Miracle-dz/UniFAR-FTUs huggingface dataset:
Introduction of a viral thymidine kinase gene and the human beta-globin gene into developmentally multipotential mouse teratocarcinoma cells.

Teratocarcinoma (TCC) stem cells provide unique prospects for the introduction of specific genes into mice, by virtue of their dual capacity for propagation in vitro and for normal differentiation in embryos. In this study, we have demonstrated that foreign genes amenable to selection in culture can be transferred into the stem cells and expressed. These cells maintain expression of the gene for long periods during differentiation in tumors in vivo in the absence of selective pressure. The cells also integrate an unlinked nonselectable gene at high frequency. Addition of the cloned herpes simplex virus (HSV) thymidine kinase (tk; ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) gene to cultures of tk(-)TCC cells yielded tk(+) colonies at a frequency of one colony per 4 mug of plasmid DNA. This transformation efficiency, although appreciably lower than for mouse L tk(-) cells, permits the isolation of many transformants. The HSV provenance of the transformed phenotype was verified by the characteristic electrophoretic mobility of the tk protein and by neutralization of the tk activity with specific antiserum. Moreover, blot hybridization tests revealed at least one intact copy of the viral tk gene integrated into the DNA of transformed cells. When injected into syngeneic mice, the cells formed solid tumors with various differentiating tissues. From blot hybridization comparisons with their cell lines of origin, seven of nine tumors examined had maintained the HSV tk gene without significant loss or rearrangement. Viral tk enzyme activity could also be demonstrated in at least some of the tumors. Cotransfer of the cloned human beta-globin gene along with the unlinked HSV tk gene was successful in 2 of 10 tk(+) transformants. Thus, defined genes can be stably introduced into TCC cells in culture and maintained in vivo in a form in which they are transcribed and translated to produce a functional protein.
Involvement of Calmodulin and Protein Kinase C in Cholecystokinin Release by Bombesin from STC-1 Cells

The mouse intestinal neuroendocrine tumor cell line STC-1 secretes cholecystokinin (CCK) and other hormones. We investigated the role of Ca2+, calmodulin (CaM), and protein kinase C (PKC) in the regulation of CCK release from STC-1 cells. Phorbol 12-myristate 13-acetate (TPA) significantly stimulated CCK release. Staurosporine significantly inhibited CCK release from STC-1 cells stimulated by TPA in a dose-dependent manner. The absence of extracellular calcium completely inhibited CCK release from TPA-stimulated STC-1 cells. Neurotensin did not stimulate CCK release from these cells. W-7, a CaM antagonist, reduced CCK release from STC-1 cells stimulated by bombesin in a dose-dependent manner. These findings suggest that CaM and PKC play an important role in the regulation of CCK release from STC-1 cells stimulated by bombesin.
Specification, implementation and verification of refactorings

Refactoring is the process of reorganising or restructuring code by means of behaviour-preserving program transformations, themselves called refactorings. Most modern development environments come with built-in support for refactoring in the form of automated refactorings that the user can perform at the push of a button. Implementing refactorings is notoriously complex, however, and even state-of-the-art implementations have very low standards of correctness and can introduce subtle changes of behaviour into refactored programs. In this thesis, we develop concepts and techniques that make it possible to give concise, modular specifications of refactorings. These specifications are precise enough to cover all details of the object language, and thus give rise to full featured, high-quality refactoring implementations. Their modularity, on the other hand, makes them amenable to formal proof, and hence opens the door to the rigorous verification of refactorings. We discuss a disciplined approach to maintaining name bindings and avoiding name capture by treating the binding from a name to the declaration it refers to as a dependency that the refactoring has to preserve. This approach readily generalises to other types of dependencies for capturing control flow, data flow and synchronisation behaviour. To implement complex refactorings, it is often helpful for the refactoring to internally work on a richer language with language extensions that make the transformation easier to express. We show how this allows the decomposition of refactorings into small microrefactorings that can be specified, implemented and verified in isolation. We evaluate our approach by giving specifications and implementations of many commonly used refactorings that are concise, yet match the implementations in the popular Java development environment Eclipse in terms of features, and outperform them in terms of correctness. We give detailed informal correctness proofs for some of our specifications, which are greatly aided by their modular structure. Finally, we discuss a rigorous formalisation of the central name binding framework used by most of our specifications in the theorem prover Coq, and show how its correctness can be established mechanically.
The binding of vinblastine by platelets in the rat.

Rats have been given i.p. injections of vinblastine tritiated in the aromatic rings (dose, approximately 0.25 mg/kg). The isotope levels in the blood were measured over a 24-hr period. The peak radioactivity was reached 1.5 hr after the injection, at which time approximately 2% of the dose was present in the circulation. In this early period, most of the radioactivity was found in the buffy coat. Blood smears of rats given tritiated vinblastine were examined autoradiographically with a “drytransfer” method developed to minimize translocation of soluble radioactive compounds. Most of the silver grains in the autoradiograms were associated with single platelets and platelet clumps; leukocytes were only slightly labeled and red cells negligibly labeled. Blood, collected 2 hr after the tritiated alkaloid was injected i.p., was fractionated by differential centrifugation. The distribution of radioactivity was approximately: plasma, 15%; red cells, 10%; leukocytes, 15%; platelets, 60%. Isotopic dilution analysis showed that unchanged vinblastine accounted for essentially all the platelet radioactivity but for only about 50% of that in the plasma. In vitro , when platelet-rich plasma was incubated with tritiated vinblastine (0.05 µg/ml plasma), 75% of the radioactivity was taken up by the platelets. It is suggested that platelets may play a role in mediating the chemotherapeutic action and pharmacological activity of the Vinca alkaloids.
The Yeast GRASP Grh1 Colocalizes with COPII and Is Dispensable for Organizing the Secretory Pathway

In mammalian cells, the ‘Golgi reassembly and stacking protein’ (GRASP) family has been implicated in Golgi stacking, but the broader functions of GRASP proteins are still unclear. The yeast Saccharomyces cerevisiae contains a single non‐essential GRASP homolog called Grh1. However, Golgi cisternae in S. cerevisiae are not organized into stacks, so a possible structural role for Grh1 has been difficult to test. Here, we examined the localization and function of Grh1 in S. cerevisiae and in the related yeast Pichia pastoris, which has stacked Golgi cisternae. In agreement with earlier studies indicating that Grh1 interacts with coat protein II (COPII) vesicle coat proteins, we find that Grh1 colocalizes with COPII at transitional endoplasmic reticulum (tER) sites in both yeasts. Deletion of P. pastoris Grh1 had no obvious effect on the structure of tER–Golgi units. To test the role of S. cerevisiae Grh1, we exploited the observation that inhibiting ER export in S. cerevisiae generates enlarged tER sites that are often associated with the cis Golgi. This tER–Golgi association was preserved in the absence of Grh1. The combined data suggest that Grh1 acts early in the secretory pathway, but is dispensable for the organization of secretory compartments.
Developments in the diagnostic procedures for von Willebrand disease

Von Willebrand disease (VWD) is the most common inherited bleeding disorder but its diagnosis can be challenging due to the heterogeneity of the disease. VWD is mainly associated with mild mucocutaneous bleeding, although there are more severe phenotypes with bleeding from the gastrointestinal tract or even the joints. Also, surgical interventions and trauma may lead to critical bleeding events. These bleeding episodes are all related to quantitative or qualitative defects of von Willebrand factor (VWF), a multimeric glycoprotein produced by endothelial cells and megakaryocytes, which mediates platelet adhesion and aggregation and binds factor VIII (FVIII) in the circulation. This review describes the diagnostic procedures required for correct diagnosis. Accurate diagnosis and classification is required for proper treatment and counseling. Assessment of bleeding starts with the medical history. After a positive bleeding or family history, subsequent laboratory investigations will start with a panel of standard screening tests for hemostatic defects. Patients suspected of having VWD will be tested for plasma VWF antigen levels, the ability of VWF to bind platelets and FVIII activity. When VWD is confirmed, a set of subtyping tests can classify the patients as VWD types 1, 2 (A, B, M or N) or 3. The performance of some additional assays and analyses, such as VWF propeptide measurement or genetic analysis, may help in identifying the pathological mechanism behind certain defects or can guide in the choice of treatment.
Variation-Aware Fault Grading

An iterative flow to generate test sets providing high fault coverage under extreme parameter variations is presented. The generation is guided by the novel metric of circuit coverage, calculated by massively parallel statistical fault simulation on GPGPUs. Experiments show that the statistical fault coverage of the generated test sets exceeds by far that achieved by standard approaches.
Improving Recommendation of Tail Tags for Questions in Community Question Answering

We study tag recommendation for questions in community question answering (CQA). Tags represent the semantic summarization of questions are useful for navigation and expert finding in CQA and can facilitate content consumption such as searching and mining in these web sites. The task is challenging, as both questions and tags are short and a large fraction of tags are tail tags which occur very infrequently. To solve these problems, we propose matching questions and tags not only by themselves, but also by similar questions and similar tags. The idea is then formalized as a model in which we calculate question-tag similarity using a linear combination of similarity with similar questions and tags weighted by tag importance.Question similarity, tag similarity, and tag importance are learned in a supervised random walk framework by fusing multiple features. Our model thus can not only accurately identify question-tag similarity for head tags, but also improve the accuracy of recommendation of tail tags. Experimental results show that the proposed method significantly outperforms state-of-the-art methods on tag recommendation for questions. Particularly, it improves tail tag recommendation accuracy by a large margin.
Multiple-Criteria Sorting Using Case-Based Distance Models With an Application in Water Resources Management

A case-based distance model to solve sorting problems in multiple-criteria decision analysis (MCDA) is developed, and its application in water resources management is presented. The sorting problem in MCDA is to arrange a set of alternatives into ordered groups. MCDA is introduced as consequence-based preference aggregation, whereby consequence and preference expressions (values and weights) are defined and combined in a sequence of steps. Then, sorting problems are defined, and some properties are explained. Based on weighted Euclidean distance, two case-based distance models are developed for sorting using weights and group thresholds obtained by assessment of a case set provided by a decision maker (DM). This case-based method can elicit the DM's preferences more expeditiously and accurately than direct inquiry. Case-based sorting model I is designed for cardinal criteria, while its extension, i.e., case-based sorting model II, can handle both cardinal and ordinal criteria. Optimization programs are employed to find the most descriptive weights and group thresholds. A case study in which Canadian municipalities are sorted according to water usage is presented.
Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2‐deficient mice

The transcription factor Nrf2 regulates the expression of antioxidant genes. Hyperglycemia‐induced oxidative stress is involved in the pathogenesis of diabetes and its complications. However, little is known about the protective role of Nrf2 in diabetes. To gain insight into the protective role of Nrf2 in diabetes we treated Nrf2 knockout (Nrf2 KO) mice with streptozotocin (STZ). The STZ Nrf2 KO mice did not develop renal hyperfiltration, which was observed in the STZ‐treated wild‐type (STZ WT) mice, but renal function gradually deteriorated over the 10‐week observation period. Urinary excretion of nitric oxide metabolites and the occurrence of 8‐nitroguanosine, which was detected in glomerular lesions, were increased in STZ Nrf2 KO mice during the early stages after treatment. In vivo electron paramagnetic resonance analysis revealed an accelerated rate of decay of the 3‐carbamoyl‐2,2,5,5‐tetramethylpyrrolidine‐1‐oxyl spin probe signal in STZ Nrf2 KO mice. The addition of superoxide dismutase prolonged the half‐life of the signal, which suggested that increased oxygen radical formation occurred in the STZ Nrf2 KO mice. These results suggested that hyperglycemia increased oxidative and nitrosative stress and accelerated renal injury in the Nrf2 KO mice and that Nrf2 serves as a defense factor against some diabetic complications.
Summary report on first , second and third generation smallpox vaccines

Content Background . 3 First generation smallpox vaccines . 3 Second generation vaccines . 11 Third generation vaccines . 15 Other smallpox vaccines . 26 Ethical considerations . 27 References . 29
The HIS4 gene from the yeast Kluyveromyces lactis

The Kluyveromyces lactis HIS4 gene was cloned by complementation of a Saccharomyces cerevisiae his4 mutant. Sequence analysis revealed a 2388 bp open reading frame encoding a single polypeptide predicted to encompass three distinct enzymatic activities (phosphoribosyl‐AMP cyclohydrolase, phosphoribosyl‐ATP pyrophosphohydrolase and histidinol dehydrogenase). This structural organization is strikingly similar to that of the His4 proteins from S. cerevisiae and Pichia pastoris. Transcript analysis detected a single mRNA species of 2.5 kb. The EMBL accession number of this gene is Y09503. © 1998 John Wiley & Sons, Ltd.
Manifestations of sexual selection may depend on the genetic basis of sex determination

A variant of the ‘handicap’ model of sexual selection is described which predicts that the evolution of ornate male traits occurs more easily in species where females are the heterogametic sex. The process occurs even when the alleles conferring high paternal ‘fitness’ remain advantageous for only a short time due to a rapidly changing physical or biotic environment: the timescale of this advantage may approach the gestation time of the organism. This provides an explanation as to why sexual selection in species where females are heterogametic (such as birds) occurs mainly by the elaboration of ornate male secondary sexual characteristics, whereas in species where females are homogametic (such as mammals) sexual selection results predominantly in inter-male rivalry and the evolution of traits such as horns, antlers and large body size. An analogy between the evolution of elaborate male traits and the evolution of warning coloration is noted.
Development and validation of a novel bioreactor system for load‐ and perfusion‐controlled tissue engineering of chondrocyte‐constructs

Osteoarthritis is a severe socio‐economical disease, for which a suitable treatment modality does not exist. Tissue engineering of cartilage transplants is the most promising method to treat focal cartilage defects. However, current culturing procedures do not yet meet the requirements for clinical implementation. This article presents a novel bioreactor device for the functional tissue engineering of articular cartilage which enables cyclic mechanical loading combined with medium perfusion over long periods of time, under controlled cultivation and stimulation conditions whilst ensuring system sterility. The closed bioreactor consists of a small, perfused, autoclavable, twin chamber culture device with a contactless actuator for mechanical loading. Uni‐axial loading is guided by externally applied magnetic fields with real‐time feedback‐control from a platform load cell and an inductive proximity sensor. This precise measurement allows the development of the mechanical properties of the cultured tissue to be monitored in real‐time. This is an essential step towards clinical implementation, as it allows accounting for differences in the culture procedure induced by patient‐variability. This article describes, based on standard agarose hydrogels of 3 mm height and 10 mm diameter, the technical concept, implementation, scalability, reproducibility, precision, and the calibration procedures of the whole bioreactor instrument. Particular attention is given to the contactless loading system by which chondrocyte scaffolds can be compressed at defined loading frequencies and magnitudes, whilst maintaining an aseptic cultivation procedure. In a “proof of principle” experiment, chondrocyte seeded agarose gels were cultured for 21 days in the bioreactor system. Intermittent medium perfusion at a steady flow rate (0.5 mL/min) was applied. Sterility and cell viability (ds‐DNA quantification and fluorometric live/dead staining) were preserved in the system. Flow induced shear stress stimulated sGAG (sulfated glycosaminoglycan) content (DMMB assay) after 21 days, which was confirmed by histological staining of Alcian blue and by immunostaining of Aggrecan. Experimental data on mechanotransduction and long‐term studies on the beneficial effects of combined perfusion and different mechanical loading patterns on chondrocyte seeded scaffolds will be published separately. Biotechnol. Bioeng. 2008;101: 714–728. © 2008 Wiley Periodicals, Inc.
Stereotactic Ablative Radiotherapy Induces Peripheral T-Cell Activation in Patients with Early-Stage Lung Cancer.

Affiliations: 1. Erasmus MC, Cancer Institute, Department of Pulmonary Medicine, Rotterdam, The Netherlands 2. Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Thoracic Oncology, Amsterdam, The Netherlands 3. Amphia Hospital, Department of Pulmonary Diseases, Breda, The Netherlands 4. Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam, The Netherlands 5. Erasmus MC, Department of Radiation Oncology, Rotterdam, The Netherlands 6. Erasmus MC, Department of Cardio-thoracic Surgery, Rotterdam, The Netherlands 7. VU Medical Center, Department of Radiation Oncology, Amsterdam, The Netherlands * Current affiliation: Academic Medical Center, Laboratory for Experimental Oncology and Radiobiology, Amsterdam, The Netherlands
Challenges and Limitations Concerning Automatic Child Pornography Classification

The huge volume of data to be analyzed in the course of child pornography investigations puts special demands on tools and methods for automated classification, often used by law enforcement and prosecution. The need for a clear distinction between pornographic material and inoffensive pictures with a large amount of skin, like people wearing bikinis or underwear, causes problems. Manual evaluation carried out by humans tends to be impossible due to the sheer number of assets to be sighted. The main contribution of this paper is an overview of challenges and limitations encountered in the course of automated classification of image data. An introduction of state-of-the-art methods, including faceand skin tone detection, faceand texture recognition as well as craniofacial growth evaluation is provided. Based on a prototypical implementation of feasible and promising approaches, the performance is evaluated, as well as their abilities and shortcomings.
Food choice ideologies: the modern manifestations of normative and humanist views of the world

Two studies examined whether everyday food choice motives (FCMs) and abstract values constitute food choice ideologies (FCIs), whether these ideologies reflect the same normativism-humanism polarity as Tomkins' theory suggests to reflect ideologies in general, and whether various dietary groups endorse FCIs in different ways. In Study 1, 82 female participants filled in the Food Choice Questionnaire, a short version of Schwartz's Value Survey, and Tomkins' Polarity Scale. The results reflected four FCIs: ecological ideology (EI), health ideology (HI), pleasure ideology (PI) and convenience ideology (CI). Study 2 (N=144) replicated the results for ecological and health ideologies but not for pleasure and convenience ideologies. In both studies, EI, which was typical for vegetarians, was associated with a humanist view of the world, whereas HI was related to a normative view of the world. The results suggest that food choice has become a new site where one expresses one's philosophy of life.
Universal behavior of time-resolved photoluminescence decays in III-V solar cells: Comparison of subcell current generation dynamics

We investigated the charge separation processes in three types of III-V solar cells with different device structures using power dependence of time-resolved photoluminescence (PL) decays. The samples were a GaAs single junction and InGaP and GaAs subcells of triple-junctions solar cells prepared with different growth techniques. All p-n junctions showed same systematic changes in the PL decay profiles with increasing excitation power. The data evidences that charge separation and recombination carrier dynamics can be probed directly in a wide range of devices with time-resolved PL decays. The optical method allows to determine the subcells electrical behavior from the PL decay time constants.
Mean cerebral blood flow measurements using phase contrast MRI in the first year of life

Alterations in cerebral blood flow (CBF) are believed to be linked to many of the neurological pathologies that affect neonates and small infants. CBF measurements are nonetheless often difficult to perform in this population, as many techniques rely on radioactive tracers or other invasive methods. In this study, mean global CBF was measured in 21 infants under the age of one, using non‐invasive MRI techniques adapted to the neonatal population. Mean CBF was computed as the ratio of blood flow delivered to the brain (measured using phase contrast MRI) and brain volume (computed by segmenting anatomical MR images). Tests in adult volunteers and repeated measurements showed the flow measurements using the proposed method to be both accurate and reproducible. It was also found that cardiac gating need not be employed in infants with no known cardiac pathology.