gebhart/patrepeval huggingface dataset:
Obligate Role of Anti-Apoptotic MCL-1 in the Survival of Hematopoietic Stem Cells (2005)

Apoptosis is important in controlling hematopoietic stem cell (HSC) numbers. However, the specific BCL-2 family member(s) that regulate HSC homeostasis are not precisely defined. We tested myeloid leukemia-1 (MCL-1) as an attractive candidate that is highly expressed in HSCs and regulated by growth factor signals. Inducible deletion of Mcl-1 in mice resulted in ablation of bone marrow. This resulted in the loss of early bone marrow progenitor populations, including HSCs. Moreover, growth factors including stem cell factor increased transcription of the Mcl-1 gene and required MCL-1 to augment survival of purified bone marrow progenitors. Deletion of Mcl-1 in other tissues, including liver, did not impair survival. Thus, MCL-1 is a critical and specific regulator essential for ensuring the homeostasis of early hematopoietic progenitors.
Improved Peptide Elution Time Prediction for Reversed-Phase Liquid Chromatography-MS by Incorporating Peptide Sequence Information (2006)

We describe an improved artificial neural network (ANN)-based method for predicting peptide retention times in reversed-phase liquid chromatography. In addition to the peptide amino acid composition, this study investigated several other peptide descriptors to improve the predictive capability, such as peptide length, sequence, hydrophobicity and hydrophobic moment, and nearest-neighbor amino acid, as well as peptide predicted structural configurations (i.e., helix, sheet, coil). An ANN architecture that consisted of 1052 input nodes, 24 hidden nodes, and 1 output node was used to fully consider the amino acid residue sequence in each peptide. The network was trained using approximately 345,000 nonredundant peptides identified from a total of 12,059 LC-MS/MS analyses of more than 20 different organisms, and the predictive capability of the model was tested using 1303 confidently identified peptides that were not included in the training set. The model demonstrated an average elution time precision of approximately 1.5% and was able to distinguish among isomeric peptides based upon the inclusion of peptide sequence information. The prediction power represents a significant improvement over our earlier report (Petritis, K.; Kangas, L. J.; Ferguson, P. L.; Anderson, G. A.; Pasa-Tolic, L.; Lipton, M. S.; Auberry, K. J.; Strittmatter, E. F.; Shen, Y.; Zhao, R.; Smith, R. D. Anal. Chem. 2003, 75, 1039-1048) and other previously reported models.
1,1'-Thiocarbonyldi-2,2'-pyridone. A new useful reagent for functional group conversions under essentially neutral conditions (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1,1'-Thiocarbonyldi-2,2'-pyridone. A new useful reagent for functional group conversions under essentially neutral conditionsSunggak Kim and Kyu Yang YiCite this: J. Org. Chem. 1986, 51, 13, 2613–2615Publication Date (Print):June 1, 1986Publication History Published online1 May 2002Published inissue 1 June 1986https://doi.org/10.1021/jo00363a046RIGHTS & PERMISSIONSArticle Views2256Altmetric-Citations76LEARN 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 InReddit PDF (426 KB) Get e-Alerts Get e-Alerts
Semaphorin 4D/Plexin-B1–mediated R-Ras GAP activity inhibits cell migration by regulating β1 integrin activity (2006)

Plexins are cell surface receptors for semaphorins and regulate cell migration in many cell types. We recently reported that the semaphorin 4D (Sema4D) receptor Plexin-B1 functions as a GTPase-activating protein (GAP) for R-Ras, a member of Ras family GTPases implicated in regulation of integrin activity and cell migration. We characterized the role of R-Ras downstream of Sema4D/Plexin-B1 in cell migration. Activation of Plexin-B1 by Sema4D suppressed the ECM-dependent R-Ras activation, R-Ras-mediated phosphatydylinositol 3-kinase activation, and beta(1) integrin activation through its R-Ras GAP domain, leading to inhibition of cell migration. In addition, inactivation of R-Ras by overexpression of the R-Ras-specific GAP or knockdown of R-Ras by RNA interference was sufficient for suppressing beta(1) integrin activation and cell migration in response to the ECM stimulation. Thus, we conclude that R-Ras activity is critical for ECM-mediated beta(1) integrin activation and cell migration and that inactivation of R-Ras by Sema4D/Plexin-B1-mediated R-Ras GAP activity controls cell migration by modulating the activity of beta(1) integrins.
Experimental Evaluation of an Adaptive Nonlinear Interference Suppressor for Multimode Transceivers (2013)

In multimode transceivers, the transmitter for one communication standard may induce a strong interference in the receiver for another standard. Using linear filtering techniques to suppress this interference requires a receiver with a very large dynamic range, leading to an excessive power consumption. A much more power efficient approach suppresses the interference using an adaptive nonlinear interference suppressor (NIS). In previous work an ideal model was used to derive an adaptation method and study the receiver performance afforded by the NIS. In this paper, we present experimental results of a receiver that uses an implementation of the NIS, fabricated in 140 nm complementary metal-oxide-semiconductor technology. Main imperfections that limit the NIS performance are identified, simple models are developed that explain the experimental results, and for the key imperfections, low-complexity digital compensation and calibration methods are proposed. These digital methods permit the use of lower-performance analogue circuits, thus further reducing the transceiver cost and power consumption. The experimental results show that the NIS can achieve a substantial interference suppression at attractive complexity and power dissipation.
Cartilage tissue engineering: its potential and uses (2005)

Cell selection, scaffold design and biological stimulation remain the challenges of function tissue engineering. Successful regeneration or replacement of damaged or diseased cartilage will depend on future advances in our understanding of the biology of cartilage and stem cells and technological development in engineering.
Evaluation of reverse transcriptase and protease inhibitors in two-drug combinations against human immunodeficiency virus replication (1996)

Current treatments for human immunodeficiency virus (HIV) include both reverse transcriptase and protease inhibitors. Results from in vitro and clinical studies suggest that combination therapy can be more effective than single drugs in reducing viral burden. To evaluate compounds for combination therapy, stavudine (d4T), didanosine (ddI), or BMS-186,318, an HIV protease inhibitor, were combined with other clinically relevant compounds and tested in a T-cell line (CEM-SS) that was infected with HIV-RF or in peripheral blood mononuclear cells infected with a clinical HIV isolate. The combined drug effects were analyzed by the methods described by Chou and Talalay (Adv. Enzyme Regul. 22:27-55, 1984) as well as by Prichard et al. (Antimicrob. Agents Chemother. 37:540-545, 1993). The results showed that combining two nucleoside analogs (d4T-ddI, d4T-zidovudine [AZT], and d4T-zalcitabine [ddC]), two HIV protease inhibitors (BMS-186,318-saquinavir, BMS-186,318-SC-52151, and BMS-186,318-MK-639) or a reverse transcriptase and a protease inhibitor (BMS-186,318-d4T, BMS-186,318-ddI, BMS-186,318-AZT, d4T-saquinavir, d4T-MK-639, and ddI-MK-639) yielded additive to synergistic antiviral effects. In general, analysis of data by either method gave consistent results. In addition, combined antiviral treatments involving nucleoside analogs gave slightly different outcomes in the two cell types, presumably because of a difference in phosphorylation patterns. Importantly, no strong antagonism was observed with the drug combinations studied. These data should provide useful information for the design of clinical trials of combined chemotherapy.
Gene therapy for non-small cell lung cancer: a preliminary report of a phase I trial of adenoviral p53 gene replacement. (1998)

The identification of genetic lesions that lead a normal cell to become malignant presents us with the opportunity of targeting those lesions as a means of therapy. Given the key role played by the tumor suppressor gene p53 in cell cycle regulation and apoptosis, and the evidence linking p53 mutations with non-small cell lung cancer, attempts at p53 replacement are a logical approach to therapy in this disease. In a phase I study, administration of an adenoviral p53 vector (Adp53) to 21 patients with advanced non-small cell lung cancer produced little toxicity. Up to six intratumoral injections at monthly intervals were well-tolerated. Expression of the p53 transgene was evident, along with potentially useful clinical responses. Time to disease progression in the indicator lesion treated with Adp53 appears to be enhanced by higher doses of vector, concomitant cisplatin therapy, and evidence of apoptosis on tumor biopsy specimens. Phase II trials should now be undertaken to determine the response rate to Adp53.
Tipranavir (PNU-140690):  A Potent, Orally Bioavailable Nonpeptidic HIV Protease Inhibitor of the 5,6-Dihydro-4-hydroxy-2-pyrone Sulfonamide Class (1998)

A broad screening program previously identified phenprocoumon (1) as a small molecule template for inhibition of HIV protease. Subsequent modification of this lead through iterative cycles of structure-based design led to the activity enhancements of pyrone and dihydropyrone ring systems (II and V) and amide-based substitution (III). Incorporation of sulfonamide substitution within the dihydropyrone template provided a series of highly potent HIV protease inhibitors, with structure-activity relationships described in this paper. Crystallographic studies provided further information on important binding interactions responsible for high enzymatic binding. These studies culminated in compound VI, which inhibits HIV protease with a Ki value of 8 pM and shows an IC90 value of 100 nM in antiviral cell culture. Clinical trials of this compound (PNU-140690, Tipranavir) for treatment of HIV infection are currently underway.
Singlet oxygen reaction. III. Solvent and temperature effects on the photosensitized oxygenation of vinyl sulfides and vinyl ethers (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSinglet oxygen reaction. III. Solvent and temperature effects on the photosensitized oxygenation of vinyl sulfides and vinyl ethersWataru Ando, Kazuo Watanabe, Junji Suzuki, and Toshihiko MigitaCite this: J. Am. Chem. Soc. 1974, 96, 21, 6766–6768Publication Date (Print):October 1, 1974Publication History Published online1 May 2002Published inissue 1 October 1974https://pubs.acs.org/doi/10.1021/ja00828a042https://doi.org/10.1021/ja00828a042research-articleACS PublicationsRequest reuse permissionsArticle Views154Altmetric-Citations32LEARN 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
Characterization of a soluble form of the C3b/C4b receptor (CR1) in human plasma. (1985)

A radioimmunoassay with the use of soluble 125I-Fab monoclonal anti-CR1 and rabbit IgG anti-CR1 bound to Staphylococcus aureus particles was employed to detect and quantitate CR1 antigen in human plasma. Among 16 normal individuals the concentration of soluble CR1 in plasma ranged from 13 to 81 ng/ml, and a similar range of concentration was found in plasma from 15 patients having systemic lupus erythematosus (SLE). The amount of plasma CR1 in normal donors, but not in SLE patients, significantly correlated with the number of CR1 sites on erythrocytes (r = 0.90, p less than 0.001), and was 7.1% of the amount of receptor that was present on erythrocytes in blood. The concentration of soluble CR1 was not diminished by ultracentrifugation or ultrafiltration of plasma, was not affected by various modes of anti-coagulation or even by clotting of blood, and did not change during incubation of blood at 4 degrees C for up to 4 hr. On sucrose density gradient ultracentrifugation of plasma the CR1 was distributed as a broad peak that overlapped the plasma protein profile. The Mr of plasma CR1 was identical to that of erythrocyte CR1 when assessed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and immunoblotting. In addition, the plasma form of CR1 exhibited the same structural phenotype as did receptor from erythrocytes of the same individual. CR1 antigen purified from plasma was as active as CR1 from erythrocytes in promoting the cleavage by factor I of C3b to iC3b, C3c, and C3dg. Therefore, a functionally and structurally intact form of soluble CR1 resides in plasma.
Targeting frequency for deletion vectors in embryonic stem cells. (1994)

We analyzed the gene targeting frequencies and recombination products generated by a series of replacement deletion vectors which target the hprt (hypoxanthine phosphoribosyltransferase) locus in mouse embryonic stem cells. We found that the targeting frequency of a 19.2-kb deletion was comparable to that of a 3-kb deletion or a conventional replacement event in which a 1.7-kb fragment was inserted into the locus. We also observed different integration patterns for these deletion vectors. A result of this finding is that a wide range of genomic deletions in embryonic stem cells is feasible.
Hepatic PCSK9 Expression Is Regulated by Nutritional Status via Insulin and Sterol Regulatory Element-binding Protein 1c (2006)

Familial autosomal dominant hypercholesterolemia is associated with high risk for cardiovascular accidents and is related to mutations in the low density lipoprotein receptor or its ligand apolipoprotein B (apoB). Mutations in a third gene, proprotein convertase subtilisin kexin 9 (PCSK9), were recently associated to this disease. PCSK9 acts as a natural inhibitor of the low density lipoprotein receptor pathway, and both genes are regulated by depletion of cholesterol cell content and statins, via sterol regulatory element-binding protein (SREBP). Here we investigated the regulation of PCSK9 gene expression during nutritional changes. We showed that PCSK9 mRNA quantity is decreased by 73% in mice after 24 h of fasting, leading to a 2-fold decrease in protein level. In contrast PCSK9 expression was restored upon high carbohydrate refeeding. PCSK9 mRNA increased by 4-5-fold in presence of insulin in rodent primary hepatocytes, whereas glucose had no effect. Moreover, insulin up-regulated hepatic PCSK9 expression in vivo during a hyperinsulinemic-euglycemic clamp in mice. Adenoviral mediated overexpression of a dominant or negative form of SREBP-1c confirmed the implication of this transcription factor in insulin-mediated stimulation of PCSK9 expression. Liver X receptor agonist T0901317 also regulated PCSK9 expression via this same pathway (a 2-fold increase in PCSK9 mRNA of primary hepatocytes cultured for 24 h in presence of 1 microm T0901317). As our last investigation, we isolated PCSK9 proximal promoter and verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG. Together, these results show that PCSK9 expression is regulated by nutritional status and insulinemia.
Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA‐074: a novel strategy for neuroprotection based on ‘calpain–cathepsin hypothesis’ (1998)

Although Cornu Ammonis (CA) 1 neurons of the hippocampus are known to be vulnerable to transient ischaemia, the mechanism of ischaemic neuronal death is still unknown, and there are very few strategies to prevent neuronal death at present. In a previous report we demonstrated micro-calpain activation at the disrupted lysosomal membrane of postischaemic CA1 neurons in the monkey undergoing a complete 20 min whole brain ischaemia. Using the same experimental paradigm, we observed that the enzyme activity of the lysosomal protease cathepsin B increased throughout the hippocampus on days 3-5 after the transient ischaemia. Furthermore, by immunocytochemistry cathepsin B showed presence of extralysosomal immunoreactivity with specific localization to the cytoplasm of CA1 neurons and the neuropil of the vulnerable CA1 sector. When a specific inhibitor of cathepsin B, the epoxysuccinyl peptide CA-074 (C18H29N3O6) was intravenously administered immediately after the ischaemic insult, approximately 67% of CA1 neurons were saved from delayed neuronal death on day 5 in eight monkeys undergoing 20 min brain ischaemia: the extent of inhibition was excellent in three of eight and good in five of eight monkeys. The surviving neurons rescued by blockade of lysosomal activity, showed mild central chromatolysis and were associated with the decreased immunoreactivity for cathepsin B. These observations indicate that calpain-induced cathepsin B release is crucial for the development of the ischaemic neuronal death, and that a specific inhibitor of cathepsin B is of potential therapeutic utility in ischaemic injuries to the human CNS.
Forensic trace DNA: a review (2010)

DNA analysis is frequently used to acquire information from biological material to aid enquiries associated with criminal offences, disaster victim identification and missing persons investigations. As the relevance and value of DNA profiling to forensic investigations has increased, so too has the desire to generate this information from smaller amounts of DNA. Trace DNA samples may be defined as any sample which falls below recommended thresholds at any stage of the analysis, from sample detection through to profile interpretation, and can not be defined by a precise picogram amount. Here we review aspects associated with the collection, DNA extraction, amplification, profiling and interpretation of trace DNA samples. Contamination and transfer issues are also briefly discussed within the context of trace DNA analysis. Whilst several methodological changes have facilitated profiling from trace samples in recent years it is also clear that many opportunities exist for further improvements.
Ruthenium-Catalyzed Transformation of Aryl and Alkenyl Triflates to Halides (2012)

Aryl triflates were transformed to aryl bromides/iodides simply by treating them with LiBr/NaI and [Cp*Ru(MeCN)(3)]OTf. The ruthenium complex also catalyzed the transformation of alkenyl sulfonates and phosphates to alkenyl halides under mild conditions. Aryl and alkenyl triflates undergo oxidative addition to a ruthenium(II) complex to form η(1)-arylruthenium and 1-ruthenacyclopropene intermediates, respectively, which are transformed to the corresponding halides.
Las ideas de niños y adolescentes acerca de algunos aspectos del mundo laboral (1995)

The study investigated the molecular mechanisms underlying the response to adverse environment in an animal model using a GxE design. Stress-related differences were visible at the genomic level through PCA analysis highlighting the high sensitivity of BALB/cJ animals to environmental stressors. Several candidate genes and gene networks reported are associated with inflammation and neurogenesis and could serve to inform candidate gene selection in human studies and provide additional insight into the pathology of Major Depressive Disorder.
<i>LRP6</i> Mutation in a Family with Early Coronary Disease and Metabolic Risk Factors (2007)

Coronary artery disease (CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. These traits showed genetic linkage to a short segment of chromosome 12p, in which we identified a missense mutation in LRP6, which encodes a co-receptor in the Wnt signaling pathway. The mutation, which substitutes cysteine for arginine at a highly conserved residue of an epidermal growth factor-like domain, impairs Wnt signaling in vitro. These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors.
LWIR focal plane with digital readout demonstrating a passive free-space optical readout link (1999)

Future high performance IR imaging system require high density focal planes containing up to one million or more detectors. Technological advances are needed to handle the resulting readout data rates in excess of Gbauds/sec and to minimize the on-focal-plane heat load caused by the currently used drivers and signal carrying cables connecting the focal plane inside the vacuum dewar with the outside signal processor. Optical interconnects are a practical alternative only for digital data because of the high non- linearity of the electrical to optical conversion process. We propose to solve these problems by A/D converting the detector signals on the focal pane (FPA) and using on-focal- plane quantum well light modulators to transform the electrical to optical signals. The latter are transmitted by a light beam from the FPA to the signal processor or the display electronics. The enabling technologies are the recently demonstrated on-focal-plane MOSAD converter achieving 14 bit dynamic range and the quantum well light modulators being develop by Lucent Technologies for highspeed bistable optical switches called SEED's for use in telecommunication. We will demonstrate one optical readout channel servicing 4 columns of a LWIR detector array mounted in an experimental dewar.