Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative characterization of direct P‐glycoprotein inhibition by St John's wort constituents hypericin and hyperforin

The ATP‐binding cassette transporter P‐glycoprotein (P‐gp) exerts a critical role in the systemic disposition of, and exposure to, lipophilic and amphipathic drugs, carcinogens, toxins and other xenobiotics. The ability of P‐gp to transfer a wide variety of structurally unrelated compounds from the cell interior across the membrane bilayer remains intriguing. Since natural product chemicals in the widely consumed St John's wort appear to exert antidepressant effects by an unknown mechanism, the constituents are frequently studied for interactions with various biomacromolecules as well as cytotoxins or isolated cells. The drug interactions caused by this widely used herbal remedy are under‐appreciated. Various clinical interactions have been observed upon the co‐administration of St John's wort, and P‐gp and CYP3A4 have been indicted as the cause. We characterized several St John's wort constituents for their interaction with P‐gp and their specific effects on the P‐gp export activity of several marker substrates. Two of these constituents, hyperforin and hypericin, inhibit the active efflux of the fluorescent markers daunorubicin (IC50 ˜ 30 μM) and calcein‐AM. Herein, we show in‐vitro results that can both explain the competing clinical observations of initial elevated exposure of P‐gp substrate drugs (P‐gp inhibition) followed by under‐exposure (P‐gp induction) when St John's wort is co‐administered, and provide a further warning against unchecked co‐administration of drugs with St John's wort.
MALDI-TOF MS analysis of ribosomal proteins coded in S10 and spc operons rapidly classified the Sphingomonadaceae as alkylphenol polyethoxylate-degrading bacteria from the environment.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) using ribosomal subunit proteins coded in the S10-spc-alpha operon as biomarkers was applied for the classification of the Sphingomonadaceae from the environment. To construct a ribosomal protein database, S10-spc-alpha operon of type strains of the Sphingomonadaceae and their related alkylphenol polyethoxylate (APEO(n) )-degrading bacteria were sequenced using specific primers designed based on nucleotide sequences of genome-sequenced strains. The observed MALDI mass spectra of intact cells were compared with the theoretical mass of the constructed ribosomal protein database. The nine selected biomarkers coded in the S10-spc-alpha operon, L18, L22, L24, L29, L30, S08, S14, S17, and S19, could successfully distinguish the Sphingopyxis terrae NBRC 15098(T) and APEO(n) -degrading bacteria strain BSN20, despite only one base difference in the 16S rRNA gene sequence. This method, named the S10-GERMS (S10-spc-alpha operon gene-encoded ribosomal protein mass spectrum) method, is a significantly useful tool for bacterial discrimination of the Sphingomonadaceae at the strain level and can detect and monitor the main APEO(n) -degrading bacteria in the environment.
Producer‐Level Benefits of Sustainability Certification

Abstract: Initiatives certifying that producers of goods and services adhere to defined environmental and social‐welfare production standards are increasingly popular. According to proponents, these initiatives create financial incentives for producers to improve their environmental, social, and economic performance. We reviewed the evidence on whether these initiatives have such benefits. We identified peer‐reviewed, ex post, producer‐level studies in economic sectors in which certification is particularly prevalent (bananas, coffee, fish products, forest products, and tourism operations), classified these studies on the basis of whether their design and methods likely generated credible results, summarized findings from the studies with credible results, and considered how these findings might guide future research. We found 46 relevant studies, most of which focused on coffee and forest products and examined fair‐trade and Forest Stewardship Council certification. The methods used in 11 studies likely generated credible results. Of these 11 studies, nine examined the economic effects and two the environmental effects of certification. The results of four of the 11 studies, all of which examined economic effects, showed that certification has producer‐level benefits. Hence, the evidence to support the hypothesis that certification benefits the environment or producers is limited. More evidence could be generated by incorporating rigorous, independent evaluation into the design and implementation of projects promoting certification.
Reliability of Deep-UV Light-Emitting Diodes

This paper analyzes the performance and reliability of deep-ultraviolet light-emitting diodes (LEDs) on AlGaN emitting at 280 and 295 nm. By means of detailed electroluminescence characterization, we show that the optical properties of the LEDs are strongly influenced by the presence of deep-level-related radiative transitions, and we separately evaluate the contribution of each of these recombination mechanisms on the overall light emission. The reliability analysis presented in this paper shows that stress determines the gradual decrease of the output power of the LEDs, which is more prominent at low measuring current levels. Degradation is attributed to the increase of the nonradiative recombination rate. By means of C-V analysis, we give evidence of modifications of the charge distribution in the active layer, taking place as a consequence of stress: this mechanism is considered to be related to the generation of new defect states near/within the active region.
Aflibercept (AVE0005): an alternative strategy for inhibiting tumour angiogenesis by vascular endothelial growth factors

Background: Aberrant angiogenesis is a landmark feature in cancer, which is important for proliferation, growth and metastasis, and is mediated by various pro-angiogenic factors. The VEGF pathway is one of the most important and best-studied angiogenic pathways. Inhibition of this pathway may provide clinical benefits to cancer patients. Objectives: Strategies to inhibit the VEGF pathway, including antibodies to VEGF, antibodies to the extracellular domain of VEGFR-1 or VEGFR-2, decoy receptors for VEGF and tyrosine kinase inhibitors of VEGFRs, are summarized. Methods: This review outlines and compares the latest development of these strategies, with emphasis on aflibercept, a novel decoy fusion protein of domain 2 of VEGFR-1 and domain 3 of VEGFR-2 with the Fc fragment of IgG1. Results: Aflibercept was shown to have early clinical activity. Multiple studies are ongoing to determine the clinical benefits of aflibercept in cancer patients.
Effects of an anaerobic lactic training session on the postural stability of athletes.

AIM The aim of this study was to analyze the short-term effects of a lactate-accumulation training session on postural stability. METHODS Fifteen athletes performed two trainings sessions (warm-up and lactic-training session). Before training (Pre), immediately after (Post(0min)), thirty minutes later (Post(30min)) and after 24 hours (Post(24h)), athletes were subject to a bipodal and a monopodal stabilometries and a lactate blood analysis to ensure a high stress level. RESULTS Variance analysis (α=0.05) showed that, in lactic training, athletes experienced an increase of length and velocity in post(0min), a decrease at post(30min) and a new decrease at post(24h), which was lower than basal values. In monopodal stability, left-leg support showed a decrease at post(0min) in anteroposterior plane of athletes after lactic training. Also, in both monopodal supports, athletes displayed higher values of length and velocity in post(0min) after lactic training, with a progressive decrease which was significant at Post(24h), when they reached baseline. CONCLUSION Right after anaerobic lactic training, center-of-pressure dispersion variables in bipodal stabilometry are worsened. Thirty minutes later, stabilometric variables are still deteriorated. At 24 hours, stabilometry is better than baseline. In monopodal support, dispersion values are worsened after lactic training and anteroposterior stability is impaired in left monopodal support, although the deterioration is less evident as time passes.
Iron overload augments the development of atherosclerotic lesions in rabbits.

Iron, a major oxidant in vivo, could be involved in atherosclerosis through the induction of the formation of oxidized LDL, a major atherogenic factor. This study was designed to test this hypothesis experimentally. Four groups of New Zealand White rabbits were included: iron-overloaded/hypercholesterolemic (group A, n = 8), iron-overloaded (group B, n = 6), hypercholesterolemic (group C, n = 6), and untreated (group D, n = 6). Iron overload was achieved by the intramuscular administration of 1.5 g of iron dextran divided in 30 doses. Hypercholesterolemia was produced by feeding rabbit chow enriched with 0.5% (wt/wt) cholesterol. Serum iron, ferritin, cholesterol, triglycerides, and lipoperoxides in serum were measured throughout the study. Lipoperoxides were measured at the end of the study in liver, aorta, and spleen homogenates. Aortas of groups A and C had multiple lesions; however, group A had greater lesional involvement than group C (P < .05). Lesions were not observed in rabbits fed normal chow (group D). As expected, serum iron and ferritin were above normal levels in groups A and B. Serum cholesterol increased in groups A and C. Lipoperoxides in liver and spleen homogenates of iron-overloaded rabbits were increased. Interestingly, iron deposits were seen by ultrastructural studies in the arterial walls of rabbits in groups A and B. Our study suggests that iron overload augments the formation of atherosclerotic lesions in hypercholesterolemic rabbits.
Manual contouring based volumetric evaluation for colorectal cancer with liver limited metastases: a comparison with RECIST.

BACKGROUND To compare response evaluation criteria in solid tumours (RECIST) and volumetric evaluation (VE) for colorectal cancer with liver-limited metastasis. PATIENTS AND METHODS VE of liver metastases was performed by manual contouring before and after chemotherapy on 45 pairs of computed tomography (CT) images in 36 patients who suffered from metastatic colorectal cancer (mCRC) with liver metastasis only. Cohen kappa was used to compare the agreement between VE and RECIST. Pearson correlation was performed for their comparison after cubic root transformation of the aggregate tumor volumes. Logistic regression was done to identify clinical and radiographic factors to account for the difference which may be predictive in overall response (OR). RESULTS There were 16 partial response (PR), 23 stable disease (SD) and 6 progressive disease (PD) cases with VE, and 14 PR, 23 SD and 8 PD with RECIST. VE demonstrated good agreement with RECIST (κ=0.779). Discordant objective responses were noted in 6 pairs of comparisons (13.3%). Pearson correlation also showed excellent correlation between VE and RECIST (r2=0.966, p<0.001). Subgroup analysis showed that VE was in slightly better agreement with RECIST for enlarging lesions than for shrinking lesions (r2=0.935 and r2=0.780 respectively). No factor was found predictive of the difference in OR between VE and RECIST. CONCLUSIONS VE exhibited good agreement with RECIST. It might be more useful than RECIST in evaluation shrinking lesions in cases of numerous and conglomerate liver metastases.
Communication Failures: An Insidious Contributor to Medical Mishaps

Purpose To describe how communication failures contribute to many medical mishaps. Method In late 1999, a sample of 26 residents stratified by medical specialty, year of residency, and gender was randomly selected from a population of 85 residents at a 600-bed U.S. teaching hospital. The study design involved semistructured face-to-face interviews with the residents about their routine work environments and activities, the medical mishaps in which they recently had been involved, and a description of both the individual and organizational contributory factors. The themes reported here emerged from inductive analyses of the data. Results Residents reported a total of 70 mishap incidents. Aspects of “communication” and “patient management” were the two most commonly cited contributing factors. Residents described themselves as embedded in a complex network of relationships, playing a pivotal role in patient management vis-à-vis other medical staff and health care providers from within the hospital and from the community. Recurring patterns of communication difficulties occur within these relationships and appear to be associated with the occurrence of medical mishaps. Conclusion The occurrence of everyday medical mishaps in this study is associated with faulty communication; but, poor communication is not simply the result of poor transmission or exchange of information. Communication failures are far more complex and relate to hierarchical differences, concerns with upward influence, conflicting roles and role ambiguity, and interpersonal power and conflict. A clearer understanding of these dynamics highlights possibilities for appropriate interventions in medical education and in health care organizations aimed at improving patient safety.
Co-relation between capacitance-voltage, conductance-voltage and photoconductive properties of the as-deposited and annealed a-Si/SiNx multilayer films prepared using hot-wire CVD

In this paper, the electrical properties of the as-deposited and the annealed a-Si/SiNx multilayer (ML) films are compared. The a-Si/SiNx ML films are prepared at 250°C using hot-wire chemical vapor deposition (HWCVD) technique. Silicon quantum dots (Si-QDs) are formed in the a-Si layers of ML films upon annealing at 850°C. Metal insulator semiconductor (MIS) structures containing the ML films are characterized with high frequency capacitance-voltage (C-V), conductance-voltage (G-V) and photo-current measurements. These characterizations show that the annealed ML films have high defects centers than the as-deposited ML films. A shift in the C-V plot and a peak shift in the G-V plot for the annealed ML film are due to the charge storage in the defects centers and the quantized states of Si-QDs. The defect centers introduced low photo-response for the annealed ML film (Si-QD structure) than the as-deposited ML films.
The Sequence of Administration of 1.5% Mepivacaine and 0.5% Bupivacaine Does Not Affect Latency of Block Onset or Duration of Analgesia in Ultrasound-Guided Interscalene Block

BACKGROUND:During peripheral nerve blockade, different local anesthetics may be sequentially administered. Typically, a short- or intermediate-acting local anesthetic is administered before a long-acting local anesthetic to achieve a block with rapid onset and long duration. However, there is a paucity of data on advantages of such sequencing. We hypothesized that when using a sequential mixture of mepivacaine and bupivacaine for ultrasound-guided interscalene block, the order of injection of the drugs does not influence the clinical characteristics of the block achieved. METHODS:Sixty-four patients undergoing arthroscopic shoulder surgery (aged 18–65 years; ASA physical status I–II) with a single-injection ultrasound-guided interscalene brachial plexus block as sole anesthetic were studied. The subjects were randomized to receive 1 of 2 local anesthetic sequences: 15 mL of mepivacaine 1.5% followed by 15 mL of bupivacaine 0.5% (group A), or the same local anesthetics in the reverse order (group B). The durations of sensory and motor block were the primary outcomes. Block onset was also assessed. RESULTS:Duration of motor block was similar between group A and group B (10.1 ± 4.7 hours vs 10.3 ± 5.1 hours, mean difference 0.2 hours, 95% confidence interval [CI] −3.3 to 2.9, P = 0.9). Duration of analgesia was also similar between group A and group B (9.5 ± 5.6 hours vs 10.2 ± 4.5 hours, mean difference 0.7 hours, 95% CI −3.2 to 1.9, P = 0.42). Onset of sensory block was similar between the 2 groups (15.9 ± 7.1 minutes for group A, 13.9 ± 7.0 minutes for group B, mean difference 1.9 minutes, 95% CI −1.4 to 5.2, P = 0.25). CONCLUSIONS:The sequence in which 15 mL mepivacaine 1.5% and 15 mL bupivacaine 0.5% are administered does not seem to have a clinically meaningful effect on duration or onset of ultrasound-guided interscalene brachial plexus block.
RF Oscillator Based on a Passive RC Bandpass Filter

A passive RC bandpass filter (BPF) based voltage-controlled-oscillator (VCO) operating at 2.5 GHz is presented. In GHz frequency range, a preferred type of an oscillator is either an LC oscillator or a ring oscillator. An LC oscillator exhibits an excellent phase noise performance while its fabrication cost is expensive due to the inductors. On the other hand, a ring oscillator can be built with standard CMOS devices resulting in a cheap fabrication cost. However, it has a poor phase noise and jitter performance and is sensitive to power supply noise. This paper proposes a RC BPF-based oscillator. Its property is closer to a LC oscillator rather than a ring oscillator and, as a result, improves the jitter performance due to power supply noise. Also, it can be fabricated in a standard CMOS process since there is no inductor. To prove the proposed concept, a RC BPF-based oscillator was designed and fabricated in a standard 0.13-mum CMOS technology. An operating frequency of 2.5 GHz and phase noise of - 95.4 dBc/Hz at 1 MHz offset was measured. Power consumption was 2.86 mW from a 1.3 V supply voltage.
Homologous and heterologous resistance in Echinostoma revolutum infections in mice

Summary Homologous and heterologous resistance in Echinostoma revolutum infections was studied in mice. A high level of homologous resistance was demonstrated in mice harbouring a 13-day-old primary E. revolutum infection with 9–10 and 11–15 worms, corresponding to a 70·0 and 66·7% reduction in the size of the established worm burden as compared with that of the challenge control group. A 14- and 20-day-old primary infection with 3–4 worms induced a level of resistance of 61·7 and 81·8% respectively, while higher worm levels of 9–10 and 11–15 induced almost complete resistance corresponding to a 95·1–100% reduction in the size of the established worm burden. Complete resistance was also demonstrated in mice challenged 8 days after elimination of a 20-day-old primary infection with 11–15 worms by anthelmintic treatment. A primary 43-day-old Schistosoma mansoni infection induced a 73·1% reduction in the size of the established E. revolutum challenge infection while infections of an age of 79 and 99 days conferred complete resistance to heterologous challenge with E. revolutum. Primary pre-patent S. mansoni infections and a patent S. bovis infection of an age of 56 days did not induce any resistance to challenge with E. revolutum. A primary 14- and 21-day-old infection of E. revolutum did not stimulate any significant level of resistance to heterologous challenge with S. mansoni.
New method for separation of subpopulations from a heterogeneous colon cancer cell line.

BACKGROUND To understand the heterogeneity of human colon cancers, a new method to separate cancer subpopulations was developed. MATERIALS AND METHODS Cells from a human colon cancer cell line, DLD-1, were seeded on an 8 microm pore membrane. After six hours, the cells which remained beneath the membrane as well as the cells which dropped onto the 24-well plate were collected. To clarify the differences between the two subpopulations, transepithelial electrical resistance (TEER) and immunocytochemistry were evaluated. RESULTS Two subpopulations, clones D and A, were separated from DLD-1 with the newly developed method. Both subpopulations showed quite different TEER values and different arrangements of cell-cell contact. In addition, the distinct subcellular localizations of claudin family proteins and zonula occludens-1 (ZO-1) were identified. CONCLUSION A new separation method to isolate colon cancer subpopulations was established in which the intercellular junctions differed. This method can be considered as a helpful tool in the investigation of colon cancer heterogeneity.
Crystal structure of an activated form of the PTS regulation domain from the LicT transcriptional antiterminator

The transcriptional antiterminator protein LicT regulates the expression of Bacillus subtilis operons involved in β‐glucoside metabolism. It belongs to a newly characterized family of bacterial regulators whose activity is controlled by the phosphoenolpyruvate:sugar phosphotransferase system (PTS). LicT contains an N‐terminal RNA‐binding domain (56 residues), and a PTS regulation domain (PRD, 221 residues) that is phosphorylated on conserved histidines in response to substrate availability. Replacement of both His207 and His269 with a negatively charged residue (aspartic acid) led to a highly active LicT variant that no longer responds to either induction or catabolite repression signals from the PTS. In contrast to wild type, the activated mutant form of the LicT regulatory domain crystallized easily and provided the first structure of a PRD, determined at 1.55 Å resolution. The structure is a homodimer, each monomer containing two analogous α‐helical domains. The phosphorylation sites are totally buried at the dimer interface and hence inaccessible to phosphorylating partners. The structure suggests important tertiary and quaternary rearrangements upon LicT activation, which could be communicated from the protein C‐terminal end up to the RNA‐binding domain.
Tracking failure process of XLPE-silicon rubber interface under impulse voltage

XLPE-silicon rubber interface is the weakest part of cable system. Dielectric breakdown called tracking failure of the interface often occurs. The failure endangers the reliability of power delivery. Massive application of power electronics easily causes over voltage or high electric field of impulse in power system, and leads to discharge or tracking failure of the interface. Therefore, it is very important to investigate the effect of impulse voltage on the tracking failure. In this paper, interface was set up by pressing together a slice of XLPE and a slice of transparent silicon rubber. High impulse voltage was applied on a pair of needle-plate electrodes which was sandwiched at the interface with their insulation distance of 10 mm. The discharge light and carbonization from discharge to the failure were recorded with a digital video recorder and then analyzed. As comparison of impulse voltage, tracking failure under AC voltage was also tested. The comparison results show that impulse over voltage leads to a short time of electric discharge of interface and produces lees heat energy. Tracking failure occurs difficultly. However, AC voltage has a longer time of over voltage in each cycle, which easily leads to arc discharge and produces a large amount of heat energy and easily causes tracking failure. It is supposed that once impulse over voltage initiates interface discharge when AC voltage is applied, interface tracking failure easily occurs. This result is important for operation of XLPE cable joint.