gebhart/patrepeval huggingface dataset:
Investigation of surface-induced alignment of liquid-crystal molecules by optical second-harmonic generation (1991)

We apply the technique of optical second-harmonic generation to study homogeneously aligned liquid-crystal cells. The surface dipole sensitivity of the technique made it possible to study the monolayer in the absence and presence of a bulk of liquid crystal. By comparing the monolayer orientational distribution functions of three surface treatments (rubbed polymer-coated substrates, rubbed surfactant-coated substrates, and substrates made from oblique evaporation of ${\mathrm{SiO}}_{\mathit{x}}$ film), we find that two different surface-originated mechanisms are effective in aligning liquid-crystal films. For rubbed polymer samples, it is shown that a short-range molecular interaction is responsible for alignment of the first monolayer, which then aligns the bulk via an epitaxylike interaction. Results on polymers with various structures and compositions and rubbed with a variety of rubbing strengths are presented. For the other surface treatments, the first monolayer is isotropically distributed, indicating that a bulk elastic interaction is responsible for the bulk alignment.
Mast Cell Homeostasis: A Fundamental Aspect of Allergic Disease (2007)

Mast cells are well known for their role in allergic disease and have recently been implicated in inflammatory disorders, including autoimmune arthritis, multiple sclerosis, and atherosclerosis. Although aberrant mast cell activation is the focus of many studies, much less is known about normal mast cell homeostasis. Because loss of the normal constraints on mast cell activation, proliferation, and survival may be central to disease etiology, understanding these issues warrants attention. This review summarizes the knowledge of mast cell homeostasis controlled by IgE and the regulatory cytokines IL-4, IL-10, and TGF-beta1. Because each of these proteins plays an important role in immune responses tied to mast cell-associated disease, this group represents a potential set of factors altered in atopic or autoimmune patients. It is interesting to note, for example, that polymorphisms within each of these factors or their receptors are linked to allergic disease. By first understanding how cytokines and IgE regulate mast cell function and survival, we may then predict how these factors may function in disease onset and progression.
Density of sodium channels in mammalian myelinated nerve fibers and nature of the axonal membrane under the myelin sheath. (1977)

The density of sodium channels in mammalian myelinated fibers has been estimated from measurements of the binding of [3H]saxitoxin to rabbit sciatic nerve. Binding both to intact and to homogenized nerve consists of a linear, nonspecific, component and a saturable component that represents binding to the sodium channel. The maximum saturable binding capacity in intact nerve is 19.9 +/- 1.9 fmol-mg wet-1; the equilibrium dissociation constant, Kt, is 3.4 +/- 2.0 nM. Homogenization makes little difference, the maximum binding capacity being 19.9 +/- 1.5 fmol-mg wet-1 with Kt = 1.3 +/- 0.7 nM. These values correspond to a density of about 700,000 sodium channels per node--i.e., about 12,000 per mum2 of nodal membrane. From the difference between the values of maximum saturable binding capacity in intact and homogenized preparation, given the statistical uncertainty of their estimate, it seems that the internodal membrane can have no more than about 25 channels per mum2. The significance of these findings for saltatory conduction and in demyelinating disease is discussed.
Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium (2002)

We have previously shown that the estrogen responsiveness of the human lactoferrin gene in a transient transfection system is mediated through an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE) 26 bp upstream from ERE. Reporter constructs containing SFRE and ERE respond to estrogen stimulation in a dose-dependent manner, whereas mutations at either one of the response elements severely impaired the estrogen responsiveness. In this study, we demonstrated that estrogen receptor (ERalpha) binds to the human lactoferrin gene ERE and forms two complexes in an electrophoresis mobility shift assay (EMSA). These complexes could be supershifted by an antibody to ERalpha. We also showed that in normal cycling women, lactoferrin gene expression in the endometrium increases during the proliferative phase and diminishes during the luteal phase. This in-vivo study thus supported the finding from transient transfection experiments that the human lactoferrin gene expression is elevated in an environment with a high level of estrogen. The estrogen effect on lactoferrin gene expression in the rhesus monkey endometrium was studied by Western blotting and immunohistochemistry. The immunohistochemistry results showed that immunoreactive lactoferrin protein was not detectable in the untreated ovariectomized monkey endometrium, was elevated by estrogen treatment, and was suppressed by sequential, combined estrogen plus progesterone treatment. In conclusion, this study has shown that lactoferrin gene expression is responsive to estrogen in primate endometrium.
Erythrocyte membrane fatty acid content in infants consuming formulas supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA): an observational study (2010)

In this observational study, we compared erythrocyte membrane fatty acids in infants consuming formula supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) with those consuming other types of milks. In 110 infants who were participants in a cohort study of otherwise healthy children at risk for developing type 1 diabetes, erythrocytes were collected at approximately 9 months of age, and fatty acid content was measured as a percentage of total lipids. Parents reported the type of milk the infants consumed in the month of and prior to erythrocyte collection: infant formula supplemented with ARA and DHA (supplemented formula), formula with no ARA and DHA supplements (non‐supplemented formula), breast milk, or non‐supplemented formula plus breast milk. Membrane DHA (4.42 versus 1.79, P < 0.001) and omega‐3 fatty acid (5.81 versus 3.43, P < 0.001) levels were higher in infants consuming supplemented versus non‐supplemented formula. Omega‐6 fatty acids were lower in infants consuming supplemented versus non‐supplemented formula (26.32 versus 29.68, P = 0.023); ARA did not differ between groups. Infants given supplemented formula had higher DHA (4.42 versus 2.81, P < 0.001) and omega‐3 fatty acids (5.81 versus 4.45, P = 0.008) than infants drinking breast milk. In infants whose mothers did not receive any dietary advice, use of supplemented formula is associated with higher omega‐3 and lower omega‐6 fatty acid status.
Detection of sequences homologous to human retroviral DNA in multiple sclerosis by gene amplification. (1989)

Twenty-one patients with multiple sclerosis, chronic progressive type, were examined for DNA sequences homologous to a human retrovirus. Genomic DNA from peripheral blood mononuclear cells was analyzed for the presence of homologous sequences to the human T-cell leukemia/lymphoma virus type I (HTLV-I) long terminal repeat, 3' gag, pol, and env domains by the enzymatic in vitro gene amplification technique, polymerase chain reaction. Positive identification of homologous pol sequences was made in the amplified DNA from six of these patients (29%). Three of these six patients (14%) also tested positive for the env region, but not for the other regions tested. In contrast, none of the samples from 35 normal individuals studied was positive when amplified and tested with the same primers and probes. Comparison of patterns obtained from controls and from patients with adult T-cell leukemia or tropical spastic paraparesis suggests that the DNA sequences identified are exogenous to the human genome and may correspond to a human retroviral species. The data support the detection of a human retroviral agent in some patients with multiple sclerosis.
Molecular Mutations and Their Cooccurrences in Cytogenetically Normal Acute Myeloid Leukemia (2017)

Adult acute myeloid leukemia (AML) clinically is a disparate disease that requires intensive treatments ranging from chemotherapy alone to allogeneic hematopoietic cell transplantation (allo-HCT). Historically, cytogenetic analysis has been a useful prognostic tool to classify patients into favorable, intermediate, and unfavorable prognostic risk groups. However, the intermediate-risk group, consisting predominantly of cytogenetically normal AML (CN-AML), itself exhibits diverse clinical outcomes and requires further characterization to allow for more optimal treatment decision-making. The recent advances in clinical genomics have led to the recategorization of CN-AML into favorable or unfavorable subgroups. The relapsing nature of AML is thought to be due to clonal heterogeneity that includes founder or driver mutations present in the leukemic stem cell population. In this article, we summarize the clinical outcomes of relevant molecular mutations and their cooccurrences in CN-AML, including <i>NPM1</i>, <i>FLT3</i><sup>ITD</sup>, <i>DNMT3A</i>, <i>NRAS</i>, <i>TET2</i>, <i>RUNX1</i>, <i>MLL</i><sup>PTD</sup>, <i>ASXL1</i>, <i>BCOR</i>, <i>PHF6</i>, <i>CEBPA</i><sup>biallelic</sup>, <i>IDH1</i>, <i>IDH2</i><sup>R140</sup>, and <i>IDH2</i><sup>R170</sup>, with an emphasis on their relevance to the leukemic stem cell compartment. We have reviewed the available literature and TCGA AML databases (2013) to highlight the potential role of stem cell regulating factor mutations on outcome within newly defined AML molecular subgroups.
ATP binding to a protease-resistant core of actin. (1976)

Actin can be cleaved by trypsin or chymotrypsin into a large, autonomous fragment with approximately 80% of the mass of the undegraded polypeptide. The protease-resistant cores obtained with either enzyme are very similar. Although the fragment does not bind calcium ions and fails to polymerize to the filamentous form of actin or to stimulate myosin adenosine triphosphatase (ATP phosphohydrolase, EC 3.6.1.3) activity, it retains the full capacity to bind ATP. This observation suggests that it represents an independent functional unit. Cleavage of globular actin with either trypsin or chymotrypsin occurs with half-times of 3 min, while that of filamentous actin proceeds with reaction half-times of 20 min for trypsin and nearly 2 hr for chymotrypsin. Denaturation and renaturation of the trypsin-resistant core shows that approximately 20% of the molecules refold to functional forms which indicates that the fragment can be considered as an independent unit of folding as well.
Frequency-stabilized lasers: a parochial review (1993)

It is hoped that this article will serve as a useful introduction to the art of stabilized lasers, especially for those who are joining this sport from other fields. It has become clear that pre- stabilization of the laser on the non-saturable resonance of a stable cavity is a good strategy: with adequate feedback system design, one can effectively replace the intrinsic noise of the laser with the measurement noise of the stabilizer system. By now sub-Hertz frequency control and optical phase locking have been demonstrated with most of these tunable sources. The ready access to modulation of the diode laser can lead to a very simple but impressive source, while the external stabilizer approach is attractive for dye and optically pumped solid-state sources. Current work on amplitude-stabilization of the laser pump may lead to reduction of the `intrinsic' solid state laser noise as well. With the current explosion of interest in atom trapping techniques we can look forward to major progress in the narrow-line laser/super- sharp absorber high resolution spectroscopy business. Applications range from atomic clocks to cold atom collision physics to tests of special relativity. The combination of ultra-stable lasers with cold atom interferometry will be especially powerful in offering new tests of atomic charge neutrality and of time reversal invariance via new limits on atomic electric dipole moments. Remarkably, a practical instrument for oil and gas prospecting might be based on a laser-diode/atom-interferometric measurement of local `g'.
Structure-activity relationships and mode of action of 5-mercapto-substituted oligo- and polynucleotides as antitemplates inhibiting replication of human immunodeficiency virus type 1 (1992)

Introduction of a reactive 5-mercapto group into some of the cytosine and/or uracil bases of various oligo- and polynucleotides by partial thiolation resulted in several potent inhibitors of the replication of human immunodeficiency virus type 1 (HIV-1) in primary human lymphocytes. These compounds exhibited little if any toxicity against uninfected peripheral blood mononuclear cells and showed 15 to 75 times higher antitemplate activity against a p66/p51 HIV-1 recombinant reverse transcriptase (RT) than against the DNA polymerase alpha from human lymphocytes. In contrast, the unthiolated oligo- and polynucleotides are void of antitemplate activity, and their apparent inhibitory effect on HIV-1 closely paralleled their toxicity for the cells. Partially thiolated poly(dC) (MPdC) was the most potent of all the compounds tested against HIV-1 in peripheral blood mononuclear cells (50% effective concentration, 1.8 micrograms/ml or 0.019 microM), while showing low cytotoxicity (greater than 100 micrograms/ml). The corresponding unmodified poly(dC) showed no anti-HIV-1 activity at 50 micrograms/ml but had pronounced cytotoxicity. MPdC was also a potent inhibitor of HIV-1 RT (50% inhibitory concentration, 0.30 micrograms/ml). The inhibitory activities of thiolated homooligo(dCs) against both HIV-1 replication and HIV-1 RT increased with increasing chain length. The heterooligonucleotides included in this study were designed as structural analogs of portions of the natural primer of HIV-1 RT, i.e., tRNA(3Lys). An 18-mer analog of the 3' terminus, complementary (antisense) to the primer-binding site of the HIV-1 genome, was attached to an oligo(dC) tail and 5-thiolated; this increased its activity and decreased its toxicity. This compound will serve as a new lead in the development of more effective antitemplates against HIV-1.
Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy (2016)

Cancer immunotherapies, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to durable responses in the clinic, but response rates remain low due to undefined suppression mechanisms. Solid tumors are characterized by a highly acidic microenvironment that might blunt the effectiveness of antitumor immunity. In this study, we directly investigated the effects of tumor acidity on the efficacy of immunotherapy. An acidic pH environment blocked T-cell activation and limited glycolysis in vitro. IFNγ release blocked by acidic pH did not occur at the level of steady-state mRNA, implying that the effect of acidity was posttranslational. Acidification did not affect cytoplasmic pH, suggesting that signals transduced by external acidity were likely mediated by specific acid-sensing receptors, four of which are expressed by T cells. Notably, neutralizing tumor acidity with bicarbonate monotherapy impaired the growth of some cancer types in mice where it was associated with increased T-cell infiltration. Furthermore, combining bicarbonate therapy with anti-CTLA-4, anti-PD1, or adoptive T-cell transfer improved antitumor responses in multiple models, including cures in some subjects. Overall, our findings show how raising intratumoral pH through oral buffers therapy can improve responses to immunotherapy, with the potential for immediate clinical translation.
A retrospective analysis of therapy for acute graft-versus-host disease: secondary treatment (1991)

We have reviewed results of secondary therapy in 427 patients with acute graft-versus-host disease (GVHD) who did not have a durable satisfactory response after primary treatment. At the beginning of secondary treatment, 320 patients (75%) had rash, 252 (59%) had liver dysfunction, and 228 (53%) had gut dysfunction. Secondary treatment was with glucocorticoids (n = 249), cyclosporine (n = 80), antithymocyte globulin (n = 114), or monoclonal antibody (n = 19) either singly (n = 390) or in combination (n = 37). Parameters of GVHD severity were recorded weekly, and responses were determined according to values at the initiation of tertiary treatment or, for patients without such treatment, using values on day 29 of secondary treatment or the last recorded values before death, whichever occurred first. Minimal criteria for improvement or deterioration were defined for each organ, but no attempt was made to define liver or gut outcome if another complication such as venocclusive disease or infectious enteritis was present. Improvement or resolution of GVHD in the respective organ was seen in 45% of patients with skin disease, 25% of patients with evaluable liver disease, and in 35% of patients with evaluable gut disease. Overall complete or partial responses were seen in 40% of patients. The highest complete response rate with secondary therapy (23%) was seen when GVHD recurred during the taper phase of primary glucocorticoid treatment and was managed by increasing the dose of glucocorticoids. Multivariate analyses were performed to identify patient, disease, or treatment factors associated with likelihood of complete response or overall improvement. A similar analysis was performed to identify covariates associated with time to treatment failure (defined as initiation of tertiary therapy or death not due to relapse of malignancy). Severe dysfunction in the skin, liver, and gut at the beginning of treatment was associated both with a decreased likelihood of complete response and an increased treatment failure rate. The times to treatment failure and the proportions of patients in various response categories were similar for primary and secondary treatment, suggesting that the potential efficacy of new immunosuppressive agents for treatment of acute GVHD can be assessed meaningfully in patients who have not responded adequately to initial therapy.
DMET™ Microarray Technology for Pharmacogenomics-Based Personalized Medicine (2010)

Human genome sequence variation in the form of single nucleotide polymorphisms (SNPs) as well as more complex structural variation such as insertions, duplications, and deletions underlies each individual's response to drugs and thus the likelihood of experiencing an adverse drug reaction. The ongoing challenge of the field of pharmacogenetics is to further understand the relationship between genetic variation and differential drug responses, with the overarching goal being that this will lead to improvements in both the safety and efficacy of drugs. The Affymetrix DMET Plus Premier Pack (DMET stands for Drug Metabolizing Enzymes and Transporters) enables highly multiplexed genotyping of known polymorphisms in Absorption, Distribution, Metabolism, and Elimination (ADME)-related genes on a single array. The DMET Plus Panel interrogates markers in 225 genes that have documented functional significance in phase I and phase II drug metabolism enzymes as well as drug transporters. The power of the DMET Assay has previously been demonstrated with regard to several different drugs including warfarin and clopidogrel. In a research study using an earlier four-color version of the assay, it was demonstrated that warfarin dosing can be influenced by a cytochrome P450 (CYP) 4F2 variant. Additionally, the assay has been used to demonstrate that CYP2C19 variants with decreased enzyme activity led to lower levels of the active clopidogrel metabolite, resulting in a decreased inhibition of platelets and a higher rate of cardiovascular events when compared to noncarriers of the DNA variant. Thus, highly multiplexed SNP genotyping focused on ADME-related polymorphisms should enable research into development of safer drugs with greater efficacy.
Alemtuzumab: a novel monoclonal antibody (2001)

Antibody-based treatment is a novel, effective management strategy for a variety of diseases. Alemtuzumab (CAMPATH) is an example of a monoclonal antibody (mAb) that was initially developed in the laboratory and has completed its journey by being approved for therapeutic use in humans. The main clinical applications of alemtuzumab include treatment of lymphoid malignancies, particularly chronic lymphocytic leukaemia (CLL) and T-cell prolymphocytic leukaemia (T-PLL) and prevention of graft versus host disease (GVHD) and graft rejection in bone marrow and solid organ transplant recipients. Alemtuzumab administration is accompanied by a characteristic first-dose reaction due to cytokine release that consists of fever, rigors, rash and, at times, dyspnea and hypotension. The most significant toxic effect is profound, prolonged lymphopenia and the subsequent increased risk of opportunistic infections; antibiotic prophylaxis is recommended for patients undergoing alemtuzumab treatment. Alemtuzumab has demonstrated clinical activity as a single agent and has an acceptable toxicity profile. It has significant therapeutic potential, especially against lymphoid malignancies.
Cadherin Switching and Bladder Cancer (2010)

Cadherin switching is an important process late in the molecular pathogenesis of bladder cancer, and it may hold some of the answers to the development of muscle invasive and metastatic disease. Thus, the cadherin cell adhesion molecules represent strong candidate biological and molecular targets for preventing disease progression, and further investigation is warranted.
Viscoelastic and optical properties of four different PDMS polymers (2015)

Polydimethylsiloxane (PDMS) is the most commonly used silicone elastomer with a wide range of applications including microfluidics and microcontact printing. Various types of PDMS are currently available, and their bulk material properties have been extensively investigated. However, because the properties are rarely compared in a single study, it is often unclear whether the large disparity of the reported data is attributable to the difference in methodology or to their intrinsic characteristics. Here we report on viscoelastic properties and optical properties of four different PDMS polymers, i.e. Sylgard-184, CY52-276, SIM-360, and KE-1606. Our results show that all the PDMSs are highly elastic rather than viscoelastic at the standard base/curing agent ratios, and their quantified elastic modulus, refractive index, and optical cleanness are similar but distinct in magnitude.
Safety Measures of L-Carnitine L-Tartrate Supplementation in Healthy Men (2001)

The purpose of this investigation was to examine the effects of ingestion of L-CARNIPURE (L-carnitine L-tartrate [LCLT]) on alterations in a complete blood cell profile and in circulating metabolic enzymes. Using a balanced, placebo (P), cross-over design (1 week washout), 10 healthy, active men volunteered and acted as their own control taking either a P or LCLT supplement (3 gday−1) for 3 weeks. Postabsorptive morning blood samples were obtained both before and after 21 days of P and LCLT supplementation. Serum samples were analyzed for clinical chemistries including a complete chemistry panel with markers of liver and renal function along with various minerals and electrolytes. In addition, whole blood was analyzed for a complete blood count with differential. It was determined that there were no statistically significant differences between the LCLT and the placebo conditions for any of the variables examined. The results of this study suggest that LCLT, when used as a dietary supplement, has no adverse effects on metabolic and hemato-logical safety variables in normally healthy en.
Bone-Graft Substitutes: Facts, Fictions, and Applications (2001)

for the Committee on Biological Implants; Greenwald, A. Seth DPhil(Oxon); Boden, Scott D. MD; Goldberg, Victor M. MD; Khan, Yusuf MS; Laurencin, Cato T. MDPhD; Rosier, Randy N. MD Author Information