Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell death in amyotrophic lateral sclerosis: interplay between neuronal and glial cells

Mutations in the gene coding for the ubiquitous, anti‐oxidant enzyme Cu,Zn superoxide dismutase (SOD1) are associated with familial amyotrophic lateral sclerosis (fALS), a fatal disease characterized by selective loss of motor neurons. Expression of a mutant SOD1 typical of fALS patients restricted to either motor neurons or astrocytes is insufficient to generate a pathological phenotype in mouse models, suggesting that a deleterious interplay between different cell types is necessary for the pathogenesis of the disease. In this study, we demonstrate the actual role of a functional cross‐talk between glial and neuronal cells expressing fALS mutant G93A‐SOD1, where an increase in the production of reactive oxygen species occurs. We show that human glioblastoma cells expressing G93A‐SOD1 induce activation of caspase‐1, release of cytokines, and activation of apoptotic pathways in cocultured human neuroblastoma cells also expressing G93A‐SOD1. Activation of caspase‐1 and caspase‐3 is observed also in neuroblastoma lines expressing other fALS‐SOD1s (G37R, G85R, and I113T) cocultured with glioblastoma lines expressing the corresponding mutant enzymes. These effects are consequent to activation of inflammatory processes in G93A‐glioblastoma cells stimulated by cocultured G93A‐neuroblastoma. Furthermore, selective death of embryonal spinal motor neurons from G93A‐SOD1 transgenic mice is induced by coculture with G93A‐glioblastoma and prevented by inhibition of NO synthase. Proinflammatory cytokines, interferon‐‐γ and nitric oxide are among the molecular signals exchanged between glial and neuronal cells that generate a functional interplay between the two cell types. This cross‐talk may be crucial for the pathogenesis of SOD1‐linked fALS but also for the more common sporadic form of the disease, where markers of increased oxidative stress and of glial activation have been found.
Public Service Delivery in the Era of Digital Governance

In an era of digital governance, information technology, internet, mobile devices, and social media have transformed the organization, management, and delivery of public services. Developing country governments around the world are gradually replacing paper-based processing and delivery with next-generation technologies to serve citizens. In Indonesia, a host of citizen-led approaches have emerged ahead of government process transformation efforts. This global expert team (GET) note examines case studies of digital-era governance (DEG), a concept put forward by Dunleavy, further developed by means of examples from Indonesia focusing on demand-side approaches to stimulate improvements in public sector performance.
Die Förderung von motivationsunterstützendem Unterricht - Ansatzpunkte und Barrieren

Lehrkrafte schatzen das Motivierungsgeschehen im Unterricht anders ein als eine Klasse. Um den Unterricht auf die Lernenden ausrichten zu konnen, brauchen sie allerdings Informationen uber deren Wahrnehmung. Mit dieser Interventionsstudie wurde untersucht, inwieweit Lehrkrafte mit Hilfe eines Monitoring-/Ruckmeldeverfahrens ein stimmiges Bild uber die Lernmotivation und die motivationsunterstutzenden Unterrichtsbedingungen entwickeln. Die Arbeit basiert auf der Selbstbestimmungstheorie der Motivation (Deci & Ryan, 1993) sowie der padagogischen Interessentheorie (Krapp & Prenzel, 1992) und wurde im Rahmen eines sechsjahrigen DFG-Projektes (Selbstbestimmt motiviertes und interessiertes Lernen in der kaufmannischen Erstausbildung) erstellt. Es werden Ergebnisse der einjahrigen, experimentellen Interventionsstudie berichtet (38 Schulklassen, N = 727, zwei kaufmannische Berufsschulklassen). Erwartet wurde, dass sich die Wahrnehmungsunterschiede zwischen Lehrkraft und Klasse verringern. Weiterhin wurde vermutet, dass die Lehrpersonen fur das Motivierungsgeschehen sensibilisiert werden und den Unterricht vermehrt auf die kognitiven und motivationalen Bedurfnisse der Auszubildenden ausrichten. In acht von 18 Experimentalklassen zeigt sich die erwartete Verringerung der Wahrnehmungsdifferenzen. In diesen Klasse erlebten sich am Ende der Intervention etwas mehr Auszubildende haufig motivationsunterstutzt, und die Zahl der eher selbstbestimmt motivierten Lernenden nahm ebenso leicht zu. Abschlussinterviews mit den Lehrkraften gaben Hinweise darauf, dass in Interventionsmasnahmen und die damit verbundenen Anregungen unterschiedlich aufgenommen und genutzt wurden; die angegebenen Barrieren werden berichtet. Auf der Basis der gewonnenen Erfahrungen werden Schlussfolgerungen fur die padagogische Praxis gezogen. Es wird ein Modell fur die erfolgversprechende Implementation des Monitoringverfahrens als Instrument der Unterrichtsentwicklung vorgeschlagen.
Comprehensive Pharmacogenomic Profiling of Malignant Pleural Mesothelioma Identifies a Subgroup Sensitive to FGFR Inhibition

Purpose: Despite intense research, treatment options for patients with mesothelioma are limited and offer only modest survival advantage. We screened a large panel of compounds in multiple mesothelioma models and correlated sensitivity with a range of molecular features to detect biomarkers of drug response. Experimental design: We utilized a high-throughput chemical inhibitor screen in a panel of 889 cancer cell lines, including both immortalized and primary early-passage mesothelioma lines, alongside comprehensive molecular characterization using Illumina whole-exome sequencing, copy-number analysis and Affymetrix array whole transcriptome profiling. Subsequent validation was done using functional assays such as siRNA silencing and mesothelioma mouse xenograft models. Results: A subgroup of immortalized and primary MPM lines appeared highly sensitive to FGFR inhibition. None of these lines harbored genomic alterations of FGFR family members, but rather BAP1 protein loss was associated with enhanced sensitivity to FGFR inhibition. This was confirmed in an MPM mouse xenograft model and by BAP1 knockdown and overexpression in cell line models. Gene expression analyses revealed an association between BAP1 loss and increased expression of the receptors FGFR1/3 and ligands FGF9/18. BAP1 loss was associated with activation of MAPK signaling. These associations were confirmed in a cohort of MPM patient samples. Conclusions: A subgroup of mesotheliomas cell lines harbor sensitivity to FGFR inhibition. BAP1 protein loss enriches for this subgroup and could serve as a potential biomarker to select patients for FGFR inhibitor treatment. These data identify a clinically relevant MPM subgroup for consideration of FGFR therapeutics in future clinical studies. Clin Cancer Res; 24(1); 84–94. ©2017 AACR.
Insulin‐like growth factor‐I‐stimulated Akt phosphorylation and oligodendrocyte progenitor cell survival require cholesterol‐enriched membranes

Previously we showed that insulin‐like growth factor‐I (IGF‐I) promotes sustained phosphorylation of Akt in oligodendrocyte progenitor cells (OPCs) and that Akt phosphorylation is required for survival of these cells. The direct mechanisms, however, by which IGF‐I promotes Akt phosphorylation are currently undefined. Recently, cholesterol‐enriched membranes (CEMs) have been implicated in regulation of growth factor‐mediated activation of the PI3K/Akt pathway and survival of mature oligodendrocytes; however, less is know about their role in OPC survival. In the present study, we investigate the role of CEMs in IGF‐I‐mediated Akt phosphorylation and OPC survival. We report that acute disruption of membrane cholesterol with methyl‐β‐cyclodextrin results in altered OPC morphology and inhibition of IGF‐I‐mediated Akt phosphorylation. We also report that long‐term inhibition of cholesterol biosynthesis with 25‐hydroxycholesterol blocks IGF‐I stimulated Akt phosphorylation and cell survival. Moreover, we show that the PI3K regulatory subunit, p85, Akt, and the IGF‐IR are sequestered within cholesterol‐enriched fractions in steady‐state stimulation of the IGF‐IR and that phosphorylated Akt and IGF‐IR are present in cholesterol‐enriched fractions with IGF‐I stimulation. Together, the results of these studies support a role for CEMs or “lipid rafts” in IGF‐I‐mediated Akt phosphorylation and provide a better understanding of the mechanisms by which IGF‐I promotes OPC survival. © 2009 Wiley‐Liss, Inc.
Role of Calpain in Human Sperm Activated by Progesterone for Fertilization

Abstract We evaluated the activation of calpain in progesterone activated human sperm. Semen collected from fertile donors with informed consent was liquefied and subjected to percoll gradient centrifugation. After exposure to different concentrations of progesterone, the samples were used for immunostaining, SDSPAGE and Western blot analysis. An increase of the intracellular free calcium concentration in the sperm following the addition of progesterone was observed using fura-2 AM. Immunostaining using an antibody against active calpain produced 6 distinct staining patterns: (1) the acrosome, (2) an equatorial segment, (3) the whole head, (4) the neck, (5) the neck and tail or (6) unstained sperm. After addition of progesterone, the predominant type changed from the neck type (90%) to the neck and tail type (79%). Western blot analysis using a procalpain and a calpain domain III antibody revealed autodigestion of calpain, indicating activation by progesterone. Using calpainspecific inhibitors it was shown that calpain activation contributes to sperm motility as well as to the acrosome reaction. These results suggest the possibility that activation of calpain in human sperm by progesterone plays an important role in fertilization.
IL-10-Producing B220+CD11c− APC in Mouse Spleen1

APC acting at the early stages of an immune response can shape the nature of that response. Such APC will include dendritic cells (DCs) but may also include populations of B cells such as marginal zone B cells in the spleen. In this study, we analyze APC populations in mouse spleen and compare the phenotype and function of B220+CD11c− populations with those of CD11c+ spleen DC subsets. Low-density B220+ cells had morphology similar to DCs and, like DCs, they could stimulate naive T cells, and expressed high levels of MHC and costimulatory molecules. However, the majority of the B220+ cells appeared to be of B cell lineage as demonstrated by coexpression of CD19 and surface Ig, and by their absence from RAG-2−/− mice. The phenotype of these DC-like B cells was consistent with that of B cells in the marginal zone of the spleen. On bacterial stimulation, they preferentially produced IL-10 in contrast to the DCs, which produced IL-12. Conventional B cells did not produce IL-10. The DC-like B cells could be induced to express low levels of the DC marker CD11c with maturational stimuli. A minority of the B220+CD11c− low-density cells did not express CD19 and surface Ig and may be a DC subset; this population also produced IL-10 on bacterial stimulation. B220+ APC in mouse spleen that stimulate naive T cells and preferentially produce IL-10 may be involved in activating regulatory immune responses.
A novel technique for removal of high density impulse noise from digital images

Mostly researchers use all pixels within a window to filter out the impulse noise. They increase the size of neighboring pixels with the increase of noise density. However, this estimate of all neighboring pixels does not give promsing results for high level of noise density. In contrast, in the paper, we propose impulse noise removal scheme that emphasizes on few noise-free pixels. The proposed iterative algorithm search the noise-free pixels within a small neighborhood. The noisy-pixel is then repalced with the average estimated from noise-free pixels. The iterative process continues until all noisy-pixels of the corrupted image are filtered. The performance of the proposed method is tested using various impulse noise corrupted images. The simulation results show the proposed scheme is capable of removing high density of impulse noise effectively while preserving the fine image details.
A Reliable Low-Overhead MAC Protocol for Multi-Channel Wireless Mesh Networks

This paper proposes a multi-channel medium access control (MAC) protocol for wireless mesh networks (WMNs) by using busy tones to prevent data packet collisions at data channels. Multi-channel MAC schemes can achieve higher network throughput than single channel MAC schemes in multi- hop wireless networks. It is especially appealing to exploit multiple channels in WMNs which has high capacity requirement to support backbone multimedia applications. Most previously proposed MAC protocols make use of the RTS/CTS mechanism to deal with data packet collisions caused by exposed/hidden terminal problems in multi-hop environment. However, when multiple channels are used for data transmissions, the traditional RTS/CTS mechanism can no longer handle the exposed/hidden terminal successfully. By investigating the special features of WMN architecture, we apply the busy tone solution into the medium access control mechanism for WMNs, in which mesh nodes have no limit on power consumption. In this paper, we clearly presented the idea and operation of our proposed multichannel MAC protocol for WMNs. Comprehensive simulations are conducted to investigate the effects of various factors on the system performance. Also, the performance of our proposed mechanism is compared with that of previous RTS/CTS-based MAC protocols.
Potent co-operation between the NUP98-NSD1 fusion and the FLT3-ITD mutation in acute myeloid leukemia induction

The NUP98-NSD1 fusion, product of the t(5;11)(q35;p15.5) chromosomal translocation, is one of the most prevalent genetic alterations in cytogenetically normal pediatric acute myeloid leukemias and is associated with poor prognosis. Co-existence of an FLT3-ITD activating mutation has been found in more than 70% of NUP98-NSD1-positive patients. To address functional synergism, we determined the transforming potential of retrovirally expressed NUP98-NSD1 and FLT3-ITD in the mouse. Expression of NUP98-NSD1 provided mouse strain-dependent, aberrant self-renewal potential to bone marrow progenitor cells. Co-expression of FLT3-ITD increased proliferation and maintained self-renewal in vitro. Transplantation of immortalized progenitors co-expressing NUP98-NSD1 and FLT3-ITD into mice resulted in acute myeloid leukemia after a short latency. In contrast, neither NUP98-NSD1 nor FLT3-ITD single transduced cells were able to initiate leukemia. Interestingly, as reported for patients carrying NUP98-NSD1, an increased Flt3-ITD to wild-type Flt3 mRNA expression ratio with increased FLT3-signaling was associated with rapidly induced disease. In contrast, there was no difference in the expression levels of the NUP98-NSD1 fusion or its proposed targets HoxA5, HoxA7, HoxA9 or HoxA10 between animals with different latencies to develop disease. Finally, leukemic cells co-expressing NUP98-NSD1 and FLT3-ITD were very sensitive to a small molecule FLT3 inhibitor, which underlines the significance of aberrant FLT3 signaling for NUP98-NSD1-positive leukemias and suggests new therapeutic approaches that could potentially improve patient outcome.
State of health estimation of Li-ion batteries using Electrochemical Impedance Spectroscopy

Since, batteries have a limited lifetime, repeated charge and discharge cycles quickly deteriorate the electrochemical properties of a battery. With the reduced capacity and several other changes in the state of health of a battery, the electronic device under operation might malfunction. The failure of electronic device during the operation can cause serious repercussions to the users in certain applications. This research was aimed to provide upgrade on Electrochemical Impedance Spectroscopy (EIS) technology to decipher the electrolytic properties and electrochemical health of the battery. The focus of this research was to design a test bet to gather experimental data of EIS scans of batteries with varying State of Health. Based on the footprints of scans, a state of health classification algorithm was proposed which categorized batteries according to the corresponding health of the battery. Tests were performed on hardware prototype to validate the designed algorithm that showed State of Health estimation accuracy of almost 90%. The main contribution of this project to existing EIS technology is the eradication of the requirement of battery modeling and parameter estimations from Nyquist plot to find the state of health of a battery (the remaining capacity of the battery). The proposed method simplifies the computational algorithm and reduces the processing time for rapid battery tester.
Enhancement of temporal and spatial synchronization of entorhinal gamma activity by phase reset

The synchronization of cortical gamma oscillatory activity (25–80 Hz) is thought to coordinate neuronal assemblies in the processing and storage of information. The mechanism by which independently oscillating and distantly located cortical zones become synchronized is presumed to involve activity in corticocortical connections, although evidence supporting this conjecture has only been indirect. In the present study, we show that activation of synaptic inputs within and to the medial entorhinal cortex (mEC) of the in vitro isolated guinea pig brain preparation resets the phase of ongoing gamma activity induced by muscarinic receptor agonism with carbachol (frequency: 24 ± 2 Hz at 32°C). Phase reset was associated with a transient enhancement of the synchronization of gamma activity recorded at distant (>1 mm) mEC sites, across which low coherence (>0.75) was observed before stimulation. This increase in synchronization, as measured by cross‐correlation analysis, was restricted to a maximal period of 200 ms after either local mEC or CA1 afferent stimulation. The results provide direct evidence that synaptic activation can enhance the rhythmic synchronization of spatially remote, independently oscillating neuronal assemblies in the mEC through a mechanism of synaptically evoked phase reset. Dynamic functional grouping of oscillatory discharges across long distances in the mEC may underlie coding processes involved in the integration and storage of incoming information and thus may be important for the role of this region in memory processes. Hippocampus 2002;12:447–456. © 2002 Wiley‐Liss, Inc.
Joint Power Control and Beamforming for Uplink Non-Orthogonal Multiple Access in 5G Millimeter-Wave Communications

In this paper, we investigate the combination of two key enabling technologies for the fifth generation wireless mobile communication, namely millimeter-wave (mm-wave) communications and non-orthogonal multiple access (NOMA). In particular, we consider a typical two-user uplink mm-wave-NOMA system, where the base station equips an analog beamforming structure with a single radio-frequency chain and serves two NOMA users. An optimization problem is formulated to maximize the achievable sum rate of the two users while ensuring a minimal rate constraint for each user. The problem turns to be a joint power control and beamforming problem, i.e., we need to find the beamforming vectors to steer to the two users simultaneously subject to an analog beamforming structure, and meanwhile control appropriate power on them. As direct search for the optimal solution of the non-convex problem is too complicated, we propose decomposing the original problem into two sub-problems that are relatively easy to solve: one is a power control and beam gain allocation problem, and the other is an analog beamforming problem under a constant-modulus constraint. The rationale of the proposed solution is verified by extensive simulations, and the performance evaluation results show that the proposed sub-optimal solution achieves a close-to-bound uplink sum-rate performance.
Enterovirus infections are associated with the induction of β‐cell autoimmunity in a prospective birth cohort study

Enterovirus infections have been associated with the manifestation of clinical type 1 diabetes in a number of reports, and recent prospective studies have suggested that enterovirus infections may initiate the autoimmune process, leading to the disease. In the present study, we analyzed the role of enterovirus infections in a Finnish birth cohort study, Diabetes Prediction and Prevention (DIPP), in which all newborn infants are screened for diabetes‐associated HLA‐DQB1 alleles, and those with an increased genetic risk are invited for prospective follow‐up. Enterovirus infections were diagnosed by serology and reverse transcriptase‐polymerase chain reaction (RT‐PCR) from serum samples taken from birth every 3–6 months. Case children included 41 infants who became positive for diabetes‐associated autoantibodies during the observation. Control children comprised altogether 196 infants who remained autoantibody negative and were matched for the time of birth, sex, and HLA‐DQB1 alleles. Enterovirus infections were more frequent in case children than in control children (P = 0.004), and the average enterovirus antibody levels were also higher in the case children (P = 0.003). Enterovirus infections were particularly frequent during the 6‐month period preceding the first detection of autoantibodies: 51% of the case children compared with 28% of the control children had an infection in that time interval (P = 0.003). There was no difference in the frequency of adenovirus infections between the groups (P = 0.9). The present results imply that enterovirus infections are associated with the appearance of β‐cell autoantibodies. A possible causal relationship is supported by the clustering of infections to the time when autoantibodies appeared. J. Med. Virol. 69:91–98, 2003. © 2003 Wiley‐Liss, Inc.
Cognitive reactivity to sad mood provocation and the prediction of depressive relapse.

CONTEXT Episode remission in unipolar major depression, while distinguished by minimal symptom burden, can also be a period of marked sensitivity to emotional stress as well as an increased risk of relapse. OBJECTIVE To examine whether mood-linked changes in dysfunctional thinking predict relapse in recovered patients who were depressed. DESIGN In phase 1 of this study, patients with major depressive disorder were randomly assigned to receive either antidepressant medication or cognitive behavior therapy. In phase 2, patients who achieved clinical remission underwent sad mood provocation and were then observed with regular clinical assessments for 18 months. SETTING Outpatient psychiatric clinics at the Centre for Addiction and Mental Health, Toronto, Ontario. PARTICIPANTS A total of 301 outpatients with major depressive disorder, aged 18 to 65 years, participated in phase 1 of this study and 99 outpatients with major depressive disorder in remission, aged 18 to 65 years, participated in phase 2. MAIN OUTCOME MEASURE Occurrence of a relapse meeting DSM-IV criteria for a major depressive episode as assessed by the longitudinal interval follow-up evaluation and a Hamilton Depression Rating Scale score of 16 or greater. RESULTS Patients who recovered through antidepressant medication showed greater cognitive reactivity following the mood provocation than those who received cognitive behavior therapy. Regardless of type of prior treatment, the magnitude of mood-linked cognitive reactivity was a significant predictor of relapse over the subsequent 18 months. Patients whose mood-linked endorsement of dysfunctional attitudes increased by a minimum of 8 points had a significantly shorter time to relapse than those whose scores were not as elevated. CONCLUSIONS The vulnerability of remitted depressed patients for illness relapse may be related to the (re)activation of depressive thinking styles triggered by temporary dysphoric states. This is the first study to link such differences to prognosis following successful treatment for depression. Further understanding of factors predisposing to relapse/recurrence in recovered patients may help to shorten the potentially lifelong course of depression.