gebhart/patrepeval huggingface dataset:
Genome-wide Allelic State Analysis on Flow-Sorted Tumor Fractions Provides an Accurate Measure of Chromosomal Aberrations (2008)

Chromosomal aberrations are a common characteristic of cancer and are associated with copy number abnormalities and loss of heterozygosity (LOH). Tumor heterogeneity, low tumor cell percentage, and lack of knowledge of the DNA content impair the identification of these alterations especially in aneuploid tumors. To accurately detect allelic changes in carcinomas, we combined flow-sorting and single nucleotide polymorphism arrays. Cells derived from archival cervical and colon cancers were flow-sorted based on differential vimentin and keratin expression and DNA content and analyzed on single nucleotide polymorphism arrays. A new algorithm, the lesser allele intensity ratio, was used to generate a molecular measure of chromosomal aberrations for each case. Flow-sorting significantly improved the detection of copy number abnormalities; 31.8% showed an increase in amplitude and 23.2% were missed in the unsorted fraction, whereas 15.9% were detected but interpreted differently. Integration of the DNA index in the analysis enabled the identification of the allelic state of chromosomal aberrations, such as LOH ([A]), copy-neutral LOH ([AA]), balanced amplifications ([AABB]), and allelic imbalances ([AAB] or [AAAB], etc.). Chromosomal segments were sharply defined. Fluorescence in situ hybridization copy numbers, as well as the high similarity between the DNA index and the allelic state index, which is the average of the allelic states across the genome, validated the method. This new approach provides an individual molecular measure of chromosomal aberrations and will likely have repercussions for preoperative molecular staging, classification, and prognostic profiling of tumors, particularly for heterogeneous aneuploid tumors, and allows the study of the underlying molecular genetic mechanisms and clonal evolution of tumor subpopulations.
Abstract B113: In vivo characterization of anti-PD-1 antibody REGN2810 in human PD-1 knock-in mice (2016)

Abstract The Programmed Death-1 (PD-1) receptor is an immunologic inhibitory checkpoint, expressed by activated T cells. PD-1 signals upon binding to its ligands PD-L1 and PD-L2 expressed on antigen presenting cells and some types of cancer cells, and delivers inhibitory signals to T cells, resulting in suppression of T-cell effector function. In cancer patients, PD-1 is expressed on tumor-infiltrating lymphocytes and inhibits antitumor immune responses through ligand binding. Clinically, it has been shown that antibodies (Abs) that block the interaction between PD-1 and PD-L1 can release the cytotoxic function of tumor-specific T cells, yielding durable objective responses in multiple cancer types. This study describes preclinical characterization of REGN2810, a fully human hinge-stabilized IgG4 monoclonal Ab that binds to the extracellular domain of human PD-1 with high affinity and specificity and inhibits interaction of PD-1 with its ligands. Taking advantage of the ability of human PD-1 to interact with murine PD-L1, we generated a mouse with human PD-1 gene knock-in allowing direct testing of our anti-human PD-1 Ab. Human PD-1 knock-in mice express a hybrid protein containing the extracellular portion of human PD-1, and transmembrane and intracellular domains of mouse PD-1. We demonstrated functional PD-1/PD-L1 signaling and immune responses in this model, and confirmed REGN2810 binding to hybrid PD-1 receptor on mouse T cells in vivo following REGN2810 injections. Prophylactic and therapeutic treatments of subcutaneous syngeneic tumors with REGN2810 in human PD-1 knock-in mice resulted in a dose-dependent suppression of tumor growth. Currently REGN2810 anti-PD-1 Ab is in phase 1 clinical trials for oncology indications. Citation Format: Elena Burova, Omaira Allbritton, William Poueymirou, Venus Lai, Janelle Waite, Dimitris Skokos, Nicholas Papadopoulos, Drew Murphy, Israel Lowy, Ella Ioffe, Gavin Thurston. In vivo characterization of anti-PD-1 antibody REGN2810 in human PD-1 knock-in mice. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B113.
Highly effective resolution of 1,3-dibenzyl-6-hydroxy-3,3a,6,6a-tetrahydro-1H-furo(3,4-d)imidazole-2,4-dione, an intermediate for biotin, with optically active amines and reutilization of the unwanted epimer. (1990)

The direct resolution of (3aRS, 6SR, 6aSR)-1, 3-dibenzyl-6-hydroxy-3, 3a, 6, 6a-tetrahydro-1H-furo[3, 4-d]imidazole-2, 4-dione [(±)-9], a key intermediate for biotin, with optically active amines was examined. Reaction of (±)-9 with cinchonidine readili gave the cinchonidine salt of the (4S, 5R)-aldehyde-carboxylic acid (12), acidification of which gave (3aS.6R, 6aR)-9, convertible to biothin. N-alkyl-D-glucamines (14) were also found to be effective resolving agents for (±)-9 applicable for industrial use. Reutilizatin of the unwanted epimer [(3aR, 6S, 6aS)-9] was effected by facile oxidation to the meso-diacid (3) with sodium chlorite.
Capping interactions in isolated .alpha. helixes: position-dependent substitution effects and structure of a serine-capped peptide helix (1993)

The influence of an amino acid on the stability of alpha-helical structure depends on the position of the residue in the helix with respect to the ends. Short alpha helices in proteins are stabilized both by H-bonding of the main-chain NH and CO groups and by capping interactions between side chains and unfulfilled peptide groups at the N and C termini. Peptide models based on consensus position-dependent helix sequences allow one to model capping effects in isolated helices and to establish a base line for these interactions in proteins. We report here an extended series of substitutions in the cap positions of our peptide models and the solution structure of peptide S3, with serine at the N-cap position defined as the N-terminal residue with partly helix and partly coil conformation. The resulting model, determined by 2D 1H NMR, is consistent with a structure at the N-cap involving H-bonding between the serine gamma oxygen and the peptide NH of the glutamic acid residue three amino acids toward the C terminus. A bifurcated H-bond of Ser O gamma with the NH of Asp5 is possible also, since this group is within interacting distance. This provides direct evidence that specific side-chain interactions with the main chain stabilize isolated alpha-helical structure.
Mouse Strain–Specific Differences in Vascular Wall Gene Expression and Their Relationship to Vascular Disease (2004)

Gene expression differences between the 2 strains suggest that aortas of C57Bl/6 mice have a higher genetic propensity to develop inflammation in response to appropriate atherogenic stimuli. This study expands the repertoire of factors in known disease-related signaling pathways and identifies novel candidate genes for future study. To gain insights into the molecular pathways that are differentially activated in strains of mice with varied susceptibility to atherosclerosis, we performed comprehensive transcriptional profiling of their vascular wall. Genes identified through these studies expand the repertoire of factors in disease-related signaling pathways and identify novel candidate genes in atherosclerosis.
N- Methyl- d -Aspartate Receptor Type 2B Is Epigenetically Inactivated and Exhibits Tumor-Suppressive Activity in Human Esophageal Cancer (2006)

Promoter hypermethylation accompanied by gene silencing is a common feature of human cancers. We identified previously several new tumor suppressor genes based on pharmacologic unmasking of the promoter region and detection of reexpression on microarray analysis. In this study, we modified the selection of candidates from our previous microarray data by excluding genes that showed basal expression in cancer cell lines. With the new method, we found novel methylated genes with 90% accuracy. Among these 33 novel methylated genes that we identified in esophageal squamous cell carcinoma (ESCC) cell lines, N-methyl-D-aspartate receptor type 2B (NMDAR2B) was of particular interest. NMDAR2B was methylated in 95% of primary human ESCC tissue specimens and 12 ESCC cell lines by sequence analysis. NMDAR2B expression was silenced in all 12 ESCC cell lines and was reactivated by the demethylating agent 5-aza-2'-deoxycytidine. Moreover, reintroduction of the gene was accompanied by marked Ca(2+)-independent apoptosis in ESCC cell lines, suggesting that NMDAR2B can suppress tumor growth. Thus, NMDAR2B promoter methylation is common in ESCC, abrogating gene transcription and leading to cellular resistance to apoptosis.
Human papillomavirus DNA and P16～(INK4A) expression in concurrent esophageal and gastric cardia cancers (2010)

AIM:To investigate the relationship between human papillomavirus (HPV) infection and concurrent esophagus and gastric cardia cancer from the same patient (CC) and examine the significance of P16 INK4A protein expression.METHODS:Polymerase chain reaction was used to detect the presence of HPV type16 (HPV16).The expression of P16 INK4A protein was detected using immunohistochemistry.RESULTS:Among the CC specimens,HPV16-DNA was found in eight cases of esophageal squamous cell carcinoma (ESCC) and five cases of gastric cardia adenocarcinoma (GCA),respectively (47% vs 29%),and two of both ESCC and GCA.P16 INK4A was highly expressed in both ESCC and GCA.In the HPV-associated positive CC,higher P16 INK4A expression was observed in the GCA than in the ESCC (75% vs 25%,P < 0.05).CONCLUSION:HPV16 as a correlated risk factor may play an important role in the development of ESCC and GCA.P16 INK4A may be a screening index in the HPVassociated carcinoma of gastric cardia.
Interleukin-18 and glycosaminoglycan binding by a protein encoded by Variola virus (2004)

Poxvirus interleukin (IL)-18 binding proteins (IL-18BPs) are soluble decoys that inhibit the activity of IL-18. The aim of this study was to demonstrate IL-18 binding activity of the Variola virus protein D7L. D7L effectively inhibited the biological activity of IL-18 in a bioassay. We compared the affinity and kinetics of D7L and the Ectromelia virus IL-18BP, p13, for human and murine IL-18 using surface plasmon resonance and no differences were detected, indicating that the differences in amino acid sequence did not affect binding or species specificity. Both proteins had higher affinity for murine than human IL-18. This was similar to human IL-18BP and the Molluscum contagiosum virus IL-18BP, which also demonstrated higher affinity for human IL-18. The host range of Variola virus is limited to humans and thus the affinity of D7L for IL-18 does not correlate with its host range. Furthermore, we demonstrated that D7L is capable of interacting with glycosaminoglycans (GAGs) via the C terminus, while p13 is not. Importantly, D7L interacted with both GAG and IL-18 simultaneously, indicating that the binding sites were distinct.
Human CD4+CD25+ thymocytes and peripheral T cells have immune suppressive activityin vitro (2001)

CD4(+)CD25(+) T cells in mice and rats are capable of transferring protection against organ-specific autoimmune disease and colitis and suppressing the proliferation of other T cells after polyclonal stimulation in vitro. Here we describe the existence in humans of CD4(+)CD25(+) T cells with the same in vitro characteristics. CD4(+)CD8(-)CD25(+) T cells are present in both the thymus and peripheral blood of humans ( approximately 10 % of CD4(+)CD8(-) T cells), proliferate poorly in response to mitogenic stimulation and suppress the proliferation of CD4(+)CD25(-) cells in co-culture. This suppression requires cell contact and can be overcome by the addition of exogenous IL-2. CD4(+)CD25(+) cells from thymus and blood were poor producers of IL-2 and IFN-gamma, and suppressed the levels of these cytokines produced by CD4(+)CD25(-) cells. However, CD4(+)CD25(+) PBL produced higher levels of IL-4 and similar amounts of IL-10 as CD4(+)CD25(-) cells. Regulatory CD4(+)CD25(+) T cells have an activated phenotype in the thymus with expression of CTLA-4 and CD122 (IL-2Rbeta). The fact that CD4(+)CD25(+) regulatory T cells are present with a similar frequency in the thymus of humans, rats and mice, suggests that the role of these cells in the maintenance of immunological tolerance is an evolutionarily conserved mechanism.
Potent Small-Molecule Binding to a Dynamic Hot Spot on IL-2 (2003)

The complexes between IL-2 and two similar small molecules, one a lead compound and the other a potent, affinity-optimized compound, were determined by X-ray crystallography. The lead compound (IC50 = 6 muM) bound to a hot spot on IL-2 in a groove that is not apparent in either the unliganded protein or a complex between IL-2 and a weakly bound drug fragment. The affinity-optimized compound (IC50 = 0.06 muM), which has an added aromatic acid fragment, bound in the same groove as the lead compound. In addition, a novel binding site was formed for the aromatic acid which is unseen in the complex with the lead compound. Thus, the hot spot on IL-2 is highly dynamic, with the protein changing form at multiple sites to maximize packing for each compound. Binding-site rigidity is often thought to play a role in high-affinity interactions. However, in this case, specific contacts between the small molecule and the protein are made despite the adaptivity of the hot spot. Given the change in morphology that was observed in IL-2, it is unlikely that a potent inhibitor could have been found by rational design. Therefore, fragment assembly methods offer the stochastic advantage of finding fragments in flexible protein regions where structural changes are unpredictable.
Fracture origins of optical fibers fabricated by hybridized process (1996)

Fracture origins of single-mode optical fibers that were produced by the CIP hybridized process consisting of overcladding a VAD-derived core rod with silica glass made from commercial silica powder were studied. It was found that there were many inclusions that caused failure of the fiber at the screening test. To identify the inclusions, the EPMA technique was successfully used and new internal defects such as a Cr, a Cr-Fe, and a Zr inclusions were found. By investigating the manufacturing process precisely, stainless steel particles and Cr/sub 2/O/sub 3/ particles in the silica powder were found to become origins of the fractures. Further, the removal of Cr/sub 2/O/sub 3/ particles by the reaction with chlorine gas at high temperature was studied, and its dependence on the reaction temperature and on the chlorine content was clarified. It was also suggested that the initial particle size of a Cr/sub 2/O/sub 3/ particle was an important factor for its elimination. The results obtained by this study should be used to remove both the Cr and the Cr-Fe inclusions.
Preparation and properties of α‐chitin‐whisker‐reinforced hyaluronan–gelatin nanocomposite scaffolds (2010)

Abstract Tissue scaffolds made of naturally derived polymers present poor mechanical properties, which may limit their actual utilization in certain areas where high strength is a key criterion. This study was aimed at developing tissue scaffolds from a 50 : 50 w/w blend of hyaluronan (HA) and gelatin (Gel) that contained different amounts of acid‐hydrolyzed α‐chitin whiskers (CWs) by a freeze‐drying method. The weight ratios of the CWs to the blend were 0–30%. These scaffolds were characterized for their physical, physicochemical, mechanical, and biological properties. Regardless of the CW content, the average pore size of the scaffolds ranged between 139 and 166 μm. The incorporation of 2% CWs in the HA–Gel scaffolds increased their tensile strength by about two times compared to those of the other groups of the scaffolds. Although the addition of 20–30% CWs in the scaffolds improved their thermal stability and resistance to biodegradation, the scaffolds with 10% CWs were the best for supporting the proliferation of cultured human osteosarcoma cells (SaOS‐2). © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Investigation of the Assembly of Comb Block Copolymers in the Solid State (2008)

Comb block copolymers are a relatively new architecture of polymer whose assembly into ordered morphologies in the solid state is largely unexplored. Thirty-two comb block copolymers with molecular weights from 168 to 4200 kg mol−1 were synthesized and assembled in the solid state into ordered morphologies with domain sizes as large as 138 nm. The individual structures of these polymers were studied by atomic force microscopy and scanning electron microscopy to identify their shapes. The solid-state morphologies of these polymers were imaged by scanning electron microscopy and small-angle X-ray scattering when permissible. Four phase maps were plotted from the 32 data points generated in this work to investigate how differences in polymer compositions affected the final morphologies. A clear relationship between the compositions of polymers and their morphologies was observed. The polymers were systematically altered to investigate the relationship between their compositions and the domain sizes of their morphologies. In one set of samples, the molecular weights of the arms were kept constant while the molecular weight of the backbone polymer was increased. In a second set of examples, the backbone polymer remained constant while the molecular weights of the arms were increased. While higher molecular weight polymers generally led to larger domain spacings in the microphase-separated structures, variations in the comb arm lengths resulted in dramatic changes in the observed solid-state morphologies. This paper is the first to provide a detailed study of a large series of comb block copolymers to relate their compositions to their assembled morphologies in the solid state.
PeroxisomeDB: a database for the peroxisomal proteome, functional genomics and disease (2006)

Peroxisomes are essential organelles of eukaryotic origin, ubiquitously distributed in cells and organisms, playing key roles in lipid and antioxidant metabolism. Loss or malfunction of peroxisomes causes more than 20 fatal inherited conditions. We have created a peroxisomal database (http://www.peroxisomeDB.org) that includes the complete peroxisomal proteome of Homo sapiens and Saccharomyces cerevisiae, by gathering, updating and integrating the available genetic and functional information on peroxisomal genes. PeroxisomeDB is structured in interrelated sections 'Genes', 'Functions', 'Metabolic pathways' and 'Diseases', that include hyperlinks to selected features of NCBI, ENSEMBL and UCSC databases. We have designed graphical depictions of the main peroxisomal metabolic routes and have included updated flow charts for diagnosis. Precomputed BLAST, PSI-BLAST, multiple sequence alignment (MUSCLE) and phylogenetic trees are provided to assist in direct multispecies comparison to study evolutionary conserved functions and pathways. Highlights of the PeroxisomeDB include new tools developed for facilitating (i) identification of novel peroxisomal proteins, by means of identifying proteins carrying peroxisome targeting signal (PTS) motifs, (ii) detection of peroxisomes in silico, particularly useful for screening the deluge of newly sequenced genomes. PeroxisomeDB should contribute to the systematic characterization of the peroxisomal proteome and facilitate system biology approaches on the organelle.
Phylogenetic analyses of Synechococcus strains (cyanobacteria) using sequences of 16S rDNA and part of the phycocyanin operon reveal multiple evolutionary lines and reflect phycobilin content. (2001)

The genus Synechococcus (cyanobacteria), while containing morphologically similar isolates, is polyphyletic and organisms presently classified as such require reclassification into several independent genera. Studies based on analysis of 16S rRNA gene sequences have shown that members of the genus Synechococcus are affiliated to three of seven deeply branching cyanobacterial lineages. In addition, some strains do not appear to be associated with any of these lineages and may represent novel clades. In this report, a cyanobacterial phylogeny based on 16S rDNA sequences, including 14 newly sequenced Synechococcus isolates, is presented. One newly sequenced Synechococcus strain (PCC 7902) did not have any close relatives amongst cyanobacterial isolates currently contained in 16S rDNA sequence databases and was only loosely affiliated to a cyanobacterial lineage in which no other Synechococcus strains were found. Three hot-spring Synechococcus isolates, including two that were newly sequenced in this study (PCC 6716 and PCC 6717), formed an additional cyanobacterial lineage. These results indicated that Synechococcus species are affiliated to five of eight deeply branching cyanobacterial lineages. Part of the phycocyanin (PC) gene sequence (cpc), including the intergenic spacer (IGS) between cpcB and cpcA and the corresponding flanking regions (cpcBA-IGS), was used to investigate relationships between closely related Synechococcus isolates. Previously described PCR primers did not amplify this region from the majority of strains under investigation, so a new set of primers was designed that allowed amplification and sequencing of the cpcBA-IGS and flanking regions from 38 Synechococcus species. Phylogenetic analysis of this region was largely consistent with that obtained from 16S rDNA sequence analysis and revealed a relationship between the primary PC DNA sequence and the phycobilin content of cells.
Androgen Receptor Immunohistochemistry as a Companion Diagnostic Approach to Predict Clinical Response to Enzalutamide in Triple-Negative Breast Cancer (2017)

At a threshold of ≥ 10% nuclear expression, the AR was associated with TNBC response to enzalutamide. However, the modest PPV may restrict its clinical application, and additional diagnostic tools may be helpful for improved patient selection.
High-level expression of active HIV-1 integrase from a synthetic gene in human cells (2000)

A synthetic gene encoding for HIV-1 integrase was designed to circumvent the intrinsic instability and the repressor elements present in the wild-type gene. High-level expression of HIV-1 integrase was obtained in various human cell lines independently of viral accessory proteins. A human 293T cell line was selected that stably expresses HIV-1 integrase and has growth kinetics comparable to the parental cell line. The enzyme was localized in the nucleus and remained stably associated with the chromosomes during mitosis. Lentiviral vector particles carrying the inactivating D64V mutation in the integrase gene were capable of stably transducing 293T cells when complemented in the producer cells with integrase expressed from the synthetic gene. When the cell line that stably expresses integrase was infected with the defective viral particles, complementation of integrase activity was detected as well. Expression of active HIV-1 integrase in human cells will facilitate the study of the interplay between host and viral factors during integration.