Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-CD22/CD20 Bispecific Antibody with Enhanced Trogocytosis for Treatment of Lupus

The humanized anti-CD22 antibody, epratuzumab, has demonstrated therapeutic activity in clinical trials of lymphoma, leukemia and autoimmune diseases, treating currently over 1500 cases of non-Hodgkin lymphoma, acute lymphoblastic leukemias, Waldenström’s macroglobulinemia, Sjögren’s syndrome, and systemic lupus erythematosus. Because epratuzumab reduces on average only 35% of circulating B cells in patients, and has minimal antibody-dependent cellular cytotoxicity and negligible complement-dependent cytotoxicity when evaluated in vitro, its therapeutic activity may not result completely from B-cell depletion. We reported recently that epratuzumab mediates Fc/FcR-dependent membrane transfer from B cells to effector cells via trogocytosis, resulting in a substantial reduction of multiple BCR modulators, including CD22, CD19, CD21, and CD79b, as well as key cell adhesion molecules, including CD44, CD62L, and β7 integrin, on the surface of B cells in peripheral blood mononuclear cells obtained from normal donors or SLE patients. Rituximab has clinical activity in lupus, but failed to achieve primary endpoints in a Phase III trial. This is the first study of trogocytosis mediated by bispecific antibodies targeting neighboring cell-surface proteins, CD22, CD20, and CD19, as demonstrated by flow cytometry and immunofluorescence microscopy. We show that, compared to epratuzumab, a bispecific hexavalent antibody comprising epratuzumab and veltuzumab (humanized anti-CD20 mAb) exhibits enhanced trogocytosis resulting in major reductions in B-cell surface levels of CD19, CD20, CD21, CD22, CD79b, CD44, CD62L and β7-integrin, and with considerably less immunocompromising B-cell depletion that would result with anti-CD20 mAbs such as veltuzumab or rituximab, given either alone or in combination with epratuzumab. A CD22/CD19 bispecific hexavalent antibody, which exhibited enhanced trogocytosis of some antigens and minimal B-cell depletion, may also be therapeutically useful. The bispecific antibody is a candidate for improved treatment of lupus and other autoimmune diseases, offering advantages over administration of the two parental antibodies in combination.
Mesophilic Mineral-Weathering Bacteria Inhabit the Critical-Zone of a Perennially Cold Basaltic Environment

The weathering of silicate in the world's critical-zone (rock-soil interface) is a natural mechanism providing a feedback on atmospheric CO2 concentrations through the carbonate-silicate cycle. We examined culturable bacterial communities from a critical-zone in western Iceland to determine the optimum growth temperature and their ability to solubilize phosphate-containing minerals, which are abundant within the critical-zone area examined here. The majority of isolated bacteria were able to solubilize mineral-state phosphate. Almost all bacterial isolates were mesophilic (growth optima of 20–45°C), despite critical-zone temperatures that were continuously below 15°C, although all isolates could grow at temperatures associated with the critical-zone (−2.8–13.1°C). Only three isolates were shown to have thermal optima for growth that were within temperatures experienced at the critical-zone. These findings show that the bacteria that inhabit the western Icelandic critical-zone have temperature growth optima suboptimally adapted to their environment, implying that other adaptations may be more important for their long-term persistance in this environment. Moreover, our study showed that the cold basaltic critical-zone is a region of active phosphate mineral-weathering.
Pharmacogenomic Modeling of Circulating Tumor and Invasive Cells for Prediction of Chemotherapy Response and Resistance in Pancreatic Cancer

Purpose: Despite a challenging prognosis, modern cytotoxic therapy can induce tumor responses and extend life in pancreatic adenocarcinoma (PDAC). Pharmacogenomic (PGx) modeling of tumor tissue can predict the efficacy of chemotherapeutic agents in preclinical cancer models. We hypothesized that PGx profiling of circulating tumor and invasive cells (CTIC) isolated from peripheral blood could predict tumor response, progression, and resistance. Experimental Design: A PGx model was created and validated in preclinical models. A prospective clinical trial was conducted. Fifty patients with advanced PDAC were enrolled. Before treatment, 10 mL of peripherally drawn blood was collected. CTICs isolated from this blood sample were expression profiled and the PGx model was used to predict effective and ineffective chemotherapeutic agents. The treating physicians were blinded to PGx prediction. Results: We found that CTICs could be reliably isolated, total RNA extracted and profiled from 10 mL of peripheral blood from patients with unresectable PDAC before chemotherapy treatment and at disease progression. Using previously created PGx models to predict chemotherapy sensitivity, we found that clinical benefit was seen for study participants treated with chemotherapy regimens predicted to be effective versus chemotherapy regimens predicted to be ineffective with regard to progression-free (10.4 mo vs. 3.6 mo; P < 0.0001; HR, 0.14) and overall survival (17.2 mo vs. 8.3 mo; P < 0.0249; HR, 0.29). Conclusions: These findings suggest that PGx profiling of CTICs can predict treatment response. Clin Cancer Res; 20(20); 5281–9. ©2014 AACR.
Bismuth-Based High-Temperature Superconductors

Overview: discovery and progress in Bi-based oxide high Tc superconductors. Physics and chemistry: crystal structure thermal and magnetic properties tunnelling phases and their relationships in the Bi-Pb-Sr-Ca-Cu-O System phase equilibria and crystal chemistry of the high-temperature superconducting compounds of the system Bi2O3-SrO-CaO-CuO intrinsic pinning radiation effects preparation of precursor powders preparation of single crystals diffusion reaction in Bi-base oxides. Bulk, wire/tape and applications: Bi-based superconductor fabricated by the floating zone method Bi-based bulk current leads and their applications power-in-tube Bi2223 Ag-sheathed tape: basic process, microstructure and critical current density thermodynamics, microstructure and critical current density in Bi, Pb(2223) tapes manufacture and properties of Bi-2212-based Ag sheathed wires Bi-2212 Ag sheathed wire properties of Bi-2212 silver-sheathed tape and its application to magnets Bi-2212/Ag composite tapes processed by Doctor Blade or dip-coating process coils, power leads, busbars and cables fabrication and characterization of HYSC coils made from Bi-2223 conductors. Thin films and applications: MOCVD growth of high-quality B12223 superconducting films layer-by-layer growth of Bi-based superlattices by molecular beam epitaxy basic properties for BSCCO devices. Outlook: future prospects. (Part contents.)
Chia induces clinically discrete weight loss and improves lipid profile only in altered previous values.

INTRODUCTION chia (Salvia hispanica L.) has an elevated concentration of dietary fiber, it has been used to weight loss and enhance blood glucose and lipid profile. However, data in human are still scarce or do not exist, according to the analyzed variable. AIM to evaluate the effect of chia supplementation in body composition, lipid profile and blood glucose in overweight or obese individuals. METHODS men and women were randomly allocated in groups that ingested 35 g of chia flour/day (CHIA; n=19; 48.8±1.8 years) or placebo (PLA; n=7; 51.4±3.1 years) for 12 weeks. Body composition and food intake were evaluated in each four weeks. Lipid profile and blood glucose were measured in the beginning and in the end of the study. RESULTS Chia induced significant intragroup reduction in body weight (-1.1±0.4 kg; p<0.05), with a greater reduction among obese than overweighed individuals (-1.6±0.4 kg; p<0.00), but without difference when compared to PLA. Waist circumference reduced 1.9±0.6 cm in CHIA group (p <0.05), but only intragroup. It was observed a reduction in total cholesterol (p=0.04) and VLDL-c (p=0.03), and an increase in HDL-c (p=0.01) but only in the groups that ingested chia flour and presented abnormal initial values. Triglycerides, blood glucose and LDL-C showed no changes for either group. CONCLUSION consumption of chia for 12 weeks promotes significant but discrete reduction in weight and waist circumference, and enhances lipid profile dependent of initial values.
The Association of Diet with Respiratory Symptoms and Asthma in Schoolchildren in Taipei, Taiwan

This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01–1.09) for exercise-induced cough to 1.09 (95% CI = 1.03–1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.
External fibronectin of cultured human fibroblasts is predominantly a matrix protein

The distribution of a major glycoprotein (fibronectin) of human fibroblast cultures was studied in immunoelectron microscopy with peroxidase- or ferritin-labeled antibodies. External fibronectin was visualized in pericellular structures, in some areas on the growth substratum, and to a lesser degree in close association with the upper and lower surface membranes of the cell. The pericellular fibronectin- containing structures consisted of amorphous or vaguely fibrillar material forming strands or patches, 50-500 nm in diameter; the structures appeared to mediate distant cell-to-cell and cell-to- substrate contacts. When in close association with the plasma membrane, fibronectin markers were seen as discrete patches. The exact relationship between this form of fibronectin and the plasma membrane, however, remained open. Filamentous material was commonly seen in the cortical cytoplasm under patches of membrane-associated fibronectin. The distribution that we observed is consistent with the proposed roles of fibronectin in cell interactions with neighboring structures and with its presence in vivo as an extracellular glycoprotein in connective tissue matrix and basal laminae.
Supporting the creative game design process with exertion cards

Advances in sensing technologies have led to research into exertion games that support physically effortful experiences. Despite the existence of theoretical frameworks that can be used to analyze such exertion experiences, there are few tools to support the hands-on practice of exertion game design. To address this, we present a set of design cards based on the "Exertion Framework", grounded in our experience of creating exertion games for over a decade. We present results demonstrating the value and utility of these Exertion Cards based on our studies of their use in three workshops held over seven sessions with 134 design students and experts. We also articulate lessons learned from transforming a theoretical framework into a design tool that aims to support designers in their practice.
Formation of Si Nanocrystals in Thin SiO2 Films for Memory Device Applications

X-ray Diffraction and Reflectivity, Transmission Electron Microscopy and Atomic Force Microscopy were applied to study the effect of thermal annealing on the properties of thin SiOx films (~ 15 nm) prepared by thermal evaporation of SiO in vacuum. It has been shown that furnace annealing at 1000 oC causes phase separation and formation of uniformly distributed Si nanocrystals into a SiO2 matrix. Clockwise hysteresis has been observed in the C-V curves measured and explained by assuming charging and discharging of the NCs with carriers, which tunnel from the Si substrate.
Early effects of modern electroconvulsive therapy on subjective memory in patients with mania or depression

Context: Although electroconvulsive therapy (ECT) is considered a very effective tool for the treatment of psychiatric diseases, memory disturbances are among the most important adverse effects. Aims: This study aimed to assess prospectively early subjective memory complaints in depressive and manic patients due to bilateral, brief-pulse ECT, at different stages of the treatment, compare the associations between psychiatric diagnosis, sociodemographic characteristics, and ECT characteristics. Settings and Design: This prospective study was done with patients undergoing ECT between November 2008 and April 2009 at a tertiary care psychiatry hospital of 2000 beds. Materials and Methods: A total of 140 patients, scheduled for ECT with a diagnosis of bipolar disorder (depressive or manic episode) or unipolar depression according to Diagnostic and Statistical Manual of Mental Disorders IV diagnostic criteria, were included in the study and invited to complete the Squire Subjective Memory Questionnaire (SSMQ) before ECT, after the first and third sessions and end of ECT treatment. Statistical Analysis: Mean values were compared with the Kruskal–Wallis test and comparison of the longitudinal data was performed with a nonparametric longitudinal data analysis method, F1_LD_F1 design. Results: SSMQ scores of the patients before ECT were zero. SSMQ scores showed a decrease after the first and third ECT sessions and before discharge, showing a memory disturbance after ECT and were significantly less severe in patients with mania in comparison to those with depression. Conclusions: These findings suggest an increasing degree of subjective memory complaints with bilateral brief-pulse ECT parallel to the increasing number of ECT sessions.
The natural history of subjective tinnitus in adults: A systematic review and meta‐analysis of no‐intervention periods in controlled trials

Tinnitus is a prevalent condition, but little has been published regarding the natural history of the condition. One technique for evaluating the long‐term progression of the disease is to examine what happens to participants in the no‐intervention control arm of a clinical trial. The aim of this study was to examine no‐intervention or waiting‐list data reported in trials, in which participants on the active arm received any form of tinnitus intervention.
Role of caspases in CD95-induced biphasic activation of acid sphingomyelinase

Acid sphingomyelinase (A-SMase) plays an important role in the initiation of CD95 signaling by forming ceramide-enriched membrane domains that enable clustering and activation of the death receptors. In TNF-R1 and TRAIL-R1/R2 signaling, A-SMase also contributes to the lysosomal apoptosis pathway triggered by receptor internalization. Here, we investigated the molecular mechanism of CD95-mediated A-SMase activation, demonstrating that A-SMase is located in internalized CD95-receptosomes and is activated by the CD95/CD95L complex in a biphasic manner. Since several caspases have been described to be involved in the activation of A-SMase, we evaluated expression levels of caspase-8, caspase-7 and caspase-3 in CD95-receptosomes. The occurrence of cleaved caspase-8 correlated with the first peak of A-SMase activity and translocation of the A-SMase to the cell surface which could be blocked by the caspase-8 inhibitor IETD. Inhibition of CD95-internalization selectively reduced the second phase of A-SMase activity, suggesting a fusion between internalized CD95-receptosomes and an intracellular vesicular pool of A-SMase. Further analysis demonstrated that caspase-7 activity correlates with the second phase of the A-SMase activity, whereas active caspase-3 is present at early and late internalization time points. Blocking caspases-7/ -3 by DEVD reduced the second phase of A-SMase activation in CD95-receptosomes suggesting the potential role of caspase-7 or -3 for late A-SMase activation. In summary, we describe a biphasic A-SMase activation in CD95-receptosomes indicating (I.) a caspase-8 dependent translocation of A-SMase to plasma membrane and (II.) a caspase-7 and/or -3 dependent fusion of internalized CD95-receptosomes with intracellular A-SMase-containing vesicles.
Kinetics Of Materials

Preface. Bibliography. Acknowldegments. Notation. Symbol Table-Roman. Symbol Table-Greek. 1. Introduction. PART I: MOTION OF ATOMS AND MOLECULES BY DIFFUSION. 2. Irreversible Thermodynamics: Coupled Forces and Fluxes. 3. Driving Forces and Fluxes for Diffusion. 4. The Diffusion Equation. 5. Solutions to the Diffusion Equation. 6. Diffusion In Multi-Component Systems. 7. Atomic Models for Diffusion. 8. Diffusion in Cerystals. 9. Diffusion Along Crystal Imperfections. 10. Diffusion in Noncrystalline Materials. PART II: MOTION OF DISLOCATIONS AND INTERFACES. 11. Motion of Dislocations. 12. Motion of Crystalline Surfaces. 13. Motion of Crystalline Interfaces. PART III MORPHOLOGICAL EVOLUTION DUE TO CAPILLARY AND APPLIED MECHANICAL FORCES. 14. Surface Evolution due to Capillary Forces. 15. Coarsening due to Capillary Forces. 16. Morphological Evolution, Diffusional Creep, and Sintering. PART IV: PHASE TRANSFORMATIONS. 17. General Features of Phase Transformations. 18. Spinodal and Order-Disorder Transformations. 19. Nucleation. 20. Growth of Phases in Concentration and Thermal Fields. 21. Concurrent Nucleation and Growth. 22. Solidification. 23. Precipitation. 24. Martensitic Transformations. Appendix A: Densities, Fractions, and Atomic Volumes of Components. Appendix B: Structure of Crystalline Interfaces. Appendix C: Capillarity and Mathematics of Space Curves and Interfaces. Illustration Credits. Cited Author Index. Figure Index. Topic Index.
Hematopoietic effect of deer antler extract fermented by Bacillus subtilis on murine marrow cells

BACKGROUND/OBJECTIVES We examined the chemical composition and the effect of fermented deer antler on hematopoietic factors in bone marrow cells. MATERIALS/METHODS For the preparation of fermented deer antler extract (FAB), fermentation was carried out using Bacillus subtilis at 30℃ for 7 days. The hematopoietic effect of FAB was investigated hematopoietic factors in marrow cells. RESULTS The contents of total sugar, sulfated glycosaminoglycans, and uronic acid and the dry weight gradually increased with fermentation time. The sialic acid content (from 0.14 mg/mL to 0.54 mg/mL) was the highest on the 4th day of fermentation after which it decreased. The proliferating activity of bone marrow cells increased with fermentation times. The levels of various hematopoietic growth factors were determined to verify the beneficial effect of deer antler extract fermented by B. subtilis on hematopoiesis. FAB increased the number of stem cell factors and granulocyte colony-stimulating factor in bone marrow cells. In addition, FAB augmented the burst-forming unit erythroid and total colonies in splenocyte-conditioned medium compared with non-fermented antler extract (NFA). However, FAB did not affect the mRNA levels of erythropoietin, an important factor for erythropoiesis. CONCLUSIONS FAB, like NFA, did not directly affect hematopoiesis, but contributed to hematopoiesis by stimulating the production of hematopoietic factors.
Evaluation of enniatins A, A1, B, B1 and beauvericin in Portuguese cereal-based foods

Sixty-one samples of Portuguese cereal-based foods were analysed for the occurrence of emerging mycotoxins called enniatins (A, A1, B and B1) and beauvericin. Samples were extracted with a mixture of acetonitrile/water (85/15, v/v) using an Ultra-Turrax homogeniser, and mycotoxins were detected with liquid chromatography coupled to a mass spectrometer. This method was validated and adequate values of recovery (70–103%) and relative standard deviation (<15%) were obtained. Signal suppression/enhancement was studied and matrix-matched calibration used to minimise this effect, but no additional clean-up step was necessary. The mass spectrometer was operated in selected reaction monitoring (SRM) mode and with selected transitions for each compound to quantify and to qualify them. Fifty-nine per cent of samples were contaminated. The percentages of enniatins were 53%, 49%, 44% and 16% for A1, B, B1, and A, respectively, and for beauvericin it was 1.6%. For the total samples, the mean contamination was 30, 24, 15, 2.1 and 0.1 ng g−1 for enniatins A1, B, B1 and A, and beauvericin, respectively. The wheat-based samples showed higher levels and greater prevalence than any other cereals monitored. These results were used to estimate the daily intake of ENs from wheat-based cereal by the Portuguese population. At the same time, the usefulness of this method in the analysis of other important mycotoxins (aflatoxin B1, ochratoxin A, deoxynivalenol, T-2 toxin, fumonisin B1 and zearalenone) was evaluated.
The role of insulin-like growth factor-I in neuroendocrine function and the consequent effects on sexual maturation: inferences from animal models.

It is known that growth hormone (GH) plays an important role in growth and development.Additionally, emerging evidence suggest that it also influences hypothalamic-pituitary-gonadal function. We have found that GH from different species has different effects in mice. In rodents, human GH (hGH) binds to both GH and prolactin (PRL) receptors; it has both somatotrophic and lactotrophic effects. Since PRL has a profound effect on neuroendocrine function, the results obtained from hGH treatment or from transgenic animals expressing the hGH gene reflect PRL-like effects of this hormone. However, bovine GH (bGH) is purely somatogenic and therefore the effects of bGH represent the function of the natural GH produced in rodents. Furthermore, our studies in mice and rats have shown that not all effects of GH are stimulatory and the duration of exposure of the hypothalamo-hypophyseal-gonadal system to GH might influence the secretions of gonadotropins and gonadal steroids. In humans, excess productions of GH in acromegaly and GH resistance in Laron syndrome adversely affect reproduction. Similarly, it has been demonstrated that in transgenic mice expressing various GH genes, in insulin-like growth factor-I (IGF-I) gene-knockout mice, in GH receptor gene-disrupted (GHR-KO) mice, and in Ames dwarf mice the onset of puberty and/or fertility is altered. Therefore, excess or subnormal secretion of GH can affect reproduction. We have shown that the hypothalamic-pituitary functions are affected in transgenic mice expressing the GH genes, Ames dwarf mice and in GH receptor gene knockout mice. The majority of the GH effects are mediated via IGF-I and the aforementioned effects may be due to the GH-induced IGF-I secretion or due to the absence of this peptide production. It is important to realize that the syntheses and actions of IGF binding proteins are controlled by IGF-I. Furthermore, some IGF binding proteins can inhibit IGF-I action. Therefore, the concentrations of IGF binding proteins and the ratio of these binding proteins and IGF-I within the body might play a pivotal role in modulating IGF-I effects on the neuroendocrine-gonadal system.