Miracle-dz/UniFAR-FTUs huggingface dataset:
(E)-Methyl N′-[1-(4-hydroxyphenyl)ethylidene]hydrazinecarboxylate

The title compound, C(10)H(12)N(2)O(3), adopts a trans configuration with respect to the C=N bond. The dihedral angle between the benzene ring and the hydrazine carboxylic acid plane is 8.29 (7)°. Mol-ecules are linked into a three-dimensional network by N-H⋯O, O-H⋯O, O-H⋯N hydrogen bonds and C-H⋯π inter-actions.
A point mutational analysis of human papillomavirus type 16 E7 protein

The E7 open reading frame of human papillomavirus type 16 (HPV16) has been shown to be selectively retained in cervical tumors and to encode both transforming and trans-activating functions in murine cells, supporting the notion that expression of E7 contributes towards the progression of premalignant cervical lesions. A comparison among E7 sequences of different HPV types reveals some homology at the amino acid level. Of particular interest are two regions, one which contains significant homology to a region of adenovirus E1a and simian virus 40 large T (LT), and a second region which contains two conserved Cys-X-X-Cys motifs. To determine the importance of these domains to the function of the E7 protein, a series of mutants carrying substitutions at amino acids in the region of E1a-LT homology and at the Cys-X-X-Cys motifs were constructed. The mutated E7 sequences were placed under the control of a strong heterologous promoter (Moloney long terminal repeat), and the activity of the mutants was assayed in NIH 3T3 cells, a cell line in which both the transforming function and the trans-activating function of E7 could be determined. A single amino acid substitution analogous to a mutation in E1a which destroys the transforming ability of this protein abolished both transformation and trans-activation by E7. Mutations at the Cys-X-X-Cys motifs demonstrated that this region contributes to the transforming potential of E7, although proteins in which both motifs were interrupted retained a low level of transforming activity. Mutations in the region of E1a-LT homology which occur within a recognition sequence for casein kinase II did not markedly affect transforming activity of E7 but severely reduced trans-activating ability. This indicates that efficient trans-activation is not required for transformation by HPV16 E7 in these cells.
The Roles of Selected Arginine and Lysine Residues of TAFI (Pro-CPU) in Its Activation to TAFIa by the Thrombin-Thrombomodulin Complex*

Thrombomodulin (TM) increases the catalytic efficiency of thrombin (IIa)-mediated activation of thrombin-activable fibrinolysis inhibitor (TAFI) 1250-fold. Negatively charged residues of the C-loop of TM-EGF-like domain 3 are required for TAFI activation. Molecular models suggested several positively charged residues of TAFI with which the C-loop residues could interact. Seven TAFI mutants were constructed to determine if these residues are required for efficient TAFI activation. TAFI wild-type or mutants were activated in the presence or absence of TM and the kinetic parameters of TAFI activation were determined. When the three consecutive lysine residues in the activation peptide of TAFI were substituted with alanine (K42/43/44A), the catalytic efficiencies for TAFI activation with TM decreased 8-fold. When other positively charged surface residues of TAFI (Lys-133, Lys-211, Lys-212, Arg-220, Lys-240, or Arg-275) were mutated to alanine, the catalytic efficiencies for TAFI activation with TM decreased by 1.7–2.7-fold. All decreases were highly statistically significant. In the absence of TM, catalytic efficiencies ranged from 2.8-fold lower to 1.24-fold higher than wild-type. None of these, except the 2.8-fold lower value, was statistically significant. The average half-life of the TAFIa mutants was 8.1 ± 0.6 min, and that of wild type was 8.4 ± 0.3 min at 37 °C. Our data show that these residues are important in the activation of TAFI by IIa, especially in the presence of TM. Whether the mutated residues promote a TAFI-TM or TAFI-IIa interaction remains to be determined. In addition, these residues do not influence spontaneous inactivation of TAFIa.
Are poor responses to praziquantel for the treatment of Schistosoma mansoni infections in Senegal due to resistance? An overview of the evidence

This paper summarizes and concludes in‐depth field investigations on suspected resistance of Schistosoma mansoni to praziquantel in northern Senegal. Praziquantel at 40 mg/kg usually cures 70–90% of S. mansoni infections. In an initial trial in an epidemic S. mansoni focus in northern Senegal, only 18% of the cases became parasitologically negative 12 weeks after treatment, although the reduction in mean egg counts was within normal ranges (86%). Among other hypotheses to explain the observed low cure rate in this focus, the possibility of drug resistance or tolerance had to be considered. Subsequent field trials with a shorter follow‐up period (6–8 weeks) yielded cure rates of 31–36%. Increasing the dose to 2 × 30 mg/kg did not significantly improve cure rates, whereas treatment with oxamniquine at 20 mg/kg resulted in a normal cure rate of 79%. The efficacy of praziquantel in this focus could be related to age and pre‐treatment intensity but not to other host factors, including immune profiles and water contact patterns. Treatment with praziquantel of individuals from the area residing temporarily in an urban region with no transmission, and re‐treatment after 3 weeks of non‐cured individuals within the area resulted in normal cure rates (78–88%). The application of an epidemiological model taking into account the relation between egg counts and actual worm numbers indicated that the low cure rates in this Senegalese focus could be explained by assuming a 90% worm reduction after treatment with praziquantel; in average endemic situations, such a drug efficacy would result in normal cure rates. Laboratory studies by others on the presence or absence of praziquantel resistance in Senegalese schistosome strains have so far been inconclusive. We conclude that there is no convincing evidence for praziquantel‐resistant S. mansoni in Senegal, and that the low cure rates can be attributed to high initial worm loads and intense transmission in this area.
UPTAKE AND METABOLISM OF GLUTAMATE IN ASTROCYTES CULTURED FROM DISSOCIATED MOUSE BRAIN HEMISPHERES

Abstract— Uptake kinetics of l‐glutamate in cultured, normal glia cells obtained from the brain hemispheres of newborn mice were measured together with the activities of the glutamate metabolizing enzymes, glutamic‐oxaloacetate‐transaminase, glutamate dehydrogenase and glutamine synthetase. During 3 weeks of culturing, the activities of the enzymes rose from low neonatal values toward the levels in the adult brain (206, 12.3 and 25.9 nmol. min−1. mg−1 cell protein for the three enzymes, respectively). The uptake kinetics indicated an unsaturable component together with an uptake following Michaelis‐Menten kinetics with a Km of 220 μm and a Vmax of 7.9 nmol. min−1. mg−1 cell protein. The saturable glutamate uptake was inhibited by d‐glutamate, l‐aspartate and α‐aminoadipate whereas l‐glutamine, GABA and glutarate had no effect. The uptake which was Ca2+‐independent had a Km for sodium of 18mm and it was stimulated by an increase in the external potassium concentration from 5 to 10 and 25 mm. The results suggest that glia cells are important for the uptake of glutamate from synaptic clefts and for the subsequent metabolism of glutamate.
An Information-Theoretic Analysis of Deep Latent-Variable Models

We present an information-theoretic framework for understanding trade-offs in unsupervised learning of deep latent-variables models using variational inference. This framework emphasizes the need to consider latent-variable models along two dimensions: the ability to reconstruct inputs (distortion) and the communication cost (rate). We derive the optimal frontier of generative models in the two-dimensional rate-distortion plane, and show how the standard evidence lower bound objective is insufficient to select between points along this frontier. However, by performing targeted optimization to learn generative models with different rates, we are able to learn many models that can achieve similar generative performance but make vastly different trade-offs in terms of the usage of the latent variable. Through experiments on MNIST and Omniglot with a variety of architectures, we show how our framework sheds light on many recent proposed extensions to the variational autoencoder family.
Los buenos vivires. Una aproximación a las corrientes teóricas del buen vivir

Nao foram muitos anos que, em diversos espacos academicos, governamentais e no interior de diferentes movimentos sociais, os debates foram posicionados entre dois conceitos que, a primeira vista, pareciam contrarios e excludentes: desenvolvimento e boa vida. Apos os efeitos devastadores do desenvolvimento economico capitalista nos ultimos seculos, mas especificamente nas ultimas quatro decadas, o conceito de desenvolvimento e fortemente questionado e, em muitos casos, se opoe ao conceito de boa vida, que ganhou notoriedade internacional depois de se tornarem principios constitucionais em Equador e Bolivia, com base em formas de vida proprias dos povos nativos andinos e amazonicos: sumak kawsay e suma qamana, principalmente. No entanto, estas nao sao as unicas expressoes de boa vida. Na verdade, nao ha um bom viver, mas diferentes maneiras de viver bem, ou muitas boas vidas. Os debates academicos sobre o assunto sao por demais necessarios e frutiferos, porque demonstram que a dialetica e a primeira expressao da vida e porque contribuem para a construcao do conhecimento plural.
Identification of three non‐VNTR MUC1‐derived HLA‐A*0201‐restricted T‐cell epitopes that induce protective anti‐tumor immunity in HLA‐A2/Kb‐transgenic mice

The human epithelial mucin MUC1 is over‐expressed in more than 90% of carcinomas of the breast, ovary, and pancreas as well as in some other tumours, making it a potential target for tumour immunotherapy. We have identified several MUC1‐derived peptides mapping outside the variable number tandem repeat region that comply with the peptide‐binding motif for HLA‐A*0201 and that become processed into stable major histocompatibility complex‐peptide complexes as assessed by in vitro assays. In A2/Kb transgenic mice, 3 peptides, namely MUC79–87 (TLAPATEPA), MUC167–175 (ALGSTAPPV) and MUC264–272 (FLSFHISNL) elicit peptide‐specific cytotoxic T lymphocyte (CTL) immunity, which protects these mice against a challenge with MUC1, A2/Kb‐expressing tumour cells. These peptides therefore represent naturally processed MUC1‐derived CTL epitopes that could be used as components in peptide‐based vaccines and for the analysis of anti‐MUC1 CTL responses in A*0201‐positive patients with MUC1‐expressing tumours. © 2001 Wiley‐Liss, Inc.
Optimal management of patients with chronic hepatitis C and comorbidities

Although HCV infection mainly induces liver injury, chronic disease is systemic. Moreover, host and viral factors, as well as comorbidities, may influence the chance of achieving a sustained virological response or disease outcome. Although there are sufficient data on the use of peg‐interferon and ribavirin in patients with comorbidities, there is very little data on first generation protease inhibitors, which include significant drug–drug interactions and have therefore been administered with caution in these patients. The availability of new, more effective direct acting antivirals should significantly change this scenario. All these issues are discussed in this review.
Hyalinizing Trabecular Tumors of the Thyroid Gland are Almost all Benign

In 1987, Carney et al reported 11 thyroid tumors with the following features: circumscription or encapsulation, trabecular architecture with intratrabecular hyalin and colloid, polygonal and spindle cells, nuclei with frequent grooves and cytoplasmic inclusions, occasional psammoma bodies, and a low mitotic rate. The neoplasms did not recur or metastasize during a follow-up period that averaged 10 years, and they were titled hyalinizing trabecular adenomas. Subsequently, the nuclear features of the neoplasm led to the introduction of 2 modified titles for it, hyalinizing trabecular tumor and hyalinizing trabecular neoplasm. Later, discovery of RET/PTC mutations in the tumor resulted in it being designated as a type of papillary thyroid carcinoma. We studied 119 neoplasms of the type outlined, collected over a 20-year period, for invasion, recurrence and metastasis, and obtained follow-up in 96% of the cases. One hundred eighteen tumors showed no evidence of aggressive behavior (capsular, vascular, and parenchymal invasion), local recurrence, or metastasis. One tumor showed vascular and capsular invasion, and pulmonary metastasis. We conclude that the overwhelming majority of hyalinizing trabecular tumors of the thyroid behave as benign neoplasms and that, at this time, hyalinizing trabecular adenoma is the most appropriate title for them.
Structural and Sequence Motifs in Dermatan Sulfate for Promoting Fibroblast Growth Factor-2 (FGF-2) and FGF-7 Activity*

Glycosaminoglycans have been implicated in the binding and activation of a variety of growth factors, cytokines, and chemokines. In this way, glycosaminoglycans are thought to participate in events such as development and wound repair. In particular, heparin and heparan sulfate have been well studied, and specific aspects of their structure dictate their participation in a variety of activities. In contrast, although dermatan sulfate participates in many of the same biological processes as heparin and heparan sulfate, the interactions of dermatan sulfate have been less well studied. Dermatan sulfate is abundant in the wound environment and binds and activates growth factors such as fibroblast growth factor-2 (FGF-2) and FGF-7, which are present during the wound repair process. To determine the minimum size and sulfation content of active dermatan sulfate oligosaccharides, dermatan sulfate was first digested and then separated by size exclusion high pressure liquid chromatography, and the activity to facilitate FGF-2 and FGF-7 was assayed by the cellular proliferation of cell lines expressing FGFR1 or FGFR2 IIIb. The minimum size required for the activation of FGF-2 was an octasaccharide and for FGF-7 a decasaccharide. Active fractions were rich in monosulfated, primarily 4-O-sulfated, disaccharides and iduronic acid. Increasing the sulfation to primarily 2/4-O-sulfated and 2/6-O-sulfated disaccharides did not increase activity. Cell proliferation decreased or was abolished with higher sulfated dermatan sulfate preparations. This indicated a preference for specific dermatan sulfate oligosaccharides capable of promoting FGF-2- and FGF-7-dependent cell proliferation. These data identify critical oligosaccharides that promote specific members of the FGF family that are important for wound repair and angiogenesis.
Convulsions on anaesthetic induction with sevoflurane in young children

Increased worldwide use for paediatric anaesthesia of the volatile anaesthetic agent sevoflurane has mainly resulted from its low blood‐gas partition coefficient and low airway irritability, providing smooth conditions for rapid induction of anaesthesia. Nevertheless, there are several clinical and experimental reports suggesting a correlation between exposure to sevoflurane and generalized clonic or tonic seizure activity. We report two clinical episodes of convulsions associated with the induction of sevoflurane anaesthesia in young children.
Ionic basis of the caesium‐induced depolarisation in rat supraoptic nucleus neurones

1 The effects of external Cs+ on magnocellular neurosecretory cells were studied during intracellular recordings from 93 supraoptic nucleus neurones in superfused explants of rat hypothalamus. 2 Bath application of 3–5 mm Cs+ provoked reversible membrane depolarisation and increased firing rate in all of the neurones tested. Voltage‐current analysis revealed an increase in membrane resistance between −120 and −55 mV. The increase in resistance was greater below −85 mV than at more positive potentials. 3 Voltage‐clamp analysis showed that external Cs+ blocked the hyperpolarisation‐activated inward current, IH. Under current clamp, application of ZD 7288, a selective blocker of IH, caused an increase in membrane resistance at voltages ⩽−65 mV. Voltage‐current analysis further revealed that blockade of IH caused hyperpolarisation when the initial voltage was < −60 mV but had no effect at more positive values. 4 Current‐ and voltage‐clamp analysis of the effects of Cs+ in the presence of ZD 7288, or ZD 7288 and tetraethyl ammonium (TEA), revealed an increase in membrane resistance throughout the range of voltages tested (−120 to −45 mV). The current blocked by Cs+ in the absence of IH was essentially voltage independent and reversed at −100 mV. The reversal potential shifted by +22.7 mV when external [K+] was increased from 3 to 9 mm. We conclude that, in addition to blocking IH, external Cs+ blocks a leakage K+ current that contributes significantly to the resting potential of rat magnocellular neurosecretory cells.
COMPARAÇÃO ENTRE DIFERENTES MÉTODOS PARA ESTIMATIVA VOLUMÉTRICA DE ESPÉCIES COMERCIAIS DA AMAZÔNIA

A floresta Amazonica apresenta especies de elevado potencial para exploracao sustentavel de madeira, entretanto, para que sejam exploradas, ha a necessidade de informacoes para estimativas precisas de seu volume de madeira. Assim, com a hipotese de que volumes estimados por diferentes metodos e os obtidos pela cubagem rigorosa sao estatisticamente iguais entre si, este trabalho teve por objetivo comparar estimativas volumetricas obtidas atraves do fator de forma, modelos volumetricos e modelo de afilamento para cinco especies comerciais da floresta amazonica. Foram cubadas 449 arvores pelo metodo de Smalian para desenvolvimento do fator de forma e ajuste das equacoes volumetricas e de afilamento. Foi utilizado o delineamento blocos ao acaso, onde cada especie foi considerada como um bloco e cada metodo de obtencao volumetrica compos um tratamento. Foi aplicada a analise de variância para verificar a existencia de diferenca significativa entre os tratamentos e entre os blocos, seguida do teste de Tukey para o nivel critico . Entre os modelos ajustados, o de Schumacher-Hall foi o que apresentou maior precisao para estimar o volume. O fator de forma medio estimado e 0,73. Nao houve diferencas estatisticas na estimativa do volume utilizando os diferentes metodos, contudo, recomenda-se utilizar o modelo de simples entrada, pois a altura para especies amazonicas e de dificil obtencao, fazendo deste metodo o mais pratico.
RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1

Editing of the pre-mRNA for the DNA repair enzyme NEIL1 causes a lysine to arginine change in the lesion recognition loop of the protein. The two forms of NEIL1 are shown here to have distinct enzymatic properties. The edited form removes thymine glycol from duplex DNA 30 times more slowly than the form encoded in the genome, whereas editing enhances repair of the guanidinohydantoin lesion by NEIL1. In addition, we show that the NEIL1 recoding site is a preferred editing site for the RNA editing adenosine deaminase ADAR1. The edited adenosine resides in an A-C mismatch in a hairpin stem formed by pairing of exon 6 to the immediate upstream intron 5 sequence. As expected for an ADAR1 site, editing at this position is increased in human cells treated with interferon α. These results suggest a unique regulatory mechanism for DNA repair and extend our understanding of the impact of RNA editing.
TOO MANY, TOO FEW, OR JUST RIGHT? THE PREDICTED NUMBER AND DISTRIBUTION OF MILKY WAY DWARF GALAXIES

We predict the spatial distribution and number of Milky Way dwarf galaxies to be discovered in the Dark Energy Survey (DES) and Large Synoptic Survey Telescope (LSST) surveys, by completeness correcting the observed Sloan Digital Sky Survey dwarf population. We apply most massive in the past, earliest forming, and earliest infall toy models to a set of dark matter-only simulated Milky Way/M31 halo pairs from the Exploring the Local Volume In Simulations project. Inclusive of all toy models and simulations, at 90% confidence we predict a total of 37–114 L ≳ 103 L☉ dwarfs and 131–782 L ≲ 103 L☉ dwarfs within 300 kpc. These numbers of L ≳ 103 L☉ dwarfs are dramatically lower than previous predictions, owing primarily to our use of updated detection limits and the decreasing number of SDSS dwarfs discovered per sky area. For an effective rlimit of 25.8 mag, we predict 3–13 L ≳ 103 L☉ and 9–99 L ≲ 103 L☉ dwarfs for DES, and 18–53 L ≳ 103 L☉ and 53–307 L ≲ 103 L☉ dwarfs for LSST. We also show that the observed spatial distribution of Milky Way dwarfs in the LSST-era will discriminate between the earliest infall and other simplified models for how dwarf galaxies populate dark matter subhalos.
How To Do It: Work with an interpreter

The Audit Commission recently highlighted the need for health services to plan language services to help the problems of poor communication facing non-English speaking patients. Doctors and other health workers need to know how to work effectively when interviewing patients with an interpreter. This article describes the different options for helping non-English speaking patients; explains how interviews should be conducted with a trained interpreter, including those using sign language; and outlines the extent of interpreting services currently available in the United Kingdom, complete with a list of addresses of organisations offering interpreting services. Patients whose first language is not English may face difficulties in being understood and in understanding diagnoses. To help such patients the health service needs to provide language services,1 which are largely of four types. Bilingual health workers--These workers remove the need for a third party to be involved and are the ideal option for most patients. Bilingual health workers are, however, few and will never be universally available. Trained interpreters--The use of a professional interpreter is the next best option. These professionals maintain a strict code of confidentiality and are skilled in interpreting the sense and intent of what is said while preserving the content of the interview. Although the provision of trained interpreters for health services appears to be increasing, their availability and use is still patchy, and doctors will often find themselves depending on informal help from friends or relatives of the patient or from untrained volunteers. Friends or relatives--The perceived advantages of using people known to the patient are that they are readily available, that they may be knowledgeable about the patient's problems, and that their presence may be a reassurance to the patient. However, the risk is that someone close to the patient will not stop their own views of the …