gebhart/patrepeval huggingface dataset:
Structure−Activity Relationships for 4-Nitrobenzyl Carbamates of 5-Aminobenz[e]indoline Minor Groove Alkylating Agents as Prodrugs for GDEPT in Conjunction with E. coli Nitroreductase (2003)

Twelve substituted 4-nitrobenzyl carbamate prodrugs of the 5-aminobenz[e]indoline class of DNA minor groove alkylating agents were prepared and tested as prodrugs for gene-directed enzyme prodrug therapy (GDEPT) using a two-electron nitroreductase (NTR) from E. coli B. The prodrugs and effectors were tested in a cell line panel comprising parental and transfected human (SKOV/Skov-NTR(neo), WiDr/WiDr-NTR(neo)), Chinese hamster (V79(puro)/V79-NTR(puro)), and murine (EMT6/EMT6-NTR(puro)) cell line pairs. In the human cell line pairs, several analogues bearing neutral methoxyethoxy-, 2-hydroxyethoxy-, or 3-hydroxypropoxy-substituted side chains were good substrates for NTR as measured by cytotoxicity ratios, with NTR-ve/NTR+ve ratios similar to the established NTR substrates CB1954 (an aziridinyl dinitrobenzamide) and the analogous bromomustard. Selectivity for NTR decreased with increasing side-chain size or the presence of a basic amine group. Low to modest selectivity was observed in the Chinese hamster-derived cell line pair; however, in the murine EMT6/EMT6-NTR(puro) cell line pair, the above hydroxyalkoxy analogues again showed significant selectivity for NTR. The activity of the 2-hydroxyethoxy analogue was evaluated against NTR-expressing EMT6 tumors comprising ca. 10% NTR+ve cells at the time of tumor treatment. A small decrease in NTR+ve cells was observed after treatment, with a lesser effect against NTR-ve target cells, but these effects were not statistically significant and were much less than for the dinitrobenzamides. These results suggest that useful GDEPT prodrugs based on the 4-nitrobenzyl carbamate and 5-aminobenz[e]indoline motifs may be developed if optimization of pharmacokinetics can be addressed.
The use of TaqMan PCR assay for detection of Bordetella pertussis infection from clinical specimens. (2002)

The TaqMan PCR assay has superior sensitivity and shorter turnaround time over culture because it can be finished within one working day. Furthermore, the same swab can be used for culture of the bacteria for antibiotic susceptibility testing. The early detection of pertussis using TaqMan PCR assay allows early intervention on the spread of the disease and the ability to culture the bacteria from the same swab, thereby eliminating the need for a second swab and allowing for detection of antibiotic resistance.
Lamin A-Dependent Nuclear Defects in Human Aging (2006)

Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.
Purification and Characterization of the Prostate Cancer-Associated Antigen: 7E11-C5 (2019)

A murine monoclonal antibody (MAb), 7E11-C5, recognizes a prostate organ-specific antigen. Under reducing conditions, the 7E11-C5 antigen exhibited major 100-Kd and minor 70-Kd bands, suggesting that the antigen comprises two peptide chains. The antigen was detected in pooled normal human seminal plasma, xenograft tissue extract of a prostate adenocarcinoma cell line, LNCaP, and tissue extracts of benign prostatic hyperplasia (BPH) and prostate carcinomas, but was not identified in any of the non-prostate tissue extracts tested. Antibodies of the three major prostate-associated antigens (prostatic acid phosphatase (PAP), prostate specific antigen (PSA) and prostate secretory protein (PSP)) were unable to block the binding of MAb 7E11-C5 to its target antigen. Western blot analysis demonstrated that there was no similarity between the 7E11-C5 antigen and these three antigens. The 7E11-C5 antigen was purified 400-fold from LNCaP xenograft tissue extract by immunoaffinity chromatography with an estimated antigen recovery of 64%. High pressure liquid chromatography (HPLC) molecular exclusion column was used to further purify the antigen and results showed that the molecular weight of the antigen, under native condition, was about 500-Kd. Biochemical characterization showed that the antigen was sensitive to both periodate oxidation and protease treatment, indicating that the antigen was a glycoprotein; both carbohydrate and peptide were required for the antigenicity. The antigen was found to be sensitive to pH 2.0, while remaining unaffected after treatment with NaOH (pH 11.0). Glycosidase treatment and lectin competitive binding study suggested that the carbohydrates involved in the antigenic determinant were galactose and N-acetyl-D-galactosamine. The antigen was not demonstrable in thin-layer chromatography (TLC) immunoblot of glycolipid extracts of LNCaP tissue. Western blot analysis of 48 serum samples from age-matched normal males, BPH patients and prostate cancer patients (stages A, B, C and D) failed to clearly show the presence of the 7E11-C5 antigen. Likewise, the antigen was not detected in these sera using a competitive binding inhibition assay. These results suggest that the antigen is either not shed into the circulation or that the antigen is either masked by serum inhibitors or disassociated into fragments not recognized by the MAb.
Migration, remittances, and agricultural productivity in small farming systems in Northwest China (2013)

Purpose The purpose of this study is to explore the relationship between migration, remittances and agricultural productivity by applying the new economics of labor migration model in the context of north‐west China. The specific objectives are to examine the impacts of rural out‐migration on agricultural productivity in various farming systems, and whether remittances have been reinvested in agriculture. Design/methodology/approach Cross‐sectional household survey data from three townships were analyzed with the three‐stage least squares (3SLS) regression model. Findings In multi‐cropping small farming systems, at least in the short run, the loss resulting from losing family labour on lower‐return grain crop production is likely to be offset by the gain from investing in capital‐intensive and profitable cash crop production. Originality/value This study provides empirical evidence for the MELM theory. It expands Taylor et al. 's studies by comparing investment behavior and production choices among multiple farm activities, and enriches previous studies by showing that the relation between remittances and agricultural investment depends on the farm activities' profitability.
Regulation of Lens Fiber Cell Differentiation by Transcription Factor c-Maf (1999)

To elucidate the regulatory mechanisms underlying lens development, we searched for members of the large Maf family, which are expressed in the mouse lens, and found three, c-Maf, MafB, and Nrl. Of these, the earliest factor expressed in the lens was c-Maf. The expression of c-Maf was most prominent in lens fiber cells and persisted throughout lens development. To examine the functional contribution of c-Maf to lens development, we isolated genomic clones encompassing the murine c-maf gene and carried out its targeted disruption. Insertion of the beta-galactosidase (lacZ) gene into the c-maf locus allowed visualization of c-Maf accumulation in heterozygous mutant mice by staining for LacZ activity. Homozygous mutant embryos and newborns lacked normal lenses. Histological examination of these mice revealed defective differentiation of lens fiber cells. The expression of crystallin genes was severely impaired in the c-maf-null mutant mouse lens. These results demonstrate that c-Maf is an indispensable regulator of lens differentiation during murine development.
Capillary Flow of Cholesteric and Smectic Liquid Crystals (1969)

It is shown theoretically that the motion of liquid crystals through capillaries may resemble that of a plug, the velocity profile being flat rather than parabolic.Received 16 June 1969DOI:https://doi.org/10.1103/PhysRevLett.23.372©1969 American Physical Society
The Effect Of Data Precision On The Calculation Of Slope And Aspect Using Gridded Dems (1992)

Plots of the frequency of occurrences of aspect angles calculated from gridded DEMs showed inordinately large spikes at the cardinal directions. Because such frequencies are not natural, the techniques of calculating slope and aspect were examined. Ultimately, the cause of the spikes was found to be the fact that the elevation values are reported only to the nearest meter. Calculations of slope and aspect angles using rounded elevation data from simulated surfaces of known slope and aspect demonstrate the nature of the problem. These simulations show that the problem of defining aspects is greatest on the most gentle slopes, as well as smaller grid spacings. Consideration was also given to various techniques of selecting elevations for deriving the parameters in the slope and aspect equations. At lower slopes, calculated aspects may be off by tens of degrees. Because there is no way to make the data more precise, researchers should exercise caution in making interpretations of aspect angles. Calculations of slope angles are affected by data precision but not as dramatically as in the calculations of aspect angles. Les tracés de la fréquence des occurences des angles d'aspect, calculés à partir de quadrillages de MNE, ont montré des pics excessivement grands vers les points cardinaux. Parce que de telles fréquences ne sont pas naturelles, on a examiné les techniques de calcul de pente et d'aspect. Finalement, on a trouvé que la présence des pics était due au fait que les valeurs d'élévation sont reportées au mètre près. Les calculs des angles de pente et d'aspect à partir de données d'élévation arrondies, provenant de surfaces de simulation de pente et d'aspect connus, démontrent bien la nature du problème. Ces simulations montrent que plus les pentes s'adoucissent et plus l'intervalle du quadrillage se rapetisse, plus le problème de définir les aspects s'accroît. On a aussi considéré diverses techniques pour choisir les élévations afin de dériver les paramètres dans les équations de pente et d'aspect. Dans les pentes les plus douces, les aspects calculés peuvent être erronés de dizaines de degrés. Parce qu'il n'est pas possible de rendre les données plus précises, les chercheurs devraient démontrer de la prudence en interprétant les angles d'aspect. Les calculs d'angles de pente sont affectés par la précision des données, mais pas aussi dramatiquement que dans les calculs d'angles d'aspect.
Testicular Biopsy Score Count – A Method for Registration of Spermatogenesis in Human Testes: Normal Values and Results in 335 Hypogonadal Males (1970)

The paper describes a new and rapid method forregistration of spermatogenesis in human testes: the testicular biopsy score count. Each tubular section is given a score from 10 to 1 according to presence or absence of the main cell types arranged in the order of maturity. Presence of spermatozoa scores 10, 9 or 8; spermatids (and no further) 7 or 6; spermatocytes (and no further) 5 or 4; only spermatogonia 3, only Sertoli cells 2 and no cells 1. The theoretical background of the score count method is discussed and it is emphasized that tissue heterogeneity, being a main point in most conditions, is exposed and evaluated by the method. Normal values are given and results obtained in 335 cases including a great variety of forms of male hypogonadism are presented. Patognomonic score counts leading to immediate diagnosis at a glance are obtained in many instances. A high correlation between testicular biopsy score count and sperm count is found and it is concluded that by this method it has for the first time become possible in man to correlate endocrine conditions with the functional state of the testicular tissue.
Radiation characterization of a dual core LEON3-FT processor (2011)

GR712RC is a dual core 32-bit fault-tolerant SPARC™V8/LEON3-FT processor that has been developed and manufactured by Ramon Chip Ltd and AeroflexGaisler AB and characterized for radiation effects. It is designed with AeroflexGaisler's intellectual property and implemented with Ramon Chip's RadSafe™ radiation-hard-by-design library in a commercial 0.18μm shallow trench isolation CMOS process. Radiation test results for total ionizing dose, single event latch-up and single event upset data with correction/data-restore methodologies are reported, demonstrating its suitability for operating in a space environment.
Comparison of the toxicity and metabolism of 9-beta-D-arabinofuranosyl-2-fluoroadenine and 9-beta-D-arabinofuranosyladenine in human lymphoblastoid cells. (1980)

The toxicity and metabolism of 9-β-d-arabinofuranosyl-2-fluoroadenine (F-ara-A), an adenosine deaminase-resistant nucleoside analog, have been compared to those of 9-β-d-arabinofuranosyladenine (ara-A) in the presence of the adenosine deaminase inhibitor, deoxycoformycin. Equal concentrations of F-ara-A and ara-A plus deoxycoformycin produced similar inhibition of growth of CCRF-CEM human lymphoblastoid cells. 9-β-d-Arabinofuranosyl-2-fluoroadenine 5′-triphosphate (F-ara-ATP) and 9-β-d-arabinofuranosyladenine 5′-triphosphate (ara-ATP), were concentratively accumulated intracellularly and exerted their major inhibitory effect on DNA synthesis. Two approaches were used to compare the effect of these nucleotide analogs on the DNA-synthetic capacity of whole cells. ( a ) The concentrations of F-ara-ATP and ara-ATP in cells incubated with the respective nucleosides were determined directly at the same time that the DNA-synthetic capacity of the cells in each culture was measured by incorporation of [3H]thymidine into DNA. Neither compound significantly affected the specific activity of cellular [3H]deoxythymidine triphosphate. ( b ) The rates of disappearance of F-ara-ATP and ara-ATP from cells washed free of the nucleosides were determined. These values were used to calculate the cellular concentration of each nucleotide analog in cells in which DNA-synthetic capacity was monitored after incubation with F-ara-A or ara-A plus deoxycoformycin and washed into fresh media. These determinations indicated that the rates of accumulation of F-ara-ATP and ara-ATP differed and were related to the concentration of the exogenous nucleoside. F-ara-ATP disappeared from cells in drug-free media at several times the rate of the disappearance of ara-ATP. However, at equal cellular concentrations, F-ara-ATP was slightly more inhibitory to the processes measured by thymidine incorporation than was ara-ATP. We conclude that F-ara-ATP and ara-ATP share a similar mechanism of action and potency of inhibition of DNA synthesis. The fact that F-ara-A retains its cytotoxic efficacy in the absence of inhibitors of adenosine deaminase provides a rationale for investigating its antitumor properties further.
LUMINOUS WITH PROMISE (2006)

RETURN TO ISSUEPREVNewsNEXTLUMINOUS WITH PROMISEVisible even from space, the conspicuous CHEMISTRY OF BIOLUMINESCENCE continues to open new research and technology nichesIVAN AMATOView Author Information C&EN WASHINGTONCite this: Chem. Eng. News 2006, 84, 49, 69–73Publication Date (Print):December 4, 2006Publication History Published online14 November 2010Published inissue 4 December 2006https://pubs.acs.org/doi/10.1021/cen-v084n049.p069https://doi.org/10.1021/cen-v084n049.p069newsACS PublicationsCopyright © 2006 American Chemical SocietyArticle Views12Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Bioluminescence,Color,Luminescence Get e-Alerts
Computational approaches for effective CRISPR guide RNA design and evaluation (2019)

The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/ CRISPR-associated (Cas) system has emerged as the main technology for gene editing. Successful editing by CRISPR requires an appropriate Cas protein and guide RNA. However, low cleavage efficiency and off-target effects hamper the development and application of CRISPR/Cas systems. To predict cleavage efficiency and specificity, numerous computational approaches have been developed for scoring guide RNAs. Most scores are empirical or trained by experimental datasets, and scores are implemented using various computational methods. Herein, we discuss these approaches, focusing mainly on the features or computational methods they utilise. Furthermore, we summarise these tools and give some suggestions for their usage. We also recommend three versatile web-based tools with user-friendly interfaces and preferable functions. The review provides a comprehensive and up-to-date overview of computational approaches for guide RNA design that could help users to select the optimal tools for their research.
Intracellular Delivery of Proteins with a New Lipid-mediated Delivery System (2001)

There are many very effective methods to introduce transcriptionally active DNA into viable cells but approaches to deliver functional proteins are limited. We have developed a lipid-mediated delivery system that can deliver functional proteins or other bioactive molecules into living cells. This delivery system is composed of a new trifluoroacetylated lipopolyamine (TFA-DODAPL) and dioleoyl phosphatidylethanolamine (DOPE). This cationic formulation successfully delivered antibodies, dextran sulfates, phycobiliproteins, albumin, and enzymes (beta-galactosidase and proteases) into the cytoplasm of numerous adherent and suspension cells. Two systems were used to demonstrate that the proteins were delivered in a functionally active form. First, intracellular beta-galactosidase activity was clearly demonstrated within X-gal-stained cells after TFA-DODAPL:DOPE-mediated delivery of the enzyme. Second, the delivery system mediated delivery of several caspases (caspase 3, caspase 8, and granzyme B) into cultured cell lines and primary cells triggering apoptosis. Mechanistic studies showed that up to 100% of the protein mixed with the lipid formulation was captured into a lipid-protein complex, and up to 50% of the input protein associated with cells. This lipid-mediated transport system makes protein delivery into cultured cells as convenient, effective, and reliable as DNA transfection.
A Simple and Efficient Method for Preparation of Monomethoxypolyethylene Glycol Activated with p-Nitrophenylchloroformate and Its Application to Modification of L-Asparaginase. (1996)

An improved, simple and efficient method for preparation of monomethoxypolyethylene glycol (PEG) activated with p-nitrophenylchloroformate (PNP-PEG) and its use as a potent modifier of protein under mild conditions are described. Modification of bovine serum albumin with PNP-PEG was compared with that done with PEG activated with N, N′-carbonyldiimidazole or cyanuric chloride. The reaction of PEG, activated with either p-nitrophenylchloroformate or cyanuric chloride, with bovine serum albumin at 4°C reached a plateau within 1h, whereas protein modification using PEG activated with N, N′-carbonyldiimidazole was rather slow and gave a low yield. The remaining activity of L-asparaginase modified with PNP-PEG was much higher than that of the enzyme modified to the same degree with PEG activated with cyanuric chloride. At a 20 molar excess of PNP-PEG having a molecular weight of 5, 000, 55% of the free amino acid groups were modified at 4°C for 2h, and the modified enzyme still had 33% residual enzyme activity. Immunochemical studies showed that the highly modified enzyme (67% modification with 18% residual enzyme activity) had lost its immunogenicity and had become much less sensitive to protease digestion.
HMGA1: A Master Regulator of Tumor Progression in Triple-Negative Breast Cancer Cells (2013)

Emerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for the first time that the high mobility group A1 (HMGA1) gene drives metastatic progression in triple negative breast cancer cells (MDA-MB-231, Hs578T) by reprogramming cancer cells to a stem-like state. Silencing HMGA1 expression in invasive, aggressive breast cancer cells dramatically halts cell growth and results in striking morphologic changes from mesenchymal-like, spindle-shaped cells to cuboidal, epithelial-like cells. Mesenchymal genes (Vimentin, Snail) are repressed, while E-cadherin is induced in the knock-down cells. Silencing HMGA1 also blocks oncogenic properties, including proliferation, migration, invasion, and orthotopic tumorigenesis. Metastatic progression following mammary implantation is almost completely abrogated in the HMGA1 knock-down cells. Moreover, silencing HMGA1 inhibits the stem cell property of three-dimensional mammosphere formation, including primary, secondary, and tertiary spheres. In addition, knock-down of HMGA1 depletes cancer initiator/cancer stem cells and prevents tumorigenesis at limiting dilutions. We also discovered an HMGA1 signature in triple negative breast cancer cells that is highly enriched in embryonic stem cells. Together, these findings indicate that HMGA1 is a master regulator of tumor progression in breast cancer by reprogramming cancer cells through stem cell transcriptional networks. Future studies are needed to determine how to target HMGA1 in therapy.