gebhart/patrepeval huggingface dataset:
Magnetic−Plasmonic Core−Shell Nanoparticles (2009)

Nanoparticles composed of magnetic cores with continuous Au shell layers simultaneously possess both magnetic and plasmonic properties. Faceted and tetracubic nanocrystals consisting of wustite with magnetite-rich corners and edges retain magnetic properties when coated with a Au shell layer, with the composite nanostructures showing ferrimagnetic behavior. The plasmonic properties are profoundly influenced by the high dielectric constant of the mixed iron oxide nanocrystalline core. A comprehensive theoretical analysis that examines the geometric plasmon tunability over a range of core permittivities enables us to identify the dielectric properties of the mixed oxide magnetic core directly from the plasmonic behavior of the core-shell nanoparticle.
Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor (1993)

Serum interleukin-10 (IL-10) was measured retrospectively in 153 patients with a fully documented history of non-Hodgkin's lymphoma (NHL) using an enzyme-linked immunosorbent assay (ELISA) detecting both human IL-10 and the Epstein-Barr virus (EBV) molecule BCRF1/viral IL-10. IL-10 was detectable in 47 (46%) of the 101 patients with active NHL, 3 of 52 (6%) patients in first partial or complete response, and none of the 60 healthy blood donors. Serum IL-10 was detectable with a similar frequency in all subtypes of NHL and in all clinical stages, as well as in EBV-seropositive and EBV-negative patients. In patients with intermediate or high-grade NHL, the presence of detectable serum IL-10 at diagnosis was correlated to a significantly shorter overall (P = .025) and progression-free (P = .030) survival. Patients with stage IV disease and detectable serum IL-10 had a particularly poor prognosis (4 years of survival: 0%). Multivariate analysis showed that IL-10 was an independent prognosis factor. These results indicate that IL-10 is detectable in a subgroup of patients with active NHL and correlates to a poor survival in patients with intermediate or high-grade NHL.
Total Synthesis of Anti-HIV Agent Chloropeptin I (2003)

A convergent diastereo- and enantioselective total synthesis of anti-HIV agent chloropeptin I is reported. Important features of the total synthesis include: (1) the use of Ti-catalyzed cyanide addition to imines to prepare a requisite amino acid moiety, (2) the discovery of the positive effect of MeOH in the Cu-mediated biaryl ether formation to afford one of the two macrocyclic peptide moieties, and (3) the discovery of the positive influence of collidine in the diastereoselective Pd-mediated cross-coupling to result in efficient formation of another macrocycle within this medicinally important molecule. This key step is performed in the presence of four unprotected phenols, two of which reside on dichlorophenylglycines.
Resurgence of Sodium Channel Research (2001)

A variety of isoforms of mammalian voltage-gated sodium channels have been described. Ten genes encoding sodium channel alpha subunits have been identified, and nine of those isoforms have been functionally expressed in exogenous systems. The alpha subunit is associated with accessory beta subunits in some tissues, and three genes encoding different beta subunits have been identified. The alpha subunit isoforms have distinct patterns of development and localization in the nervous system, skeletal and cardiac muscle. In addition, many of the isoforms demonstrate subtle differences in their functional properties. However, there are no clear subfamilies of the channels, unlike the situation with potassium and calcium channels. The subtle differences in the functional properties of the sodium channel isoforms result in unique conductances in specific cell types, which have important physiological effects for the organism. Small alterations in the electrophysiological properties of the channel resulting from mutations in specific isoforms cause human diseases such as periodic paralysis, long QT syndrome, and epilepsy.
Estradiol induces proliferation of peroxisome-like microbodies and the production of 3-hydroxy fatty acid diesters, the female pheromones, in the uropygial glands of male and female mallards (1991)

During the mating season the female mallards produce sex pheromones, diesters of 3-hydroxy fatty acids, in their uropygial glands. Subcellular fractionation by sucrose and Nycodenz density gradient centrifugations and electron microscopic examination of the fractions showed that diesters of 3-hydroxy acids and the enzymes that catalyze the formation and esterification of the 3-hydroxy fatty acids are located in the catalase-containing fractions, probably peroxisomes, whereas monoester synthesizing activities are located in the endoplasmic reticulum. Fatty acyl-CoA reductase that would provide fatty alcohol needed for the synthesis of monoester and diester waxes was found both in the peroxisomal and endoplasmic reticulum fraction. Upon daily intramuscular injection of estradiol into the females in the nonmating season, the short chain monoester waxes of the uropygial glands were replaced by long chain monoester waxes, and subsequently the monoester waxes were replaced by diester waxes. Injection of thyroxine with estradiol hastened the induction of the compositional changes including diester synthesis. Similar changes, including the synthesis of the female pheromones, were induced in the uropygial glands by the hormone treatment of males that do not normally produce diesters at any time during their life cycle. The structure and composition of the diesters induced by hormone treatment of both males and females were identical to those of the female pheromones produced during their mating season. Electron microscopic examination of diaminobenzidine-treated glands showed that peroxisomes proliferated in the gland of the females in the mating season and in the estradiol-treated males that produce the diesters.
Matrix‐assisted laser desorption/ionization mass spectrometry of sphingo‐ and glycosphingo‐lipids (1995)

Abstract Sphingo‐ and glycosphingo‐lipids were examined by matrix‐assisted laser desorption/ionization mass spectrometry on a time‐of‐flight (TOF) and a magnetic sector mass spectrometer with 2,5‐dihydroxybenzoic acid (2,5‐DHB), sinapinic acid, α‐cyano‐4‐hydroxycinnamic acid, 2‐(4‐hydroxyphenylazo)benzoic acid (HABA) and esculetin as the matrices. Strong signals were produced by all lipids tested, with many of the compounds producing structurally useful fragment ions. Neutral glycosphingolipids gave the best signals in the positive‐ion mode with 2,5‐DHB, α‐cyano‐4‐hydroxycinnamic acid and esculetin. When 2,5‐DHB was used as the matrix, glycosphingolipids that did not contain HexNAc residues tended to fragment between the sugar and ceramide moieties to give ions revealing the saccharide and lipid contents. Other matrices tended not to induce this fragmentation but, instead, produced ions resulting from loss of that acylamide from the ceramide moiety. These ions revealed the distribution of carbon atoms between the acyl and sphingosine chains. Fragmentation of the oligosaccharide chain of glycolipids that did contain HexNAc groups tended to be more random than that seen when HexNAc was absent and provided considerable sequence information. The acidic gangliosides produced broad, unresolved fragment ion peaks on the TOF spectrometer. Fragmentation was the result of both decarboxylation and loss of sialic acids. On the magnetic sector instrument, these fragment ions were sharp and well resolved. Additional fragment ions resulting from glycosidic cleavages provided information about the sequence of sugars in the oligosaccharide chain. Negative‐ion signals ([M − H]) − from the acidic glycosphingolipids were generally better defined than those in the positive‐ion spectra as the result of a reduction in alkali metal adduct and salt formation.
Cloning of the human erythropoietin receptor gene (1991)

We have isolated and characterized a genomic clone of the human erythropoietin (Epo) receptor from a placental genomic library using a cDNA probe for the murine Epo receptor. The coding region spans about 6.5 kb with seven intervening sequences ranging in size from 81 bp to 2.1 kb. A stretch of 123 purines is found in the 5′ region from -456 to -578 upstream from the first codon and flanking the Alu repetitive sequences located further upstream. The human Epo receptor contains a palindromic sequence 5′ of the translated region that consists of an almost perfect inverted repeat of 12 nucleotides (CAGCTGC(G/C)TCCG) centered about G at -92 from the first codon. An inverted SP1 binding site (CCGCCC) and an inverted GATA-1 binding site (TTATCT) are located at positions -151 and -179, respectively, and CACCC sequences are located at -585 and further upstream. No TATA or CAAT sequences are in this 5′ flanking region. However, this region as far as -275 has a 72% GC content compared with an overall GC content of 56%. A 1-kb BamHI fragment of the human Epo receptor containing 700 bp of sequences 5′ of the coding region was transcribed in an in vitro transcription assay; initiation of transcription appeared to be around 132 +/- 5 just downstream from the inverted SP1 site at -151. T1 analysis of human Epo receptor messenger RNA also maps the site of transcription initiation to this region. Within 180 nucleotides 5′ to the first exon are three regions with 70% or greater homology with the murine Epo receptor. The study of this gene, including its similarities with the murine Epo receptor, should help elucidate aspects of the transcriptional and possible translational control of the Epo receptor in human erythroid cells and thus its role in signal transduction and erythroid differentiation.
Efficacy and safety of dinaciclib vs ofatumumab in patients with relapsed/refractory chronic lymphocytic leukemia (2017)

To the editor:

Novel approaches targeting molecules involved in intracellular pathways that are crucial for the survival and proliferation of the leukemic clone have been recently approved for the treatment of chronic lymphocytic leukemia (CLL) patients. Nevertheless, CLL remains incurable outside
LETTERS TO THE EDITOR (1998)

Redmond, H. Paul M.Ch. F.R.C.S.I.; Bouchier-Hayes, D. M.Ch., F.R.C.S.I., F.A.C.S. Author Information
Differences in Lymphocyte Electron Transport Gene Expression Levels Between Subjects With Bipolar Disorder and Normal Controls in Response to Glucose Deprivation Stress (2007)

<h3>Context</h3> Bipolar disorder (BPD) is among the top 10 causes of disability worldwide. Recent findings on the etiology of the disease point to a disturbed mitochondrial energy metabolism in the brain of subjects with BPD. <h3>Objective</h3> To test whether gene transcripts for proteins of the mitochondrial respiratory chain have altered levels in glucose-deprived lymphocytes from patients with BPD. <h3>Design</h3> Microarrays were used to measure gene expression levels in fresh lymphocytes and in lymphocytes cultured for 5 days in regular or low-glucose medium. <h3>Setting</h3> Subjects with BPD were recruited through the Schizophrenia and Bipolar Disorders Program, McLean Hospital, Belmont, Mass. Controls were recruited through advertising. <h3>Patients</h3> A total of 21 patients with BPD (inpatients and outpatients) and 21 control subjects. <h3>Main Outcome Measure</h3> Expression levels for genes of proteins involved in mitochondrial respiration. <h3>Results</h3> We found an opposite molecular response of control and BPD lymphocytes to glucose deprivation. Whereas lymphocytes of normal controls responded to glucose deprivation with an up-regulation of nuclear transcripts for proteins of the electron transfer chain, subjects with BPD had a tendency to down-regulate these transcripts. <h3>Conclusions</h3> The results suggest that the normal molecular adaptation to energy stress is deficient in lymphocytes from patients with BPD.
A Merger of Rational Drug Design and Combinatorial Chemistry Development and Application of Peptide Secondary Structure Mimetics (2000)

Recent efforts toward the development of peptide secondary structure mimetics at Molecumetics Ltd. for the discoveries of new drug candidates utilizing combinatorial chemistry with solid phase synthesis are described.
ISO/MPEG Audio Coding (1997)

The Moving Pictures Expert Group within the International Organization of Standardization (ISO/MPEG) has developed, and is presently developing, a series of audiovisual standards. Its audio coding standard MPEG Phase 1 is the first international standard in the field of high quality digital audio compression and has been applied in many areas, both for consumer and professional audio. Typical application areas for digital audio are in the fields of audio production, program distribution and exchange, digital sound broadcasting, digital storage, and various multimedia applications. This paper will describe in some detail the main features of MPEG Phase 1 coders. As a logical further step in digital audio a multichannel audio standard MPEG Phase 2 is being standardized to provide an improved stereophonic image for audio-only applications including teleconferencing and for improved television systems. The status of this standardization process will be covered briefly.
The Role of IFN in Respiratory Syncytial Virus Pathogenesis (2002)

Formalin-inactivated respiratory syncytial virus (RSV) vaccine preparations have been shown to cause enhanced disease in naive hosts following natural infection. In this study we demonstrate a similar pattern of enhanced disease severity following primary RSV infection of IFN-nonresponsive STAT1(-/-) mice. STAT1(-/-) mice showed markedly increased illness compared with wild-type BALB/c animals following RSV inoculation despite similar lung virus titers and rates of virus clearance. Histologically, STAT1(-/-) animals had eosinophilic and neutrophilic pulmonary infiltrates not present in wild-type or IFN-gamma(-/-)-infected mice. In cytokine analyses of infected lung tissue, IFN-gamma was induced in both STAT1(-/-) and wild-type mice, with preferential IL-4, IL-5, and IL-13 induction only in the STAT1(-/-) animals. Eotaxin was detected in the lungs of both wild-type and STAT1(-/-) mice following infection, with a 1.7-fold increase over wild-type in the STAT1(-/-) mice. Using a peptide epitope newly identified in the RSV fusion protein, we were able to demonstrate that wild-type memory CD4(+) T cells stimulated by this peptide produce primarily IFN-gamma, while STAT1(-/-)CD4(+) cells produce primarily IL-13. These findings suggest that STAT1 activation by both type I (alphabeta) and type II (gamma) IFNs plays an important role in establishing a protective, Th1 Ag-specific immune response to RSV infection.
Sexual Desire Disorders in Women (2006)

The prelims comprise: Definition Prevalence Pathophysiology Clinical History Clinical Evaluation Treatment
Probiotic Escherichia coli Nissle 1917 Inhibits Leaky Gut by Enhancing Mucosal Integrity (2007)

This study convincingly demonstrates that probiotic EcN is able to mediate up-regulation of ZO-1 expression in murine IECs and confer protection from the DSS colitis-associated increase in mucosal permeability to luminal substances.
Safety, Immunogenicity, and Induction of Immunologic Memory by a Serogroup C Meningococcal Conjugate Vaccine in Infants (2000)

Our data indicate that meningococcal C conjugate vaccine is safe and immunogenic and results in immunologic memory when given with other routinely administered vaccines to infants at 2, 3, and 4 months of age. JAMA. 2000;283:2795-2801
Regulation of Fibroblast Growth Factor-23 Signaling by Klotho (2006)

The aging suppressor gene Klotho encodes a single-pass transmembrane protein. Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that Klotho and FGF23 may function in a common signal transduction pathway(s), we investigated whether Klotho is involved in FGF signaling. Here we show that Klotho protein directly binds to multiple FGF receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23.
Functional analysis of Gln-237 mutants ofHhal methyltransferase (1995)

When the HhaI (cytosine-5) methyltransferase (M.HhaI) binds DNA it causes the target cytosine to be flipped 180 degrees out of the helix. The space becomes occupied by two amino acids, Ser-87 and Gln-237, which enter the helix from opposite sides and form a hydrogen bond to each other. Gln-237 may be involved in specific sequence recognition since it forms three hydrogen bonds to the orphan guanosine, which is the partner of the target cytosine. We have prepared all 19 mutants of Gln-237 and tested their biochemical properties. We find that mutations of this residue greatly affect the stability of the M.HhaI-DNA complex without affecting the enzyme's specificity for the target sequence. Surprisingly, all mutants retain detectable levels of enzymatic activity.
Effects of phrixotoxins on the Kv4 family of potassium channels and implications for the role of Ito1 in cardiac electrogenesis (1999)

1. In the present study, two new peptides, phrixotoxins PaTx1 and PaTx2 (29-31 amino acids), which potently block A-type potassium currents, have been purified from the venom of the tarantula Phrixotrichus auratus. 2. Phrixotoxins specifically block Kv4.3 and Kv4.2 currents that underlie I(to1), with an 5 < IC50 < 70 nM, by altering the gating properties of these channels. 3. Neither are the Shaker (Kv1), Shab (Kv2) and Shaw (Kv3) subfamilies of currents, nor HERG, KvLQT1/IsK, inhibited by phrixotoxins which appear specific of the Shal (Kv4) subfamily of currents and also block I(to1) in isolated murine cardiomyocytes. 4. In order to evaluate the physiological consequences of the Ito1 inhibition, mice were injected intravenously with PaTx1, which resulted in numerous transient cardiac adverse reactions including the occurrence of premature ventricular beats, ventricular tachycardia and different degrees of atrioventricular block. 5. The analysis of the mouse electrocardiogram showed a dose-dependent prolongation of the QT interval, chosen as a surrogate marker for their ventricular repolarization, from 249 +/- 11 to 265 +/- 8 ms (P < 0.05). 6. It was concluded that phrixotoxins, are new and specific blockers of Kv4.3 and Kv4.2 potassium currents, and hence of I(to1) that will enable further studies of Kv4.2 and Kv4.3 channel and/or I(to1) expression.
New therapeutic principles in dyslipidaemia: focus on LDL and Lp(a) lowering drugs (2013)

Dyslipidaemias play a key role in determining cardiovascular risk; the discovery of statins has contributed a very effective approach. However, many patients do not achieve, at the maximal tolerated dose, the recommended goals for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol, and apolipoprotein B (apoB). Available agents combined with statins can provide additional LDL-C reduction, and agents in development will increase therapeutic options impacting also other atherogenic lipoprotein classes. In fact, genetic insights into mechanisms underlying regulation of LDL-C levels has expanded potential targets of drug therapy and led to the development of novel agents. Among them are modulators of apoB containing lipoproteins production and proprotein convertase subtilisin/kexin type-9 inhibitors. Alternative targets such as lipoprotein(a) also require attention; however, until we have a better understanding of these issues, further LDL-C lowering in high and very high-risk patients will represent the most sound clinical approach.
Regulation of Metastases by Signal Transducer and Activator of Transcription 3 Signaling Pathway: Clinical Implications (2007)

Numerous cytokines, growth factors, and oncogenic proteins activate signal transducer and activator of transcription 3 (Stat3), which has been recognized as one of the common pathways in cancer cells. Stat3 signaling affects the expression and function of a variety of genes that are critical to cell survival, cell proliferation, invasion, angiogenesis, and immune evasion. Evidently, the Stat3 signaling pathway regulates cancer metastasis and constitutes a potential preventive and therapeutic target for cancer metastasis.
Plasma concentrations of melatonin in panic disorder (1990)

Nocturnal plasma melatonin concentrations were measured in seven patients with panic disorder and eight healthy control subjects. The five patients who had never received psychotropic medication had significantly greater melatonin concentrations from 4:00 a.m. to 7:00 a.m. than the control subjects. In addition it is possible that a phase delay occurred in these unmedicated patients. The findings are discussed in terms of previous studies showing increased melatonin in manic patients and the effect of intense stress on melatonin synthesis. The two patients who had been medication free for only 1 week showed a decreased melatonin rhythm, which is consistent with previous findings in medicated patients.
Microclusters of inhibitory killer immunoglobulin–like receptor signaling at natural killer cell immunological synapses (2006)

We report the supramolecular organization of killer Ig-like receptor (KIR) phosphorylation using a technique applicable to imaging phosphorylation of any green fluorescent protein-tagged receptor at an intercellular contact or immune synapse. Specifically, we use fluorescence lifetime imaging (FLIM) to report Förster resonance energy transfer (FRET) between GFP-tagged KIR2DL1 and a Cy3-tagged generic anti-phosphotyrosine monoclonal antibody. Visualization of KIR phosphorylation in natural killer (NK) cells contacting target cells expressing cognate major histocompatibility complex class I proteins revealed that inhibitory signaling is spatially restricted to the immune synapse. This explains how NK cells respond appropriately when simultaneously surveying susceptible and resistant target cells. More surprising, phosphorylated KIR was confined to microclusters within the aggregate of KIR, contrary to an expected homogeneous distribution of KIR signaling across the immune synapse. Also, yellow fluorescent protein-tagged Lck, a kinase important for KIR phosphorylation, accumulated in a multifocal distribution at inhibitory synapses. Spatial confinement of receptor phosphorylation within the immune synapse may be critical to how activating and inhibitory signals are integrated in NK cells.
Virus-encoded proteinases of the picornavirus super-group. (1997)

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