Miracle-dz/UniFAR-FTUs huggingface dataset:
Ubiquitin Lys63 is involved in ubiquitination of a yeast plasma membrane protein

We have recently reported that the yeast plasma membrane uracil permease undergoes cell‐surface ubiquitination, which is dependent on the Npi1/Rsp5 ubiquitin–protein ligase. Ubiquitination of this permease, like that of some other transporters and receptors, signals endocytosis of the protein, leading to its subsequent vacuolar degradation. This process does not involve the proteasome, which binds and degrades ubiquitin–protein conjugates carrying Lys48‐linked ubiquitin chains. The data presented here show that ubiquitination and endocytosis of uracil permease are impaired in yeast cells lacking the Doa4p ubiquitin–isopeptidase. Both processes were rescued by overexpression of wild‐type ubiquitin. Mutant ubiquitins carrying Lys→Arg mutations at Lys29 and Lys48 restored normal permease ubiquitination. In contrast, a ubiquitin mutated at Lys63 did not restore permease polyubiquitination. Ubiquitin–permease conjugates are therefore extended through the Lys63 of ubiquitin. When polyubiquitination through Lys63 is blocked, the permease still undergoes endocytosis, but at a reduced rate. We have thus identified a natural target of Lys63‐linked ubiquitin chains. We have also shown that monoubiquitination is sufficient to induce permease endocytosis, but that Lys63‐linked ubiquitin chains appear to stimulate this process.
Potentiation of Friend Viral Leukemogenesis by 9,10-Dimethyl-1,2-benzanthracene in Two Strains of Mice 1

Abstract The polycyclic aromatic hydrocarbon, 9,10-dimethyl-1,2-benzanthracene (DMBA) produced malignancy involving the spleen in SJL/J and B10SJF1 mice when injected ip at 500 μg per mouse either alone or in combination with threshold doses of Friend leukemia virus (FLV). The mice that received both chemical and virus died significantly sooner than mice that received either chemical or virus alone, and a synergism between DMBA and FLV was demonstrated in both the virus-resistant B10SJF1 hybrids and virus-sensitive SJL/J mice.
Mitochondrial tRNA mutations are associated with maternally inherited hypertension in two Han Chinese pedigrees

We report here the clinical, genetic, molecular, and biochemical evaluations in two Han Chinese families with maternally inherited hypertension. Fourteen of 20 adult matrilineal relatives of these families exhibited a wide range of severity in hypertension, while none of offspring of affected fathers had hypertension. The age‐at‐onset of hypertension in matrilineal relatives varied from 37 years to 83 years, with an average of 55 and 66 years, respectively. Mutational analysis of their mitochondrial genomes identified the m.4353T>C mutation in the tRNA, in conjunction with the known m.593C>T mutation in the tRNAPhe and m.5553C>T mutation in the tRNATrp. Northern analysis revealed that m.4353T>C, m.593C>T and m.5553C>T mutations caused ∼66%, 65%, and 12% reductions in the steady‐state level of tRNAGln, tRNAPhe and tRNATrp, respectively. An in vivo protein labeling analysis showed ∼35% reduction in the rate of mitochondrial translation in cells carrying these tRNA mutations. Impaired mitochondrial translation is apparently a primary contributor to the reduced rates of overall respiratory capacity, malate/glutamate‐promoted respiration, succinate/glycerol‐3‐phosphate‐promoted respiration, or N,N,N′,N′‐tetramethyl‐p‐phenylenediamine/ascorbate‐promoted respiration and the increasing level of reactive oxygen species in the cells carrying these mtDNA mutations. These data demonstrate that mitochondrial dysfunction caused by mitochondrial tRNA mutations is associated with essential hypertension in these families. Hum Mutat 33:1285–1293, 2012. © 2012 Wiley Periodicals, Inc.
A simplified model for dynamic behavior of permanent magnet synchronous generator for direct drive wind turbines

In this paper, a simplified model to represent variable speed wind turbines in power system dynamics simulations is presented. This model is based in the use of controls-oriented model for permanent magnet synchronous generator supplying voltage-stiff bus system, including intrinsic torque/load properties. First, the modeling approach is commented upon and models of the subsystems of which a variable speed wind turbine consists are discussed. Then, time-domain simulations have been performed for one study case in order to demonstrate the suitable use of the model proposed in this paper. Results have shown that the model developed performs satisfactorily for slow dynamic when compared with the results obtained from simulation considering the detailed model.
Intestinal pathology associated with Trichostrongylus colubriformis infection in sheep: histology

Observations were made on the histology of tissues from the first 6–10 m of the small intestine from both sheep infected with Trichostrongylus colubriformis and from uninfected controls. In uninfected animals, and in distal samples from infected lambs, villi were tall and covered by tall columnar epithelium, the intestinal crypts were convoluted and the lamina propria was only moderately cellular. In tissues with sub-total villus atrophy and a convoluted surface, the superficial epithelium was usually low columnar, often with an indistinct brush border. More severely affected mucosa was flat, with low surface epithelium and protruding crypt openings. The flat surfaces frequently had leaks of eosinophilic material and polymorphonuclear cells between enterocytes, or through erosions in the epithelium. Such defects were smaller and less frequent in mucosa with a convoluted surface. There were increased mitoses in intestinal crypts and a heavy inflammatory cell infiltrate in the lamina propria. Mast cell, globule leucocyte and theliolymphocyte numbers were not increased in infected sheep.
The Impact of Systemic Vasoconstrictors on the Cerebral Circulation of Anesthetized Patients

Background The effect of vasoconstrictors on intracerebral hemodynamics in anesthetized patients is controversial. The influence of phenylephrine and norepinephrine on the cerebral circulation was investigated in isoflurane‐ or propofol‐anesthetized patients using transcranial Doppler ultrasonography. Methods Forty patients were randomly assigned to have vasoconstrictor tests with norepinephrine or phenylephrine during either isoflurane or propofol anesthesia. Blood flow velocities were simultaneously measured in the middle cerebral artery and ipsilateral extracranial internal carotid artery. Baseline recordings were done during stable anesthesia in a supine position (test 0). A second series of measurements were performed after norepinephrine or phenylephrine had increased mean arterial blood pressure by about 20% (test 1). With maintained norepinephrine or phenylephrine infusion, a final series of results were obtained after the increased mean arterial blood pressure was counteracted by a slightly head‐up patient position (test 2). Results Both vasoconstrictors significantly increased mean flow velocities in the middle cerebral artery (norepinephrine: 43 +/‐ 11 cm/s to 49 +/‐ 11 cm/s; phenylephrine: 43 +/‐ 8 cm/s to 48 +/‐ 9 cm/s; +/‐ SD) and internal carotid artery (norepinephrine: 27 +/‐ 7 cm/s to 31 +/‐ 8 cm/s; phenylephrine: 27 +/‐ 9 cm/s to 31 +/‐ 10 cm/s) in the isoflurane‐but not in the propofol‐anesthetized patients. In the head‐up position, only small and insignificant flow velocity changes were observed in both cerebral arteries independent of the vasoconstrictor or background anesthetic. Conclusions The results of the present study indicate that norepinephrine and phenylephrine do not directly affect intracranial hemodynamics in anesthetized patients, but rather that hemodynamic changes observed with vasoconstrictors reflect the effect of the background anesthetic agents on cerebral pressure autoregulation.
Multiscale Retinex

While the retinex theory aimed at explaining human color perception, its derivations have led to eﬃcient algorithms enhancing local image contrast, thus permitting among other features, to “see in the shadows”. Among these derived algorithms, Multiscale Retinex is probably the most successful center-surround image ﬁlter. In this paper, we oﬀer an analysis and implementation of Multiscale Retinex. We point out and resolve some ambiguities of the method. In particular, we show that the important color correction ﬁnal step of the method can be seriously improved. This analysis permits to formulate an automatic implementation of Multiscale Retinex which is as faithful as possible to the one described in the original paper. Overall, this implementation delivers excellent results and conﬁrms the validity of Multiscale Retinex for image color restoration and contrast enhancement. Nevertheless, while the method parameters can be ﬁxed, we show that a crucial choice must be left to the user, depending on the lightning condition of the image: the method must either be applied to each color independently if a color balance is required, or to the luminance only if the goal is to achieve local contrast enhancement. Thus, we propose two slightly diﬀerent algorithms to deal with both cases.
Ethnicity and the Course of Tardive Dyskinesia in Outpatients Presenting to the Motor Disorders Clinic at the Maryland Psychiatric Research Center

Background: Although newly emergent tardive dyskinesia (TD) is less of a concern, about one-fourth to one-third of patients on or previously on chronic first-generation antipsychotic agents have TD. The long-term course and outcome, as well as their predictors, are unknown. Earlier studies identify ethnicity as one of the risk factors for the development of TD, and case reports have noted a preponderance of African-American males in cohorts of patients with tardive dystonia. The current study examines the anatomic distribution and course of TD in a cohort of schizophrenia patients of European and African descent with TD who were referred to the Motor Disorders Clinic (MDC). Methods: We evaluated data collected on 1149 TD patients who were given a focused neurologic examination for movement disorders. Movements were evaluated with the MPRC Scale for Involuntary Movements (IMS). All patients met RDC-TD criteria for diagnosis of persistent TD. One to 10-year follow-up data on 528 patients were evaluated to examine the course of TD following recommendations made to referring primary clinicians. Suggested interventions to referring primary clinicians included dose reduction of first-generation antipsychotic medication, or switching to a second-generation antipsychotic. Results: Initial evaluation included 701 European American (EA) patients and 448 African-American (AA) patients. AA patients had a significantly higher proportion of males [χ2(1) = 7.50, P < 0.05]. EA subjects had a higher mean age than AA patients 42.8 ± 11.2 and 39.8 ± 10.4, respectively [F(1,1147) = 22.27, P < 0.05]. Mean neuroleptic exposure (chlorpromazine equivalents) was similar in both groups after controlling for differences in age. Follow-up data analyzed in 528 patients (329 EA and 199AA) showed a significant ethnicity by TD interaction [F(1,504) = 4.26, P < 0.05]. Examination of body distribution of dyskinetic movements showed an effect of ethnicity. Subsequent analyses suggest EA patients experienced more improvement in TD over the course of follow up [F(1,319) = 22.39, P < 0.05] compared with AAs [F(1,189) = 1.58, P > 0.05]. These findings were unchanged when age, change in antipsychotic drug dose, and duration of follow-up were covaried. Conclusion: Reports from earlier studies note ethnicity (African descent) as a risk factor in the development of TD. Our study findings suggest ethnicity might be an important factor in predicting a poor course of TD.
Vitamin D and Cardiovascular Risk in Children

Objective: Vitamin D is a group of fat-soluble molecules that are structurally similar to steroids. Emerging data have led to the hypothesis that Vitamin D plays a role in the regulation of many physiological processes beyond calcium and phosphorus homeostasis. With this review, we aimed to summarize the changes in Vitamin D levels in children with cardiovascular diseases based on the literature. In addition, we also reviewed the potential mechanisms underlying cardiovascular diseases associated with Vitamin D deficiency or insufficiency. Data Sources: The articles in English were searched from PubMed (1968–2016) and EMBASE (1991–2016), with the keywords of “Vitamin D AND cardiovascular diseases” and “Vitamin D AND children. ” Study Selection: Original articles and critical reviews about Vitamin D and cardiovascular risk in children were selected for review. Researches focused on adults were excluded. Results: Studies have shown that several pediatric cardiovascular diseases may be associated with Vitamin D deficiency or insufficiency, including hypertension, orthostatic intolerance, and Kawasaki disease. Conclusions: Vitamin D may play a role in the regulation of the cardiovascular system. Further investigation would hopefully disclose the usefulness of Vitamin D as a biomarker for cardiovascular diseases in children.
Regulation of the Renal Sodium-Dependent Phosphate Cotransporter NaPi2 (Npt2) in Acute Renal Failure due to Ischemia and Reperfusion

Background: Acute renal failure (ARF) is associated with hyperphosphatemia and decreased urinary phosphate excretion. The present study was undertaken to characterize the effects of ARF due to ischemia and reperfusion on renal phosphate transport and on gene and pro- tein expression of type IIa NaPi cotransporter (Npt2) the physiologically most relevant renal sodium-dependent phosphate cotransporter. Methods: The following groups of rats with intact parathyroid glands were studied: (1) sham operated (sham); (2) after 1 h ischemia by bilateral renal artery clamping (I), and after 1 h ischemia and reperfusion of 1 h (I + R 1 h); (3) 24 h (I + R 24 h); (4) 48 h (I + R 48 h), and (5) 72 h (I + R 72 h) duration. The effect of ARF on Npt2 mRNA and protein expression was also examined after parathyroidectomy (PTX) of 2 and 4 days’ duration. Results: Ischemia and reperfusion were associated with increases in plasma creatinine, hyperphosphatemia, and with decreased tubular phosphate reabsorption. Npt2 mRNA was significantly downregulated in the cortex, maximal at 24 and 48 h of reperfusion. The degree of Npt2 mRNA downregulation was not affected by PTX of 2–4 days’ duration. The abundance of Npt2 protein in proximal tubular apical brush border membrane was markedly decreased after reperfusion. Npt2 protein, however, was more abundant in PTX animals than in those with intact parathyroids and a similar degree of renal insufficiency. The immunohistochemical analysis of proximal tubular apical brush border membrane showed a progressive decrease of Npt2 protein labeling after ischemia and reperfusion, with progressive regeneration after 72 h. Conclusion: These results suggest that downregulation of Npt2 protein may contribute to the decreased tubular reabsorption of phosphate in acute ischemic renal failure and hyperphosphatemia.
The Influences of Cognitive Resources on Adaptation and Old Age

In the Georgia Centenarian Study, cognitive resources were estimated by fluid and crystallized intelligence, acquisition and retrieval of new information, retrieval of familiar information, and problem-solving ability in community-dwelling and nondemented adults ranging from sixty to one hundred plus years of age. Five clusters of results were found: 1) cognitive performances were lower for the older cohorts; 2) when cognitive activities were dependent on everyday experiences, no age-related problem-solving decline was found; 3) physical health and mental health can significantly influence cognitive performances; 4) cognitive and personality factors can combine to account for a larger amount of adaptation variance than can be accounted for by either of the factors alone; and 5) individuals with a high level of intelligence and affect sustain their instrumental activities of daily living. Cognitive resources were an important contributor to successful adaptation for the oldest-old.
Table of Content Comparison of Neural Network and Fast Fourier Transform Based Selective 1 Harmonic Extraction and Total Harmonic Reduction for Power Electronic Converters

A new strategy to estimate harmonic distortion from an AC line is presented for power electronic converters. An Adaptive linear neural network (ADALINE) is used to determine precisely the necessary currents in order to cancel harmonics. The proposed strategy is based on an original decomposition of the measured currents to specify the neural network inputs. This new decomposition is based on the Fourier series analysis of the current signals and Least Mean Square (LMS) training algorithm carries out the weights. This new estimation strategy appreciably improves the performances of traditional compensating methods and is valid both for single-phase and three-phase systems. The proposed strategy also allows extracting the harmonics individually. The method is based on the extraction of fundamental components of distorted line current using an ADALINE network. The output of the ADALINE is compared with distorted supply current to construct modulating signals and to generate PWM pulses for active line conditioner. Speed and accuracy of ADALINE results in improved performance of the active power line filter. In this paper converter is used as a non-linear load. The performance of ADALINE is verified with single phase fully controlled AC-DC converter simulated with neural network based active filter using MATLAB/SIMULINK. Also in this paper, harmonic components can be selectively extracted using ADALINE network and harmonic content analyzed by artificial neural network (ANN) is compared with the Fast Fourier Transform (FFT).
MRI versus Ultrasonography and Mammography for Preoperative Assessment of Breast Cancer

Mammography and ultrasonography are traditional for preoperative estimation of breast cancer size; magnetic resonance imaging (MRI) is more recent but not as well studied. We compared ultrasonography, mammography, and MRI for preoperative imaging of primary breast cancer presenting as a mass in patients treated at our center over a 2-year period. Of the 61 breast cancers with all three imaging modalities performed, 52 were infiltrating ductal cancer, 5 were infiltrating lobular cancer, 2 were ductal carcinoma in situ, and 2 were other histologic types. When pathologic size was used to determine the accuracy of imaging assessments, the Pearson correlation coefficient was better for MRI (r = 0.80) than ultrasonography (r = 0.57) or mammography (r = 0.26). Mean tumor size was 2.1 cm by mammography, 1.73 cm by ultrasonography, 2.65 cm by MRI, and 2.76 cm by pathology. MRI-based tumor size was within 1 cm of pathologic size in 44 (72%) tumors, > 1 cm above pathologic size in 6 (10%) tumors, and > 1 cm below pathologic size in 11 (18%) tumors. We conclude that MRI is more accurate than either ultrasonography or mammography for assessment of the size of primary breast cancer presenting as a mass.
Risk factors for third degree perineal ruptures during delivery

term effects and complications. Another paper presented at the International Continence Society meeting in Finland drew the conclusion that there is a definite ‘learning curve’ with the tensionfree vaginal tape operation and that the operation should only be performed by experienced urogynaecologists. As we do not know the surgeons’ level of skill in this study, we are uncertain about their rates of cure and complications in the long term. We are therefore anxious that articles written by urologists and urogynaecologists with an interest in the treatment of incontinence portray the tension-free vaginal tape operation as easy. This may encourage generalists who have never performed a sling operation or needle suspension and who may have little experience of cystoscopy to attempt the tension-free vaginal tape operation. One of us (N.N.) has been on a ‘training course’ to learn the techniques of the tension-free vaginal tape operation and has a certificate to prove it. This training course is inadequate. The instructors assumed that we had all used a cystoscope, but this was not the case. We believe that the tension-free vaginal tape operation is easy only for surgeons who have a special interest in female urinary incontinence. Women must be made aware that this is a new procedure and although technically simple in experienced hands, the long term results and complications are as yet unknown.
Astrocytes Secrete Exosomes Enriched with Proapoptotic Ceramide and Prostate Apoptosis Response 4 (PAR-4)

Background: In AD, amyloid protein is associated with neurodegeneration, which may involve amyloid effects on astrocytes. Results: In astrocytes, amyloid peptide triggers secretion of proapoptotic exosomes (“apoxosomes”) that are associated with ceramide and PAR-4. Conclusion: Activation of nSMase2 and expression of PAR-4 is critical for the secretion of apoxosomes and glial apoptosis. Significance: Apoxosomes may contribute to glial apoptosis, and therefore, neurodegeneration in AD. Amyloid protein is well known to induce neuronal cell death, whereas only little is known about its effect on astrocytes. We found that amyloid peptides activated caspase 3 and induced apoptosis in primary cultured astrocytes, which was prevented by caspase 3 inhibition. Apoptosis was also prevented by shRNA-mediated down-regulation of PAR-4, a protein sensitizing cells to the sphingolipid ceramide. Consistent with a potentially proapoptotic effect of PAR-4 and ceramide, astrocytes surrounding amyloid plaques in brain sections of the 5xFAD mouse (and Alzheimer disease patient brain) showed caspase 3 activation and were apoptotic when co-expressing PAR-4 and ceramide. Apoptosis was not observed in astrocytes with deficient neutral sphingomyelinase 2 (nSMase2), indicating that ceramide generated by nSMase2 is critical for amyloid-induced apoptosis. Antibodies against PAR-4 and ceramide prevented amyloid-induced apoptosis in vitro and in vivo, suggesting that apoptosis was mediated by exogenous PAR-4 and ceramide, potentially associated with secreted lipid vesicles. This was confirmed by the analysis of lipid vesicles from conditioned medium showing that amyloid peptide induced the secretion of PAR-4 and C18 ceramide-enriched exosomes. Exosomes were not secreted by nSMase2-deficient astrocytes, indicating that ceramide generated by nSMase2 is critical for exosome secretion. Consistent with the ceramide composition in amyloid-induced exosomes, exogenously added C18 ceramide restored PAR-4-containing exosome secretion in nSMase2-deficient astrocytes. Moreover, isolated PAR-4/ceramide-enriched exosomes were taken up by astrocytes and induced apoptosis in the absence of amyloid peptide. Taken together, we report a novel mechanism of apoptosis induction by PAR-4/ceramide-enriched exosomes, which may critically contribute to Alzheimer disease.