Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidermal growth factor induces dose‐dependent calcium oscillations in single fura‐2–loaded Hepatocytes

Digital imaging fluorescence microscopy has been used to investigate epidermal growth factor–induced calcium responses of fura‐2–loaded hepatocytes in primary culture at the single‐cell level. Epidermal growth factor induced oscillations in cytosolic free calcium ([Ca2+]i) consisting of a periodic train of spikes unlike the monophasic elevation in cell suspensions reported previously. In this study, 79% of the cells in the microscopic field responded to 0.1 nmol/L epidermal growth factor, and 78% of the responsive cells displayed oscillations. However, the frequency of oscillations differed considerably from cell to cell. [Ca2+]i measurement in a cell population was simulated using these data, but only a slightly biphasic pattern was obtained, indicating the significance of single‐cell measurement of [Ca2+]i. Because considerable heterogeneity existed in the sensitivity to epidermal growth factor between the cells, single hepatocytes were stimulated sequentially with increasing concentrations of epidermal growth factor to investigate the dose dependence of the oscillations. The frequency of the oscillations increased with increasing epidermal growth factor concentration, but the amplitude was similar for all concentrations, suggesting the existence of frequency‐encoded information even in the pathway through tyrosine kinase for epidermal growth factor signaling. The pattern of the oscillations with epidermal growth factor, especially the latency, was considerably different from that with phenylephrine, which is known to use the phosphatidylinositol pathway, possibly because of the difference in the pathway toward phosphatidylinositol turnover between these agonists. Additional stimulation with phenylephrine of epidermal growth factor–stimulated hepatocytes increased the frequency of oscillations induced by epidermal growth factor, suggesting that phenylephrine, known as a comitogen for hepatocytes, enhanced the epidermal growth factor–induced calcium signaling by increasing the frequency of [Ca2+]i oscillations. (HEPATOLOGY 1992;16:479–486.)
Financial conditions and corporate investment: evidence from Vietnam

Purpose This study aims to investigate the influence of macro-financial conditions on firm-level capital allocation as a micro-transmission mechanism of monetary policy in Vietnam. Design/methodology/approach The authors employ a dynamic model of investment based on the Euler equation approach that allows for financial frictions. The financial conditions are proxied by a composite index of the current states of financial variables, including interest rates, exchange rates, stock prices, and credit demand – which captures short-term shocks in monetary transmission channels. Corporate financing constraints, as a reflection of financial frictions, are measured by the sensitivity of investment to internal funds, which are extensively examined in terms of both negative and positive cash flows. Findings In the presence of a non-monotonic (or U-shaped) investment–cash flow relation, the empirical evidence from Vietnamese listed firms indicates that financial conditions affect investment behavior for only firms with negative cash flows, in the sense that better financial conditions alleviate the level of “negative” financing constraints (i.e. the sensitivity of investment to negative cash flow). This effect is greater for larger firms and more likely pronounced for firms without state ownership. Originality/value This study contributes to the literature on corporate financing constraints in a manner of considering the macroeconomic dimension, specifically exploring the asymmetric impacts of financial conditions on the investment sensitivity to cash flow.
The experience of knee arthritis in athletic young and middle-aged adults: an heuristic study.

OBJECTIVE To gain a better understanding of the experience of living with tibiofemoral osteoarthritis (OA) as young and middle-aged adults. METHODS Heuristic qualitative research methods were used. Four informants between the ages of 25 and 45 years diagnosed with tibiofemoral OA were purposively sampled. Informants were white, college educated, middle class, and physically active. Informants were interviewed for 4 hours. Interviews were transcribed verbatim and analyzed according to a van Kaam method modified by Moustakas. RESULTS Living with tibiofemoral OA involved pain, fear, isolation, helplessness, and loss of function, identity, and perceived control. The informants struggled with adapting to their pathology. Behavior change and activity modification were difficult and seemed to be related to the physical, sociologic, and psychologic aspects of pathology. CONCLUSIONS A biopsychosocial model of chronic pathology was developed that may guide health professionals in treating and developing interventions for younger adults with arthritis.
Multi-Chromatic Analysis of SAR Images for Coherent Target Detection

This work investigates the possibility of performing target analysis through the Multi-Chromatic Analysis (MCA), a technique that basically explores the information content of sub-band images obtained by processing portions of the range spectrum of a synthetic aperture radar (SAR) image. According to the behavior of the SAR signal at the different sub-bands, MCA allows target classification. Two strategies have been experimented by processing TerraSAR-X images acquired over the Venice Lagoon, Italy: one exploiting the phase of interferometric sub-band pairs, the other using the spectral coherence derived by computing the coherence between sub-band images of a single SAR acquisition. The first approach introduces the concept of frequency-persistent scatterers (FPS), which is complementary to that of the time-persistent scatterers (PS). FPS and PS populations have been derived and analyzed to evaluate the respective characteristics and the physical nature of the targets. Spectral coherence analysis has been applied to vessel detection, according to the property that, in presence of a random distribution of surface scatterers, as for open sea surfaces, spectral coherence is expected to be proportional to sub-band intersection, while in presence of manmade structures it is preserved anyhow. First results show that spectral coherence is well preserved even for very small vessels, and can be used as a complementary information channel to constrain vessel detection in addition to classical Constant False Alarm Rate techniques based on the sole intensity channel.
TESTING THE EFFECTS OF MATING SYSTEM VARIATION ON RATES OF MOLECULAR EVOLUTION IN PRIMATES

Post‐copulatory sexual selection has been proposed to drive the rapid evolution of reproductive proteins, and, more recently, to increase genome‐wide mutation rates. Comparisons of rates of molecular evolution between lineages with different levels of female multiple mating represent a promising, but under‐utilized, approach for testing the effects of sperm competition on sequence evolution. Here, I use comparisons between primate species with divergent mating systems to examine the effects of sperm competition on reproductive protein evolution, as well as on sex‐averaged mutation rates. Rates of nonsynonymous substitution are higher for testis‐specific genes along the chimpanzee lineage in comparison to the human lineage, consistent with expectations. However, the data reported here do not allow firm conclusions concerning the effects of mating system on genome‐wide mutation rates, with different results obtained from different species pairs. Ultimately, comparative studies encompassing a range of mating systems and other life history traits will be required to make broad generalizations concerning the genomic effects of sperm competition.
Community‐acquired methicillin‐resistant Staphylococcus aureus skin infections: a review of epidemiology, clinical features, management, and prevention

Community‐acquired methicillin‐resistant Staphylococcus aureus (CAMRSA) infection is a global problem of epidemic proportions. Many of the patients who develop CAMRSA skin lesions do not have infection‐associated risk factors. Abscess, abscess with accompanying cellulitis, and cellulitis are the most common presentations of cutaneous CAMRSA infection; occasionally, these CARMSA‐related lesions are misinterpreted as spider or insect bites. Other manifestations of cutaneous CAMRSA infection include impetigo, folliculitis, and acute paronychia. The management of CAMRSA skin infection includes incision and drainage, systemic antimicrobial therapy, and adjuvant topical antibacterial treatment. In addition, at the initial visit, bacterial culture of the lesion should be considered. Direct skin‐to‐skin contact, damage to the skin surface, sharing of personal items, and a humid environment are potential mechanisms for the acquisition and transmission of cutaneous CAMRSA infection. Measures that strive to eliminate these causes are useful for preventing the spread of CAMRSA skin infection.
Sense of Coherence and Quality of Life in Women Family Members of the Seriously Mentally Ill

Providing care to a family member with serious mental illness (SMI) can reduce a family's quality of life. Quality of life, however, can be positively influenced by the caregiver's sense of coherence (SOC). Antonovsky's Salutogenic Health Model was examined in this secondary analysis of data from 60 women family members of adults with SMI. The results indicated that greater perceived stress decreased SOC and QoL, greater SOC enhanced QoL, and SOC partially mediated the effects of perceived stress on QoL. The findings suggest the need for reducing stress and strengthening SOC to promote optimal QoL for family members of adults with SMI.
Assessing the Macroeconomic Effects of LTROs During the Great Recession

In response to the 2008–2009 crisis, faced with distressed financial intermediaries, the European Central Bank (ECB) embarked in longer term refinancing operations (LTROs) with full allotment. Using an estimated DSGE model with a frictional banking sector, we find that such liquidity injections have played a key role in averting a major credit crunch. A counterfactual analysis suggests that, absent these nonconventional measures, output, consumption, investment, and the GDP deflator would have been 2.5%, 0.5%, 9.7%, and 0.5% lower on average over 2009, respectively.
Influence of implantation temperature on the formation of hydrogen-related defects in InP

The evolution of hydrogen-related defects introduced in the InP lattice due to the implantation and subsequent annealing is investigated as a function of the implantation temperature, that was varied from -15 °C to 230 °C. Implanted and annealed samples were analyzed by optical microscopy, SIMS and FTIR. The obtained results are discussed in terms of the formation of VInHx complexes that seems to be efficient H trapping centers, probably being the precursors of the fracture process in InP.
Proteomic analysis of protein nitration in rat cerebellum: effect of biological aging

3‐Nitrotyrosine (3‐NT) is a useful biomarker of increasing oxidative stress and protein nitration during biological aging. The proteomic analysis of cerebellar homogenate from Fisher 344/Brown Norway (BN/F1) rats shows an age‐dependent increase in protein nitration, monitored by western‐blot analysis after two‐dimensional gel electrophoresis (2DE), mainly in the acidic region. Analysis of in‐gel digests by nanoelectrospray (NSI)‐MS/MS resulted in the identification of 16 putatively nitrated proteins. The selective isolation of nitrated proteins using immunoprecipitation, followed by SDS‐PAGE and in‐gel digest/NSI‐MS/MS analysis led to the identification of 22 putatively nitrated proteins, of which 7 were identical to those detected after 2DE. When proteins were separated by solution isoelectrofocusing and analyzed by NSI MS/MS, we obtained MS/MS spectra of 3‐NT containing peptides of four proteins – similar to ryanodine receptor 3, low density lipoprotein related receptor 2, similar to nebulin‐related anchoring protein isoform C and 2,3 cyclic nucleotide 3‐phosphodiesterase. Although the functional consequences of protein nitration for these targets are not yet known, our proteomic experiments serve as a first screen for the more targeted analysis of nitrated proteins from aging cerebellum for functional characterization.
8-bit DAC with partial randomization dynamic element matching for nonlinear distortion correction

Digital-to-analog converter (DAC) circuit component errors create non-uniform quantization code widths and nonlinear distortion in the DAC's output. In this project, a low complexity 8-bit digital-to-analog converter with partial randomization dynamic element matching (DEM) technique is designed to eliminate pulse shape, timing, and amplitude errors arising from component mismatches as sources of nonlinear distortion in high-resolution DACs. The benefit of this technique is that it gives significantly reduced hardware complexity with no reduction in performance. Simulation results show that nonlinear distortion is greatly suppressed with partial randomization DEM, which offers considerable additional reduction in hardware complexity. In conclusion, this study showed another technique which intends to increase the accuracy and spectral purity of the output signal in data converters.
External validation of the modified Glasgow prognostic score for renal cancer

Purpose: The modified Glasgow prognostic Score (mGPS) incorporates C-reactive protein and albumin as a clinically useful marker of tumor behavior. The ability of the mGPS to predict metastasis in localized renal cell carcinoma (RCC) remains unknown in an external validation cohort. Patients and Methods: Patients with clinically localized clear cell RCC were followed for 1 year post-operatively. Metastases were identified radiologically. Patients were categorized by mGPS score as low-risk (mGPS = 0 points), intermediate-risk (mGPS = 1 point) and high-risk (mGPS = 2 points). Univariate, Kaplan-Meier and multivariate Cox regression analyses examined Recurrence -free survival (RFS) across patient and disease characteristics. Results: Of the 129 patients in this study, 23.3% developed metastases. Of low, intermediate and high risk patients, 10.1%, 38.9% and 89.9% recurred during the study. After accounting for various patient and tumor characteristics in multivariate analysis including stage and grade, only mGPS was significantly associated with RFS. Compared with low-risk patients, intermediate- and high-risk patients experienced a 4-fold (hazard ratios [HR]: 4.035, 95% confidence interval [CI]: 1.312-12.415, P = 0.015) and 7-fold (HR: 7.012, 95% CI: 2.126-23.123 P < 0.001) risk of metastasis, respectively. Conclusions: mGPS is a robust predictor of metastasis following potentially curative nephrectomy for localized RCC. Clinicians may consider mGPS as an adjunct to identify high-risk patients for possible enrollment into clinical trials or for patient counseling
The influence of psychological flexibility on life satisfaction and mood in muscle disorders.

PURPOSE/OBJECTIVE Acceptance and commitment therapy (ACT), a newer type of behavior therapy that targets psychological flexibility, may have particular utility in the context of muscle disorders. However, there has been no formal investigation of psychological flexibility in this population. This longitudinal observational study investigated whether psychological flexibility is cross-sectionally related to, and prospectively influential on, life satisfaction and mood in muscle disorders. METHODS Data were collected via online questionnaire batteries, completed at baseline and then repeated 4 months later. Cross-sectional and prospective regression analyses examined relationships between validated measures of disability level, psychological flexibility (experiential avoidance, cognitive fusion, and valued living) and illness perceptions (a psychological variable with known influence in muscle disorders), and outcomes (life satisfaction, anxiety, and depression). RESULTS A sample of 137 people with a range of muscle disorders participated. In cross-sectional analyses, psychological flexibility explained significant unique variance in addition to illness perceptions (ΔR2 = 0.17-0.34, p < .001). In prospective analyses, psychological flexibility alone was predictive of change in life satisfaction (ΔR2 = 0.04, p = .01) and anxiety (ΔR2 = 0.03, p = .04) over 4 months. No independent variables were predictive of change in depression over 4 months, and disability level had no significant influence on outcomes. CONCLUSIONS Psychological flexibility influences important outcomes in muscle disorders. Experimental studies are required to establish if increased psychological flexibility leads to improved outcomes. (PsycINFO Database Record
4-(4-(Dimethylamino)phenyl)-1-methylpyridinium (APP+) Is a Fluorescent Substrate for the Human Serotonin Transporter*

Monoamine transporters terminate synaptic neurotransmission and are molecular targets for antidepressants and psychostimulants. Fluorescent reporters can monitor real-time transport and are amenable for high-throughput screening. However, until now, their use has mostly been successful to study the catecholamine transporters but not the serotonin (5HT) transporter. Here, we use fluorescence microscopy, electrophysiology, pharmacology, and molecular modeling to compare fluorescent analogs of 1-methyl-4-phenylpyridinium (MPP+) as reporters for the human serotonin transporter (hSERT) in single cells. The fluorescent substrate 4-(4-(dimethylamino)phenyl)-1-methylpyridinium (APP+) exhibits superior fluorescence uptake in hSERT-expressing HEK293 cells than other MPP+ analogs tested. APP+ uptake is Na+- and Cl−-dependent, displaced by 5HT, and inhibited by fluoxetine, suggesting APP+ specifically monitors hSERT activity. ASP+, which was previously used to study catecholamine transporters, is 10 times less potent than APP+ at inhibiting 5HT uptake and has minimal hSERT-mediated uptake. Furthermore, in hSERT-expressing oocytes voltage-clamped to −60 mV, APP+ induced fluoxetine-sensitive hSERT-mediated inward currents, indicating APP+ is a substrate, whereas ASP+ induced hSERT-mediated outward currents and counteracted 5HT-induced hSERT currents, indicating ASP+ possesses activity as an inhibitor. Extra-precise ligand receptor docking of APP+ and ASP+ in an hSERT homology model showed both ASP+ and APP+ docked favorably within the active region; accordingly, comparable concentrations are required to elicit their opposite electrophysiological responses. We conclude APP+ is better suited than ASP+ to study hSERT transport fluorometrically.
Use and withdrawal of immunosuppressors in primary Sjögren's syndrome.

OBJECTIVES To assess the use and causes of withdrawal of glucocorticoids and immunosuppressors among patients with primary Sjögren's syndrome (pSS) in the clinical setting. METHODS We retrospectively reviewed the medical records of 155 pSS patients and registered demographics, glandular/extraglandular features, serological data, cumulative ESSDAI and SSDDI. A single rheumatologist attributed the indication and cause of withdrawal of glucocorticoids and immunosuppressors. RESULTS 92.2% of the patients were female, mean age 57.4±14.7 years and median follow-up 11 years. One hundred and four (67%) patients received glucocorticoids and/or immunosuppressors: 3.8% only glucocorticoids, 43.9% only immunosuppressors and 56.5% their combination. The most used drugs were antimalarials (46.4%), prednisone (36.7%), azathioprine (AZA) (23.8%) and methotrexate (MTX) (18%). At the multivariate analysis, the presence of non-erosive arthritis OR 5.02 (95% CI 1.74-14.47, p=0.003) and the median cumulative ESSDAI score OR 1.10 (95% CI 1.03-1.17, p=0.002) were associated with the use of these drugs. The causes of withdrawal were: 39% improvement, 35.2% patient's own decision, 18.1% toxicity and 11% lack of efficacy. We found toxicity in 14.2% MTX users, 9.7% for AZA, 9.7% for antimalarials and 7.6% for cyclophosphamide. CONCLUSIONS More than half the patients received glucocorticoids and/or immunosuppressors and a not negligible number decided on their own to suspend them, alerting physicians of secondary adverse events and tolerability.
Sensing homology at the strand-swapping step in lambda excisive recombination.

lambda Site-specific recombination requires a short stretch of sequence homology that might be sensed during strand swapping, during ligation and/or during isomerization of the obligate Holliday junction intermediate. Here, we use half-att site suicide substrates to study single and double top-strand-transfers, isolated from the subsequent steps of the reaction. The double-strand-transfer is analogous to a top-strand exchange and consists of one normal top-strand and one "contrary" bottom-strand to top-strand ligation between the half-att site substrate and its full-site partner. The resulting covalent three-way DNA junctions are poor substrates for resolution in the forward or reverse direction. We show that both the rate and the efficiency of Y-junction formation are homology dependent. Pairing of three nucleotides (either in the forward or in the contrary alignment) provides maximal stability to strand swapping. Complementary base-pairing next to one top-strand site (with or without ligation) stimulates strand-transfer at the other mismatched site. The data suggest that homology can be sensed at the strand-swapping step before ligation. However, homology also stimulates ligation and stabilizes the products, as is evident from the different rates of closed Y-junction formation in the presence or absence of homology. Furthermore, under recombination conditions, single top-strand-transfers are subject to reversal even in the presence of sequence homology; stability depends on a double-strand-transfer, i.e. dissociation of covalent Int.
Diosmin‐induced increase in sensitivity to Ca2+ of the smooth muscle contractile apparatus in the rat isolated femoral vein

The effect of diosmin, a flavone derivative, on the Ca2+ sensitivity of the venous contractile apparatus was investigated in chemically (β‐escin) skinned strips from the rat isolated femoral vein. Diosmin (0.5–10 μm) shifted to the left the concentration‐response curve to Ca2+ (0.05–5 μm). The maximal effect was observed in the presence of 1 μm diosmin which increased the contractile response evoked by 0.15 μm Ca2+ from 26.3% to 78.9% of the maximal Ca2+‐induced response. This work demonstrates that the venotonic action of diosmin involves an increase in the Ca2+ sensitivity of the contractile apparatus. Such a mechanism of action could represent a new and important means of therapeutic control of vasomotor activity.