Miracle-dz/UniFAR-FTUs huggingface dataset:
Dose‐Dependent, K+‐Stimulated Efflux of Endogenous Taurine from Primary Astrocyte Cultures Is Ca2+‐Dependent

The K+‐stimulated efflux of endogenous taurine from primary rat cerebellar astrocyte cultures prepared from 7–9‐day‐old rats was studied at 16–18 days in vitro using HPLC analysis. Taurine efflux was dose‐dependent at K+ concentrations between 10 mM and 80 mM, with an EC50 of approximately 50 mM. Maximum stimulation of efflux above basal levels ranged from 56% at 10 mM K+ (204 pmol/min/mg protein) to 470% at 80 mM K+ (960 pmol/min/mg protein). Removal of Ca2+ from the buffer and the addition of either 1 mM EGTA or 10 mM Mg2+ abolished K. +‐stimulated efflux. Taurine efflux peaked and fell in parallel with the K+ concentration, but with an approximate lag of 3–5 min. The time course and amount of preloaded [3H]taurine released did not differ significantly from that seen for endogenous efflux. Basal taurine efflux varied inversely with the extracellular concentration of Ca2+ over the concentration range 0–5.0 mM. The observed Ca2+ dependence is consistent with a role for Ca2+ in the regulation of taurine release. Furthermore, taurine release from astrocytes in response to elevated K+ may reflect a neuromodulatory role for this amino acid in the CNS.
Sorafenib Inhibits the Hepatocyte Growth Factor–Mediated Epithelial Mesenchymal Transition in Hepatocellular Carcinoma

The epithelial mesenchymal transition (EMT) has emerged as a pivotal event in the development of the invasive and metastatic potentials of cancer progression. Sorafenib, a VEGFR inhibitor with activity against RAF kinase, is active against hepatocellular carcinoma (HCC); however, the possible involvement of sorafenib in the EMT remains unclear. Here, we examined the effect of sorafenib on the EMT. Hepatocyte growth factor (HGF) induced EMT-like morphologic changes and the upregulation of SNAI1 and N-cadherin expression. The downregulation of E-cadherin expression in HepG2 and Huh7 HCC cell lines shows that HGF mediates the EMT in HCC. The knockdown of SNAI1 using siRNA canceled the HGF-mediated morphologic changes and cadherin switching, indicating that SNAI1 is required for the HGF-mediated EMT in HCC. Interestingly, sorafenib and the MEK inhibitor U0126 markedly inhibited the HGF-induced morphologic changes, SNAI1 upregulation, and cadherin switching, whereas the PI3 kinase inhibitor wortmannin did not. Collectively, these findings indicate that sorafenib downregulates SNAI1 expression by inhibiting mitogen-activated protein kinase (MAPK) signaling, thereby inhibiting the EMT in HCC cells. In fact, a wound healing and migration assay revealed that sorafenib completely canceled the HGF-mediated cellular migration in HCC cells. In conclusion, we found that sorafenib exerts a potent inhibitory activity against the EMT by inhibiting MAPK signaling and SNAI1 expression in HCC. Our findings may provide a novel insight into the anti-EMT effect of tyrosine kinase inhibitors in cancer cells. Mol Cancer Ther; 10(1); 169–77. ©2011 AACR.
The Effects of Disclosure and Analyst Regulations on the Relevance of Analyst Characteristics for Explaining Analyst Forecast Accuracy

We posit and find an effect of disclosure and analyst reporting regulations implemented from 2000 through 2003 (including Regulation Fair Disclosure, the Sarbanes-Oxley Act, and the Global Settlement Act) on the importance of analyst and forecast characteristics for analyst forecast accuracy. In particular, following the enactment of these regulations, more experienced analysts and All-Star analysts do not maintain their superior forecast accuracy, and analysts employed by large brokerage houses perform worse than other analysts. In addition, following the enactment of these regulations, we find a decrease in the importance of analyst effort, the number of industries and firms followed, days elapsed since the last forecast, and forecast horizon. While the importance of bold upward forecast revisions does not change, bold downward revisions lose their relevance for forecast accuracy after 2003. Finally, we find an increase in the important of prior forecast accuracy. We also posit and find that the importance of these characteristics varies with the precision of publicly available information. Specifically, the decrease in the importance of most analyst and forecast characteristics and the increase in the importance of prior forecast accuracy are greater when the precision of publicly available information is low. Overall, our results suggest that the positive effects of experience, effort, brokerage house size, and All-Star status on forecast accuracy in the pre-regulation period were because of the information advantages that these analysts enjoyed (rather than their ability to generate private information). In contrast, our results suggest that prior forecast accuracy is related to analysts’ ability to generate private information. Because investors consider analyst and forecast characteristics when they form expectations about earnings, our findings can help investors to better assess and use analyst forecasts.
An Escherichia coli chromosomal "addiction module" regulated by guanosine [corrected] 3',5'-bispyrophosphate: a model for programmed bacterial cell death.

"Addiction modules" consist of two genes. In most of them the product of one is long lived and toxic while the product of the second is short lived and antagonizes the toxic effect; so far, they have been described mainly in a number of prokaryotic extrachromosomal elements responsible for the postsegregational killing effect. Here we show that the chromosomal genes mazE and mazF, located in the Escherichia coli rel operon, have all of the properties required for an addiction module. Furthermore, the expression of mazEF is regulated by the cellular level of guanosine [corrected] 3',5'-bispyrophosphate, the product of the RelA protein under amino acid starvation. These properties suggest that the mazEF system may be responsible for programmed cell death in E. coli and thus may have a role in the physiology of starvation.
Measuring Smile Curves in Global Value Chains

The concept and logic of the "smile curve" in the context of global value chains has been widely used and discussed at the individual firm level, but rarely identified and investigated at the country and industry levels by using real data. This paper proposes an idea, based on an inter-country input-output model, to consistently measure both the strength and length of linkages between producers and consumers along global value chains. This idea allows for better identification and mapping of smile curves for countries and industries according to their positions and degrees of participation in a given conceptual value chain. Using the 1995-2011 World Input-Output Tables, several conceptual value chains are investigated, including exports of electrical and optical equipment from China and Mexico and exports of automobiles from Japan and Germany. The identified smile curves provide a very intuitive and visual image, which can significantly improve our understanding of the roles played by different countries and industries in global value chains. Further, the smile curves help identify the benefits gained by these countries and industries through their participation in global trade.
Comparison of Vasoactive Response of Left and Right Internal Thoracic Arteries to Isosorbide‐Dinitrate and Nitroglycerin:

Abstract Objective: The internal thoracic artery (ITA) is the most important graft in coronary artery bypass grafting. Its distal region is, however, prone to vasospasm. We studied the effects of nitroglycerin (NTG) and isosorbide‐dinitrate (DSDN) on distal segments of left versus right ITA. Methods: Rings of distal segments (6 to 9 mm proximal to bifurcation) of the human left and right ITA were studied. After baseline contraction of the rings, achieved using 60 mmol/L of KCl, they were exposed to increasing doses of ISDN and NTG (10 to 100 μg/ml), and dose‐response curves were recorded. Results: The contractile response of left ITA rings to KCl were significantly lower than those of right ITA rings (1.87 ± 0.25 g versus 3.5 ± 0.61 g, p < 0.005). Both nitrates inhibited the contractile response in a concentration‐dependent manner, with relaxing effects of ISDN higher than those of NTG (p < 0.01) in both left and right ITA rings. Conclusions: The distal segment of the left ITA is less prone to vasospasm than that of the right. ISDN has a considerably higher relaxant effect on this segment than NTG. We therefore recommend favoring high doses of ISDN over NTG as an antispastic measure. (J Card Surg 2003; 18:279‐285)
A Distributed Algorithm for Virtual Backbone Construction with Cellular Structure in WSNs

The normal node in wireless sensor networks (WSNs) often has no constant energy supply. To make efficient use of limited energy resources significant, a major way to save limited energy resources is constructing a smaller virtual backbone in WSNs. In this paper, we propose a distributed algorithm for virtual backbone construction with cellular structure in WSNs (DBC), which is an improvement of algorithm ABP (Duresi and Paruchuri, 2008) and minimize the distortion of constructed cellular structure by improving the way of calculating strategic points using 1-hop neighbor information. Our simulation results show that algorithm DBC has smaller virtual backbone than algorithm ABP, and the number of backbone nodes is much fewer than that one.
Interaction between developmental and cell cycle regulators is required for morphogenesis in Aspergillus nidulans

In Aspergillus nidulans, mutation of the transcriptional regulator brlA arrests formation of asexual spore‐forming structures called conidiophores but does not hinder vegetative hyphal growth. During conidiophore development a 6‐fold, brlA‐dependent increase in the kinase activities of NIMXcdc2 and NIMA occurs. A similar level of kinase induction was promoted by ectopic expression of brlA. Northern and Western analysis revealed marked induction of nimXcdc2 mRNA after ectopic expression of brlA and increased amounts of NIMXcdc2. Therefore, nimXcdc2 is developmentally regulated by brlA indicating a direct role for brlA in the regulation of cell cycle genes. That correct regulation of nimXcdc2 is important for normal development was further supported by analysis of conidiophore development and septation in cell cycle specific mutants. Most noticeably, the nimXcdc2AF mutation promoted inappropriate septation and hindered the switch from filamentous growth to budding growth seen during conidiophore development. Therefore, in contrast to the situation previously reported for other multicellular eukaryotes, interaction between developmental regulators and cell cycle regulators is essential for normal morphogenesis in A.nidulans.
Dermoscopy in general dermatology: practical tips for the clinician

In addition to its well‐documented value in improving the diagnosis of skin tumours, dermoscopy is continually gaining appreciation in the field of general dermatology. Dermoscopy has been shown to facilitate the clinical recognition of several inflammatory and infectious diseases, as well as their discrimination from skin tumours. Moreover, recent data indicate that it might also be profitable in assessing the outcome and adverse effects of various treatments. Application of dermoscopy should follow the standard procedure of acquiring information from patient history and clinically evaluating the number, location and morphology of the lesion(s). Four parameters should be assessed when applying dermoscopy in the realm of inflammatory and infectious diseases: (i) morphological vascular patterns; (ii) arrangement of vascular structures; (iii) colours; and (iv) follicular abnormalities, while the presence of other specific features (clues) should also be evaluated. It must be underlined that dermoscopic findings should always be interpreted within the overall clinical context of the patient, integrated with information from the history and the macroscopic examination. With new evidence continuously being gathered, the dermatoscope gradually acquires a role similar to the stethoscope of general practitioners, becoming an irreplaceable clinical tool for dermatologists. In this article, we provide a succinct summary of existing data on dermoscopy in general dermatology. Practical tips are suggested, which can assist clinicians in profitably utilizing and applying the available knowledge in their everyday practice.
Bone marrow involvement is not associated with the clinical outcomes of gastric mucosa-associated lymphoid tissue lymphoma

ABSTRACT Objective Bone marrow (BM) examination is recommended as part of the initial staging work-up in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the clinical significance of BM involvement in gastric MALT lymphoma patients has not been evaluated. Materials and methods From November 1995 to September 2014, 496 subjects who were diagnosed with gastric MALT lymphoma and underwent BM examination were eligible to be included in this study. BM involvement was found in 33 patients (6.7%) by retrospective review, and after exclusions, the clinical outcomes of 28 patients with BM involvement and 412 patients without BM involvement were evaluated. Results When comparing the characteristics of patients, age (median 60 vs. 53 years, p = 0.007) and Helicobacter pylori infection rate (71.0% vs. 85.5%, p = 0.040) were different between patients with and without BM involvement, while the location, macroscopic findings, and depth of invasion were similar. The overall complete remission (CR) rate was 85.2% during a median follow-up period of 42 months (interquartile range, 23–66 months) and did not differ between the two groups (78.6 and 85.7%, p = 0.280). Eradication therapy was performed as the first-line treatment in 18 of the 28 patients (64.3%) with BM involvement, and CR was achieved in 13 patients (72.2%). Logistic regression analysis showed that age and location in the upper part of the stomach were factors related to remission failure. Conclusion Gastric MALT lymphoma has a favorable outcome, and eradication therapy can be justified in selected cases even with BM involvement, when these patients are closely monitored.
The role of T lymphocytes in bone metabolism

Summary: Recent findings from animal models suggest that the bone loss induced by estrogen deficiency may stem in large measure from a pathological upregulation of the adaptive immune response. While the role of activated T cells in the osteoporosis driven by inflammatory conditions and infection has been well documented, only recently has the role of T cells in the bone destruction associated with estrogen deficiency begun to be appreciated. In vivo and in vitro models of postmenopausal osteoporosis demonstrate that estrogen deficiency leads to an increase in the adaptive immune function that culminates in an increased production of tumor necrosis factor α (TNF) by activated T cells. TNF increases osteoclast (OC) formation and bone resorption both directly and by augmenting the sensitivity of maturing OCs to the essential osteoclastogenic factor receptor activator of nuclear factor κB ligand. The activation and expansion of TNF‐producing T cells are key steps in estrogen deficiency‐driven bone loss and are regulated by multiple interacting cytokines including transforming growth factor‐β, interleukin‐7, and interferon‐γ, as well as by the process of antigen presentation. Herein, we review the experimental evidence that suggests estrogen prevents bone loss by regulating T‐cell function and immune cell bone interactions.
Regulation of c‐fos expression in senescing Werner syndrome fibroblasts differs from that observed in senescing fibroblasts from normal donors

The Werner syndrome (WS) is a segmental progeroid syndrome caused by a recessive mutation (WRN) mapped to 8p12. The replicative life spans of somatic cells cultured from WS patients are substantially reduced compared to age‐matched controls. Certain molecular concomitants of the replicative decline of normal fibroblast cultures have recently been defined, and it appears that multiple changes in gene expression accompany normal cell senescence. If the mechanisms by which WS cells exit the cell cycle were entirely comparable, the molecular markers of senescence should be identical in normal and WS cells. We find that this is not the case. The constitutive expression of statin, a nuclear protein associated with the nonproliferating state, was comparably expressed in normal and WS senescent cells. Likewise, the steady state levels of p53, a protein known to be involved in the G1 checkpoint of the cell cycle, were similar in early‐passage fibroblasts from normal and WS subjects. The levels of p53 were not increased in senescent fibroblasts, whether derived from normal or WS subjects. By contrast, the inducibility of mRNA and protein expression of the c‐fos protooncogene is preserved in late‐passage WS cells. This is in contrast to what is observed in late‐passage fibroblasts from normal subjects. Additional genotypes will have to be examined, however, to determine the specificity of this new aspect of the WS phenotype. © 1995 Wiley‐Liss, Inc.
Ceftriaxone therapy of serious bacterial infections in adults

We evaluated the efficacy and safety of ceftriaxone in 50 adults with serious infections, usually giving 1 g every 12 h. Of the 35 patients who could be evaluated for clinical efficacy, 15 had failed on previous therapy, 15 had nosocomial infections, and all but 1 had underlying diseases. One patient had three sites of infection. Favorable responses were seen in 34 of 37 infections, including 11 of 13 respiratory tract infections, all 7 urinary tract infections, all 12 skin and soft tissue infections, 1 of 2 bone and joint infections, a catheter-related septicemia, a liver abscess, and an otitis media and externa. Favorable bacteriological responses were seen for 48 of 58 organisms. This included 6 of 7 Staphylococcus aureus strains, 14 of 16 other aerobic gram-positive cocci, 18 of 20 Enterobacteriaceae, 6 of 9 Pseudomonas aeruginosa, and 1 of 2 anaerobes. Peak plasma ceftriaxone levels on day 1 were 152 micrograms/ml by bioassay and 78 micrograms/ml by high-pressure liquid chromatography. Four of the 31 initial isolates of aerobic gram-negative rods developed resistance to ceftriaxone on disk diffusion testing. Diarrhea occurred in 3 of 50 patients. All three had received a higher than usual dose. Drug administration was stopped twice, once for a thrombocytopenia and once for a thrombocytopenia with leukopenia. Neither problem could be attributed exclusively to ceftriaxone. Other adverse reactions were eosinophilia, abdominal pain, inguinal candidiasis, and nonsuppurative phlebitis. Even among debilitated adults, ceftriaxone was safe and effective in a twice daily regimen.
The Relationship between Childhood Obesity, Low Socioeconomic Status, and Race/Ethnicity: Lessons from Massachusetts.

BACKGROUND Previous studies have shown race/ethnicity, particularly African American and/or Hispanic status, to be a predictor of overweight/obese status in children. However, these studies have failed to adjust for low socioeconomic status (SES). This study assessed whether race/ethnicity remained an independent predictor of childhood obesity when accounting for variations in SES (low-income) among communities in Massachusetts. METHODS This study was based on 2009 summarized data from 68 Massachusetts school districts with 111,799 students in grades 1, 4, 7, and 10. We studied the relationship between the rate of overweight/obese students (mean = 0.32; range = 0.10-0.46), the rate of African American and Hispanic students (mean = 0.17; range = 0.00-0.90), and the rate of low-income students (mean = 0.27; range = 0.02-0.87) in two and three dimensions. The main effect of the race/ethnicity rate, the low-income rate, and their interaction on the overweight and obese rate was investigated by multiple regression modeling. RESULTS Low-income was highly associated with overweight/obese status (p < 0.0001), whereas the effect of race/ethnicity (p = 0.27) and its interaction (p = 0.23) with low-income were not statistically significant. For every 1% increase in low-income, there was a 1.17% increase in overweight/obese status. This pattern was observed across all African American and Hispanic rates in the communities studied. CONCLUSIONS Overweight/obese status was highly prevalent among Massachusetts students, varying from 10% to 46% across communities. Although there were higher rates of overweight/obese status among African American and Hispanic students, the relationship disappeared when controlling for family income. Our findings suggest low SES plays a more significant role in the nation's childhood obesity epidemic than race/ethnicity.
Gastrointestinal stromal tumor: Computed tomographic features.

AIM Gastrointestinal stromal tumor (GIST) is a rare type of cancer. Computed tomography (CT) is an imaging modality of choice for diagnosing GIST. The aim of this retrospective study was to review the CT imaging features of 17 GIST patients. METHODS From 1995 to 2003, there were 47 patients with pathologically proven GISTs at our hospital. Of these, 17 patients underwent preoperative CT. We collected and analyzed these CT images. The CT imaging features included tumor diameter, number and location, tumor margin, location of metastasis, hounsfield units of tumor and effect of contrasts. In addition, we also recorded the surgical findings, including complications, tumor size and location for comparative analysis. RESULTS The results showed that 12 (70%) tumors were located in the stomach and five (30%) were located in the jejunum mesentery. GISTs were extraluminal in 12 (70%) patients. The tumor margins of 13 (76%) tumors were well defined and irregular in four (24%). The effect of contrast enhancement on GIST CT imaging was homogenous enhancement in 13 (76%) and heterogeneous enhancement in four (24%). The hounsfield units (HU) were 30.41 +/-5.01 for precontrast images and postcontrast hounsfield units were 51.80 +/- 9.24. CONCLUSION The stomach was the commonest site of GIST occurrence among our patients. The CT features of GIST were well-defined tumor margins, homogenous enhancement on postcontrast CT images.
Pharmacological characterization of morphine-6 beta-glucuronide, a very potent morphine metabolite.

Morphine-6 beta-glucuronide is a major metabolite of morphine with potent analgesic actions. To define more fully the importance of this compound in morphine action, we have compared the analgesic actions of morphine and its 6 beta-glucuronide metabolite after both peripheral and central administration. Given s.c. , morphine-6 beta-glucuronide elicited analgesia with an effect approximately twice that of morphine due, in part, to its long duration of action and also inhibited gastrointestinal motility. Both actions were easily reversed by naloxone (s.c.). However, when injected either i.c. v. or intrathecally, morphine-6 beta-glucuronide was approximately 90- and 650-fold more potent an analgesic than morphine, respectively. Whereas morphine in these studies was equipotent at both levels of the neuraxis as an analgesic, the 6 beta-glucuronide was approximately 5-fold more effective at the level of the spinal cord than supraspinally. The mu 1-selective antagonist naloxonazine blocked the analgesic effect of systemic and i.c. v. morphine-6 beta-glucuronide much as it blocked morphine, implying a role for mu1 receptors in these actions. Like morphine, morphine-6 beta-glucuronide analgesia after intrathecal injection was not sensitive to naloxonazine, suggesting a mu2 mechanism within the spinal cord. Together, these results imply that morphine-6 beta-glucuronide elicited its analgesic actions through the same receptor mechanisms as morphine. Mice highly tolerant to morphine after implantation of morphine pellets showed cross-tolerance to morphine-6 beta-glucuronide (s.c.). The high potency of morphine-6 beta-glucuronide strongly suggests that this metabolite plays an important role in morphine's actions.