Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantification and Analysis of Epigenetic Regulation of Brain-Derived Neurotrophic Factor (BDNF) in Huntington’s Disease

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder that affects motor coordination and cognitive function. HD neuropathology is characterized by substantial loss of medium spiny neurons in the striatum. Brain derived neurotrophic factor (BDNF) plays fundamental roles in the survival and activity of neurons, including striatal cells that die in HD. Previous reports shown substantial alterations in BDNF levels in the brains of HD cases; however, limited studies have explored the changes in BDNF across clinical stages of HD and levels present in peripheral fluids. We hypothesized that BDNF is increasingly deregulated during HD progression, and could be detected in plasma and saliva. Moreover, we propose that changes in BDNF gene expression may result from alterations in epigenetic mechanisms, specifically aberrant DNA methylation at the BDNF promoter; as previously reported to occur in other neurodegenerative disorders. We optimized an ELISA to measure BDNF in patients in different HD clinical stages and control subjects. We found lower levels of BDNF in saliva from subjects with the HTT gene mutation, regardless of HD clinical disease status in comparison to non-carriers. No changes in BDNF were found in plasma. We also determined the methylation levels at BDNF promoter IV by pyrosequencing. We found CpG sites differentially methylated in subjects with the HTT gene mutation. In summary, our preliminary studies suggest that BDNF protein levels and promoter methylation patterns may be associated with the huntingtin mutation and although they may be potentially indicative of the carrier status, fail to predict HD clinical progression.
REVIEW Biased β 2 -adrenoceptor signalling in heart failure: pathophysiology and drug discovery

The body is constantly faced with a dynamic requirement for blood ﬂow. The heart is able to respond to these changing needs by adjusting cardiac output based on cues emitted by circulating catecholamine levels. Cardiac β -adrenoceptors transduce the signal produced by catecholamine stimulation via G s proteins to their downstream effectors to increase heart contractility. During heart failure, cardiac output is insufﬁcient to meet the needs of the body; catecholamine levels are high and β -adrenoceptors become hyperstimulated. The hyperstimulated β 1 -adrenoceptors induce a cardiotoxic effect, which could be counteracted by the cardioprotective effect of β 2 -adrenoceptor-mediated G i signalling. However, β 2 -adrenoceptor-G i signalling negates the stimulatory effect of the G s signalling on cardiomyocyte contraction and further exacerbates cardiodepression. Here, further to the localization of β 1 - and β 2 -adrenoceptors and β 2 -adrenoceptor-mediated β -arrestin signalling in cardiomyocytes, we discuss features of the dysregulation of β -adrenoceptor subtype signalling in the failing heart, and conclude that G i -biased β 2 -adrenoceptor signalling is a pathogenic pathway in heart failure that plays a crucial role in cardiac remodelling. In contrast, β 2 -adrenoceptor-G s signalling increases cardiomyocyte contractility without causing cardiotoxicity. Finally, we discuss a novel therapeutic approach for heart failure using a G s -biased β 2 -adrenoceptor agonist and a β 1 -adrenoceptor antagonist in combination. This combination treatment normalizes the β -adrenoceptor subtype signalling in the failing heart and produces therapeutic effects that outperform traditional heart failure therapies in animal models. The present review illustrates how the concept of biased signalling can be applied to increase our understanding of the pathophysiology of diseases and in the development of novel therapies. couples to the heterotrimeric G protein G s , leading to its activation and dissociation into the G α s subunit and G βγ dimers. The activated G α s subunit activates AC which then produces cAMP to activate PKA. PKA phosphorylates effector proteins to increase cardiomyocyte contractility. The β 2 -adrenoceptor couples to both G s and G i proteins. It also responds to CA stimulation and mediates a mild contractile response via the G s -AC-cAMP-PKA signalling cascade. The inotropic effect is mild because β 2 -adrenoceptor also activates G i proteins which inhibit the production of cAMP by AC.
Analysis of TRIP Expression in Different Types of Skin Tumor

: TRAF-interacting protein (TRIP) is a ubiquitously expressed nucleolar E3 ubiquitin ligase. Ubiquitination of proteins is a post-translational modification, which decides on the cellular fate of the protein. TRIP in vivo substrate has not been yet identified. However, TRIP has been shown to play an important role in cellular proliferation, especially in keratinocytes. TRIP was found to be up-regulated in basal cell carcinoma (BCC) at the mRNA level. This prompted us to elucidate its role in skin proliferative diseases such as cancer by analyzing its expression in BCCs at protein level and in squamous cell carcinoma (SCC) at mRNA and protein level. To that purpose, we performed a real-time PCR (qPCR) analysis followed by an immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded (FFPE) biopsies. The real-time PCR was performed on 12 RNA samples of which 6 were extracted from SCC biopsies and 6 from normal human skin. The results were statistically insignificant. Further analyses are needed on new RNA samples. The IHC assay was performed on 20 biopsies from BCCs, 21 biopsies from SCCs and on 5 tissues from normal human skin. The results obtained showed an extensive expression of TRIP in keratinocytes nuclei. Due to various limitations related to the technique and to doubts about preservation of the antigens in the tissues from normal human skin, we could not highlight a clear difference in TRIP expression between the different tissues. In conclusion, further analyses are needed on new RNA samples (qPCR) and on better preserved FFPE tissues from normal skin (IHC) to assess TRIP relative expression in BCCs and SCCs versus normal human skin.
Acute and Chronic Renal Effects of Recombinant Human TGF- b 2 in the Rat

The expression of transforming growth factor- b (TGF- b ) correlates with the incidence of renal glomerular and interstitial injury, however, nothing is known of the effect of these proteins on renal hemodynamics. This study examines the renal hemodynamic and morphologic effects of recombinant human TGF- b 2 in normal male Sprague Dawley rats. Acute infusion of TGF- b 2 (1.2 m g/kg per min) induced no hemodynamic changes, except for a modest though significant fall in mean arterial pressure. Administering TGF- b 2 at vary-ing doses (20, 100, and 400 m g/kg) for 9 wk caused modest increases in systolic BP and proteinuria and minimal tubular interstitial fibrosis, however, renal hemodynamic end points were not significantly altered. TGF- b 2 (800 m g/kg) was also administered to volume-depleted rats for 7 consecutive days. In contrast to the findings in volume-replete animals, administration of TGF- b 2 to volume-depleted rats caused a marked reduction in GFR and medullary blood flow. Histologic fibrosis of the medullary vasa recta and cortical interstitium was seen, but glomeruli were unaffected. Thus, acute and short-term chronic TGF- b 2 administration did not induce major renal changes in the volume-replete state, however, TGF- b 2 combined with volume depletion caused
Fast FPGA-Placement Using a Gradient Descent Based Algorithm

—Programmable circuits and, nowadays, especially Field-Programmable Gate Arrays (FPGAs) are widely applied in computationally demanding signal processing applications. Considering modern, agile hardware/software codesign approaches, an Electronic Design Automation (EDA) process not only needs to deliver high quality results, but also has to be swift because software compilation is already distinctly faster. Slow EDA tools can in fact act as a kind of show-stopper for an agile development process. One of the major problems in EDA is the placement of the technology-mapped netlist to the target architecture. In this work, a method to reduce the runtime of the netlist placement for FPGAs is evaluated. The approach is a variation of analytical placement, with the distinction that a gradient descent is used for the optimization of the placement. This work is an extended version of a previous publication of the authors on this topic. Additionally, it is based on previous publications of the authors, in which a placement algorithm using self-organizing maps is introduced and optimized. In comparison, the gradient placement approach is shown to be up to 3.8 times faster than the simulated annealing based reference. The quality regarding the critical path is shown to be about 43 percent worse on average. The bounding-box and routing-resource costs are shown to be about equal to the reference.
Factors in£uencing the detection of bacterial cells using £uorescence in situ hybridization (FISH) : A quantitative review of published reports

Fluorescence in situ hybridization (FISH) is widely used to describe bacterial community composition and, to a lesser extent, to describe the physiological state of cells. One of the limitations of the technique is that the effectiveness of the detection of target cells appears to vary widely. Here, we present a quantitative review of published reports on the percentage of cells detected using the common EUB338 probe (%Eub) in aquatic ecosystems. The %Eub varies from 1 to 100% in the different published reports, with an average of 56%. There is a methodological component in this variation, with a significant effect of the fluorochrome type and the stringency conditions of the reaction. But there is also a strong environmental component, and the type of ecosystem and dominant phylogenetic group significantly influence %Eub. We argue that the optimization of the FISH protocol to describe the phylogenetic composition of bacterial assemblages will probably lead to techniques that are not effective to describe the physiological state of cells. 9 2003 of Microbiological Societies. by Elsevier B.V. All
Studying unbalanced workload and buffer allocation of production systems using multi-objective optimisation

Numerous studies have investigated the effects of unbalanced service times and inter-station buffer sizes on the efficiency of discrete part, unpaced production lines. There are two main disadvantages of many of these studies: (1) only some predetermined degree of imbalance and patterns of imbalance have been evaluated against the perfectly balanced configuration, making it hard to form a general conclusion on these factors; (2) only a single objective has been set as the target, which neglects the fact that different patterns of imbalance may outperform with respect to different performance measures. Therefore, the aim of this study is to introduce a new approach to investigate the performance of unpaced production lines by using multiple-objective optimisation. It has been found by equipping multi-objective optimisation with an efficient, equality constraints handling technique, both the optimal pattern and degree of imbalance, as well as the optimal relationship among these factors and the performance measures of a production system can be sought and analysed with some single optimisation runs. The results have illustrated that some very interesting relationships among the key performance measures studied, including system throughput, work-in-process and average buffer level, could only be observed within a truly multi-objective optimisation context. While these results may not be generalised to apply to any production lines, the genericity of the proposed simulation-based approach is believed to be applicable to study any real-world, complex production lines.
COMPARATIVE STUDIES OF THE PHYTOCHEMICAL SCREENING AND PROXIMATE POTENTIALS OF THE METHANOLIC EXTRACTS OF CYMBOPOGON ATTRACTUS AND OCIMUM GRATISSIMUM LEAVES GROWN IN NIGERIA

The phytochemical composition and proximate potentials of cymbopogon attractus and ocimum gratissimum were investigated. The proximate analysis in % showed that ocimum gratissimum had the highest amount of moisture content, ash content, crude protein and carbohydrate of 81.62, 3.03, 5.58 and 8.87 respectively while cymbopogon attractus had the lowest amount of moisture content, ash content, crude protein and carbohydrate with 76.98, 1.69, 2.87 and 8.27 respectively. Though cymbopogon attractus recorded 1.38 and 8.84 for both ether extract and crude fibre while ocimum gratissimum had 0.79 and 3.80 for ether extract and crude fibre respectively.The phytochemical analysis of the plants showed that the two plants contained alkaloid, tannins, saponins, flavonoids, phlobatanin and anthraquinone. While, cardiac glycoside,triterpenoids and reducing compound were found in cymbogopon attractus but absent in ocimum gratssimum. However, the study also revealed that steroid was present in ocimum gratissimum but absent in cymbopogon attractus while protein was not found in both plants. The presence of these phytochemicals account for their medicinal potential as well as their utility as prophylactics. This study showed the presence of steroids in ocimum gratissimum which accounts for its irritative ability in the mouth when rawly eaten while the presence of cardiac glycoside and triterpenoids in cymbopogon attractus are responsible for its sour taste.
LETTERS TO THE EDITOR Troglitazone Ameliorates Insulin Resistance in Patients with Werner’s Syndrome—Author’s Response

We the article by Izumino et al. (1), which suggests a therapeutic use of troglitazone, an insulin sensitizer, in Werner’s syndrome as well as in noninsulin-dependent diabetes mellitus (NIDDM). We here report another possible benefit of troglitazone treatment: pre-ventionofatherosclerosis.Wemeasuredtheintimalandmedialcomplexthickness(IMT)ofcommoncarotidarteryusingB-modeultrasoundtechniquetoevaluateearlyatheroscleroticlesions(2). Firstweinvesti-gatedtherelationshipbetweenIMTandurinaryC-peptidelevels(u-CPR)orinsulindosagein106JapanesesubjectswithNIDDM[52malesand54females,age62.5yr( se 0.9)yr]. Eighty-oneofthemwerereceiving insulin treatment, and the others were taking sulfonylureas. u-CPR of 24-hr urine samples were measured with a radioimmunoassay kit and were expressed as a mean value in three consecutive days. IMT values showed a positive correlation with both u-CPR (r 5 0.655, P , 0.0001) and insulin dosage, calculated as an average dose per day (r 5 0.399, P , 0.005). The correlation remained significant after adjusting for HbA Ic , body mass index, age, serum total cholesterol, and triglyceride levels. Second, we examined the effect of short-term treatment with troglita- zone (400 mg daily for 3 months) on IMT in 33 patients with NIDDM. Before troglitazone treatment they had been treated with sulfonylureas (32 glibenclamide and 1 gliclazide), which were continued in the same doses during the troglitazone treatment. Thirty-two diabetic subjects (29 receiving sulfonylureas and 3 diet alone) were examined as control group. The group given troglitazone There is ample evidence for the suitability of noninvasive measure- ment of systolic time intervals to detect positive inotropic effects inde-pendent of reflectory changes in heart rate (1, 2). The method is easy to handle, has a very high sensitivity and reproducibility, and has a high signal-to-noise ratio. These advantages favor this technique for the char- acterization of systolic inotropic drug effects compared with echocar-diography, which has a significantly higher short-term and day-to-day variability and is susceptible to observer-related influences We con-sideritthereforeunlikelythatwehavemissedamajor(directorindirect)positiveinotropiceffectinourexperiments.WeneverthelessagreewiththecommentthattheperipheralvasodilatingeffectofPTHrPdeservesfurtherstudies. Ourexperimentswerebasedon in vivo animal data and were de- signed to investigate short-term hemodynamic effects of PTHrP. It is apparent that the doses used in our experiments predominantly reflect pharmacological effects of PTHrP. Studies that could resolve the ques-tion by Selvais et al. whether increased paracrine PTHrP in vivo studies are limited to exogenous
Prevalence and Reasons for the use of Psychoactive Drugs Among University Students of Medical Sciences in Yazd, Iran

Background: Drug use has always been suggested as the ﬁrst preventable agent of various diseases and deaths around the world. Nowadays, this problem is more prevalent among young people and students of universities that are at risk. Objectives: Due to the newness of the case and legal restrictions on the consumption of psychoactive drugs in Iran, there are no statistics regarding the prevalence of consuming these drugs; therefore, it was decided to determine the prevalence and causes of tendencytowardstheconsumptionof psychoactivedrugsamongstudentsof YazdShahidSadoughiUniversityof MedicalSciences. Methods: Thepresentresearchwasacrosssectionalstudy,throughwhich250studentsof YazdUniversityof MedicalScienceswere selected using systematic random sampling and investigated in 2015. Data was collected through a self-made questionnaire and then analyzed using the SPSS software version 22 at a signiﬁcance level of P = 0.05 using frequency tables, chart, Chi-square, and logistic regression test. Results: Theprevalenceof psychoactivedrugsconsumptionwas5.6%. Themostimportantfactorof tendencytowardsconsumption of psychoactive drugs among students has been failure to meet their emotional needs (35.7%), yet taking pleasure has been the mainspring for consuming these drugs in most cases (50%). There was a statistical signiﬁcant relationship between psychoactive drugs consumption and age, place of residence, drug history in parents, and being exposed to cigarette smoke throughout the day (P < 0.05). The most commonly estimated odds ratio (OR = 13.08) was related to non-native students. Conclusions: Due to the relatively high prevalence of psychoactive drugs consumption in students of medical sciences as mes-sengers of health, holding life skill workshops and consulting with students, providing appropriate recreational facilities seem essential in order to reduce the prevalence and prevent this dilemma.
2 Secreted Phospholipases A Surfactant Phospholipid Hydrolysis by Inhibitory Effects of Surfactant Protein A on

Hydrolysis of surfactant phospholipids by secreted phospholipases A 2 (sPLA 2 ) contributes to surfactant dysfunction in acute respiratory distress syndrome. The present study demonstrates that sPLA 2 -IIA, sPLA 2 -V, and sPLA 2 -X efﬁciently hydrolyze surfactant phospholipids in vitro. In contrast, sPLA 2 -IIC, -IID, -IIE, and -IIF have no effect. Since puriﬁed surfactant protein A (SP-A) has been shown to inhibit sPLA 2 -IIA activity, we investigated the in vitro effect of SP-A on the other active sPLA 2 and the consequences of sPLA 2 -IIA inhibition by SP-A on surfactant phospholipid hydrolysis. SP-A inhibits sPLA 2 -X activity, but fails to interfere with that of sPLA 2 -V. Moreover, in vitro inhibition of sPLA 2 -IIA-induces surfactant phospholipid hydrolysis correlates with the concentration of SP-A in surfactant. Intratracheal administration of sPLA 2 -IIA to mice causes hydrolysis of surfactant phosphatidylglycerol. Interestingly, such hydrolysis is signiﬁcantly higher for SP-A gene-targeted mice, showing the in vivo inhibitory effect of SP-A on sPLA 2 -IIA activity. Administration of sPLA 2 -IIA also induces respiratory distress, which is more pronounced in SP-A gene-targeted mice than in wild-type mice. We conclude that SP-A inhibits sPLA 2 activity, which may play a protective role by maintaining surfactant integrity during lung injury. The Journal of Immunology, 2003, 171: 995–1000.
Femtosecond Pulse Laser Near-Field Ablation of Ag Nanorods

Ag nanorods (Ag NRs) with a mean aspect ratio of 3.9 were prepared through a wet-chemical method, and the absorption spectra for various aspect ratios were obtained. The morphology transformation of Ag NRs irradiated with a femtosecond pulse laser was investigated through transmission electron microscopy (TEM). The near-field ablation was dependent on the laser polarization and wavelength. Laser-induced high electric field intensity was observed at the ends, middle, and junctions of the Ag NRs under various ablation conditions. Through simulation, the evolution mechanism was analyzed in detail. The effect of laser polarization angle on plasmonic junction welding was also investigated. By controlling the electronic field distribution, several nanostructures were obtained: bone-shaped NRs, T-shaped NRs, dimers, trimers, curved NRs, and nanodots. This study suggests a potentially useful approach for the reshaping, cutting, and welding of nanostructures.
Socio Demography and Physical Environment Factors Against the Incidence of Dengue Hemorrhagic Fever in Delta Pawan District,

Dengue Hemorrhagic Fever is an environmentally-based dangerous disease which is still a world health problem. WHO noted that Indonesia is a country with the highest cases of Dengue Hemorrhagic Fever (DHF) in Southeast Asia (WHO, 2016). In 2019 the cases increased with the number of cases 137.761. West Kalimantan Province is one of the 5 th highest provinces out of 34 provinces in Indonesia for 2018. Ketapang Regency is in the first place with the highest number of cases in Delta Pawan District. The purpose of this study was to determine the effect of socio demography and physical environment on the incidence of Dengue Hemorrhagic Fever. This study used a case control design. The research sample was 132 respondents (66 cases and 66 controls) respondents obtained by purposive sampling technique. Data collection techniques by interviewing, questionnaires, and observations. Data analysis using chi-square. The results showed that there was a relationship between income (p = 0.024), ventilation (p = 0.005) and water reservoirs (p = 0.023). There was no relationship between population mobility (p = 0.601) and house distance (p = 0.577) with the incidence of dengue hemorrhagic fever. The conclusion of this