gebhart/patrepeval huggingface dataset:
Dll4–Notch signaling in Flt3-independent dendritic cell development and autoimmunity in mice (2012)

Delta-like ligand 4 (Dll4)-Notch signaling is essential for T cell development and alternative thymic lineage decisions. How Dll4-Notch signaling affects pro-T cell fate and thymic dendritic cell (tDC) development is unknown. We found that Dll4 pharmacological blockade induces accumulation of tDCs and CD4(+)CD25(+)FoxP3(+) regulatory T cells (T(reg) cells) in the thymic cortex. Both genetic inactivation models and anti-Dll4 antibody (Ab) treatment promote de novo natural T(reg) cell expansion by a DC-dependent mechanism that requires major histocompatibility complex II expression on DCs. Anti-Dll4 treatment converts CD4(-)CD8(-)c-kit(+)CD44(+)CD25(-) (DN1) T cell progenitors to immature DCs that induce ex vivo differentiation of naive CD4(+) T cells into T(reg) cells. Induction of these tolerogenic DN1-derived tDCs and the ensuing expansion of T(reg) cells are Fms-like tyrosine kinase 3 (Flt3) independent, occur in the context of transcriptional up-regulation of PU.1, Irf-4, Irf-8, and CSF-1, genes critical for DC differentiation, and are abrogated in thymectomized mice. Anti-Dll4 treatment fully prevents type 1 diabetes (T1D) via a T(reg) cell-mediated mechanism and inhibits CD8(+) T cell pancreatic islet infiltration. Furthermore, a single injection of anti-Dll4 Ab reverses established T1D. Disease remission and recurrence are correlated with increased T(reg) cell numbers in the pancreas-draining lymph nodes. These results identify Dll4-Notch as a novel Flt3-alternative pathway important for regulating tDC-mediated T(reg) cell homeostasis and autoimmunity.
Substrate-strained silicon technology: process integration [CMOS technology] (2004)

We demonstrate a 60 nm gate length substrate-strained Si CMOS technology and the fastest reported ring oscillator speed of 6.5 ps at 1.2 V operation. The largest enhancement (15%) in I/sub on/-I/sub off/ characteristics without correction for self-heating effects is also reported. The substrate-strained Si process is optimized to enhance manufacturability and circumvent difficulties associated with the integration of the strained Si/SiGe heterostructure. We also report a phenomenon responsible for increased the off state leakage in strained Si devices and a way to suppress it. Surmounting key integration challenges faced by the Si/SiGe heterostructure is critical for its introduction as a manufacturable process.
The Effect of Copper Tripeptide and Tretinoin on Growth Factor Production in a Serum-Free Fibroblast Model (2001)

Normal fibroblasts treated with tretinoin produced more bFGF than did controls, and this might partially explain the clinically observed tightening effects of tretinoin. Normal and keloid-producing dermal fibroblasts treated with copper tripeptide secreted less TGF-beta1 than did controls, suggesting a possible clinical use for decreasing excessive scar formation.
Epidermal Growth Factor Receptor-dependent Control of Keratinocyte Survival and Bcl-xL Expression through a MEK-dependent Pathway (2001)

Previous work has shown that the epidermal growth factor receptor (EGFR) tyrosine kinase moiety provides protection to normal human keratinocytes against apoptosis. This protection is, at least in part, due to EGFR-dependent expression of the antiapoptotic Bcl-2 family member, Bcl-x(L). Here we focused on intracellular signaling pathways relevant to keratinocyte survival and/or Bcl-x(L) expression. By using pharmacological inhibitors and dominant negative expression constructs, we observed that phosphatidylinositol 3-kinase/AKT and phospholipase C gamma/protein kinase C alpha activation were required for keratinocyte survival independently of EGFR activation or Bcl-x(L) expression. By contrast, MEK activity required EGFR activation and, as shown by use of the MEK inhibitor PD98059 and a dominant negative MEK construct, was necessary for Bcl-x(L) expression and survival. Consistent with an earlier study, blocking SRC kinase activities similarly led to down-regulation of Bcl-x(L) protein expression and impaired keratinocyte survival. In conclusion, our results demonstrate that EGFR-dependent MEK activity contributes to both Bcl-x(L) expression and survival of normal keratinocytes. Other signaling pathways (i.e. phosphatidylinositol 3-kinase/AKT and phospholipase C gamma/protein kinase C alpha) are obligatory to keratinocyte survival but not to Bcl-x(L) expression, and control of these pathways by EGFR activation is not rate-limiting to normal keratinocyte survival.
Radiofrequency Catheter Ablation of the Atria Reduces Inducibility and Duration of Atrial Fibrillation in Dogs (1995)

RFCA in open-chest dogs produces partial vagal denervation and reduces the inducibility of AF.
Kinetic Characterization and Phosphoregulation of the Francisella tularensis 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase (MEP Synthase) (2009)

Deliberate and natural outbreaks of infectious disease underscore the necessity of effective vaccines and antimicrobial/antiviral therapeutics. The prevalence of antibiotic resistant strains and the ease by which antibiotic resistant bacteria can be intentionally engineered further highlights the need for continued development of novel antibiotics against new bacterial targets. Isoprenes are a class of molecules fundamentally involved in a variety of crucial biological functions. Mammalian cells utilize the mevalonic acid pathway for isoprene biosynthesis, whereas many bacteria utilize the methylerythritol phosphate (MEP) pathway, making the latter an attractive target for antibiotic development. In this report we describe the cloning and characterization of Francisella tularensis MEP synthase, a MEP pathway enzyme and potential target for antibiotic development. In vitro growth-inhibition assays using fosmidomycin, an inhibitor of MEP synthase, illustrates the effectiveness of MEP pathway inhibition with F. tularensis. To facilitate drug development, F. tularensis MEP synthase was cloned, expressed, purified, and characterized. Enzyme assays produced apparent kinetic constants (K(M)(DXP) = 104 microM, K(M)(NADPH) = 13 microM, k(cat)(DXP) = 2 s(-1), k(cat)(NADPH) = 1.3 s(-1)), an IC(50) for fosmidomycin of 247 nM, and a K(i) for fosmidomycin of 99 nM. The enzyme exhibits a preference for Mg(+2) as a divalent cation. Titanium dioxide chromatography-tandem mass spectrometry identified Ser177 as a site of phosphorylation. S177D and S177E site-directed mutants are inactive, suggesting a mechanism for post-translational control of metabolic flux through the F. tularensis MEP pathway. Overall, our study suggests that MEP synthase is an excellent target for the development of novel antibiotics against F. tularensis.
중량줄넘기 운동의 생리적 효과 (1997)

중량줄넘기 운동의 생리적 효과. 운동과학, 제6권 제1호, 1-12, 1977. 중량줄넘기 운동훈련의 생리적 효과를 규명코자 운동훈련 경험이 없는 14명의 남자 중학생을 한 집단 7명씩 일반 및 중량줄넘기 운동훈련 집단에 무선배정하고 이들을 대상으로 각각 무게 200g의 일반줄넘기 및 무게 500g의 중량줄넘기 운동훈련을 1일 5분간, 주 6회 빈도로 6주간 실시하였다. 일반 및 중량줄넘기운동시의 평균 운동강도는 각각 75.8% 및 82.2% HRreserve였다. 준최대 부하운동에 대한 호흡순환계 반응과 근력, 근파워 및 무산소성 운동역치 등을 운동훈련전 측정치들과 비교하고 훈련집단 간에도 비교 관찰하였던 바, 각 평균치의 차의 유의성을 t(independent, paired t) 검정법을 이용하여 p<.05의 유의수준에서 규명하여 다음의 결론을 얻었다. 장기적인 줄넘기 운동훈련으로 비훈련자의 무산소성 운동역치가 개선되고 동일강도 준최대 부하운동시의 V˙E, V˙O₂, V˙CO₂, R, HR 등의 요인이 저하된다. 비훈련자의 악력과 하지근 파워도 줄넘기 운동훈련으로 개선될 수 있다. 이상과 같은 줄넘기 운동의 생리적 효과는 일반 줄넘기 운동훈련보다 중량줄넘기 운동훈련의 경우가 보다 우수하다.
Effect of feed and bleed rate on hybridoma cells in an acoustic perfusion bioreactor: Part I. Cell density, viability, and cell‐cycle distribution (2004)

For the development of optimal perfusion processes the effect of the feed and bleed rate on cell growth in a perfusion bioreactor was studied. The viable-cell density, viability, growth, death, and lysis rate and cell-cycle distribution of a hybridoma cell line producing an IgG1 were studied over a range of specific feed and bleed rates. It was found that the feed and bleed rates applied in the different cultures could be divided into two regions based on the viable-cell density and cell-cycle distribution. The cultures in the first region, low feed rates (0.5 and 1.0 d(-1)) combined with low bleed rates (0.05 and 0.10 d(-1)), were nutrient-limited, as an increase in the feed rate resulted in an increase in the viable-cell density. The cultures in the second region, high feed and bleed rates, were nonnutrient-limited. In this region the viable-cell density decreased more or less linearly with an increase in the bleed rate and was independent of the feed rate. This suggests that the cells were limited by a cell-related factor. Comparison of Trypan-blue dye-exclusion measurements and lactate-dehydrogenase activity measurements revealed that cell lysis was not negligible in this bioreactor set-up. Therefore, lactate-dehydrogenase activity measurements were essential to measure the death rate accurately. The specific growth rate was nearly constant for all tested conditions. The viability increased with an increase of the bleed rate and was independent of the feed rate. Furthermore, the specific productivity of monoclonal antibody was constant under all tested conditions. For the optimal design of a perfusion process it should first be established whether viability is an important parameter. If not, a bleed rate as low as possible should be chosen. If low viabilities are to be avoided, the bleed rate chosen should be higher, with the value depending on the desired viability. Next, the feed rate should be set at such a rate that the cells are just in the nonnutrient-limited region.
Modulation of Wnt signaling influences fracture repair (2010)

While the importance of Wnt signaling in skeletal development and homeostasis is well documented, little is known regarding its function in fracture repair. We hypothesized that activation and inactivation of Wnt signaling would enhance and impair fracture repair, respectively. Femoral fractures were generated in Lrp5 knockout mice (Lrp5-/-) and wild-type littermates (Lrp5+/+), as well as C57BL/6 mice. Lrp5-/- and Lrp5+/+ mice were untreated, while C57BL/6 mice were treated 2x/week with vehicle or anti-Dkk1 antibodies (Dkk1 Ab) initiated immediately postoperatively (Day 0) or 4 days postoperatively (Day 4). Fractures were radiographed weekly until sacrifice at day 28, followed by DXA, pQCT, and biomechanical analyses. Lrp5-/- mice showed impaired repair compared to Lrp5+/+ mice, as evidenced by reduced callus area, BMC, BMD, and biomechanical properties. The effects of Dkk1 Ab treatment depended on the timing of initiation. Day 0 initiation enhanced repair, with significant gains seen for callus area, BMC, BMD, and biomechanical properties, whereas Day 4 initiation had no effect. These results validated our hypothesis that Wnt signaling influences fracture repair, with prompt activation enhancing repair and inactivation impairing it. Furthermore, these data suggest that activation of Wnt signaling during fracture repair may have clinical utility in facilitating fracture repair.
Yield Management at American Airlines (1992)

Critical to an airline's operation is the effective use of its reservations inventory. American Airlines began research in the early 1960s in managing revenue from this inventory. Because of the problem's size and difficulty, American Airlines Decision Technologies has developed a series of OR models that effectively reduce the large problem to three much smaller and far more manageable subproblems: overbooking, discount allocation, and traffic management. The results of the subproblem solutions are combined to determine the final inventory levels. American Airlines estimates the quantifiable benefit at $1.4 billion over the last three years and expects an annual revenue contribution of over $500 million to continue into the future.
High-titer packaging cells producing recombinant retroviruses resistant to human serum (1995)

Novel retroviral protein expression constructs were designed to retain minimal retroviral sequences and to express dominant selectable markers by reinitiation of translation after expression of the viral genes. HT1080 cells were selected as producer cells for their ability to release high-titer viruses that are resistant to inactivation by human serum. Two HT1080-based packaging cell lines which produce Moloney murine leukemia virus cores with envelope glycoproteins of either amphotropic murine leukemia virus (FLYA13 line) or cat endogenous virus RD114 (FLYRD18 line) are described. Direct comparison with previous retroviral packaging systems indicated that 100-fold-higher titers of helper-free recombinant viruses were released by the FLYA13 and FLYRD18 lines.
Leucine‐rich repeat kinase 2 (LRRK2): A key player in the pathogenesis of Parkinson's disease (2008)

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, with a prevalence of more than 1% after the age of 65 years. Mutations in the gene encoding leucine-rich repeat kinase-2 (LRRK2) have recently been linked to autosomal dominant, late-onset PD that is clinically indistinguishable from typical, idiopathic disease. LRRK2 is a multidomain protein containing several protein interaction motifs as well as dual enzymatic domains of GTPase and protein kinase activities. Disease-associated mutations are found throughout the multidomain structure of the protein. LRRK2, however, is unique among the PD-causing genes, because a missense mutation, G2019S, is a frequent determinant of not only familial but also sporadic PD. Thus, LRRK2 has emerged as a promising therapeutic target for combating PD. In this Mini-Review, we look at the current state of knowledge regarding the domain structure, amino acid substitutions, and potential functional roles of LRRK2.
Augmentation of Human Immunodeficiency Virus Type 1 Gene Expression by Tumor Necrosis Factor α (1989)

It is now well established that cytokines are involved in the regulation of gene expression from HIV-1 LTR. The present study provides evidence that TNF-α stimulates HIV-1 gene expression and that the enhancer sequence within the HIV-1 LTR is involved in the stimulation. These results support the idea that immunologic stimulation and infection may trigger the development of clinical AIDS in individuals latently infected with HIV-1.
A systematic degradation of zincophorin: a stereoselective synthesis of the C17-C25 fragment (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA systematic degradation of zincophorin: a stereoselective synthesis of the C17-C25 fragmentRobert E. Zelle, Michael P. DeNinno, Harold G. Selnick, and Samuel J. DanishefskyCite this: J. Org. Chem. 1986, 51, 25, 5032–5036Publication Date (Print):December 1, 1986Publication History Published online1 May 2002Published inissue 1 December 1986https://pubs.acs.org/doi/10.1021/jo00375a060https://doi.org/10.1021/jo00375a060research-articleACS PublicationsRequest reuse permissionsArticle Views656Altmetric-Citations34LEARN 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
Platelet-derived growth factor A chain: gene structure, chromosomal location, and basis for alternative mRNA splicing. (1988)

Genomic clones encoding the A chain of platelet-derived growth factor (PDGF) have been isolated. The gene contains seven exons spanning about 24 kilobases of DNA. The positions of intervening sequences closely match those of the related B-chain (c-sis) gene on chromosome 22. In situ hybridization was used to localize the PDGF A-chain gene to the distal portion of the short arm of chromosome 7 (7p21-p22). Within the (G + C)-rich 5' region, a single transcriptional start site was identified approximately equal to 36 base pairs downstream of a TATAA consensus promoter element. The three size classes of A-chain mRNA probably arise by selection of alternative poly(A) sites in exon 7, but only a single consensus AATAAA signal was identified in this region. Two functionally different A-chain precursors, which differ by the presence or absence of a basic C terminus, are generated as a result of alternative mRNA splicing events, which include or exclude exon 6. This and other structural features of the A-chain gene suggest that PDGF expression may be modulated at transcriptional and post-transcriptional levels.
A Randomized Trial Comparing Activated Thromboplastin Time With Heparin Assay in Patients With Acute Venous Thromboembolism Requiring Large Daily Doses of Heparin (1994)

The heparin assay is a safe and effective method for monitoring heparin treatment in patients with acute venous thromboembolism whose APTT remains subtherapeutic despite large daily doses of heparin. In such patients, dosage escalation can be avoided if the heparin level is therapeutic.
Low Pressure CO2 Storage of Raw Milk: Microbiological Effects (2005)

The effects of holding raw milk under carbon dioxide pressures of 68 to 689 kPa at temperatures of 5, 6.1, 10, and 20 degrees C on the indigenous microbiota were investigated. These pressure-temperature combinations did not cause precipitation of proteins from the milk. Standard plate counts from treated milks demonstrated significantly lower growth rate compared with untreated controls at all temperatures, and in some cases, the treatment was microcidal. Raw milk treated with CO2 and held at 6.1 degrees C for 4 d exhibited reduced bacterial growth rates at pressures of 68, 172, 344, and 516 kPa; and at 689 kPa, demonstrated a significant loss of viability in standard plate count assays. The 689-kPa treatment also reduced gram-negative bacteria and total Lactobacillus spp. The time required for raw milk treated at 689 kPa and held at 4 degrees C to reach 4.30 log10 cfu/mL increased by 4 d compared with untreated controls. Total coliform counts in the treated milk were maintained at 1.95 log10 cfu/mL by d 9 of treatment, whereas counts in the control significantly increased to 2.61 log10 cfu/mL by d 4 and 2.89 log10 cfu/mL by d 9. At d 8, Escherichia coli counts had not significantly changed in treated milk, but significantly increased in the control milk. Thermoduric bacteria counts after 8 d were 1.32 log10 cfu/mL in treated milk and 1.98 log10 cfu/mL in control milk. These data indicated that holding raw milk at low CO2 pressure reduces bacterial growth rates without causing milk protein precipitation. Combining low CO2 pressure and refrigeration would improve the microbiological quality and safety of raw milk and may be an effective strategy for shipping raw single strength or concentrated milk over long distances.
Identification of the ligand-binding domains of CD22, a member of the immunoglobulin superfamily that uniquely binds a sialic acid-dependent ligand. (1995)

CD22 is a B cell-restricted member of the immunoglobulin (Ig) superfamily that functions as an adhesion receptor for leukocytes and erythrocytes. CD22 is unique among members of the Ig superfamily in that it has been suggested to bind a series of sialic acid-dependent ligands, potentially through different functional domains expressed by different splice variants of CD22. In this study, the epitopes identified by a large panel of function-blocking and non-function-blocking CD22 monoclonal antibodies were localized to specific Ig-like domains, revealing that all function-blocking monoclonal antibodies bound to the first and/or second Ig-like domains. Consistent with a single ligand-binding region, the two amino-terminal domains were the functional unit that mediated CD22 adhesion with lymphocytes, neutrophils, monocytes, and erythrocytes. The predominant cell surface species of CD22 was a full length 140,000 relative molecular mass seven Ig-like domain glycoprotein and a minor 130,000 relative molecular mass form lacking the fourth domain. While the two amino-terminal Ig-like domains of CD22 are structurally similar to those found in other members of the Ig superfamily involved in cell adhesion and containing an amino acid sequence motif associated with integrin recognition, site-directed mutagenesis of critical residues surrounding this motif did not disrupt CD22-mediated adhesion. These results demonstrate that the unique ligand-binding properties of CD22 are distinct from those of other members of the Ig superfamily involved in integrin-mediated cell adhesion.
Treatment of Intractable Rheumatoid Arthritis With Combined Cyclophosphamide, Azathioprine, and Hydroxychloroquine (1986)

Cyclophosphamide, azathioprine, and hydroxychloroquine sulfate were prescribed for 31 patients (26 women and five men) with rheumatoid arthritis refractory to conventional therapy. Maintenance drug dosages (mean +/- SD) were as follows: cyclophosphamide, 30 +/- 24 mg/day; azathioprine, 74 +/- 44 mg/day; and hydroxychloroquine sulfate, 210 +/- 92 mg/day. Disease suppression began in 30 patients within three to 24 months (mean, nine months). Results after 43 months (range, 12 to 102 months) were as follows: 16, complete remission; seven, near remission; seven, partial disease suppression; one, no response. None remained in prolonged remission without some form of therapy. Treatment was discontinued in three patients because of pulmonary infection (two) or thrombocytopenia (one). Four patients had five malignant neoplasms (surgical cures) before therapy (two breast, one colon, one melanoma, one endometrial); four patients developed a malignant neoplasm during combined drug therapy (one colon, one endometrial, one lung, one erythroleukemia); and three died. The absolute risk of malignancy from combined drug therapy is still unclear. We concluded that combined use of remittive agents may have promise in treatment of severe rheumatoid arthritis; cyclophosphamide should be replaced with a nonalkylating agent; and the place of combined drug therapy remains uncertain in the absence of controlled trials.