Miracle-dz/UniFAR-FTUs huggingface dataset:
LiCABEDS II. Modeling of Ligand Selectivity for G-Protein-Coupled Cannabinoid Receptors

The cannabinoid receptor subtype 2 (CB2) is a promising therapeutic target for blood cancer, pain relief, osteoporosis, and immune system disease. The recent withdrawal of Rimonabant, which targets another closely related cannabinoid receptor (CB1), accentuates the importance of selectivity for the development of CB2 ligands in order to minimize their effects on the CB1 receptor. In our previous study, LiCABEDS (Ligand Classifier of Adaptively Boosting Ensemble Decision Stumps) was reported as a generic ligand classification algorithm for the prediction of categorical molecular properties. Here, we report extension of the application of LiCABEDS to the modeling of cannabinoid ligand selectivity with molecular fingerprints as descriptors. The performance of LiCABEDS was systematically compared with another popular classification algorithm, support vector machine (SVM), according to prediction precision and recall rate. In addition, the examination of LiCABEDS models revealed the difference in structure diversity of CB1 and CB2 selective ligands. The structure determination from data mining could be useful for the design of novel cannabinoid lead compounds. More importantly, the potential of LiCABEDS was demonstrated through successful identification of newly synthesized CB2 selective compounds.
An Exact Test for the Association Between the Disease and Alleles at Highly Polymorphic Loci with Particular Interest in the Haplotype Analysis

Summary. The association analysis between the disease and genetic alleles is one of the simple methods for localizing the susceptibility locus in the genes. For revealing the association, several statistical tests have been proposed without discussing explicitly the alternative hypotheses. We therefore specify two types of alternative hypotheses (i.e., there is only one susceptibility allele in the locus, and there is an extension or shortening of alleles associated with the disease) and derive exact tests for the respective hypotheses. We also propose to combine these two tests when the prior knowledge is not sufficient enough to specify one of these two hypotheses. In particular, these ideas are extended to the haplotype analysis of three‐way association between the disease and bivariate allele frequencies at two closely linked loci. As a by‐product, a factorization of the probability distribution of the three‐way cell frequencies under the null hypothesis of no three‐way interaction is obtained.
Educational Evaluation: Ethnography in Theory, Practice, and Politics

PART ONE: CONTEXTUAL FRAMEWORK Beyond the Status Quo in Ethnographic Educational Evaluation - David M Fetterman The Ethnographic Evaluator - David M Fetterman PART TWO: THEORY Theory in Educational Evaluation, Or What is Wrong with Generic-Brand Anthropology? - Elaine L Simon The Use of Explicit Anthropological Theory in Educational Evaluation - Mary A Pitman and Marion L Dobbert A Case Study Attrition in Zairian Secondary Schools - John D Studstill Ethnographic Evaluation and Sociocultural Systems PART THREE: PRACTICE Combining Ethnographic and Experimental Methods in Educational Research - Joseph A Maxwell, Philip G Bashook and Leslie J Sandlow A Case Study Qualitative Methodology in the Evaluation of Early Childhood Bilingual Curriculum Models - Ray A Chesterfield PART FOUR: POLITICS Use of Ethnographic Techniques for Evaluation in a Large School District - Barbara G Ferrell and Donald W Compton The Vanguard Case `Posin' to be Chosen' - Richard A Marotto An Ethnographic Study of In-School Truancy PART FIVE: CONCLUSION The Evolution of A Discipline - David M Fetterman
Effective and efficient object-based image retrieval using visual phrases

In this paper, we draw an analogy between image retrieval and text retrieval and propose a visual phrase-based approach to retrieve images containing desired objects. The visual phrase is defined as a pair of adjacent local image patches and is constructed using data mining. We devise methods on how to construct visual phrases from images and how to encode the visual phrase for indexing and retrieval. Our experiments demonstrate that visual phrase-based retrieval approach can be very efficient and can be 20% more effective than its visual word-based counterpart.
NMDA receptors and the differential ischemic vulnerability of hippocampal neurons

Transient cerebral ischemia causes an inhomogeneous pattern of cell death in the brain. We investigated mechanisms, which may underlie the greater susceptibility of hippocampal CA1 vs. CA3 pyramidal cells to ischemic insult. Using an in vitro oxygen–glucose deprivation (OGD) model of ischemia, we found that N‐methyl‐d‐aspartate (NMDA) responses were enhanced in the more susceptible CA1 pyramidal cells and transiently depressed in the resistant CA3 pyramidal cells. The long‐lasting potentiation of NMDA responses in CA1 cells was associated with delayed cell death and was prevented by blocking tyrosine kinase‐dependent up‐regulation of NMDA receptor function. In CA3 cells, the energy deprivation‐induced transient depression of NMDA responses was converted to potentiation by blocking protein phosphatase signalling. These results suggest that energy deprivation differentially shifts the intracellular equilibrium between the tyrosine kinase and phosphatase activities that modulate NMDA responses in CA1 and CA3 pyramidal cells. Therapeutic modulation of tyrosine phosphorylation may thus prove beneficial in mitigating ischemia‐induced neuronal death in vulnerable brain areas.
Undirected and Interpretable Continuous Topic Models of Documents

We propose a new type of undirected graphical model suitable for topic modeling and dimensionality reduction for large text collections. Unlike previous Boltzmann machine and harmonium based methods, this new model represents words using Discrete distributions akin to traditional ‘bag-of-words’ methods. However, in contrast to directed topic models such as latent Dirichlet allocation, each word is drawn from a distribution that takes into account all possible topics, as opposed to a topic-specific distribution. Furthermore, our models use positive continuous valued latent variables and learn more interpretable latent topic spaces than previous undirected techniques. As other undirected models, once such models have been learned, inference required for representing a document in the latent space is fast. We present document retrieval experiments showing the benefits of our new approach.
Clinical implications of insulin-like growth factor II mRNA-binding protein 3 expression in non-small cell lung carcinoma

In order to examine the role of insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression for the prognostic evaluation of non-small cell lung carcinoma (NSCLC), a total of 186 breast cancer patients, with adjacent non-tumor lung tissues, were selected for immunohistochemical staining of IMP3 protein. The NSCLC tissues and paired adjacent non-tumor tissues of six patients were quantified using reverse transcription quantitative polymerase chain reaction. The correlations between IMP3 overexpression and the clinical features of NSCLC were evaluated using the χ2 test and Fisher’s exact test. The survival rate was calculated using the Kaplan-Meier method, and the association between prognostic factors and patient survival was also analyzed by Cox’s proportional hazards models. The results showed that IMP3 protein exhibited a mainly cytoplasmic staining pattern in the NSCLC tissues. The positive rate of IMP3 protein expression was 74.7% (139/186) in the NSCLC tissues and was significantly higher than the rate of 19.9% (37/186) in the adjacent non-tumor tissues. The expression rate of the NQO1 protein was correlated with a large tumor size, poor differentiation, lymph node metastasis, late clinical stage, and disease-free and overall survival rates in the NSCLC patients. In the early- and late-stage NSCLC groups, the disease-free and overall survival rates of the patients with IMP3 expression were significantly lower than those of the patients without IMP3 expression. Further analysis using Cox’s proportional hazard regression model revealed that IMP3 expression was a significant independent hazard factor for the overall survival rate of patients with NSCLC. In conclusion, the present study found that IMP3 plays a significant role in the progression of NSCLC, and that it may potentially be used as an independent biomarker for prognostic evaluation of the cancer.
Ageing and vascular ageing

There is an age related decline in various physiological processes. Vascular ageing is associated with changes in the mechanical and the structural properties of the vascular wall, which leads to the loss of arterial elasticity and reduced arterial compliance. Arterial compliance can be measured by different parameters like pulse wave velocity, augmentation index, and systemic arterial compliance. There is evidence that arterial compliance is reduced in disease states such as hypertension, diabetes, and end stage renal failure. Changes in arterial compliance can be present before the clinical manifestation of cardiovascular disease. Pharmacological and non-pharmacological measures have been shown to improve arterial compliance. Arterial compliance may constitute an early cardiovascular risk marker and may be useful in assessing the effects of drugs on the cardiovascular system. Pharmacogenetics and genetics of arterial compliance in the future will improve our knowledge and understanding about vascular ageing.
An Interaction Behavior Verification Model Based on AOP Technology

In order to measure the trust for software behavior in trusted computing, a software behavior analysis and verification model based on Aspect Oriented Programming (AOP) is proposed. The model about software behavior description, software behavior monitoring, software behavior analysis and verification are designed and descried. The model is deployed on a system for test. The test resultheindicates the model's feasibility and validity.
Energy-Efficient Handoff Decision Algorithms for CSH-MU Mobility Solution

Vertical handoff (VHO) is the key feature to increase the seamless services availability (i.e., cloud services) in a heterogeneous network environment that especially plays an important role in emergency use cases for reliable information retrieval. For precise handoff decisions, latest proposed vertical handoff decision algorithms (VHDA) are, however, too complex and do not consider the restricted access to decision metrics of mobile phones with limited system resources. For addressing this issue and to benefit earlier from seamless service provisioning, we present feasible client based VHDA solutions ensuring context-aware QoS (i.e., high throughput, low power consumption) for specific use cases. Unlike related approaches, our solutions run completely locally on mobile phones without any required modifications on network side. In terms of performance analysis, we design a comprehensive simulation model for comparing the suggested VHDA solutions with different complexity levels. Moreover, we analyze the impact of an energy model, which is derived from experimental measurements, on handoff decision quality and the improvement of battery usage. Simulation results illustrate that VHDAs with energy model enhance the QoS of handoff decisions in terms of high throughput and low power consumption compared to a less approach.
Automatically locating relevant programming help online

While maintaining software systems, developers often encounter compilation errors and runtime exceptions that they do not know how to solve. Solutions to these errors can often be found through discussions with other developers on the Internet. Unfortunately, many of these online discussions do not contain relevant answers. We have developed an approach to automatically query and analyze online discussions to locate relevant solutions to programming problems. Our tool, called Dora, is integrated into Visual Studio and allows developers to query and evaluate solutions within their development environment, enabling them to reduce context switching between their development tasks and their search sessions. We have performed a semi-controlled experiment to validate the utility of our search approach with 18 tasks, finding that our approach provides 55% more relevant results than traditional web searching approaches.
Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs)

These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.
Structure of SL4 RNA from the HIV-1 packaging signal.

The NMR-based structure is described for an RNA model of stem-loop 4 (SL4) from the HIV-1 major packaging domain. The GAGA tetraloop adopts a conformation similar to the classic GNRA form, although there are differences in the details. The type II tandem G.U pairs have a combination of wobble and bifurcated hydrogen bonds where the uracil 2-carbonyl oxygen is hydrogen-bonded to both G,H1 and G,H2. There is the likelihood of a Na(+) ion coordinated to the four carbonyl oxygens in the major groove for these G.U pairs and perhaps to the N7 lone pairs of the G bases as well. A continuous stack of five bases extends over nearly the whole length of the stem to the base of the loop in the RNA 16mer: C15/U14/G13/G5/C6. There is no evidence for a terminal G.A pair; instead, G1 appears quite unrestrained, and A16 stacks on both C15 and G2. Residues G2 through G5 exhibit broadened resonances, especially G3 and U4, suggesting enhanced mobility for the 5'-side of the stem. The structure shows G2/G3/U4 stacking along the same strand, nearly isolated from interaction with the other bases. This is probably an important factor in the signal broadening and apparent mobility of these residues and the low stability of the 16mer hairpin against thermal denaturation.
Service-Level Agreements in Call Centers: Perils and Prescriptions

Acall center with both contract and noncontract customers was giving priority to the contract customers only in off-peak hours, precisely when having priority was least important. In this paper, we investigate whether this is rational behavior on the part of the call center and what the implications are for customers. In particular, we show that under contracts on the percentile of delay, which are commonly used in the call center industry, this is rational behavior, at least under the approximating asymptotic regime considered in this paper. We then suggest other contracts that do not result in this type of undesirable behavior from a contract customer's perspective. We compare the performance of the different contracts in terms of mean, variance, and outer percentiles of delay for both customer types using both numerical and asymptotic heavy-traffic analyses. We argue that including terms reflecting the second moment of delay in a contract would be beneficial to contract customers and, in a sense, fairer.
Berberine-induced pigment dispersion in Bufo melanostictus melanophores by stimulation of beta-2 adrenergic receptors

Abstract Reduced production of melanin by decreased or the absence of melanocytes leads to various hypopigmentation disorders, and the development of melanogenetic agents for photoprotection and hypopigmentation disorders is one of the top priority areas of research. Hence, the present study was carried out to elucidate the ability of berberine, a principal active ingredient present in the roots of the herb Berberis vulgaris to stimulate pigment dispersion in the isolated skin melanophores of the toad Bufo melanostictus. In the present study, mean melanophore size index of the isolated skin melanophores of B. melanostictus was assayed after treating with various concentrations of berberine. A marked melanin dispersion response leading to skin darkening was observed in the isolated melanophores of toad in response to berberine, which was found to be mediated through beta-2 adrenergic receptors. The physiologically significant dose-related melanin dispersion effects of berberine per se were found to be completely abolished by propranolol, which is a specific beta-2 adrenergic receptor blocker. These per se melanin dispersal effects were also found to be markedly potentiated by isoprenaline, which is a specific beta-adrenoceptor agonist. The results indicate that berberine causes a tremendous, dose-dependent, physiologically significant pigment dispersing in the isolated skin melanophores of B. melanostictus.
Does Lumbar Facet Arthrosis Precede Disc Degeneration?: A Postmortem Study

It is believed lumbar degeneration begins in the disc, where desiccation and collapse lead to instability and compensatory facet arthrosis. We explored the contrary contention that facet degeneration precedes disc degeneration by examining 647 skeletal lumbar spines. Using facet osteophytosis as a measure of facet degeneration and vertebral rim osteophytosis as a measure of disc degeneration, we assumed bone degeneration in both locations equally reflected the progression of those in the soft tissues. We graded arthrosis Grade 0 to 4 on a continuum from no arthritis to ankylosis. The data were analyzed for different age groups to examine patterns of degeneration with age. Specimens younger than 30 years of age had a higher prevalence of facet osteophytosis compared with vertebral rim osteophotosis at L1-L2 and L2-L3. Specimens aged 30 to 39 years showed more facet osteophytosis than vertebral rim osteophytosis at L4-L5. Specimens older than 40 years, however, showed more vertebral rim osteophytosis compared with facet osteophytosis at all levels except L4-L5 and L5-S1. This skeletal study suggests facet osteophytosis appears early in the degenerative process, preceding vertebral rim osteophytosis of degenerating intervertebral discs. However, once facets begin deteriorating with age, vertebral rim osteophytosis overtakes continued facet osteophytosis. These data challenge the belief that facet osteophytosis follows vertebral rim osteophytosis; rather, it appears vertebral rim osteophytosis progresses more rapidly in later years, but facet osteophotosis occurs early, predominating in younger individuals.
Non-isotopic RNase cleavage assay for mutation detection in MEFV, the gene responsible for familial Mediterranean fever, in a cohort of Greek patients

Background: The MEFV gene is responsible for familial Mediterranean fever (FMF). Several disease associated mutations have been identified. The range of genetic variation in MEFV in Greek patients has not been determined. Objective: To describe a method that facilitates the routine screening of the entire coding sequence of MEFV (excluding exon 1). Methods: The non-isotopic RNase cleavage assay (NIRCA) was optimised and used as a first step screening method to screen exons 2 to 10 of MEFV. Exons 2 and 10 were analysed separately at DNA level, while exons 3 to 9 were analysed together at cDNA level. The sample group consisted of 26 FMF patients diagnosed using established clinical criteria, six asymptomatic relatives, 12 patients with atypical clinical manifestations, nine patients suffering from various inflammatory diseases, and three normal individuals. All were analysed by NIRCA for mutations in the MEFV gene and direct sequencing was applied subsequently to confirm the results. Results:MEFV mutations were identified in 25 of 26 typical FMF patients and in two of 12 patients with atypical manifestations. NIRCA results were in concordance with sequencing findings in all sequences analysed, suggesting that the method is highly reliable in this disease. Sixteen alterations of MEFV were identified (eight missense mutations and eight single nucleotide polymorphisms). Conclusions: NIRCA can be used for rapid screening of the coding sequence of the MEFV gene in patients suspected of suffering from FMF.
2 . Comparative Advantage with Two Goods : Ricardo , Haberler

This paper reviews the theoretical development of the concept of comparative advantage, starting with the two-good model of Ricardo and the two-good extension and reinterpretation by Haberler. In both, the presence of comparative advantage provides the scope for countries to gain from trade by specializing, and the pattern of that trade is explained by the pattern of comparative advantage. These strong results of the twogood model can be extended under certain circumstances to multiple goods and countries, but under more general assumptions such strong results no longer are assured. Instead one can derive much weaker results, usually in the form of correlations between comparative advantage and trade, and these weaker results hold in a much wider variety of circumstances. The paper examines those assumptions that permit such generalizations, but then also examines when those assumptions are most likely to fail, and what happens as a result.
Apratoxin A Reversibly Inhibits the Secretory Pathway by Preventing Cotranslational Translocation

Apratoxin A is a potent cytotoxic marine natural product that rapidly inhibits signal transducer and activator of transcription (STAT) 3 phosphorylation by an undefined mechanism. We have used biochemical and proteomics approaches to illuminate upstream molecular events. Apratoxin A inhibits Janus kinase (JAK)/STAT signaling through rapid down-regulation of interleukin 6 signal transducer (gp130). Apratoxin A also depletes cancer cells of several cancer-associated receptor tyrosine kinases by preventing their N-glycosylation, leading to their rapid proteasomal degradation. A proteomics approach revealed that several proteins in the endoplasmic reticulum, the site of N-glycoprotein synthesis, are down-regulated upon apratoxin A exposure. Using in vitro cell free systems, we demonstrated that apratoxin A prevents cotranslational translocation of proteins destined for the secretory pathway. This process is reversible in living cells. Our study indicates that apratoxins are new tools to study the secretory pathway and raises the possibility that inhibition of cotranslational translocation may be exploited for anticancer drug development.