Miracle-dz/UniFAR-FTUs huggingface dataset:
Performance characteristics of an FT MS‐based workflow for label‐free differential MS analysis of human plasma: standards, reproducibility, targeted feature investigation, and application to a model of controlled myocardial infarction

Proteomics is undergoing a rapid transformation from a qualitative global peptide sequencing discipline into a quantitative, reproducibility‐driven practice. Nowhere is this more evident than in the rapidly expanding field of protein biomarker discovery where the general goal is to uncover statistically robust patterns of differential expression between or among subjects/samples representing distinct biological/temporal states. This report presents the analytical characterization of a label‐free LC FT‐ICR‐MS workflow for differential proteomics analysis of human plasma. The key elements discussed include (i) methodologies for performing properly replicated experiments with highly reproducible sample preparation and analysis, including the use of internal standards to quantify variance at different steps in the process, (ii) a new methodology for performing sample re‐analysis that uses off‐line targeted robotic acquisition of complementary spectral data (e.g. ECD and/or IRMPD) to enhance the identification of differentially expressed peptides/proteins, and (iii) data processing pipelines capable of integrating the automatic statistical analysis of the label‐free (LC‐) MS signal, together with the intuitive and highly interactive curation and annotation of differential features using the output from standard sequence database search programs. We illustrate the application of the complete sample‐to‐annotated‐differential‐peptides (‐proteins) workflow by describing the acquisition and analysis of a large multidimensional dataset from patients undergoing a controlled myocardial infarction resulting in an experimental setup in which each patients serve as their own control. Furthermore, we discuss a couple illustrative examples of mid‐level proteins observed in this study whose plasma concentrations change consistently within and across patients, in a treatment‐ and time‐dependent fashion.
Implementation of loop-shaping compensators to increase the transparency bandwidth of a scaled telemanipulation system

This paper describes the implementation of a two-channel position-force control architecture on a three degree-of-freedom scaled master-slave telemanipulation system. The architecture enables the authors to address both the transparency bandwidth and stability robustness of the system. First, the uncompensated transparency and stability robustness of the bilateral telemanipulation system are experimentally assessed. Then, loop-shaping compensators are used to increase the transparency bandwidth, while maintaining the stability robustness of the system, and the results are compared with those of the uncompensated system.
Effects of Different Spices Used in Production of Fermented Sausages on Growth of and Curvacin A Production by Lactobacillus curvatus LTH 1174

ABSTRACT Lactobacillus curvatus LTH 1174, a fermented sausage isolate, produces the listericidal bacteriocin curvacin A. The effect of different spices relevant for the production of fermented sausages was investigated in vitro through laboratory fermentations with a meat simulation medium and an imposed pH profile relevant for Belgian-type fermented sausages. The influence on the growth characteristics and especially on the kinetics of curvacin A production with L. curvatus LTH 1174 was evaluated. Pepper, nutmeg, rosemary, mace, and garlic all decreased the maximum specific growth rate, while paprika was the only spice that increased it. The effect on the lag phase was minor except for nutmeg and especially for garlic, which increased it, yet garlic was stimulatory for biomass production. The maximum attainable biomass concentration (Xmax) was severely decreased by the addition of 0.40% (wt/vol) nutmeg, while 0.35% (wt/vol) garlic or 0.80% (wt/vol) white pepper increased Xmax. Nutmeg decreased both growth and bacteriocin production considerably. Garlic was the only spice enhancing specific bacteriocin production, resulting in higher bacteriocin activity in the cell-free culture supernatant. Finally, lactic acid production was stimulated by the addition of pepper, and this was not due to the manganese present because an amount of manganese that was not growth limiting was added to the growth medium. Addition of spices to the sausage mixture is clearly a factor that will influence the effectiveness of bacteriocinogenic starter cultures in fermented-sausage manufacturing.
Development of gatifloxacin-loaded cationic polymeric nanoparticles for ocular drug delivery

Abstract The present investigation aimed at improving the ocular bioavailability of gatifloxacin by prolonging its residence time in the eye and reducing problems associated with the drug re-crystallization after application through incorporation into cationic polymeric nanoparticles. Gatifloxacin-loaded nanoparticles were prepared via the nanoprecipitation and double emulsion techniques. A 50:50 Eudragit® RL and RS mixture was used as cationic polymer with other formulation parameters varied. Prepared nanoparticles were evaluated for size, zeta potential, and drug loading. An optimized formulation was selected and further characterized for in vitro drug release, cytotoxicity, and antimicrobial activity. The double emulsion method produced larger nanoparticles than the nanoprecipitation method (410 nm and 68 nm, respectively). Surfactant choice also affected particle size and zeta potential with Tween 80 producing smaller-sized particles with higher zeta potential than PVA. However, the zeta potential was positive at all experimental conditions investigated. The optimal formulation produced by double emulsion technique and has achieved 46% drug loading. This formulation had optimal physicochemical properties with acceptable cytotoxicity results, and very prolonged release rate. The particles antimicrobial activities of the selected formulation have been tested against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and showed prolonged antimicrobial effect for gatifloxacin.
Brain‐type creatine kinase activates neuron‐specific K+‐Cl– co‐transporter KCC2

GABA, a major inhibitory neurotransmitter in the adult CNS, is excitatory at early developmental stages as a result of the elevated intracellular Cl– concentration ([Cl–]i). This functional switch is primarily attributable to the K+‐Cl– co‐transporter KCC2, the expression of which is developmentally regulated in neurons. Previously, we reported that KCC2 interacts with brain‐type creatine kinase (CKB). To elucidate the functional significance of this interaction, HEK293 cells were transfected with KCC2 and glycine receptor α2 subunit, and gramicidin‐perforated patch‐clamp recordings were performed to measure the glycine reversal potential (Egly), giving an estimate of [Cl–]i. KCC2‐expressing cells displayed the expected changes in Egly following alterations in the extracellular K+ concentration ([K+]o) or administration of an inhibitor of KCCs, suggesting that the KCC2 function was being properly assessed. When added into KCC2‐expressing cells, dominant‐negative CKB induced a depolarizing shift in Egly and reduced the hyperpolarizing shift in Egly seen in response to a lowering of [K+]o compared with wild‐type CKB. Moreover, 2,4‐dinitrofluorobenzene (DNFB), an inhibitor of CKs, shifted Egly in the depolarizing direction. In primary cortical neurons expressing CKB, the GABA reversal potential was also shifted in the depolarizing direction by DNFB. Our findings suggest that, in the cellular micro‐environment, CKB activates the KCC2 function.
Looking for adolescents' well-being: self-efficacy beliefs as determinants of positive thinking and happiness

SUMMARY Aims – The present study is part of a longitudinal project aimed at identifying the personal characteristics and the developmental pathways conducive to successful adaptation from childhood to adulthood. The study examined the concurrent and longitudinal impact of self-efficacy beliefs on subjective well-being in adolescence, namely positive thinking and happiness. Positive thinking has been operationalized as the latent dimension underlying life satisfaction, self-esteem and optimism. Happiness has been operationalized as the difference between positive and negative affects, as they are experienced in a variety of daily situations. Methods – In a group of 664 Italian adolescents, a structural model positing adolescents' emotional and interpersonal self-efficacy beliefs as proximal and distal determinants of positive thinking and happiness has been tested. Results – Findings attest to the impact of affective and interpersonal-social self-efficacy beliefs on positive thinking and happiness both concurrently and longitudinally. Conclusions – Adolescents' self-efficacy beliefs to manage positive and negative emotions and interpersonal relationships contribute to promote positive expectations about the future, to mantain a high self-concept, to perceive a sense of satisfaction for the life and to experience more positive emotions. Declaration of Interest: none.
An ARDL Analysis on the Internet Usage Rate and the Wealth of Malaysians

The objective of this study is to examine the relationship between gross national income per capita and the internet usage rate per 100 people of an emerging economy Malaysia both in the short and long-run. Autoregressive Distributed Lag Modeling Approach (ARDL) was used to analyze the thirteen-year time series collected for these two variables. Empirical findings from the econometrics analysis reported a significant long-run and short-run relationship between these two variables. Hence, this study concludes that, enhancing internet usage among the public and private sectors is a pertinent strategy for Malaysia towards achieving a higher wealth status for its people.
Hodgkin's disease: Unfolding concepts concerning its nature, management and prognosis

The evolution of our concepts concerning the fundamental nature and natural history of Hodgkin's disease is reviewed. Recent evidence establishes that it is indeed a malignant neoplasm, albeit a curious one, the giant cells of which display aneuploid karyotypes, often with marker chromosomes indicating their clonal derivation, and the functional and surface marker properties of cells of the mononuclear phagocyte series. The disease tends initially to spread by contiguity from one lymph node chain to others with which direct lymphatic channel communications exist. Essentially all patients, even those with limited disease, have some degree of impairment of cell‐mediated immunity, apparently due to inhibition of T‐lymphocyte function. Lymphangiography, computed tomography, and laparotomy with splenectomy have greatly improved the accuracy of clinical staging. Total lymphoid megavoltage radiotherapy and/or multidrug combination chemotherapy now permit the eradication of disease of all stages, resulting in a dramatic improvement in prognosis and an increasing frequency of permanent cure of this once inevitably fatal condition.
Eltanolone as an Alternative to Propofol for Ambulatory Anesthesia

The intravenous (IV) steroid anesthetic, eltanolone, compares favorably to propofol with respect to its induction characteristics.This double-blind investigation was designed to compare the induction and recovery profile of eltanolone (versus propofol) when it was used for both induction and maintenance of ambulatory anesthesia. Eighty-three consenting ASA physical status I-III outpatients undergoing minor gynecologic or urologic procedures lasting 10-40 min were randomly assigned to one of three anesthetic treatment groups. All patients received midazolam, 2 mg IV, and fentanyl, 50 micro g IV, before induction of anesthesia. The control group (Group 1) was induced with propofol, 2.4 mg/kg IV (18-60 yr or ASA physical status I or II) or 1.6 mg/kg IV (61-80 yr and/or ASA physical status III), followed by intermittent bolus doses of 0.6 mg/kg IV in combination with N2 O 67% for maintenance of anesthesia. In Group 2, anesthesia was induced with eltanolone, 0.75 mg/kg IV, (18-60 yr and/or ASA physical status I or II) or 0.5 mg/kg IV (61-80 yr and/or ASA physical status III), and maintained with intermittent bolus injections of 0.2 mg/kg IV and N2 O 67%. Group 3 received eltanolone, 1.0 mg/kg IV (18-60 yr and/or ASA physical status I or II), or 0.75 mg/kg IV (61-80 yr and/or ASA physical status III), followed by intermittent bolus injections of 0.2 mg/kg IV and N2 O 67%. In addition to recording the induction and recovery times and side effects, psychomotor testing was performed before and at 30-min intervals after anesthesia. Induction times (57 +/- 23, 67 +/- 26, and 61 +/- 22 s, respectively) were similar in all three groups. Although eltanolone produced no pain on injection (versus 52% in the propofol group), 10% of the eltanolone-treated patients (versus none in the propofol group) developed transient cutaneous (rash-like) reactions. The total dose of study medication used during the anesthetic period was 9.2 +/- 3.7 mg [center dot] kg-1 [center dot] h-1 in the propofol group compared with 3.3 +/- 1.4 mg [center dot] kg-1 [center dot] h-1 and 3.3 +/- 1.9 mg [center dot] kg-1 [center dot] h-1 in Groups 2 and 3, respectively. Early recovery times were significantly shorter after propofol anesthesia. However, times to ambulation, micturition, and being judged "fit for discharge," as well as recovery of cognitive function, were similar in all three groups. Although ethanolone seems to be a safe and effective IV anesthetic, these data suggest that it is unlikely to replace propofol in the ambulatory setting. Implications: Eltanolone is an investigational steroid anesthetic that causes less pain on injection and less cardiovascular depression than propofol (the most widely used intravenous anesthetic in the outpatient setting). Unfortunately, emergence from anesthesia after ambulatory surgery is slower with eltanolone compared with propofol. Therefore, it is unlikely that eltanolone will replace propofol for outpatient anesthesia. (Anesth Analg 1997;85:801-7)
Introduction to the Corporate Governance of Religion

Stationed at the border between the past and the present, the corporate governance of religion is concerned with the governance mechanisms by which religious organizations are controlled and directed. Building on similarities between contemporary organizations and their predecessors in Roman Catholic monasticism, this essay illustrates that studying the past can be of enormous benefit. It allows us to see familiar problems in a new light: for example, bureaucratic rules – nowadays no longer linked to efficiency – that emerged in Catholic orders and enabled organizational learning, innovations, and survival in uncertain environments. The study of the past is also an appreciation for the kind of governance mechanisms that have staying power: Catholic orders can be viewed as pioneers of corporate governance and show what kind of governance is suitable to reduce agency problems. Finally, when abstract organizational theories are presented in a historical context it makes them more palatable, more understandab.
Tension transients during steady shortening of frog muscle fibres.

Single intact fibres from frog muscle at 0‐1 degrees C were stimulated to produce isometric tetani at a sarcomere length of about 2.25 micron, using a spot‐follower apparatus to control the length of the central part of a fibre. When the plateau of the tetanus was reached the fibre was forced to shorten by applying a step and ramp length change in an approximation to an isotonic release. When tension had reached a steady level, Ti, during shortening, tension transients were elicited by applying step changes of length, complete within 0.2 ms, ranging from a stretch of 1.5 nm per half‐sarcomere to a release of 6 nm per half‐sarcomere. The tension transients recorded during shortening were qualitatively similar to those previously recorded in isometric tetani. There were four phases: phase 1, the change of tension during the step; phase 2, a rapid partial recovery of tension; phase 3, a delay or reversal of recovery; phase 4, a slower recovery of tension to the level before the step was applied. Measurements were made of the extreme tension, T1, attained during a step, and the level, T2, to which tension recovers in phase 2. The excursion of tension, [T1‐Ti], during a small step of given size, fell with increase of shortening velocity, reaching about 40% of the isometric value near the maximum velocity of shortening. T2 fell as shortening velocity was increased and the fraction of steady tension recovered, T2/Ti, also decreased, so that the proportion of tension recovery in phase 4 increased. All the recovery phases became progressively more rapid with increase of shortening velocity. The early tension response was matched with a delay‐line simulator so as to estimate the value of the instantaneous stiffness. Stiffness during shortening was found to decrease approximately linearly with tension, reaching about 35% of the isometric value as tension approached zero. It was impossible to match the early tension response in a rapidly shortening fibre without assuming decreased stiffness. The decline of stiffness is interpreted as due largely to reduced number of attached cross‐bridges, but quantitative estimates would be affected by possible filament compliance and non‐linearity of cross‐bridge stiffness. The decrease in T2 also suggests fewer cross‐bridges are attached as shortening velocity increases, but uncertainties about the processes determining phase 2 during shortening do not permit a precise estimate of stiffness to be made. (ABSTRACT TRUNCATED AT 400 WORDS)
Accuracy of transient elastography in the assessment of chronic hepatitis C-related liver cirrhosis.

PURPOSE Staging liver cirrhosis is essential for the management of chronic hepatitis C (CHC). The current meta-analysis evaluated the accuracy of transient elastography for detecting liver cirrhosis in patients with CHC. METHODS Either prospective or retrospective studies, including cohort and cross sectional studies, in patients diagnosed with chronic hepatitis C, as assessed by transient elastography, were searched from Medline, Cochrane, EMBASE, and Google Scholar databases until March 3, 2015, using the terms "transient elastography, chronic hepatitis C and liver cirrhosis". The primary outcome analyzed was the diagnostic performance, which included sensitivity, specificity, diagnostic odds ratio and area under the receiver-operating characteristic (ROC) curve. RESULTS Data from 24 articles included in the meta-analysis demonstrated high sensitivity (84%) and specificity (90%) of transient elastography (TE) for assessing liver cirrhosis patients with HCV. Subgroup analysis of patients by underlying diseases revealed a sensitivity and specificity of 91% and 92% (HCV alone), 100% and 75% (HCV-liver transplant), 83.6% and 89.7% (HIV/HCV co-infection) and 97.1% and 90.7% (recurrent CHC after liver transplantation). The pooled diagnostic odds ratio was 61.57 (95% CI, 39.5 - 96.00) and the area under the summary ROC curves was 0.952 ± 0.008, suggesting high diagnostic accuracy of TE. CONCLUSION Transient elastography can accurately predict liver cirrhosis in patients with hepatitis C, with a sensitivity and specificity of 84% and 90%, respectively. The present results further validate the utility of TE in staging liver cirrhosis in chronic HCV infections.
DDB, a Putative DNA Repair Protein, Can Function as a Transcriptional Partner of E2F1

ABSTRACT The transcription factor E2F1 is believed to be involved in the regulated expression of the DNA replication genes. To gain insights into the transcriptional activation function of E2F1, we looked for proteins in HeLa nuclear extracts that bind to the activation domain of E2F1. Here we show that DDB, a putative DNA repair protein, associates with the activation domain of E2F1. DDB was identified as a heterodimeric protein (48 and 127 kDa) that binds to UV-damaged DNA. We show that the UV-damaged-DNA binding activity from HeLa nuclear extracts can associate with the activation domain of E2F1. Moreover, the 48-kDa subunit of DDB, synthesized in vitro, binds to a fusion protein of E2F1 depending on the C-terminal activation domain. The interaction between DDB and E2F1 can also be detected by coimmunoprecipitation experiments. Immunoprecipitation of an epitope-tagged DDB from cell extracts resulted in the coprecipitation of E2F1. In a reciprocal experiment, immunoprecipitates of E2F1 were found to contain DDB. Fractionation of HeLa nuclear extracts also revealed a significant overlap in the elution profiles of E2F1 and DDB. For instance, DDB, which does not bind to the E2F sites, was enriched in the high-salt fractions containing E2F1 during chromatography through an E2F-specific DNA affinity column. We also observed evidence for a functional interaction between DDB and E2F1 in living cells. For instance, expression of DDB specifically stimulated E2F1-activated transcription. In addition, the transcriptional activation function of a heterologous transcription factor containing the activation domain of E2F1 was stimulated by coexpression of DDB. Moreover, DDB expression could overcome the retinoblastoma protein (Rb)-mediated inhibition of E2F1-activated transcription. The results suggest that this damaged-DNA binding protein can function as a transcriptional partner of E2F1. We speculate that the damaged-DNA binding function of DDB, besides repair, might serve as a negative regulator of E2F1-activated transcription, as damaged DNA will sequester DDB and make it unavailable for E2F1. Furthermore, the binding of DDB to damaged DNA might be involved in downregulating the replication genes during growth arrest induced by damaged DNA.
The effect of absolute lymphocyte count recovery kinetics on survival after autologous stem cell transplantation for non-Hodgkin's lymphoma

Absolute lymphocyte count (ALC) >or=500 cells/microl at day 15 after autologous stem cell transplantation (ASCT) is a powerful independent, prognostic indicator for survival in multiple hematological malignancies. A limitation in these studies was the selection of a single time point (day 15 post-ASCT) as the only discriminator of clinical outcome in relation to ALC recovery. We hypothesized there is a continuous and not discrete relationship between ALC recovery and clinical outcome post-ASCT in NHL. Therefore, we analyzed 274 consecutive patients who underwent ASCT for NHL between 1987 and 2001. The primary end point was to assess the impact of the kinetics of post-ASCT lymphocyte recovery>or=500 cells/microl (K-ALC) on overall survival (OS) and progression-free survival (PFS). K-ALC was a predictor of OS and PFS when the Cox proportional hazards model was used with K-ALC entered as a continuous variable (p<0.0001). Multivariate analysis demonstrated K-ALC recovery post-ASCT to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that the K-ALC post-ASCT is associated with clinical outcome in NHL.