gebhart/patrepeval huggingface dataset:
Organocatalytic Enantioselective Michael and Hetero-Michael Reactions (2007)

The enantioselective methods reported to date for carrying out conjugate additions of carbon- and heteroatom-centered nucleophiles to electron-deficient olefins, using small chiral organic molecules as catalysts, are reviewed.
Noncovalent PEGylation by Polyanion Complexation as a Means To Stabilize Keratinocyte Growth Factor-2 (KGF-2) (2011)

Repifermin, a truncated form of fibroblast growth factor-10 (FGF-10) also known as keratinocyte growth factor-2 (KGF-2), is a heparin-binding protein with potent regenerative properties. The protein unfolds and aggregates at relatively low temperature (~37 °C). Electrostatic interactions between polyanions and several FGFs have been reported to enhance the thermal stability of these proteins. Polyethylene glycol (PEG) was grafted to the polyanions pentosan polysulfate (PPS) and dextran sulfate (DS) as an alternative means to stabilize and noncovalently PEGylate KGF-2. Physical characteristics of KGF-2:polyanion-PEG complexes were examined using a variety of methods including circular dichroism (CD), intrinsic tryptophan fluorescence, differential scanning calorimetry, and dynamic light scattering. When compared to KGF-2 alone, subtle changes in CD spectra and fluorescence emission maxima were found when KGF-2 was formulated with the synthetic PEG-polyanions. Highly PEGylated polyanions (DS-PEG5) did not bind KGF-2 as well as conjugates with fewer PEG chains. The molecular weight of PEG did not have a noticeable effect on KGF-2 binding to the various PEG-polyanion conjugates. At optimal molar ratios, PPS-PEG and DS-PEG conjugates were able to stabilize KGF-2 by increasing the melting temperature by approximately 9-17 °C. Thus, polyanion-PEG conjugates improved the stability of KGF-2 and also offered a new electrostatic PEGylation scheme that may be extrapolated to other heparin-binding proteins.
Assessment of small RNA sorting into different extracellular fractions revealed by high-throughput sequencing of breast cell lines (2015)

Intercellular communication can be mediated by extracellular small regulatory RNAs (sRNAs). Circulating sRNAs are being intensively studied for their promising use as minimally invasive disease biomarkers. To date, most attention is centered on exosomes and microRNAs as the vectors and the secreted species, respectively. However, this field would benefit from an increased understanding of the plethora of sRNAs secreted by different cell types in different extracellular fractions. It is still not clear if specific sRNAs are selected for secretion, or if sRNA secretion is mostly passive. We sequenced the intracellular sRNA content (19-60 nt) of breast epithelial cell lines (MCF-7 and MCF-10A) and compared it with extracellular fractions enriched in microvesicles, exosomes and ribonucleoprotein complexes. Our results are consistent with a non-selective secretion model for most microRNAs, although a few showed secretion patterns consistent with preferential secretion. On the contrary, 5' tRNA halves and 5' RNA Y4-derived fragments of 31-33 were greatly and significantly enriched in the extracellular space (even in non-mammary cell lines), where tRNA halves were detected as part of ∼45 kDa ribonucleoprotein complexes. Overall, we show that different sRNA families have characteristic secretion patterns and open the question of the role of these sRNAs in the extracellular space.
Characterization of the Oligosaccharides Associated with the Human Ovarian Tumor Marker CA125 (2003)

CA125 is a mucin commonly employed as a diagnostic marker for epithelial ovarian cancer. Induction of humoral responses to CA125 leads to increased survival times in patients with this form of cancer, suggesting a potential role for this mucin in tumor progression. In this study, oligosaccharides linked to CA125 derived from the human ovarian tumor cell line OVCAR-3 were subjected to rigorous biophysical analysis. Sequencing of the O-glycans indicates the presence of both core type 1 and type 2 glycans. An unusual feature is the expression of branched core 1 antennae in the core type 2 glycans. CA125 is also N-glycosylated, expressing primarily high mannose and complex bisecting type N-linked glycans. High mannose type glycans include Man5-Man9GlcNAc2. The predominant N-glycans are the biantennary, triantennary, and tetraantennary bisecting type oligosaccharides. Remarkably, the N-glycosylation profiles of CA125 and the envelope glycoprotein gp120 (derived from H9 lymphoblastoid cells chronically infected with HIV-1) are very similar. The CA125-associated N-glycans have also recently been implicated in crucial recognition events involved in both the innate and adaptive arms of the cell-mediated immune response. CA125 may therefore induce specific immunomodulatory effects by employing its carbohydrate sequences as functional groups, thereby promoting tumor progression. Immunotherapy directed against CA125 may attenuate these immunosuppressive effects, leading to the prolonged survival of patients with this extremely serious form of cancer.
Immunochemical analysis of the interaction of p53 with MDM2;--fine mapping of the MDM2 binding site on p53 using synthetic peptides. (1994)

The function of p53 is modulated by binding to a number of cellular and viral proteins, such as MDM2 and SV40 large T antigen. An initial immunochemical characterization of the p53-MDM2 complex in a rat fibroblast cell line (Clone 6) suggested that the anti-p53 monoclonal antibody Bp53-19 failed to immunoprecipitate the complex, and only recognized a fraction of the available p53 protein. Following the recent identification of the Bp53-19 epitope at the N-terminal end of p53, in the vicinity of where MDM2 protein was known to bind, we investigated the possibility that Bp53-19 might identify a region of p53 that interacts with MDM2 protein. MDM2 was found to bind with great specificity to short synthetic peptides derived from the N-terminus of p53. Several p53 synthetic peptides libraries, and an alanine substitution series at the optimal binding site, were used to establish the MDM2 binding site, in fine detail, to the sequence TFSGLW (aa 18-23) in mouse and TFSDLW in man (aa 18-23). The key residues required for MDM2 binding are almost identical to those required for the monoclonal antibody Bp53-19 to bind and this region of p53 is recognised by many other anti-p53 antibodies.
Inhibition of Cell Growth and Shoot Development by a Specific Nucleotide Sequence in a Noncoding Viroid RNA (2003)

Viroids are small noncoding and infectious RNAs that replicate autonomously and move systemically throughout an infected plant. The RNAs of the family Pospiviroidae contain a central conserved region (CCR) that has long been thought to be involved in replication. Here, we report that the CCR of Potato spindle tuber viroid (PSTVd) also plays a role in pathogenicity. A U257A change in the CCR converted the intermediate strain PSTVd(Int) to a lethal strain that caused severe growth stunting and premature death of infected plants. PSTVd with nucleotide U257 changed to C or G did not cause such symptoms. The pathogenic effect of the U257A substitution was abolished by a C259U substitution in the same RNA. Analyses of the pathogenic effects of the U257A substitution in three other PSTVd variants established A257 as a new pathogenicity determinant that functions independently and synergistically with the classic pathogenicity domain. The U257A substitution did not alter PSTVd secondary structure, replication levels, or tissue tropism. The stunted growth of PSTVd(Int)U257A-infected tomato plants resulted from restricted cell expansion but not cell division or differentiation. This was correlated positively with the downregulated expression of an expansin gene, LeExp2. Our results demonstrate that specific nucleotides in a noncoding, pathogenic RNA have a profound effect in altering distinct cellular responses, which then lead to well-defined alterations in plant growth and developmental patterns. The feasibility of correlating viroid RNA sequence/structure with the altered expression of specific host genes, cellular processes, and developmental patterns makes viroid infection a valuable system in which to investigate host factors for symptom expression and perhaps also to characterize the mechanisms of RNA regulation of gene expression in plants.
Large-Scale and Automated DNA Sequence Determination (1991)

DNA sequence analysis is a multistage process that includes the preparation of DNA, its fragmentation and base analysis, and the interpretation of the resulting sequence information. New technological advances have led to the automation of certain steps in this process and have raised the possibility of large-scale DNA sequencing efforts in the near future [for example, 1 million base pairs (Mb) per year]. New sequencing methodologies, fully automated instrumentation, and improvements in sequencing-related computational resources may render genome-size sequencing projects (100 Mb or larger) feasible during the next 5 to 10 years.
A connectionist approach to conceptual information retrieval (1987)

This report proposes that recent advances using low-level connectionist representations offer new possibilities to those interested in free text information retrieval (IR). The AIR system demonstrates that this representation suits the IR domain well, particularly the special problems attending the more sophisticated forms of conceptual retrieval required in legal applications. Also, the natural way in which connectionist representations allow learning means that AIR can avoid the high costs associated with manual indexing while providing comparable results. The paper begins by motivating the importance of legal information retrieval, from the perspectives of both the Law and artificial intelligence (AI). Our approach is then compared to traditional methods for IR, and to more recent work using higher-level symbolic representations from AL After a brief introduction to connectionist representations in general, the AIR system is presented. The paper closes with evidence that this system does, in fact, begin to support the use of those “open textured” concepts that make the Law both a very difficult and a very illuminating domain for AI research.
Updates in non-small cell lung cancer - insights from the 2009 45th annual meeting of the American Society of Clinical Oncology (2010)

We have reviewed the pivotal presentations in non-small cell lung cancer (NSCLC) from the 2009 annual meeting of the American Society of Clinical Oncology. We have discussed the scientific data, the impact on standards of care, and ongoing clinical trials.In patients with early-stage NSCLC, there is still no data to support the superiority of either neoadjuvant or adjuvant chemotherapy. However, adjuvant cisplatin-based chemotherapy has sustained the survival benefits after median follow-up of more than 9 years. The first-line treatment with inhibitors of epidermal growth factor receptor (EGFR) could be considered for the treatment of EGFR mutated patients with metastatic disease.Several maintenance studies with cytotoxic or biological agents have also demonstrated promising outcomes. Finally, novel targeted agents such as inhibitors of histone deacetylase and multi-targeted tyrosine kinase inhibitor have shown promising activity in NSCLC treatment.
meso-Dihydroguaiaretic Acid and its Derivatives2 (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTmeso-Dihydroguaiaretic Acid and its Derivatives2Anthony W. SchreckerCite this: J. Am. Chem. Soc. 1957, 79, 14, 3823–3827Publication Date (Print):July 1, 1957Publication History Published online1 May 2002Published inissue 1 July 1957https://pubs.acs.org/doi/10.1021/ja01571a054https://doi.org/10.1021/ja01571a054research-articleACS PublicationsRequest reuse permissionsArticle Views211Altmetric-Citations14LEARN 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
Screening by Chest Radiograph and Lung Cancer Mortality (2011)

clinicaltrials.gov Identifier: NCT00002540.
Taste-Signaling Proteins Are Coexpressed in Solitary Intestinal Epithelial Cells (2006)

The taste system, made up of taste receptor cells clustered in taste buds at the surface of the tongue and the soft palate, plays a key role in the decision to ingest or reject food and thereby is essential in protecting organisms against harmful toxins and in selecting the most appropriate nutrients. To determine if a similar chemosensory system exists in the gastrointestinal tract, we used immunohistochemistry and real-time polymerase chain reaction (PCR) to investigate which taste-signaling molecules are expressed in the intestinal mucosa. The PCR data showed that T1r1, T1r2, T1r3, alpha-gustducin, phospholipase Cbeta2 (PLCbeta2), and Trpm5 are expressed in the stomach, small intestine, and colon of mice and humans, with the exception of T1r2, which was not detected in the mouse and human stomach or in the mouse colon. Using transgenic mice expressing enhanced green fluorescent protein under the control of the Trpm5 promoter, we found colocalization of Trpm5 and alpha-gustducin in tufted cells at the surface epithelium of the colon, but these cells did not express T1r3 or PLCbeta2. In the duodenal glands, 43%, 33%, and 38% of Trpm5-expressing cells also express PLCbeta2, T1r3, or alpha-gustducin, respectively. The duodenal gland cells that coexpress PLCbeta2 and Trpm5 morphologically resemble enteroendocrine cells. We found a large degree of colocalization of Trpm5, alpha-gustducin, T1r1, and T1r3 in tufted cells of the duodenal villi, but these cells rarely expressed PLCbeta2. The data suggest that these duodenal cells are possibly involved in sensing amino acids.
Partial denaturation of transthyretin is sufficient for amyloid fibril formation in vitro (1992)

Amyloid diseases are caused by the self-assembly of a given protein into an insoluble cross-beta-sheet quaternary structural form which is pathogenic. An understanding of the biochemical mechanism of amyloid fibril formation should prove useful in understanding amyloid disease. Toward this end, a procedure for the conversion of the amyloidogenic protein transthyretin into amyloid fibrils under conditions which mimic the acidic environment of a lysosome has been developed. Association of a structured transthyretin denaturation intermediate is sufficient for amyloid fibril formation in vitro. The rate of fibril formation is pH dependent with significant rates being observed at pHs accessible within the lysosome (3.6-4.8). Far-UV CD spectroscopic studies suggest that transthyretin retains its secondary structural features at pHs where fibrils are formed. Near-UV CD studies demonstrate that transthyretin has retained the majority of its tertiary structure during fibril formation as well. Near-UV CD analysis in combination with glutaraldehyde cross-linking studies suggests that a pH-mediated tetramer to monomer transition is operative in the pH range where fibril formation occurs. The rate of fibril formation decreases markedly at pHs below pH 3.6, consistent with denaturation to a monomeric TTR intermediate which has lost its native tertiary structure and capability to form fibrils. It is difficult to specify with certainty which quaternary structural form of transthyretin is the amyloidogenic intermediate at this time. These difficulties arise because the maximal rate of fibril formation occurs at pH 3.6 where tetramer, traces of dimer, and significant amounts of monomer are observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Deletions in the 5' region of dystrophin and resulting phenotypes. (1994)

Deletions in the dystrophin gene give rise to both Duchenne and Becker muscular dystrophies. Good correlation is generally found between the severity of the phenotype and the effect of the deletion on the reading frame: deletions that disrupt the reading frame result in a severe phenotype, while in frame deletions are associated with a milder disease course. Rare exceptions to this rule, mainly owing to frameshift mutations in the 5' region of the gene (in particular deletions involving exons 3 to 7) which are associated with a milder than expected phenotype, have been reported previously. In order to characterise better the relationship between genotype and phenotype as a result of mutations arising in the 5' region of the gene, we have studied a large cohort of patients with small in frame and out of frame deletions in the first 13 exons of the dystrophin gene. Fifty-five patients with a deletion in this area were identified; approximately one third of them had a phenotype different from that theoretically expected. Patients were divided into two groups: (1) patients with a severe clinical phenotype despite the presence of a small, in frame deletion and (2) patients with a mild phenotype and an out of frame deletion. Noticeable examples observed in the first group were Duchenne boys with a deletion of exon 5, of exon 3, and of exons 3-13. In the second group we observed several patients with an intermediate or Becker phenotype and out of frame deletions involving not only the usual exons 3-7 but also 5-7 and 3-6. These data indicate that a high proportion of patients with a deletion in the 5' end of the gene have a phenotype that is not predictable on the basis of the effect of the deletion on the reading frame. The N-terminus of dystrophin has at least one actin binding domain that might be affected by the small, in frame deletions in this area. The effect of the in frame deletions of exon 3, 5, and 3-13 on this domain might account for the severe phenotype observed in these patients. Other mechanisms, such as unexpected effect of the deletion on splicing behaviour, might, however, also be implicated in determining the phenotype outcome.
Hydrolysis of ortho esters: further investigation of the factors that control the rate-determining step (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrolysis of ortho esters: further investigation of the factors that control the rate-determining stepY. Chiang, A. J. Kresge, M. O. Lahti, and D. P. WeeksCite this: J. Am. Chem. Soc. 1983, 105, 23, 6852–6855Publication Date (Print):November 1, 1983Publication History Published online1 May 2002Published inissue 1 November 1983https://pubs.acs.org/doi/10.1021/ja00361a017https://doi.org/10.1021/ja00361a017research-articleACS PublicationsRequest reuse permissionsArticle Views730Altmetric-Citations7LEARN 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
Radiometric framework for image mosaicking (2005)

Nonuniform exposures often affect imaging systems, e.g., owing to vignetting. Moreover, the sensor's radiometric response may be nonlinear. These characteristics hinder photometric measurements. They are particularly annoying in image mosaicking, in which images are stitched to enhance the field of view. Mosaics suffer from seams stemming from radiometric inconsistencies between raw images. Prior methods feathered the seams but did not address their root cause. We handle these problems in a unified framework. We suggest a method for simultaneously estimating the radiometric response and the camera nonuniformity, based on a frame sequence acquired during camera motion. The estimated functions are then compensated for. This permits image mosaicking, in which no seams are apparent. There is no need to resort to dedicated seam-feathering methods. Fundamental ambiguities associated with this estimation problem are stated.
Solar Thermochemical CO2 Splitting Utilizing a Reticulated Porous Ceria Redox System (2012)

A solar cavity-receiver containing a reticulated porous ceramic (RPC) foam made of pure CeO2 has been experimentally investigated for CO2 splitting via thermochemical redox reactions. The RPC was directly exposed to concentrated thermal radiation at mean solar flux concentration ratios of up to 3015 suns. During the endothermic reduction step, solar radiative power inputs in the range 2.8–3.8 kW and nominal reactor temperatures from 1400 to 1600 °C yielded CeO2−δ with oxygen deficiency δ ranging between 0.016 and 0.042. In the subsequent exothermic oxidation step at below about 1000 °C, CeO2−δ was stoichiometrically reoxidized with CO2 to generate CO. The solar-to-fuel energy conversion efficiency, defined as the ratio of the calorific value of CO (fuel) produced to the solar radiative energy input through the reactor’s aperture and the energy penalty for using inert gas, was 1.73% average and 3.53% peak. This is roughly four times greater than the next highest reported values to date for a solar-driven device. The fuel yield per cycle was increased by nearly 17 times compared to that obtained with optically thick ceria felt because of the deeper penetration and volumetric absorption of high-flux solar irradiation.
Induction of Adult Neurogenesis (2003)

A bstract : Over most of the past century, it was thought that the adult brain was completely incapable of generating new neurons. However, in the last decade, the development of new techniques has resulted in an explosion of new research showing that (i) neurogenesis, the birth of new neurons, is not restricted to embryonic development, but normally also occurs in two limited regions of the adult mammalian brain (the olfactory bulb and the dentate gyrus of the hippocampus); (ii) that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain; and (iii) that it is possible to induce neurogenesis even in regions of the adult mammalian brain, like the neocortex, where it does not normally occur, via manipulation of endogenous multipotent precursors in situ . In the neocortex, recruitment of small numbers of new neurons can be induced in a region‐specific, layer‐specific, and neuronal type‐specific manner, and newly recruited neurons can form long‐distance connections to appropriate targets. This suggests that elucidation of the relevant molecular controls over adult neurogenesis from endogenous neural precursors/stem cells may allow the development of neuronal replacement therapies for neurodegenerative disease and other central nervous system injuries that may not require transplantation of exogenous cells.