gebhart/patrepeval huggingface dataset:
Tryptophan Promoter Derivatives on Multicopy Plasmids: A Comparative Analysis of Expression Potentials in Escherichia coli (1990)

A collection of variant plasmids expressing either Escherichia coli galactokinase or human serum albumin under the control of several E. coli trp promoter derivatives were constructed and studied for both efficiency of expression and regulation by tryptophan. Several variables, including the length of the upstream region, tandem duplications of a core promoter, and the insertion of the trp repressor trpR gene onto the expression vector, were studied. It is shown that derivatives containing sequences upstream from the -35 region or multiple copies of the trp promoter produce twofold higher levels of protein than plasmids with a minimal trp promoter truncated at -40. We show that the expression of a heterologous protein such as albumin can be significantly improved (13% vs. 7% of total proteins) if both the upstream trp promoter region, which enhances promoter strength, and an intact trpR gene, are included on the plasmids.
Paradoxical Effect of Isoniazid on the Activity of Rifampin-Pyrazinamide Combination in a Mouse Model of Tuberculosis (2009)

To investigate the antagonism between isoniazid (INH) and rifampin (rifampicin) (RIF)-pyrazinamide (PZA) combination observed in Mycobacterium tuberculosis-infected mice, extensive pharmacokinetic studies of INH were performed and followed by experiments to assess the impact of increasing doses of INH on the antimicrobial activity of RIF-PZA combination. INH at 6.25 mg/kg of body weight produced a maximum concentration of drug in serum (Cmax) value of 4 microg/ml and an area under the concentration-time curve from 0 to 24 h (AUC(0-24)) value of 4.9 microg x h/ml, the former being close to the Cmax value observed after the standard 5-mg/kg dose in humans. INH at 25 mg/kg produced a Cmax value of 22 microg/ml and an AUC(0-24) value of 29 microg x h/ml, the latter being close to the AUC observed after a 5-mg/kg dose of INH in humans with the slow acetylation phenotype. Beginning 2 weeks after aerosol infection with M. tuberculosis, mice were treated for 8 weeks with INH at twofold-increasing doses, ranging from 1.56 to 50 mg/kg, either alone or in combination with RIF-PZA. Given alone, INH exhibited dose-dependent activity. Combined with RIF-PZA, INH exhibited dose-dependent antagonism of RIF-PZA activity. To determine the individual components of RIF-PZA combination with which INH was antagonistic, mice were treated for 8 weeks with RIF alone, PZA alone, RIF-PZA, and INH at 3.125, 12.5, or 50 mg/kg either alone or combined with RIF or PZA. Addition of INH to RIF had additive activity, whereas addition of INH to PZA resulted in a negative interaction. Finally, a 10-mg/kg dose of INH in mice may best represent the 5-mg/kg dose in humans and decrease the antagonism of INH with RIF-PZA.
Nonviral gene transfer to skeletal, smooth, and cardiac muscle in living animals (2005)

The study of muscle physiology has undergone many changes over the past 25 years and has moved from purely physiological studies to those intimately intertwined with molecular and cell biological questions. To ask these questions, it is necessary to be able to transfer genetic reagents to cells both in culture and, ultimately, in living animals. Over the past 10 years, a number of different chemical and physical approaches have been developed to transfect living skeletal, smooth, and cardiac muscle systems with varying success and efficiency. This review provides a survey of these methods and describes some more recent developments in the field of in vivo gene transfer to these various muscle types. Both gene delivery for overexpression of desired gene products and delivery of nucleic acids for downregulation of specific genes and their products are discussed to aid the physiologist, cell biologist, and molecular biologist in their studies on whole animal biology.
A New Diterpene Glycoside from Stevia rebaudiana (2011)

From the commercial extract of the leaves of Stevia rebaudiana, a new diterpene glycoside was isolated besides the known steviol glycosides including stevioside, rebaudiosides A-F, rubusoside and dulcoside A. The new compound was identified as 13-[(2-O-β-D-glucopyranosyl-3-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-(2-O-α-L-rhamnopyranosyl-β-D-glucopyranosyl) ester (1) on the basis of extensive spectroscopic (NMR and MS) and chemical studies.
Characterization of the inflammatory response to proteinase‐activated receptor‐2 (PAR2)‐activating peptides in the rat paw (1999)

In the present study, we have observed the development of an inflammatory reaction in the rat hindpaw, following the injection of specific agonists of PAR2 (two PAR2 activating peptides). This inflammation was characterized by oedema and granulocyte infiltration. Two selective PAR2 activating peptides, SLGRL-NH2 and trans-cinnamoyl-LIGRLO-NH2 induced significant oedema in the rat hindpaw from 1-6 h following subplantar injection. Six hours after the PAR2-activating peptide injection, the paw tissues showed a complete disruption of tissue architecture along with an inflammatory cell infiltrate. In the inflamed paw, PAR2-immunoreactivity was expressed on endothelial cells as well as on the infiltrating inflammatory cells. The oedema induced by the injection of the two PAR2 activating peptides was slightly reduced in rats pre-treated with compound 48/80, but was not modified by pre-treatment of rats with cromolyn, a mast cell stabilizer. Pre-treatment of rats with a cyclo-oxygenase inhibitor (indomethacin) or a nitric oxide synthase inhibitor (L-N(omega)-nitro-L-arginine methyl ester) had no effect on the oedema induced by the PAR2-activating peptides. These results demonstrate that the administration of PAR2-activating peptides into the rat paw induced an acute inflammatory response characterized by a persistent oedema (at least 6 h) and granulocyte infiltration. The PAR2-induced inflammatory response occurred through a mechanism largely independent of mast cell activation, and of the production of prostanoids and nitric oxide.
Metabolic effects of heparin on rat cervical epithelial cells (1987)

The glycosaminoglycan heparin inhibits the growth of a number of different cell types in vitro including smooth muscle cells, mesangial cells, fibroblasts, and rat cervical epithelial cells (RCEC). Studies investigating the antiproliferative effects of heparin on smooth muscle cells have demonstrated the site of the cell cycle block and revealed several metabolic alterations that could be causally associated with growth inhibition. We have investigated these metabolic parameters in RCEC to determine whether they are also associated with the antiproliferative effects of heparin in epithelial cells. Heparin acts rapidly to inhibit RCEC growth with inhibition detectable by autoradiography 7 h after the addition of heparin. Heparin treated RCEC begin to enter S-phase 12 h after the removal of heparin. These findings suggest that heparin blocks RCEC in the early-to-mid G1 phase of the cell cycle rather than late in G1 or early in S-phase as has previously been demonstrated for smooth muscle cells. Unlike smooth muscle cells, the uptake of thymidine and uridine is not inhibited by heparin in RCEC. Treatment of medium with heparin-Sepharose does not reduce the subsequent growth of RCEC; heparin inhibits the growth of RCEC in heparin-Sepharose treated medium in a manner identical to that in nontreated medium. Therefore the growth inhibitory effects of heparin cannot be explained by the inactivation of mitogens present in serum. In contrast to its effects on smooth muscle cells, heparin treatment of RCEC does not result in a reduction in the binding of epidermal growth factor (EGF) to the cells. These results indicate that although heparin inhibits the growth of a variety of cell types, significant differences exist in the responses of the different cells to heparin.
[Precision medical treatment of non-adenocarcinoma NSCLC patients with EGFR mutation]. (2017)

EGFR tyrosine kinase inhibitors (TKIs) treatment has been established as standard therapy for EGFR-mutated adenocarcinomas. In the studies which published prospective randomized trials comparing EGFR TKIs with chemotherapy, a very low percentage of EGFR-mutated non-adenocarcinomas was enrolled in clinical trials. The efficacy of TKIs treatment for EGFR-mutated non-adenocarcinomas and their relationship with clinicopathological characteristics remain debatable. The results of retrospective studies show that the frequency of EGFR mutation is lower in non-adenocarcinoma than that of adenocarcinoma and efficacy of TKIs treatment for non-adenocarcinoma is inferior to adenocarcinoma. Smoking status is significantly associated with the efficacy of TKIs treatment for EGFR-mutated non-adenocarcinomas. The EGFR mutation rate and efficacy of TKIs treatment in adenosquamous cell carcinoma are higher than those of squamous cell carcinoma or large cell lung carcinoma. It may be concluded that the incidence of EGFR mutations in patients with non-adenocarcinoma NSCLC from mainland China is not very low and it is reasonable that EGFR TKIs could be an option for the treatment of EGFR-mutated non-adenocarcinoma NSCLC, especially for patients with adenosquamous histology and non-smokers. It is necessary to conduct a large-sample prospective study to understand the clinicopathological characteristics of non-adenocarcinomas and to evaluate the efficacy of EGFR TKI treatment or/and chemotherapy for EGFR-mutated non-adenocarcinoma NSCLC.
Antisense inhibition of single copy N-myc expression results in decreased cell growth without reduction of c-myc protein in a neuroepithelioma cell line. (1990)

The N-myc gene is transiently expressed during normal embryonic development and abnormally expressed in several tumors of neuroendocrine origin. Little is known of the function of the N-myc gene product in either normal or neoplastic tissue. We utilized synthetic antisense oligodeoxynucleotides to specifically inhibit N-myc gene expression in the neuroepithelioma cell line CHP100. These cells contain single copy N-myc alleles but overexpress c-myc. N-myc antisense oligomer treatment was found to be growth inhibitory without affecting levels of c-myc protein. N-myc antisense oligomer-treated cells also lost the characteristic cellular heterogeneity displayed by CHP100 in vitro.
The relationship between blood thiamine levels and dietary thiamine content in diabetic outpatients and healthy subjects. (1987)

Forty-six diabetic outpatients consumed (1,533 +/- 308 kcal (mean +/- SD) per day, 205 +/- 42 g of carbohydrates, 73 +/- 18 g of protein, 49 +/- 18 g of fat, and 0.05 +/- 0.34 mg of thiamine. No significant correlation was found in 46 diabetic between blood thiamine level and the intake of dietary energy, carbohydrate or thiamine. In 13 healthy subjects given prepared diets, a significant correlation was found between blood thiamine level and dietary thiamine content, thiamine content per 1,000 kcal, and 24-h urinary thiamine amount divided by urinary creatinine. When 9 healthy subjects (6 males, 3 females) consumed 1,600 kcal with 0.6 mg of thiamine for two days, their blood thiamine level was 47 +/- 29.1 ng/ml before and 29.7 +/- 7.1 ng/ml after eating the diet, showing low blood thiamine levels due to the low content of dietary thiamine. When 5 or 6 healthy female subjects consumed 1,400 kcal with 1.6 mg of thiamine or 2,000 kcal with 1.9 mg of thiamine for two days, their blood thiamine level was 45.3 +/- 4.8 ng/ml or 57.7 +/- 8.4 ng/ml before and 51.5 +/- 11.7 ng/ml or 56.4 +/- 11.7 ng/ml after eating the diets, respectively. In both diabetic outpatients and healthy subjects, a significant positive correlation was found between blood thiamine levels and dietary thiamine concentrations per 1,000 kcal, and a significant positive correlation was also found between erythrocyte transketolase activity and dietary thiamine content.(ABSTRACT TRUNCATED AT 250 WORDS)
The coil–globule transition: Radius of gyration of polystyrene in cyclohexane (1980)

The temperature dependence of the radius of gyration of polystyrene (MW=2.6×107) in cyclohexane in the good through poor solvent regimes was obtained by analysis of the angular dependence of the autocorrelation function of light scattered from the solution. The observed transition in polymer dimensions through the coil to globule states is in good agreement with the predictions of mean field theory.
Exact Analysis of Ligand-Induced Dimerization of Monomeric Receptors (2008)

This paper analyzes the equilibria involved in the dimerization of monomeric receptors with homo-bifunctional ligands. We provide analytical expressions that can be used to estimate the concentration of each species present in a mixture of homo-bifunctional ligand and monomeric proteins, given initial conditions defining the total concentration of bivalent ligand [L2]0, the total concentration of protein [P]0, one dissociation constant Kd, and a parameter to account for cooperativity alpha. We demonstrate that the fraction of protein present in a complex of two proteins and one bivalent ligand (P x L2 x P) is maximized at [L2]0 = Kd/2 + [P]0/2.
Neoadjuvant Androgen Withdrawal Therapy Decreases Local Recurrence Rates Following Tumor Excision in the Shionogi Tumor Model (1997)

Neoadjuvant androgen withdrawal decreases local recurrence and positive margin rates by 50% after tumor excision in the Shionogi tumor model. Although this model cannot address the issue of effect of neoadjuvant therapy on subclinical metastases, extrapolation of these results to the clinical disease suggests that neoadjuvant therapy may help to decrease not only the positive margin rates but also the subsequent risk of local recurrence following radical prostatectomy.
Effects of oestradiol and tamoxifen on oxytocin-induced phospholipase C activation in human myometrial cells (1995)

The role of oestradiol in the control of uterine responsiveness to oxytocin was investigated by measuring oxytocin-induced phospholipase C activation in [3H]inositol-labelled cultured human myometrial cells. Addition of oestradiol to steroid-free culture medium (10% (v/v) fetal calf serum treated with dextran-coated charcoal in phenol red-free medium) enhanced formation of inositol phosphates and this effect was completely abolished by the anti-oestrogen tamoxifen. The inhibitory effect of tamoxifen on oxytocin-induced phospholipase C activation occurred in both steroid-free and complete culture medium; it was time- and concentration-dependent and was only partly reversed by oestradiol. When phospholipase C was activated with PGF2 alpha or fluoroaluminate instead of oxytocin, oestradiol and tamoxifen had the same stimulatory and inhibitory effects, respectively. The inhibitory effect of tamoxifen could not be prevented by treating the cells with pertussis toxin. Moreover, the effect of tamoxifen was not mediated by inhibition of protein kinase C, since the use of staurosporine (a protein kinase inhibitor) resulted in potentiation of phospholipase C activation by oxytocin. Both oestradiol and tamoxifen increased [3H]inositol incorporation into cellular lipids and cell proliferation. These results suggest that oestradiol enhances myometrial responsiveness to oxytocin and other agonists by facilitating phospholipase C activation at a post-receptor level. This effect is antagonized by tamoxifen; however, tamoxifen also has oestrogen-independent inhibitory effects.
A phase II trial of gefitinib in patients with non‐metastatic hormone‐refractory prostate cancer (2007)

Gefitinib has no single-agent activity in non-metastatic HRPC, as assessed by decreases in serum PSA level. This phase II study also confirmed the well-established favourable tolerability profile of gefitinib monotherapy.
Differential susceptibility of primary and established human glioma cells to adenovirus infection: targeting via the epidermal growth factor receptor achieves fiber receptor-independent gene transfer. (1998)

Adenovirus (Ad) vectors are promising for gene therapy of glioma due to their ability to achieve efficient gene transfer upon intratumoral administration. Yet in this context, Ad mediates widespread gene transfer to both tumor and surrounding parenchyma. Ad entry is dependent upon the expression of fiber receptors, such as coxsackie/adenovirus receptor, and alpha(v) integrins on the target cells for binding and internalization, respectively. We hypothesized that the susceptibility of human gliomas to Ad would likely be heterogeneous due to variable expression of these receptors. It was found that established human glioma cell lines exhibited differential susceptibility to Ad-mediated gene transfer, which correlated directly with the level of radiolabeled Ad binding and with the expression of coxsackie/adenovirus receptor but not with the expression of alpha(v) integrins. To circumvent the lack of fiber receptors and to target Ad gene transfer specifically to tumor cells, we used a bispecific antibody conjugate to ablate Ad binding to fiber receptors and retarget binding to the epidermal growth factor receptor (EGFR), a tumor-associated marker negligibly expressed in normal, mitotically quiescent neural tissues. The results demonstrate that EGFR-targeted Ad gene transfer was EGFR specific and independent of fiber-fiber receptor interactions. Furthermore, EGFR targeting significantly enhanced Ad gene delivery to 7 of 12 established glioma cell lines and to 6 of 8 cultured primary gliomas. Interestingly, EGFR-targeted Ad gene transfer did not correlate with EGFR expression across cell lines, suggesting the importance of other factors. This study establishes that fiber receptor expression limits the utility of Ad vectors for gene transfer to glioma cells and suggests that targeting Ad via EGFR may prove valuable for tumor-specific gene transfer to high-grade gliomas. These findings have key relevance in the context of Ad vector-based approaches for glioma gene therapy.
Efficient sequence detection for intersymbol interference channels with run-length constraints (1994)

This paper addresses the data detection problem of intersymbol interference (ISI) channels with a specific modulation code-constraint known as the (d, k) run-length-limited (RLL) constraint, a popular modulation code-constraint for data storage channels as well as certain communication channels. A computationally efficient sequence detection algorithm is proposed which yields a performance close to that of the maximum likelihood sequence detector when applied to such ISI channels. The proposed detector is derived as a high signal-to-noise ratio approximation to the delay-constrained optimum detector, one which minimizes the symbol error probability given a fixed decision-delay constraint. The proposed algorithm is essentially a fixed-delay tree search (FDTS) algorithm with systematic ambiguity checking and is closely related to existing finite-depth tree search algorithms. It is observed that long critical error events common in uncoded ISI channels are eliminated by the RLL constraint. Based on this observation, we show that for some important RLL constrained channels, the proposed FDTS algorithm yields the same minimum Euclidean distance between distinguishable channel output sequences as the unconstrained maximum likelihood sequence detector.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Robust Principal Component Analysis? (2009)

This paper is about a curious phenomenon. Suppose we have a data matrix, which is the superposition of a low-rank component and a sparse component. Can we recover each component individually? We prove that under some suitable assumptions, it is possible to recover both the low-rank and the sparse components exactly by solving a very convenient convex program called Principal Component Pursuit; among all feasible decompositions, simply minimize a weighted combination of the nuclear norm and of the L1 norm. This suggests the possibility of a principled approach to robust principal component analysis since our methodology and results assert that one can recover the principal components of a data matrix even though a positive fraction of its entries are arbitrarily corrupted. This extends to the situation where a fraction of the entries are missing as well. We discuss an algorithm for solving this optimization problem, and present applications in the area of video surveillance, where our methodology allows for the detection of objects in a cluttered background, and in the area of face recognition, where it offers a principled way of removing shadows and specularities in images of faces.
γ-Selective directed catalytic asymmetric hydroboration of 1,1-disubstituted alkenes (2012)

Directed catalytic asymmetric hydroborations of 1,1-disubstituted alkenes afford γ-dioxaborato amides and esters in high enantiomeric purity (90-95% ee).
Prediction of Hepatic Clearance from Microsomes, Hepatocytes, and Liver Slices (1997)

(1997). Prediction of Hepatic Clearance from Microsomes, Hepatocytes, and Liver Slices. Drug Metabolism Reviews: Vol. 29, No. 4, pp. 891-922.
Cross Talk between Cancer and Mesenchymal Stem Cells through Extracellular Vesicles Carrying Nucleic Acids (2016)

Extracellular vesicles (EVs) are considered to be a novel complex mechanism of cell communication within the tumor microenvironment. EVs may act as vehicles for transcription factors and nucleic acids inducing epigenetic changes in recipient cells. Since tumor EVs may be present in patient biological fluids, it is important to investigate their function and molecular mechanisms of action. It has been shown that tumor cells release EVs, which are capable of regulating cell apoptosis, proliferation, invasion, and epithelial-mesenchymal transition, as well as to suppress activity of immune cells, to enhance angiogenesis, and to prepare a favorable microenvironment for metastasis. On the other hand, EVs derived from stromal cells, such as mesenchymal stem cells (MSCs), may influence the phenotype of tumor cells through reciprocal cross talk greatly influenced by the transcription factors and nucleic acids they carry. In particular, non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs, have recently been identified as the main candidates for the phenotypic changes induced in the recipient cells by EVs. ncRNAs, which are important regulators of mRNA and protein expression, can function either as tumor suppressors or as oncogenes, depending on their targets. Herein, we have attempted to revise actual evidence reported in the literature on the role of EVs in tumor biology with particular regard to the cross talk of ncRNAs between cancer cells and MSCs.
Pathogenesis, etiology and epidemiology of myelodysplastic syndromes. (1998)

The initiation processes for the development of MDS remain unknown. A poorly defined transforming event affects a pluripotent or multipotent progenitor cell in the bone marrow, conferring a growth advantage upon it and eventually establishing clonal hematopoiesis. An important pathogenetic mechanism in MDS is premature intramedullary cell death via excessive apoptosis, explaining the apparent paradox of a cellular marrow in combination with peripheral cytopenias (ineffective hematopoiesis). Therapy-related MDS/AML following exposure to alkylating agents is the only clear etiological factor thus identified. Increasing evidence for exposure to benzene and radiation and the development of MDS is emerging. Benzene hematotoxicity is mediated via both genotoxic and non-genotoxic mechanisms, leading to aplasia, apoptosis and initiation (via genetic mutation) of clonal disorders such as MDS. Further studies of benzene hematotoxicity and therapy-related MDS should provide models for the elucidation of initiation events in MDS pathogenesis. The importance of such studies is emphasized by the rising frequency of MDS which largely reflects improved diagnostic criteria, increased physician awareness and extended use of diagnostic procedures in the elderly. Demographic changes will lead to a marked increase in MDS over the next few decades.