Miracle-dz/UniFAR-FTUs huggingface dataset:
Correction: Ablation of Tumor Necrosis Factor Is Associated with Decreased Inflammation and Alterations of the Microbiota in a Mouse Model of Inflammatory Bowel Disease

There are errors in the third sentence of the Abstract. The third sentence should instead be two separate sentences, which should read as follows: However, some patients are non-responsive to this therapy, eventually become refractory to therapy, or may develop harmful side-effects. Alterations in the microbiota that are associated with the lack of TNF could be a contributing cause of the therapeutic insufficiency seen in some patients.
Enhancement of selective tumor cell binding by activated murine macrophages in response to phorbol myristate acetate.

The fundamental biology of how stable cell-cell bonds develop between activated macrophages and tumor cells, although essential to lysis of the neoplastic targets, remains poorly understood. To investigate whether this phenomenon could be pharmacologically manipulated, we analyzed the effect of phorbol diesters on tumor cell binding by macrophages. Activated murine peritoneal macrophages, treated in vitro with as little as 1 ng/ml of phorbol myristate acetate (PMA), bound significantly more tumor cells than did untreated macrophages. The effect was induced rapidly by PMA (i.e., maximum enhancement was seen within 15 min) and resulted in an average approximately twofold increase in the number of targets bound. The interaction between PMA-treated activated macrophages and tumor cells was completed much more rapidly than by untreated macrophages. The enhanced binding was seen only in macrophages treated with biologically active phorbol esters. Only the selective interaction between activated macrophages and tumor cells was affected (i.e., PMA treatment had no effect on nonselective interactions between activated macrophages and non-neoplastic targets or between nonactivated macrophages and any type of target). Pretreatment of activated macrophages with PMA apparently altered the requirements for microfilaments and microtubules in establishing binding, because cytochalasin B and colchicine, which inhibited control binding, as well as phagocytosis, had no effect on PMA-enhanced binding. PMA treatment did not alter energy requirements for binding, however, because low temperature (4 degrees C) or inhibitors of glycolysis and oxidative phosphorylation blocked both control and PMA-enhanced binding. The enhancement of binding apparently was not due to large quantities of secreted oxygen metabolites but did correlate closely with increased spreading and surface area of the macrophages. PMA treatment resulted in enhanced expression of trypsin-sensitive tumor-cell binding sites on the macrophage surface. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of macrophage membrane proteins labeled with 125I by the lactoperoxidase method revealed at least four trypsin-sensitive cell surface proteins that were re-expressed after PMA treatment. The data suggest that rearrangement and/or induced expression of surface binding sites may be an important step in the binding of tumor cells and indicate that PMA is a useful pharmacologic probe in dissecting the establishment of such binding into discrete steps.
The Future of Human-Computer Interaction

Personal computing launched with the IBM PC. But popular computing—computing for the masses—launched with the modern WIMP (windows, icons, mouse, pointer) interface, which made computers usable by ordinary people. As popular computing has grown, the role of HCI (human-computer interaction) has increased. Most software today is interactive, and code related to the interface is more than half of all code. HCI also has a key role in application design. In a consumer market, a product’s success depends on each user’s experience with it. Unfortunately, great engineering on the back end will be undone by a poor interface, and a good UI can carry a product in spite of weaknesses inside.
The enzymic hydrolysis of glutamine and its spontaneous decomposition in buffer solutions.

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Statistical approaches for evaluating surrogate outcomes in clinical trials: A systematic review

ABSTRACT The use of surrogate outcomes that predict treatment effect on an unobserved true outcome may have substantial economic and ethical advantages, through reducing the length and size of clinical trials. There has been extensive investigation of the best means of evaluating putative surrogates. We present a systematic review on the evolution of statistical methods for validating surrogates starting from the defining paper of Prentice (1989). We highlight the fundamental differences in the current statistical evaluation approaches, their advantages and disadvantages, and examine the understanding and perceptions of investigators in this area.
Advances in Brief The Collaboration of Both Humoral and Cellular HER-2 / neu-targeted Immune Responses Is Required for the Complete Eradication of HER-2 / neu-expressing Tumors 1

HER-2/neu (neu) transgenic mice (neu-Nmice), which express the nontransforming rat proto-oncogene, demonstrate immunological tolerance to neu that is similar to what is encountered in patients withneuexpressing breast cancer. We have shown previously that a significant increase in neu-specific T cells, but no induction of neu-specific antibody, is seen after neu-specific vaccination inneu-N mice. In contrast, a significant induction of both neu-specific T-cell and antibody responses is found in nontoleragenic FVB/N mice after vaccination. These mice are fully protected from a s.c. challenge with NT cells, a mammary tumor cell line derived from a spontaneous tumor that arose in aneu-N mouse, whereas neu-N mice are not. In this study, we demonstrate that CD4 T celldepleted FVB/N mice show no induction of neu-specific IgG after vaccination and are unable to reject an NT challenge (0 of 10 mice were tumor free). Conversely, the depletion of natural killer cells has no effect on vaccine-mediated tumor rejection (100% of mice were tumor free). In CD8 T cell-depleted animals, where vaccine-induced neu-specific IgG titers were normal, NT growth was delayed, but only 10% of mice remained tumor free, demonstrating that neu-specific IgG alone is insufficient for protection from NT challenge. To directly assess the necessity for the combination of neu-specific cellular and humoral immune responses, severe combined immunodeficient mice were given an adoptive transfer of CTLs plus IgG derived from FVB/N mice. Animals that were given CTLs that recognized an irrelevant antigen plus neu-specific IgG developed tumors at a rate similar to CD8 T cell-depleted FVB/N mice. Animals receiving an adoptive transfer of neu-specific CTLs plus control IgG derived from naive FVB/N mice were only partially protected from NT challenge (50% of animals were tumor free). However, only animals receiving the combination of neu-specific CTLs and neu-specific IgG were fully protected from NT challenge (100% of animals were tumor free). These studies specifically define the immunological requirements for the eradication of neu-expressing tumors in this model system, demonstrating that both cellular and humoral neu-specific responses are necessary for protection from an NT challenge. These data suggest that vaccines optimized to induce maximal Tand B-cell immunity to neu, and possibly to similar putative tumor-rejection antigens, may lead to more potentin vivo antitumor immunity.
Hydration shells exchange charge with their protein

Investigation of the interaction between a protein and its hydration shells is an experimental and theoretical challenge. Here, we used ultrasonic pressure waves in aqueous solutions of a protein to explore the conformational states of the protein and its interaction with its hydration shells. In our experiments, the amplitude of an ultrasonic pressure wave is gradually increased (0–20 atm) while we simultaneously measure the Raman spectra from the hydrated protein (β-lactoglobulin and lysozyme). We detected two types of spectral changes: first, up to 70% increase in the intensity of the fluorescence background of the Raman spectrum with a typical relaxation time of 30–45 min. Second, we detect changes in the vibrational Raman spectra. To clarify these results we conducted similar experiments with aqueous solutions of amino acids and ethanol. These experiments led us to conclude that, without the presence of an ultrasonic pressure, a protein and its hydration shells are in thermodynamic and charge equilibrium, i.e. a protein and its hydration shells exchange charges. The ultrasonic wave disrupts these equilibria which are regained within 30–45 min after the ultrasonic pressure is shut off.
Quantitative enzyme radioautography with 3H-Ro 41-1049 and 3H-Ro 19- 6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain

Monoamine oxidases A and B (MAO-A and MAO-B) oxidatively deaminate neurotransmitter and xenobiotic amines. Since the cellular localization of the isoenzymes in the CNS and peripheral organs determines to a large extent which substrate has access to which isoenzyme, knowledge of their tissue distribution and cellular localization is essential. Here we describe how reversible and selective inhibitors of MAO-A and MAO-B [Ro 41–1049 and Ro 19–6327 (lazabemide), respectively] can be used, as tritiated radioligands, to map the distribution and abundance of the enzymes in microscopic regions of the rat CNS and peripheral organs, and human brain by quantitative enzyme radioautography. The in vitro binding characteristics of both radiolabeled inhibitors revealed them to be selective, high-affinity ligands for the respective enzymes. KD and Bmax values for 3H-Ro 41–1049 in rat cerebral cortex were 10.7 nM and 7.38 pmol/mg protein, respectively, and for 3H-Ro 19–6327 were 18.4 nM and 3.45 pmol/mg protein, respectively. In accordance with their potencies as enzyme inhibitors, binding to MAO-A and MAO-B was competitively inhibited by clorgyline (IC50 = 1.4 nM) and L-deprenyl (selegiline; IC50 = 8.0 nM), respectively. The capacities of various rat and human tissues to bind the radioligands correlated extremely well with their corresponding enzyme activities. As revealed by the respective binding assays, the distribution and abundance of MAO-A and MAO-B in the tissues investigated differed markedly. MAO-A was most abundant in the locus coeruleus, paraventricular thalamus, bed nucleus of the stria terminalis, median habenular nucleus, ventromedial hypothalamus, raphe nuclei, solitary tract nucleus, inferior olives, interpeduncular nucleus, claustrum, and numerous peripheral tissues, including liver, vas deferens, heart, superior cervical ganglion, and exocrine and endocrine pancreas. In contrast, MAO-B was most abundant in the ependyma, circumventricular organs, olfactory nerve layer, periventricular hypothalamus, cingulum, hippocampal formation, raphe nuclei, paraventricular thalamus, mammillary nuclei, cerebellar Bergmann glia cells, liver, posterior pituitary, renal tubules, and endocrine pancreas. The cellular localization of the isoenzymes in both rat and human brain differs markedly and does not reflect the distribution of the presumed natural substrates, for example, absence of MAO-A in serotoninergic neurons. Indeed, the present evidence suggests that, whereas MAO-A is found in noradrenergic and adrenergic neurons, MAO-B occurs in astrocytes, serotoninergic neurons, as well as ventricular cells, including most circumventricular organs. The physiological roles of the enzymes are discussed in the light of these findings, some of which were unexpected. (ABSTRACT TRUNCATED AT 400 WORDS)
An Improved Fuzzy Collaborative System for Predicting the Unit Cost of a DRAM Product

Accurately predicting the unit costs of products enables an enterprise to estimate the future profits on which conducting financial or production planning can be based. However, performing such predictions is difficult because of the uncertainty of the unit cost learning process. A few fuzzy collaborative forecasting methods have been proposed in the past to address this difficulty. However, these methods exhibit some limitations such as a time‐consuming collaboration process, the existence of low‐quality experts, and insufficient global optimality of the solution. To resolve these problems, this study designed an improved fuzzy collaborative forecasting system. The proposed system exhibits the following innovative features. First, software agents substitute real experts to automate the collaboration process for enhancing efficiency. A quadratic programming approximation approach is then applied to improve the global optimality of the solution. The proposed methodology was tested with a real case from a dynamic random access memory factory. The experimental results showed that the proposed methodology can improve the forecasting accuracy and precision efficiently by systematically adding agents to the fuzzy collaborative forecasting system. In addition, the effectiveness of the proposed methodology is also robust to the existence of a low‐quality expert.
Pattern mixture models for longitudinal quality of life studies in advanced stage disease

Analyses of longitudinal quality of life (QOL) for patients with advanced stage disease are frequently plagued by problems of non‐random drop‐out attributable to deteriorating health and/or death. As an example, Moinpour et al. cite specific challenges which limited their report and assessment of QOL for patients treated for advanced stage colorectal cancer in a clinical trial of several chemotherapeutic regimes performed by the Southwest Oncology Group. A particular source of confusion that arises in studies of advanced stage disease is whether or not to differentiate loss of follow‐up due to death from drop‐out where the patient is still alive but has dropped from the study. In this paper we examine exploratory data techniques for longitudinal QOL data with non‐random missingness due to drop‐out and censorship by death. We propose a pattern mixture model for longitudinal QOL, time of drop‐out and survival, which allows for straightforward implementation of sensitivity analyses and explicit comparisons to the raw data. Our method is illustrated in the context of analysing the data and addressing the challenges posed by Moinpour et al. Copyright © 2003 John Wiley & Sons, Ltd.
Specific immunoglobulin E antibodies to peanut over time in relation to peanut intake, symptoms and age

The clinical outcome of peanut allergy and some factors associated with development of peanut allergy remain unsolved. It has not been clarified to what extent peanut intake affects immunoglobulin (IgE) antibody formation in peanut sensitized individuals. The aim of the study was to investigate the development of peanut hypersensitivity in children and adolescents with specific IgE antibodies to peanut, using questionnaires and current serum tests and comparing it to information obtained 5–6 yr earlier, to investigate how peanut intake during this period related to subject age, IgE antibody levels and symptoms and to investigate what information this patient group was given at the time of diagnosis regarding avoidance of peanut related food. All patients with detectable peanut‐specific IgE antibodies investigated during 1994–1996 deriving from two allergy laboratories in the western region of Sweden were traced and reinvestigated (n=132). A total of 111 subjects (63 with peanut allergy and 48 peanut sensitized) participated in the questionnaire. Eighty‐six of them consented to be enrolled in a further interview and renewed testing of specific IgE antibody to peanut 5 yr later. All tests were done using the Pharmacia CAP system®. Increased IgE antibody levels during follow‐up was related to age; subjects 0–6 yr at initial test occasion were more likely to have higher IgE antibody class than the older individuals (p=0.018). Exposure to peanut during the study, i.e. 5–6 yr since diagnosis, did not seem to affect the result. During the follow‐up period, 29 out of 86 (34%) increased their IgE antibody class. At the second test occasion the remaining subjects had similar (28%) or lowered (38%) levels of IgE antibodies. Exposure to peanut during follow‐up was more common in subjects with IgE antibody class 1–3 compared to subjects with high value (>3) at the initial test (p=0.003). Reported symptoms during follow‐up were also more common in subjects with initially high IgE antibody value. Individuals with initially high IgE antibodies to peanut had been given more information about peanut allergy and cross‐reacting allergens than other individuals. The subjects over 6 yr of age showed a decrease in peanut‐specific IgE class over a 5‐yr period. Together with the literature, our result suggest that follow‐up and renewed testing is recommended, since there may be a change in IgE antibody classes and clinical sensitivity over time. Even in Sweden, with a low consumption of peanuts, the youngest individuals with peanut sensitization experienced a similar course of events that has been reported in other countries.
Growth Hormone-Releasing Peptides and Their Analogs

Growth hormone-releasing peptides (GHRPs) are a series of hepta (GHRP-1)- and hexapeptides (GHRP-2, GHRP-6, Hexarelin) that have been shown to be effective releasers of GH in animals and humans. More recently, a series of nonpeptidyl GH secretagogues (L-692,429, L-692,585, MK-0677) were discovered using GHRP-6 as a template. Some cyclic peptides as well as penta-, tetra-, and pseudotripeptides have also been described. This review summarizes recent developments in our understanding of the GHRPs, as well as the current nonpeptide pharmacologic analogs. GHRPs and their analogs have no structural homology with GHRH and act via specific receptors present at either the pituitary or the hypothalamic level. The GHRP receptor has recently been cloned and it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. Although the exact mechanism of action of GHRPs has not been fully established, there is probably a dual site of action on both the pituitary and the hypothalamus, possibly involving regulatory factors in addition to GHRH and somatostatin. Moreover, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. The marked GH-releasing activity of GHRPs is reproducible and dose-related after intravenous, subcutaneous, intranasal, and even oral administration. The GH-releasing effect of GHRPs is the same in both sexes, but undergoes age-related variations. It increases from birth to puberty and decreases in aging. The GH-releasing activity of GHRPs is synergistic with that of GHRH and not affected by opioid receptor antagonists, while it is only blunted by inhibitory influences that are known to nearly abolish the effect of GHRH, such as neurotransmitters, glucose, free fatty acids, glucocorticoids, rhGH, and even exogenous somatostatin. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states, such as acromegaly, anorexia nervosa, and hyperthyroidism. On the other hand, GHRPs and their analogs have been reported to be effective in idiopathic short stature, in some situations of GH deficiency, in obesity, and in hypothyroidism, while in patients with pituitary stalk disconnection and in Cushing's syndrome the somatotrope responsiveness to GHRPs is almost absent. A potential role in the treatment of short stature, aging, catabolic states, and dilated cardiomyopathy has been envisaged.
Sentiment-Based Commercial Real Estate Forecasting with Google Search Volume Data

Purpose – This article examines internet search query data provided by ‘Google Trends’, with respect to its ability to serve as a sentiment indicator and improve commercial real estate forecasting models for transactions and price indices.Methodology – The study uses data from the two largest data providers of US commercial real estate repeat sales indices, namely CoStar and Real Capital Analytics. We design three groups of models: baseline models including fundamental macro data only, those including Google data only and models combining both sets of data.One-month-ahead forecasts based on VAR models are conducted to compare the forecast accuracy of the models.Findings – The empirical results show that all models augmented with Google data, combining both macro and search data, significantly outperform baseline models which abandon internet search data. Models based on Google data alone, outperform the baseline models in 82% of cases. The models achieve a reduction over the baseline models of the mean squared forecasting error (MSE) for transactions and prices of up to 35% and 54% respectively.Practical Implications – The results suggest that Google data can serve as early market indicators. The findings of this study suggest that the inclusion of Google search data in forecasting models can improve forecast accuracy significantly. This implies that commercial real estate forecasters should consider incorporating this free and timely data set into their market forecasts or when performing plausibility checks for future investment decisions.Originality – This is the first paper applying Google search query data to the commercial real estate sector.