gebhart/patrepeval huggingface dataset:
Increasing Echinocandin Resistance in Candida glabrata: Clinical Failure Correlates With Presence of FKS Mutations and Elevated Minimum Inhibitory Concentrations (2013)

Echinocandin resistance is increasing, including among FLC-resistant isolates. The new Clinical and Laboratory Standards Institute clinical breakpoints differentiate wild-type from C. glabrata strains bearing clinically significant FKS1/FKS2 mutations. These observations underscore the importance of knowing the local epidemiology and resistance patterns for Candida within institutions and susceptibility testing of echinocandins for C. glabrata to guide therapeutic decision making.
Study of the effect of different aluminium surface pretreatments on the deposition of thin non‐functional silane coatings (2004)

Abstract This paper focuses on the effect of aluminium surface pretreatment on the formation of thin non‐functional silane films. Three pretreatments were used to prepare the aluminium surface before the deposition of silane films. The generated surfaces were characterized before and after the silane film deposition by infrared spectroscopic ellipsometry (IRSE) and by the combination of SEM, AES and spectroscopic ellipsometry (SE), respectively. It is demonstrated that the amounts of hydroxyl groups at the aluminium surface provided by the different pretreatments strongly influence the initiation and the formation of the silane films. Copyright © 2004 John Wiley &amp; Sons, Ltd.
A mouse model of paralytic myelitis caused by enterovirus D68 (2017)

In 2014, the United States experienced an epidemic of acute flaccid myelitis (AFM) cases in children coincident with a nationwide outbreak of enterovirus D68 (EV-D68) respiratory disease. Up to half of the 2014 AFM patients had EV-D68 RNA detected by RT-PCR in their respiratory secretions, although EV-D68 was only detected in cerebrospinal fluid (CSF) from one 2014 AFM patient. Given previously described molecular and epidemiologic associations between EV-D68 and AFM, we sought to develop an animal model by screening seven EV-D68 strains for the ability to induce neurological disease in neonatal mice. We found that four EV-D68 strains from the 2014 outbreak (out of five tested) produced a paralytic disease in mice resembling human AFM. The remaining 2014 strain, as well as 1962 prototype EV-D68 strains Fermon and Rhyne, did not produce, or rarely produced, paralysis in mice. In-depth examination of the paralysis caused by a representative 2014 strain, MO/14-18947, revealed infectious virus, virion particles, and viral genome in the spinal cords of paralyzed mice. Paralysis was elicited in mice following intramuscular, intracerebral, intraperitoneal, and intranasal infection, in descending frequency, and was associated with infection and loss of motor neurons in the anterior horns of spinal cord segments corresponding to paralyzed limbs. Virus isolated from spinal cords of infected mice transmitted disease when injected into naïve mice, fulfilling Koch's postulates in this model. Finally, we found that EV-D68 immune sera, but not normal mouse sera, protected mice from development of paralysis and death when administered prior to viral challenge. These studies establish an experimental model to study EV-D68-induced myelitis and to better understand disease pathogenesis and develop potential therapies.
Neural effects on sinus rate and atrioventricular conduction produced by electrical stimulation from a transvenous electrode catheter in the canine right pulmonary artery. (1980)

We studied the effects on sinus rate and atrioventricular (AV) conduction of electrical stimulation from a 12-polar electrode catheter advanced into the right pulmonary artery of 21 anesthetized dogs. In each experiment, the distal tip of the electrode catheter was positioned at a standard fluoroscopic site, and a sequence of bipolar electrograms was recorded during sinus rhythm from the 11 adjacent catheter electrode pairs using a standardized technique. Within each sequence of electrograms, a characteristic change in the polarity of the atrial complexes was identified at a site in the proximal right pulmonary artery. This recording site was labeled the site of initial polarity transition. Stimulus-strength response testing was performed from each catheter electrode pair during spontaneous sinus rhythm and during atrial fibrillation sustained by rapid atrial pacing. The least stimulus strengths required to slow sinus rate or to depress AV conduction were obtained using an electrode pair at a proximal right pulmonary artery site identified as the optimal stimulation site. This stimulation site was at, or immediately proximal to, the recording site of initial polarity transition. Stimulation distal to the site of initial polarity transition precipitated atrial fibrillation using stimulus strengths which were very low compared to stimulus strengths required to precipitate atrial fibrillation at more proximal sites. Negative chronotropic and negative dromotropic effects persisted throughout 5-minute periods of stimulation from the optimal stimulation site and could be modulated by varying stimulus parameters. Using neurophysiological and neuropharmacological techniques, we demonstrated that these effects were produced by stimulation of preganglionic parasympathetic efferent nerve fibers.
Detection of biomarker in breath: A step towards noninvasive diabetes monitoring (2008)

Along with more than two hundred volatile organic compounds (VOCs), acetone is also a normal constituent of breath of healthy individuals, albeit in the sub-ppm range, and its concentration increases in diabetic patients. Considering the importance of breath acetone as a biomarker of diabetes, some studies have already been made to measure breath acetone concentration (and correlate with blood sugar level) using GC-MS. There are a few reports of measuring breath acetone concentration using semiconductor sensor in the background of air (i.e. in the absence of VOCs present in normal breath and hence the question of selectivity remains in the real situation) and at a higher concentration (above 10 ppm). We report excellent sensitivity of sonochemically prepared nanosized gamma-Fe2O3 sensors towards sub-ppm acetone (pathological range) in the background of human breath. Our preliminary results should stimulate further research towards developing cheap, rugged and compact semiconductor sensors for noninvasive monitoring of diabetes.
Recursive parameter estimation (1990)

Abstract The use of recursive filtering techniques for parameter estimation in a variety of areas is reviewed. In particular, the Kalman filter algorithm is described, along with several variations, including square‐root, UDU T and information filters. The solution to parameter estimation problems is discussed for both linear and non‐linear models. Applications described include calibration, curve resolution in spectroscopy, chromatography, electrochemistry, kinetic analysis and process monitoring.
Bone Marrow Processing and Purging: a Practical Guide (1991)

INTRODUCTION AND GENERAL GUIDELINES. Preface (Adrian P. Gee). An Introduction to Bone Marrow Transplantation and Processing (A. John Barrett). Regulatory Aspects of Bone Marrow Processing and Purging (Curtis L. Scribner). Quality Control in Bone Marrow Processing (Adrian P. Gee). HARVESTING, SHIPPING, AND NUCLEATED CELL SEPARATION. Bone Marrow Harvesting and Reinfusion (Jennifer G. Treleaven). Transportation of Bone Marrow for In Vitro Processing and Transplantation (William E. Janssen and Carlos Lee). Nucleated Cell Separation Using the Fenwall CS-3000' (Herbert M. Cullis, Ellen Areman, and Charles S. Carter). Use of the Cobe 2991' Cell Processor for Bone Marrow Processing (John D. McMannis). Bone Marrow Processing With the Haemonetics V50 Plus' (MaryLynne Hartl). BONE MARROW EVALUATION. Bone Marrow Cell Counting: Methodological Issues (Elizabeth J. Read, Charles S. Carter, and Herbert M. Cullis). Detection of Metastatic Tumor Cells in Bone Marrow (Thomas J. Moss). Flow Cytometric Analysis of Human Bone Marrow (James G. Bender and Dennis Van Epps). Quantitative Assays for Human Hemopoietic Progenitor Cells (Heather J. Sutherland, Allen C. Eaves, and Connie J. Eaves). LYMPHOCYTE DEPLETION FOR ALLOGENEIC TRANSPLANTATION. Lymphocyte Dose Modification of the Bone Marrow Allograft Using Elutriation (Stephen J. Noga, Janice M. Davis, and Albert D. Donnenberg). T Cell Depletion of Allogeneic Human Bone Marrow Grafts by Soybean Lectin Agglutination and either Sheep Red Blood Cell Rosetting or Adherence on the CD5/CD8 Cellector' (Nancy H. Collins, Nancy A. Kernan, Sharon A. Blean, and Richard J. O'Reilly). Immunotoxin-Mediated Depletion of CD5+ T Cells from Bone Marrow for Graft-vs.-Host Disease Prophylaxis (Joseph H. Antin, Howard J. Weinstein, and Barbara Bierer). The Use of Campath' Monoclonal Antibodies for Ex Vivo Treatment of Bone Marrow (Derwood Pamphilon). AUTOLOGOUS BONE MARROW PURGING. The Use of 4-HC in Autologous Purging (Scott D. Rowley and Janice Davis). Extracorporeal Purging of Bone Marrow Grafts by Dye-Sensitized Photoirradiation (Fritz Sieber). Monoclonal Antibodies and Complement for Autologous Marrow Purging (Edward D. Ball). The Immunomagnetic Manipulation of Bone Marrow (John T. Kemshead). Combined Purging Approaches in Autologous Transplantation (Elizabeth J. Shpall, Robert C. Bast, Charles S. Johnston, William P. Peters, and Roy B. Jones). MARROW CRYOPRESERVATION AND FUTURE TRENDS. Cryopreservation of Human Bone Marrow Grafts (Ping Law and Harold Meryman). Simplified Bone Marrow Cryopreservation Using Dimethylsulfoxide and Hydroxyethyl Starch as Cryoprotectants (Patrick J. Stiff). Selection of Human Hemopoietic Stem Cells (Peter Lansdorp and Terry E. Thomas). Genetic Manipulation of Human Marrow: Gene Transfer Using Retroviruses (Philip Hughes and R. Keith Humphries). c. 360 pp., 33 tables, 52 illus., 7x10, due November 1991, ISBN 0-8493-6402-7.
Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2α subunit of NuRD (2001)

Macromolecular complexes containing histone deacetylase and ATPase activities regulate chromatin dynamics and are vitally responsible for transcriptional gene silencing in eukaryotes. The mechanisms that target these assemblies to specific loci are not as well understood. We show that the corepressor KAP-1, via its PHD (plant homeodomain) and bromodomain, links the superfamily of Krüppel associated box (KRAB) zinc finger proteins (ZFP) to the NuRD complex. We demonstrate that the tandem PHD finger and bromodomain of KAP-1, an arrangement often found in cofactor proteins but functionally ill-defined, form a cooperative unit that is required for transcriptional repression. Substitution of highly related PHD fingers or bromodomains failed to restore repression activity, suggesting high specificity in their cooperative function. Moreover, single amino acid substitutions in either the bromodomain or PHD finger, including ones that mimic disease-causing mutations in the hATRX PHD finger, abolish repression. A search for effectors of this repression function yielded a novel isoform of the Mi-2alpha protein, an integral component of the NuRD complex. Endogenous KAP-1 is associated with Mi-2alpha and other components of NuRD, and KAP-1-mediated silencing requires association with NuRD and HDAC activity. These data suggest the KRAB-ZFP superfamily of repressors functions to target the histone deacetylase and chromatin remodeling activities of the NuRD complex to specific gene promoters in vivo.
Constrained Cartesian motion control for teleoperated surgical robots (1996)

This paper addresses the problem of optimal motion control for teleoperated surgical robots, which must maneuver in constrained workspaces, often through a narrow entry portal into the patient's body. The control problem is determining how best to use the available degrees of freedom of a surgical robot to accomplish a particular task, while respecting geometric constraints on the work volume, robot mechanism, and the specific task requirements. We present a method of formulating desired motions as sets of task goals in any number of coordinate frames (task frames) relevant to the task, optionally subject to additional linear constraints in each of the task frames. Mathematically, the kinematic control problem is posed as a constrained quadratic optimization problem and is shown to be computable in real time on a PC. We will present experimental results of the application of this control methodology to both kinematically deficient and kinematically redundant robots. Specifically, we will discuss the control issues within the context of a representative set of tasks in robot-assisted laparoscopy, which includes (but is not limited to) teleoperated navigation of a laparoscopic camera attached to a surgical robot. A system based on this control formalism has been used in preclinical in vivo studies at the Johns Hopkins University Medical Center and the early experience with the system will be summarized.
Cost-effectiveness of linezolid versus vancomycin in mechanical ventilation-associated nosocomial pneumonia caused by methicillin-resistant staphylococcus aureus (2005)

Despite the higher price per unit, linezolid was more cost-effective than vancomycin.
Cell cycle modulation by a multitargeted antifolate, LY231514, increases the cytotoxicity and antitumor activity of gemcitabine in HT29 colon carcinoma. (1999)

The proliferation rate of HT29 colon carcinoma cells was decreased by the multitargeted antifolate (MTA), LY231514. This effect correlated with a buildup of cells near the G1-S interface after 24 h of incubation, and a synchronized progression of the population through S phase during the next 24 h. MTA treatment (0.03-3 microM) was minimally cytotoxic (20-30%) to HT29 cells after a 24-h exposure, and no dose response was observed. In contrast, the nucleoside analogue gemcitabine (GEM) was cytotoxic (IC50, 0.071 +/- 0.011 microM; IC90, 0.648 +/- 0.229 microM) after a 24-h exposure. We hypothesized that pretreatment of these cells with MTA would increase the potency of GEM by synchronizing the population for DNA synthesis. The cytotoxicity of GEM increased 2-7-fold when MTA was administered 24 h before GEM (IC50, 0.032 +/- 0.009 microM; IC90, 0.094 +/- 0.019 microM). In addition, an increase in cell kill for the combination compared with GEM alone (IC99, 12 microM for GEM alone; IC99, 0.331 microM for combination) was observed. No increase in potency or cell kill was observed when the two compounds were added simultaneously. MTA pretreatment also potentiated the cytotoxicity of a 1-h exposure to GEM. These cell-based observations were extended to evaluate the schedule-dependent interaction of these two agents in vivo using a nude mouse HT29 xenograft tumor model. At the doses tested, MTA alone (100 mg/kg) had a marginal effect on tumor growth delay, whereas GEM (80 mg/kg) produced a statistically significant tumor growth delay. In combination, the increase in tumor growth delay was greatest when MTA was administered before GEM, compared with simultaneous drug administration or the reverse sequence, e.g., GEM followed by MTA. The effect of sequential administration of MTA followed by GEM was greater than additive, indicating synergistic interaction of these agents. Thus, in vitro, MTA induced cell cycle effects on HT29 cells that resulted in potentiation of the cytotoxicity of GEM. In vivo, combination of these two drugs also demonstrated a schedule-dependent synergy that was optimal when MTA treatment preceded GEM.
Triple-Negative Breast Cancer: An Unmet Medical Need (2011)

Triple-negative breast cancer, characterized by tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or HER-2 genes, represents an important clinical challenge because these cancers do not respond to endocrine therapy or other available targeted agents. The metastatic potential in triple-negative breast cancer is similar to that of other breast cancer subtypes, but these tumors are associated with a shorter median time to relapse and death. One important goal is therefore the identification of prognostic factors and markers to reliably select high and low risk subsets of patients with triple-negative disease for different treatment approaches of subtypes with differential responsiveness to specific agents. However, a reliable prognostic marker has been elusive, and markers have been inconsistently useful. For example, epidermal growth factor receptor (EGFR) has been studied, but there is still a lack of agreement on a standard assay or cutoff for EGFR expression levels with respect to prognosis. Similarly, because triple-negative status is sometimes used as a surrogate for basal-like breast cancer, specific basal markers have been explored. Indeed, trials designed to accrue patients with basal-like breast cancer using ER/PR and HER-2 negativity may provide only an approximation of the triple-negative population and are sometimes reanalyzed using more specific indicators like CK 5/6, EGFR status, and others, again marred by discordances. Chemotherapy remains the mainstay of treatment of triple-negative breast cancer, but important limitations still need to be overcome in the next few years if any significant clinical strides are to be made. Current treatment strategies for triple-negative disease include anthracyclines, taxanes, ixabepilone, platinum agents, and biologic agents. More recently, EGFR inhibition has been proposed as a therapeutic mechanism in triple-negative breast cancer, again with mixed results. Agents that target poly(ADP-ribose) polymerase and androgen receptors have also been proposed in these patients or subsets of them, and ongoing trials should result in definitive guidance with respect to the value of these agents in triple-negative disease. Triple-negative breast cancer is clearly a distinct clinical subtype, from the perspective of both ER and HER-2 expression, but further subclassification is needed. At present, there is not a clear, proven effective single agent that targets a defining vulnerability in triple-negative breast cancer. This article will review the clinical problem of triple-negative disease, potential prognostic factors, demonstrated efficacy of currently available therapeutic options, and new potential therapies.
Splice Variants of Type VIII Adenylyl Cyclase (1996)

Three alternatively spliced type VIII adenylyl cyclase messages have been identified by cDNA cloning and amplification from rat brain cDNA. Type VIII-A was previously referred to simply as type VIII (Cali, J. J., Zwaagstra, J. C., Mons, N., Cooper, D. M. F., and Krupinski, J. (1994) J. Biol. Chem. 269, 12190-12195). The types VIII-B and -C cDNAs differ from that of type VIII-A by deletion of 90 and 198 base pair exons, respectively, which encode a 30-amino acid extracellular domain with two consensus sites for N-linked glycosylation and a 66-amino acid cytoplasmic domain. Stable expression of types VIII-A, -B, and -C cDNAs in human embryonal kidney 293 (HEK-293) cells leads to the appearance of novel proteins, which are recognized by type VIII-specific antibodies and which co-migrate with immunoreactive species detected on immunoblots of rat brain membranes. Types VIII-A and -C are modified by N-linked glycosylation, while type VIII-B is insensitive to treatment with N-glycosidase F. An influx of extracellular Ca2+ stimulates cAMP accumulation in HEK-293 cells stably expressing type VIII-A, -B, or -C, but not in control cells. Adenylyl cyclase activity of each of the variants is stimulated by Ca2+/calmodulin and the EC50 for activation of type VIII-C is one fourth of that for either type VIII-A or -B. Type VIII-C also has a distinct Km for substrate, which is approximately 4-12-fold higher than that for types VIII-A or -B depending on whether Mn2+ or Mg2+ is the counterion for ATP. The differences in the structural and enzymatic properties of these three variants are discussed.
Experimental Alteration of Chinchilla Middle Ear Mucosae by Bacterial Neuraminidase (1986)

Streptococcus pneumoniae secretes a variety of extracellular glycosidase including a neuraminidase which has been found in middle ear effusion from patients with both acute and chronic otitis media. This enzyme cleaves sialic acid from membrane glycoproteins, thereby exposing galactose residues, the penultimate sugar. The ability of partially purified neuraminidase to alter the middle ear mucosa was investigated in the chinchilla. After incubation with neuraminidase, chinchilla middle ears were removed and exposed to galactose residues labeled with tritium. Membrane glycoproteins were solubilized and separated according to molecular weight by sodium dodecylsulfate electrophoresis. Increases in tritium incorporation, when compared to control incubations, indicated that galactose residues had been exposed and sialic acid residues removed from glycoproteins of both high and low molecular weight. Such membrane destruction could contribute significantly to the pathology of otitis media with effusion.
Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics (2017)

In vitro incubation of nanomaterials with plasma offer insights on biological interactions, but cannot fully explain the in vivo fate of nanomaterials. Here, we use a library of polymer nanoparticles to show how physicochemical characteristics influence blood circulation and early distribution. For particles with different diameters, surface hydrophilicity appears to mediate early clearance. Densities above a critical value of approximately 20 poly(ethylene glycol) chains (MW 5 kDa) per 100 nm<sup>2</sup> prolong circulation times, irrespective of size. In knockout mice, clearance mechanisms are identified for nanoparticles with low and high steric protection. Studies in animals deficient in the C3 protein showed that complement activation could not explain differences in the clearance of nanoparticles. In nanoparticles with low poly(ethylene glycol) coverage, adsorption of apolipoproteins can prolong circulation times. In parallel, the low-density-lipoprotein receptor plays a predominant role in the clearance of nanoparticles, irrespective of poly(ethylene glycol) density. These results further our understanding of nanopharmacology.Understanding the interaction between nanoparticles and biomolecules is crucial for improving current drug-delivery systems. Here, the authors shed light on the essential role of the surface and other physicochemical properties of a library of nanoparticles on their in vivo pharmacokinetics.
A Mechanism-Based Inactivator for Histone Demethylase LSD1 (2006)

Histone demethylase LSD1 is a flavin-dependent amine oxidase that catalyzes the oxidative removal of one or two methyl groups from the methyl-lysine-4 side chain of histone H3. We have designed and synthesized two peptide-based inhibitor analogues that block LSD1. One of these inhibitors, compound 1, contains a propargylamine functionality and shows time-dependent inactivation of LSD1. Peptide substrate, diMeK4H3-21, protected LSD1 against inactivation by 1 in a concentration-dependent fashion. Mass spectrometric analysis showed that 1 forms a covalent interaction with FAD. Compound 1 did not detectably inhibit monoamine oxidase B in the concentration range studied. Compound 1 is thus a selective, mechanism-based inactivator of LSD1 and is likely to serve as a useful tool in the study of histone modifications and chromatin remodeling.