Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamically varying interactions between heregulin and ErbB proteins detected by single-molecule analysis in living cells

Heregulin (HRG) belongs to the family of EGFs and activates the receptor proteins ErbB3 and ErbB4 in a variety of cell types to regulate cell fate. The interactions between HRG and ErbB3/B4 are important to the pathological mechanisms underlying schizophrenia and some cancers. Here, we observed the reaction kinetics between fluorescently labeled single HRG molecules and ErbB3/B4 on the surfaces of MCF-7 human breast cancer cells. The equilibrium association and the dissociation from equilibrium were also measured using single-molecule imaging techniques. The unitary association processes mirrored the EGF and ErbB1 interactions in HeLa cells [Teramura Y, et al. (2006) EMBO J 25:4215–4222], suggesting that the predimerization of the receptors, followed by intermediate formation (between the first and second ligand-binding events to a receptor dimer), accelerated the formation of doubly liganded signaling dimers of the receptor molecules. However, the dissociation analysis suggested that the first HRG dissociation from the doubly liganded dimer was rapid, but the second dissociation from the singly liganded dimer was slow. The dissociation rate constant from the liganded monomer was intermediate. The dynamic changes in the association and dissociation kinetics in relation to the dimerization of ErbB displayed negative cooperativity, which resulted in apparent low- and high-affinity sites of HRG association on the cell surface.
Ground state of the supermembrane on a pp wave

We consider the ground state of a supermembrane on the maximally supersymmetric pp-wave background by using the quantum-mechanical procedure of de Wit, Hoppe, and Nicolai. On the pp-wave background the ground state has a nontrivial structure even in the zero-mode Hamiltonian. The supergravity multiplet in flat space comes to split with a certain energy difference. We explicitly derive the supersymmetric ground-state wave function for the zero-mode Hamiltonian, which is obviously normalizable. Moreover, we discuss the nonzero-mode Hamiltonian and construct an example of the ground-state wave function with the truncation of variables, whose ${L}^{2}$ norm can be represented by an asymptotic series.
On-the-Fly Constraint Mapping across Web Query Interfaces

Recently, the Web has been rapidly “deepened” with the prevalence of databases online and becomes an important frontier for data integration. On this deep Web, a significant amount of information can only be accessed as response to dynamically issued queries to the query interface of a back-end database, instead of by traversing static URL links. Such a query interface expresses a set of constraint templates, where each constraint template states how an attribute can be queried. To enable automatic query mediation among heterogenous deep Web sources, it is critical to automatically translate those constraints, which we name as constraint mapping . I n particular, this paper aims at enabling on-the-fly constraint mapping, toward on-the-fly integration of Web databases, due to the the large scale and dynamic nature of the deep Web. Such on-the-fly query translation poses a significant new challenge on the generality and extensibility of the translation framework. Existing works pursue a per-source rule-driven framework and thus cannot satisfy such requirements. In contrast, we propose a generic type-based search-driven translation framework by considering the constraint mapping for each data type as a search problem. In particular, in this paper, we develop search algorithms for text and numeric types. Our experiments over real deep Web sources show that our approach is promising as a principle way to mediate queries for large scale integration.
Classes and Narrowing Selectivity of Olfactory Receptor Neurons of Xenopus laevis Tadpoles

In olfactory receptor neurons (ORNs) of aquatic animals amino acids have been shown to be potent stimuli. Here we report on calcium imaging experiments in slices of the olfactory mucosa of Xenopus laevis tadpoles. We were able to determine the response profiles of 283 ORNs to 19 amino acids, where one profile comprises the responses of one ORN to 19 amino acids. 204 out of the 283 response profiles differed from each other. 36 response spectra occurred more than once, i.e., there were 36 classes of ORNs identically responding to the 19 amino acids. The number of ORNs that formed a class ranged from 2 to 13. Shape and duration of amino acid-elicited [Ca2+]i transients showed a high degree of similarity upon repeated stimulation with the same amino acid. Different amino acids, however, in some cases led to clearly distinguishable calcium responses in individual ORNs. Furthermore, ORNs clearly appeared to gain selectivity over time, i.e., ORNs of later developmental stages responded to less amino acids than ORNs of earlier stages. We discuss the narrowing of ORN selectivity over stages in the context of expression of olfactory receptors.
Characterization of tpp1+ as Encoding a Main Trehalose-6P Phosphatase in the Fission YeastSchizosaccharomyces pombe

ABSTRACT We have characterized an open reading frame of 2,454 bp on chromosome I of Schizosaccharomyces pombe as the gene encoding trehalose-6P phosphatase (tpp1+). Disruption of tpp1+ caused in vivo accumulation of trehalose-6P upon heat shock and prevented cell growth at 37 to 40°C. Accumulation of trehalose-6P in cells bearing a chromosomal disruption of the tpp1+ gene and containing a plasmid with tpp1+ under the control of the thiamine-repressible promotor correlated withtpp1+ repression. The level oftpp1+ mRNA rose upon heat shock, osmostress, or oxidative stress and was negatively controlled by cyclic AMP-dependent protein kinase activity. Expression oftpp1+ during oxidative or osmotic stress, but not during heat shock, was under positive control by thewis1-sty1 (equivalent to phh1 andspc1) mitogen-activated protein kinase pathway. Analysis of Tpp1 protein levels suggests that the synthesis of trehalose-6P phosphatase may also be subjected to translational or posttranslational control.
Prospective Observational Study of Imatinib Therapy in Japanese Patients with Advanced Gastrointestinal Stromal Tumors: Long-term Follow-up and Second Malignancy

Abstract Objective Limited data are available concerning long-term results of imatinib therapy in patients with advanced gastrointestinal stromal tumors. We aimed to clarify the long-term outcomes of imatinib therapy in Japanese patients with advanced gastrointestinal stromal tumors. Methods A prospective, observational study of imatinib therapy for unresectable and metastatic gastrointestinal stromal tumors was conducted in our institution. Imatinib was initiated at a dose of 400 mg daily and continued until disease progression. Safety, efficacy and long-term tolerability and survival were evaluated in an intent-to-treat population. The median follow-up period in this study was 68 months. Results Seventy patients were enrolled between December 2001 and December 2009. Treatment-related Grade 3/4 adverse events occurred in 49 patients (70.0%). Although 14 patients required adverse effect management with hospitalization, only 5 patients (7.1%) withdrew from the treatment owing to imatinib intolerance. The tumor response and clinical benefit rates were 61.4 and 85.7%, respectively. Thirty-seven patients (52.9%) maintained the treatment at 400 mg daily imatinib, whereas 33 patients (47.1%) had their dose reduced to 300 mg daily or less. The overall survival rate at 5 years was 60.9% and the median survival time was 70 months. The median progression-free survival time of all the 70 enrolled patients was 30 months. Seven patients (10.0%) suffered from second malignancies, including three patients with genitourinary carcinomas. Conclusions Despite the need for dose reduction, the long-term results of imatinib therapy for advanced gastrointestinal stromal tumors were good in Japanese patients. Physicians should pay attention to the occurrence of second malignancies during imatinib therapy for gastrointestinal stromal tumor patients.
Effect of a novel phosphorus-containing compound on the flame retardancy and thermal degradation of intumescent flame retardant polypropylene

A novel flame retardant, tetra(5,5-dimethyl-1,3- dioxaphosphorinanyl-2-oxy) neopentane (DOPNP), was synthesized successfully, and its structure was characterized by FT-IR, 1H NMR, and 31P NMR. The thermogravimetric analysis (TGA) results demonstrate that DOPNP showed a good char-forming ability. Its initial decomposition temperature was 236.4°C based on 1% mass loss, and its char residue was 41.2 wt % at 600°C, and 22.9 wt % at 800°C, respectively. The flame retardancy and thermal degradation behavior of novel intumescent flame-retardant polypropylene (IFR-PP) composites containing DOPNP were investigated using limiting oxygen index (LOI), UL-94 test, TGA, cone calorimeter (CONE) test, and scanning electron microscopy (SEM). The results demonstrate that DOPNP effectively raised LOI value of IFR-PP. When the loading of IFR was 30 wt %, LOI of IFR-PP reached 31.3%, and it passed UL-94 V-0. TGA results show that DOPNP made the thermal decomposition of IFR-PP take place in advance; reduced the thermal decomposition rate and raised the residual char amount. CONE results show that DOPNP could effectively decrease the heat release rate peak of IFR-PP. A continuous and compact char layer observed from the SEM further proved the flame retardance. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.
Binding and Scattering in Two-Dimensional Systems: Applications to Quantum Wires, Waveguides and Photonic Crystals

Bound States in Low-Dimensional Systems. - Transmission and Conductance in Tubes. - Waveguide Measurements of the Properties of Curved Tubes. - Binding and Transmission in Wires and Waveguides. - Two-Dimensional Systems with Finite Periodic Structure. - Localized Modes in Photonic Crystals. - Epilogue. - Comparison of Various Approximate Quantum Wells. - Conducting Sphere on a Grounded Surface.
Cell-type specific mechanisms of D-serine uptake and release in the brain

Accumulating evidence during the last decade established that D-serine is a key signaling molecule utilized by neurons and astroglia in the mammalian central nervous system. D-serine is increasingly appreciated as the main physiological endogenous coagonist for synaptic NMDA receptors at central excitatory synapses; it is mandatory for long-term changes in synaptic strength, memory, learning, and social interactions. Alterations in the extracellular levels of D-serine leading to disrupted cell-cell signaling are a trademark of many chronic or acute neurological (i.e., Alzheimer disease, epilepsy, stroke) and psychiatric (i.e., schizophrenia) disorders, and are associated with addictive behavior (i.e., cocaine addiction). Indeed, fine tuning of the extracellular levels of D-serine, achieved by various molecular machineries and signaling pathways, is necessary for maintenance of accurate NMDA receptor functions. Here, we review the experimental data supporting the notion that astroglia and neurons use different pathways to regulate levels of extracellular D-serine.
Calcium/Calmodulin-Dependent Protein Kinase Is Negatively and Positively Regulated by Calcium, Providing a Mechanism for Decoding Calcium Responses during Symbiosis Signaling[W][OPEN]

This study dissects the regulation of a calcium/calmodulin-dependent protein kinase (CCaMK) during symbiotic signaling and reveals that CCaMK is both negatively and positively regulated by calcium to create a robust molecular switch that is responsive to calcium concentrations associated with both the basal state and with oscillations. The establishment of symbiotic associations in plants requires calcium oscillations that must be decoded to invoke downstream developmental programs. In animal systems, comparable calcium oscillations are decoded by calmodulin (CaM)–dependent protein kinases, but symbiotic signaling involves a calcium/CaM–dependent protein kinase (CCaMK) that is unique to plants. CCaMK differs from the animal CaM kinases by its dual ability to bind free calcium, via calcium binding EF-hand domains on the protein, or to bind calcium complexed with CaM, via a CaM binding domain. In this study, we dissect this dual regulation of CCaMK by calcium. We find that calcium binding to the EF-hand domains promotes autophosphorylation, which negatively regulates CCaMK by stabilizing the inactive state of the protein. By contrast, calcium-dependent CaM binding overrides the effects of autophosphorylation and activates the protein. The differential calcium binding affinities of the EF-hand domains compared with those of CaM suggest that CCaMK is maintained in the inactive state at basal calcium concentrations and is activated via CaM binding during calcium oscillations. This work provides a model for decoding calcium oscillations that uses differential calcium binding affinities to create a robust molecular switch that is responsive to calcium concentrations associated with both the basal state and with oscillations.
Changes in Coronary Heart Disease Risk Among Japanese

Heart disease is the second most prominent cause of mortality in Japan, and coronary heart disease (CHD) accounts for approximately half of heart disease–related deaths.1 The CHD mortality rate in Japan has been one-third to one-fifth that in the United States,1–5 even when validated fatal CHD and sudden cardiac deaths were compared.3–5 However, there is growing concern about a possible increase in the incidence of and mortality from CHD because of the westernization of lifestyles such as high-fat diets and sedentary work patterns associated with socioeconomic development since the 1960s.6–11 The present report reviews original articles on population-based surveys of the mortality, incidence, and risk factors of CHD. It focuses on their trends since the 1960s because Japan has experienced rapid changes in lifestyles and environment accompanying socioeconomic development and maturation. To identify the relevant literature, PubMed was searched for articles published from 1963 through June 2007. The following search key words were used: coronary heart disease or coronary artery disease or ischemic heart disease or myocardial infarction ; mortality or incidence or risk factor ; Japan or Japanese ; and epidemiology . Bibliographies of key articles were reviewed and experts in the field were consulted to identify all of the major population-based studies. ### Trends in Mortality From CHD Age-adjusted mortality rates from CHD declined 50% for men and 65% for women between 1969 and 19928,9 and has continued to decline.1,2 According to the World Health Organization database, the age-adjusted annual CHD mortality rate in 2000 was 37 per 100 000 for men and 18 per 100 000 for women, which was the lowest among developed countries.2 There are, however, sex, age, and regional variations in CHD mortality trends.9 The age-adjusted CHD mortality rates declined from 57 per 100 000 in 1969 to 1970 to 27 per …
Parent-of-origin Effect in Schizophrenia and Non-affective Psychoses: Evidence from Dermatoglyphics

Objective: This study aims at examining “parent-of-origin effect” (POE) in dermatoglyphic patterns among patients with schizophrenia and non-affective psychoses. Materials and Methods: Dermatoglyphic comparison was carried out for schizophrenia patients (n=200) and healthy controls (HC) (n=100). In addition, the effect of family history and POE was examined in the dermatoglyphic pattern. Results: Schizophrenia patients compared to HC had significantly lower left total finger ridge count (LTFRC) (t=3.63, P<0.001), right total finger ridge count (RTFRC) (t=4.86, P<0.001), and absolute finger ridge count (ATFRC) (t=4.80, P<0.001) compared to HC. It was also noted that patient group had significantly higher average number of arches (t=2.20, P=0.03). The comparison between the same sex POE group and the opposite sex POE group revealed that significant differences exist in LTFRC (t=2.91, P<0.01) and ATFRC (t=2.30, P=0.02). The same sex group also had lesser number of whorls compared to opposite sex group (t=2.04, P=0.04). Conclusions: The same sex parental inheritance group seem to be more developmentally compromised than the opposite sex parental inheritance group indicating a significant POE. Complex epigenetic mechanisms along with hormonal modulation could explain the sex specific disease phenotype expression, which is a plausible explanation as in the present study.
Autism: The Empathizing–Systemizing (E‐S) Theory

The mind‐blindness theory of autism spectrum conditions has been successful in explaining the social and communication difficulties that characterize these conditions but cannot explain the nonsocial features (the narrow interests, need for sameness, and attention to detail). A new theory, the empathizing–systemizing (E‐S) theory, is summarized, which argues two factors are needed to explain the social and nonsocial features of the condition. This is related to other cognitive theories such as the weak central coherence theory and the executive dysfunction theory. The E‐S theory is also extended to the extreme male brain theory as a way of understanding the biased sex ratio in autism. Etiological predictions are discussed, as are the clinical applications arising from the E‐S theory.
Hepatic stellate cell activation in liver transplant patients with hepatitis C recurrence and in non‐transplanted patients with chronic hepatitis C

The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen‐producing cells in the liver, can occur in these patients as compared to non‐LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer‐based morphometric analysis of α‐smooth muscle actin (αSMA)‐positive cells and the hepatic TGFβ1 expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non‐LT patients with chronic hepatitis C, and 16 controls. Hepatic αSMA and TGFβ1 expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in αSMA and TGFβ1 expression was observed between LT and non‐LT patients with hepatitis C, with the exception of a higher transforming growth factor β‐1 (TGFβ1) expression in non‐LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and αSMA and TGFβ1 expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFβ1 expression in the grafts of these patients as compared to non‐LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFβ1 expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered. Liver Transpt 13:1017–1027, 2007. © 2007 AASLD.
Methylation-Associated Silencing of the Heat Shock Protein 47 Gene in Human Neuroblastoma

Hypermethylation of gene promoter CpG islands is a frequent mechanism for gene inactivation in a variety of human cancers, including neuroblastoma (NB). We demonstrated recently that treatment with the demethylating agent 5′-aza-2′-deoxycytidine (5-Aza-dC) significantly inhibited NB growth in vivo. In an effort to identify the genes and biological pathways that are responsible for the impaired NB tumor growth observed after treatment with 5-Aza-dC, we performed genome-wide gene expression analysis of control and treated NBL-W-S NB cells. We found ≥3-fold changes in expression of 44 genes that play roles in angiogenesis, apoptosis, cell adhesion, transcriptional regulation, and signal transduction. The gene encoding heat shock protein 47 (Hsp47), a collagen-specific molecular chaperon, was up-regulated >80-fold after 5-Aza-dC treatment. Expression studies confirmed that Hsp47 is silenced in a subset of NB cell lines and tumors. We also show that silencing of Hsp47 in NB cells is associated with aberrant methylation of promoter CpG islands and that Hsp47 expression can be restored after treatment with 5-Aza-dC. A strong correlation between Hsp47 and collagen type I and IV expression was seen in NB cells. Interestingly, tumorigenicity was inversely correlated with the level of collagen expression in NB cell lines, and higher levels of collagen were detected in mature NB tumors that are associated with favorable outcome compared with undifferentiated, advanced-stage NBs. Our studies support a role for Hsp47 in the regulation of collagen type I and IV production in NB cells and suggest that the level of collagen expression may influence NB tumor phenotype.
Perceived need to take medication is associated with medication non-adherence in patients with rheumatoid arthritis

Background This is the first cross-sectional study that aims to examine associations between beliefs about medication and non-adherence in patients with rheumatoid arthritis (RA) using disease-modifying antirheumatic drugs, taking potential psychological confounders into account. Methods Eligible patients (diagnosed with RA for ≥1 year or ≥18 years, using greater than or equal to one disease-modifying antirheumatic drug) were included by their rheumatologist during regular outpatient visits between September 2009 and September 2010. Included patients received questionnaires. The Beliefs about Medicines Questionnaire was used to measure the perceived need to take medication (necessity beliefs), the concerns about taking medication (concern beliefs), general medication beliefs, and attitudes toward taking medication. Medication non-adherence (no/yes) was measured using the Compliance Questionnaire Rheumatology (CQR). Associations between beliefs and non-adherence, and the influence of demographical, clinical, and psychological factors (symptoms of anxiety/depression, illness cognitions, self-efficacy) were assessed using logistic regression. Results A total of 580 of the 820 eligible patients willing to participate were included in the analyses (68% female, mean age 63 years, 30% non-adherent to their medication). Weaker necessity beliefs (OR [odds ratio]: 0.8, 95% CI [confidence interval]: 0.8–0.9) and an unfavorable balance between necessity and concern beliefs (OR: 0.9, 95% CI: 0.9–1.0) were associated with CQR non-adherence. Also, having an indifferent attitude toward medication (no/yes) was associated with CQR non-adherence (OR: 5.3, 95% CI: 1.1–25.8), but the prevalence of patients with an indifferent attitude toward medication was low. The associations were barely confounded by demographical, clinical, and psychological factors. Conclusion Increasing necessity beliefs about medication in clinical practice might be worthwhile in improving medication adherence in RA patients.