Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical applications of denaturing high-performance liquid chromatography-based genotyping.

AIM To develop and evaluate heteroduplex forming templates (HFTs) as a common set of molecular standards for genotyping by denaturing high-performance liquid chromatography (DHPLC) using hypervariable regions of human mitochondrial DNA (mtDNA) as a model system. METHODS Hypervariable regions 1 and 2 from the mtDNA D-loop of 22 maternally related and unrelated human volunteers were amplified by polymerase chain reaction (PCR) and individually mixed with each of three HFTs. Following denaturation and reannealing of the mixture, the resulting hetero- and homoduplicies were separated by DHPLC using temperature-modulated heteroduplex analysis. RESULTS Each of three HFTs, when cross-hybridized with a target mtDNA amplicon, induced the formation of an assemblage hetero- and homoduplex peaks, which were uniquely characteristic of a given mtDNA sequence variant. The mtDNA DHPLC profiles obtained in the current study were identical between maternal relatives and different between unrelated individuals--consistent with uniparental maternal inheritance of mtDNA in humans. CONCLUSION DHPLC in combination with a common set of HFTs targeted to a locus of interest can be used as a reliable means of genotyping. DHPLC profiles can be readily stored as a bit-coded string of hetero- and homoduplex peak retention times to form a searchable database. This approach to DHPLC genotyping will have immediate utility in extended pedigree analyses, where it will allow rapid sorting and/or confirmation of maternal lineages. Additional applications of DHPLC profiling include the discovery and scoring of clinically relevant nuclear and mitochondrial loci.
Genetic ablation of ryanodine receptor 2 phosphorylation at Ser‐2808 aggravates Ca2+‐dependent cardiomyopathy by exacerbating diastolic Ca2+ release

Phosphorylation at Ser‐2808 is suggested to result in RyR2 hyperactivity, i.e. ‘leakiness’, thus contributing to the pathology of cardiac diseases. We studied the effect of disabling phosphorylation at Ser‐2808 of RyR2 in a genetic model of Ca2+‐dependent cardiomyopathy, which was caused by leaky RyR2. RyR2 phosphorylation was high at Ser‐2808 in myocytes expressing wild‐type (WT) RyR2; protein phosphatase increased RyR2 leakiness in cells expressing WT, but not in mutant RyR2s with disabled Ser‐2808 phosphorylation sites. Rather than alleviating cardiac disease, ablation of the Ser‐2808 exacerbated the disease phenotype by reducing survival, impairing in vivo cardiac function and enhancing RyR2 Ca2+ leak and mitochondrial damage. These results suggest a novel mode of RyR2 regulation via dephosphorylation at Ser‐2808 in normal and diseased hearts.
Pastoral community coping and adaptation strategies to manage household food insecurity consequent to climatic hazards in the cattle corridor of Uganda

ABSTRACT Establishing short and long term measures that pastoral and agropastoral households use to ensure they have access to food in periods of climate extremes could provide insights into ways to support households in similar conditions. Using semi-structured elicitation, 15 purposively selected participants from case households and 13 community leaders, in the central cattle corridor of Uganda were interviewed in January to February 2013. Thematic analysis revealed four coping strategies: harvesting immature food crops, selling off cattle, searching for alternative water sources and using alternative non-production-based means to access food. Three adaptation strategies identified were: diversifying livelihood activities, changing agricultural practices and investing in alternative water sources. Several strategies were related to incremental crop system changes, to maintain the existing way of practice. However, some were transformational, like formerly specialized livestock keepers taking on crop farming. Some strategies presented environmentally erosive effects; which could be curbed by evaluating the opportunity cost of diversification and transformative practices in relation to incremental adaptation. Insights gleaned could assist researchers to consider aspects for in-depth adaptation analysis and inform on how policies and institutions in Uganda could be used to facilitate, rather than undermine, pastoralists’ coping and adaptation; and thus guide interventions to strengthen food security.
Prospective analysis of treatment outcome and prognostic factors in patients with T‐cell lymphomas treated by CEOP‐B: single institutional study

The important prognostic factors were evaluated for T‐cell non‐Hodgkin lymphoma (NHL) patients in a prospective study using the CEOP‐B protocol [a modified cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)‐like regimen that uses epirubicin instead of doxorubicin with the addition of bleomycin]. Fifty‐two patients were enrolled in the study. The overall response rate was 63·5%. The median progression‐free survival (PFS) and median overall survival (OS) was 18·0 and 39·5 months respectively. The most common toxicity was neutropenia. The factors related to poor outcome were a high International Prognostic Index (IPI) and a high ‘B’ score (bone marrow involvement, B symptoms, bulky disease). We developed a new prognostic model, namely the Prognostic Group for T cell NHL (PGT) that included four groups: PGT1 (low IPI/low B score), PGT2 (low IPI/high B score), PGT3 (high IPI/Low B score) and PGT4 (high IPI/Low B score). OS and PFS (not reached, 48 months) in the PGT1 group were significantly longer than those (11·5 and 4·8 months) in PGT2. The same result was observed in the PGT3 and PGT4 groups. The CEOP‐B regimen was moderately active and tolerable for T‐cell NHL patients, and the PGT system might be useful for the prediction of long‐term survival of T‐cell NHL patients.
Antioxidant properties of Lactobacillus and its protecting effects to oxidative stress Caco-2 cells.

This study was designed to analyse the antioxidant capacity of lactic acid bacteria (LAB) in order to provide characteristic parameters and theoretical basis for its further utilization as a natural antioxidant . Further experiment was carried out to study its protection mechanism through oxidative stress C aco-2 cell model in vitro. For this purpose, antioxidative activity of cell s and different cellular fractions of Lactobacillus delbrueckii (ATCC7830) was evaluated by scavenging capacity of superoxide anion free radicals (SAFR)ˇ� reducing power and total antioxidant capacity assay. Low dose of H2O2 (100μmol/L) was used to establish oxidative damaged model on Caco-2 cells, the bacteria’s protecting effect on the damaged cells was further researched. The results showed that extracellular secretions of Lactobacillus delbrueckii has the strongest antioxidant activity, following by cells, and cells can clear superoxide radicals. The ability to scavenge SAFR of this LAB was (42.4±0.32) % (cell lysates, the highest) , the reducing power was (3.01±0.20, cell extracellular secretions, the highest), and the total antioxidant ability was ( 4.32±0.36, cell extracellular secretions, the highest). The above antioxidative character made this LAB possible to protect Caco-2 cells being damaged by low dose of H2O2. Further analysis showed that the total antioxidant capacity (T-AOC) of culture supernatant and lysate were significantly increased compared with the negative control group and the oxidative stress group (p<0.01). Also increased the anti-superoxide anion (O 2- ) free radicals (p<0.01) level. All the results indicate that different fractions from lactic acid bacteria have various capabilities on reducing power , scavenging superoxide anion free radicals ability and total antioxidant capacity. Extracellular secretions have the most obvious antioxidant character. Lactobacillus delbrueckii could protect Caco-2 cells under oxidative stress by increasing its antioxidative function in vitro.
OPTIMAS: Overwrite Purging Through In-Execution Memory Address Snooping to Improve Lifetime of NVM-Based Scratchpad Memories

SRAM-based scratchpad memories (SPMs) used in embedded systems impose high leakage power. Designing SPMs based on non-volatile memories (NVMs) were proposed as NVMs have negligible leakage power. The main problem of utilizing NVMs across the SPM is their limited number of write cycles (endurance). This problem threatens the reliability of NVM-based SPMs. To alleviate the problem of limited endurance in NVM-based SPMs, this paper proposes a method, called overwrite purging through in-execution memory address snooping (OPTIMAS). The main idea behind the proposed method is to control the lifetime of NVM-based SPMs, directly by a hardware unit, outside of the SPM mapping algorithm. This idea enables the possibility of using traditional SRAM-based mapping algorithms in NVM-based SPMs. OPTIMAS controls the wear-out of NVM-based SPMs based on the recent write behavior of each block during the runtime of the programs. OPTIMAS is evaluated from the lifetime, energy consumption, and performance point of views. The simulation results show up to two orders of magnitude improvement in lifetime, an average of 50% reduction in dynamic energy consumption, and negligible performance overhead (less than 1%). Furthermore, it is shown that while OPTIMAS is orthogonal to all other approaches, it benefits from significant lifetime improvement in comparison with the state-of-the-art approaches.
Critical Review: Is PROMPT an effective treatment method for adults with acquired apraxia of speech and coexisting aphasia?

This critical review examines the evidence from studies on the effectiveness of PROMPT therapy in the treatment of individuals with acquired apraxia of speech and coexisting aphasia. Four studies that met search criteria were obtained, all of which used single-subject multiple-baseline designs. This evidence-based literature review suggests that PROMPT therapy may be an effective treatment for patients with apraxia of speech and a concomitant aphasia, however more research is required to gain confidence in such a recommendation.
The effect of ethanol on one‐carbon metabolism: Increased methionine catabolism and lipotrope methyl‐group wastage

Deficiency of choline and methionine produces hepatic steatosis similar to that seen with ethanol, and supplementation with these lipotropes can prevent ethanol‐induced fatty liver. These effects are thought to occur through alterations in membrane phospholipid metabolism, but the mechanism whereby this occurs and the precise nature of the changes brought about by ethanol in the interactions of choline and methionine metabolism remain unclear. Through the known effects on hepatic glutathione (which requires as a precursor a product of methionine catabolism), ethanol might affect hepatic one‐carbon metabolism, which requires the participation of both methionine and choline in the transfer of methyl groups. This has been investigated with a radiorespirometric technique to assess the in vivo oxidation of the methyl groups of lipotropes and their intermediates in ethanol‐ and control‐fed rats. Enzyme activities of one‐carbon transfer reactions and the hepatic levels of methionine and α‐aminobutyrate, an end product of methionine catabolism, have been measured. The effect of ethanol feeding on hepatic S‐adenosylmethionine and S‐adenosylhomocysteine has also been assessed. Ethanol increases the oxidation to carbon dioxide of the methyl group of methionine by a factor of 2.9 (p = 0.002) and produces a 3.6‐fold (p = 0.0001) accumulation of α‐aminobutyrate, indicating a marked increase in methionine catabolism. Hepatic methionine levels are unchanged by ethanol, however, and this may be explained by a dramatic increase in the turnover of the methyl groups of choline and betaine in response to ethanol (times 3.6 and 4.2, respectively, p < 0.003), suggesting greatly increased use of the choline oxidation pathway to remethylate homocysteine through betaine homocysteine methyltransferase. The activity of this enzyme is more than doubled (p = 0.002) in ethanol‐fed animals, and that of methionine synthase is significantly decreased. Hepatic S‐adenosylmethionine is decreased by ethanol (59.6 vs. 100.9 nmol/gm, p < 0.001), possibly representing increased consumption, and S‐adenosylhomocysteine is increased. We propose that ethanol stimulates catabolism of methionine to generate cysteine and replenish glutatione, but at the same time, the cell attempts to conserve methionine through a futile cycle of enhanced choline oxidation. The result is a dramatic wastage of methyl groups. (HEPATOLOGY 1993;18:984‐989).
Epidural spinal tumor and periaortitis as rare complications of Wegener’s granulomatosis

This case report describes findings in a 61-year-old woman who manifested scleritis, small pulmonary nodules, otitis media, periaortitis, and progressive epidural spinal tumor, associated with elevated serum myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) levels. She was clinically diagnosed with Wegener’s granulomatosis, although vasculitis was not diagnosed due to the lack of typical histological findings. We discuss the differential diagnosis in this patient, and the association of MPO-ANCA with periaortitis or epidural spinal tumor.
Cognitive flexibility and decision‐making in a model of conditional visuomotor associations

Arbitrary visuomotor associations map a stimulus onto a particular response upon reinforcing rewards. Changes in the associations between stimuli and responses require the neural networks to discard the already learned mappings and build new ones. This is a key aspect of cognitive flexibility. In addition, learning within this experimental paradigm requires a trial‐and‐error exploration strategy of the available stimulus–response associations. A system performing this task must be able to both build up mappings for stimulus–response associations and at the same time perform non‐deterministically to explore the behavioural space until it reaches certainty. We hypothesize an integrate‐and‐fire network model that accounts for the neurophysiological data of a conditional visuomotor association task and is able to show non‐deterministic behaviour. We aim at identifying multistable attractor regimes in the network dynamics, which intrinsically enable the system to make errors and thereby to perform trial‐and‐error exploration. Our model combines cognitive flexibility with multistable attractors in neurodynamical systems, believed to be the basis of decision‐making. If multistable attractors support the exploration of the behavioural space, then our model predicts that the brain should respond stochastically with correct or incorrect activity to visuomotor associations until it has reached certainty. This should be visible not only in the corresponding activity in the premotor area, but also in activity corresponding to other associations or even other stimuli in the prefrontal cortex.
Direct thrust and velocity measurement for a micro UAV rotor

Thrust and velocity sensing is very important for the control of micro UAVs. Contemporary high-performance quadrotor motion control relies on accurate high-speed trajectory sensing. However, position and velocity sensing is challenging outside of an indoor Vicon arena: GPS is slow and noisy, optical flow sensors do not work far from ground, and pitot tubes perform poorly at low speeds. Our approach is to use a compact force-torque sensor to directly measure rotor forces and pitch-roll torques. The sensor is constructed from MEMS barometers encapsulated in an elastic compound, attached to a load plate. The sensor can provide sub-mN thrust force sensing at 1 kHz, with torque sensitivity better than 0.1 mN-m. Using a lumped parameter model of rotor induced drag and flapping torque-velocity coupling, we can accurately estimate translational velocity of a rotor. The velocity output is linear for translational velocities from below 0.25 to over 0.8 ms
Factors associated with failure of emergency wait-time targets for high acuity discharges and intensive care unit admissions.

OBJECTIVE Ontario established emergency department length-of-stay (EDLOS) targets but has difficulty achieving them. We sought to determine predictors of target time failure for discharged high acuity patients and intensive care unit (ICU) admissions. METHODS This was a retrospective, observational study of 2012 Sunnybrook Hospital emergency department data. The main outcome measure was failing to meet government EDLOS targets for high acuity discharges and ICU emergency admissions. The secondary outcome measures examined factors for low acuity discharges and all admissions, as well as a run chart for 2015 - 2016 ICU admissions. Multiple logistic regression models were created for admissions, ICU admissions, and low and high acuity discharges. Predictor variables were at the patient level from emergency department registries. RESULTS For discharged high acuity patients, factors predicting EDLOS target failure were having physician initial assessment duration (PIAD)>2 hours (OR 5.63 [5.22-6.06]), consultation request (OR 10.23 [9.38-11.14]), magnetic resonance imaging (MRI) (OR 19.33 [12.94-28.87]), computed tomography (CT) (OR 4.24 [3.92-4.59]), and ultrasound (US) (OR 3.47 [3.13-3.83]). For ICU admissions, factors predicting EDLOS target failure were bed request duration (BRD)>6 hours (OR 364.27 [43.20-3071.30]) and access block (AB)>1 hour (OR 217.27 [30.62-1541.63]). For discharged low acuity patients, factors predicting failure for the 4-hour target were PIAD>2 hours (OR 15.80 [13.35-18.71]), consultation (OR 20.98 [14.10-31.22]), MRI (OR 31.68 [6.03-166.54]), CT (OR 16.48 [10.07-26.98]), and troponin I (OR 13.37 [6.30-28.37]). CONCLUSION Sunnybrook factors predicting failure of targets for high acuity discharges and ICU admissions were hospital-controlled. Hospitals should individualize their approach to shortening EDLOS by analysing its patient population and resource demands.
A New Method of Employing the Principle of Maximum Entropy to Retrieve the Risk Neutral Density

This paper suggests a new method of implementing the principle of maximum entropy to retrieve the risk neutral density of future stock, or any other asset, returns from European call and put prices. Instead of options prices used by previous studies the method maximizes the entropy measure subject to values of the risk neutral moments. These moments can be retrieved from market option prices in a first step, at each point of time. Compared to other existing methods of retrieving the risk neutral density based on the principle of maximum entropy, the benefits of the method that the paper suggests is the use of all the available information provided by the market more sufficiently. To evaluate the performance of the suggested method, the paper compares the new method proposed to other risk neutral density estimation techniques based on a number of simulation and empirical exercises.
Using appreciative inquiry to implement person-centred dementia care in hospital wards

The quality of care of persons with dementia in hospitals is not optimal and can be challenging. Moreover, staff may find difficulty in translating what they have learned during training into practice. This paper report the development and evaluation of a set of workshops using an appreciative inquiry approach to implement person-centred dementia care in two hospital wards. Staff worked collaboratively to develop a ward vision and to implement a number of action plans. Using appreciative inquiry approach, staff attitudes towards persons with dementia improved, inter-professional collaboration was enhanced and small changes in staff practices were noted. Dementia care in hospitals can be enhanced by empowering staff to take small but concrete actions after they engage in appreciative inquiry workshops, during which they are listened to and appreciated for what they can contribute.
A Chimeric Transmembrane Domain Directs Endothelial Nitric-oxide Synthase Palmitoylation and Targeting to Plasmalemmal Caveolae*

The endothelial nitric-oxide synthase (eNOS), a key signaling protein, undergoes a series of covalent modifications, including co-translational N-myristoylation at Gly2, as well as post-translational thiopalmitoylation at Cys15 and Cys26. Myristoylation of eNOS is required for the subsequent palmitoylation of the enzyme, and both acylations are required for the efficient subcellular targeting of eNOS to plasmalemmal caveolae. We constructed chimeric cDNAs encoding proteins comprised of various acylation-deficient eNOS mutants fused at their N termini to the hydrophobic transmembrane domain of the glycoprotein CD8 and characterized these constructs in transient transfection experiments in COS-7 cells. One construct (termed CD8-myr−eNOS) encodes a fusion protein comprised of the eNOS myristoylation-deficient mutant coupled to the CD8 transmembrane domain. In biosynthetic labeling experiments using [3H]palmitic acid, we found that the CD8-myr−eNOS chimera undergoes palmitoylation. Subcellular fractionation showed that the CD8-myr−eNOS chimera is targeted to caveolae. We also constructed and characterized a cDNA encoding the CD8 transmembrane domain fused to the palmitoylation-deficient mutant eNOS (in which Cys15 and Cys26 are changed to serine). This chimera (termed CD8-myr−·palm−eNOS) did not undergo palmitoylation, indicating that the palmitoylation seen with the CD8·myr−eNOS fusion protein occurs on the same residues as in the wild-type enzyme. Importantly, the CD8-myr−·palm−eNOS fusion protein remained efficiently targeted to caveolae, in contrast to the palm−eNOS mutant lacking the CD8 transmembrane domain, which has nominal caveolar localization. A construct encoding the CD8 transmembrane domain alone was insufficient for selective targeting to caveolae. These results indicate that membrane targeting per se, but not necessarily myristoylation, is sufficient for eNOS palmitoylation and localization to plasmalemmal caveolae, and suggest further that sequences within eNOS itself, in addition to its palmitoylation sites, facilitate the selective localization of the enzyme within caveolae.
Ectopic Expression of VvMybPA2 Promotes Proanthocyanidin Biosynthesis in Grapevine and Suggests Additional Targets in the Pathway1[W][OA]

Grapevine (Vitis vinifera) proanthocyanidins contribute to plant defense mechanisms against biotic stress and also play a critical role in organoleptic properties of wine. In grapevine berry, these compounds are mainly accumulated in exocarps and seeds in the very early stages of development. A previous study has already identified VvMybPA1 as the first transcription factor involved in the regulation of the proanthocyanidin pathway during seed development in grapevine. A novel Myb factor, VvMybPA2, which is described in this study, is in contrast mainly expressed in the exocarp of young berries and in the leaves. This transcription factor shows very high protein sequence homology with other plant Myb factors, which regulate flavonoid biosynthesis. Ectopic expression of either VvMybPA1 or VvMybPA2 in grapevine hairy roots induced qualitative and quantitative changes of the proanthocyanidin profiles. High-throughput transcriptomic analyses of transformed grapevine organs identified a large set of putative targets of the VvMybPA1 and VvMybPA2 transcription factors. Both genes significantly activated enzymes of the flavonoid pathway, including anthocyanidin reductase and leucoanthocyanidin reductase 1, the specific terminal steps in the biosynthesis of epicatechin and catechin, respectively, but not leucoanthocyanidin reductase 2. The functional annotation of the genes whose expression was modified revealed putative new actors of the proanthocyanidin pathway, such as glucosyltransferases and transporters.