gebhart/patrepeval huggingface dataset:
High plasma norepinephrine attenuates the dynamic heart rate response to vagal stimulation (2003)

To better understand the pathophysiological significance of high plasma norepinephrine (NE) concentration in regulating heart rate (HR), we examined the interactions between high plasma NE and dynamic vagal control of HR. In anesthetized rabbits with sinoaortic denervation and vagotomy, using a binary white noise sequence (0–10 Hz) for 10 min, we stimulated the right vagus and estimated the transfer function from vagal stimulation to HR response. The transfer function approximated a first-order low-pass filter with pure delay. Infusion of NE (100 μg · kg −1 · h −1 iv) attenuated the dynamic gain from 6.2 ± 0.8 to 3.9 ± 1.2 beats · min −1 · Hz −1 ( n = 7, P &lt; 0.05) without affecting the corner frequency or pure delay. Simultaneous intravenous administration of phentolamine (1 mg · kg −1 · h −1 ) and NE (100 μg · kg −1 · h −1 ) abolished the inhibitory effect of NE on the dynamic gain (6.3 ± 0.8 vs. 6.4 ± 1.3 beats · min −1 · Hz −1 , not significant, n = 7). The inhibitory effect of NE at infusion rates of 10, 50, and 100 μg · kg −1 · h −1 on dynamic vagal control of HR was dose-dependent ( n = 5). In conclusion, high plasma NE attenuated the dynamic HR response to vagal stimulation, probably via activation of α-adrenergic receptors on the preganglionic and/or postganglionic cardiac vagal nerve terminals.
Impact of intraocular lens material and design on light scatter: In vitro study (2014)

The baseline straylight levels of IOLs were design and material dependent (hydrophobic < hydrophilic; monofocal < diffractive multifocal). Most monofocal IOLs had straylight levels below the levels in a 20-year-old human crystalline lens.
Balancing false alarms and hits in Spoken Term Detection (2010)

This paper presents methods to improve retrieval of Out-Of-Vocabulary (OOV) terms in a Spoken Term Detection (STD) system. We demonstrate that automated tagging of OOV regions helps to reduce false alarms while incorporating phonetic confusability increases the hits. Additional features that boost the probability of a hit in accordance with the number of neighboring hits for the same query and query-length normalization also improve the overall performance of the spoken-term detection system. We show that these methods can be combined effectively to provide a relative improvement of 21% in Average Term Weighted Value (ATWV) on a 100-hour corpus with 1290 OOV-only queries and 2% relative on the NIST 2006 STD task, where only 16 of the 1107 queries were OOV terms. Lastly, we present results to show that the proposed methods are general enough to work well in query-by-example based spoken-term detection, and in mismatched situations when the representation of the index being searched through and the queries are not generated by the same system.
Micro‐Raman spectroscopy of Si‐, C‐, Mg‐ and Be‐implanted GaN layers (2004)

Abstract We have carried out a systematic Raman study on Si‐, C‐, Mg‐ and Be‐implanted GaN layers. In the as‐implanted GaN layers, new Raman bands around 293–300, 360 and 666–671 cm −1 have appeared. From the phonon‐dispersion curves for hexagonal GaN, the 293–300 cm −1 and 666–671 cm −1 bands are assigned to the highest acoustic‐phonon branch and the optical‐phonon branch at the Brillouin zone boundaries, respectively. Several new modes at 168, 199, 320 and 346 cm −1 are also observed in the Raman spectra of Be‐implanted GaN after post‐implantation annealing and could be associated with Be‐related local vibrational modes in GaN. In the Si‐implanted GaN, we have also observed a new local vibrational mode at 612 cm −1 after thermal annealing. Copyright © 2004 John Wiley &amp; Sons, Ltd.
Color Test for the Measurement of Antibody to T-Strain Mycoplasmas (1966)

Purcell, Robert H. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), D. Taylor-Robinson, D. Wong, and R. M. Chanock. Color test for the measurement of antibody to T-strain mycoplasmas. J. Bacteriol. 92:6-12. 1966.-A metabolic inhibition technique for the measurement of antibody to T-strain mycoplasmas was developed, based upon the ability of T-strain mycoplasmas to metabolize urea with the concomitant production of ammonia, and the ability of specific antiserum to inhibit this ammonia production. Phenol red added to the medium served as an indicator of pH change resulting from ammonia production. Specific antiserum to T-strain mycoplasma T-960 was prepared. The T-strain organism was shown to be serologically distinct from the recognized large-colony mycoplasmas. Antibody to mycoplasma strain T-960 in human sera was demonstrated with the metabolic inhibition technique.
Anti-Cytokine Therapeutics: History and Update (2009)

Anti-cytokine therapy has promoted a revolution in the treatment of several inflammatory disorders during the past 10 years. Despite their medical and commercial success, they exhibit several drawbacks: difficulties of production, excessive costs, and a few side-effects. A promising alternative to the passive infusion of monoclonal antibodies or soluble cytokine receptors is the use of the active anti-cytokine immune therapy (ACIT). Surprisingly, clinical studies suggested the interest of this approach during the late 1980's, even before the advent of anti-cytokine passive immunotherapy. In this review, we first explain the involvement of several cytokines in many common diseases involving cytokine overproduction, and identify key targets for anti-cytokine treatments. We then present an update on current advances in preclinical and clinical development of passive anti-cytokine therapeutic approaches. We further discuss progresses in the promising field of active anti-cytokine immunotherapy. Cytokine receptors biologics and small molecules developed using structure/function information, which also constitute important options for treating the cytokine-mediated diseases, are not discussed in this review.
On the Learnability of Random Deep Networks (2019)

In this paper we study the learnability of random deep networks both theoretically and experimentally. On the theoretical front, assuming the statistical query model, we show that the learnability of random deep networks with sign activation drops exponentially with their depths; under plausible conjectures, our results extend to ReLu and sigmoid activations. The core of the arguments is that even for highly correlated inputs, the outputs of deep random networks are near-orthogonal. On the experimental side, we find that the learnability of random networks drops sharply with depth even with the state-of-the-art training methods.
MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH) (2009)

The asparaginyl hydroxylase FIH [factor inhibiting HIF (hypoxia-inducible factor)] was first identified as a protein that inhibits transcriptional activation by HIF, through hydroxylation of an asparagine residue in the CAD (C-terminal activation domain). More recently, several ARD [AR (ankyrin repeat) domain]-containing proteins were identified as FIH substrates using FIH interaction assays. Although the function(s) of these ARD hydroxylations is unclear, expression of the ARD protein Notch1 was shown to compete efficiently with HIF CAD for asparagine hydroxylation and thus to enhance HIF activity. The ARD is a common protein domain with over 300 examples in the human proteome. However, the extent of hydroxylation among ARD proteins, and the ability of other members to compete with HIF-CAD for FIH, is not known. In the present study we assay for asparagine hydroxylation in a bioinformatically predicted FIH substrate, the targeting subunit of myosin phosphatase, MYPT1. Our results confirm hydroxylation both in cultured cells and in endogenous protein purified from animal tissue. We show that the extent of hydroxylation at three sites is dependent on FIH expression level and that hydroxylation is incomplete under basal conditions even in the animal tissue. We also show that expression of MYPT1 enhances HIF-CAD activity in a manner consistent with competition for FIH and that this property extends to other ARD proteins. These results extend the range of FIH substrates and suggest that cross-competition between ARDs and HIF-CAD, and between ARDs themselves, may be extensive and have important effects on hypoxia signalling.
Phase-coherent frequency comparison of optical clocks using a telecommunication fiber link (2009)

We have explored the performance of two ldquodark fibersrdquo of a commercial telecommunication fiber link for a remote comparison of optical clocks. These fibers establish a network in Germany that will eventually link optical frequency standards at PTB with those at the Institute of Quantum Optics (IQ) at the Leibniz University of Hanover, and the Max Planck Institutes in Erlangen (MPL) and Garching (MPQ). We demonstrate for the first time that within several minutes a phase coherent comparison of clock lasers at the few 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-15</sup> level can also be accomplished when the lasers are more than 100 km apart. Based on the performance of the fiber link to the IQ we estimate the expected stability for the link from PTB to MPQ via MPL that bridges a distance of approximately 900 km.
When NK cells overcome their lack of education (2012)

Cells of the immune system have evolved various molecular mechanisms to sense their environment and react to alterations of self. NK cells are lymphocytes with effector and regulatory functions, which are remarkably adaptable to changes in self. In a study published in this issue of the JCI, Tarek and colleagues report the clinical benefits of manipulating NK cell adaptation to self in an innovative mAb-based therapy against neuroblastoma (NB). This novel therapeutic strategy should stimulate further research on NK cell therapies.
Dynamic gene expression profiling of Escherichia coli in carbon source transition from glucose to acetate (2006)

DNA microarray was used to study the transcription profiling of Escherichia coli adapting to acetate as a sole carbon source. Bacteria grown in glucose minimal media were used as a reference. The dynamic expression levels of 3,497 genes were monitored at seven time points during this adaptation. Among the central metabolic genes, the glycolytic and glucose phosphotransferase genes were repressed as the bacteria entered stationary phase, whereas the glyoxylate pathway, TCA cycle, and gluconeogenic genes were induced. Distinct induction or repression patterns were recognized among different pathway genes. For example, the repression of glycolytic genes and the induction of gluconeogenic ones started immediately after glucose was depleted. On the other hand, the regulation of the pentose phosphate pathway genes and glyoxylate genes gradually responded to the glucose depletion or was more related to growth in acetate. When the whole genome was considered, many of the CRP, FadR, and Cra regulons were immediately responsive to the glucose depletion, whereas the σ s , Lrp, and IHF regulons were gradually responsive to the glucose depletion. The expression profiling also provided differential regulations between isoenzymes; for example, malic enzymes A (sfcA) and B (maeB). The expression profiles of three genes were confirmed with RT-PCR.
Paradigm shift in oncology: targeting the immune system rather than cancer cells (2015)

The clinical benefits obtained with rituximab in the treatment of CD20(+) B-cell malignancies and of imatinib in the treatment of Phi(+) leukaemias have opened a new era in oncology, transforming the concepts of tumour-targeted therapies and personalised medicine into reality. Since then, many tumour-targeted monoclonal antibodies and tyrosine kinase inhibitors have been approved for the treatment of cancers. Compared to conventional chemotherapies, these new drugs have more specificity against cancer cells and less systemic toxicities. However, like conventional chemotherapies, they often provide limited therapeutic benefits with short-lasting tumour responses as the vast majority of cancers become resistant to these drugs over time. Therefore, tumour-targeted therapies are an incremental innovation as compared to historical chemotherapies. Recently, a paradigm shift has been brought to the clinic with drugs targeting immune cells rather than cancer cells with the aim of stimulating the anti-tumour immune response of patients against their own cancer. Immunomodulatory drugs such as anti-CTLA4 and anti-PD-1 have generated long-lasting tumour responses when used as single agent in patients with refractory/relapsing cancers such as metastatic melanomas, renal cell carcinoma or non-small-cell lung carcinoma. These new immune-targeted therapies are therefore a disruptive innovation in cancer treatment: they demonstrate that long-lasting clinical benefits could be obtained by targeting molecules involved in the immune tolerance of cancer cells rather than by targeting oncogenic drivers or antigens expressed by cancer cells.
Transmission of gigawatt-level microwave using a beam-rotating mode converter in a relativistic backward wave oscillator (2010)

Gigawatt-level circularly polarized radiation was transmitted using a coaxial beam rotating antenna in an X-band relativistic backward wave oscillator. The mode conversion from the TM01 mode to the circularly polarized TE11-like mode was experimentally and numerically shown. The simulated radiation pattern was in good agreement with the measured radiation pattern.
Amyloid fibres of Sup35 support a prion-like mechanism of inheritance in yeast (1998)

Conference Article| August 01 1998 Amyloid fibres of Sup35 support a prion-like mechanism of inheritance in yeast S. Lindquist; S. Lindquist 1 1To whom correspondence should be addressed. Search for other works by this author on: This Site PubMed Google Scholar S. K. DebBurman; S. K. DebBurman 1Howard Hughes Medical Institute, The Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar J. R. Glover; J. R. Glover 1Howard Hughes Medical Institute, The Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar A. S. Kowal; A. S. Kowal 1Howard Hughes Medical Institute, The Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar J.-J. Liu; J.-J. Liu 1Howard Hughes Medical Institute, The Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar E. C. Schirmer; E. C. Schirmer 1Howard Hughes Medical Institute, The Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar T. R. Serio T. R. Serio 1Howard Hughes Medical Institute, The Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1998) 26 (3): 486–490. https://doi.org/10.1042/bst0260486 Article history Received: March 23 1998 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation S. Lindquist, S. K. DebBurman, J. R. Glover, A. S. Kowal, J.-J. Liu, E. C. Schirmer, T. R. Serio; Amyloid fibres of Sup35 support a prion-like mechanism of inheritance in yeast. Biochem Soc Trans 1 August 1998; 26 (3): 486–490. doi: https://doi.org/10.1042/bst0260486 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: GFP, Green Fluorescent Protein This content is only available as a PDF. © 1998 Biochemical Society1998 Article PDF first page preview Close Modal You do not currently have access to this content.
85. Development of Zinc Finger Nucleases for Therapeutic Gene Correction of Sickle Cell Anemia (2005)

Top of pageAbstract
We have developed an efficient strategy for introducing precise sequence changes into the human genome, and have initiated studies to apply our methods to the treatment of human disease. Our approach relies on our capacity to design Zinc Finger Protein Nucleases (ZFNs) to bind and cleave virtually any chosen location in the genome. In the first step, a double-stranded break is introduced within the targeted locus using a pair of designed ZFNs that function as a heterodimer. Next, a homologous donor DNA molecule is provided as a recombination substrate to direct precise alterations in the sequence flanking the break site. Recently it was demonstrated that this method can be used to modify an endogenous gene sequence with very high efficiency (>15% of all target sequences)1.

We have now begun developing this approach for the treatment of monogenic diseases. In the present application, ZFNs have been developed to target the |[beta]|-globin gene sequence at the precise location of the mutation causing sickle cell anemia. Development proceeded in several stages. First, a panel of candidate ZFNs was designed and tested for the ability to bind DNA in vitro. The ZFN pair with the highest affinity was then shown to efficiently cleave a DNA fragment corresponding to the |[beta]|-globin locus at the chosen target site. Importantly, the lead ZFN dimer also discriminated well against the corresponding sequence from the highly sequence-related globin paralogs. Next, the binding properties of the lead pair were further improved via site directed mutagenesis and the expansion of the DNA-binding domain of one of the ZFNs from four to six fingers, increasing the DNA recognition sequence from 12 to 18 bp. Finally, the resultant lead pair was tested in cells to determine its ability to cleave the globin target sequence in a chromosomal context. In this assay, the target sequence is embedded within a defective GFP reporter gene that is integrated into the genome of 293 cells. Cleavage of the target and subsequent repair of the GFP gene can be monitored by recovery of green fluorescence, and we observed efficient GFP conversion in this system. These experiments suggest that the current lead pair may be suitable for development of a therapeutic gene correction approach to sickle cell anemia, and we have initiated studies to test the ability of these ZFPs to mediate gene correction at the endogenous |[beta]|-globin locus.
Transition-metal phosphors with emission peak maximum on and beyond the visible spectral boundaries (2023)

Third-row transition-metal complexes displaying efficient true-blue (∼460–470 nm) and near infrared (∼700–1000 nm) emissions were strategically analyzed.
Supporting Figures S1-S4 from Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer (2023)

&lt;p&gt;S1: SARDs inhibit AR mutant activity. S2: UT-155-dependent degradation is selective to the AR. S3: UT-155 degrades wildtype and Y267 phospho mutant ARs. S4. UT-155 inhibits AR ABCD and AR-V7 induced activity.&lt;/p&gt;
Pathologic Examination Accurately Predicts Prognosis in Mucinous Cystic Neoplasms of the Pancreas (1999)

The behavior of pancreatic mucinous cystic neoplasms has long been debated. Some authors contend that histologically benign neoplasms can recur and metastasize. We reviewed the gross and microscopic findings and outcomes of 61 mucinous cystic neoplasms diagnosed at The Johns Hopkins Hospital from March 20, 1984 to July 8, 1998. Each neoplasm was placed into one of four categories based on complete histologic examination: invasive mucinous cystadenocarcinoma, mucinous cystic neoplasm with in situ carcinoma, borderline mucinous cystic neoplasm, and mucinous cystadenoma. Neoplasms in the latter three categories were included only if they were entirely resected and completely examined. Patient outcomes were obtained from hospital records and patient and physician follow-up. Twenty (33%) of the patients had invasive mucinous cystadenocarcinomas, and they had 2- and 5-year disease-specific survival rates of 67% and 33% (mean follow-up of survivors, 4.2 years), respectively. Nine (15%) patients had mucinous cystic neoplasms with in situ carcinoma (mean follow-up of survivors, 4.1 years). Five (8.2%) patients had borderline mucinous cystic neoplasms (mean follow-up of survivors, 5.6 years). Twenty-seven (44%) patients had mucinous cystadenomas (mean follow-up of survivors, 5.1 years). No mucinous cystadenoma, borderline mucinous cystic neoplasm, or mucinous cystic neoplasm with in situ carcinoma recurred or metastasized. No patient with the diagnosis of mucinous cystadenoma, borderline mucinous cystic neoplasm, or mucinous cystic neoplasm with in situ carcinoma died of disease. The difference in disease-specific survival rates between patients with invasive mucinous cystadenocarcinomas and those with noninvasive tumors was significant (p < 0.0001, log-rank test). One case, originally showing only benign histology on incisional biopsy, contained foci of invasive carcinoma on complete resection. Completely resected and entirely examined mucinous cystadenomas, borderline mucinous cystic neoplasms, and mucinous cystic neoplasms with in situ carcinoma follow benign courses. Because invasive carcinoma can be focal, failure to study an entire mucinous cystic neoplasm may result in the miscategorization of a malignant neoplasm as benign.
Surface markers in stem cells and cancer from the perspective of glycomic analysis (2012)

Most cancers are detected when patients present with symptoms, and at that point the disease is usually quite advanced and often not curable. Therefore, new biomarkers are needed for detection and therapy. The recent success of using monoclonal antibodies against nonprotein gangliosides for the treatment of high-risk neuroblastoma provides an incentive to search for new glycan-targeted immunotherapies for cancer using markers found through glycomic analysis as targets. Since more than 85% of cell surface components are glycosylated, glycomic analysis is useful to probe systematically the cancer cell surface, in search for novel glycoproteins and glycolipids. Furthermore, cancer cells tend to dedifferentiate and express many oncofetoproteins, since human embryonic stem cells (ESCs) are derived from epiblast of embryo, representing the early stage of normal embryonic development before gastrulation. Unique ESC surface markers are likely to be found in cancer cells, but not in normal mature tissues. Moreover, stem cells and cancer cells share several common features in related regulatory mechanisms and signaling pathways. Thus, identification of the cancer stem cells in cancer and definition of the glycoproteomic changes that accompany their transformation are important for the development of strategies for early detection and treatment of cancer.
RAND Review: Vol. 34, No. 2, Summer 2010 (2010)

Features discuss retirement patterns of baby boomers, marijuana legalization, drug enforcement in Europe, and No Child Left Behind; news items cover the Gulf coast, food allergies, the U.S. health reform law, police benefits, and Pakistani militants.