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The state-sanctioned Shanghai International Film Festival (SIFF) is the only film festival accredited by the Fédération Internationale des Associations de Producteurs de Films (FIAPF) in the Greater China region. This paper intends to explore the perceived paradoxes of the SIFF by approaching its vaguely defined vision of “being international/internationalization” (or guojihua). The vision of guojihua has, at best, fuelled the persistent efforts of the SIFF to emulate the globally standardized festival framework and redirect the global capital flow into its newly installed film market. On the other hand, the SIFF has been reluctant to use one of its most precious cultural legacies – the cosmopolitanism of the Republican era – as a branding resource. The main argument is that the weakened connection between the SIFF and its locality/cultural memory is not only a result of the superficial understanding of guojihua, but also of the fact that the central and the local government often hold conflicting ideas regarding the social engineering of Shanghai’s image. [ABSTRACT FROM AUTHOR]

Background. Elevated concentrations of cardiac biomarkers, such as troponins and natriuretic peptides, have been shown to be predictive of poorer long-term cardiovascular outcomes in stable patients with end-stage renal disease (ESRD). However, little is known about the relationship between elevated concentrations of these cardiac markers and underlying coronary artery pathology in these patients. The aim of the present study was to investigate associations between coronary artery calcification (CAC) and the concentrations of cardiac biomarkers in ESRD patients.Methods. We conducted a cross-sectional study of 38 asymptomatic patients (median age, 54 years; 26 males, 12 females; diabetic, 39%) who were undergoing chronic haemodialysis. In these patients, pre-dialysis circulating concentrations of cardiac troponin T (cTnT), cardiac troponin I (cTnI), creatine kinase-MB (CK-MB) and B-type natriuretic peptide (BNP) were measured. We quantified the level of CAC by multirow spiral computed tomography to obtain a CAC score. CAC scores =?400 were defined as being indicative of severe CAC.Results. Severe CAC was detected in 17 patients (45%). The degree of CAC severity was positively associated (P<0.05) with cTnT concentrations. Thus, 15% of patients had severe CAC in the lowest tertile of cTnT, 50% had severe CAC in the middle third, and 69% in the highest third. Similarly, the degree of severity of CAC was positively associated (P<0.01) with cTnI concentrations across concentration categories. In contrast, there was no association between the degree of CAC severity and the concentrations of either BNP or CK-MB. A logistic regression analysis revealed that elevated concentrations of cTnT (=?median vs

This paper describes a series of physically-based crystal plasticity finite element method (CPFEM) simulations of long-term creep and creep rupture of Grade 91 steel. It is Part 2 of a two part series of papers. Part 1 describes the simulation framework; this part focuses on specific simulations and on how the predicted long-term creep properties of Grade 91 compare to the assumptions used in current high temperature design practices. This work extends the model developed in Part 1 to look at creep properties at different temperatures, principal stresses, and multiaxial stress states. The simulations show that empirically extrapolating creep rupture stresses from short-term experimental data may substantially over predict the actual long-term creep properties of Grade 91. Additionally, the CPFEM calculations predict a transition from notch strengthening creep behavior for high values of maximum principal stress and moderate notch severity to notch weakening behavior for low principal stresses and more severe notches. The latter regime better categorizes conditions in engineering components designed for long term elevated temperature use, which implies Grade 91 may be a notch weakening material in actual service. This would have a significant impact on high temperature design practices, though confirmatory test data on long-life, low stress notched specimens is difficult to obtain. Finally, one advantage of the physically-based modeling approach adopted here is that the simulation results also elucidate the microstructural mechanisms causing the macroscopic trends in engineering properties predicted by the simulations. This paper shows that the detailed micromechanical mechanisms predicted by the CPFEM simulations can be abstracted with a simple micromechanical model that can be used to both explain the detailed results and make improved predictions of engineering properties from experimental data. [ABSTRACT FROM AUTHOR]

This paper presents a physically-based microstructural model for creep rupture at 600 °C for Grade 91 steel. The model includes constitutive equations that reflect various observed phenomena in Grade 91, and it is incorporated into a mesoscale finite element model with explicit geometry for the prior austenite grains and grain boundaries. Creep within the grains is represented using crystal plasticity for dislocation motion and recovery along with linear viscous diffusional creep for point defect diffusion. The grain boundary models include physics-based models for cavity growth and nucleation that accurately capture tertiary creep and creep rupture. Simulations of creep at 100 MPa are performed, and the contribution of each mechanism is analyzed. The overarching goal is to gain a mechanistic understanding of the material to improve the prediction of creep rupture for long service lives in elevated temperature operating conditions. The creep response of the material at different stress levels, stress states, and temperatures is studied in Part 2 of this paper in order to determine the implications of the simulations on high temperature design practice. Furthermore, the second part explores the effect of triaxial stress states on the creep response and finds a transition from notch-strengthening behavior at high stress to notch-weakening behavior at lower stresses. [ABSTRACT FROM AUTHOR]

Background: Over 30 million people in the United States (over 9%) have been diagnosed with diabetes. About 25% of people with diabetes will experience a diabetic foot ulcer (DFU) in their lifetime. Unresolved DFUs may lead to sepsis and are the leading cause of lower-limb amputations. DFU rates can be reduced by screening patients with diabetes to enable risk-based interventions. Skin temperature assessment has been shown to reduce the risk of foot ulceration. While several tools have been developed to measure plantar temperatures, they only measure temperature once a day or are designed for clinic use only. In this report, wireless sensor-embedded socks designed for daily wear are introduced, which perform continuous temperature monitoring of the feet of persons with diabetes in the home environment. Combined with a mobile app, this wearable device informs the wearer about temperature increases in one foot relative to the other, to facilitate early detection of ulcers and timely intervention.Objective: A pilot study was conducted to assess the accuracy of sensors used in daily wear socks, obtain user feedback on how comfortable sensor-embedded socks were for home use, and examine whether observed temperatures correlated with clinical observations.Methods: Temperature accuracy of sensors was assessed both prior to incorporation in the socks, as well as in the completed design. The measured temperatures were compared to the reference standard, a high-precision thermostatic water bath in the range 20°C-40°C. A total of 35 patients, 18 years of age and older, with diabetic peripheral neuropathy were enrolled in a single-site study conducted under an Institutional Review Board-approved protocol. This study evaluated the usability of the sensor-embedded socks and correlated the observed temperatures with clinical findings.Results: The temperatures measured by the stand-alone sensors were within 0.2°C of the reference standard. In the sensor-embedded socks, across multiple measurements for each of the six sensors, a high agreement (R2=1) between temperatures measured and the reference standard was observed. Patients reported that the socks were easy to use and comfortable, ranking them at a median score of 9 or 10 for comfort and ease of use on a 10-point scale. Case studies are presented showing that the temperature differences observed between the feet were consistent with clinical observations.Conclusions: We report the first use of wireless continuous temperature monitoring for daily wear and home use in patients with diabetes and neuropathy. The wearers found the socks to be no different from standard socks. The temperature studies conducted show that the sensors used in the socks are reliable and accurate at detecting temperature and the findings matched clinical observations. Continuous temperature monitoring is a promising approach as an early warning system for foot ulcers, Charcot foot, and reulceration. [ABSTRACT FROM AUTHOR]

The laser-induced plume is an essential physical phenomenon during high power fiber laser welding. Its physical nature can be investigated by diagnosing its temperature. In order to overcome the lack of sufficient line spectra in the temperature diagnosis, the continuous spectrum method (based on the continuous spectrum and Wien’s displacement law) is thus developed in this research. The optical spectra emitted by the plume or plasma were detected by using a SP-2500i spectrometer during bead-on-plate welding with an IPG YLS-6000 fiber laser or fiber laser-arc hybrid. The rationality of the continuous spectrum method was evaluated by comparing the plasma temperatures diagnosed by applying the continuous spectrum and line spectra. The results reveal that the continuous spectrum method used in temperature diagnosis is rational. When the line spectra cannot be detected due to an increase in detected height, the plume temperature can be still obtained by using the continuous spectrum method. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a complex disease comprising multiple distinct subtypes with different genetic features and pathological characteristics. Although a large number of antineoplastic compounds have been approved for clinical use, patient-to-patient variability in drug response is frequently observed, highlighting the need for efficient treatment prediction for individualized therapy. Several patient-derived models have been established lately for the prediction of drug response. However, each of these models has its limitations that impede their clinical application. Here, we report that the whole-tumor cell culture (WTC) ex vivo model could be stably established from all breast tumors with a high success rate (98 out of 116), and it could reassemble the parental tumors with the endogenous microenvironment. We observed strong clinical associations and predictive values from the investigation of a broad range of BC therapies with WTCs derived from a patient cohort. The accuracy was further supported by the correlation between WTC-based test results and patients' clinical responses in a separate validation study, where the neoadjuvant treatment regimens of 15 BC patients were mimicked. Collectively, the WTC model allows us to accomplish personalized drug testing within 10 d, even for small-sized tumors, highlighting its potential for individualized BC therapy. Furthermore, coupled with genomic and transcriptomic analyses, WTC-based testing can also help to stratify specific patient groups for assignment into appropriate clinical trials, as well as validate potential biomarkers during drug development. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome characterized by high blood pressure and vascular remodeling in the pulmonary arterioles, which is also a rapidly progressing disease of the lung vasculature with a poor prognosis. Although PAH medication made great advances in recent years, the efficacy and safety of the medication are unsatisfactory. Therefore, we aimed to update and expand previous studies to explore the efficacy and safety of PAH-targeted medications. Methods: Relevant articles were searched and selected from published or publicly available data in PubMed, Cochrane Library, CNKI, PsycInfo, and MEDLINE (from inception until October 1st, 2020). To assess the efficacy and safety of PAH therapies, five efficacy outcomes [6-minute walking distance (6MWD), mean pulmonary arterial pressure (mPAP), WHO functional class (WHO FC) improvement, clinical worsening, death] and two safety outcomes [adverse events (AEs), serious adverse events (SAEs)] were selected. And 6MWD was regarded as the primary efficacy outcome. Results: 50 trials included with 10 996participants were selected. In terms of efficacy, all targeted drugs were more effective than placebo. For 6MWD, BosentanþSildenafil, Sildenafil, BosentanþIloprost were better than others. BosentanþIloprost and BosentanþSildenafil were better for mPAP. BosentanþIloprost and AmbrisentanþTadalafil were more effective in improving WHO FC. BosentanþTadalafil and BosentanþIloprost had the Ambrisentan probability to reduce the incidence of clinical worsening. It is demonstrated that Ambrisentan had clear benefits in reducing all-cause mortality. In terms of safety, no therapies had been shown to reduce the incidence of SAEs significantly, and AmbrisentanþTadalafil significantly increased the incidence of AEs. Conclusions: Phosphodiesterase 5 inhibitor (PDE5i) þ Endothelin Receptor Antagonists (ERA) seems to be better therapy for PAH. Prostacyclin analogs (ProsA) þ ERA appear promising, though additional data is warranted. [ABSTRACT FROM AUTHOR]

Rationale: Quantitatively relating 13C/12C, 2H/1H and 18O/16O ratios of plant α- cellulose and 2H/1H of n-alkanes to environmental conditions and metabolic status should ideally be based on the leaf, the plant organ most sensitive to environmental change. The fact that leaf organic matter is composed of isotopically different heterotrophic and autotrophic components means that it is imperative that one be able to disentangle the relative heterotrophic and autotrophic contributions to leaf organic matter. Methods: We tackled this issue by two-dimensional sampling of leaf water and α- cellulose, and specific n-alkanes from greenhouse-grown immature and mature and field-grown mature banana leaves, taking advantage of their large areas and thick waxy layers. Leaf water, α-cellulose and n-alkane isotope ratios were then characterized using elemental analysis isotope ratio mass spectrometry (IRMS) or gas chromatography IRMS. A three-member (heterotrophy, autotrophy and photoheterotrophy) conceptual linear mixing model was then proposed for disentangling the relative contributions of the three trophic modes. Results: We discovered distinct spatial leaf water, α-cellulose and n-alkane isotope ratio patterns that varied with leaf developmental stages. We inferred from the conceptual model that, averaged over the leaf blade, only 20% of α-cellulose in banana leaf is autotrophically laid down in both greenhouse-grown and field-grown banana leaves, while approximately 60% and 100% of n-alkanes are produced autotrophically in greenhouse-grown and field-grown banana leaves, respectively. There exist distinct lateral (edge to midrib) gradients in autotrophic contributions of α-cellulose and n-alkanes. Conclusions: Efforts to establish quantitative isotope-environment relationships should take into account the fact that the evaporative leaf water 18O and 2H enrichment signal recorded in autotrophically laid down α-cellulose is significantly diluted by the heterotrophically formed α-cellulose. The δ2H value of field-grown mature banana leaf n-alkanes is much more sensitive than α-cellulose as a recorder of the growth environment. Quantitative isotope-environment relationship based on greenhouse-grown n-alkane δ2H values may not be reliable. [ABSTRACT FROM AUTHOR]

Rationale: Although the ²H/¹H ratio of the carbon-bound hydrogens (C-Hs) in α-cellulose extracted from higher plants has long been used successfully for climate, environmental and metabolic studies, the assumption that bleaching with acidified NaClO2 to remove lignin before pure α-cellulose can be obtained does not alter the ²H/¹H ratio of α-cellulose C-Hs has nonetheless not been tested. Methods: For reliable application of the ²H/¹H ratio of α-cellulose C-H, we processed plant materials representing different phytochemistries and photosynthetic carbon assimilation modes in isotopically contrasting bleaching media (with an isotopic difference of 273 mUr). All the isotope ratios were measured by elemental analyzer/isotope ratio mass spectrometry (EA/IRMS). Results: Our results show that H from the bleaching medium does appear in the final pure α-cellulose product, although the isotopic alteration to the C-H in α-cellulose due to the incorporation of processing H from the medium is small if isotopically “natural” water is used to prepare the processing medium. However, under prolonged bleaching such an isotope effect can be significant, implying that standardizing the bleaching process is necessary for reliable ²H/¹H measurement. Conclusions: The currently adopted method for removing lignin for α-cellulose extraction from higher plant materials with acidified NaClO2 bleaching is considered acceptable in terms of preserving the isotopic fidelity if isotopically “natural” water is used to prepare the bleaching solution. [ABSTRACT FROM AUTHOR]

High levels of ecto-5'-nucleotidase (CD73) have been implicated in immune suppression and tumor progression, and have also been observed in cancer patients who progress on anti-PD-1 immunotherapy. Although regulatory T cells can express CD73 and inhibit T cell responses via the production of adenosine, less is known about CD73 expression in other immune cell populations. We found that tumor-infiltrating NK cells upregulate CD73 expression and the frequency of these CD73-positive NK cells correlated with larger tumor size in breast cancer patients. In addition, the expression of multiple alternative immune checkpoint receptors including LAG-3, VISTA, PD-1, and PD-L1 was significantly higher in CD73-positive NK cells than in CD73-negative NK cells. Mechanistically, NK cells transport CD73 in intracellular vesicles to the cell surface and the extracellular space via actin polymerization-dependent exocytosis upon engagement of 4-1BBL on tumor cells. These CD73-positive NK cells undergo transcriptional reprogramming and upregulate IL-10 production via STAT3 transcriptional activity, suppressing CD4-positive T cell proliferation and IFN-γ production. Taken together, our results support the notion that tumors can hijack NK cells as a means to escape immunity and that CD73 expression defines an inducible population of NK cells with immunoregulatory properties within the tumor microenvironment. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the expression profile of CYGB, its potential neuroprotective function, and underlying molecular mechanisms using a model of neonatal hypoxia-ischemia (HI) brain injury. Cygb mRNA and protein expression were evaluated within the first 36 h after the HI model was induced using RT-PCR and Western blotting. Cygb mRNA expression was increased at 18 h in a time-dependent manner, and its level of protein expression increased progressively in 24 h. To verify the neuroprotective effect of CYGB, a gene transfection technique was employed. Cygb cDNA and shRNA delivery adenovirus systems were established (Cygb-cDNA-ADV and Cygb-shRNA-ADV, respectively) and injected into the brains of 3-day-old rats 4 days before they were induced with HI treatment. Rats from different groups were euthanized 24 h post-HI, and brain samples were harvested. 2,3,5-Triphenyltetrazolium chloride, TUNEL, and Nissl staining indicated that an up-regulation of CYGB resulted in reduced acute brain injury. The superoxide dismutase level was found to be dependent on expression of CYGB. The Morris water maze test in 28-day-old rats demonstrated that CYGB expression was associated with improvement of long term cognitive impairment. Studies also demonstrated that CYGB can up-regulate mRNA and protein levels of VEGF and increase both the density and diameter of the microvessels but inhibits activation of caspase-2 and -3. Thus, this is the first in vivo study focusing on the neuroprotective role of CYGB. The reduction of neonatal HI injury by CYGB may be due in part to antioxidant and antiapoptotic mechanisms and by promoting angiogenesis. [ABSTRACT FROM AUTHOR]

Apolipoprotein (apo) E4, a 299-aa protein and a major risk factor for Alzheimer's disease, can be cleaved to generate C-terminal-truncated fragments that cause neurotoxicity in vitro and neurodegeneration and behavioral deficits in transgenic mice. To investigate this neurotoxicity, we expressed apoE4 with C- or N-terminal truncations or mutations in transfected Neuro-2a cells. ApoE4 (1-272) was neurotoxic, but full-length apoE4(1-299) and apoE4(1-240) were not, suggesting that the lipid-binding region (amino acids 241-272) mediates the neurotoxicity and that amino acids 273-299 are protective. A quadruple mutation in the lipid-binding region (I250A, F257A, W264R, and V269A) abolished the neurotoxicity of apoE4(1-272), and single mutations in the region of amino acids 273-299 (L279Q, K282A, or Q284A) made full-length apoE4 neurotoxic. Immunofluorescence staining showed that apoE4(1-272) formed filamentous inclusions containing phosphorylated tau in some cells and interacted with mitochondria in others, leading to mitochondrial dysfunction as determined by MitoTracker staining and flow cytometry. ApoE4(241-272) did not cause mitochondrial dysfunction or neurotoxicity, suggesting that the lipid-binding region alone is insufficient for neurotoxicity. Truncation of N-terminal sequences (amino acids 1-170) containing the receptor-binding region (amino acids 135-150) and triple mutations within that region (R142A, K146A, and R147A) abolished the mitochondrial interaction and neurotoxicity of apoE4(1-272). Further analysis showed that the receptor-binding region is required for escape from the secretory pathway and that the lipid-binding region mediates mitochondrial interaction. Thus, the lipid- and receptor-binding regions in apoE4 fragments act together to cause mitochondrial dysfunction and neurotoxicity, which may be important in Alzheimer's disease pathogenesis.

Background: Exercise-induced dyspnea is a frequent feature in patients with hyperthyroidism., Hypothesis: Data from clinical studies to elucidate the origin of this symptom are lacking. In the current study, we examined the hemodynamic and oxygenation responses to exercise and beta-adrenergic blockade in patients with hyperthyroidism and their relationship with dyspnea., Methods: Hemodynamic studies were performed under resting conditions and after isotonic exercise in 15 patients with hyperthyroidism and 11 control subjects. Exercise was applied using a bicycle ergometer, with progressive loads. In the hyperthyroid group, measurements were repeated at rest and during supine exercise after administering 15 mg of intravenous metoprolol., Results: End-diastolic pulmonary artery pressure and cardiac index were higher in the hyperthyroid group than in controls (18.6 +/- 5.3 vs. 11.2 +/- 4.9 mmHg; p = 0.02, and 6.0 +/- 1.7 vs. 2.8 +/- 0.5 l/min/m2; p = 0.0001, respectively). After exercise, there was an increase in end-diastolic pulmonary artery pressure in the hyperthyroid group (18.6 +/- 5.3 to 25.5 +/- 9.9 mmHg; p = 0.02), revealing impaired cardiocirculatory reserve. Pulmonary arteriolar resistance increased significantly in parallel with end-diastolic pulmonary artery pressure after drug administration, suggesting an inadequate cardiovascular response after beta blockade in patients with hyperthyroidism., Conclusion: We observed that functional left ventricular reserve is impaired in patients with hyperthyroidism, suggesting an explanation for the frequent symptom of dyspnea and impaired exercise tolerance. Moreover, we also suggest that beta-adrenergic blockade may adversely affect cardiovascular function in patients with hyperthyroidism.