Miracle-dz/UniFAR-FTUs huggingface dataset:
Isolation and characterization of a Clostridium botulinum C2 toxin-resistant cell line: evidence for possible involvement of the cellular C2II receptor in growth regulation

Clostridium botulinum C2 toxin, which consists of the binding component C2II and the enzyme component C2I, acts on eukaryotic cells by selective ADP-ribosylation of G-actin. To obtain C2 toxin-resistant cells, we mutagenized CHO-K1 cells with N-nitroso-N-methylurea and selected for C2 resistance. Cells which survived the selection procedure with 50 ng of C2I and 100 ng of C2II per ml were obtained with a frequency of 30 x 10(-6). The colony-forming ability of CHO wild-type cells was reduced to 50% with 10 ng of C2I and 20 ng of C2II per ml. In contrast, the colony-forming ability of the isolated CHO mutant cells was not influenced by up to 200 ng of C2I and 400 ng of C2II per ml. Toxin-induced ADP-ribosylation of G-actin was not impaired in lysates of mutant cells. The C2 toxin-resistant phenotype remained sensitive to the cell-rounding activities of cytotoxins from C. perfringens (iota-toxin), C. novyi, C. difficile, and C. botulinum (C3) and to cytochalasin D. Binding of component C2II was impaired in resistant CHO cells, suggesting mutation of the toxin cell surface receptor. Serum factors protected wild-type cells against the cytotoxic effect of C2 toxin. Furthermore, the C2-resistant phenotype correlated with an increased serum dependency. The data suggest that the action of C. botulinum C2 toxin is mediated by its binding and uptake via a cell surface receptor which might be involved in growth regulation.
Air Pollution and Exacerbation of Asthma in African-American Children in Los Angeles

Significant increases in asthma morbidity and mortality in the United States have occurred since the 1970s, particularly among African-Americans. Exposure to various environmental factors, including air pollutants and allergens, has been suggested as a partial explanation of these trends. To examine relations between several air pollutants and asthma exacerbation in African-Americans, we recruited a panel of 138 children in central Los Angeles. We recorded daily data on respiratory symptoms and medication use for 13 weeks and examined these data in conjunction with data on ozone (O3) nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), meteorological variables, pollens, and molds. Using generalized estimating equations, we found associations between respiratory symptom occurrence and several environmental factors. For example, new episodes of cough were associated with exposure to PM10 (OR = 1.25; 95% CI = 1.12–1.39; interquartile range [IQR] = 17 &mgr;g/m3, 24-hour average), PM2.5 (OR = 1.10; 95% CI = 1.03–1.18; IQR = 30 &mgr;g/m3, 12-hour average), NO2, and the molds Cladosporium and Alternaria, but not with exposure to O3 or pollen. The factors PM10 and O3 were associated with the use of extra asthma medication. For this population several bioaerosols and air pollutants had effects that may be clinically significant.
Is there a relationship between light touch-pressure sensation and functional hand ability?

Purpose. To investigate and compare the level of light touch-pressure sensation as tested via the Semmes Weinstein monofilament (SWM) test with the level of functional hand ability. Methods. Twenty-seven persons with isolated sensory deficit due to leprosy and 31 healthy controls were tested in the Occupational Therapy department of a hospital for patients with Hansen's disease. Palmar light touch thresholds were determined by SMW testing. Functional hand ability was tested via the Jebsen-Taylor Hand Function Test (JTHFT) and the Functional Dexterity Test (FDT). All participants were measured by manual muscle testing (MMT) to exclude any motor impairment. Data analysis compared sensory thresholds and level of functional hand ability between the two groups and examined the relationship between the variables. Results. In the group with sensory deficit, the sensory thresholds were significantly higher than in the control group. Significant correlations were found between the sensory thresholds measured by the SWM test and the FDT and JTHFT scores, with higher correlations found for tasks entailing manipulation of small objects. Conclusions. The findings support the existence of a relationship between sensory light touch thresholds tested by the Semmes Weinstein monofilaments (SWMs) and hand function. However, the SWM test alone is not sufficient as an indicator of hand function and must therefore be supplemented with other hand function tests.
Anti-inflammatory potential of a lipid-based formulation of a rotenoid-rich fraction prepared from Boerhavia diffusa

Abstract Context: Boerhavia diffusa L. (Nyctaginaceae) roots are used in Ayurveda for treating inflammatory diseases. Generally poor oral bioavailability is a major problem associated with herbal drugs. Objective: To develop a phospholipid complex of rotenoid-rich fraction (RRF) and evaluate its in vivo anti-inflammatory activity and pharmacokinetic study. Materials and methods: RRF was prepared from a 70% ethanol extract of B. diffusa roots. This RRF was complexed with phosphatidylcholine by refluxing in 70% ethanol. In vivo anti-inflammatory activity of RRF-PC and RRF was determined using the carrageenan-induced rat paw edema method, at a dose equivalent to 100 mg/kg p.o. of RRF. Edema volume was calculated at 3 and 5 h. The plasma concentration of boeravinone B was estimated in rats at a same dose level. Blood samples were collected at 1, 2, 4, 6, 8, 10, 12, 24, and 36 h. Results: 1H and 31P NMR spectra of RRF-PC showed up-field shift of protons of the +N(CH3)3 group (3.37 → 3.23) and the phosphorus atom (−1.26 → −1.57 ppm), respectively, which confirmed phospholipid complex formation between phosphatidylcholine [PO4 and +N(CH3)3 groups] and phytoconstituents by hydrogen bonding. The RRF-PC showed significantly enhanced in vivo anti-inflammatory activity (64%) as compared with RRF (48%) and ibuprofen (50%) at 5 h (p < 0.001). Furthermore, detected plasma concentration of boeravinone B was two times higher in RRF-PC (75 ng/mL) as compared with RRF (40 ng/mL). Conclusion: The present study demonstrated an increased anti-inflammatory potential and higher plasma level of boeravinone B in lipid-based formulation (RRF-PC) as compared with RRF.
The crusade of digital disruption

Purpose This paper aims to help managers understand digital disruption and implement strategies that will support the digital transformation of companies. Traditional companies need to learn from disruptive ventures and reimagine their business models based on digitalization. Design/methodology/approach The study is based on multiple case studies of both disruptive startups and established organizations navigating digital transformations. Findings The authors introduce three levels of digitalization to build a framework of six different value creation stages that result from digitalization. Companies need to create digital products, enhance their processes with digital technology and most important reimagine their business models. Practical implications Managers receive guidance on how to deal with digital disruption. They can learn from pathfinding companies that successfully leveraged digital technology to create and capture new value. Originality/value The original contribution of this paper is a simple and useful framework to understand and leverage digital disruption.
A Rate Adaptive Hybrid MAC Protocol for Wireless Cellular Networks

Efficient medium access control (MAC) protocol plays a critical role in wireless mobile networks. In this paper, we propose a rate adaptive hybrid MAC (RAH-MAC) protocol to support differential services in wireless cellular networks. RAH-MAC is a hybrid of polling and contention MAC protocol. In RAH-MAC, when a mobile terminal (MT) has data to send, it first uses the contention time slot to join the BS polling list. The contention time is dynamically allocated based on the system traffic load. An MT with high priority services has high priority to access the contention channel. The BS allocates a data transmission time slot for a registered MT. The time slot duration is based on the MT's demanded service class. An MT transmits data after it receives the polling message from the BS. The data transmission rate is adaptively adjusted based on the channel conditions. The simulation results show that RAH- MAC is superior to the existing MAC protocols.
The fabrication of dense and uniform InAs nanowire arrays

Nanowires are important candidates for use in future electronics, photonics and thermoelectrics applications. We focus here in particular on nanowires for use in thermoelectric power generation and present a method of fabricating dense uniform InAs nanowire arrays amenable to future incorporation of advanced heterostructures that could further increase the thermoelectric performance of these nanowires. In these applications it will be important to have the nanowires densely packed in order to give an appreciable amount of power output. Here we present the fabrication of such dense arrays, using metal-particle seeded growth and chemical beam epitaxy, where the metal particles are defined by electron beam lithography, metal evaporation and lift-off. We evaluate the potential of chemical beam epitaxy for the growth of dense, freestanding InAs nanowire arrays and describe the process that enabled us to achieve areal packing densities of up to 19% with a variation of only a few per cent in nanowire diameter and height. We close by discussing how even higher areal packing densities can be achieved.
Sensitivity of gait parameters to the effects of anti‐inflammatory and opioid treatments in knee osteoarthritis patients

The study aim was to address the need for objective markers of pain‐modifying interventions by testing the hypothesis that selective gait measures of knee joint loading can distinguish differences between non‐steroidal anti‐inflammatory (NSAID), analgesic treatment (opioid‐receptor agonist), and placebo in patients medial knee osteoarthritis (OA). A randomized, single‐blind washout, double‐blind treatment, double‐dummy cross‐over trial using three treatment arms placebo, opioid (Oxycodone), and NSAID (Celecoxib) in medial compartment knee OA patients. Six patients with Kellgren–Lawrence radiographic severity grades of 2 or 3 completed six testing sessions (gait and pain assessment) at 2‐week intervals. A significant increase was found in the knee total reaction moment and vertical ground reaction force (GRF) for Celecoxib compared to placebo (p = 0.005, p = 0.003), but not for Oxycodone compared to placebo (p = 0.20, p = 0.27) treatments. Walking speed was significantly higher for the Celecoxib and Oxycodone compared to placebo treatment (p = 0.041 and p = 0.031, respectively). Self‐reported function (WOMAC scores) was not different among treatments (p > 0.05). The changes in total reaction moments and GRFs for only the NSAID suggest that greater increases in joint loading occurs when joint inflammation is treated in addition to pain. The total knee reaction moment, representing the magnitude of the extrinsic moment, appears to be a sensitive marker, more so than self‐reported metrics, for evaluating knee OA treatment effects. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1118–1124, 2012
The effects of social context and defensiveness on the physiological responses of repressive copers.

In previous research (T.L. Newton & R.J. Contrada, 1992), social context was found to moderate exaggerated physiological reactivity among individuals identified as using a repressive coping style. In this experiment, 119 undergraduates were classified into low-anxious, high-anxious, repressor, and defensive high-anxious coping categories. All participants completed a stressful speech task under either a public or private social context condition. The experimental social context was related to physiological reactivity and self-reported affect but did not moderate reactivity among repressive copers. Additionally, reactivity among repressive copers was not attributable to high defensiveness alone. Consistent with a theory of emotional inhibition, nonspecific skin conductance responses, but not heart rate, discriminated between repressors and nonrepressors.
Increase of proliferating oligodendroglial progenitors in the adult mouse brain upon Sonic hedgehog delivery in the lateral ventricle

Sonic hedgehog signaling is required for the maintenance of stem cell niches in the postnatal subventricular zone and the proliferation of neural progenitors in the mature hippocampus. We show here that delivery of Sonic hedgehog protein into the lateral ventricle of adult mice increases cell proliferation in the corpus callosum and cerebral cortex. In this latter area, the number of neural progenitors expressing the proteoglycan NG2 is enhanced 2 days after the injection. In both areas, mRNA up‐regulation of the transcriptional target gene Patched was observed in cells expressing the oligodendroglial transcription factor Olig1. Twenty‐six days following the adenovirus‐mediated delivery of Sonic hedgehog into the lateral ventricle, newly generated cells in the cerebral cortex and in the corpus callosum are influenced towards the initial steps of oligodendrogenesis, as indicated by a 50% increase in the number of cells expressing the oligodendroglial marker DM20. Our experiments demonstrate that the number of oligodendrocyte precursor cells in the cerebral cortex and corpus callosum can be increased upon delivery of Sonic hedgehog proteins and highlight the potential capacity of the adult brain to mobilize a pool of premyelinating cells.
CRITICAL CARE THERAPEUTICS

Injury or stress generates a vigorous metabolic response designed to establish the metabolic priorities required for the repair of injured tissues. In this condition, hormones commonly found to be elevated in the plasma include glucagon, catecholamines, glucocorticoids, growth hormone, aldosterone, and antidiuretic hormone. This hormonal profile results in rapid lysis of body protein, an increased rate of fat oxidation, and water and salt conservation. Rates of gluconeogenesis and ureagenesis are accelerated and may result in significant losses in lean body mass, a process that, if allowed to progress, will adversely affect patient survival. Exogenous nutrients provided to the critically ill patient may be poorly tolerated and may result in complications. Dextrose and intravenous fat emulsions provide the major sources of parenteral, nonprotein energy. These energy sources may not be metabolized efficiently in these patients, even though energy expenditure in this condition is increased significantly. Measurement of urinary nitrogen losses yields evidence useful in assessing the patient's degree of stress. In this manner, the patient's energy and protein requirements may be estimated. Formulations of amino acids, including the branched-chain amino acids, in higher concentrations have been reported to have anticatabolic effects and may improve the maintenance of lean body mass in stressed individuals. The stressed patient is prone to metabolic complications and, therefore, requires more careful monitoring of fluid, electrolyte, and acid-base balance, as well as renal, pulmonary, and liver function. Nutritional status is difficult to assess, since negative nitrogen balance may persist and the visceral proteins such as Addresscorrespondence and reprint requests to Jay M. Mirtallo,M.S., B.S.Pharm. , Division of Pharmacy Practice, College of Pharmacy, The Ohio State University, Columbus, OH 43210. KENNETH A. KUDSK, M.D., is Resident in Surgery, Department of Surgery, College of Medicine; and JAY M. MIRTALLO, M.S., B.S.Pharm. , is Clinical Pharmacist, Department of Pharmacy, University Hospitals, and Assistant Clinical Professor, Division of Pharmacy Practice, College of Pharmacy, The Ohio State University, Columbus, OH 43210. JOSEPH F. DASTA, M.S.(Pharm.), is Assistant Professor, Divisionof Pharmacy Practice, College of Pharmacy, and Assistant Professor, Department of Anesthesiology, Collegeof Medicine,The Ohio State University, 500 W. 12th Ave., Columbus, OH 43210. This article has been selected for PhannaCE testing. It may be used for cont inuing education credit in the United States and Canada. DIGP is a member of the Council on the Continuing Edu cation Unit (CEU) and is approved by the American Council on Pharmaceutical Education as a provider of cont inuing education (provider number 180-407 ) . transferrin become altered in stress and, therefore, may not respond to nutritional intervention alone. The goal of nutritional therapy is the preservation of lean body mass by the safe and efficacious provision of metabolic substrate, thus improving patient survival. Drug Intell Clin Pharm 1983;17:501-6.
Treatment of osteoporosis and prevention of new fractures: role of intravenously administered bisphosphonates.

OBJECTIVE To evaluate the usefulness of intravenously administered bisphosphonates for improving absorption, tolerability, adherence, and outcomes in the treatment and prevention of osteoporosis. METHODS Data published from 1996 to 2009 relevant to the treatment of osteoporosis, with emphasis on bisphosphonates, fracture risk, adherence to therapy, frequency of dosing, intravenous treatment, tolerability, cost-effectiveness, and quality of life, were reviewed. RESULTS Although bisphosphonates are currently the standard of care for treatment of postmenopausal osteoporosis and osteoporosis in men, oral formulations are associated with poor absorption and potential irritation of the upper gastrointestinal tract. These issues necessitate complicated and restrictive dosing regimens, which in turn lead to poor compliance and persistence. Intravenous formulations such as 3 mg of ibandronate given quarterly and 5 mg of zoledronic acid administered once yearly avoid problems relating to absorption and tolerability by bypassing the gastrointestinal tract. Intravenously administered ibandronate is presumed (by virtue of similar or superior improvements in bone mineral density) to have antifracture efficacy similar to that of orally administered ibandronate given daily, which has been shown to produce significant reductions in vertebral fractures during a 3-year period in comparison with placebo. Zoledronic acid, 5 mg once yearly, has been shown to produce a significant reduction in the risk of morphometric vertebral fractures, clinical vertebral fractures, hip fractures, and nonvertebral fractures versus placebo during a 3-year interval in patients with postmenopausal osteoporosis and also to yield a significantly decreased risk for new clinical fractures versus placebo in patients with recent low-trauma hip fracture. Both agents have favorable safety and tolerability profiles. CONCLUSION Intravenously administered bisphosphonates have the potential to increase compliance and persistence with therapy in patients with osteoporosis and to improve patient outcomes.
Application of a Rapid and Integrated Analysis System (RIAS) as a High-Throughput Processing Tool for In Vitro ADME Samples by Liquid Chromatography/Tandem Mass Spectrometry

Over the past decade, drug discovery programs have started to address the optimization of key ADME properties already at an early stage of the process. Hence, analytical chemists have been confronted with tremendously rising sample numbers and have had to develop methodologies accelerating quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS). This article focuses on the application of a generic and fully automated LC/MS/MS, named Rapid and Integrated Analysis System (RIAS), as a high-throughput platform for the rapid quantification of drug-like compounds in various in vitro ADME assays. Previous efforts were dedicated to the setup and feasibility study of a workflow-integrated platform combining a modified high-throughput liquid handling LC/MS/MS system controlled by a customized software interface and a customized data-processing and reporting tool. Herein the authors present an extension of this previously developed basic application to a broad set of ADME screening campaigns, covering CYP inhibition, Caco-2, and PAMPA assays. The platform is capable of switching automatically between various ADME assays, performs MS compound optimization if required, and provides a speed of 8 s from sample to sample, independently of the type of ADME assay. Quantification and peak review are adopted to the high-throughput environment and tested against a standard HPLC-ESI technology.
A Bispecific HER2-Targeting FynomAb with Superior Antitumor Activity and Novel Mode of Action

Upregulation of HER2 is a hallmark of 20% to 30% of invasive breast cancers, rendering this receptor an attractive target for cancer therapy. Although HER2-targeting agents have provided substantial clinical benefit as cancer therapeutics, there is a need for the development of new agents aiming at circumventing anti-HER2 resistance. On the basis of the approved antibody pertuzumab, we have created a panel of bispecific FynomAbs, which target two epitopes on HER2. FynomAbs are fusion proteins of an antibody and a Fyn SH3–derived binding protein. One bispecific FynomAb, COVA208, was characterized in detail and showed a remarkable ability to induce rapid HER2 internalization and apoptosis in vitro. Moreover, it elicited a strong inhibition of downstream HER2 signaling by reducing HER2, HER3, and EGFR levels in vitro and in vivo. Importantly, COVA208 demonstrated superior activity in four different xenograft models as compared with the approved antibodies trastuzumab and pertuzumab. The bispecific FynomAb COVA208 has the potential to enhance the clinical efficacy and expand the scope of HER2-directed therapies, and delineates a paradigm for designing a new class of antibody-based therapeutics for other receptor targets. Mol Cancer Ther; 13(8); 2030–9. ©2014 AACR.
The Effect of Fluid Replacement on Endurance Performance

The purpose of this study was to examine the effects of fluid replacement on power output (PO), rating of perceived exertion (RPE), heart rate (HR), body weight (BW), urine osmolarity (Uosm), and urine electrolyte concentrations ([UNa+], [UK+], [UCl-]) in physically active men (n = 4) and women (n = 7). The participants were asked to generate their highest possible PO during 60 minutes of cycling under 3 randomized conditions: ingestion of (a) no fluid (trial 1); (b) 1200 ml of distilled water (trial 2); and (c) 1200 ml of Gatorade (trial 3). BW and urine volume (Vu) were measured before and after the ride to determine sweat rate [(SR = ΔBW + Vfluid intake + Vu)/time]. The results indicated that there were no significant differences between trials for PO (123–127 W), RPE (14), HR (140–142 b·min−1), and SR (11.9–12.4 ml·min−1). However, [UNa+] was significantly (p < 0.05) lower postexercise for all 3 trials, and [UCl-] was significantly reduced following trials 2 and 3. There was a significant increase (p < 0.001) in BW postexercise for trials 2 and 3 when compared with the no-fluid trial; however, the effects of water and Gatorade were similar. These results suggest that fluid replacement during 1 hour of moderately intense cycling does not enhance performance in physically active men and women who are normally hydrated.