gebhart/patrepeval huggingface dataset:
Resistance mechanisms in human sarcoma mutants derived by single-step exposure to paclitaxel (Taxol). (1996)

A fluctuation analysis experiment was performed by exposing 15 expanded populations of MES-SA sarcoma cells to paclitaxel (Taxol) at a concentration of 10 nM for 7 days. The mutation rate was approximately 8 multiplied by 10(-7)/cell generation. ANOVA supports a stochastic cell survival mechanism of spontaneous mutation rather than induction of an adaptive response under these selection conditions. Surviving colonies were found in 12 populations, 9 of which had clones that remained resistant to paclitaxel after a 2-month period of propagation. Analysis of mdr1 gene expression by reverse transcription PCR demonstrated positive clones in 4 of the 9 populations with stable resistance. Accumulation of [(3)H]paclitaxel was decreased in these clones but not in the mdr1-negative clones compared with parental cells. A high degree of resistance to paclitaxel (36- to 93-fold) was selected by this single drug exposure in all 9 stably resistant mutants. Those with mdr1 activation demonstrated a broad cross-resistance to vinblastine, doxorubicin, and etoposide, whereas the other 6 mutants were cross-resistant only to the Vinca alkaloids. Because tubulins are the target molecules for paclitaxel cytotoxicity, we evaluated total tubulin content by immunoblotting and performed semiquantitative reverse transcription PCR analysis for expression of the alpha-tubulin isotypes B alpha 1, K alpha 1 and H alpha 44, the beta-tubulin isotypes M40, beta9, 5beta, beta2 and beta4, and gamma-tubulin. Total tubulin content was decreased significantly in one of the single-step mutants. All surviving clones, both resistant and sensitive to paclitaxel, displayed reduced expression of the 5beta and beta 4 beta-tubulin isotype transcripts in comparison with the parental cell line. These data suggest that stringent exposure to paclitaxel selected clones with reduced transcript levels of 5beta and beta4 beta-tubulin isotypes, but that these reduced levels were not directly involved in the resistance of the clones to paclitaxel. The results suggest an important role for non-multidrug-resistant mechanisms of resistance to paclitaxel. These mechanisms do not involve reduced drug accumulation and provide cross-resistance among both paclitaxel and tubulin depolymerizing agents.
A New Enzymatic Method for the Measurement of Creatinine Involving a Novel ATP-dependent Enzyme,<i>N</i>-Methylhydantoin Amidohydrolase (1995)

A new enzymatic method for the measurement of serum and urine creatinine is described. The method is based on a novel microbial creatinine degradation pathway via N-methylhydantoin [Shimizu et al., Clin. Chim. Acta, 185, 241-252 (1989)]. By using two novel enzymes, N-methylhydantoin amidohydrolase and N-carbamoylsarcosine amidohydrolase, as key enzymes, coupled with a colorimetric procedure for hydrogen peroxide detection, the creatinine level can be measured. The results obtained for human serum and urine show good correlation with those obtained by a standard chemical method based on the Jaffe reaction. The new method is simple and specific, and shows excellent sensitivity and reliability.
Corrosion in Low and High Temperature Fuel Cells—An Overview (1987)

Fuel cell anodes operate in a reducing atmosphere, whereas cathodes operate under strongly oxidizing conditions, in difficult electrolytic environments. Electrochemical corrosion can limit the working cathode potential, hence fuel cell operating efficiency, as well as fuel cell lifetime. The four principal classes of electrolyte are aqueous alkali, aqueous acid, and two high temperature, CO2-rejecting systems: molten alkali carbonates (~ 650 C) and solid oxide ionic conductors (1000 C). For the aqueous electrolytes, thermodynamically stable cathode materials include some of the noble metals and a range of passive oxides (restricted to Nb and Ta oxides in acid media). However, various kinetically stable carbons permit the possibility of inexpensive cathode construction materials and catalyst supports that are stable to 80 C and to over 200 C in alkaline and acid fuel cells, respectively. The corrosion rates of these cathode components (and those of the supported platinum catalyst in acid media) ultimately limit fuel cell life and performance. In contrast, the high temperature cells show few corrosion problems, provided that the electronically conducting parts in contact with both anode and cathode atmospheres are protected by suitable dielectric coatings to prevent a direct ionic pathway between anodic and cathodic sites.
Flash calcines of kaolinite: kinetics of isothermal dehydroxylation of partially dehydroxylated flash calcines and of flash calcination itself (1992)

Kaolinite has been flash calcined to produce calcines kinetically frozen at different levels of dehydroxylation. The kinetics of subsequent isothermal dehydroxylation of the calcines were consistent with a three-dimensional diffusion model. Activation energies and rate constants generally decrease as dehydroxylation of the calcine increases. A decrease in reaction rate at high levels of dehydroxylation is consistent with collapse of the interlamellar space, restricting diffusion of water out of the particles. The kinetics of flash calcination were shown to obey the same principles as isothermal dehydroxylation.
POSTURING FOR ADHESIVE OBSTRUCTION OF BOWEL. (1964)

Summary

1
In selected patients, clinically diagnosed adhesive obstruction of bowel can sometimes be relieved by posturing. This forestalls intubation or operation.

2
The considerations which led to trial of this treatment are mentioned.

3
Successful postures are described.

4
Posturing should not be used if a closed loop of small bowel or a colonic obstruction is suspected.

5
If unsuccessful, posturing must not delay intubation or operation.

6
Posturing in the post-operative period may have some value in preventing adhesions.
Finite deformation biphasic material properties of bovine articular cartilage from confined compression experiments (1997)

In 1990, Holmes and Mow [Journal of Biomechanics 23, 1145-1156] developed a hyperelastic biphasic theory to describe finite deformation behaviors of articular cartilage. To date, however, no experimental finite deformation studies have been made to assess the ability of this constitutive model to describe its finite deformation behaviors (e.g. kinetic creep and stress-relaxation, and equilibrium responses). The objectives of this study are: (1) to investigate whether this hyperelastic biphasic theory can be used to curve-fit the finite deformation compressive stress-relaxation behavior of the tissue, and from this procedure, to calculate its material coefficients; and (2) to investigate whether the theory, together with the calculated material coefficients, can accurately predict the outcome of an independent creep experiment followed by cyclical loading of the tissue. To achieve these objectives, circular cylindrical cartilage plugs were tested in confined compression in both stress-relaxation and creep experiments. Results demonstrated that curve-fits of the stress-relaxation experiments produced nonlinear generalized correlation coefficients of r2 = 0.99 +/- 0.02 (mean +/- standard deviation); theoretical predictions of the creep test differed on average by 10.0% +/- 2.0% relative to experimental results. When curve-fitting the creep experiments as well, it was found that the permeability coefficients differed from those obtained from the stress-relaxation experiments (k0,cr = 2.2 +/- 0.8 x 10(-15) m4 N-1 s-1 and Mcr = 0.4 +/- 0.8 vs k0,sr = 2.7 +/- 1.5 x 10(-15) m4 N-1 s-1, and Msr = 2.2 +/- 1.0); these differences may be attributed to imprecisions in the curve-fitting procedure stemming from the low sensitivity of the stress-relaxation and creep behaviors to large variations of M in the permeability function. Advantages and limitations of this theoretical model are presented in the text.
Aβ Immunotherapy Protects Morphology and Survival of Adult-Born Neurons in Doubly Transgenic APP/PS1 Mice (2009)

The hippocampus is heavily affected by progressive neurodegeneration and beta-amyloid pathology in Alzheimer's disease (AD). The hippocampus is also one of the few brain regions that generate new neurons throughout adulthood. Because hippocampal neurogenesis is regulated by both endogenous and environmental factors, we determined whether it benefits from therapeutic reduction of beta-amyloid peptide (Abeta)-related toxicity induced by passive Abeta immunotherapy. Abeta immunotherapy of 8-9-month-old mice expressing familial AD-causing mutations in the amyloid precursor protein and presenilin-1 genes with an antibody against Abeta decreased compact beta-amyloid plaque burden and promoted survival of newly born neurons in the hippocampal dentate gyrus. As these neurons matured, they exhibited longer dendrites with more complex arborization compared with newly born neurons in control-treated transgenic littermates. The newly born neurons showed signs of functional integration indicated by expression of the immediate-early gene Zif268 in response to exposure to a novel object. Abeta immunotherapy was associated with higher numbers of synaptophysin-positive synaptic boutons. Labeling dividing progenitor cells with a retroviral vector encoding green fluorescent protein (GFP) showed that Abeta immunotherapy restored the impaired dendritic branching, as well as the density of dendritic spines in new mature neurons. The presence of cellular prion protein (PrP(c)) on the dendrites of the GFP(+) newly born neurons is compatible with a putative role of PrP(c) in mediating Abeta-related toxicity in these cells. In addition, passive Abeta immunotherapy was accompanied by increased angiogenesis. Our data establish that passive Abeta immunotherapy can restore the morphological maturation of the newly formed neurons in the adult hippocampus and promote angiogenesis. These findings provide evidence for a role of Abeta immunotherapy in stimulating neurogenesis and angiogenesis in transgenic mouse models of AD, and they suggest the possibility that Abeta immunotherapy can recover neuronal and vascular functions in brains with beta-amyloidosis.
Simian virus 40 infectious entry by a caveolae pathway does not directly involve MHC class I proteins (1996)

Viral infection of cells often requires many host cell factors. Despite the identification of numerous viral receptor molecules relatively little is known about the roles of these molecules in viral entry, and intracellular targeting. Major histocompatibility complex (MHC) class I proteins are components of the Simian Virus 40 (SV40) cell surface receptor. This interaction between virus and host cell is of interest since MHC class I proteins have typically been studied for their importance in cellular immune responses. MHC class I proteins acquire antigenic peptides in the endoplasmic reticulum (ER). SV40 is unique in its ability to target the ER from the cell surface. Thus, the possibility exists that surface MHC class I proteins may recycle and target the ER. A major question is do MHC class I proteins internalize and target SV40 to the ER. The goal of this thesis was to better characterize SV40 entry, and determine if MHC class I proteins are directly involved in viral internalization. Basic studies were therefore conducted to determine the fate of MHC class I proteins on fibroblasts. SV40 entry into cells was found to occur rather slowly. The majority of preadsorbed virions remain at the cell surface for up to 2.5 hours. Furthermore, three hours were required for preadsorbed SV40 to internalize and escape antiserum neutralization. This suggests that SV40 infectious entry is relatively slow. Cytosol acidification greatly reduced clathrin-dependent endocytosis, but had no inhibitory effect on SV40 infectious entry. Therefore, SV40 infectious entry does not occur by receptor-mediated endocytosis. Treatment of cells with PMA, nystatin, or filipin prevents internalization via caveolae. All three treatments prevented SV40 infectious entry. Thus, caveolae may be the sites of SV40 penetration into cells. To evaluate the role of MHC class I proteins in SV40 endocytosis, cell surface proteins were labeled with $\\sp{125}$I. Protease treatment of cells was used to distinguish proteins that have internalized from those remaining at the cell surface. Protease resistant $\\sp{125}$I-MHC class I proteins were not detected in the absence, or presence of SV40. Furthermore, a $\\sp{125}$I-MHC class I protein-specific monoclonal antibody did not internalize into cells. These results suggest that surface MNC class I proteins are not internalized into cells, and SV40 does not induce their internalization. Truncated $\\sp{125}$I-MHC class I proteins were detected in the media. 1,10-phenanthroline prevented accumulation of $\\sp{125}$I-MHC class I proteins in the media. Thus, metalloprotease activity is involved in shedding of surface MHC class I proteins from CV-1 cells. The loss of the B$\\sb2$-microglobulin subunit from the MHC class I heavy chain was found to precede metalloprotease cleavage of the heavy chain. Collectively, these results suggest that the fate of MHC class I proteins on fibroblast is shedding into the media, and these molecules are probably not directly involved in SV40 entry.
Aluminum Nanoparticles as Substrates for Metal-Enhanced Fluorescence in the Ultraviolet for the Label-Free Detection of Biomolecules (2009)

We use finite-difference time-domain calculations to show that aluminum nanoparticles are efficient substrates for metal-enhanced fluorescence (MEF) in the ultraviolet (UV) for the label-free detection of biomolecules. The radiated power enhancement of the fluorophores in proximity to aluminum nanoparticles is strongly dependent on the nanoparticle size, fluorophore-nanoparticle spacing, and fluorophore orientation. Additionally, the enhancement is dramatically increased when the fluorophore is between two aluminum nanoparticles of a dimer. Finally, we present experimental evidence that functionalized forms of amino acids tryptophan and tyrosine exhibit MEF when spin-coated onto aluminum nanostructures.
Mutation of a Shc Binding Site Tyrosine Residue in ErbB3/HER3 Blocks Heregulin-dependent Activation of Mitogen-activated Protein Kinase (1998)

The ErbB2 and ErbB3 proteins together constitute a functional coreceptor for heregulin (neuregulin). Heregulin stimulates the phosphorylation of both coreceptor constituents and initiates a variety of other signaling events, which include phosphorylation of the Shc protein. The role of Shc in heregulin-stimulated signal transduction through the ErbB2.ErbB3 coreceptor was investigated here. Heregulin was found to promote ErbB3/Shc association in NIH-3T3 cells expressing endogenous ErbB2 and recombinant ErbB3. A mutant ErbB3 protein was generated in which Tyr-1325 in a consensus Shc phosphotyrosine-binding domain recognition site was mutated to Phe (ErbB3-Y/F). This mutation abolished the association of Shc with ErbB3 and blocked the activation of mitogen-activated protein kinase by heregulin. Whereas heregulin induced mitogenesis in NIH-3T3 cells transfected with wild-type ErbB3 cDNA, this mitogenic response was markedly attenuated in NIH-3T3 cells transfected with the ErbB3-Y/F cDNA. These results showed a specific interaction of Shc with the ErbB3 receptor protein and demonstrated the importance of this interaction in the activation of mitogenic responses by the ErbB2. ErbB3 heregulin coreceptor complex.
Treatment of Advanced Kaposiʼs Sarcoma Using a Combination of Bleomycin and Vincristine (1990)

Eighteen patients with disseminated AIDS-related Kaposi's sarcoma (KS) and compromised bone marrow function were treated with a relatively non-myelosuppressive regimen of bleomycin and vincristine (BV). At study entry, the patients presented with the following median laboratory values: hemoglobin of 9.5 g/dl, granulocyte counts of 1,173/mm3, platelet counts of 218,000/mm3, and CD4 lymphocyte counts of 58/mm3. All patients had extensive Kaposi's sarcoma. Nine patients had visceral involvement: four with pulmonary involvement, two with gastrointestinal involvement, and three with both. Following a median number of seven cycles of biweekly chemotherapy, complete or partial tumor responses were achieved in 13 patients (72%). Two patients experienced bleomycin-induced skin toxicities, whereas 10 others (55%) experienced peripheral sensory neuropathy requiring vincristine dose reductions. Opportunistic infections had occurred in 11 patients prior to initiation of chemotherapy and in 16 after initiation of chemotherapy. Despite the frequent development of opportunistic infections, BV chemotherapy was relatively well tolerated and resulted in a high response rate in this patient population that presented with suboptimal marrow function and extremely low CD4 lymphocyte counts.
The impact of different forms of statistical information on reading efficiency, effect, and mental workload: An eye-tracking study (2011)

The statistical information, in general, can be visually presented in the three basic forms: statistical information in text (text for short), statistical graph, and statistical graph with text (i.e. the combination of graph and text). The impact of the different forms on people's understanding of the statistical information is still unclear. To address this issue, this study using eye-tracking investigated the reading efficiency (reading time), reading effect (accuracy) and mental workload (pupil diameter) during 36 subjects reading the statistical information presented in any of the three forms. The results showed that: (1) the reading time: the statistical graph was significantly shorter than the text and statistical graph with text, which suggests that the reading efficiency of statistical graph is higher than other forms; (2) the accuracy: there were no significant differences among the three forms, which suggests that there are no significant difference on the reading effect; (3) the pupil diameter: both statistical graph and statistical graph with text were significantly smaller than the text, which reveals that the statistical graph and statistical graph with text in mental workload are significantly lower than the text. The findings also provide the evidences for the reason why people prefer the statistical information presented in the form of the statistical graph with text.
Standard Oral Melphalan Chemotherapy for AL Amyloidosis Revisited Using the Serum Free Light Chain Assay. (2005)

Abstract Treatment of systemic AL amyloidosis (AL) remains difficult, especially in older and sicker patients in whom dose intensive therapies are often associated with unacceptable morbidity and mortality. Many such patients continue to be treated with oral melphalan ± prednisone (MP) despite early trials having shown only very modest clinical efficacy, presumably encouraged by its perceived low toxicity. The recent advent of the sensitive nephelometric serum free light chain (sFLC) assay has for the first time enabled the typically subtle underlying clonal disease to be monitored in an effective quantitative manner in the majority of patients with AL. We report here sFLC responses and clinical outcome of patients with AL who received MP first-line and underwent serial evaluations at the UK National Amyloidosis Centre. The 90 patients comprised 46 males and 44 females with a median age of 68yrs (range 43–83). Median number of organs involved was 3 (1–4), including kidneys in 72%, heart in 56%, and liver in 29%. 16 (17%) had ≥ NYHA class III heart failure. Median ECOG performance status was 1. Median follow-up was 2.3 yrs (0.3–14). 60 patients received oral melphalan with prednisone, and 30 received single agent melphalan. Patients received a median of 6 cycles of treatment (range 1– 26), and the sFLC assay was scheduled following each cycle after availability of the assay and retrospectively on stored sera for earlier patients. Haematological response data using sFLC assay were evaluable in 54 (60%). Responses were defined as complete response (CR) - sustained normalisation of sFLC ratio, partial response (PR) - sustained ≥50% reduction in pre-treatment clonal isotype. There was a haematological response in 22 (40%) of evaluable patients. 4 (7%) had a complete response, 18 (33%) had a partial response and 32 (59%) did not respond. 42% of patients treated with single agent melphalan responded compared with 39% of those treated with melphalan and prednisone (p=0.8). Responders received a median 6 cycles of treatment, and complete responders received a median of 14 cycles. Non-responders received a median of 5 cycles of treatment. The median time to commencing further chemotherapy was 5 months. The median overall survival (OS) was 5.8yrs, but most patients received further salvage treatments and the influence of MP treatment on OS could not be ascertained. Toxicities during MP were seen in 13 (14%) cases, including myelodysplasia in 2 patients. There were no treatment related deaths. In conclusion, use of the sFLC assay confirms that response of the underlying clonal plasma cell disease to standard oral melphalan and prednisone is poor in AL amyloidosis, and that response is usually very delayed even among patients who respond completely. Encouragingly however, toxicity was low among this relatively old and sick cohort of patients. These findings support frequent sFLC measurements in AL patients receiving MP to enable rational treatment decisions to be made at the earliest opportunity.
Overproduction of selenocysteine tRNA in Chinese hamster ovary cells following transfection of the mouse tRNA[Ser]Sec gene (1998)

Selenocysteine insertion during selenoprotein biosynthesis begins with the aminoacylation of selenocysteine tRNA[ser]sec with serine, the conversion of the serine moiety to selenocysteine, and the recognition of specific UGA codons within the mRNA. Selenocysteine tRNA[ser]sec exists as two major forms, differing by methylation of the ribose portion of the nucleotide at the wobble position of the anticodon. The levels and relative distribution of these two forms of the tRNA are influenced by selenium in mammalian cells and tissues. We have generated Chinese hamster ovary cells that exhibit increased levels of tRNA[ser]sec following transfection of the mouse tRNA[ser]sec gene. The levels of selenocysteine tRNA[ser]sec in transfectants increased proportionally to the number of stably integrated copies of the tRNA[ser]sec gene. Although we were able to generate transfectants overproducing tRNA[ser]sec by as much as tenfold, the additional tRNA was principally retained in the unmethylated form. Selenium supplementation could not significantly affect the relative distributions of the two major selenocysteine tRNA[ser]sec isoacceptors. In addition, increased levels of tRNA[ser]sec did not result in measurable alterations in the levels of selenoproteins, including glutathione peroxidase.
Potential of glyburide to reduce intracerebral edema in brain metastases (2014)

Metastatic disease to the brain results in significant morbidity because of edema in the central nervous system. Current anti-edema therapies are either expensive or result in unwanted long-term side effects. Sulfonylurea receptor 1 (Sur1) is a transmembrane protein that, when activated in the central nervous system, allows for unregulated sodium influx into cells, a process that has been linked to cytotoxic edema formation in ischemic stroke, subarachnoid hemorrhage, spinal cord injury, traumatic brain injury, and, most recently, brain metastases. In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema.