Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental Evidence of Phosphoenolpyruvate Resynthesis from Pyruvate in Illuminated Leaves1[W]

Day respiration is the cornerstone of nitrogen assimilation since it provides carbon skeletons to primary metabolism for glutamate (Glu) and glutamine synthesis. However, recent studies have suggested that the tricarboxylic acid pathway is rate limiting and mitochondrial pyruvate dehydrogenation is partly inhibited in the light. Pyruvate may serve as a carbon source for amino acid (e.g. alanine) or fatty acid synthesis, but pyruvate metabolism is not well documented, and neither is the possible resynthesis of phosphoenolpyruvate (PEP). Here, we examined the capacity of pyruvate to convert back to PEP using 13C and 2H labeling in illuminated cocklebur (Xanthium strumarium) leaves. We show that the intramolecular labeling pattern in Glu, 2-oxoglutarate, and malate after 13C-3-pyruvate feeding was consistent with 13C redistribution from PEP via the PEP-carboxylase reaction. Furthermore, the deuterium loss in Glu after 2H3-13C-3-pyruvate feeding suggests that conversion to PEP and back to pyruvate washed out 2H atoms to the solvent. Our results demonstrate that in cocklebur leaves, PEP resynthesis occurred as a flux from pyruvate, approximately 0.5‰ of the net CO2 assimilation rate. This is likely to involve pyruvate inorganic phosphate dikinase and the fundamental importance of this flux for PEP and inorganic phosphate homeostasis is discussed.
Antarctic Bottom Water Variability in a Coupled Climate Model

Abstract The natural variability of the Weddell Sea variety of Antarctic Bottom Water (AABW) is examined in a long-term integration of a coupled climate model. Examination of passive tracer concentrations suggests that the model AABW is predominantly sourced in the Weddell Sea. The maximum rate of the Atlantic sector Antarctic overturning (ψatl) is shown to effectively represent the outflow of Weddell Sea deep and bottom waters and the compensating inflow of Warm Deep Water (WDW). The variability of ψatl is found to be driven by surface density variability, which is in turn controlled by sea surface salinity (SSS). This suggests that SSS is a better proxy than SST for post-Holocene paleoclimate reconstructions of the AABW overturning rate. Heat–salt budget and composite analyses reveal that during years of high Weddell Sea salinity, there is an increased removal of summertime sea ice by enhanced wind-driven ice drift, resulting in increased solar radiation absorbed into the ocean. The larger ice-free regi.
Study on the Relationship between Knowledge Acquisition and Enterprise Performance: The Mediating Effect of Technological Capability

With the arrival of knowledge economy era, knowledge has become an important basis for improving enterprise performance and obtaining competitive advantage. Through knowledge acquisition, enterprises can promote their technological capability and further improve their performance effectively. This paper aims to find out the relationships among knowledge acquisition, technological capability and enterprise performance. Firstly, related literature is reviewed and the relationships among knowledge acquisition, technological capability and enterprise performance are analyzed theoretically. And we believe that knowledge acquisition has a positive effect on technological capability and enterprise performance, and technological capability has a mediating effect on the relationship between knowledge acquisition and enterprise performance. And then, the paper, applying data from the survey of 151 enterprises, conducts an empirical study to prove our ideas. And the results indicate that knowledge acquisition can affect enterprise performance directly and through the mediating effect of technological capability.
Effect of the callipyge phenotype and cooking method on tenderness of several major lamb muscles.

We conducted three experiments to determine the effects of the callipyge phenotype on the tenderness of several major lamb muscles and to determine the effect of method of cookery on the tenderness of callipyge lamb at 7 d postmortem. In Exp. 1, chops from normal (n = 23) and callipyge (n = 16) carcasses were open-hearth-broiled. Warner-Bratzler shear force values of longissimus, gluteus medius, semimembranosus, biceps femoris, semitendinosus, adductor, and quadriceps femoris were 123, 44, 28, 26, 19, 16, and 13% greater, respectively, for callipyge (P < .05). In Exp. 2, muscles from normal (n = 18) and callipyge (n = 18) carcasses were oven-roasted. Shear force of triceps brachii was 11% greater for callipyge (P < .001); however, phenotype did not affect shear force of supraspinatus (P = .87) or psoas major (P = .64). In Exp. 3, a trained sensory panel evaluated leg roasts and open-hearth-broiled leg chops from normal (n = 60) and callipyge lamb carcasses (n = 60). Callipyge chops were less tender than normal chops (P < .05). Regardless of callipyge phenotype, muscles were more (P < .05) tender when roasted; however, the effect of method of cookery on tenderness scores was greater for callipyge muscles than for normal muscles. Callipyge roasts and normal roasts had similar tenderness (P = .58), and callipyge roasts were more tender than normal chops (P < .05). Regardless of cooking method, callipyge samples were less juicy than normal samples (P < .05). These data demonstrate that the callipyge phenotype will likely reduce consumer satisfaction due to reduced tenderness and juiciness; however, reduced tenderness in callipyge leg muscles could be prevented by ovenroasting.
The panic-agoraphobic spectrum: a descriptive approach to the assessment and treatment of subtle symptoms.

OBJECTIVE Psychiatric classification is still a topic of considerable discussion and debate in spite of major advances in the past two decades. The debate involves categorical versus dimensional approaches, cutoff numbers of symptoms to define a case, degree of impairment, objective diagnostic criteria versus more theoretically based criteria, episodic versus trait-like symptoms, and the role of atypical and subclinical symptoms. All of these issues have been raised for the anxiety disorders and depression. This article presents the conceptualization of a relatively novel and testable approach to the diagnosis and classification of panic and agoraphobia, the panic-agoraphobic spectrum, and pilot data on a new questionnaire to assess it. METHOD Pilot testing of the Panic-Agoraphobic Spectrum Questionnaire was undertaken with 100 inpatients who had lifetime diagnoses of panic disorder, unipolar depression, comorbid panic and unipolar depressive disorders, or an eating disorder. The instrument emphasizes impairment related to 144 behaviors and experiences in seven panic-agoraphobic symptom domains. RESULTS Patients with panic disorder scored highest on the questionnaire, and those with comorbid depression showed even greater severity of illness. The scores of the patients with eating disorders and of the depressed patients differed from those of the other groups but also differed from 0. CONCLUSIONS The spectrum model of panic and agoraphobia is a flexible and comprehensive means of describing this clinical complex. The proposed model, complementary to the categorical approach, presumably expresses a unitary pathophysiology. Its usefulness is discussed in terms of its value for patient-therapist communication, outcome measures, identification of subtle personality traits, and subtyping of patients for research and treatment.
PUVA photocarcinogenesis in Cheshire

SIR, I ligh total do.ses of PUVA are a well-established risk faetor for the (Jevelopment of cutaneous squamous cell carcinoma, though the risk of basal cell carcinoma is not necessarily increased.' *" In 1995 we also undertook a retrospective study on the incidence of cutaneous carcinomas in psoriatic patients (mainly skin type II) undergoing PUVA therapy in our District Genera! Hospital. \\\ a\ailablc PUVA patient treatment records on 178 subjects, for 1978 to 1995, were examined, from which 150 hospital case notes ucrt available. The PUVA regimen started at a dose of l -3J/cm" twice a week and increased by 0 5J/cm at each attendance to the limit of skin tolerance, usually 5-6J/cm^ (maximum lOJ/cm ). On skin clearance, the frequency of treatment was reduced, to zero where possible. All patients were given 8-methoxypsoraIen in a dose of O'5-O 6 mg/kg 2 h before irradiation with an F85/1OO\V lamp (spectral range 310410 nm).
Elimination of symbiotic Aeromonas spp. from the intestinal tract of the medicinal leech, Hirudo medicinalis, using ciprofloxacin feeding.

The use of the medicinal leech (Hirudo medicinalis) in promoting venous drainage in tissues whose vitality is threatened by venous congestion and obstruction, especially in plastic and reconstructive surgery, has been complicated by infections caused by Aeromonas spp. These are leech endosymbionts for which patients undergoing hirudotherapy frequently receive systemic chemoprophylaxis. In order to evaluate the possibility of rendering leeches safe for use on patients, H. medicinalis were fed artificially with a 2 g/L arginine solution (used as a phagostimulant) supplemented with ciprofloxacin (100 mg/L). Aeromonads were detected in 57 out of 80 control leeches (71.3%), but in none of the 56 leeches treated with ciprofloxacin (p <0.001). Treated leeches survived for up to 4 months. Tested weekly, 61% of these leeches took human blood for at least 4 weeks after treatment and all remained negative for aeromonads. All water samples in which leeches were kept before treatment were contaminated with Aeromonas spp. ; none were detected in any of the NaCl/arginine solutions with which treated animals were fed. Molecular characterization of two phenotypically distinct isolates using gyrB sequencing showed that one clustered tightly with A. veronii and the other was closely related to A. media. Other environmental bacteria and fungi were isolated from 26.5% of treated leeches that had taken a blood meal 1-4 weeks after treatment. Ciprofloxacin reduced the number of leech-associated aeromonads to undetectable levels for extended periods. Most treated leeches were ready to take a blood meal after treatment, suggesting the possibility of using ciprofloxacin-treated leeches instead of chemoprophylaxis in patients undergoing hirudotherapy.
Predictive value of different proportion of lesion HLA-G expression in colorectal cancer

Differential expression of HLA-G has been observed among cancer types and tumors from individuals with the same type of cancer; however, its clinical significance is rather limited. In this study, expression and predictive relevance of HLA-G expression in 457 primary colorectal cancer (CRC, ncolon = 232, nrectal = 225) patients was investigated. Data showed 70.7% (323/457) of the CRC were HLA-G expression when the above 5% (HLA-GLow) was considered as positive, which wasn't associated with patient survival (p = 0.109). However, HLA-G expression above 55% (HLA-GHigh) was associated with a worse prognosis of CRC patients (p = 0.042). Furthermore, a shorter survival was found for the female (p = 0.042) and elder (p = 0.037) patients whose HLA-G expression was above HLA-GLow level. HLA-G expression above HLA-GHigh level showed a worse prognosis for female (p = 0.013), elder (p = 0.023), colon cancer (p = 0.016), advanced tumor burden (T3+4, p = 0.018), regional lymph node status (N1+2, p = 0.044), and advanced clinical stage patients (AJCC III+IV, p = 0.037). In conclusion, our results demonstrated for the first time that combination of differential lesion HLA-G expression notably improved the value of traditional survival prediction for CRC patients.
The Small Molecules AZD0530 and Dasatinib Inhibit Dengue Virus RNA Replication via Fyn Kinase

ABSTRACT In this study, we characterized the antiviral mechanism of action of AZD0530 and dasatinib, two pharmacological inhibitors of host kinases, that also inhibit dengue virus (DV) infection. Using Northern blot and reporter replicon assays, we demonstrated that both small molecules inhibit the DV2 infectious cycle at the step of steady-state RNA replication. In order to identify the cellular target of AZD0530 and dasatinib mediating this anti-DV2 activity, we examined the effects of RNA interference (RNAi)-mediated depletion of the major kinases known to be inhibited by these small molecules. We determined that Fyn kinase, a target of both AZD0530 and dasatinib, is involved in DV2 RNA replication and is probably a major mediator of the anti-DV activity of these compounds. Furthermore, serial passaging of DV2 in the presence of dasatinib led to the identification of a mutation in the transmembrane domain 3 of the NS4B protein that overcomes the inhibition of RNA replication by AZD0530, dasatinib, and Fyn RNAi. Although we observed that dasatinib also inhibits DV2 particle assembly and/or secretion, this activity does not appear to be mediated by Src-family kinases. Together, our results suggest that AZD0530 and dasatinib inhibit DV at the step of viral RNA replication and demonstrate a critical role for Fyn kinase in this viral process. The antiviral activity of these compounds in vitro makes them useful pharmacological tools to validate Fyn or other host kinases as anti-DV targets in vivo.
A Phase I Clinical Trial and Independent Patient-Derived Xenograft Study of Combined Targeted Treatment with Dacomitinib and Figitumumab in Advanced Solid Tumors

Purpose: This phase I, open-label, single-arm trial assessed the safety and tolerability of dacomitinib–figitumumab combination therapy in patients with advanced solid tumors. Experimental Design: A standard 3 + 3 dose escalation/de-escalation design was utilized. Starting doses were figitumumab 20 mg/kg administered intravenously once every 3 weeks and dacomitinib 30 mg administered orally once daily. We also performed an independent study of the combination in patient-derived xenograft (avatar mouse) models of adenoid cystic carcinoma. Results: Of the 74 patients enrolled, the most common malignancies were non–small cell lung cancer (24.3%) and colorectal cancer (14.9%). The most common treatment-related adverse events in the 71 patients who received treatment across five dose levels were diarrhea (59.2%), mucosal inflammation (47.9%), and fatigue and acneiform dermatitis (45.1% each). The most common dose-limiting toxicity was mucosal inflammation. Dosing schedules of dacomitinib 10 or 15 mg daily plus figitumumab 20 mg/kg every 3 weeks after a figitumumab loading dose were tolerated by patients over multiple cycles and considered recommended doses for further evaluation. Objective responses were seen in patients with adenoid cystic carcinoma, ovarian carcinoma, and salivary gland cancer. Pharmacokinetic analysis did not show any significant drug−drug interaction. In the adenoid cystic carcinoma xenograft model, figitumumab exerted significant antitumor activity, whereas dacomitinib did not. Figitumumab-sensitive tumors showed downregulation of genes in the insulin-like growth factor receptor 1 pathway. Conclusions: Dacomitinib−figitumumab combination therapy was tolerable with significant dose reductions of both agents to less than the recommended single-agent phase II dose of each drug. Preliminary clinical activity was demonstrated in the potential target tumor adenoid cystic carcinoma. Clin Cancer Res; 23(5); 1177–85. ©2016 AACR. See related commentary by Sundar et al., p. 1123
Human cytomegalovirus infection in tumor cells of the nervous system is not detectable with standardized pathologico-virological diagnostics.

BACKGROUND Experimental findings have suggested that human cytomegalovirus (HCMV) infection of tumor cells may exert oncomodulatory effects that enhance tumor malignancy. However, controversial findings have been published on the presence of HCMV in malignant tumors. Here, we present the first study that systematically investigates HCMV infection in human nervous system tumors by highly sensitive immunohistochemistry in correlation with the HCMV serostatus of the patients. METHODS Immunohistochemical and quantitative PCR-based methods to detect different HCMV antigens and genomic HCMV DNA were optimized prior to the investigation of pathological samples. Moreover, the pathological results were matched with the HCMV serostatus of the patients. RESULTS HCMV immediate-early, late, and pp65 antigens could be detected in single cells from HCMV strain Hi91-infected UKF-NB-4 neuroblastoma cells after 1:1024 dilution with noninfected UKF-NB-4 cells. Genomic HCMV DNA could be detected in copy numbers as low as 430 copies/mL. However, we did not detect HCMV in tumors from a cohort of 123 glioblastoma, medulloblastoma, or neuroblastoma patients. Notably, we detected nonspecifically positive staining in tumor tissues of HCMV seropositive and seronegative glioblastoma patients. The HCMV serostatus of 67 glioblastoma patients matched the general epidemiological prevalence data for Western countries (72% of female and 57% of male glioblastoma patients were HCMV seropositive). Median survival was not significantly different in HCMV seropositive versus seronegative glioblastoma patients. CONCLUSIONS The prevalence of HCMV-infected tumor cells may be much lower than previously reported based on highly sensitive detection methods.
A Study on the Effects of Loneliness, Depression and Perceived Social Support on Problematic Internet Use among University Students

Abstract The present study investigated the effects of loneliness, depression and perceived social support on problematic Internet use among university students. The participants were 459 students at two universities in Turkey. The study data were collected with a Questionnaire Form, Problematic Internet Use Scale (PIUS), University of California at Los Angeles (UCLA) Loneliness Scale (Version 3), Multidimensional Scale of Perceived Social Support (MSPSS) and Beck Depression Inventory (BDI). The Mann-Whitney U Test and Kruskal-Wallis one-way analysis of variance were conducted to examine the differences; and correlation and regression analyses were used to examine the relationships between variables. There was a positive significant correlation between the PIUS and MSPSS and the UCLA Loneliness Scale and a negative significant correlation between the PIUS and Beck Depression Scale (BDS). The female students had higher total PIUS scores. The results also illustrated that there was a statistically significant difference in total PIUS scores according to having a social network account.
Descent Directions of Quasi-Newton Methods for Symmetric Nonlinear Equations

In general, when a quasi-Newton method is applied to solve a system of nonlinear equations, the quasi-Newton direction is not necessarily a descent direction for the norm function. In this paper, we show that when applied to solve symmetric nonlinear equations, a quasi-Newton method with positive definite iterative matrices may generate descent directions for the norm function. On the basis of a Gauss--Newton based BFGS method [D. H. Li and M. Fukushima, SIAM J. Numer. Anal. , 37 (1999), pp. 152--172], we develop a norm descent BFGS method for solving symmetric nonlinear equations. Under mild conditions, we establish the global and superlinear convergence of the method. The proposed method shares some favorable properties of the BFGS method for solving unconstrained optimization problems: (a) the generated sequence of the quasi-Newton matrices is positive definite; (b) the generated sequence of iterates is norm descent; (c) a global convergence theorem is established without nonsingularity assumption on the Jacobian. Preliminary numerical results are reported, which positively support the method.
Vaccinia Mature Virus Fusion Regulator A26 Protein Binds to A16 and G9 Proteins of the Viral Entry Fusion Complex and Dissociates from Mature Virions at Low pH

ABSTRACT Vaccinia mature virus enters cells through either endocytosis or plasma membrane fusion, depending on virus strain and cell type. Our previous results showed that vaccinia virus mature virions containing viral A26 protein enter HeLa cells preferentially through endocytosis, whereas mature virions lacking A26 protein enter through plasma membrane fusion, leading us to propose that A26 acts as an acid-sensitive fusion suppressor for mature virus (S. J. Chang, Y. X. Chang, R. Izmailyan R, Y. L. Tang, and W. Chang, J. Virol. 84:8422–8432, 2010). In the present study, we investigated the fusion suppression mechanism of A26 protein. We found that A26 protein was coimmunoprecipitated with multiple components of the viral entry-fusion complex (EFC) in infected HeLa cells. Transient expression of viral EFC components in HeLa cells revealed that vaccinia virus A26 protein interacted directly with A16 and G9 but not with G3, L5 and H2 proteins of the EFC components. Consistently, a glutathione S-transferase (GST)-A26 fusion protein, but not GST, pulled down A16 and G9 proteins individually in vitro. Together, our results supported the idea that A26 protein binds to A16 and G9 protein at neutral pH contributing to suppression of vaccinia virus-triggered membrane fusion from without. Since vaccinia virus extracellular envelope proteins A56/K2 were recently shown to bind to the A16/G9 subcomplex to suppress virus-induced fusion from within, our results also highlight an evolutionary convergence in which vaccinia viral fusion suppressor proteins regulate membrane fusion by targeting the A16 and G9 components of the viral EFC complex. Finally, we provide evidence that acid (pH 4.7) treatment induced A26 protein and A26-A27 protein complexes of 70 kDa and 90 kDa to dissociate from mature virions, suggesting that the structure of A26 protein is acid sensitive.
A systematic review of sugammadex vs neostigmine for reversal of neuromuscular blockade

We reviewed systematically sugammadex vs neostigmine for reversing neuromuscular blockade. We included 17 randomised controlled trials with 1553 participants. Sugammadex reduced all signs of residual postoperative paralysis, relative risk (95% CI) 0.46 (0.29–0.71), p = 0.0004 and minor respiratory events, relative risk (95% CI) 0.51 (0.32–0.80), p = 0.0034. There was no difference in critical respiratory events, relative risk (95% CI) 0.13 (0.02–1.06), p = 0.06. Sugammadex reduced drug‐related side‐effects, relative risk (95% CI) 0.72 (0.54–0.95), p = 0.02. There was no difference in the rate of postoperative nausea or the rate of postoperative vomiting, relative risk (95% CI) 0.94 (0.79–1.13), p = 0.53, and 0.87 (0.65–1.17), p = 0.36 respectively.
Exercise stroke volume and heart rate response differ in right and left heart failure

In pulmonary arterial hypertension (PAH), the exercise‐induced increase in stroke volume (SV) is limited by the increase in pulmonary artery pressure. In left heart failure (LHF), systemic arterial pressure increases little during exercise, and the SV increase is limited by the left ventricle itself. These differences might be reflected by a dissimilar SV and heart rate (HR) response to exercise, which could have important therapeutic implications, for example in beta‐blocker therapy. Therefore, we tested the hypothesis that SV and HR responses during exercise are different between PAH and LHF patients.