Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of histone methylation catalyzed by protein lysine methyltransferase SET7/9 and origin of product specificity

Methylation of certain lysine residues in the N-terminal tails of core histone proteins in nucleosome is of fundamental importance in the regulation of chromatin structure and gene expression. Such histone modification is catalyzed by protein lysine methyltransferases (PKMTs). PKMTs contain a conserved SET domain in almost all of the cases and may transfer one to three methyl groups from S-adenosyl-l-methionine (AdoMet) to the ε-amino group of the target lysine residue. Here, quantum mechanical/molecular mechanical molecular dynamics and free-energy simulations are performed on human PKMT SET7/9 and its mutants to understand two outstanding questions for the reaction catalyzed by PKMTs: the mechanism for deprotonation of positively charged methyl lysine (lysine) and origin of product specificity. The results of the simulations suggest that Tyr-335 (an absolute conserved residue in PKMTs) may play the role as the general base for the deprotonation after dissociation of AdoHcy (S-adenosyl-l-homocysteine) and before binding of AdoMet. It is shown that conformational changes could bring Y335 to the target methyl lysine (lysine) for proton abstraction. This mechanism provides an explanation why methyl transfers could be catalyzed by PKMTs processively. The free-energy profiles for methyl transfers are reported and analyzed for wild type and certain mutants (Y305F and Y335F) and the active-site interactions that are of importance for the enzyme's function are discussed. The results of the simulations provide important insights into the catalytic process and lead to a better understanding of experimental observations concerning the origin of product specificity for PKMTs.
Plasma vasopressin, oxytocin, estradiol, and progesterone related to water and sodium excretion in normal pregnancy and gestational hypertension

Objective. To investigate associations between plasma oxytocin and vasopressin concentrations and renal water and sodium excretion during normal pregnancy in comparison with gestational hypertension. Design. A prospective open trial conducted in the 12th, 24th, and 36th weeks of gestation. Settings. Seven antenatal clinics in Sweden. Participants. Thirty‐seven normotensive women, 15 women with gestational hypertension, and five women with mild preeclampsia. Main outcome measures. Hormones were analyzed with radioimmunoassay. Albumin, osmolality, sodium, and urea were analyzed by routine methods. Results. Blood pressure was elevated in the hypertensive women and body mass index in mild preeclampsia from week 12. Renal sodium excretion did not differ between groups or weeks and mean renal free water clearance was negative. In normotensive women, the vasopressin concentration was 1.1±0.2 (week 12) and 0.7±0.1 pmol/L (week 36: p = 0.053). In hypertensive women, vasopressin concentration was 1.7±1.0 pmol/L, week 12, and 0.7±0.1 pmol/L in week 36 (ns). In normotensive women, oxytocin concentration increased from 23±1 pmol/L in week 12 to 48±3 pmol/L in week 36 (p<0.001). Corresponding values in hypertensive women were 36±11 (week 12) and 55±5 pmol/L (week 36: ns). In all groups, plasma estradiol concentration increased. Plasma progesterone increased until week 24 in normotensive and hypertensive women with further increase in normotensive women. Conclusions. The low plasma vasopressin and increasing plasma oxytocin concentrations with unchanged water and sodium excretion indicate that oxytocin assists vasopressin in concentrating urine during pregnancy.
Assessment of left ventricular torsion in patients with anterior wall myocardial infarction before and after revascularization using speckle tracking imaging.

BACKGROUND Rotation of the left ventricular (LV) apex to the base, or LV torsion, is related to myocardial contractility and structure and has recently been recognized as a sensitive indicator of cardiac performance, but it has been difficult to measure. The recent development of 2-dimensional (2D) speckle tracking imaging (STI) may provide a powerful means of assessing LV torsion. This study was conducted to evaluate the global and regional LV twist in patients with anterior wall myocardial infarction (AMI) disease before and after revascularization by STI. METHODS 2D STI was performed in 35 AMI patients before and one month after revascularization, as well as in 32 normal controls. Left ventricular global and regional rotations were obtained at basal and apical short-axis levels; LV torsion was defined as apical rotation relative to the base. The time sequences were normalized to the percentage of systolic and diastolic duration. RESULTS Before revascularization, LV peak regional and global torsion in patients with AMI were significantly reduced as the result of reduced apical and basal rotation relative to those of normal control group (all P < 0.001); most significantly in the anterior and anterior-septal regions (P < 0.001); one month after revascularization, there were significant changes in peak rotation at either the base or apex relative to pre-revascularization values (all P < 0.001). Similarly, peak regional and global LV torsion were increased significantly (all P < 0.001). Global torsion inversely correlated with EDV (r = -0.605, P = 0.028) and ESV (r = -0.638, P = 0.019); and positively correlated with LVEF (r = 0.630, P = 0.021). Tight relations were also found between torsion and LV longitudinal and short axis function. CONCLUSIONS Systolic torsion was decreased in AMI patients. Revascularization therapy can improve the LV function of the AMI patients. STI has a potential to quantify left ventricular global and segment torsion in patients with AMI, and may make the assessment more available in clinical and research cardiology.
The Influence of Gonadal Hormones on Neuronal Excitability, Seizures, and Epilepsy in the Female

Summary: It is clear from both clinical observations of women, and research in laboratory animals, that gonadal hormones exert a profound influence on neuronal excitability, seizures, and epilepsy. These studies have led to a focus on two of the primary ovarian steroid hormones, estrogen and progesterone, to clarify how gonadal hormones influence seizures in women with epilepsy. The prevailing view is that estrogen is proconvulsant, whereas progesterone is anticonvulsant. However, estrogen and progesterone may not be the only reproductive hormones to consider in evaluating excitability, seizures, or epilepsy in the female. It seems unlikely that estrogen and progesterone would exert single, uniform actions given our current understanding of their complex pharmacological and physiological relationships. Their modulatory effects are likely to depend on endocrine state, relative concentration, metabolism, and many other factors. Despite the challenges these issues raise to future research, some recent advances have helped clarify past confusion in the literature. In addition, testable hypotheses have developed for complex clinical problems such as “catamenial epilepsy. ” Clinical and animal research, designed with the relevant endocrinological and neurobiological issues in mind, will help advance this field in the future.
Outcomes research, cost containment, and the fear of health care rationing.

Expectations are high for the Agency for Health Care Policy and Research, established by the 101st Congress to promote research on medical outcomes and develop guidelines for practice. Physicians and patients expect that such research will make it possible to sort out what works in medicine and learn how to make clinical decisions that reflect more truly the needs and wants of individual patients. Many business leaders, third-party payers, and policy makers believe that this effort will lead to the development of practice guidelines, which in turn will reduce the pressure for growth and produce a leaner, trimmer health care .
Otolith Dysfunction During Vertiginous Attacks in Ménière's Disease

Objective—Vertiginous attacks of Ménière's disease (MD) are characterized by various types of vertigo, namely rotatory vertigo, dizziness and drop attack. When a patient complains of dizziness without spontaneous nystagmus, otolith dysfunction cannot be ruled out. The purpose of this study was to evaluate otolith dysfunction during vertiginous attacks of MD or delayed endolymphatic hydrops. Material and Methods—Vestibular function tests were carried out daily for several days in 11 patients (MD, n = 9; delayed endolymphatic hydrops, n = 2) during vertiginous attacks. Otolith function was evaluated by means of the static torsional position of both eyes [static ocular torsion (OT)] whilst in an upright position. We defined otolith dysfunction as an abnormal change (range) in OT without spontaneous nystagmus or as an abnormal change in OT without a change in spontaneous nystagmus. Results—Four patients had an abnormal change (range) in OT without spontaneous nystagmus or an abnormal change in OT without a change in spontaneous nystagmus during vertiginous attacks of MD. Conclusions—Otolith dysfunction occurs in patients during vertiginous attacks of MD. In cases of ataxia without spontaneous nystagmus, otolith dysfunction most likely causes atypical attacks of MD.
Myocardial reperfusion injury.

Lethal reperfusion injury is a paradoxical type of myocardial injury caused by the restoration of coronary blood flow after an ischemic episode. This review focuses on the mechanisms of the injury, on attempts to protect the heart against it, and on promising new approaches to cardioprotection during percutaneous coronary intervention.
Experience of Mini-Percutaneous Nephrolithotomy in the Treatment of Large Impacted Proximal Ureteral Stones

Objectives: To evaluate the efficacy and safety of mini- percutaneous nephrolithotomy (PCNL) in the treatment of large impacted proximal ureteral stones. Methods: We retrospectively reviewed the outcomes of 163 patients who underwent mini-PCNL between January 2006 and August 2010. Mean age was 48.6 years and mean stone size was 18.4 mm. Hydronephrosis and/or hydroureterosis appeared in all patients. In the prone position, percutaneous access (16-Fr sheath) was established by placement of an access needle into the intended calyx under fluoroscopic guidance or combined with ultrasound guidance for complete obstruction by stones while the contrast agent cannot transit. Pneumatic or ultrasonic probes were used throughout ureterorenoscopy for lithotripsy. The ureteral stents and nephrostomy tube were placed at the end of the procedure. Mean drop in hemoglobin, operative time, success rate, hospital stay, and complications were assessed. Results: Mini-PCNL operations were performed successfully in all patients. Mean operation time was 37 min. Mean postoperative hospital stay was 3.6 days. All cases were followed up for 6-20 months. No major complications like hemorrhage, perforation or organic injury were noted during the operation or postoperatively. The stone-free rate in all patients was 95.7%. Calculus had no recurrence during the follow-up period. Hydronephrosis and hydroureterosis disappeared or were relieved. Conclusions: Mini-PCNL is a safe and effective therapy for large impacted proximal ureteral stones.
Anti-coagulation therapy following coronary endarterectomy in patient with coronary artery bypass graft

Background: Since there is a lack of research on postoperative anticoagulation protocol in patients undergoing coronary artery bypass graft (CABG) / coronary endarterectomy (CE), we recommend a new protocol for anticoagulation in these patients. Methods: In this double-blind randomized clinical trial study, 52 patients undergoing CABG / CE entered the study and were divided into two groups. In group 1, the patients were given warfarin(international normalized ratio (INR) between 2-3) together with 80 mg aspirin daily for 3 months. In group 2, the patients were given 75 mg plavix daily together with 80 mg aspirin daily for 3 months. We evaluated patients with electrocardiography, echocardiography and checking ceratin phosphokinase MB and troponin I in the several stages. The data were analysed SPSS Version18 software. Results: There was no significant difference between pre and post-operative Ejection fraction in patients with plavix (P=0.21) and warfarin (P=0.316) regimen. However, wall mrotion score was significantly better in clopidogrel – aspirin patients in late (3 months) post operation (p<0.001). Conclusions: Since warfarin has serious hemorrhagic complications and requires closed monitoring of serum drug activity by serial INR checking, it is recommended that clopidogrel – aspirin can be the preferred alternative anticoagulation therapy in CABG / CE patients.
On iterative decoding of polar codes: Schedule-dependent performance and constructions

Polar codes asymptotically achieve the symmetric capacity of any binary-input discrete memoryless channel under sequential decoding algorithms such as successive cancellation decoding. However, for applications with high throughput requirements, other decoding approaches may be a better fit, as sequential decoders are inherently difficult to parallelize in order to increase their throughput. Iterative belief-propagation decoding may pose a valid approach for such parallel decoders. In this work, we present an extensive study of polar codes under both sequential and parallel message schedules in iterative decoding, and reveal a strong dependency of the code performance on the schedule used for decoding. To overcome performance impairments observed when using polar codes optimized for sequential scheduling under parallel schedules, we present a method to optimize codes for iterative decoders working with parallel scheduling.
Discovering an optimal set of minimally contrasting acoustic speech units: a point of focus for whole-word pattern matching

This paper presents a computational model that can automati­ cally learn words, made up from emergent sub-word units, with no prior linguistic knowledge. This research is inspired by cur­ rent cognitive theories of human speech perception, and there­ fore strives for ecological plausibility with the desire to build more robust speech recognition technology. Firstly, the par­ ticulate structure of the raw acoustic speech signal is derived through a novel acoustic segmentation process, the ‘acoustic DP-ngram algorithm’. Then, using a cross-modal association learning mechanism, word models are derived as a sequence of the segmented units. An efficient set of sub-word units emerge as a result of a general purpose lossy compression mechanism and the algorithms sensitivity to discriminate acoustic differ­ ences. The results show that the system can automatically derive robust word representations and dynamically build re­ usable sub-word acoustic units with no pre-defined languagespecific rules. Index Terms: speech perception, segmentation, classification
Editorial: faecal microbiota transplantation for ulcerative colitis—not quite there yet? Authors’ reply

1. Costello SP, Soo W, Bryant RV, Jairath V, Hart AL, Andrews JM. Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis. Aliment Pharmacol Ther. 2017;46:213-224. 2. Paramsothy S, Kamm MA, Kaakoush NO, et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trials. Lancet. 2017;389:1218-1228. 3. Costello S, Waters O, Bryant R, et al. Short duration, low intensity pooled faecal microbiota transplantation induces remission in patients with mild-moderately active ulcerative colitis: a randomised controlled trial. J Crohns Colitis. 2017;11(Suppl. 1):S23. 4. Moayyedi P, Surette MG, Kim PT, et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomised controlled trial. Gastroenterology. 2015;149:102-109. 5. Rossen NG, Fuentes S, van der Spek MJ, et al. Findings from a randomised controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology. 2015;149:110-118. 6. Zuo T, Wong SH, Lam K, et al. Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome. Gut. 2017;1-10. 7. Nakatsuji T, Chen TH, Narala S, et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci Transl Med 2017;9:pii: eaah4680.
New Insights into the Potential Roles of 3-Iodothyronamine (T1AM) and Newly Developed Thyronamine-Like TAAR1 Agonists in Neuroprotection

3-Iodothyronamine (T1AM) is an endogenous high-affinity ligand of the trace amine-associated receptor 1 (TAAR1), detected in mammals in many organs, including the brain. Recent evidence indicates that pharmacological TAAR1 activation may offer a novel therapeutic option for the treatment of a wide range of neuropsychiatric and metabolic disorders. To assess potential neuroprotection by TAAR1 agonists, in the present work, we initially investigated whether T1AM and its corresponding 3-methylbiaryl-methane analog SG-2 can improve learning and memory when systemically administered to mice at submicromolar doses, and whether these effects are modified under conditions of MAO inhibition by clorgyline. Our results revealed that when i.p. injected to mice, both T1AM and SG-2 produced memory-enhancing and hyperalgesic effects, while increasing ERK1/2 phosphorylation and expression of transcription factor c-fos. Notably, both compounds appeared to rely on the action of ubiquitous enzymes MAO to produce the corresponding oxidative metabolites that were then able to activate the histaminergic system. Since autophagy is key for neuronal plasticity, in a second line of experiments we explored whether T1AM and synthetic TAAR1 agonists SG1 and SG2 were able to induce autophagy in human glioblastoma cell lines (U-87MG). After treatment of U-87MG cells with 1 μM T1AM, SG-1, SG-2 transmission electron microscopy (TEM) and immunofluorescence (IF) showed a significant time-dependent increase of autophagy vacuoles and microtubule-associated protein 1 light chain 3 (LC3). Consistently, Western blot analysis revealed a significant increase of the LC3II/LC3I ratio, with T1AM and SG-1 being the most effective agents. A decreased level of the p62 protein was also observed after treatment with T1AM and SG-1, which confirms the efficacy of these compounds as autophagy inducers in U-87MG cells. In the process to dissect which pathway induces ATG, the effects of these compounds were evaluated on the PI3K-AKT-mTOR pathway. We found that 1 μM T1AM, SG-1 and SG-2 decreased pAKT/AKT ratio at 0.5 and 4 h after treatment, suggesting that autophagy is induced by inhibiting mTOR phosphorylation by PI3K-AKT-mTOR pathway. In conclusion, our study shows that T1AM and thyronamine-like derivatives SG-1 and SG-2 might represent valuable tools to therapeutically intervene with neurological disorders.
Rheological Characterization of Bio-Oils from Pilot Scale Microwave Assisted Pyrolysis

Renewable energy is gaining importance in satisfying environmental concerns and addressing economical concerns over fossil fuel usage. Lignocellulosic materials are the most abundant renewable resources on earth (Lynd et al., 2005). Energy can be obtained from biomass either biochemically or thermochemically. In the biochemical process, pretreatment of biomass is a necessary and the first step in opening up structure of the biomass cell wall to permit the access of enzymes to cellulose and hemicellulose. Pyrolysis, gasification, and combustion are the three main thermochemical processes to get energy from biomass. Combustion has a maximum efficiency of more than 30% (Yu et al., 2007). Because gasification offers higher efficiency compared to combustion, it has attracted a high level of interest (Bridgwater, 2004). According to Wornat et al (1994), the burning of bio-oils produced through the pyrolysis of biomass is more efficient. Bio-oil also offers advantages in storage and transport and in its versatility as an energy carrier and as a source of chemicals (Bridgwater, 2004). The thermochemical process can convert a low-carbohydrate or non-fermentable biomass to alcohol fuels, thus adding technological robustness to efforts to achieve the 30 x 30 goal. Pyrolysis is an endothermic reaction wherein thermal decomposition occurs in the absence of oxygen. It is always the first step in gasification and combustion, wherein partial or total oxidation of the substrate occurs. Gas is the main product (85%) in gasification, whereas biooil (70-80%) is the main product in most types of pyrolysis. The yield of pyrolysis products such as syngas/ producer gas (mixture of CO and H2), bio-oil, and bio-char (charcoal) would vary depending upon the pyrolysis methods (conventional, fast, vacuum, flash, and ultra), biomass characteristics (feedstock type, moisture content, particle size), and reaction parameters (rate of heating, temperature, and residence time). Bridgwater (2003) listed four essential features to get bio-oil from fast pyrolysis: very high heating rates (1000°C/s), high heat transfer rates (600-1000 W/cm2), short vapor residence times (typically <2 s), and rapid cooling of pyrolysis vapors and aerosols. Because the heart of a fast pyrolysis process is the reactor, during the last two decades several different reactor designs to meet the rapid heattransfer requirements have been explored. Achieving very high heating and heat transfer rates during pyrolysis usually require a finely ground biomass feed. Pyrolysis using microwave irradiation is one of the many ways of converting biomass into high value products and chemicals. Not only does microwave assisted pyrolysis (MAP) not require a high degree of grinding (e.g., large chunk of wood logs can be used) as required in
Biliary stenting versus bypass surgery for the palliation of malignant distal bile duct obstruction: A meta‐analysis

The objective of this analysis is to compare endoscopic stenting with surgical bypass in patients with unresectable, malignant, distal common bile duct obstruction using the technique of meta‐analysis. The inclusion criteria for the studies were randomized patient assignment, publication in the English language, 20 or more patients per group, all patients followed up until death, and follow‐up and complications reported in an equivalent way for both treatment arms. Data extraction was performed independently by 2 of the authors. The number of treatment failures, serious complications, requirement for additional treatment sessions, and 30‐day mortality were extracted. Three existing trials met the inclusion criteria, all of which compared surgery with the use of plastic stents. There were no studies identified that used metallic expandable stents. For the rate of treatment failure and serious complications, the odds ratios (ORs) of the 3 trials were heterogeneous, and no summary ORs were calculated. More treatment sessions were required after stent placement than after surgery, and a common OR was estimated to be 7.23 (95% confidence interval [CI], 3.73 to 13.98). Thirty‐day mortality was not significantly different (OR = 0.522; 95% CI, 0.263 to 1.036). Although surgical bypass required fewer additional treatment sessions, existing data do not allow a definitive conclusion on which treatment is preferable. A larger randomized controlled trial using newer metallic stents and proper quality‐of‐life instruments is required.