K filaments have a higher Young's modulus compared to wild type filaments, i.e. the E145K-lamin A sheets are more rigid than wild type laminae of comparable thickness.
Metabolism and mis-metabolism of the neuropathological signature protein TDP-43

ABSTRACT TDP-43 (also known as TARDBP) is a pathological signature protein of neurodegenerative diseases, with TDP-43 proteinopathies including frontotemporal lobar degeneration (FTLD)-TDP and amyotrophic lateral sclerosis (ALS)-TDP. These TDP-43 proteinopathies are characterized by cytoplasmic insoluble TDP-43-positive aggregates in the diseased cells, the formation of which requires the seeding of TDP-25 fragment generated by caspase cleavage of TDP-43. We have investigated the metabolism and mis-metabolism of TDP-43 in cultured cells and found that endogenous and exogenously overexpressed TDP-43 is degraded not only by the ubiquitin proteasome system (UPS) and macroautophagy, but also by the chaperone-mediated autophagy (CMA) mediated through an interaction between Hsc70 (also known as HSPA8) and ubiquitylated TDP-43. Furthermore, proteolytic cleavage of TDP-43 by caspase(s) is a necessary intermediate step for degradation of the majority of the TDP-43 protein, with the TDP-25 and TDP-35 fragments being the main substrates. Finally, we have determined the threshold level of the TDP-25 fragment that is necessary for formation of the cytosolic TDP-43-positive aggregates in cells containing the full-length TDP-43 at an elevated level close to that found in patients with TDP-43 proteinopathies. A comprehensive model of the metabolism and mis-metabolism of TDP-43 in relation to these findings is presented.
Effects of a 10-week in-season eccentric-overload training program on muscle-injury prevention and performance in junior elite soccer players.

PURPOSE To analyze the effect of an eccentric-overload training program (ie, half-squat and leg-curl exercises using flywheel ergometers) with individualized load on muscle-injury incidence and severity and performance in junior elite soccer players. METHODS Thirty-six young players (U-17 to U-19) were recruited and assigned to an experimental (EXP) or control group (CON). The training program consisted of 1 or 2 sessions/wk (3-6 sets with 6 repetitions) during 10 wk. The outcome measured included muscle injury (incidence per 1000 h of exposure and injury severity) and performance tests (countermovement jump [CMJ], 10-m and 20-m sprint test). RESULTS Between-groups results showed a likely (ES: 0.94) lower number of days of absence per injury and a possible decrement of incidence per 1000 h of match play in EXP than in CON. Regarding muscle performance, a substantial better improvement (likely to very likely) was found in 20-m sprint time (ES: 0.37), 10-m flying-sprint time (ES: 0.77), and CMJ (ES: 0.79) for EXP than for CON. Within-group analysis showed an unclear effect in each variable in CON. Conversely, substantial improvements were obtained in CMJ (ES: 0.58), 20-m sprint time (ES: 0.32), 10-m flying-sprint time (ES: 0.95), and injury severity (ES: 0.59) in EXP. Furthermore, a possible decrement in total injury incidence was also reported in EXP. CONCLUSIONS The eccentric-based program led to a reduction in muscle-injury incidence and severity and showed improvements in common soccer tasks such as jumping ability and linear-sprinting speed.