Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of intestinal P-glycoprotein in the plasma and fecal disposition of docetaxel in humans.

Multidrug resistance (MDR)-1-P-glycoprotein (P-gp) is a drug-transporting protein that is abundantly present in biliary ductal cells and epithelial cells lining the gastrointestinal tract. Here, we have determined the role of P-gp in the metabolic disposition of the antineoplastic agent docetaxel (Taxotere) in humans. Pharmacokinetic profiles were evaluated in five cancer patients receiving treatment cycles with docetaxel alone (100 mg/m2 i.v. over a 1-h period) and in combination with a new potent inhibitor of P-gp activity, R101933 (200-300 mg b.i.d.). The terminal disposition half-life and total plasma clearance of docetaxel were not altered by treatment with oral R101933 (P > or = 0.27). The cumulative fecal excretion of docetaxel, however, was markedly reduced from 8.47 +/- 2.14% (mean +/- SD) of the dose with the single agent to less than 0.5% in the presence of R101933 (P = 0.0016). Levels of the major cytochrome P450 3A4-mediated metabolites of docetaxel in feces were significantly increased after combination treatment with R101933 (P = 0.010), indicating very prominent and efficient detoxification of reabsorbed docetaxel into hydroxylated compounds before reaching the systemic circulation. It is concluded that intestinal P-gp plays a principal role in the fecal elimination of docetaxel by modulating reabsorption of the drug after hepatobiliary secretion. In addition, the results indicate that inhibition of P-gp activity in normal tissues by effective modulators, and the physiological and pharmacological consequences of this treatment, cannot be predicted based on plasma drug monitoring alone.
Characterization of the cellulose-binding domain of the Clostridium cellulovorans cellulose-binding protein A

Cellulose-binding protein A (CbpA), a component of the cellulase complex of Clostridium cellulovorans, contains a unique sequence which has been demonstrated to be a cellulose-binding domain (CBD). The DNA coding for this putative CBD was subcloned into pET-8c, an Escherichia coli expression vector. The protein produced under the direction of the recombinant plasmid, pET-CBD, had a high affinity for crystalline cellulose. Affinity-purified CBD protein was used in equilibrium binding experiments to characterize the interaction of the protein with various polysaccharides. It was found that the binding capacity of highly crystalline cellulose samples (e.g., cotton) was greater than that of samples of low crystallinity (e.g., fibrous cellulose). At saturating CBD concentration, about 6.4 mumol of protein was bound by 1 g of cotton. Under the same conditions, fibrous cellulose bound only 0.2 mumol of CBD per g. The measured dissociation constant was in the 1 microM range for all cellulose samples. The results suggest that the CBD binds specifically to crystalline cellulose. Chitin, which has a crystal structure similar to that of cellulose, also was bound by the CBD. The presence of high levels of cellobiose or carboxymethyl cellulose in the assay mixture had no effect on the binding of CBD protein to crystalline cellulose. This result suggests that the CBD recognition site is larger than a simple cellobiose unit or more complex than a repeating cellobiose moiety. This CBD is of particular interest because it is the first CBD from a completely sequenced nonenzymatic protein shown to be an independently functional domain.
Lifelong Learning for Visual Recognition Systems

Recent breakthroughs of machine learning and visual recognition are fundamentally impacting our today’s society. Two impressive show-cases are autonomous vehicles in automotive industry or smart diagnosis systems in modern health care. However, current solutions are static by design, i.e., once they are trained, they heavily rely on non-changing environments and tasks. In contrast, humans are incredibly successful in adapting to new environments by asking appropriate questions, in recognizing previously unseen objects, and in interactively expanding their knowledge over time. In this thesis, we draw inspiration from human learning by transferring individual aspects to continuously learning systems and introduce the lifelong learning cycle as a combination of involved topics. Replacing static with continuously learning systems poses a multitude of challenges and interesting questions. As a first step towards lifelong learning systems, we provide solutions to four involved areas: large-scale learning, incremental learning, active learning, and feature learning. In the area of large-scale learning, we show how to learn Gaussian process models from large labeled datasets by exploiting inherent properties of histogram intersection kernels. Our techniques overcome complexity limitations of common kernel-based methods with respect to memory demand and computation time and are applicable to all stages of inference, including training, optimization of hyperparameters, classification, and uncertainty prediction. To also incorporate new data over time, we additionally present efficient incremental learning techniques for different aspects of inference with Gaussian process models. We further contribute to the field of active learning, which is similar to the dialog of a child’s questions and its parent’s answers. Using active learning, a lifelong learning system can decide for which image with unknown content it shall request a label such that the information gained by the system is maximized. Based on existing selection criteria, we derive efficient realizations for the specific choice of Gaussian process models. In addition, we introduce the new concept of estimated model output changes which approximates the estimated reduction of empirical risk. Finally, we extend our techniques to multi-class scenarios with unnameable instances to handle objects which are even unknown to the expert-in-the-loop. To represent new object categories appropriately, we finally introduce techniques for mining exemplar-specific patch features. These representations can be learned in a supervised or unsupervised manner and correspond to mid-level features like object parts. Furthermore, we show how to exploit expensive expert annotations, e.g., manually labeled part positions in animal images. The presented
Aggregation of Heterogeneously Related Information with Extended Geometric Bonferroni Mean and Its Application in Group Decision Making

Capturing specific interrelationship among input arguments has great importance in the process of aggregation as they may change the aggregation result significantly, which can lead viable changes in the overall decision outcome. In this study, we attempt to aggregate a set of inputs with certain heterogeneous interrelationship pattern among them. To do this, we introduce a new aggregation operator, which we call the extended geometric Bonferroni mean. We investigate its properties and develop an algorithm to learn its associated parameters based on decision maker's perceived view toward the aggregation process. Moreover, to learn such heterogeneous relationship among the inputs from the data set, we provide a learning algorithm. Examples are given to illustrate the realization of algorithm and to show certain advantages over the existing aggregation operators.
Leader Behavior as a Determinant of Health at Work: Specification and Evidence of Five Key Pathways

The extent to which leadership influences employee health and the processes that underlie its effects are not well understood at present. With the aim of filling this gap, we review four distinct forms of leader behavior (task-oriented, relationship-oriented, change-oriented, and passive/destructive) and clarify the different ways in which these can be expected to have a bearing on employee health. Next, we present a model that integrates and extends these insights. This model describes five pathways through which leader behavior can influence the health of organizational members and summarizes what we know about the most important determinants, processes (mediators) and moderators of these relationships. These involve leaders engaging in person-focused action, system- or team-focused action, action to moderate the impact of contextual factors, climate control and identity management, and modelling. Finally, we identify important gaps and opportunities in the literature that need to be addressed in future research. A key conclusion is that while much has been done to explore some key pathways between leadership and health, others remain underexplored. We also outline how future research might address these in the context of a more expansive theoretical, empirical and practical approach to this emerging field of research.
LIN 28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans

Ho-Chou Tu, Sarah Schwitalla, Zhirong Qian, Grace S. LaPier, Alena Yermalovich, Yuan-Chieh Ku, Shann-Ching Chen, Srinivas R. Viswanathan, Hao Zhu, Reiko Nishihara, Kentaro Inamura, Sun A Kim, Teppei Morikawa, Kosuke Mima, Yasutaka Sukawa, Juhong Yang, Gavin Meredith, Charles S. Fuchs, Shuji Ogino, and George Q. Daley Division of Pediatric Hematology/Oncology, Boston Children’s Hospital, Boston, Massachusetts 02115, USA; Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA; Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA; Thermo Fisher Scientific, Incorporated, South San Francisco, California 94080, USA; Children’s Medical Center Research Institute, University of Texas Southwestern, Dallas, Texas 75390, USA; Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA; Harvard Medical School, Boston, Massachusetts 02115, USA; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA; Howard Hughes Medical Institute, Boston, Massachusetts 02138, USA
Beautiful Minds : Physical Attractiveness and Research Productivity in Economics

This study examines the impact of physical attractiveness of on productivity. Previous literature found a strong impact on wages and career progression, which can be either due to discrimination in favour of good-looking people or can reflect an association between attractiveness and productivity. We utilize a context where there is no or limited face-to-face interaction, academic publishing, so that scope for beauty-based discrimination should be limited. Using data on 2,800 authors who published their papers in 16 economics journals in 2012, we find a significantly positive effect of authors’ attractiveness on research productivity measured by citations, journal ranking, and journal impact factor. Other strong predictors of productivity are team size (positive effect on productivity) and work tenure (negative effect). These results are obtained with both OLS and quantile regression. Our results suggest that physical attractiveness has important benefits even in the absence of face-to-face interactions.
Conceptualizing Initial Trust in Internet Banking Services: A Pilot Study

The adoption rate of Internet banking services (IBS) is considered to be relatively high in the developed countries; which is not the case for developing countries. The lack of trust plays a vital role in discouraging users from adopting IBS. Therefore, initial trust could be the starting point of making customers comfortable processing their banking transactions online. This study aims to propose a conceptual model of initial trust in IBS in developing countries. The proposed model integrates its constructs from: the trust literature, diffusion of innovation theory (DoI), and Hofstede’s national culture theory. This paper also aims to develop and validate a research instrument in order to examine the proposed model. We conducted a pilot study in Jordan, which is one of the developing countries, and refined the model and its instrument based on the obtained results.
The Four-Point Scoring System for the Clock Drawing Test Does Not Differentiate between Alzheimer's Disease and Vascular Dementia

The purpose of this study was to explore the sensitivity and specificity of the Clock Drawing Test by using a widely employed four-point scoring system to discriminate between patients with Alzheimer's disease or vascular dementia. Receiver operating characteristic analysis indicated that the Clock Drawing Test was able to distinguish between normal elders and those with a dementia diagnosis. The cutoff score for differentiating patients with Alzheimer's disease from normal participants was = 3. The cutoff score for differentiating those with vascular disease from normal participants was = 3. Overall, the four-point scoring system demonstrated good sensitivity and specificity for identifying cognitive dysfunction associated with dementia; however, the current findings do not support the utility of the four-point scoring system in discriminating Alzheimer's disease and vascular dementia.
Subsequent leukaemia in autoimmune disease patients

Previous studies have shown that patients diagnosed with some autoimmune (AI) diseases are at an increased risk of leukaemia but limited data are available on survival. We systematically analysed the risks (standardized incidence ratio, SIR) and survival (hazard ratio, HR) in nine types of leukaemia among 402 462 patients hospitalized for any of 33 AI diseases and compared to persons not hospitalized for AI diseases. Risk for all leukaemia was increased after 13 AI diseases and survival was decreased after six AI diseases. SIRs were increased after all AI diseases for seven types of leukaemia, including SIR 1·69 (95% confidence interval (CI): 1·29–2·19) for acute lymphoblastic leukaemia (ALL), 1·85 (95% CI: 1·65–2·07) for acute myeloid leukaemia, 1·68 (95% CI: 1·37–2·04) for chronic myeloid leukaemia, 2·20 (95% CI: 1·69–2·81) for ‘other myeloid leukaemia’, 2·45 (95% 1·99–2·98) for ‘other and unspecified leukaemia’, 1·81 (95% CI: 1·11–2·81) for monocytic leukaemia, and 1·36 (95% CI: 1·08–1·69) for myelofibrosis. The HRs were increased for four types of leukaemia, most for myelofibrosis (1·74, 95% CI: 1·33–2·29) and ALL (1·42, 95% CI: 1·03–1·95). Some AI diseases, including rheumatoid arthritis, were associated with increased SIRs and HRs in many types of leukaemia. The present data showed increases in risk and decreases in survival for many types of leukaemia after various AI diseases. Leukaemia is a rare complication in AI disease but findings about this comorbidity at the time of leukaemia diagnosis may help to optimize the treatment and improve survival.
Genetics of uveal melanoma

In this review, we discuss the genetic features of uveal melanoma and the different available genetic and genomic tests. Despite improvements in diagnosis and treatment of this intraocular tumor, there has not been a change in survival in the past few decades. Insights into the molecular changes in uveal melanoma have provided us with the opportunity to assess the risk of metastatic disease for individual patients. There are few treatments available for metastasized uveal melanoma and, in a relatively short time-frame, patients with this condition die because of this metastasis. The focus of research may need to shift towards adjuvant therapies for high-risk uveal melanomas.
THE TRITONE PARADOX AMONG CHINESE CHILDREN AGED 12 AND 13

The tritone paradox is produced by a basic pattern that consists of an ordered pair of Shepard tones that are related by a half-octave (i.e., a tritone). When listeners judge whether such tone pairs ascend or descend in pitch, their judgments show systematic relationships to the positions of the tones along the pitch-class circle: Tones in one region of the circle are heard as higher and tones in the opposite region are heard as lower. However, listeners disagree as to which tones are heard as higher and which as lower; further, their perceptions vary with their languages or dialects, which in turn involve differing pitch ranges for speech. Studies on the tritone paradox have so far studied only non-tone language speakers, and teenage children have not so far been tested. This study explored perception of the tritone paradox in Chinese children aged 12 and 13 who were living in Beijing. All subjects spoke Mandarin, but the dialects that were spoken by their family members varied. Overall, a very strong tritone paradox was obtained. Pitch classes B and C tended to be judged as higher than the other pitch classes, with the plot of peak pitch classes falling off on either side of these. This finding probably reflects the most frequent pitch ranges of speech in Northern Chinese Mandarin dialects.
Effects of Dietary Fat on Cholesterol Metabolism: Regulation of Plasma LDL Concentrations

INTRODUCTION . 241 EFFECTS O F DIETARY FATTY ACIDS O N PLASMA LIPOPROTEIN CONCENTRATIONS I N H U M A N S . 242 B A C K G R O U N D . 242 RECENT M E T A A N A L Y S E S . 242 C O M P A R A T I V E EFFECTS OF D I F F E R E N T S A T U R A T E D FATTY A C I D S . 244 T R A N S F A T T Y A C I D S . 245 N-3 P O L Y U N S A T U R A T E D F A T T Y A C I D S . 245 REGULATION O F LOW DENSITY LIPOPROTEIN METABOLISM . 246 MECHANISMS WHEREBY DIETARY FATTY ACIDS MAY I N F L U E N C E PLASMA L D L CONCENTRATIONS . 249
Indium-111-DTPA-octreotide uptake measured in normal and abnormal pituitary glands.

UNLABELLED Pituitary uptake of [111In-DTPA]-octreotide is highly variable, and no formal methods for quantification have been described. Conflicting results have therefore been published as to the presence of somatostatin receptors in nonsecreting adenoma of the pituitary gland. The aim of the present study was to define the most accurate method for the analysis of [111In-DTPA]-octreotide SPECT studies of the pituitary gland. METHODS We used a multidetector brain SPECT camera to measure pituitary uptake of [111In-DTPA]-octreotide in healthy volunteers and patients with and without pituitary adenoma. For quantification, two methods were compared, one involving a manually drawn ROI and one a fixed ROI, as to their reliability and discriminative power. The optimal time interval after injection was also studied in the volunteers. RESULTS Optimal images were obtained 24 hr after injection. Correction for background activity is not useful in view of the very low counts at that time which result in highly fluctuating ratios. Lower variability was observed in the fixed ROI method in which activity was expressed as counts corrected for dosage and body weight. CONCLUSION A fixed ROI method without background correction is the most reliable way to measure pituitary uptake of [111In-DTPA]-octreotide. This method allows for good separation of somatostatin-receptor-positive adenomas from normal pituitary glands.
Counteracting adriamycin-induced oxidative stress by administration of N-acetyl cysteine and vitamin E

Abstract Adriamycin (ADR), a cytotoxic antineoplastic drug, is used in the treatment of various solid tumors. However, its efficacy continues to be challenged by significant toxicities including nephrotoxicity. In the present study, the effects of N-acetyl cysteine (NAC) and vitamin E, known antioxidants, were investigated on ADR-induced peroxidative damage in rat kidney. Adult male albino rats of Wistar strain were administered ADR as a single dose (10mg/kg body weight, i.v.). Histopathological studies indicated that ADR-treated kidney sections show focal tubular necrosis and casts. ADR-injected rats showed a significant decline in the activities/levels of enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) and non-enzymic antioxidants (thiols, vitamin C and vitamin E) with high malondialdehyde levels. The extent of nephrotoxicity was evident from the increased activities of urinary marker enzymes (alkaline phosphatase, lactate dehydrogenase and γ-glutamyltransferase). Treatment with NAC and vitamin E (50mg/kg b.w., i.p.) 1day prior to ADR administration maintained near normal activities of the enzymes, significantly reduced lipid peroxidation and prevented the necrosis caused by ADR, thereby proving to be an effective thiol replenishing agent and antioxidant.
Interactions of MAP 17 with the NaPi-IIa / PDZK 1 protein complex in renal proximal tubular cells

Pribanic, Sandra, Serge Mike Gisler, Desa Bacic, Caveh Madjdpour, Nati Hernando, Victor Sorribas, Andrea Gantenbein, Jürg Biber, and Heini Murer. Interactions of MAP17 with the NaPi-IIa/PDZK1 protein complex in renal proximal tubular cells. Am J Physiol Renal Physiol 285: F784–F791, 2003. First published July 1, 2003; 10.1152/ajprenal.00109. 2003. —An essential role in phosphate homeostasis is played by Na/Pi cotransporter IIa that is localized in the brush borders of renal proximal tubular cells. Recent studies identified several PDZ proteins interacting with the COOH-terminal tail of NaPi-IIa, such as PDZK1 and NHERF-1. Here, by using yeast two-hybrid screen of mouse kidney cDNA library, we attempted to find proteins interacting with the NH2-terminal part of NaPi-IIa. We identified MAP17, a 17-kDa membrane protein that has been described to be associated with various human carcinomas, but it is also expressed in normal kidneys. Results obtained by various in vitro analyses suggested that MAP17 interacts with the fourth domain of PDZK1 but not with other PDZ proteins localized in proximal tubular brush borders. As revealed by immunofluorescence, MAP17 was abundant in S1 but almost absent in S3 segments. No alterations of the apical abundance of MAP17 were observed after maneuvers undertaken to change the content of NaPi-IIa (parathyroid hormone treatment, different phosphate diets). In agreement, no change in the amount of MAP17 mRNA was observed. Results obtained from transfection studies using opossum kidney cells indicated that the apical localization of MAP17 is independent of PDZK1 but that MAP17 is required for apical localization of PDZK1. In summary, we conclude that MAP17 1) interacts with PDZK1 only, 2) associates with the NH2 terminus of NaPi-IIa within the PDZK1/NaPi-IIa/ MAP17 complex, and 3) acts as an apical anchoring site for PDZK1.
Alligator Diet in Relation to Alligator Mortality on Lake Griffin, FL

Abstract Alligator mississippiensis (American Alligators) demonstrated low hatch-rate success and increased adult mortality on Lake Griffin, FL, between 1998 and 2003. Dying Lake Griffin alligators with symptoms of poor motor coordination were reported to show specific neurological impairment and brain lesions. Similar lesions were documented in salmonines that consumed clupeids with high thiaminase levels. Therefore, we investigated the diet of Lake Griffin alligators and compared it with alligator diets from two lakes that exhibited relatively low levels of unexplained alligator mortality to see if consumption of Dorosoma cepedianum (gizzard shad) could be correlated with patterns of mortality. Shad in both lakes Griffin and Apopka had high levels of thiaminase and Lake Apopka alligators were consuming greater amounts of shad relative to Lake Griffin without showing mortality rates similar to Lake Griffin alligators. Therefore, a relationship between shad consumption alone and alligator mortality is not supported.