Miracle-dz/UniFAR-FTUs huggingface dataset:
Triheptanoin Protects Motor Neurons and Delays the Onset of Motor Symptoms in a Mouse Model of Amyotrophic Lateral Sclerosis

There is increasing evidence that energy metabolism is disturbed in Amyotrophic Lateral Sclerosis (ALS) patients and animal models. Treatment with triheptanoin, the triglyceride of heptanoate, is a promising approach to provide alternative fuel to improve oxidative phosphorylation and aid ATP generation. Heptanoate can be metabolized to propionyl-CoA, which after carboxylation can produce succinyl-CoA and thereby re-fill the tricarboxylic acid (TCA) cycle (anaplerosis). Here we tested the hypothesis that treatment with triheptanoin prevents motor neuron loss and delays the onset of disease symptoms in female mice overexpressing the mutant human SOD1G93A (hSOD1G93A) gene. When oral triheptanoin (35% of caloric content) was initiated at P35, motor neuron loss at 70 days of age was attenuated by 33%. In untreated hSOD1G93A mice, the loss of hind limb grip strength began at 16.7 weeks. Triheptanoin maintained hind limb grip strength for 2.8 weeks longer (p<0.01). Loss of balance on the rotarod and reduction of body weight were delayed by 13 and 11 days respectively (both p<0.01). Improved motor function occurred in parallel with alterations in the expression of genes associated with muscle metabolism. In gastrocnemius muscles, the mRNA levels of pyruvate, 2-oxoglutarate and succinate dehydrogenases and methyl-malonyl mutase were reduced by 24–33% in 10 week old hSOD1G93A mice when compared to wild-type mice, suggesting that TCA cycling in skeletal muscle may be slowed in this ALS mouse model at a stage when muscle strength is still normal. At 25 weeks of age, mRNA levels of succinate dehydrogenases, glutamic pyruvic transaminase 2 and the propionyl carboxylase β subunit were reduced by 69–84% in control, but not in triheptanoin treated hSOD1G93A animals. Taken together, our results suggest that triheptanoin slows motor neuron loss and the onset of motor symptoms in ALS mice by improving TCA cycling.
Prognostic importance of plasma total magnesium in a cohort of cats with azotemic chronic kidney disease

Background Hypomagnesemia is associated with increased mortality and renal function decline in humans with chronic kidney disease (CKD). Magnesium is furthermore inversely associated with fibroblast growth factor 23 (FGF23), an important prognostic factor in CKD in cats. However, the prognostic significance of plasma magnesium in cats with CKD is unknown. Objectives To explore associations of plasma total magnesium concentration (tMg) with plasma FGF23 concentration, all‐cause mortality, and disease progression in cats with azotemic CKD. Animals Records of 174 client‐owned cats with IRIS stage 2‐4 CKD. Methods Cohort study. Cats with azotemic CKD were identified from the records of two London‐based first opinion practices (1999–2013). Possible associations of baseline plasma tMg with FGF23 concentration and risks of death and progression were explored using, respectively, linear, Cox, and logistic regression. Results Plasma tMg (reference interval, 1.73–2.57 mg/dL) was inversely associated with plasma FGF23 when controlling for plasma creatinine and phosphate concentrations (partial correlation coefficient, −0.50; P < .001). Hypomagnesemia was observed in 12% (20/174) of cats, and independently associated with increased risk of death (adjusted hazard ratio, 2.74; 95% confidence interval [CI], 1.35–5.55; P = .005). The unadjusted associations of hypermagnesemia (prevalence, 6%; 11/174 cats) with survival (hazard ratio, 2.88; 95% CI, 1.54–5.38; P = .001), and hypomagnesemia with progressive CKD (odds ratio, 17.7; 95% CI, 2.04–154; P = .009) lost significance in multivariable analysis. Conclusions and Clinical Importance Hypomagnesemia was associated with higher plasma FGF23 concentrations and increased risk of death. Measurement of plasma tMg augments prognostic information in cats with CKD, but whether these observations are associations or causations warrants further investigation.
Placental membrane aging and HMGB1 signaling associated with human parturition

Aging is associated with the onset of several diseases in various organ systems; however, different tissues may age differently, rendering some of them dysfunctional sooner than others. Placental membranes (fetal amniochorionic membranes) protect the fetus throughout pregnancy, but their longevity is limited to the duration of pregnancy. The age-associated dysfunction of these membranes is postulated to trigger parturition. Here, we investigated whether cellular senescence—the loss of cell division potential as a consequence of stress—is involved in placental membrane function at term. We show telomere reduction, p38 MAPK activation, increase in p21 expression, loss of lamin B1 loss, increase in SA-β-galactosidase, and senescence-associated secretory phenotype (SASP) gene expression in placental membranes after labor and delivery (term labor [TL]) compared to membranes prior to labor at term (term, not-in-labor [TNIL]). Exposing TNIL placental membranes to cigarette smoke extract, an oxidative stress inducer, also induced markers of cellular senescence similar to those in TL placental membranes. Bioinformatics analysis of differentially expressed SASP genes revealed HMGB1 signaling among the top pathways involved in labor. Further, we show that recombinant HMGB1 upregulates the expression of genes associated with parturition in myometrial cells. These data suggest that the natural physiologic aging of placental tissues is associated with cellular senescence and human parturition.
The relation of sulfur metabolism to acid-base balance and electrolyte excretion: the effects of DL-methionine in normal man.

It has been known for many years that most of the inorganic sulfate in the urine is derived from the oxidation of sulfur-containing organic compounds. In the classical calculation of the "acidbase balance" of food each Mole of sulfur in the ash is assigned an acid equivalence of two, thus assuming its quantitative conversion to sulfuric acid or to some other strong acid or acids which yield a total of two equivalents of hydrogen ion
Voting for Women in Belgium's Flexible List System

Proportional electoral systems tend to be more beneficial for women's descriptive representation than majority systems. However, within proportional systems the gender equality of election outcomes differs, highlighting the importance of studying the actual use of electoral provisions in proportional representation (PR) systems. Therefore, we investigate the determinants of voting for female candidates in Belgium's local elections. This case is particularly interesting given the equal number of men and women on the candidate lists due to quota regulations, the possibility to cast multiple preference votes (lowering competition), and the high visibility of these local elections and its candidates. At the individual level, we find that women are more likely than men to vote for several women, yet same-sex voting is more common among men. Politically sophisticated respondents vote more often for candidates of both sexes. Against our expectations, a left-wing orientation does not increase the likelihood of voting for women. At the electoral district level, a larger supply of women at the top list position increases the chance to vote for this top woman, but there is no spillover effect to women lower on the list. District magnitude affects the number of preference votes but, against expectations, not the likelihood of voting for women.
Habitual intake of anthocyanins and flavanones and risk of cardiovascular disease in men12

Background: Although increased fruit intake reduces cardiovascular disease (CVD) risk, which fruits are most beneficial and what key constituents are responsible are unclear. Habitual intakes of flavonoids, specifically anthocyanins and flavanones, in which >90% of habitual intake is derived from fruit, are associated with decreased CVD risk in women, but associations in men are largely unknown. Objective: We examined the relation between habitual anthocyanin and flavanone intake and coronary artery disease and stroke in the Health Professionals Follow-Up Study. Design: We followed 43,880 healthy men who had no prior diagnosed CVD or cancer. Flavonoid intake was calculated with the use of validated food-frequency questionnaires. Results: During 24 y of follow-up, 4046 myocardial infarction (MI) and 1572 stroke cases were confirmed by medical records. Although higher anthocyanin intake was not associated with total or fatal MI risk, after multivariate adjustment an inverse association with nonfatal MI was observed (HR: 0.87; 95% CI: 0.75, 1.00; P = 0.04; P-trend = 0.098); this association was stronger in normotensive participants (HR: 0.81; 95% CI: 0.69, 0.96; P-interaction = 0.03). Anthocyanin intake was not associated with stroke risk. Although flavanone intake was not associated with MI or total stroke risk, higher intake was associated with a lower risk of ischemic stroke (HR: 0.78; 95% CI: 0.62, 0.97; P = 0.03, P-trend = 0.059), with the greatest magnitude in participants aged ≥65 y (P-interaction = 0.04). Conclusions: Higher intakes of fruit-based flavonoids were associated with a lower risk of nonfatal MI and ischemic stroke in men. Mechanistic studies and clinical trials are needed to unravel the differential benefits of anthocyanin- and flavanone-rich foods on cardiovascular health.
[Therapeutic effects of acupuncture combined with rehabilitation training on dysphagia in post-stroke pseudobulbar palsy].

OBJECTIVE To compare the therapeutic effects on dysphagia in post-stroke pseudobulbar palsy between the combined treatment with acupuncture and rehabilitation training and the combined treatment with low-frequency electrical therapy and rehabilitation training and to explore its more effective therapy, using the ultrasonographic examination. METHODS A total of 60 patients of dysphagia in post-stroke pseudobulbar palsy were randomly assigned into an observation group and a control group, 30 cases in each one. The rehabilitation treatment was provided in the two groups. Additionally, in the observation group, acupuncture was used at the three-tongue points [Shanglianquan (Extra), located in the depression between the lingual bone and the border of lower jaw, 1 cun inferior to the midline of the jaw; and the other two points, located at 0.8 cun bilateral to Shanglianquan (Extra)], bilateral Fengchi (GB 20) and Fengfu (GV 16). After arrival of qi, the last two tongue-points were stimulated with electricity, with disperse-dense wave, periodically at 2 Hz, 10 Hz and 100 Hz, at the interval of 3 s, lasting for 30 min. Bilateral Fengchi (GB 20) was stimulated with electricity, with disperse-dense wave and the same frequency as above, lasting for 30 min. In the control group, the low-frequency electrical stimulation was adopted. The electrodes were placed on the bilateral sides of the midline of the throat, 30 min each time. The treatment was for 1 month in the two groups, once a day. The scores of the standardized swallowing assessment (SSA) and the videofluoroscopy swallowing study (VFSS) were observed and the reducing rate of the hyoid-thyroid cartilage distance was determined with ultrasound quantitative measure. RESULTS After treatment, SSA scores of the two groups were all lower than those before treatment and VFSS scores were higher than those before treatment (all P<0.05). The above scores in the observation group were better than those in the control group (both P<0.05). The reducing rates of the hyoid-thyroid cartilage distance were higher than those before treatment in the two groups (both P<0.05). The result in the observation group was higher than that in the control group (P<0.05). CONCLUSION The treatments with acupuncture and rehabilitation training or with the low-frequency electrical therapy and rehabilitation obtain the effects on dysphagia in post-stroke pseudobulbar palsy in the patients. The effects of the combined treatment with acupuncture and rehabilitation training are better. The ultrasonographic technology effectively and quantitatively analyzes the changes in the glossopharyngeal complex in the patients of dysphagia.
Comparative study on effects of four energy plants growth on chemical fractions of heavy metals and activity of soil enzymes in copper mine tailings

ABSTRACT Four gramineous energy plants, Miscanthus sacchariflorus, M. floridulus, Phragmites australis, and Arundo donax were grown on copper tailings in the field for four years. Their phytoremediation potential was examined in terms of their effects on the fractions of heavy metals and soil enzyme activities. Results showed that plantation of these four gramineous plants has improved the proportion of organic material (OM)-binding fraction of heavy metals in copper tailings as a whole, and reduced the proportion of exchangeable and residual fractions. In particular, M. sacchariflorus growth improved significantly the proportion of the OM-binding fractions of Cu (1.73 times), Cd (1.71 times), Zn (1.18 times), and Pb (3.14 times) (P < 0.05) and reduced markedly the residual fractions of Cu (64.45%), Cd (82.38%), Zn (61.43%), and Pb (73.41%) (P < 0.05). Except for A. donax, the growth of other three energy plants improved the activity of phosphatase, urease and dehydrogenase in copper tailings to some extent. In particular, the activity of soil phosphatase and urease in planted tailings differed significantly from that of control (P < 0.05). The effect of M. sacchariflorus growth on soil enzyme was the highest, followed by P. australis, M. floridulus, and A. donax. The content of each heavy metal fraction in soil was correlated with soil enzyme activities, especially the content of OM-binding fraction, which correlated significantly with the activities of phosphatase, urease and dehydrogenase in soil. According to the effects of four gramineous plants growth on activity of soil enzymes and fractions of heavy metals, M. sacchariflorus had the optimal effects for phytoremediation. Therefore, M. sacchariflorus was a candidate plant with great potential for the revegetation of heavy metal tailings.
Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

A large series of variously substituted amino(pyren-1-yl)methylphosphonic acid derivatives was synthesized using a modified aza-Pudovik reaction in 20–97% yields. The fluorescence properties of the obtained compounds were investigated revealing that N-alkylamino(pyren-1-yl)methylphosphonic derivatives are stronger emissive compounds than the corresponding N-aryl derivatives. N-Benzylamino(pyren-1-yl)methylphosphonic acid displayed strong fluorescence (ΦF = 0.68) in phosphate-buffered saline (PBS). The influence of a series of derivatives on two colon cancer cell lines HT29 and HCT116 was also investigated. The most promising results were obtained for N-(4-methoxyphenyl)amino(pyren-1-yl)methylphosphonate, which was found to be cytotoxic for the HCT116 cancer cell line (IC50 = 20.8 μM), simultaneously showing weak toxicity towards normal lymphocytes (IC50 = 230.8 µM).
Learning Translations via Images: A Large Multilingual Dataset and Comprehensive Study

We conduct the most comprehensive study to date into translating words via images. To facilitate research on the task, we introduce a large-scale multilingual corpus of images, each labeled with the word it represents. Past datasets have been limited to only a few high-resource languages and unrealistically easy translation settings. In contrast, we have collected by far the largest available dataset for this task, with images for approximately 10,000 words in each of 100 languages. We run experiments on a dozen high resource languages and 20 low resources languages, demonstrating the effect of word concreteness and part-of-speech on translation quality. To improve image-based translation, we introduce a novel method of predicting word concreteness from images, which improves upon previously state-of-the-art unsupervised techniques. This allows us to predict when image-based translation may be effective, enabling consistent improvements to a state-of-the-art text-based word translation system. Our code and dataset will be made available.
Protein side‐chain rearrangement in regions of point mutations

A major problem in predicting amino acid side‐chain rearrangements following point mutations is the potentially large search space. We analyzed a nonredundant data set of 393 Protein Data Bank protein pairs, each consisting of structures differing in one amino acid, to determine the number of residues changing conformation in the region of mutation. In 91–95% of cases, two or fewer residues underwent side‐chain conformational change. If mutation sites with backbone displacements were excluded, the number increased to 97%. The majority of rearrangements (over 60%) were due to the inherent flexibility of side‐chains, as derived from analysis of a control set of protein subunits whose crystal structures were determined more than once. Different amino acids demonstrated different degrees of flexibility near mutation sites. Large polar or charged residues, and serine, are more flexible, while the aromatic amino acids, and cysteine, are less so. This pattern is common to the inherent side‐chain flexibility, as well as the increased flexibility at ligand binding sites and mutation sites. The probability for conformational change was correlated with B‐factor, frequency of the side‐chain conformation in proteins and solvent accessibility. The last trend was stronger for aromatic and hydrophilic residues than for hydrophobic ones. We conclude that the search space for predicting side‐chain conformations in the region of mutation can be effectively restricted. However, the overall ability to predict a particular side‐chain conformation, or to check predictions according to individual existing structures, is limited. These findings may be useful in deriving empirical rules for modeling side‐chain conformations. Proteins 2003;50:272–282. © 2002 Wiley‐Liss, Inc.
A Novel Wound Rotor Type for Brushless Doubly Fed Induction Generator

The rotor configuration of the brushless doubly fed induction generator (BDFIG) plays an important role in its performance. In order to make the magnetomotive force (MMF) space vector in one set rotor windings to couple both magnetic fields with different pole-pair and have low resistance and inductance, this paper presents a novel wound rotor type for BDFIG with low space harmonic contents. In accordance with the principles of slot MMF harmonics and unequal element coils, this novel rotor winding is designed to be composed of three-layer unequal-pitch unequal-turn coils. The optimal design process and rules are given in detail with an example. The performance of a 700kW 2/4 pole-pair prototype with the proposed wound rotor is analyzed by the finite element simulation and experimental test, which are also carried out to verify the effectiveness of the proposed wound rotor configuration.
Quantitative program slicing: Separating statements by relevance

Program slicing is a popular but imprecise technique for identifying which parts of a program affect or are affected by a particular value. A major reason for this imprecision is that slicing reports all program statements possibly affected by a value, regardless of how relevant to that value they really are. In this paper, we introduce quantitative slicing (q-slicing), a novel approach that quantifies the relevance of each statement in a slice. Q-slicing helps users and tools focus their attention first on the parts of slices that matter the most. We present two methods for quantifying slices and we show the promise of q-slicing for a particular application: predicting the impacts of changes.
Why are top universities losing their lead? An economics modelling-based approach

Scientific output of lower-ranked institutions is catching up with leading universities. We present a simple, conceptual model of research production describing the dynamic interaction between inputs (research staff and funding) and outputs (publications and citations). Results support an ‘emergent’ phase of science with elite leading universities, evolving to a ‘mature’ phase of consolidation, standardization, and catch-up of follower universities. Productivity differences between senior and junior researchers and the ‘start-up’ costs of research equipment may explain this, together with advances in information technology. Improved detection and support of emergent sciences may be achieved by specialized data analysis and directed research funding. Copyright , Beech Tree Publishing.
Epigenetic silencing of lncRNA MORT in 16 TCGA cancer types

We have previously described a hominid-specific long non-coding RNA, MORT (also known as ZNF667-AS1, Gene ID: 100128252), which is expressed in all normal cell types, but epigenetically silenced during cancer-associated immortalization of human mammary epithelial cells. Initial analysis of The Cancer Genome Atlas (TCGA) showed that 15 of 17 cancer types, which represent the 10 most common cancers in women and men, display DNA methylation associated MORT silencing in a large fraction of their tumors. In this study we analyzed MORT expression and DNA methylation state in the remaining 16 TCGA cancer types not previously reported. Seven of the 16 cancer types showed DNA methylation linked MORT silencing in a large fraction of their tumors. These are carcinomas (cervical cancer, and cancers of esophagus, stomach, and bile duct), and the non-epithelial tumors mesothelioma, sarcoma, and uterine carcinosarcoma. Together with the findings from our previous report, MORT expression is silenced by aberrant DNA methylation in 22 of 33 of TCGA cancer types. These 22 cancers include most carcinoma types, blood derived cancers and sarcomas. In conclusion, results suggest that the MORT gene is one of the most common epigenetic aberrations seen in human cancer. Coupled with the timing of MORT gene silencing during in vitro epithelial cell immortalization and its occurrence early in the temporal arc of human carcinogenesis, this provides strong circumstantial evidence for a tumor suppressor role for MORT.
The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats

Background: Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Methods: Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. Results: Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months. Conclusion: Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings.