gebhart/patrepeval huggingface dataset:
Serum- and oncoprotein-mediated induction of a gene with sequence similarity to the gene encoding carcinoembryonic antigen. (1989)

We describe the molecular identification of a gene, designated T1, whose expression in mouse NIH 3T3 cells is strongly induced by the Ha-ras(EJ) and v-mos oncogenes and by serum. The T1 gene encodes a 38.5-kDa protein, as predicted from its primary sequence and shown by in vitro translation. The protein was processed at its amino terminus and extensively modified by N-linked glycosylation in vitro in the presence of microsomal vesicles. Sequence comparison of T1 with the MIPSX data base (Max-Planck-Institut für Biochemie, Martinsried/Munich) revealed similarity to the human carcinoembryonic antigen, a tumor marker which is overexpressed in colon adenocarcinomas and in fetal tissues. Considerable sequence similarity has also been observed to the short conserved region of other proteins which, like carcinoembryonic antigen, are encoded by members of the immunoglobulin gene superfamily.
In Vivo Base Editing of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) as a Therapeutic Alternative to Genome Editing (2017)

These results demonstrate the ability to precisely introduce therapeutically relevant nucleotide variants into the genome in somatic tissues in adult mammals, as well as highlighting a potentially safer alternative to therapeutic genome editing.
Umbilical Cord Mesenchymal Stem Cells: Adjuvants for Human Cell Transplantation (2007)

The Wharton's jelly of the umbilical cord is rich in mesenchymal stem cells (UC-MSCs) that fulfill the criteria for MSCs. Here we describe a novel, simple method of obtaining and cryopreserving UC-MSCs by extracting the Wharton's jelly from a small piece of cord, followed by mincing the tissue and cryopreserving it in autologous cord plasma to prevent exposure to allogeneic or animal serum. This direct freezing of cord microparticles without previous culture expansion allows the processing and freezing of umbilical cord blood (UCB) and UC-MSCs from the same individual on the same day on arrival in the laboratory. UC-MSCs produce significant concentrations of hematopoietic growth factors in culture and augment hematopoietic colony formation when co-cultured with UCB mononuclear cells. Mice undergoing transplantation with limited numbers of human UCB cells or CD34(+) selected cells demonstrated augmented engraftment when UC-MSCs were co-transplanted. We also explored whether UC-MSCs could be further manipulated by transfection with plasmid-based vectors. Electroporation was used to introduce cDNA and mRNA constructs for GFP into the UC-MSCs. Transfection efficiency was 31% for cDNA and 90% for mRNA. These data show that UC-MSCs represent a reliable, easily accessible, noncontroversial source of MSCs. They can be prepared and cryopreserved under good manufacturing practices (GMP) conditions and are able to enhance human hematopoietic engraftment in SCID mice. Considering their cytokine production and their ability to be easily transfected with plasmid-based vectors, these cells should have broad applicability in human cell-based therapies.
A History of Allogeneic Hematopoietic Cell Transplantation (2009)

This chapter contains sections titled: The beginning Early clinical studies Advances from animal studies Advances in knowledge of histocompatibility Renewed clinical studies History is now References
Photo-induced Radical Rearrangements of Hypoiodite of N-Acetyljervine and the Related C-nor-D-Homosteroid in the Presence of Mercury(II) Oxide and Iodine (1981)

Abstract Irradiation of the hypoiodite of N-acetyljervine in benzene containing mercury(II) oxide and iodine gave a mixture of products. The major product was N-acetyl-11-oxojerva-5,12(13)-dien-3β-yl N-acetyl-A-homo-4-oxa-11-oxojerva-5,12(13)-dien-3α-yl ether (4) (25%). Four minor products, N-acetyl-2-iodo-11-oxo-A-nor-2,3-secojerva 5,12(13)-dien-3-yl formate, N-acetyl-3α,5-epoxy-6α-iodo-A-homo-4-oxa-5α-jerva-5,12(13)-dien-11-one, N-acetyl-4-oxajerva-5,12(13)-dien-11-one, and N-acetyl-4-oxa-A-homojerva-5,12(13)-diene-3,11-dione, were also isolated. Irradiation of the hypoiodite of 3β-hydroxy-17-ethyletiojerv-5-ene-11,20-dione also gave a dimer corresponding to 4. The formation of 4 as the major product contrasts with the result of the corresponding reaction of cholesterol.
Characteristics and evaluation criteria of substrate-based manufacturing. Is roll-to-roll the best solution for printed electronics? (2014)

The vast majority of publications covering the manufacturing of printed electronics employ a web-fed roll-to-roll process. However, other principles of substrate transport are well established in printing science and industry. The focus on roll-to-roll in the scientific community therefore remains ambiguous. In an attempt to structure the discussion about upscaling organic electronics production, we extend existing classifications of substrate-based manufacturing, which is not limited to the field of printed electronics. Production processes can be classified by five key components: manufacturing technology, contact topology, substrate transport, substrate velocity, substrate feed and the degree of integration. This paper reviews four different substrate transport principles: roll-to-roll, sheet-to-sheet, sheets-on-shuttle and hybrid forms like roll-to-sheet. Besides basic working principles, both chances and limitations are discussed. Due to their individual complexity, a sound comparison ought not be reduced to a few key figures. In fact, the selection of the substrate transport requires an in-depth analysis of the individual production process. To aid decision-making, we introduce a hierarchy of 19 attributes covering aspects of production flexibility, quality, reliability, productivity and operations.
P-cadherin and the journey to cancer metastasis (2015)

P-cadherin is a classical cell-to-cell adhesion molecule with a homeostatic function in several normal tissues. However, its behaviour in the malignant setting is notably dependent on the cellular context. In some tumour models, such as melanoma and oral squamous cell carcinoma, P-cadherin acts as a tumour suppressor, since its absence is associated with a more aggressive cancer cell phenotype; nevertheless, the overexpression of this molecule is linked to significant tumour promoting effects in the breast, ovarian, prostate, endometrial, skin, gastric, pancreas and colon neoplasms. Herein, we review the role of P-cadherin in cancer cell invasion, as well as in loco-regional and distant metastatic dissemination. We focus in P-cadherin signalling pathways that are activated to induce invasion and metastasis, as well as cancer stem cell properties. The signalling network downstream of P-cadherin is notably dependent on the cellular and tissue context and includes the activation of integrin molecules, receptor tyrosine kinases, small molecule GTPases, EMT transcription factors, and crosstalk with other cadherin family members. As new oncogenic molecular pathways mediated by P-cadherin are uncovered, putative therapeutic options can be tested, which will allow for the targeting of invasion or metastatic disease, depending on the tumour model.
Inhibitory activity spectrum of reuterin produced by Lactobacillus reuteri against intestinal bacteria (2007)

Our data showed that intestinal bacteria were very sensitive to reuterin and that their intracellular concentration of LMW-SH was not directly linked to their capacity to resist reuterin or hydrogen peroxide. This suggests that detoxification by LMW-SH such as glutathione is not a general mechanism and that other mechanisms are probably involved in bacterial tolerance to reuterin and hydrogene peroxide.
A Single Short Stretch of Homology Between Adenoviral Vector and Packaging Cell Line Can Give Rise to Cytopathic Effect-Inducing, Helper-Dependent E1-Positive Particles (2002)

An undesirable byproduct from recombinant adenoviral vectors is the emergence of replication competent adenovirus (RCA) that result from rare homologous recombination events between the viral E1-containing (permissive) mammalian host cell genome and the virus itself, restoring the E1 gene to the viral genome. To reduce or eliminate the problem of RCA, we evaluated production of a first generation Ad5 vector (Ad5FGF4) in the cell line PER.C6. This E1-transformed human cell line contains only Ad5 nucleotides 459-3510, which precludes double crossover-type homologous recombination because the Ad5FGF-4 only contains 5' Ad5 sequence up to nucleotide 453. The Ad5FGF4 vector does, however, retain 177 nucleotides of the 3' end of the E1B-55K gene that are also present in PER.C6. With only this single region of homology between vector and cell line, we were surprised to detect virus-specific cytopathic effects (CPE) in our cell-based assay for RCA. This CPE-inducing agent was amplified in nonpermissive A549 cells but also supported amplification of the parental Ad5FGF-4. Because we were unable to isolate the CPE-inducing agent in pure form we first identified it as atypical RCA. Polymerase chain reaction (PCR) and Southern blot experiments identified viral DNA segments in which recombination had occurred between the 177 nucleotides of E1B present in both Ad5FGF-4 and PER.C6. The atypical RCA genomes contain a copy of the original (PGK promoter-E1 gene carrying) plasmid used in the construction of the PER.C6 cell line and they retained the parental FGF-4 transgene. However, significant deletions occurred within the recombined genomes in compensation for the large insertion from PER.C6 sequences and resulted in the loss of essential viral genes. This deletion renders these recombinant viruses replication defective, requiring helper functions from remaining parental Ad5FGF-4 for amplification. These atypical RCA entities may be more properly designated as helper-dependent E1-positive particles (HDEPs). This finding shows the importance of avoiding the use of "nonmatched" vectors where any overlap exists between the recombinant vector and E1 sequences in the packaging cell line. The cloning of the FGF-4 transgene into an adenoviral vector specifically "matched" for PER.C6 (lacking the 177 nucleotide region of homology) has allowed extensive virus propagation (Ad5.1FGF-4) with no CPE- or HDEP-like events yet detected.
Melting and Welding Semiconductor Nanowires in Nanotubes (2001)

Significant melting point depression and large hysteresis during the melting–recrystallization cycle are observed for semiconductor Ge nanowires encapsulated within carbon nanotubes. The capability of cutting, linking (see cover), and welding (see Figure) nanowires at relatively modest temperatures may provide a new approach to integrating these 1D nanostructures into functional devices and circuitry.
Issues and Challenges in the Establishment of Continuous Improvement in Vietnam (2015)

A better understanding of Vietnamese management is important for both practitioners and academics because of the huge and continuing growth of business activity in Vietnam. In particular, information about the Vietnamese use of continuous improvement (CI) practices is valuable because these have underpinned the success of both western and Asian companies in recent decades. Using the case-study method based on over 60 in-depth interviews with executives, managers, supervisors, and employees of nine leading companies in Vietnam and information gathered from discussions with 440 business and non-business leaders, practitioners, and academics, this paper shows that Vietnamese organizations face numerous challenges when implementing and sustaining CI practices. The findings highlight the tendency of Vietnamese organizations to pursue “shortcut” strategies that prevent them from competing higher up the value-added chain. Maintaining “face” is vital to the Vietnamese and this is a major cultural challenge for organizations in their CI efforts. The paper recommends that Vietnamese organizations address these challenges by pursuing CI more aggressively and investing in human resource development to build capabilities for the future. The Vietnamese government, which is the main engine of change in the country, should promote the use of CI by funding education and training in its methods.
Mines Safety and Inspection Laws in Western Australia (1999)

The legislation dealing with mines safety laws in Western Australia changed quite dramatically in the 1990's.This article provides an overview of the Mines Safety and Inspection Act 1994 (WA) and describes the main features of the current legislation and some of the legal cases that have arisen from it.
The Tumor Microenvironment Regulates Sensitivity of Murine Lung Tumors to PD-1/PD-L1 Antibody Blockade (2017)

Immune checkpoint inhibitors targeting the interaction between programmed cell death-1 (PD-1) and its ligand PD-L1 induce tumor regression in a subset of non-small cell lung cancer patients. However, clinical response rates are less than 25%. Evaluation of combinations of immunotherapy with existing therapies requires appropriate preclinical animal models. In this study, murine lung cancer cells (CMT167 and LLC) were implanted either orthotopically in the lung or subcutaneously in syngeneic mice, and response to anti-PD-1/PD-L1 therapy was determined. Anti-PD-1/PD-L1 therapy inhibited CMT167 orthotopic lung tumors by 95%. The same treatments inhibited CMT167 subcutaneous tumors by only 30% and LLC orthotopic lung tumors by 35%. CMT167 subcutaneous tumors had more Foxp3<sup>+</sup> CD4<sup>+</sup> T cells and fewer PD-1<sup>+</sup> CD4<sup>+</sup> T cells compared with CMT167 orthotopic tumors. Flow cytometric analysis also demonstrated increased abundance of PD-L1<sup>high</sup> cells in the tumor microenvironment in CMT167 tumor-bearing lungs compared with CMT167 subcutaneous tumors or LLC tumor-bearing lungs. Silencing PD-L1 expression in CMT167 cells resulted in smaller orthotopic tumors that remained sensitive to anti-PD-L1 therapy, whereas implantation of CMT167 cells into PD-L1<sup>-</sup> mice blocked orthotopic tumor growth, indicating a role for PD-L1 in both the cancer cell and the microenvironment. These findings indicate that the response of cancer cells to immunotherapy will be determined by both intrinsic properties of the cancer cells and specific interactions with the microenvironment. Experimental models that accurately recapitulate the lung tumor microenvironment are useful for evaluation of immunotherapeutic agents. <i>Cancer Immunol Res; 5(9); 767-77. ©2017 AACR</i>.
Major role for ACE-independent intrarenal ANG II formation in type II diabetes (2009)

Combination therapy of angiotensin-converting enzyme (ACE) inhibition and AT(1) receptor blockade has been shown to provide greater renoprotection than ACE inhibitor alone in human diabetic nephropathy, suggesting that ACE-independent pathways for ANG II formation are of major significance in disease progression. Studies were performed to determine the magnitude of intrarenal ACE-independent formation of ANG II in type II diabetes. Although renal cortical ACE protein activity [2.1 +/- 0.8 vs. 9.2 +/- 2.1 arbitrary fluorescence units (AFU) x mg(-1) x min(-1)] and intensity of immunohistochemical staining were significantly reduced and ACE2 protein activity (16.7 +/- 3.2 vs. 7.2 +/- 2.4 AFU x mg(-1) x min(-1)) and intensity elevated, kidney ANG I (113 +/- 24 vs. 110 +/- 45 fmol/g) and ANG II (1,017 +/- 165 vs. 788 +/- 99 fmol/g) levels were not different between diabetic and control mice. Afferent arteriole vasoconstriction due to conversion of ANG I to ANG II was similar in magnitude in kidneys of diabetic (-28 +/- 3% at 1 microM) and control (-23 +/- 3% at 1 microM) mice; a response completely inhibited by AT(1) receptor blockade. In control kidneys, afferent arteriole vasoconstriction produced by ANG I was significantly attenuated by ACE inhibition, but not by serine protease inhibition. In contrast, afferent arteriole vasoconstriction produced by intrarenal conversion of ANG I to ANG II was significantly attenuated by serine protease inhibition, but not by ACE inhibition in diabetic kidneys. In conclusion, there is a switch from ACE-dependent to serine protease-dependent ANG II formation in the type II diabetic kidney. Pharmacological targeting of these serine protease-dependent pathways may provide further protection from diabetic renal vascular disease.
Parabacteroides distasonis attenuates toll‐like receptor 4 signaling and Akt activation and blocks colon tumor formation in high‐fat diet‐fed azoxymethane‐treated mice (2018)

Gut dysbiosis may play an etiological role in colorectal tumorigenesis. We previously observed that the abundance of Parabacteroides distasonis (Pd) in stool was inversely associated with intestinal tumor burden and IL-1β concentrations in mice. Here, we assessed the anti-inflammatory capacity of Pd membrane fraction (PdMb) in colon cancer cell lines. In addition, we tested whether Pd could suppress colon tumorigenesis in mice. Six-week-old male A/J mice were fed a low-fat (LF) diet, high-fat (HF) diet or HF+ whole freeze-dried Pd (HF + Pd, 0.04% wt/wt) for 24 weeks. After 1 week on diet, mice received 4 weekly injections of azoxymethane. PdMb robustly suppressed the production of pro-inflammatory cytokines and lowered the abundance of MyD88 and pAkt (ser473) induced by E. coli lipopolysaccharide in colon cancer cell lines. Moreover, PdMb induced apoptosis in colon cancer cell lines and blocked TLR4 activation in a reporter line. Colon tumors were observed in 0% of LF (0 of 19), 25% of HF (5 of 20) and 0% of HF + Pd mice (0 of 20) (p = 0.005). The latter group also displayed a lower abundance of MyD88 and pAkt (ser473) in colonic mucosa than HF mice. Taken together, these data suggest that Pd has anti-inflammatory and anti-cancer properties that are likely mediated by the suppression of TLR4 and Akt signaling, as well as promotion of apoptosis. Further work is needed to confirm these findings in additional models and fully elaborate the mechanism of action.
Phase II enzymes and bioactivation (1995)

A colloquium entitled Phase II enzymes and bioactivation was held during the 10th International Symposium on Microsomes and Drug Oxidations in Toronto, Ont., on July 20, 1994. This colloquium was a tribute in recognition of the contributions by Dr. James R. Gillette in advancing our understanding of drug metabolism and chemical toxicity. A major focus of the colloquium was formation of conjugates such as those with glutathione (GSH) that may not lead to detoxification but to bioactivation. The GSH conjugates may be further metabolized to reactive species that cause toxicity. The nephrotoxicity of hydroquinone and bromobenzene is mediated via quinone - glutathione conjugates, and is manifested in cellular changes, including induction of the gadd-153 and hsp-70 mRNA. The formation of GSH conjugates is also involved in the bioactivation of the vicinal dihalopropane 1,2-dibromo-3-chloropropane; cytotoxic lesions are observed in the kidney and testes The evidence indicates that conjugation is mediated by the GSH S-transferases. The symposium also covered aspects of the importance of conjugation in the pharmacokinetics of certain drugs. Conjugation reactions including sulfation are markedly influenced by the manner in which the liver processes the drug. Characteristics such as erythrocyte binding, as in the case of acetaminophen, become limiting factors in the conjugation reactions. Conjugation reactions can lead to a different outcome, such as acquired drug resistance. Conjugation of metallothioneins with the alkylating mustard drugs melphalan and chlorambucil can lead to the formation of protein adducts. Conjugation of reactive intermediates with these small molecular weight proteins may be considered as a phase II reaction and a mechanism of detoxification. A different pathway for the metabolism of xenobiotics is catalyzed by the carboxylesterases, a family of enzymes that is involved in hydrolysis of chemical compounds, generally leading to detoxification. Three rat esterases have been purified, cloned, and characterized. Two forms, hydrolase A and hydrolase B, are present in liver microsomes in a number of species, including the human. These are also detected in extrahepatic tissues. A third esterase, hydrolase S, is found in rat liver microsomes and rat serum, and may be a serum carboxylesterase secreted from the liver. A better knowledge of esterases will advance our understanding of pharmacokinetics and mechanisms of the effects of chemicals such as phenacetin and acetaminophen, two drugs that Dr. Gillette has worked with extensively. The data presented herein reflect the new and innovative approaches that have been adopted to investigate various aspects of chemical toxicity and drug metabolism. These data also indicate that significant insights are likely to come from integrated approaches utilizing established toxicological techniques together with those from other disciplines, including molecular biology and analytical chemistry.
Human cytomegalovirus IE1 and IE2 proteins block apoptosis (1995)

Human cytomegalovirus-infected fibroblasts are resistant to the induction of apoptosis by superinfection with a mutant adenovirus unable to produce the viral E1B 19-kDa protein that normally causes an E1A protein-mediated apoptotic response. Two cytomegalovirus gene products that block apoptosis were identified. The IE1 and IE2 proteins each inhibit the induction of apoptosis by tumor necrosis factor alpha or by the E1B 19-kDa-protein-deficient adenovirus but not by irradiation with UV light. Our results suggest a new physiological role for the IE1 and IE2 proteins in the human cytomegalovirus replication cycle.
Seeing beyond adversity (2004)

St Dunstan’s is a charity that helps blind ex-service men and women to live independently. Daniel Allen paid a visit
Reactions of Manganese Porphyrins with Peroxynitrite and Carbonate Radical Anion (2003)

We have studied the reaction kinetics of ten manganese porphyrins, differing in their meso substituents, with peroxynitrite (ONOO-) and carbonate radical anion (CO3.) using stopped-flow and pulse radiolysis, respectively. Rate constants for the reactions of Mn(III) porphyrins with ONOO- ranged from 1 x 10(5) to 3.4 x 10(7) m(-1) s(-1) and correlated well with previously reported kinetic and thermodynamic data that reflect the resonance and inductive effects of the substituents on the porphyrin ring. Rate constants for the reactions of Mn(III) porphyrins with CO3. ranged from 2 x 10(8) to 1.2 x 10(9) m(-1)s(-1) at pH <or= 8.5 and increased with pH as a consequence of the ionization of the complexes. Mn(II) porphyrins reacted with CO3. with rate constants ranging from 1 x 10(9) to 5 x 10(9) m(-1)s(-1) at pH 10.4. Hence, fast scavenging of ONOO- and CO3. by manganese porphyrins could occur in vivo because of the catalytic reduction at the expense of a number of cellular reductants. Additionally, we determined the pKa of the axial water molecules of the Mn(III) complexes at pH 7.5-13.2 by spectrophotometric titration. Results were consistent with two acid-base equilibria for most of the complexes studied. The pKa values also correlated with the resonance and inductive effects of the substituents. The correlations of E(1/2) with the rate constants with ONOO- and with the pKa values display a deviation from linearity when N-alkylpyridinium substituents included N-alkyl moieties longer than ethyl, which is interpreted in terms of a decrease in the local dielectric constant.