Miracle-dz/UniFAR-FTUs huggingface dataset:
a V b 3 Integrin-Targeted Radionuclide Therapy with 64 Cu-cyclam-RAFT-c (-RGDfK-) 4

The transmembrane cell adhesion receptor aVb3 integrin (aVb3) has been identified as an important molecular target for cancer imaging and therapy. We have developed a tetrameric cyclic RGD (Arg-Gly-Asp) peptide–based radiotracer Cu-cyclam-RAFT-c(-RGDfK-)4, which successfully captured aVb3-positive tumors and angiogenesis by PET. Here, we subsequently evaluated its therapeutic potential and side effects using an established aVb3-positive tumor mouse model. Mice with subcutaneous U87MG glioblastoma xenografts received single administrations of 37 and 74 MBq of Cu-cyclamRAFT-c(-RGDfK-)4 (37 MBq/nmol), peptide control, or vehicle solution and underwent tumor growth evaluation. Side effects were assessed in tumor-bearing and tumor-free mice in terms of body weight, routine hematology, and hepatorenal functions. Biodistribution of Cu-cyclam-RAFT-c(-RGDfK-)4 with ascendingpeptidedoses (0.25–10nmol) andwith the therapeutic dose of 2 nmol were determined at 3 hours and at various time points (2minutes–24hours) postinjection, respectively, based on which radiation-absorbed doses were estimated. The results revealed that Cu-cyclam-RAFT-c(-RGDfK-)4 dose dependently slowed down the tumor growth. Themean tumor doses were 1.28 and 1.81 Gy from 37 and 74 MBq of Cu-cyclam-RAFT-c (-RGDfK-)4, respectively. Peptide dose study showed that the tumor uptake of Cu-cyclam-RAFT-c(-RGDfK-)4 dose dependently decreased at doses 1 nmol, indicating a saturation of aVb3 with the administered therapeutic doses (1 and 2 nmol). Combined analysis of the data from tumor-bearing and tumorfree mice revealed no significant toxicity caused by 37–74 MBq of Cu-cyclam-RAFT-c(-RGDfK-)4. Our study demonstrates the therapeutic efficacy and safety of Cu-cyclam-RAFT-c (-RGDfK-)4 for aVb3-targeted radionuclide therapy. Cucyclam-RAFT-c(-RGDfK-)4 would be a promising theranostic drug for cancer imaging and therapy. Mol Cancer Ther; 15(9); 1–
Desarrollo de un protocolo de seguimiento a largo plazo de los organismos clave para el funcionamiento de los bosques mediterráneos

Los Programas de Seguimiento de los Parques Nacionales pueden emplearse para averiguar que procesos estan produciendo los cambios observados y actuar en consecuencia siempre y cuando esten bien disenados, esto es, se basen en la medida rigurosa de caracteristicas importantes, sintetizadas y combinadas en modelos dinamicos del funcionamiento del sistema objeto de seguimiento. En este trabajo se completa el desarrollo de un protocolo de seguimiento de las poblaciones de organismos clave para el funcionamiento de los bosques mediterraneos de encina Quercus ilex, esto es, de la especie vegetal dominante y los animales y plantas que influyen, positiva o negativamente, en su regeneracion natural, y se revisan los resultados preliminares del analisis de las bases de datos generadas hasta el momento.
Mood Spectrum in Patients with Different Painful Temporomandibular Disorders

Abstract The purpose of this study was to investigate for difference in the prevalence of mood disorders between patients with different painful temporomandibular disorders (TMD). After a sample size necessary for the study was calculated, 60 patients with a painful TMD were selected and divided into the following groups: myofascial pain (n=20), temporomandibular joint (TMJ) pain (n=18), combined myofascial and TMJ pain (n=22). Two distinct comparison groups were selected: subjects with a non-painful TMD (n=25) and TMD-free subjects (n=29). All participants filled out a self-report validated instrument (MOODS-SR) to evaluate psychopathological symptoms related to mood disturbances. A one-way analysis of variance (ANOVA) with Bonferroni’s post hoc test for multiple comparisons was performed to investigate for significant differences among the groups. The three groups of patients with painful TMD scored significantly higher than comparison groups in all MOODS-SR domains investigating depression, but no difference was shown between subjects with myofascial pain and those with TMJ pain. No significant differences among the groups emerged for the presence of manic symptoms, indicating that depressive disorders associated with TMD are not an expression of a more complex manic depressive illness. The study concluded that the presence of depressive symptoms in TMD patients seems to be related to the presence of a painful condition and seems to be unrelated to the location of pain. Furthermore, depressive disturbances in painful TMD patients affect the whole spectrum of depressive psychopathology.
Towards a Unified Theory of Timed Automata

Title of dissertation: TOWARDS A UNIFIED THEORY OF TIMED AUTOMATA Peter Christopher Fontana, Doctor of Philosophy, 2014 Dissertation directed by: Professor Rance Cleaveland Department of Computer Science Timed automata are finite-state machines augmented with special clock variables that reflect the advancement of time. Able to both capture real-time behavior and be verified algorithmically (model-checked), timed automata are used to model real-time systems. These observations have led to the development of several timed-automata verification tools that have been successfully applied to the analysis of a number of different systems; however, the practical utility of timed automata is undermined by the theories underlying different tools differing in subtle but important ways. Since algorithmic results that hold for the variant used by one tool may not apply to another variant, this complicates the application of different tools to different models. The thesis of this dissertation is this: the theory of timed automata can be unified, and a practical unified approach to timedautomata model checking can be built around the paradigm of proof search. First, this dissertation establishes the mutual expressivity of timed automata variants, thereby providing precise characterizations of when theoretical results of one variant apply to other variants. Second, it proves powerful expressive properties about different logics for timed behavior, and as a result, enlarges the set of verifiable properties. Third, it discusses an implementation of a verification tool for an expressive fixpoint-based logic, demonstrating an application of this newly developed theory. The tool is based on a proof-search paradigm; verifying timed automata involves constructing proofs using proof rules that enable verification problems to be translated into subproblems that must be solved. The tool’s performance is optimized by using derived proof rules, thereby providing a theoretically sound basis for faster model checking. Last, this dissertation utilizes the proofs generated during verification to gain additional information about the vacuous satisfaction of certain formulae: whether the automaton satisfied a formula by never satisfying certain premises of that specification. This extra information is often obtained without significantly decreasing the verifier’s performance. TOWARDS A UNIFIED THEORY OF TIMED AUTOMATA
Cost-effectiveness of vaccination against herpes zoster

Herpes zoster (HZ) is a common disease among elderly, which may develop into a severe pain syndrome labeled postherpetic neuralgia (PHN). A live-attenuated varicella zoster virus vaccine has been shown to be effective in reducing the incidence and burden of illness of HZ and PHN, providing the opportunity to prevent significant health-related and financial consequences of HZ. In this review, we summarize the available literature on cost-effectiveness of HZ vaccination and discuss critical parameters for cost-effectiveness results. A search in PubMed and EMBASE was performed to identify full cost-effectiveness studies published before April 2013. Fourteen cost-effectiveness studies were included, all performed in western countries. All studies evaluated cost-effectiveness among elderly above 50 years and used costs per quality-adjusted life year (QALY) gained as primary outcome. The vast majority of studies showed vaccination of 60- to 75-year-old individuals to be cost-effective, when duration of vaccine efficacy was longer than 10 years. Duration of vaccine efficacy, vaccine price, HZ incidence, HZ incidence and discount rates were influential to the incremental cost-effectiveness ratio (ICER). HZ vaccination may be a worthwhile intervention from a cost-effectiveness point of view. More extensive reporting on methodology and more detailed results of sensitivity analyses would be desirable to address uncertainty and to guarantee optimal comparability between studies, for example regarding model structure, discounting, vaccine characteristics and loss of quality of life due to HZ and PHN.
The Transcription Factor Protein Sox11 Enhances Early Osteoblast Differentiation by Facilitating Proliferation and the Survival of Mesenchymal and Osteoblast Progenitors*

Background: Sox11 deletion mice exhibit developmental defects, yet the detailed roles of Sox11 in osteogenesis are unknown. Results: Sox11 stimulated proliferation and survival of mesenchymal and osteoblast precursor cells through up-regulation of Tead2, as well as stimulated osteogenesis via Runx2 and Osterix. Conclusion: Sox11 positively regulates osteogenesis. Significance: Novel functions of Sox11 and its target genes during osteogenesis were established. Sox11 deletion mice are known to exhibit developmental defects of craniofacial skeletal malformations, asplenia, and hypoplasia of the lung, stomach, and pancreas. Despite the importance of Sox11 in the developing skeleton, the role of Sox11 in osteogenesis has not been studied yet. In this study, we identified that Sox11 is an important transcription factor for regulating the proliferation and survival of osteoblast precursor cells as well as the self-renewal potency of mesenchymal progenitor cells via up-regulation of Tead2. Furthermore, Sox11 also plays an important role in the segregation of functional osteoblast lineage progenitors from osteochondrogenic progenitors. Facilitation of osteoblast differentiation from mesenchymal cells was achieved by enhanced expression of the osteoblast lineage specific transcription factors Runx2 and Osterix. Morpholino-targeted disruption of Sox11 in zebrafish impaired organogenesis, including the bones, which were under mineralized. These results indicated that Sox11 plays a crucial role in the proliferation and survival of mesenchymal and osteoblast precursors by Tead2, and osteogenic differentiation by regulating Runx2 and Osterix.
Tuition fees, self-esteem and social heterogeneity

Modelling students' behaviour in relation to tuition fees is a complex task since students' ‘talent’ is not common knowledge. Students observe a private noisy signal of their abilities, while university receives noisy information based on the quantitative and qualitative data provided by university applicants. In this article, we add the heterogeneity of the population to this model: we assume that this heterogeneity means that the perception of skills among a part of the population is biased and underestimates the capabilities of its members to succeed in the higher education system. Our conclusions differ from those derived in the literature and show in particular that the optimal tuition fees for a given number of students are lower than those obtained for a homogeneous population.
La maladie thrombo-embolique veineuse au Cameroun (à propos de 18 cas)

○ Le but de cette etude etait de decrire les caracteristiques cliniques et echographiques des thromboses veineuses profondes des membres inferieurs et embolies pulmonaires observees au Centre d'exploration cardiovasculaire de Yaounde, Cameroun, en soulignant l'apport diagnostique de l'echo-doppler veineux. Quarante-sept explorations veineuses ultra sonographiques ont ete realisees dans notre Centre entre le le janvier 1998 et le 31 decembre 1999 avec un appareil de marque Logic 400 MD (General Electrics) suivant une technique classique. Une thrombose veineuse profonde a ete diagnostiquee dans 18 cas (38,2 %) chez 10 hommes et 8 femmes, âges en moyenne de 46 ans (extremes: 24 a 71 ans). Le thrombus etait localise au niveau des veines saphenes internes, poplitees ou surales dans 12 cas, au niveau de la veine femorale commune ou profonde dans 4 cas et 2 fois seulement dans la veine iliaque externe. Les facteurs de risque de thrombose veineuse les plus frequents dans notre serie etaient le contexte chirurgical, un mauvais terrain veineux, des antecedents de thrombose veineuse et l'obesite morbide (66,8 % de cas). L'alitement prolonge, une neoplasie (Kaposi des membres inferieurs) etaient plus rares (22,2 %). Six embolies pulmonaires (33,3 %) sont survenues pendant la periode d'observation, dont 3 (50 %) mortelles. Ces resultats, tout en marquant la relative rarete de la maladie thrombo-embolique dans notre milieu, en soulignent neanmoins l'existence, et font considerer, au vu du nombre de cas repertories d'embolie pulmonaire, souvent mortels, la necessite d'un traitement preventif systematique avec de l'heparine chez les patients noirs africains a risque.
Tweet Content Related to Sexually Transmitted Diseases: No Joking Matter

Background Online social media, such as the microblogging site Twitter, have become a space for speedy exchange of information regarding sexually transmitted diseases (STDs), presenting a potential risk environment for how STDs are portrayed. Examining the types of “tweeters” (users who post messages on Twitter) and the nature of “tweet” messages is important for identifying how information related to STDs is posted in online social media. Objective The intent of the study was to describe the types of message emitters on Twitter in relation to two different STDs—chlamydia and human immunodeficiency virus (HIV)—as well as the nature of content tweeted, including how seriously the topic was treated. Methods We used the Twitter search engine to look for tweets posted worldwide from August 1-7, 2013, and from September 1-7, 2013, containing the words “chlamydia” or “HIV”, and the hashtags “#chlamydia” or “#HIV”. Tweeters were classified by two independent reviewers according to the type of avatar of the user (human, logo, or fantasy), the identification of the emitter (identifiable, semi-identifiable, or non-identifiable), and the source (private company, general media, scientific media, non-governmental, individual account, academic institution, government department, or undefined). Tweet messages were also independently classified according to their nature (serious or jokes/funny), and whether their main message was factual or of a personal nature/experience. Results A total of 694 tweets were posted by 426 different users during the first 7 days of August and September, containing the hashtags and/or simple words “chlamydia” and/or “HIV”. Jokes or funny tweets were more frequently posted by individual users (89%, 66/74), with a human avatar (81%, 60/74), from a non-identifiable user (72%, 53/74), and they were most frequently related to chlamydia (76%, 56/74). Serious tweets were most frequently posted by the general media (20.6%, 128/620), using a logo avatar (66.9%, 415/620), and with identifiable accounts (85.2%, 528/620). No government departments, non-governmental organizations, scientific media, or academic institutions posted a joke on STDs. A total of 104 of these analyzed tweets were re-tweeted messages, belonging to 68 unique tweets. The content was serious (99%, 67/68), factual (90%, 52/58), and about HIV (85%, 58/68). Conclusions Social media such as Twitter may be an important source of information regarding STDs provided that the topic is presented appropriately. Reassuringly, the study showed that almost 9/10 of tweets on STDs (chlamydia and HIV) were of serious content, and many of the tweets that were re-tweeted were facts. The jokes that were tweeted were mainly about chlamydia, and posted by non-identifiable emitters. We believe social media should be used to an even larger extent to disseminate correct information about STDs.
The significance of serum soluble IL‐2 receptor as a marker for active visceral leishmaniasis in Sicilian patients

Sera from nine Sicilian patients with confirmed visceral leishmaniasis (Leishmania donovani infantum; VL), at the moment of the diagnosis, during the course of the disease and after clinical recovery, were analysed for the concentration of soluble IL‐2 receptor (sIL‐2R). The results show that sIL‐2R is a marker of disease activity, since it is in high concentration at the beginning of infection and returns to the normal range following successful chemotherapy. At the same time of serum analysis for sIL‐2R, peripheral blood mononuclear cells (PBMC) of VL patients were stimulated with phytohaemagglutinin (PHA) or antigen and supernatant tested for IL‐2 and interferon‐gamma (IFN‐γ) production. Data demonstrate that there is an inverse relation between concentration of IL‐2 and IFN‐γ in the supernatants and sIL‐2R secretion in the sera.
Challenges for the Future

pajares@eis.uva. es Abstract . The purpose of this paper is to analyse the main challenges that the University of Valladolid (UVa) will face in the future, and the role of Information and Communication Technologies in order to succeed these challenges. After seven centuries of history involved in academic activities, our university has to produce high quality research, and to design study programs attractive enough to encourage foreign students to come to Valladolid. In the knowledge economy, our university should be the driving force of the economic growth of the Region of Castile and Leon; efficient management systems are an initial condi-tion to
Reduction of waste product excretion via nutrient control: Possible strategies for maximizing product and cell yields on serum in cultures of mammalian cells

Mammalian cells grown in culture excrete lactic acid and ammonium ions in quantities that may limit growth and reduce product synthesis. Frequent replenishment of the culture medium is often necessary to prevent waste product accumulation which could inhibit cell growth. Since increased medium replenishment results in increased usage of animal serum, the most expensive raw material, excessive production of waste products lowers the cell and product yield on serum, and hence increases production costs. Strategies for reducing the production of lactic acid and ammonium bymammalian cells via controlled addition of glucose and glutamine will be demonstrated. Mathematical relations coupling ammonium and glutamine kinetics will be described. Additionally, a method for automatic on‐line estimation of the cell concentration was developed. This method involves calculating the ATP production rate from the oxygen uptake rate and the lactic acid production rate. Automatic online estimation of the cell concentration is critical if nutrient levels in large‐scale mammaliancell cultures are to be accurately maintained via process control.
Die Europäisierung des schweizerischen Rechts

Die Rechtsentwicklung in der Europaischen Union (EU) beeinflusst das schweizerische Recht erheblich. Dieser Prozess erfolgt auf zwei Ebenen: Zum einen existiert zwischen der Schweiz und der EU ein engmaschiges Vertragsnetz. Rund zwanzig bilaterale Hauptabkommen und gegen hundert Sekundarabkommen fuhren zur weitgehenden Teilintegration der Schweiz in den europaischen Binnenmarkt. Die Umsetzung dieser Abkommen im schweizerischen Recht und ihre Anwendung im Alltag haben weit reichende Konsequenzen fur die Schweiz. Zum anderen ubernimmt die Schweiz autonom EU-Recht, ohne dass entsprechende Anpassungen staatsvertraglich ausgelost werden. Im Zentrum steht die Politik der Europavertraglichkeit des schweizerischen Rechts, welche als allgemeingultige Rechtsetzungsmaxime seit 1988 jedes Rechtsetzungsverfahren auf Bundesebene begleitet und die Epoche des autonomen Nachvollzugs eingelautet hat.
Admission to Intensive Care for Palliative Care or Potential Organ Donation: Demographics, Circumstances, Outcomes, and Resource Use

Objectives: To describe the characteristics, circumstances, change over time, resource use, and outcomes of patients admitted to ICUs in Australia and New Zealand for the purposes of “palliative care of a dying patient” or “potential organ donation,” and compare with actively managed ICU patients. Design: A retrospective study of data from the Australian and New Zealand Intensive Care Society Adult Patient Database and a nested cohort analysis of a single center. Setting: One hundred seventy-seven ICUs in Australia and New Zealand and a nested analysis of one university-affiliated hospital ICU in Melbourne, VIC, Australia. Patients: Three thousand seven hundred “palliative care of a dying patient” and 1,115 “potential organ donation” patients from 2007 to 2016. The nested cohort included 192 patients. Interventions: No interventions. Data extracted included patient demographics, diagnoses, length of stay, circumstances, and outcome of admission. Measurements and Main Results: ICU admissions for “palliative care of a dying patient” and “potential organ donation” increased from 179 in 2007 to 551 in 2016 and from 44 in 2007 to 174 in 2016 in each respective group, though only the “potential organ donation” cohort showed an increase in proportion of total ICU admissions. Lengths of stay in ICU were a mean of 33.8 hours (median, 17.5; interquartile range, 6.4–38.8) and 44.7 hours (26.6; 16.0–44.6), respectively, compared with 74.2 hours (41.5; 21.7–77.0) in actively managed patients. Hospital mortality was 86.6% and 95.9%, respectively. In the nested cohort of 192 patients, facilitating family discussions about goals of treatment and organ donation represented the most common reason for ICU admission. Conclusions: Patients admitted to ICU to manage end-of-life care represent a small proportion of overall ICU admissions, with an increasing proportion of “potential organ donation” admissions. They have shorter ICU lengths of stay than actively managed patients, suggesting resource use for these patients is not disproportionate.
Craniocervical Artery Dissection: Clinical and Imaging Mid-term Follow Up

Background and objective: To analyze the temporal evolution of imaging findings and clinical follow up in craniocervical arterial dissection (CAD) patients. Methods: 32 patients (M: F=23: 9, mean age=49) with radiographic evidence of at least one of the suggestive imaging findings of CAD (arterial stenosis, arterial occlusion, luminal ectasia, pseudoaneurysm, and dissection flap) were performed. Median imaging follow up period was 89 days (SD=36.69). Clinical symptoms on presentation and follow up were also analyzed. Results: 21 patients had spontaneous dissection (65.6%). 11 had a history of trauma (34.4%). 14 (43.8%) patients presented with a stroke or TIA. Other presenting symptoms include headache (n=4, 12.5%), neck pain (n=9, 28.1%) and Horner’s syndrome (n=5, 15.6%). Involved arteries included Internal carotid artery (n=21, 65.6%), vertebral artery (n=10, 31.3%), and common carotid artery (n=3, 9.4%). Initial imaging findings included, arterial stenosis (n=23, 72%), arterial occlusion (n=6, 19%), ectasis of the lumen (n=7, 22%), pseudoaneurysm (n=12, 38%), and dissection flap (n=12, 38%). 21 patients were managed with anti-coagulation and 3 with an antiplatelet agent. On follow up imaging, arterial stenosis was improved in 73.6% (14/19), worse in 5.3% and no interval change in 21.1%. Regarding the pseudoaneurysm on presentation, no change in shape and size in 64% (7/11) and 2 patients developed new pseudoaneurysm. One patient developed a TIA (3.7%, n=1/27) during follow up. Conclusion: Post-dissection vascular imaging findings are dynamic. With medical management, more than 60% of the arterial stenosis lesions have improved within 3 months, and the risk of repeated neurological events were very low.