gebhart/patrepeval huggingface dataset:
Role of cancer stem cells in racial disparity in colorectal cancer (2016)

Although African-Americans (AAs) have a higher incidence of colorectal cancer (CRC) than White people, the underlying biochemical mechanisms for this increase are poorly understood. The current investigation was undertaken to examine whether differences in self-renewing cancer stem/stem-like cells (CSCs) in the colonic mucosa, whose stemness is regulated by certain microRNAs (miRs), could partly be responsible for the racial disparity in CRC. The study contains 53 AAs and 47 White people. We found the number of adenomas and the proportion of CD44(+) CD166(- ) CSC phenotype in the colon to be significantly higher in AAs than White people. MicroRNAs profile in CSC-enriched colonic mucosal cells, expressed as ratio of high-risk (≥3 adenomas) to low-risk (no adenoma) CRC patients revealed an 8-fold increase in miR-1207-5p in AAs, compared to a 1.2-fold increase of the same in White people. This increase in AA was associated with a marked rise in lncRNA PVT1 (plasmacytoma variant translocation 1), a host gene of miR-1207-5p. Forced expression of miR-1207-5p in normal human colonic epithelial cells HCoEpiC and CCD841 produced an increase in stemness, as evidenced by morphologically elongated epithelial mesenchymal transition( EMT) phenotype and significant increases in CSC markers (CD44, CD166, and CD133) as well as TGF-β, CTNNB1, MMP2, Slug, Snail, and Vimentin, and reduction in Twist and N-Cadherin. Our findings suggest that an increase in CSCs, specifically the CD44(+) CD166(-) phenotype in the colon could be a predisposing factor for the increased incidence of CRC among AAs. MicroRNA 1207-5p appears to play a crucial role in regulating stemness in colonic epithelial cells in AAs.
Free‐Radical‐Based, Specific Desulfurization of Cysteine: A Powerful Advance in the Synthesis of Polypeptides and Glycopolypeptides (2007)

Being specific: The specific conversion of Cys (seleno-Cys) into Ala by a free-radical-mediated reduction can be achieved in an aqueous medium under mild conditions (see scheme, PG=protecting group). The conversion can be achieved in the presence of all 20 natural amino acids as well as a range of functional groups. This native chemical ligation followed by the Cys into Ala conversion will enable the synthesis of complex peptides and glycopeptides. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z704195_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Use of short‐term efficacy/toxicity tradeoffs to select second‐line drugs in rheumatoid arthritis. A metaanalysis of published clinical trials (1992)

In the short-term context of clinical trials, antimalarial drugs and MTX have the best efficacy/toxicity tradeoffs and may, therefore, be the preferred drugs.
Systemic Errors in Quantitative Polymerase Chain Reaction Titration of Self-Complementary Adeno-Associated Viral Vectors and Improved Alternative Methods (2011)

Self-complementary AAV (scAAV) vector genomes contain a covalently closed hairpin derived from a mutated inverted terminal repeat that connects the two monomer single-stranded genomes into a head-to-head or tail-totail dimer.We found that during quantitative PCR (qPCR) this structure inhibits the amplification of proximal amplicons and causes the systemic underreporting of copy number by as much as 10-fold.We show that cleavage of scAAV vector genomes with restriction endonuclease to liberate amplicons from the covalently closed terminal hairpin restores quantitative amplification, and we implement this procedure in a simple, modified qPCR titration method for scAAV vectors.In addition, we developed and present an AAV genome titration procedure based on gel electrophoresis that requires minimal sample processing and has low interassay variability, and as such is well suited for the rigorous quality control demands of clinical vector production facilities.
Self-Propagating Assembly of a Molecular-Based Multilayer (2008)

Accelerated growth of a molecular-based material that is an active participant in its continuing self-propagated assembly has been demonstrated. This nonlinear growth process involves diffusion of palladium into a network consisting of metal-based chromophores linked via palladium.
Identification of the human prostatic carcinoma oncogene PTI-1 by rapid expression cloning and differential RNA display. (1995)

Elucidating the relevant genomic changes mediating development and evolution of prostate cancer is paramount for effective diagnosis and therapy. A putative dominant-acting nude mouse prostatic carcinoma tumor-inducing gene, PTI-1, has been cloned that is expressed in patient-derived human prostatic carcinomas but not in benign prostatic hypertrophy or normal prostate tissue. PTI-1 was detected by cotransfecting human prostate carcinoma DNA into CREF-Trans 6 cells, inducing tumors in nude mice, and isolating genes displaying increased expression in tumor-derived cells by using differential RNA display (DD). Screening a human prostatic carcinoma (LNCaP) cDNA library with a 214-bp DNA fragment found by DD permitted the cloning of a full-length 2.0-kb PTI-1 cDNA. Sequence analysis indicates that PTI-1 is a gene containing a 630-bp 5' sequence and a 3' sequence homologous to a truncated and mutated form of human elongation factor 1 alpha. In vitro translation demonstrates that the PTI-1 cDNA encodes a predominant approximately 46-kDa protein. Probing Northern blots with a DNA fragment corresponding to the 5' region of PTI-1 identifies multiple PTI-1 transcripts in RNAs from human carcinoma cell lines derived from the prostate, lung, breast, and colon. In contrast, PTI-1 RNA is not detected in human melanoma, neuroblastoma, osteosarcoma, normal cerebellum, or glioblastoma multiforme cell lines. By using a pair of primers recognizing a 280-bp region within the 630-bp 5' PTI-1 sequence, reverse transcription-PCR detects PTI-1 expression in patient-derived prostate carcinomas but not in normal prostate or benign hypertrophic prostate tissue. In contrast, reverse transcription-PCR detects prostate-specific antigen expression in all of the prostate tissues. These results indicate that PTI-1 may be a member of a class of oncogenes that could affect protein translation and contribute to carcinoma development in human prostate and other tissues. The approaches used, rapid expression cloning with the CREF-Trans 6 system and the DD strategy, should prove widely applicable for identifying and cloning additional human oncogenes.
Interstrand Cross-Link Formation in Duplex and Triplex DNA by Modified Pyrimidines (2008)

DNA interstrand cross-links have important biological consequences and are useful biotechnology tools. Phenylselenyl substituted derivatives of thymidine (1) and 5-methyl-2'-deoxycytidine (5) produce interstrand cross-links in duplex DNA when oxidized by NaIO4. The mechanism involves a [2,3]-sigmatropic rearrangement of the respective selenoxides to the corresponding methide type intermediates, which ultimately produce the interstrand cross-links. Determination of the rate constants for the selenoxide rearrangements indicates that the rate-determining step for cross-linking is after methide formation. Cross-linking by the thymidine derivative in duplex DNA shows a modest kinetic preference when flanked by pyrimidines as opposed to purines. In contrast, the rate constant for cross-link formation from 5 opposite dG in duplex DNA is strongly dependent upon the flanking sequence and, in general, is at least an order of magnitude slower than that for 1 in an otherwise identical sequence. Introduction of mispairs at the base pairs flanking 5 or substitution of the opposing dG by dI significantly increases the rate constant and yield for cross-linking, indicating that stronger hydrogen bonding between the methide derived from it and dG compared to dA and the respective electrophile derived from 1 limits reaction by increasing the barrier to rotation into the required syn-conformation. Incorporation of 1 or 5 in triplex forming oligonucleotides (TFOs) that utilize Hoogsteen base pairing also yields interstrand cross-links. The dC derivative produces ICLs approximately 10x faster than the thymidine derivative when incorporated at the 5'-termini of the TFOs and higher yields when incorporated at internal sites. The slower, less efficient ICL formation emanating from 1 is attributed to reaction at N1-dA, which requires local melting of the duplex. In contrast, 5 produces cross-links by reacting with N7-dG. The cross-linking reactions of 1 and 5 illustrate the versatility and utility of these molecules as mechanistic probes and tools for biotechnology.
Transcriptional Regulation of thephoPROperon inBacillus subtilis (2004)

When Bacillus subtilis is subjected to phosphate starvation, the Pho regulon is activated by the PhoP-PhoR two-component signal transduction system to elicit specific responses to this nutrient limitation. The response regulator, PhoP, and its cognate histidine sensor kinase, PhoR, are encoded by the phoPR operon that is transcribed as a 2.7-kb bicistronic mRNA. The phoPR operon is transcribed from two sigma(A)-dependent promoters, P(1) and P(2). Under conditions where the Pho regulon was not induced (i.e., phosphate-replete conditions or phoR-null mutant), a low level of phoPR transcription was detected only from promoter P(1). During phosphate starvation-induced transition from exponential to stationary phase, the expression of the phoPR operon was up-regulated in a phosphorylated PhoP (PhoP approximately P)-dependent manner; in addition to P(1), the P(2) promoter becomes active. In vitro gel shift assays and DNase I footprinting experiments showed that both PhoP and PhoP approximately P could bind to the control region of the phoPR operon. The data indicate that while low-level constitutive expression of phoPR is required under phosphate-replete conditions for signal perception and transduction, autoinduction is required to provide sufficient PhoP approximately P to induce other members of the Pho regulon. The extent to which promoters P(1) and P(2) are activated appears to be influenced by the presence of other sigma factors, possibly the result of sigma factor competition. For example, phoPR is hyperinduced in a sigB mutant and, later in stationary phase, in sigH, sigF, and sigE mutants. The data point to a complex regulatory network in which other stress responses and post-exponential-phase processes influence the expression of phoPR and, thereby, the magnitude of the Pho regulon response.
Automatic Hardware Synthesis for a Hybrid Reconfigurable CPU Featuring Philips CPLDs (1998)

A high-level architecture of a Hybrid Reconfigurable CPU, based on a Philips-supported core processor, is introduced. It features the Philips XPLA2 CPLD as a reconfigurable functional unit. A compilation chain is presented, in which automatic implementation of time-critical program segments in custom hardware is performed. The entire process is transparent from the programmer's point of view. The hardware synthesis module of the chain, which translates segments of assembly code into a hardware netlist, is discussed in details. Application examples are also presented.
New trends in umbilical cord blood transplantation (2005)

Since the first report of a successful umbilical cord blood transplantation in 1988, there has been great interest in the use of cord blood as an alternative stem cell source to treat cancer and genetic diseases. More than 4000 cord blood transplantations have been performed worldwide. In this review, the scientific rationale for this therapy, as well as related preclinical studies, cord blood banking issues, and ethical concerns, will be addressed. Results of studies in both pediatric and adult transplantation will be discussed. Finally, new indications for cord blood use and emerging technologies will be addressed.
[Gene expression profiling of human ovarian epithelial tumors by digo nucleotide microarray]. (2001)

Gene expression of human ovarian carcinoma cell lines and epithelial ovarian tumors was examined by oligonucleotide microarray for about 6000 human cDNAs. (1) Comparison of gene expression between CDDP-sensitive human ovarian serous adenocarcinoma cell lines and CDDP-resistant cell lines revealed that gamma-glutamylcysteine synthetase, glutathione peroxidase-like protein, dehydrogenase (UGDH), NAD(P)H: quinoneoxireductase, glucose-6-phosphatase, ornithine decarboxylase and dihydrodiol dehydrogenase were associated with a mechanism of CDDP-resistance. Comparison of gene expression between taxol-sensitive human ovarian cell lines and taxol-resistant cell lines showed that up-regulation of 30 kinds of gene expression including MDR and semaphorin E in taxol-resistant cell lines. (2) Comparison of gene expression among serous adenocarcinomas, clear cell adenocarcinomas and non-cancerous ovarian tissues by hierarchical clustering demonstrated that clear difference between carcinomas and non-cancerous ovarian tissues but not obvious difference between serous and clear adenocarcinomas. Genes that were up- and down-regulated specifically in these two types of ovarian carcinomas were further selected by the criteria that difference in the mRNA level by more than 4-fold between tumors and non-cancerous tissues. Tissue type specific alterations of gene expression are likely to play important roles in the carcinogenesis of epithelial ovarian tumors. cDNA microarray is a powerful and high-throughput tool to analyze gene expression of cancer development.
Managing refractory glaucoma with a fixed combination of bimatoprost (0.03%) and timolol (0.5%) (2008)

Glaucoma is a chronic progressive optic neuropathy characterized by progressive loss of retinal ganglion cells, which manifests clinically with loss of optic disc neuroretinal rim tissue, defects in the retinal nerve fiber layer, and deficits on functional visual field testing. The goal of glaucoma treatment is to reduce the intraocular pressure to a level that prevents or minimizes the progressive loss of vision. The current standard of management for the newly diagnosed primary open angle glaucoma (PAOG) patient is to start topical medication. Available topical medications include: beta-adrenergic antagonists, alpha-adrenergic agonists, carbonic anhydraze inhibitors, prostaglandin analogues and miotics. In some patients, IOP is not adequately controlled by monotherapy. In those refractory patients, where more efficacy is required, shifting to another medication or adding a second medication is indicated. The complimentary action between two drugs serves as the basis for combination medications. One avenue of delivering a second medication is through a fixed combination medication that has the advantage of providing two medicines within one drop. Bimatoprost/timolol represents a new fixed combination which is clinically and statistically more effective than either of its active constituents for patients with refractory glaucoma. As regard the safety of the combination, there were no signs or symptoms of intolerance and the incidence of conjunctival hyperemia was clinically and statistically significantly less than each of the two components separately. Bimatoprost/timolol fixed combination offers cost and time savings, which may enhance compliance; also reducing the amount of preservative applied to the eye, will improve tolerability and may also favorably improve eventual surgical outcomes in patients who might require filtering procedures.
The Politics of Cultural Conservatism in Colonial Botswana: Queen Seingwaeng's Zionist Campaign in the Bakgatla Reserve, 1937-1947 (1998)

Studies of Christian Zionist churches in southern Africa have suggested that they were non-political. This paper puts the growth of Zionism among the BaKgatla in the context of local political struggles and the life of Queen Seingwaeng, mother of Chief Molefi. She was politically important from the 1910s until the 1960s, articulating the views of ordinary people otherwise considered politically helpless. She led popular opposition to the ''progressive'' authoritarianism of Regent 1sang, promoting the restoration of her son Molefi to chieftainship through religious movements in the 1930s-andjoining the Zion Christian Church in 1938. However, by 1947, Seingwaeng and the Zionists were seen as a political threat by Molefi and the ruling elite, who expelled them from BaKgatla territory. Molefi was reconciled with his mother in 1955, but she did not return home to Mochudi until 1967, nine years after his death. In 1947, Queen Mother Seingwaeng was beaten in public by her son Molefi, kgosi (king) of the BaKgatla, for refusing to abandon the Zion Christian Church (ZCC). She was a large, strong woman, known for her quiet, respectful demeanour, and then sixty-four. Molefi ordered her and the other Zionists to be rounded up and put on an open lorry and driven out of Mochudi, the Kgatla capital. Seingwaeng spent the next seventeen years in exile at Lentswe-Ie-Moriti, a farm 460 kilometres from Mochudi. She lived as a ZCC member until her death in 1967, which came nearly ten years after her son's life ended in a car crash. She closed her life in much the same fashion as she had spent it, as a warm but deeply religious person. Before Molefi had been born, Seingwaeng was raised in the Dutch Reformed Church (DRC) and was married to Molefi's father at the age of twenty-two, in a grand ceremony at the new DRC church in Mochudi. As a member of the women's kopano and regular attendant at Sunday services, she remained a steadfast DRC member into the 1930s, when she joined a breakaway church led by the Reverend Thomas Phiri. When his church faltered, Seingwaeng joined Ipelegeng, whose mission included consulting dingaka, persons adept in African religion. Soon, she and other Ipelegeng entered the ZCC of Joseph Lekganyane of Pieters burg and established colonial Botswana's first ZCC congregation, in Mochudi. Like the Ipelegeng, Seingwaeng's ZCC prayed for the restoration of Molefi as Kgatla kgosi, because they believed his troubles, and those of the BaKgatla, were the
Substrates for cytochemical demonstration of enzyme activity. V. Thymidine 3'- and 5'-(5-bromo-4-chloro-3-indolyl)phosphates (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSubstrates for cytochemical demonstration of enzyme activity. V. Thymidine 3'- and 5'-(5-bromo-4-chloro-3-indolyl)phosphatesJerome P. Horwitz and Joseph V. FreislerCite this: J. Med. Chem. 1970, 13, 5, 1024–1025Publication Date (Print):September 1, 1970Publication History Published online1 May 2002Published inissue 1 September 1970https://pubs.acs.org/doi/10.1021/jm00299a073https://doi.org/10.1021/jm00299a073research-articleACS PublicationsRequest reuse permissionsArticle Views136Altmetric-Citations5LEARN 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 optionsGet e-Alertsclose Get e-Alerts
Active management of a heterogeneous energy store for electric vehicles (2011)

The successful introduction of electric vehicles continues to be stifled by the high cost and limited performance life of battery technology. We assert that a disruptive improvement in systems-level cost-of-performance is possible by employing a rate-heterogeneous energy storage system, combining low-rate batteries and high-rate supercapacitors, that is mated to a predictive control system that optimizes power management by exploiting topographic information, traffic history, and specific driver performance. Such predictive power management, optimizing energy storage throughout episodes of vehicle acceleration and regenerative braking, has the potential to significantly decrease the total energy duty on the vehicle's batteries.
Apolipoprotein E and β‐amyloid (1–42) regulation of glycogen synthase kinase‐3β (2003)

Glycogen synthase kinase-3beta (GSK-3beta) is implicated in regulating apoptosis and tau protein hyperphosphorylation in Alzheimer's disease (AD). We investigated the effects of two key AD molecules, namely apoE (E3 and E4 isoforms) and beta-amyloid (Abeta) 1-42 on GSK-3beta and its major upstream regulators, intracellular calcium and protein kinases C and B (PKC and PKB) in human SH-SY5Y neuroblastoma cells. ApoE3 induced a mild, transient, Ca2+-independent and early activation of GSK-3beta. ApoE4 effects were biphasic, with an early strong GSK-3beta activation that was partially dependent on extracellular Ca2+, followed by a GSK-3beta inactivation. ApoE4 also activated PKC-alpha and PKB possibly giving the subsequent GSK-3beta inhibition. Abeta(1-42) effects were also biphasic with a strong activation dependent partially on extracellular Ca2+ followed by an inactivation. Abeta(1-42) induced an early and potent activation of PKC-alpha and a late decrease of PKB activity. ApoE4 and Abeta(1-42) were more toxic than apoE3 as shown by MTT reduction assays and generation of activated caspase-3. ApoE4 and Abeta(1-42)-induced early activation of GSK-3beta could lead to apoptosis and tau hyperphosphorylation. A late inhibition of GSK-3beta through activation of upstream kinases likely compensates the effects of apoE4 and Abeta(1-42) on GSK-3beta, the unbalanced regulation of which may contribute to AD pathology.
The total synthesis of tetracycline (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe total synthesis of tetracyclineHarry H. Wasserman, Ta Jung. Lu, and Ian A. ScottCite this: J. Am. Chem. Soc. 1986, 108, 14, 4237–4238Publication Date (Print):July 1, 1986Publication History Published online1 May 2002Published inissue 1 July 1986https://pubs.acs.org/doi/10.1021/ja00274a072https://doi.org/10.1021/ja00274a072research-articleACS PublicationsRequest reuse permissionsArticle Views823Altmetric-Citations16LEARN 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 optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts