Miracle-dz/UniFAR-FTUs huggingface dataset:
PINK1 suppresses alpha-synuclein-induced neuronal injury: a novel mechanism in protein phosphatase 2A activation

Alpha-synuclein (α-Syn) and phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced putative kinase (PINK) 1 are proteins found in Lewy bodies, which are a pathological hallmark of Parkinson’s disease (PD). PINK1 overexpression suppresses α-Syn-induced phenotypes and increases lifespan and health in an animal model of PD. It has been suggested that the two proteins regulate protein phosphatase (PP) 2A activity, but the underlying mechanisms and neuroprotective action of PP2A against PD-associated pathology are unknown. We found that α-Syn overexpression in SK-N-SH neuroblastoma cells and primary cortical neurons caused mitochondrial dysfunction and cell injury via phosphorylation of PP2A at Tyr307 and inhibition of its activity. Concomitant overexpression of PINK1 reversed this effect and restored the activity. The level of phospho-activated Src was increased in cells overexpressing α-Syn, which was reversed by co-expressing PINK1, suggesting that the latter suppressed α-Syn-induced PP2A inactivation by inhibiting Src activity. Calmodulin/Src complex formation was also enhanced in α-Syn-overexpressing cells, which was reversed by co-expression of PINK1 as a result of reduced mitochondrial Ca2+ releasing. Interestingly, the protective effects of PINK1 in α-Syn induced models were abolished by treatment with the PP2A inhibitor okadaic acid, indicating that PP2A is a target of PINK1. These findings indicate that PINK1 protects against α-Syn-induced neurodegeneration by promoting the dissociation of the calmodulin/Src complex and inhibiting Src, thereby enhancing PP2A activity. This was supported by the observation that PP2A activity was decreased in PD patients, which was negatively correlated with Hoehn and Yahr scores. Our results provide novel insight into the mechanisms underlying neurodegeneration in PD as well as possible avenues for therapeutic intervention in the treatment of this disease.
The effects of monosodium glutamate and aspartame on rat hippocampal N-methyl-D-aspartate receptor subunits and oxidative stress biomarkers

Object: Food additives have been used widely for promotion of food safety, flavoring and coloring. We aimed to investigate the effects of Monosodium Glutamate and Aspartame on hippocampal N-methyl D-aspartate receptor subunits and serum antioxidant enzymes and total oxidative stress indices. Materials and methods: Rats were randomly divided into four groups: Control, MSG (Monosodium Glutamate: 120 mg/kg), ASP (Aspartame: 40 mg/kg) and MSG + ASP for 8 weeks. NMDA receptor subunits, the oxidative stress indices and serum parameters were measured in hippocampal tissue and serum. Results: MSG and ASP consumption significantly increased MDA and NMDA receptor subunit levels (NR1, NR2A and NR2B) in hippocampus and decreased serum SOD and GSH-Px activities. There was no significant difference in serum MDA levels and total oxidative stress indices. Conclusion: MSG and ASP consumption alters NMDA receptor levels and may contribute to the pathogenesis of some neurodegenerative disorders via excitotoxicity.
Does competition for nanomolar phosphate supply explain the predominance of the cyanobacterium Synechococcus?

Experimental work during a cruise along a W‐E transect in the Mediterranean Sea suggests that (1) orthophosphate concentrations in the upper photic zone show a decreasing trend from the west to the east reaching levels well below 1 nM and (2) microorganisms in the 0.6–2ߝµm size fraction, probably Synechococcus, have, in addition to high affinity for orthophosphate, significantly higher maximum uptake rates than heterotrophic bacteria or eukaryotic algae. These specific advantages concerning orthophosphate uptake at low (<5 nM) as well as at relatively high (5–25 nM) concentrations could explain both general Synechococcus abundance in P‐depleted environments and transient blooms of this species in the open ocean where episodic orthophosphate nanopulse events are likely to occur.
Training Deep Neural Networks for Reverberation Robust Speech Recognition

Recently hybrid systems of deep neural networks (DNNs) and hidden Markov models (HMMs) have shown state of the art results on various speech recognition tasks. Best results were achieved by training large neural networks (NNs) on huge data sets ( ≥ 2000h [11, 16, 20]). The required training data is often generated using different methods of data augmentation. We show that a simple approach using room impulse response (RIR) can be used to train systems more robust to reverberation. The method does not require multiple microphones or complex signal processing techniques. On a test set simulating large rooms we show improvements from 59.7% word error rate (WER) down to 41.9%. In case of known large lectures rooms with varying microphone positions the approach can be used to adopt the system to the environment. We compare systems trained with RIRs from one room, multiple rooms and simulated rooms.
Modal analysis/filtering to estimate time-varying MIMO-OFDM channels

In the multipatb multiple-input multiple-output (MIMO) channel, long-term/large-scale properties (e.g., delays, angles, powers) remain approximately constant over many coherence times (i.e., over many Doppler periods) and define the structural terms of the propagation channel referred as delay (powers and delays) and angular (powers and angles of departure and arrival) modes of the channel. Effective improvement of the channel estimate is obtained by estimating delay and angular modal spaces via modal analysis and by filtering the (original) least squares channel estimates as projection onto the modal spaces. The paper also provides experimental validation of the overall method with realistic channel models
Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations.

CONTEXT Germline mutations of the genes encoding succinate dehydrogenase subunits B (SDHB) and D (SDHD) predispose to paraganglioma syndromes type 4 (PGL-4) and type 1 (PGL-1), respectively. In both syndromes, pheochromocytomas as well as head and neck paragangliomas occur; however, details for individual risks and other clinical characteristics are unknown. OBJECTIVE To determine the differences in clinical features in carriers of SDHB mutations and SDHD mutations. DESIGN, SETTING, AND PATIENTS Population-based genetic screening for SDHB and SDHD germline mutations in 417 unrelated patients with adrenal or extra-adrenal abdominal or thoracic pheochromocytomas (n = 334) or head and neck paragangliomas (n = 83), but without syndromic features, from 2 registries based in Germany and central Poland, conducted from April 1, 2000, until May 15, 2004. MAIN OUTCOME MEASURES Demographic and clinical findings with respect to gene mutation in SDHB vs SDHD compared with nonmutation carriers. RESULTS A total of 49 (12%) of 417 registrants carried SDHB or SDHD mutations. In addition, 28 SDHB and 23 SDHD mutation carriers were newly detected among relatives of these carriers. Comparison of 53 SDHB and 47 SDHD total mutation carriers showed similar ages at diagnosis but differences in penetrance and of tumor manifestations. Head and neck paragangliomas (10/32 vs 27/34, respectively, P<.001) and multifocal (9/32 vs 25/34, respectively, P<.001) tumors were more frequent in carriers of SDHD mutations. In contrast, SDHB mutation carriers have an increased frequency of malignant disease (11/32 vs 0/34, P<.001). Renal cell cancer was observed in 2 SDHB mutation carriers and papillary thyroid cancer in 1 SDHB mutation carrier and 1 SDHD mutation carrier. CONCLUSIONS In contrast with SDHD mutation carriers (PGL-1) who have more frequent multifocal paragangliomas, SDHB mutation carriers (PGL-4) are more likely to develop malignant disease and possibly extraparaganglial neoplasias, including renal cell and thyroid carcinomas. Appropriate and timely clinical screening is recommended in all patients with PGL-1 and PGL-4.
Using qualitative data to enhance our understanding of the reasons young people decline Structured Diabetes Education programmes

AIM To explore the reasons young people with type 1 diabetes decline Structured Diabetes Education from the perspectives of the young people themselves, their parents and diabetes educators. BACKGROUND Structured Diabetes Education programmes that are evidence based and quality assured are a key component to empowering people with diabetes to self-manage effectively. However, research reveals that uptake of structured education programmes is disappointingly low. DESIGN Qualitative cross-sectional study involving participants from Northern Ireland and England. METHODS Twenty young people with type 1 diabetes (13-22 years) who had declined Structured Diabetes Education within the past 2 years, 17 parents of a young person with type 1 diabetes and 16 diabetes educators participated in semistructured interviews and focus groups. RESULTS Three main themes emerged from across all three groups: timing, access and communication issues. In addition, a lack of understanding by the referrer was cited by some young people and their parents. Diabetes educators were sympathetic and understood many of the reasons why Structured Diabetes Education was declined. Solutions were proposed to overcome expressed barriers. CONCLUSIONS Although the expressed reasons for declining might suggest that the young people simply did not prioritise education, this study adds a more nuanced scenario to the debate. The interviews revealed the tensions that exist between people's daily commitments and their need to self-manage their diabetes. The young people and their parents must be given a much stronger sense of the importance of Structured Diabetes Education and ways to accommodate attendance must be sought. Diabetes educators must be able to better promote the importance of Structured Diabetes Education. RELEVANCE TO CLINICAL PRACTICE As optimal glycaemic control is so vital for long-term health, there is an urgent need to understand how to respond more fully to the needs of young people who have type 1 diabetes.
The effect of anonymity on the WTA - WTP gap in endowment effect games

The Effect of Anonymity on the WTA – WTP Gap in Endowment Effect Games. (May 2012) Gregory Cohen Department of Economics Texas A&M University Research Advisor: Dr. Alex Brown Department of Economics I conducted experiments to determine whether anonymity affects the gap between the willingness to accept (WTA) and willingness to pay (WTP) in endowment effect games. Earlier research theorizes complete anonymity is necessary to eliminate the contamination of “signaling” within the endowment effect game. The “signaling” results when buyers over-value their items and sellers under-value the items they are trading for to signal they are good bargainers, which leads to suboptimal decisions. I find that the difference between an anonymous treatment and a non-anonymous treatment yield WTA – WTP gaps that are not statistically significant. I utilize a dictator game to ensure my anonymity procedure is sufficient.
LRP1 Suppresses Bone Resorption in Mice by Inhibiting the RANKL‐Stimulated NF‐κB and p38 Pathways During Osteoclastogenesis

Single‐nucleotide polymorphisms in the LRP1 gene coding sequence are associated with low bone mass, and cell culture studies suggest that LRP1 plays a role in osteoblast proliferation and osteoblast‐mediated osteoclastogenesis. However, the in vivo function of LRP1 in bone homeostasis has not been explored. In this work, we studied the osteoclast‐specific role of LRP1 in bone homeostasis using a Ctsk‐Cre;Lrp1f/f mouse model on the C57BL/6J background. These mice had a dramatically decreased trabecular bone mass with markedly more osteoclasts, while the osteoblast activity was unaffected or slightly increased. The cortical bone parameters were largely unaltered. Upon RANKL treatment, Lrp1‐deficient bone marrow monocytes more efficiently differentiated into osteoclasts and showed elevated p65 NFκB and p38 signaling. Consistently, Lrp1‐overexpressing Raw264.7 cells were desensitized to RANKL‐induced p38 and p65 activation and osteoclastogenesis. Moreover, RANKL treatment led to a sharp decrease of LRP1 protein and RNA in BMMs. Overall, our data suggest that osteoclast‐expressed LRP1 is a crucial regulator of bone mass. It inhibits the NFκB and p38 pathways and lessens the efficiency of RANKL‐induced osteoclastogenesis. © 2018 American Society for Bone and Mineral Research.
Consumer health organisations for chronic conditions: why do some people access them and others don’t?

Background Consumer health organisations (CHOs), which operate outside the mainstream healthcare system with a specific focus on supporting people to self-manage their health conditions, have become widespread. Yet, there has been little systematic research into CHOs, including their perceived benefits and barriers, which encourage or deter their access by people with a variety of chronic health conditions. Aim This study explored the benefits of CHOs in self-management and also the barriers that inhibit their access, from the perspective of people with chronic conditions and their unpaid carers. Methods In-depth, semi-structured interviews were completed with 97 participants across four regions of Australia. The sample included a high representation of people from culturally and linguistically diverse backgrounds and Aboriginal and Torres Strait Islander people as well as non-indigenous Australians. Findings Three inter-related themes were identified that represented the benefits of involvement and participation in CHOs: knowledge and information, connection and support and experiential learning. However, limited access pathways emerged as a barrier that inhibited a person’s entry into CHOs. Furthermore, the person’s beliefs and experiences about their own health condition(s) also inhibited their continued participation in CHO programmes. Conclusion Although our findings confirm that CHOs are a valuable resource in alleviating the ‘work of being a patient’ for some people, there seems to be some barriers that prevent their full access and utilisation. Structured integration systems to increase the reliable delivery and accessibility of CHOs are needed to ensure that people who would benefit from accessing them can do so.
Scale-Out Acceleration for Machine Learning

The growing scale and complexity of Machine Learning (ML) algorithms has resulted in prevalent use of distributed general-purpose systems. In a rather disjoint effort, the community is focusing mostly on high performance single-node accelerators for learning. This work bridges these two paradigms and offers CoSMIC, a full computing stack constituting language, compiler, system software, template architecture, and circuit generators, that enable programmable acceleration of learning at scale. CoSMIC enables programmers to exploit scale-out acceleration using FPGAs and Programmable ASICs (P-ASICs) from a high-level and mathematical Domain-Specific Language (DSL). Nonetheless, CoSMIC does not require programmers to delve into the onerous task of system software development or hardware design. CoSMIC achieves three conflicting objectives of efficiency, automation, and programmability, by integrating a novel multi-threaded template accelerator architecture and a cohesive stack that generates the hardware and software code from its high-level DSL. CoSMIC can accelerate a wide range of learning algorithms that are most commonly trained using parallel variants of gradient descent. The key is to distribute partial gradient calculations of the learning algorithms across the accelerator-augmented nodes of the scale-out system. Additionally, CoSMIC leverages the parallelizability of the algorithms to offer multi-threaded acceleration within each node. Multi-threading allows CoSMIC to efficiently exploit the numerous resources that are becoming available on modern FPGAs/P-ASICs by striking a balance between multi-threaded parallelism and single-threaded performance. CoSMIC takes advantage of algorithmic properties of ML to offer a specialized system software that optimizes task allocation, role-assignment, thread management, and internode communication. We evaluate the versatility and efficiency of CoSMIC for 10 different machine learning applications from various domains. On average, a 16-node CoSMIC with UltraScale+FPGAs offers 18.8× speedup over a 16-node Spark system with Xeon processors while the programmer only writes 22–55 lines of code. CoSMIC offers higher scalability compared to the state-of-the-art Spark; scaling from 4 to 16 nodes with CoSMIC yields 2.7× improvements whereas Spark offers 1.8×. These results confirm that the full-stack approach of CoSMIC takes an effective and vital step towards enabling scale-out acceleration for machine learning.
Genomic resources and microarrays for the common carp Cyprinus carpio L.

The common carp is an important fish species satisfying ornamental, food and recreational fisheries’ needs worldwide, but in common with other cyprinid fishes, it is particularly renowned for its environmental tolerance. Investigating the mechanistic basis of growth, disease and environmental tolerance is greatly enhanced by access to a comprehensive list of gene sequences and post-genomic technologies. The current status of genomic resources is described for this species including 40 k cDNA clone collections, their associated expressed sequence tags (ESTs) and a developing series of 13 k–26 k cDNA microarrays fabricated from amplicons. The arrays have been directed at questions of response to environmental stress (cold and hypoxia), viral and bacterial disease and ectoparasite infection. Consequently, clones from a wide range of tissues were prepared. The authors discuss how these resources were generated and their application. Evidence is presented supporting that the carp microarray may also be useful as a heterologous set of probes in studies of other fish species.
Relationship between Asymmetry of Gait and Muscle Torque in Patients after Unilateral Transfemoral Amputation

Many studies have shown that unilateral transfemoral amputation involves asymmetric gait. Transfemoral amputation leads to muscle atrophy in a tight stump resulting in asymmetry in muscle torque between the amputated and intact limb. This research is aimed at verifying if a relationship between torque values of hip joint flexors and extensors and gait asymmetry in patients with TFA exists. Fourteen adult subjects with unilateral TFA took part in the experiment. Gait symmetry was evaluated based on the ground reaction force (GRF). Measurements of muscle torque of hip flexors and extensors were taken with a Biodex System. All measurements were taken under isokinetic (60°/s and 120°/s) and isometric conditions. The symmetry index of vertical GRF components was from 7.5 to 11.5%, and anterio-posterior GRF from 6.2 to 9.3%. The symmetry index for muscle torque was from 24.3 to 44% for flexors, from 39 to 50.5% for extensors, and from 28.6 to 50% in the flexor/extensor ratio. Gait asymmetry correlated with muscle torque in hip joint extensors. Therapy which enhances muscle torque may be an effective form of patient therapy. The patient needs to undergo evaluation of their muscle strength and have the therapy programme adjusted to their level of muscle torque deficit.
European symposium on the awareness of allergy: report of the promotional campaign in the European Parliament (26–28 April 2016)

From 26 to 28 of April 2016, an allergy awareness campaign was organized by the European Academy of Allergy and Clinical Immunology and the European Federation of Allergy and Airway Diseases Patients Associations in the European Parliament in Brussels, with support of the European Parliament's Interest group on Allergy and Asthma and was co‐hosted by the Members of the European Parliament David Borrelli, Sirpa Pietikainen and Nessa Childers. Skin prick tests (SPTs) were performed to gain attention for the increasing prevalence of allergic airway diseases in Europe. Since more than 30% of the total European population suffers from airway allergies and asthma, reaching a higher level of awareness and elaboration of an active prevention plan is mandatory. Of the 406 individuals undergoing SPT in the European Parliament, 211 participants (52%) reported to have suffered from an allergy in the past, with allergic symptoms being present in the nose and eyes (40% and 36%, respectively), the skin (27%), lower airways (14%) and the gut (8%). Of the 381 SPT with reliable results, cutaneous hypersensitivity was found in 201 (53%) participants. Of those with positive SPT (n = 201), 70 participants (35%) were monosensitized while 131 participants (65%) were polysensitized. The positive skin reactions were found mostly for grass pollen (n = 108), followed by Dermatophagoides pteronyssinus (n = 105), Dermatophagoides farina (n = 96) and birch pollen (n = 85). Of note, 54 individuals (14% of the total tested population) without reported allergy or allergic symptoms showed a positive SPT without clinical relevance. This report summarizes the main idea and goals of the symposium: chronic airway diseases are a major and growing health problem in Europe. Therefore, a joint preventive action plan needs to be developed for a better health status of European citizens.
Executive Function and Depression as Independent Risk Factors for Postoperative Delirium

Background:Postoperative delirium has been associated with greater complications, medical cost, and increased mortality during hospitalization. Recent evidence suggests that preoperative executive dysfunction and depression may predict postoperative delirium; however, the combined effect of these risk factors remains unknown. This study examined the association among preoperative executive function, depressive symptoms, and established clinical predictors of postoperative delirium among 998 consecutive patients undergoing major noncardiac surgery. Methods:A total of 998 patients were screened for postoperative delirium (n = 998) using the Confusion Assessment Method as well as through retrospective chart review. Patients underwent cognitive, psychosocial, and medical assessments preoperatively. Executive function was assessed using the Concept Shifting Task, Letter-Digit Coding, and a modified Stroop Color Word Interference Test. Depression was assessed by the Beck Depression Inventory. Results:Preoperative executive dysfunction (P = 0.007) and greater levels of depressive symptoms (P = 0.049) were associated with a greater incidence of postoperative delirium, independent of other risk factors. Secondary analyses of cognitive performance demonstrated that the Stroop Color Word Interference Test, the executive task with the greatest complexity in this battery, was more strongly associated with postoperative delirium than simpler tests of executive function. Furthermore, patients exhibiting both executive dysfunction and clinically significant levels of depression were at greatest risk for developing delirium postoperatively. Conclusions:Preoperative executive dysfunction and depressive symptoms are predictive of postoperative delirium among noncardiac surgical patients. Executive tasks with greater complexity are more strongly associated with postoperative delirium relative to tests of basic sequencing.