Miracle-dz/UniFAR-FTUs huggingface dataset:
Caracterización de micelas de gangliósidos modificadas con moléculas de reconocimiento celular como estrategia de direccionamiento de fármacos

Una de las estrategias terapeuticas actuales contra el cancer esta orientada a mejorar la efectividad de los farmacos anticancerigenos existentes mediante el desarrollo de sistemas innovadores de transporte [13,14] que permitan modificar las caracteristicas farmacocineticas y de biodistribucion de los principios activos. En esta linea, recientemente desarrollamos una nanoestructura micelar compuesta por monosialoglicoesfingolipidos (GM1) capaces de transportar farmacos hidrofobicos (Ptx) y anfipaticos (Doxo) con alta eficiencia [80,81]. En este trabajo se planteo modificar estas micelas mediante la incorporacion de una molecula de reconocimiento celular, con el objetivo de focalizar la accion citotoxica del farmaco vehiculizado hacia las celulas tumorales. Se evaluo la incorporacion de moleculas de reconocimiento celular como el acido folico, anticuerpos, espermidina y lipoproteinas en las micelas de GM1, se caracterizaron las estructuras resultantes y se determino la actividad farmacologica de las micelas modificadas. Algunas de las estructuras obtenidas, como GM1-espermidina y GM1-LDL mostraron diferencias significativas respecto a las micelas de GM1 en la internalizacion de farmacos frente a lineas tumorales in vitro. En el caso de GM1-IgG, si bien los resultados de actividad biologica in vitro de los farmacos vehiculizados no mostraron diferencias respecto al efecto de los mismos farmacos transportados en micelas de GM1 sin anticuerpos, se demostro que los anticuerpos forman complejos estables con las micelas, mantienen su capacidad de reconocimiento especifico y no son desplazados por otras proteinas plasmaticas. Esto permite proponer al complejo GM1-IgG/farmaco como un sistema mixto, en el cual se puede combinar la accion efectora de los anticuerpos con el efecto biologico de los farmacos. Finalmente, se demostro que moleculas pequenas como el acido Folico (AF) pueden ser incorporadas en la estructura micelar aplicando diferentes estrategias. En las condiciones evaluadas, las micelas modificadas con AF no revelaron diferencias significativas de actividad respecto a las micelas de GM1 frente a celulas tumorales RF positivas. El conjunto de resultados presentados en este trabajo nos permiten concluir que es posible modificar las micelas de GM1 con moleculas de reconocimiento celular de diferente naturaleza, posibilitando el diseno de micelas funcionales con caracteristicas adecuadas para aplicaciones farmacologicas.
Réflexions autour de la méthodologie de vérification des circuits multi-horloges : analyse qualitative et automatisation

Depuis plusieurs annees, le marche des circuits integres numeriques requiert des systemes de plus en plus complexes dans un temps toujours plus reduit. Afin de repondre a ses deux exigences, les industriels de la conception font appel a des fournisseurs externes proposant des circuits fonctionnant sur des signaux d'horloge dedies. Lorsque ces derniers communiquent entre eux, les horloges d'emission et de reception ne sont pas les memes, on parle de « Clock Domain Crossing » (CDC). Les CDC correspondent a des communications asynchrones et peuvent provoquer des dysfonctionnements critiques. Par ailleurs, ces problemes etant intermittents et complexes a analyser, ils ne peuvent pas etre exhaustivement verifies avec des methodes telles que l’analyse de timing ou la simulation fonctionnelle. Avec l'augmentation du nombre de CDC dans les circuits, les industriels de la conception assistee par ordinateur (EDA) ont propose des solutions logicielles specialisees dans la verification statique des CDC. Cependant, les circuits developpes etant en constante evolution, les outils ne sont pas en mesure de s’adapter. Pour pallier ces problemes, la verification industrielle des CDC est basee sur la specification de contraintes et d'exclusions par l'utilisateur. Ces actions, qui se substituent aux outils, peuvent masquer des bugs. De plus, l’effort humain requis par cette approche n’est pas compatible avec le temps alloue au developpement de circuits industriels. Nous avons donc cherche a automatiser la verification en proposant des solutions basees sur des proprietes formelles. Les travaux ont consiste a analyser les differentes techniques de conception et de verification des CDC a travers l’evaluation des principaux outils du marche. A partir des resultats obtenus, nous avons formalise les problemes pratiques et propose des modeles permettant d’obtenir des resultats exhaustifs automatiquement. Les essais ont ete realises sur un sous-systeme a base de processeurs (CPUSS) developpe chez STMicroelectronics. L'adoption de nos modeles permet une verification complete des CPUSS de maniere automatique ce qui est essentiel dans un environnement industriel competitif. En effet, le nombre d’informations devant etre specifiees par l’utilisateur a ete reduit de moitie pour chacun des outils evalues. Par ailleurs, ces travaux ont montre que l’axe de developpement des outils CDC avec l’ajout de fonctionnalites telles que les flots hierarchiques ou l’injection de fautes n’ameliore pas la qualite de resultats. Une collaboration ayant ete mise en place avec les principaux fournisseurs outils, certaines solutions seront probablement integrees aux outils dans les annees a venir.
Beyond the urban mask

Despite the great importance of cities, relatively little consistent information about their internal configuration (structure, cover and materials) is available. The World Urban Database and Access Portal Tools (WUDAPT) initiative aims at the acquisition, storage and dissemination of data on the form and function of cities indifferent levels. At the lowest level, the Local Climate Zone (LCZ) scheme provides a basic description of urban structure. This scheme is a climate-based typology of urban and natural landscapes that also provides relevant information on basic physical properties of the landscape, which can be used in modelling and observational studies. The LCZ scheme has large potential as a standard generic description of urban areas. In this paper the scheme and our standard mapping approach are presented, followed by recent improvements and research on object-based image analysis, transferability of trained LCZ classifiers, quality of crowd contributions, and the use of other data sources and methods.
Phantom authority, self-selective recruitment and retention of members in virtual communities: The case of Wikipedia

Virtual communities constitute a building block of the information society. These organizations appear capable to guarantee unique outcomes in voluntary association since they cancel physical distance and ease the process of searching for like-minded individuals. In particular, open source communities, devoted to the collective production of public goods, show efficiency properties far superior to the traditional institutional solutions to the public goods issue (e.g. property rights enforcement and secrecy). This paper employs team and club good theory as well as transaction cost economics to analyse the Wikipedia online community, which is devoted to the creation of a free encyclopaedia. An interpretative framework explains the outstanding success of Wikipedia thanks to a novel solution to the problem of graffiti attacks - the submission of undesirable pieces of information. Indeed, Wiki technology reduces the transaction cost of erasing graffiti and therefore prevents attackers from posting unwanted contributions. The issue of the sporadic intervention of the highest authority in the system is examined, and the relatively more frequent local interaction between users is emphasized. The constellation of different motivations that participants may have is discussed, and the barriers-free recruitment process analysed. A few suggestions, meant to encourage long term sustainability of knowledge assemblages, such as Wikipedia, are provided. Open issues and possible directions for future research are also discussed.
Use of Alemtuzumab and Tacrolimus Monotherapy for Cadaveric Liver Transplantation: With Particular Reference to Hepatitis C Virus

We have proposed that the mechanisms of alloengraftment and variable acquired tolerance can be facilitated by minimum posttransplant immunosuppression. It was further suggested that the efficacy of minimalistic treatment could be enhanced by preoperative recipient conditioning with an antilymphoid antibody preparation. A total of 76 adults (38 hepatitis C virus [HCV]−, 38 HCV+) were infused with 30 mg alemtuzumab before primary cadaveric liver transplantation and maintained afterward on daily monotherapy unless breakthrough rejection mandated additional agents. In stable patients, the intervals between tacrolimus doses were lengthened (“spaced weaning”) after approximately 4 months. Eighty-four contemporaneous nonlymphoid-depleted liver recipients (58 HCV−, 26 HCV+) were treated with conventional postoperative immunosuppression. The overall incidence of rejection was similar with the two strategies of immunosuppression. With follow-ups of 14 to 22 months, patient and primary graft survival in HCV− cases are 97% and 90%, respectively, with alemtuzumab depletion plus minimal immunosuppression versus 71% and 70%, respectively, under conventional immunosuppression. In HCV+ recipients, current patient and graft survival in the alemtuzumab-pretreated group are 71% and 70% versus 65% and 54%, respectively, under conventional treatment. With both strategies of immunosuppression, the adverse effect of preexisting HCV on survival parameters and graft function already was significant at the 1-year milestone, but its extent was not evident until the second year. With or without HCV, 62% of the 64 surviving lymphoid-depleted patients are on spaced immunosuppression, and four patients receive no immunosuppression. Lymphoid depletion with alemtuzumab and minimalistic maintenance immunosuppression is a practical strategy of liver transplantation in HCV− recipients but not HCV+ recipients.
Inhibitory activity of double‐sequence analogues of trypsin inhibitor SFTI‐1 from sunflower seeds: an example of peptide splicing

Four 28‐amino acid peptides were synthesized whose sequences comprised two molecules of trypsin inhibitor sunflower trypsin inhibitor 1 (SFTI‐1) bound through a peptide bond. The peptides in their reactive positions (5 and 19 of the peptide chain) contain two Lys ([KK]BiSFTI‐1) and two Phe ([FF]BiSFTI‐1) residues, along with a combination of the amino acid residues named thereafter [KF]BiSFTI‐1 and [FK]BiSFTI‐1. Association constants of the analogues determined with trypsin and chymotrypsin, respectively, indicated that they were potent inhibitors of cognate proteinases. An MS study of the associates revealed that incubation of the compounds with the proteinases resulted in cutting out a fragment of the peptide chain to restore the native monocyclic molecule of SFTI‐1 or its analogue [Phe5]SFTI‐1. This process, analogous to that of the DNA and protein splicing, can be referred to as ‘peptide splicing’.
Stable isotopes and diet : You are what you eat

Archaeologists frequently use many different sources of information to reconstruct ancient diets, including faunal and macrobotanical remains, pollen and phytoliths, as well as pottery residues, coprolites, and indirect sources such as skeletal pathology, dental wear patterns, artistic depictions, and ethnographic observations. In most cases, however, the result is only the determination of the menu, and with the exception of animal foods, without any quantitative estimate of their importance. Furthermore, these data almost always pertain to groups of people and represent a time span of multiple generations if not a century or more. In the late 1970s, though, a new area of dietary research developed based on the isotopic composition of human bone. This work began with the observation that radiocarbon dates on the remains of certain plants such as maize were offset from dates obtained on other remains from the same archaeological context. With the determination that this was due to maize having a different photosynthetic pathway than most plants, which results in a different relative quantity of carbon-14 (and carbon-13) in its tissues, it was realized that carbon isotope ratios in consumer tissues (e.g. bone) would also be affected, and therefore the measurement of carbon isotope ratios could be used to indicate the importance of maize in human diets [1, 2]. Following the observation that nitrogen isotope ratios also vary between different food sources, especially marine vs. terrestrial [3], the stable isotope analysis of human bone quickly became a widely applied technique, especially in areas where isotopically diverse food sources are known to have existed. Analyses of human bone offer the specific advantage relative to faunal and floral
Salvage techniques in traumatic cardiac arrest: thoracotomy, extracorporeal life support, and therapeutic hypothermia

Purpose of reviewSurvival from traumatic cardiac arrest is associated with a very high mortality despite aggressive resuscitation including an Emergency Department thoracotomy (EDT). Novel salvage techniques are needed to improve these outcomes. Recent findingsMore aggressive out-of-hospital interventions, such as chest decompression or thoracotomy by emergency physicians or anesthesiologists, seem feasible and show some promise for improving outcomes. For trauma patients who suffer severe respiratory failure or refractory cardiac arrest, there seems to be an increasing role for the use of extracorporeal life support (ECLS), utilizing heparin-bonded systems to avoid systemic anticoagulation. The development of exposure hypothermia is associated with poor outcomes in trauma patients, but preclinical studies have consistently demonstrated that mild, therapeutic hypothermia (34 °C) improves survival from severe hemorrhagic shock. Sufficient data exist to justify a clinical trial. For patients who suffer a cardiac arrest refractory to EDT, induction of emergency preservation and resuscitation by rapid cooling to a tympanic membrane temperature of 10 °C may preserve vital organs long enough to allow surgical hemostasis, followed by resuscitation with cardiopulmonary bypass. SummarySalvage techniques, such as earlier thoracotomy, ECLS, and hypothermia, may allow survival from otherwise lethal injuries.
Acute mountain sickness in travelers who consulted a pre-travel clinic.

BACKGROUND The main objective of this study was to investigate the incidence and predictors of acute mountain sickness (AMS) in travelers who consulted a pre-travel clinic and the compliance with advices concerning this condition. METHODS A post-travel questionnaire was sent to clients of five travel clinics who planned to climb above 2,000 m. RESULTS The response was 77% and the data of all 744 respondents who stayed above 2,500 m were used for the analysis. Eighty-seven percent (646) read and understood the written advices on AMS. The incidence of AMS was 25% (184), and the predictors were previous AMS [odds ratio (OR) 2.2], female sex (OR 1.6), age (OR 0.98 per year), maximum sleeping altitude (OR 1.2 per 500 m), and the number of nights between 1,500 and 2,500 m (OR 0.9 per night). Eighty-seven percent of respondents understood the written advices about AMS but 21% did not read or understand the use of acetazolamide. Forty percent spent less than two nights between 1,500 and 2,500 m and 43% climbed more than 500 m/d once above 2,500 m. Acetazolamide was brought along by 541 respondents (72%) and 116 (16%) took it preventively. Of those with AMS 62 (34%) took acetazolamide treatment and 87 (47%) climbed higher despite AMS symptoms. The average preventive dose of acetazolamide was 250 mg/d, while the average curative dose was 375 mg/d. We found no relation between acetazolamide prevention and AMS (p = 0.540). CONCLUSIONS The incidence of AMS in travelers who stayed above 2,500 m was 25%. Predictors were previous AMS, female sex, age, maximum overnight altitude, and the number of nights between 1,500 and 2,500 m. Only half of these travelers followed the preventive and curative advices and 21% did not read or understand the use of acetazolamide. We found no preventive effect of a low dose of acetazolamide in this retrospective observational study.
The usefulness of elemental iron for cereal flour fortification: a SUSTAIN Task Force report. Sharing United States Technology to Aid in the Improvement of Nutrition.

Fortification of cereal flours may be a useful public health strategy to combat iron deficiency. Cereal flours that are used shortly after production (e.g., baking flour) can be fortified with soluble iron compounds, such as ferrous sulfate, whereas the majority of flours stored for longer periods is usually fortified with elemental iron powders to avoid unacceptable sensory changes. Elemental iron powders are less well absorbed than soluble iron compounds and they vary widely in their absorption depending on manufacturing method and physicochemical characteristics. Costs vary with powder type, but elemental iron powders are generally less expensive than ferrous sulfate. This review evaluates the usefulness of the different elemental iron powders based on results from in vitro studies, rat assays, human bioavailability studies, and efficacy studies monitoring iron status in human subjects. It concludes that, at the present time, only electrolytic iron powder can be recommended as an iron fortificant. Because it is only approximately half as well absorbed as ferrous sulfate, it should be added to provide double the amount of iron.
Vaccine Therapy of Cancer

Recent studies in tumor immunology led to the identification and molecular characterization of many human tumor-associated protein antigens (TAA) which are recognized by T lymphocytes as HLNpeptide complexes on the surface of cancer cells. More than one hundred of such peptides have been defined which can be recognized either by CD8+ cytotoxic or by CD4+ helper T lymphocytes. The availability of these peptides has resulted in the initiation of clinical studies in subjects with metastatic cancer aimed at assessing the therapeutic potential of active immunization (vaccination) with such peptides. However, only a limited number of TAA peptides, mostly recognizable by CD8+ T cells in melanoma patients, could be tested in the clinic. Partial and complete tumor regressions were observed in some clinical trials though only in approximately 10-30% of patients treated. No serious side effects were reported. These clinical responses, however, were often not asso-
Extracorporeal membrane oxygenation support in refractory cardiogenic shock: treatment strategies and analysis of risk factors.

Two centrifugal pumps, the RotaFlow (Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) and Levitronix CentriMag (Levitronix LCC, Waltham, MA, USA), used in central or peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) support systems have been investigated, in terms of double-center experience, as treatment for patients with refractory cardiogenic shock (CS). Between January 2006 and December 2012, 228 consecutive adult patients were supported on RotaFlow (n=213) or CentriMag (n=15) ECMO, at our institutions (155 men; age 58.3±10.5 years, range: 19-84 years). Indications for support were: failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n=118) and primary donor graft failure (n=37); postacute myocardial infarction CS (n=27); acute myocarditis (n=6); and CS on chronic heart failure (n=40). A peripheral ECMO setting was established in 126 (55.2%) patients while it was established centrally in 102 (44.7%). Overall mean support time was 10.9±9.7 days (range: 1-43 days). Eighty-four (36.8%) patients died on ECMO. Overall success rate, in terms of survival on ECMO (n=144), weaning from mechanical support (n=107; 46.9%), bridge to mid-long-term ventricular assist device (n=6; 2.6%), and bridge to heart transplantation (n=31; 13.5%), was 63.1%. One hundred twenty-two (53.5%) patients were successfully discharged. Stepwise logistic regression identified blood lactate level and MB isoenzyme of creatine kinase (CK-MB) relative index at 72 h after ECMO initiation, and number of packed red blood cells (PRBCs) transfused on ECMO as significant predictors of mortality on ECMO (P=0.010, odds ratio [OR]=2.94; 95% confidence interval [CI]=1.10-3.14; P=0.010, OR=2.82, 95% CI=1.014-3.721; and P=0.011, OR=2.69; 95% CI=1.06-4.16, respectively). Central ECMO population had significantly higher rate of continuous veno-venous hemofiltration need and bleeding requiring surgery events compared with the peripheral ECMO setting population. No significant differences were seen by comparing the RotaFlow and CentriMag populations in terms of device performance. At follow-up, persistent heart failure with left ventricle ejection fraction (LVEF)≤40% was a risk factor after hospital discharge. Patients with a poor hemodynamic status may benefit from rapid central or peripheral insertion of ECMO. The blood lactate level, CK-MB relative index, and PRBCs transfused should be strictly monitored during ECMO support. In addition, early ventricular assist device placement or urgent listing for heart transplant should be considered in patients with persistent impaired LVEF after ECMO.
Purification of a new neurotrophic factor from mammalian brain.

We report the purification from pig brain of a factor supporting the survival of, and fibre outgrowth from, cultured embryonic chick sensory neurons. The purified factor migrates as one single band, mol. wt. 12 300, on gel electrophoresis in the presence of sodium dodecylsulphate (SDS) and is a basic molecule (pI greater than or equal to 10.1). Approximately 1 microgram factor was isolated from 1.5 kg brain. The final degree of purification was estimated to be 1.4 X 10(6)‐fold, and the specific activity 0.4 ng/ml/unit, which is similar to that of nerve growth factor (NGF) using the same assay system. This factor is the first neurotrophic factor to be purified since NGF, from which it is clearly distinguished because it has different antigenic and functional properties.
Outcomes of Wilms’ Tumor in Eastern China: 10 Years of Experience at a Single Center

ABSTRACT Purpose: Wilms’ tumor (WT), or nephroblastoma, is the most common renal malignancy of childhood, and its outcome varies. We aimed to retrospectively review the clinical parameters and outcomes of WT cases treated at our medical center to identify factors associated with its prognosis. Methods: We retrospectively reviewed WT patients who had undergone surgery and other therapy in our hospital from May 1998 to May 2008. Demographic features, mode of presentation, stage of tumor, histopathologic results, and survival rates were evaluated. Results: Our study included 67 children with WT; 38 were males and 29 were females. The mean age at onset was 39 months. Eighteen cases were diagnosed as Stage I, 23 as Stage II, 20 as Stage III, and 6 as Stage IV. Nephroureterectomy was the initial treatment in 57 children. There were 46 (68.7%) cases of favorable histology and 21 (31.3%) cases of unfavorable (anaplastic) histology. The rates of four-year event-free survival and overall survival were 78.3% and 81%, respectively. The four-year overall survival rate for cases of favorable histology (85.8%) was higher than for those with unfavorable histology (71.4%; p =.028). Conclusions: The outcomes of WT patients in our institution were little poorer than for those of the third National Wilms Tumor Study. Advanced clinical stage at presentation, unfavorable histology, tumor rupture, relapse, delay of radiotherapy due to ignorance, and premature ending of treatment were the important factors that impacted on the outcome of WT.