gebhart/patrepeval huggingface dataset:
The neural cell adhesion molecule N-CAM enhances L1-dependent cell-cell interactions. (1990)

On neural cells, the cell adhesion molecule L1 is generally found coexpressed with N-CAM. The two molecules have been suggested, but not directly shown, to affect each other's function. To investigate the possible functional relationship between the two molecules, we have characterized the adhesive interactions between the purified molecules and between cultured cells expressing them. Latex beads were coated with purified L1 and found to aggregate slowly. N-CAM-coated beads did not aggregate, but did so after addition of heparin. Beads coated with both L1 and N-CAM aggregated better than L1-coated beads. Strongest aggregation was achieved when L1-coated beads were incubated together with beads carrying both L1 and N-CAM. In a binding assay, the complex of L1 and N-CAM bound strongly to immobilized L1, but not to the cell adhesion molecules J1 or myelin-associated glycoprotein. N-CAM alone did not bind to these glycoproteins. Cerebellar neurones adhered to and sent out processes on L1 immobilized on nitrocellulose. N-CAM was less effective as substrate. Neurones interacted most efficiently with the immobilized complex of L1 and N-CAM. They adhered to this complex even when its concentration was at least 10 times lower than the lowest concentration of L1 found to promote adhesion. The complex became adhesive for cells only when the two glycoproteins were preincubated together for approximately 30 min before their immobilization on nitrocellulose. The adhesive properties between cells that express L1 only or both L1 and N-CAM were also studied. ESb-MP cells, which are L1-positive, but N-CAM negative, aggregated slowly under low Ca2+. Their aggregation could be completely inhibited by antibodies to L1 and enhanced by addition of soluble N-CAM to the cells before aggregation. N2A cells, which are L1 and N-CAM positive aggregated well under low Ca2+. Their aggregation was partially inhibited by either L1 or N-CAM antibodies and almost completely by the combination of both antibodies. N2A and ESb-MP cells coaggregated rapidly and their interaction was similarly inhibited by L1 and N-CAM antibodies. These results indicate that L1 is involved in two types of binding mechanisms. In one type, L1 serves as its own receptor with slow binding kinetics. In the other, L1 is modulated in the presence of N-CAM on one cell (cis-binding) to form a more potent receptor complex for L1 on another cell (trans-binding).
Hormonal control of gene expression: multiplicity and versatility of cyclic adenosine 3',5'-monophosphate-responsive nuclear regulators. (1993)

A central goal of modern biology is to obtain insights into the molecular mechanisms by which extracellular stimuli modulate the expression of specific genes in a temporal and/or tissue-specific manner. These mechanisms are central to processes such as cellular growth, differentiation, and response to environmental changes. This review focuses on the mechanisms that underlie CAMP-induced changes in gene expression. The CAMP-signalling pathway is one of the major intracellular signal transduction pathways operating in eukaryotic cells (1, 2). The intracellular concentration of CAMP is increased upon stimulation of the adenylyl cyclases. This results in activation of the catalytic subunit of protein kinase-A (PKA), which, in turn, phosphorylates a number of substrates (2). Several genes have been found to be inducible upon an increase in intracellular CAMP concentrations (2, 4). In some cases, activation of specific G-protein-coupled receptors by the respective ligands has been shown to result in either stimulation or repression of CAMP-induced gene expression (4). The identification of CAMP response elements (CREs) in the promoters of several CAMP-inducible genes provided the first link between activation of PKA and CAMP-induced gene expression (5-7; see Ref. 4 for a review). Subsequently, it was shown that specific nuclear factors bind to the various CREs. These proteins were of heterogeneous size and characteristics, suggesting the presence of a family (8). The identification and cloning of the gene encoding for
Lack of Change in Perinatal Mortality in the United States, 2014-2016. (2018)

Perinatal mortality (late fetal death at 28 weeks or more and early neonatal death under age 7 days) can be an indicator of the quality of health care before, during, and after delivery (1,2). The U.S. perinatal mortality rate based on the date of the last normal menses (LMP) declined 30% from 1990-2011, but was stable from 2011-2013 (1,3). In 2014, National Center for Health Statistics (NCHS) transitioned to the use of the obstetric estimate of gestational age (OE), introducing a discontinuity in perinatal measures for earlier years (4,5). This report presents trends in perinatal mortality, as well as its components, late fetal and early neonatal mortality, for 2014-2016. Also shown are perinatal mortality trends by mother's age, race and Hispanic origin, and state for 2014-2016 and state perinatal rates for 2016.
Expansion of human cord blood CD34+CD38−cells in ex vivo culture during retroviral transduction without a corresponding increase in SCID repopulating cell (SRC) frequency: dissociation of SRC phenotype and function (2000)

Current procedures for the genetic manipulation of hematopoietic stem cells are relatively inefficient due, in part, to a poor understanding of the conditions for ex vivo maintenance or expansion of stem cells. We report improvements in the retroviral transduction of human stem cells based on the SCID-repopulating cell (SRC) assay and analysis of Lin− CD34+CD38−cells as a surrogate measure of stem cell function. Based on our earlier study of the conditions required for ex vivo expansion of Lin−CD34+ CD38− cells and SRC, CD34+–enriched lineage–depleted umbilical cord blood cells were cultured for 2 to 6 days on fibronectin fragment in MGIN (MSCV-EGFP-Neo) retroviral supernatant (containing 1.5% fetal bovine serum) and IL-6, SCF, Flt-3 ligand, and G-CSF. Both CD34+CD38− cells (20.8%) and CFC (26.3%) were efficiently marked. When the bone marrow of engrafted NOD/SCID mice was examined, 75% (12/16) contained multilineage (myeloid and B lymphoid) EGFP+ human cells composing as much as 59% of the graft. Half of these mice received a limiting dose of SRC, suggesting that the marked cells were derived from a single transduced SRC. Surprisingly, these culture conditions produced a large expansion (166-fold) of cells with the CD34+CD38− phenotype (n = 20). However, there was no increase in SRC numbers, indicating dissociation between the CD34+CD38− phenotype and SRC function. The underlying mechanism involved apparent downregulation of CD38 expression within a population of cultured CD34+CD38+ cells that no longer contained any SRC function. These results suggest that the relationship between stem cell function and cell surface phenotype may not be reliable for cultured cells. (Blood. 2000;95:102-110)
T-cell dependent immunogenicity of protein therapeutics: Preclinical assessment and mitigation (2013)

Protein therapeutics hold a prominent and rapidly expanding place among medicinal products. Purified blood products, recombinant cytokines, growth factors, enzyme replacement factors, monoclonal antibodies, fusion proteins, and chimeric fusion proteins are all examples of therapeutic proteins that have been developed in the past few decades and approved for use in the treatment of human disease. Despite early belief that the fully human nature of these proteins would represent a significant advantage, adverse effects associated with immune responses to some biologic therapies have become a topic of some concern. As a result, drug developers are devising strategies to assess immune responses to protein therapeutics during both the preclinical and the clinical phases of development. While there are many factors that contribute to protein immunogenicity, T cell- (thymus-) dependent (Td) responses appear to play a critical role in the development of antibody responses to biologic therapeutics. A range of methodologies to predict and measure Td immune responses to protein drugs has been developed. This review will focus on the Td contribution to immunogenicity, summarizing current approaches for the prediction and measurement of T cell-dependent immune responses to protein biologics, discussing the advantages and limitations of these technologies, and suggesting a practical approach for assessing and mitigating Td immunogenicity.
Structural and Physicochemical Features of Titanium Silicalites (1997)

Abstract The review presents a comparison and discussion of the substantial amount of information about the state and coordination of titanium ions in titanium silicalites. The results from structural characterization of titanium silicalites with spectral, electrochemical, and quantum-chemical methods with emphasis on location of the Ti ions in framework or extraframework positions, their coordination, and the relationship of some spectral features to concrete structures at the atomic level are summarized. The main methods for the determination of some specific characteristics of titanium silicalite samples are considered—presence of metal ion impurities, extraframework titania, acidity, hydrophobicity, diffusion, and other sterical restrictions. Speculations on how these properties influence the catalytic activities and selectivities of the samples are discussed. Some experimental results for interaction of molecules—solvents, water, and hydrogen peroxide—with titanium silicalites are also presented. The review could be used as an appropriate basis for continuation of the discussion on molecular aspects of catalytic activity of titanium silicalites in partial oxidation with hydrogen peroxide.
Multi-step microfluidic droplet processing: kinetic analysis of an in vitro translated enzyme (2009)

Microdroplets in water-in-oil emulsions can be used as microreactors with volumes 10(3) to 10(9) times smaller than the smallest working volumes in a microtitre plate well (1-2 microL). However, many reactions and assays require multiple steps where new reagents are added at defined times, to start, modify or terminate a reaction. The most flexible way to add new reagents to pre-formed droplets is by controlled, pairwise droplet fusion. We describe a droplet-based microfluidic system capable of performing multiple operations, including pairwise droplet fusion, to analyze complex and sequential multi-step reactions. It is exemplified by performing a series of six on-chip and two off-chip operations which enable the coupled in vitro transcription and translation of cotA laccase genes in droplets and, after performing a controlled fusion with droplets containing laccase assay reagents, the end-point and kinetic analysis of the catalytic activity of the translated protein. In vitro translation and the laccase assay must be performed sequentially as the conditions for the laccase assay are not compatible with in vitro translation. Droplet fusion was performed by electrocoalescence at a rate of approximately 3000 fusion events per second and nearly 90% of droplets were fused one-to-one (one droplet containing in vitro translated laccase fused to one droplet containing the reagents for the laccase assay). The ability to uncouple the enzymatic assay from in vitro translation greatly extends the range of activities of in vitro translated proteins that can potentially be screened in droplet-based microfluidic systems. Furthermore, the system also opens up the possibility of performing a wide range of other new (bio)chemical reactions in droplets.
The effects of 4 mrad of γ irradiation on the initial mechanical properties of bone‐patellar tendon‐bone grafts (1994)

Pairs of frozen human patellar tendon-bone (PTB) ligament allografts were exposed to either 0 or 4 Mrad of gamma irradiation sterilization, the latter value based on recent reports suggesting higher dosage levels for adequate sterilization against the human immunodeficiency virus. All specimens were subjected to three levels of loading: lower functional loads, higher functional loads, and failure. Lower functional loads were simulated by performing in vitro static and cyclic creep tests, similar to loads that the surgeon and patient would apply before and after implantation, respectively. Higher functional loads, simulating moderate activities of daily living, were represented by the slope of the linear portion of the force-elongation curve or linear stiffness. Failure or trauma was then simulated by failing the grafts in tension at a high strain rate. We found that the irradiation treatment shortened the tendon by only 0.6 mm, which was nevertheless statistically significant (p < 0.01). By contrast, 4 Mrad did not significantly alter either static or cyclic creep (p > 0.05) at lower functional loads. Instead, irradiation produced the greatest changes during failure testing, reducing both the graft's linear stiffness by 12% (p < 0.025) and maximum force by 26% (p < 0.001). Although our data do not describe how an allograft might perform during the early healing and later collagen-remodelling phases, such in vitro studies remain important if we are to optimize allograft properties before arthroscopic anterior and posterior cruciate ligament reconstruction.
Cross-Couplings of Unactivated Secondary Alkyl Halides:  Room-Temperature Nickel-Catalyzed Negishi Reactions of Alkyl Bromides and Iodides (2003)

The development of a nickel- or palladium-catalyzed method for cross-coupling unactivated secondary alkyl halides has been a long-standing challenge in synthetic chemistry. This communication describes a simple catalyst system-Ni(cod)2/s-Bu-Pybox-that achieves room-temperature Negishi reactions of an array of functionalized primary and secondary alkyl bromides and iodides.
The mpl ligand: molecular and cellular biology of the critical regulator of megakaryocyte development. (1994)

The development of blood cells requires the interplay of hematopoietic stem and progenitor cells, marrow stroma and polypeptide growth factors. Although many proteins are thought to support the expansion of megakaryocytic precursor cells (e.g., interleukin [IL]-3, c-kit ligand [KL]), identification of the late-acting, lineage-specific growth factor for platelet production, termed Thrombopoietin (Tpo), has remained elusive. Recently, characterization of the proto-oncogene c-mpl revealed structural homology with the hematopoietic cytokine receptor family. Based on the cell of origin of its cDNA, we hypothesized that the ligand for c-mpl might be identical with Tpo. Using BaF3 cells engineered to express c-mpl, we employed a functional expression strategy to clone its cDNA. At low concentrations, the recombinant protein supports the growth of megakaryocytic colonies, alone and together with either IL-3 or KL. For IL-3 this appears to be additive, for KL, true synergy was detected. At higher concentrations, the mpl ligand (ML) alone supported a near maximal number of very large megakaryocytic colonies. Using suspension cultures and human megakaryocytic cell lines, we have also shown that ML induces the terminal differentiation of megakaryocytes by enhancing polyploidization and surface membrane expression of GPIb and IIb/IIIa. Moreover, the development of megakaryocytes in vitro appears to be absolutely dependent on the presence of ML. Following receptor engagement, ML induces tyrosine phosphorylation of a number of membrane associated kinases and adaptor molecules, including SHC, JAK2, PLC-gamma and the mpl receptor itself.(ABSTRACT TRUNCATED AT 250 WORDS)
Daratumumab resistance is frequent in advanced‐stage multiple myeloma patients irrespective ofCD38 expression and is related to dismal prognosis (2018)

Responses to daratumumab and combinations in patients with advanced MM, particularly with extramedullary disease, are low and short-lived, stressing the administration of this agent should be early in the course of the disease.
The Theory of Homogeneous Turbulence (1953)

Preface 1. Introduction 2. Mathematics representation of the field of turbulence 3. The kinematics of homogeneous turbulence 4. Some linear problems 5. General dynamics of decay 6. The universal equilibrium theory 7. Decay of the energy-containing eddies 8. The probability distribution of u(x) Bibliography of research on homogeneous turbulence Index.
Swainsonine Augments the Cytotoxicity of Human Lymphokine-Activated Killer Cells Against Autologous Thyroid Cancer Cells (1994)

Our results suggest that SW might have potential immunomodulatory properties in the treatment of thyroid cancer.
Tipifarnib and Bortezomib Are Synergistic and Overcome Cell Adhesion–Mediated Drug Resistance in Multiple Myeloma and Acute Myeloid Leukemia (2006)

It has been established in preclinical models of multiple myeloma and acute myeloid leukemia (AML) that the bone marrow microenvironment provides protection from chemotherapy- and death receptor-mediated apoptosis. This form of resistance, termed de novo drug resistance, occurs independent of chronic exposure to cancer-related therapies and likely promotes the development of multidrug resistance. Consequently, it is of major interest to identify compounds or drug combinations that can overcome environment-mediated resistance. In this study, we investigated the activity of tipifarnib (Zarnestra, formerly R115777) combined with bortezomib (Velcade, formerly PS-341) in microenvironment models of multiple myeloma and AML. The combination proved to be synergistic in multiple myeloma and AML cell lines treated in suspension culture. Even in tumor cells relatively resistant to tipifarnib, combined activity was maintained. Tipifarnib and bortezomib were also effective when multiple myeloma and AML cells were adhered to fibronectin, providing evidence that the combination overcomes cell adhesion-mediated drug resistance (CAM-DR). Of importance, activation of the endoplasmic reticulum stress response was enhanced and correlated with apoptosis and reversal of CAM-DR. Multiple myeloma and AML cells cocultured with bone marrow stromal cells also remained sensitive, although stromal-adhered tumor cells were partially protected (relative to cells in suspension or fibronectin adhered). Evaluation of the combination using a transwell apparatus revealed that stromal cells produce a protective soluble factor. Investigations are under way to identify the cytokines and/or growth factors involved. In summary, our study provides the preclinical rationale for trials testing the tipifarnib and bortezomib combination in patients with multiple myeloma and AML.
Computational identification of non-coding RNAs in Saccharomyces cerevisiae by comparative genomics (2003)

We screened for new structural non-coding RNAs (ncRNAs) in the genome sequence of the yeast Saccharomyces cerevisiae using computational comparative analysis of genome sequences from five related species of Saccharomyces. The screen identified 92 candidate ncRNA genes. Thirteen showed discrete transcripts when assayed by northern blot. Of these, eight appear to be novel ncRNAs ranging in size from 268 to 775 nt, including three new H/ACA box small nucleolar RNAs.
Sampling artifacts in single-cell genomics cohort studies (2020)

Abstract Robust protocols and automation now enable large-scale single-cell RNA and ATAC sequencing experiments and their application on biobank and clinical cohorts. However, technical biases introduced during sample acquisition can hinder solid, reproducible results and a systematic benchmarking is required before entering large-scale data production. Here, we report the existence and extent of gene expression and chromatin accessibility artifacts introduced during sampling and identify experimental and computational solutions for their prevention.
High dose inhaled corticosteroids and dose dependent loss of diabetic control (1998)

We report a case of loss of diabetic control in a patient given high doses of inhaled fluticasone propionate for asthma.

A 67 year old man who had had asthma for 10 years was referred for respiratory assessment. He had had non-insulin dependent diabetes mellitus for 40 years and was taking glibenclamide 5 mg and metformin 1700 mg daily. Glycaemic control was monitored every six weeks in an outpatient clinic using the percentage of glycated haemoglobin (haemoglobin A1c) (Corning-Drew Glycomat low pressure chromatography system).1 The normal range is <6% and the within batch coefficient of variation is 2.6% and 1.5% for concentrations of 7% and 10% respectively. …
PIK3CA Mutations and PTEN Loss Correlate with Similar Prognostic Factors and Are Not Mutually Exclusive in Breast Cancer (2007)

PIK3CA mutations and PTEN loss were not mutually exclusive events and associated with similar prognostic factors.
Temperature Triggered Self-Assembly of Polypeptides into Multivalent Spherical Micelles (2007)

We report herein thermally responsive elastin-like polypeptides (ELPs) in a linear AB diblock architecture with an N-terminal peptide ligand that self-assemble into spherical micelles when heated slightly above body temperature. A series of 10 ELP block copolymers (ELP(BC)'s ) with different molecular weights and hydrophilic-to-hydrophobic block ratios were genetically synthesized by recursive directional ligation. The self-assembly of these polymers from unimers into micelles was investigated by light scattering, fluorescence spectroscopy, and cryo-TEM. These ELP(BC)'s undergo two phase transitions as a function of solution temperature: a unimer-to-spherical micelle transition at an intermediate temperature and a micelle-to-bulk aggregate transition at a higher temperature when the hydrophilic-to-hydrophobic block ratio is between 1:2 and 2:1. The critical micelle temperature is controlled by the length of the hydrophobic block, and the size of the micelle is controlled by both the total ELP(BC) length and hydrophilic-to-hydrophobic block ratio. These polypeptide micelles display a critical micelle concentration in the range 4-8 microM demonstrating the high stability of these structures. These studies have also identified a subset of ELP(BC)'s bearing terminal peptide ligands that are capable of forming multivalent spherical micelles that present multiple copies of the ligand on their corona in the clinically relevant temperature range 37-42 degrees C and target cancer cells. These ELP(BC)'s may be useful for drug targeting by thermally triggered multivalency. More broadly, the design rules uncovered by this study should be applicable to the design of other thermally reversible nanoparticles for diverse applications in medicine and biology.
Contributions of Upper Airway Mechanics and Control Mechanisms to Severity of Obstructive Apnea (2003)

The contributions of pharyngeal mechanical abnormalities, flow demand, and compensatory effectiveness to obstructive sleep apnea severity were determined in 82 patients. Flow demand was estimated from mean inspiratory flow on continuous positive airway pressure. Mechanical load on upper airway muscles was estimated from minimal effective continuous positive airway pressure, flow demand, and minimum flow observed during brief pressure dial downs. Compensatory effectiveness was estimated by relating polysomnographic severity and mechanical load. Mechanical load was more severe in men, in supine position, and in older and heavier patients. Higher flow demand contributed significantly to mechanical load in men and in those who are obese. At the same mechanical load, severity was independent of age, sex, or body mass index but was greater in the supine position and in REM sleep. Mechanical load accounted for only 34% of variability in severity. Eighty-two percent of patients experienced periods of stable breathing despite mechanical loads that would produce continuous cycling without compensation. I conclude that most patients can adequately compensate for the abnormal mechanics, at least part of the time. Higher flow demand contributes to severity in men and in obesity. Severity is largely due to factors other than mechanical load. Compensatory effectiveness is impaired in the supine position and in REM sleep, but not by age, sex, or body mass index.