gebhart/patrepeval huggingface dataset:
NEW METHOD OF TOPOGRAPHICAL OPHTHALMOMETRY ???ITS THEORETICAL AND CLINICAL APPLICATIONS (1962)

Translated by** Eugene Eagle† San Francisco, California *Translation submitted on October 13, 1961, for publication in the May, 1962, issue of the American Journal of Optometry and Archives of American Academy of Optometry. **Translation from Bulletins et Mémoires De La Société Francaise D'Ophthalmologie, Vol. 73, pages 688–716, 1960. †Optometrist. ‡This ophthalmometer will be available in this country through Lux Optical Company 1561 Fillmore Street, San Francisco, California.
Transforming Growth Factor-βs Are Essential for the Development of Midbrain Dopaminergic NeuronsIn VitroandIn Vivo (2003)

Development of midbrain dopaminergic neurons is known to depend on inductive signals derived from the ventral midline, including Sonic hedgehog (Shh) as one of the identified molecules. Here we show that in addition to Shh, transforming growth factor (TGF)-beta is required for both induction and survival of ventrally located midbrain dopaminergic neurons. Like Shh, TGF-beta is expressed in early embryonic structures such as notochord and floor plate, as well as in the area where midbrain dopaminergic neurons are developing. Treatment of cells dissociated from the rat embryonic day (E) 12 midbrain floor with TGF-beta significantly increases the number of tyrosine hydroxylase (TH)-positive dopaminergic neurons within 24 hr. Neutralization of TGF-beta in vitro completely abolishes the induction of dopaminergic neurons. In the absence of TGF-beta, Shh cannot induce TH-positive neurons, and vice versa, neutralizing endogenous Shh abolishes the capacity of TGF-beta to induce dopaminergic neurons in vitro. Furthermore, neutralization of TGF-beta in vivo during chick E2-7 but not E4-7 resulted in a significant reduction in TH-positive neurons in the ventral midbrain floor but not in the locus coeruleus or diencephalon, which suggests that the TGF-beta is required for the induction of mesencephalic dopaminergic neurons with a critical time period at E2/E3. Furthermore, neutralization of TGF-beta between E6 and 10, a time period during maturation of mesencephalic dopaminergic neurons when no further inductive cues are required, also resulted in a significant loss of dopaminergic neurons, suggesting that TGF-beta is required for the promotion of survival of ventral midbrain dopaminergic neurons as well. Together, our results identify TGF-beta as an essential mediator for the induction and maintenance of midbrain dopaminergic neurons.
Studies on Nucleic Acid Antagonists. VII. Synthesis and Characterization of 1, 4, 6-Triazaindenes (5H-Pyrrolo[3, 2-d]pyrimidines) (1964)

1, 4, 6-Triazaindene and its derivatives corresponding to the naturally occurring purine bases were synthesized from the 1, 4, 6-triazaindenes reported in the preceding paper. The structures of these derivatives were confirmed by investigating them on their physico-chemical properties such as ultraviolet absorption and nuclear magnetic resonance spectra.
SET‐LRP of N,N‐dimethylacrylamide and of N‐isopropylacrylamide at 25 °C in protic and in dipolar aprotic solvents (2010)

Abstract The single‐electron transfer living radical polymerization (SET‐LRP) of water‐soluble monomers, N , N ‐dimethylacrylamide (DMA) and N ‐isopropylacrylamide (NIPAM), initiated with 2‐methylchloropropionate (MCP) in dipolar aprotic and protic solvents is reported. The radical polymerization of acrylamides is characterized by higher rate constants of propagation and bimolecular termination than acrylates. Therefore, the addition of CuCl 2 is required to mediate deactivation in the early stages of the reaction. Through the use of Cu(0)‐wire/Me 6 ‐TREN catalysis, conditions were optimized to minimize the amount of externally added CuCl 2 required to maintain a linear evolution of molecular weight and narrow molecular weight distribution. By using less CuCl 2 additive, the amount of soluble copper species that must ultimately be removed from the reaction mixture is reduced. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1752–1763, 2010
Structure-based identification of an inducer of the low-pH conformational change in the influenza virus hemagglutinin: irreversible inhibition of infectivity (1997)

Past efforts to employ a structure-based approach to design an inhibitor of the fusion-inducing conformational change in the influenza virus hemagglutinin (HA) yielded a family of small benzoquinones and hydroquinones. The most potent of these, tert-butyl hydroquinone (TBHQ), inhibits both the conformational change in HA from strain X:31 influenza virus and viral infectivity in tissue culture cells with 50% inhibitory concentrations in the micromolar range (D. L. Bodian, R. B. Yamasaki, R. L. Buswell, J. F. Stearns, J. M. White, and I. D. Kuntz, Biochemistry 32:2967-2978, 1993). A new structure-based inhibitor design search was begun which involved (i) the recently refined crystal structure (2.1-A resolution) of the HA ectodomain, (ii) new insights into the conformational change, and (iii) improvements in the molecular docking program, DOCK. As a result, we identified new inhibitors of HA-mediated membrane fusion. Like TBHQ, most of these molecules inhibit the conformational change. One of the new compounds, however, facilitates rather than inhibits the HA conformational change. Nonetheless, the facilitator, diiodofluorescein, inhibits HA-mediated membrane fusion and, irreversibly, infectivity. We further characterized the effects of inhibitors from both searches on the conformational change and membrane fusion activity of HA as well as on viral infectivity. We also isolated and characterized several mutants resistant to each class of inhibitor. The implications of our results for HA-mediated membrane fusion, anti-influenza virus therapy, and structure-based inhibitor design are discussed.
Transforming growth factor-beta suppresses human B lymphocyte Ig production by inhibiting synthesis and the switch from the membrane form to the secreted form of Ig mRNA (1991)

Transforming growth factor-beta (TGF-beta) inhibits B cell Ig secretion and reduces B cell membrane Ig expression. The addition of TGF-beta to human B lymphocyte cultures stimulated with Staphylococcus aureus Cowan strain I and IL-2 completely inhibited B cell Ig secretion (greater than 90%) and decreased B cell surface IgM, IgD, kappa L chain, and lambda L chain expression. In contrast, TGF-beta had only minimal effects on two other B cell membrane proteins, HLA-DR and CD20. Internal labeling with [35S]methionine and immunoprecipitation with anti-IgM, anti-kappa, and anti-lambda antibodies revealed a striking reduction in kappa L chain in the presence of TGF-beta. A less pronounced reduction in lambda L chain and microH chain was also noted. Northern blot analysis of RNA purified from B cells treated with TGF-beta for varying time intervals revealed a significant decrease in steady state kappa and lambda L chain mRNA levels. Furthermore, a significant decrease in the switch from the membrane forms of mu and gamma to their respective secreted forms was noted in the presence of TGF-beta. Nuclear run-on experiments demonstrated decreased transcription of kappa L chain. The effects of TGF-beta on two transcriptional regulatory factors, Oct-2 and nuclear factor (NF) kappa B, known to be important in Ig gene transcription were examined. Oct-2 mRNA levels and both Oct-2 and NF-kappa B proteins in nuclear extracts were not altered by treatment with TGF-beta. In contrast, levels of the transcriptional factor AP-1, which is not known to be important in B cell Ig production, were reduced by TGF-beta. These findings demonstrate that TGF-beta decreases B lymphocyte Ig secretion by inhibiting the synthesis of Ig mRNA and inhibiting the switch from the membrane form to the secreted forms of mu and gamma mRNA. The mechanism by which TGF-beta inhibits Ig chain synthesis is unclear although it does not involve inhibition of the binding of NF-kappa B or Oct-2 to their respective target sequences.
Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines (2003)

The term 'catastrophic' antiphospholipid syndrome (APS) is used to define an accelerated form of APS resulting in multiorgan failure. Although catastrophic APS patients represent less than 1% of all patients with APS, they are usually in a life-threatening medical situation that requires high clinical awareness. The careful and open discussion of several proposals by all participants in the presymposium workshop on APS consensus, held in Taormina on occasion of the 10th International Congress on aPL and chaired by Munther A Khamashta and Yehuda Shoenfeld (29 September 2002), has allowed the acceptation of a preliminary set of classification criteria. On the other hand, the optimal management of catastrophic APS must have three clear aims: to treat any precipitating factors (prompt use of antibiotics if infection is suspected, amputation for any necrotic organ, high awareness in patients with APS who undergo an operation or an invasive procedure), to prevent and to treat the ongoing thrombotic events and to suppress the excessive cytokine 'storm'. Anticoagulation (usually intravenous heparin followed by oral anticoagulants), corticosteroids, plasma exchange, intravenous gammaglobulins and, if associated with lupus flare, cyclophosphamide, are the most commonly used treatments for catastrophic APS patients.
Implementing efficient fault containment for multiprocessors (1996)

article Free Access Share on Implementing efficient fault containment for multiprocessors: confining faults in a shared-memory multiprocessor environment Authors: Mendel Rosenblum Stanford Univ., Stanford, CA Stanford Univ., Stanford, CAView Profile , John Chapin Stanford Univ., Stanford, CA Stanford Univ., Stanford, CAView Profile , Dan Teodosiu Stanford Univ., Stanford, CA Stanford Univ., Stanford, CAView Profile , Scott Devine Stanford Univ., Stanford, CA Stanford Univ., Stanford, CAView Profile , Tirthankar Lahiri Stanford Univ., Stanford, CA Stanford Univ., Stanford, CAView Profile , Anoop Gupta Stanford Univ., Stanford, CA Stanford Univ., Stanford, CAView Profile Authors Info & Claims Communications of the ACMVolume 39Issue 9Sept. 1996 pp 52–61https://doi.org/10.1145/234215.234471Published:01 September 1996Publication History 11citation500DownloadsMetricsTotal Citations11Total Downloads500Last 12 Months6Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Early Carcinogenesis Involves the Establishment of Immune Privilege via Intrinsic and Extrinsic Regulation of Indoleamine 2,3-dioxygenase-1: Translational Implications in Cancer Immunotherapy (2014)

Although prolonged genetic pressure has been conjectured to be necessary for the eventual development of tumor immune evasion mechanisms, recent work is demonstrating that early genetic mutations are capable of moonlighting as both intrinsic and extrinsic modulators of the tumor immune microenvironment. The indoleamine 2,3-dioxygenase-1 (IDO) immunoregulatory enzyme is emerging as a key player in tumor-mediated immune tolerance. While loss of the tumor suppressor, BIN-1, and the over-expression of cyclooxygenase-2 have been implicated in intrinsic regulation of IDO, recent findings have demonstrated the loss of TβRIII and the upregulation of Wnt5a by developing cancers to play a role in the extrinsic control of IDO activity by local dendritic cell populations residing within tumor and tumor-draining lymph node tissues. Together, these genetic changes are capable of modulating paracrine signaling pathways in the early stages of carcinogenesis to establish a site of immune privilege by promoting the differentiation and activation of local regulatory T cells. Additional investigation of these immune evasion pathways promises to provide opportunities for the development of novel strategies to synergistically enhance the efficacy of the evolving class of T cell-targeted "checkpoint" inhibitors.
Evolution of Amber Suppressor tRNAs for Efficient Bacterial Production of Proteins Containing Nonnatural Amino Acids (2009)

Applied evolution: Regions of the M. jannaschii tyrosyl tRNACUA thought to interact with elongation factor Tu were randomized, and the resulting tRNA libraries were subjected to in vitro evolution. The tRNAs identified resulted in significantly improved yields of proteins containing nonnatural amino acids. In some cases, the degree of improvement varied in an amino acid dependent manner. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cyclin‐dependent kinase inhibitors for treating cancer (2001)

Cyclin dependent kinases (Cdks) are essential enzymes for the control of cell cycle progression. Inhibitors of cyclin-dependent kinases are anticipated to possess therapeutic utility against a wide variety of proliferative diseases, especially cancer. The field of published small molecule Cdk inhibitors is briefly reviewed here as background to a summary of work on a class of pyrido[2,3-d]pyrimidine Cdk inhibitors. Compounds from this class are described that display potency against cyclin D/Cdk4 up to IC(50) = 0.004 microM. Good to moderate selectivity for cyclin D/Cdk4 is also reported for compounds in this structural class. Structure-activity relationship data are presented for substitution at the C2 and N8 positions and these data are interpreted in the context of a binding model that is based on the Cdk2 crystal structure. A representative cyclin D/Cdk4 inhibitor (compound 56) is demonstrated to selectively inhibit the proliferation of an Rb(+) cell line vs. a matched Rb(-) cell line and to produce a distinct G(1) block consistent with cyclin D/Cdk4 inhibition in cells.
Expression of the human B-cell surface protein CD20: alteration by phorbol 12-myristate 13-acetate. (1987)

The monoclonal antibody 1F5 recognizes human B-cell surface protein CD20 and can activate resting B cells; with this antibody we found CD20 to be a 35/37-kDa non-disulfide-linked protein. The protein has a pI of 7.5-8.0 and is phosphorylated in B-cell lines, tonsillar B cells, and peripheral blood B cells. Both CD20 surface expression and phosphorylation are increased on buoyant tonsillar B cells activated in vivo. Because phorbol 12-myristate 13-acetate (PMA) supports the activation signal initiated by monoclonal antibody 1F5, we studied the effect of PMA on CD20 expression. After brief incubation with mitogenic levels of PMA, the number of dense tonsillar B cells positive for CD20 protein transiently decreased. Paradoxically, the cells remaining positive had more surface CD20 than did control cells, and these remaining surface CD20 molecules were hyperphosphorylated. Furthermore, PMA not only induced phosphorylation of CD20 protein on Raji cells but also increased the internalization of CD20 molecules; both phosphorylation and internalization of CD20 molecules were decreased with the protein kinase C inhibitor palmitoyl carnitine. Conditions that increase CD20 phosphorylation are shown also to increase surface mobility of the molecule, suggesting that CD20 protein internalization may be a critical early event for B-cell entry into the G1 phase of the cell cycle.
Human High Molecular Weight–Melanoma-Associated Antigen: Utility for Detection of Metastatic Melanoma in Sentinel Lymph Nodes (2008)

HMW-MAA is more sensitive and specific than MART-1, S-100p, and HMB-45 for IHC-based detection of SLN micrometastases. SLN PEAT-based detection specificity of melanoma micrometastases can be improved by IHC with HMW-MAA-specific mAbs.
Effects of intracardiac bradykinin on T2-T5 medial spinothalamic cells (1985)

Effects of injecting bradykinin (2 micrograms/kg) into the left atrium on spinothalamic tract neurons projecting to medial thalamus (M-STT cells), to the ventral posterior lateral nucleus of the thalamus (L-STT cells), or to both (LM-STT cells) were examined in 18 monkeys (Macaca fascicularis) anesthetized with alpha-chloralose. Bradykinin increased cell activity in 11/16 M-STT cells, 10/15 L-STT cells, and 4/7 LM-STT cells. One M-STT cell was inhibited. Peak responses to bradykinin of the three cell groups were not different. LM-STT cells began to respond and reached peak responses slightly earlier than the other two groups. Six M-STT, four L-STT, and two LM-STT cells became entrained to the cardiac cycle during their responses to bradykinin. Responses to bradykinin were not dependent on the type of somatic input or cell location. Responding cells most often received A delta- and C-fiber sympathetic input, but some responding cells had only A delta-input. These results demonstrate that in addition to L-STT cells STT cells projecting to the medial thalamus respond to a potentially noxious cardiac stimulus. These cells may participate in the motivational-affective component of cardiac pain.
Fluctuating cognition in dementia with Lewy bodies and Alzheimer's disease is qualitatively distinct (2004)

Fluctuations occurring in DLB have particular characteristics that are distinguishable from fluctuations occurring in AD. Interpretation and application of the fluctuation criterion continues to limit the diagnostic sensitivity of the consensus criteria for DLB. Findings suggest that explicit documentation and a wider appreciation of these distinctions could improve the reliability with which less experienced clinicians identify this core diagnostic feature in the clinical setting.
Calming the storm in HLH (2019)

corroborate the proposal of PI3K/AKT/ GSK-3b/NF-kB
Bcr-Abl kinase modulates the translation regulators ribosomal protein S6 and 4E-BP1 in chronic myelogenous leukemia cells via the mammalian target of rapamycin. (2003)

Identification of signaling pathways downstream of Abl tyrosine kinase may increase our understanding of the pathogenesis of chronic myelogenous leukemia (CML) and suggest strategies to improve clinical treatment of the disease. By combining the use of a phosphospecific antibody recognizing a substrate motif of serine/threonine kinases with bioinformatics, we found that the translational regulators ribosomal protein S6 and 4E-BP1 are constitutively phosphorylated in CML cells. Experiments with specific inhibitors indicated the phosphorylation is downstream of Bcr-Abl kinase and the mammalian target of rapamycin (mTOR). These results suggest that Bcr-Abl may regulate translation of critical targets in CML cells via mTOR. They also provide a rationale for testing the combination of mTOR inhibitors with the Abl kinase inhibitor imatinib in patients with CML. The mTOR inhibitor rapamycin enhanced imatinib-mediated killing of CML cell lines in vitro, and it overcame imatinib resistance in cells with Bcr-Abl gene amplification.
AAVS1-Targeted Plasmid Integration in AAV Producer Cell Lines (2017)

Adeno-associated virus (AAV) producer cell lines are created via transfection of HeLaS3 cells with a single plasmid containing three components (the vector sequence, the AAV rep and cap genes, and a selectable marker gene). As this plasmid contains both the cis (Rep binding sites) and trans (Rep protein encoded by the rep gene) elements required for site-specific integration, it was predicted that plasmid integration might occur within the AAVS1 locus on human chromosome 19 (chr19). The objective of this study was to investigate whether integration in AAVS1 might be correlated with vector yield. Plasmid integration sites within several independent cell lines were assessed via Southern, fluorescence in situ hybridization (FISH) and PCR analyses. In the Southern analyses, the presence of fragments detected by both rep- and AAVS1-specific probes suggested that for several mid- and high-producing lines, plasmid DNA had integrated into the AAVS1 locus. Analysis with puroR and AAVS1-specific probes suggested that integration in AAVS1 was a more widespread phenomenon. High-producing AAV2-secreted alkaline phosphatase (SEAP) lines (masterwell 82 [MW82] and MW278) were evaluated via FISH using probes specific for the plasmid, AAVS1, and a chr19 marker. FISH analysis detected two plasmid integration sites in MW278 (neither in AAVS1), while a total of three sites were identified in MW82 (two in AAVS1). An inverse PCR assay confirmed integration within AAVS1 for several mid- and high-producing lines. In summary, the FISH, Southern, and PCR data provide evidence of site-specific integration of the plasmid within AAVS1 in several AAV producer cell lines. The data also suggest that integration in AAVS1 is a general phenomenon that is not necessarily restricted to high producers. The results also suggest that plasmid integration within the AAVS1 locus is not an absolute requirement for a high vector yield.
Facile Synthesis of 5,10-Diaryl-5,10-dihydrophenazines and Application to EL Devices (2003)

[structures: see text] An efficient method for the synthesis of 5,10-diaryldihydrophenazine was developed using a recently developed Pd(0)-mediated cross-coupling reaction. The products 1k and 3c showed excellent properties as hole injection materials in electroluminescent (EL) devices.