gebhart/patrepeval huggingface dataset:
Isolation and identification of a diuretic hormone from the tobacco hornworm, Manduca sexta (1989)

A diuretic hormone (DH) has been isolated from pharate adult heads of Manduca sexta by a nine-step purification procedure. The primary structure of the amino-terminal 40 residues was determined by sequence analysis of intact DH. The structure of an amidated carboxyl-terminal tryptic hexapeptide was characterized by sequence analysis of the peptide, and this hexapeptide was later compared by reversed-phase liquid chromatography with two synthetic hexapeptides with the free acid or amide at the carboxyl terminus. The complete structure of M. sexta DH was established as a 41-residue peptide without disulfide bonds: H-Arg-Met-Pro-Ser-Leu-Ser-Ile-Asp-Leu-Pro-Met-Ser-Val-Leu-Arg-Gln-Lys-Leu-Ser -Leu-Glu-Lys-Glu-Arg-Lys-Val-His-Ala-Leu-Arg-Ala-Ala-Ala-Asn-Arg-Asn-Phe-Leu- Asn-Asp-Ile-NH(2). M. sexta DH was synthesized and shown to have chromatographic and biological properties identical with those of the native material. Synthetic DH stimulated fluid excretion in vivo upon injection into larval M. sexta and newly emerged adult Pieris rapae. M. sexta DH has considerable sequence homology with corticotropin-releasing factor, urotensin I, and sauvagine.
Are patents for methods of medical treatment contrary to theordre publicand morality or “generally inconvenient”? (2004)

"No one has advanced a just and logical reason why reward for service to the public should be extended to the inventor of a mechanical toy and denied to the genius whose patience, foresight, and effort have given a valuable new [discovery] to mankind" (Katopis CJ. Patents v patents: policy implications of recent patent legislation. St John's Law Review 1997;71:329). The law around the world permits the granting of patents for drugs, medical devices, and cosmetic treatment of the human body. At the same time, patentability for a method of treatment of the same body is denied in some countries on various public policy grounds. Is there any logical justification for this distinction? Are methods of medical treatment not as vital to the health or even to the life of a patient as drugs or medical devices? Why is a cosmetic result patentable and a curative result not?
The Importance of Solvates (2006)

This chapter contains sections titled: Introduction Terminology and Classification of Solvates General Terms and Definitions Types of Solvates Stoichiometric Solvates Non-stoichiometric Solvates Classification Models of Hydrates Statistical Aspects and Frequency of Solvates Generation and Characterization of Solvates Stability and Solubility of Solvates Processing of Solvates Relevance, Problems and Potential Benefits Patents Conclusions References
Ultrathin Coatings on Nano-LiCoO2for Li-Ion Vehicular Applications (2010)

To deploy Li-ion batteries in next-generation vehicles, it is essential to develop electrodes with durability, high energy density, and high power. Here we report a breakthrough in controlled full-electrode nanoscale coatings that enables nanosized materials to cycle with durable high energy and remarkable rate performance. The nanoparticle electrodes are coated with Al(2)O(3) using atomic layer deposition (ALD). The coated nano-LiCoO(2) electrodes with 2 ALD cycles deliver a discharge capacity of 133 mAh/g with currents of 1400 mA/g (7.8C), corresponding to a 250% improvement in reversible capacity compared to bare nanoparticles (br-nLCO), when cycled at this high rate. The simple ALD process is broadly applicable and provides new opportunities for the battery industry to design other novel nanostructured electrodes that are highly durable even while cycling at high rate.
Transmembrane signaling by epidermal growth factor receptors lacking autophosphorylation sites (1993)

Mutant epidermal growth factor (EGF) receptors in which the five known tyrosine autophosphorylation sites (tyrosines 992, 1068, 1086, 1148, and 1173) were replaced with phenylalanine residues were expressed in NIH-3T3 cells (5F-EGFR) and transmembrane signaling parameters compared with cells expressing wild-type EGF receptor (WT-EGFR). Mutant and wild-type clones were chosen expressing similar numbers of receptors and Scatchard analysis of 125I-EGF binding showed high and low affinity binding of equal affinities for both receptor types. EGF stimulated tyrosine phosphorylation of proteins to a much lesser degree in cells expressing 5F-EGFR relative to cells expressing WT-EGFR. Tyrosine phosphorylation of the 5F-EGFR was 2-4% of WT-EGFR. Surprisingly, cells expressing WT-EGFR or 5F-EGFR showed little difference in dose response of EGF-stimulated [3H]thymidine incorporation or EGF stimulation of mitogen-activated protein kinase activity. However, EGF did not induce anchorage-independent growth of cells expressing 5F-EGFR to the same extent as it did for cells expressing WT-EGFR. EGF treatment of 5F-EGFR cells failed to elicit an increase in phosphatidylinositol 3-kinase activity or to stimulate hydrolysis of phosphoinositides or tyrosine phosphorylation of phospholipase C-gamma 1. These data suggest that a significant proportion of EGF receptor signaling can occur through receptors with altered capacity to interact with src homology 2 domain-containing proteins.
Latent human herpesvirus 6 infection of human monocytes/macrophages (1991)

Human herpesvirus 6 (HHV-6) DNA was detected in peripheral blood from exanthem subitum patients during the acute and convalescent phases of infection using the polymerase chain reaction. Although DNA could be detected in non-adherent and adherent mononuclear cells during the acute phase, it was detected predominantly in adherent cells during the convalescent phase; furthermore, viral DNA was found in adherent cells of healthy adults. When adherent mononuclear cells were cultured in vitro, virus was found to replicate well in differentiated cells cultured for 7 days in vitro before infection. When cells were cultured for more than 1 month, no detectable antigen and no evidence of virus growth was observed, but viral DNA could be detected. These apparently latently infected monocytes were treated with phorbol ester, after which virus could be recovered from the cultures. Therefore, we have developed an in vitro latency system for HHV-6; our results suggest that HHV-6 may latently infect monocytes in vivo and in vitro and that it may be reactivated in cells by some factors.
The influence of microencapsulation using Eudragitr` RS100 on the hydrolysis kinetics of acetylsalicylic acid (1997)

Homogeneous Eudragit RS100 matrix microspheres containing molecularly dispersed acetylsalicylic acid (ASA) were prepared in order to investigate the effect of encapsulation on the decomposition rate of a hydrolytically susceptible drug. ASA-loaded microspheres of this non-eroding polymer matrix were analysed at predetermined time points following immersion of the microspheres in temperature controlled buffer systems at pH 1.2 or pH 12.1 at 30, 40 or 50 degrees C. The mass balance of the total amount of solutes (ASA and SA) initially located within the microsphere interior was equal to the sum of the amount of solutes remaining in the microsphere interior and the amount of solutes in the aqueous phase at any time during the course of the study. Each analysis involved the quantitation of four species; the drug and decomposition product, salicylic acid (SA), in both the microspheres phase and the external aqueous phase. A simple model system using first-order rate approximations for the concurrent Fickian diffusion and hydrolysis decomposition of the drug resulted in a multiexponential expression which adequately described the time-course profile of the drug. SA-loaded microspheres were used as a control under similar conditions to determine the magnitude of the contribution of microsphere phase hydrolysis of ASA to the overall rate of drug loss from the microspheres. Results indicated that microspheres phase hydrolysis of ASA was minimal. Even after 900 h of immersion in pH 12.1 buffer some ASA remained within the microsphere. It is postulated that the matrix incorporated drug is essentially shielded from hydrolytic attack until it is liberated into the external aqueous environment. Electrostatic association of the drug with the charged quaternary residues in the polymer along with the limiting availability of water within the microsphere may be responsible for the observed stability of ASA in aqueous swollen ASA-loaded Eudragit microspheres.
Solving the Java object storage problem (1998)

Today's Internet driven view of information systems is helping to popularize Java as an application development language. Developers are beginning to use Java to create multi tier application architectures that often integrate relational data stores with new data types, in order to package information in easier to use, dynamic ways. Java's object oriented nature is ideally suited to this new world. Using objects, Java developers can encapsulate both data and data manipulation methods to give applications a runtime dynamism and self-contained intelligence that is difficult to achieve using other methods. Java application developers need to be able to store these Java objects-technically, to give them persistence-in order to take advantage of these capabilities. We examine the development issues surrounding Java object storage, including a brief overview of the ODMG Java binding, a standard that adds object persistence to Java. We compare this with the much greater level of effort required to implement the same application using the lower level JDBC interface, which supports Java object storage in relational databases. The ODMG binding for Java and JDBC are not competitive specifications: ODMG interfaces can be built on top of JDBC.
Long-Range Synchronization of γ and β Oscillations and the Plasticity of Excitatory and Inhibitory Synapses: A Network Model (2002)

The ability of oscillating networks to synchronize despite significant separation in space, and thus time, is of biological significance, given that human gamma activity can synchronize over distances of several millimeters to centimeters during perceptual and learning tasks. We use computer simulations of networks consisting of excitatory pyramidal cells (e-cells) and inhibitory interneurons (i-cells), modeling two tonically driven assemblies separated by large (>or=8 ms) conduction delays. The results are as follows. 1) Two assemblies separated by large conduction delays can fire synchronously at beta frequency (with i-cells firing at gamma frequency) under two timing conditions: e-cells of (say) assembly 2 are still inhibited "delay + spike generation milliseconds" after the e-cell beat of assembly 1; this means that the e-cell inhibitory postsynaptic potential (IPSP) cannot be significantly shorter than the delay (2-site effect). This implies for a given decay time constant that the interneuron --> pyramidal cell conductances must be large enough. The e-cell IPSP must last longer than the i-cell IPSP, i.e., the interneuron --> pyramidal cell conductance must be sufficiently large and the interneuron --> interneuron conductance sufficiently small (local effect). 2) We define a "long-interval doublet" as a pair of interneuron action potentials-separated by approximately "delay milliseconds"-in which a) the first spike is induced by tonic inputs and/or excitation from nearby e-cells, while b) the second spike is induced by (delayed) excitation from distant e-cells. "Long-interval population doublets" (long-interval doublets of the i-cell population) are necessary for synchronized firing in our networks. Failure to produce them leads to almost anti-phase activity at gamma frequency. 3) An (almost) anti-phase oscillation is the most stable oscillation pattern of two assemblies that are separated by axonal conduction delays of approximately one-half a gamma period (delays from 8 to 17 ms in our simulations) and that are firing at gamma frequency. 4) Two assemblies separated by large conduction delays can synchronize their activity with the help of interneuron plasticity. They can also synchronize without pyramidal cell --> pyramidal cell connections being present. The presence of pyramidal cell --> pyramidal cell connections allows, however, for synchronization if other parameters are at inappropriate values for synchronization to occur. 5) Synchronization of two assemblies separated by large conduction delays with the help of interneuron plasticity is not simply due to slowing down of the oscillation frequency. It is reached with the help of a "synchronizing-weak-beat," which induces sudden changes in the oscillation period length of the two assemblies.
Use of the Intracellular Fluorescent Dye CFSE to Monitor Lymphocyte Migration and Proliferation (2009)

The stable incorporation of the intracellular fluorescent dye 5-(and -6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) into cells provides a powerful tool to monitor cell migration, and to quantify cell division, because of the sequential decrease in fluorescent labeling in daughter cells. CFSE-labeled lymphocytes have been used to analyze the relationship between cell division and differentiation of cell function, and cell proliferation versus apoptosis, both in vivo and in vitro, and have allowed analysis of the site of response to antigens in vivo.
Different domains of the glucagon and glucagon‐like peptide‐1 receptors provide the critical determinants of ligand selectivity (2003)

(1) Glucagon and glucagon-like peptide-1 (GLP-1) are homologous peptide hormones with important functions in glucose metabolism. The receptors for glucagon and GLP-1 are homologous family B G-protein coupled receptors. The GLP-1 receptor amino-terminal extracellular domain is a major determinant of glucagon/GLP-1 selectivity of the GLP-1 receptor. However, the divergent residues in glucagon and GLP-1 that determine specificity for the GLP-1 receptor amino-terminal extracellular domain are not known. Less is known about how the glucagon receptor distinguishes between glucagon and GLP-1. (2) We analysed chimeric glucagon/GLP-1 peptides for their ability to bind and activate the glucagon receptor, the GLP-1 receptor and chimeric glucagon/GLP-1 receptors. The chimeric peptide GLP-1(7-20)/glucagon(15-29) was unable to bind and activate the glucagon receptor. Substituting the glucagon receptor core domain with the GLP-1 receptor core domain (chimera A) completely rescued the affinity and potency of GLP-1(7-20)/glucagon(15-29) without compromising the affinity and potency of glucagon. Substituting transmembrane segment 1 (TM1), TM6, TM7, the third extracellular loop and the intracellular carboxy-terminus of chimera A with the corresponding glucagon receptor segments re-established the ability to distinguish GLP-1(7-20)/glucagon(15-29) from glucagon. Corroborant results were obtained with the opposite chimeric peptide glucagon(1-14)/GLP-1(21-37). (3) The results suggest that the glucagon and GLP-1 receptor amino-terminal extracellular domains determine specificity for the divergent residues in the glucagon and GLP-1 carboxy-terminals respectively. The GLP-1 receptor core domain is not a critical determinant of glucagon/GLP-1 selectivity. Conversely, the glucagon receptor core domain contains two or more sub-segments which strongly determine specificity for divergent residues in the glucagon amino-terminus.
Synthesis of 3'-thioribonucleosides and their incorporation into oligoribonucleotides via phosphoramidite chemistry. (1997)

Oligoribonucleotides containing 3'-S-phosphorothiolate linkages are valuable probes in nucleic acid biochemistry, but their accessibility has been limited because 3'-thioribonucleoside phosphoramidites have not been available. We synthesized 3'-thioribonucleoside derivatives (C, G, and U) via glycosylations of nucleoside bases with 3-S-thiobenzoyl-5-O-toluoyl-1,2-O-diacetylfuranose 5, which was obtained from 1 ,2-O-isopropylidene-5-O-toluoyl-3-trifluoromethane-sulfonyl-alpha-D-x ylofuranose 2 by SN2 displacement with sodium thiobenzoate. Additionally, a 3'-thioinosine derivative was prepared from inosine via direct modification of the ribose, analogous to the previously reported synthesis of 3'-thioadenosine, except that the intermediate 2',3'-epoxide 9 was first protected as the 5'-O-tert-butyldiphenylsilyl ether prior to subsequent synthetic steps. This hydrophobic silyl group facilitated extraction and isolation of synthetic intermediates. After removal of the protecting groups, the 3'-thionucleosides (C, G, U, and I) were treated with 2,2'-dipyridyl disulfide to protect the free thiol group as a disulfide. The 3'-thionucleosides were converted to the corresponding phosphorothioamidites using procedures analogous to those for standard phosphoramidites. The amino groups of 3'-thiocytidine and 3'-thioguanosine were protected as benzoyl and isobutyryl amides, respectively, and the 5'- and 2'-hydroxyl groups of each nucleoside were protected as dimethoxytrityl and tert-butyldimethylsilyl ethers, respectively. The 3'-thiol group was deprotected by reduction with DTT and phosphitylated to afford analytically pure 3'-S-phosphorothioamidites 15, which were incorporated into oligoribonucleotides by solid-phase synthesis. Chemical assays and mass spectrometry of the synthetic RNA showed that ribose-3'-S-phosphorothiolate linkages were installed correctly and efficiently into RNA oligonucleotides using phosphoramidite chemistry.
Direct measurement of human movement by accelerometry (2008)

Human movement has been the subject of investigation since the fifth century when early scientists and researchers attempted to model the human musculoskeletal system. The anatomical complexities of the human body have made it a constant source of research to this day with many anatomical, physiological, mechanical, environmental, sociological and psychological studies undertaken to define its key elements. These studies have utilised modern day techniques to assess human movement in many illnesses. One such modern technique has been direct measurement by accelerometry, which was first suggested in the 1970s but has only been refined and perfected during the last 10-15 years. Direct measurement by accelerometry has seen the introduction of the successful implementation of low power, low cost electronic sensors that have been employed in clinical and home environments for the constant monitoring of patients (and their controls). The qualitative and quantitative data provided by these sensors make it possible for engineers, clinicians and physicians to work together to be able to help their patients in overcoming their physical disability. This paper presents the underlying biomechanical elements necessary to understand and study human movement. It also reflects on the sociological elements of human movement and why it is important in patient life and well being. Finally the concept of direct measurement by accelerometry is presented with past studies and modern techniques used for data analysis.
Direct stimulatory effect of low-intensity 670 nm laser irradiation on human endothelial cell proliferation (2003)

Low-intensity laser irradiation influences EC proliferation and might thereby contribute to the increase in angiogenesis and the acceleration of wound healing in vivo.
Transcriptional Regulation of Estrogen Receptor in Breast Carcinomas (1995)

An important transcriptional regulatory element of the estrogen receptor (ER) gene that binds a protein expressed in ER-positive breast carcinomas has been identified. Using a transient expression assay, we identified a 75-bp region of the 5' untranslated leader of the ER gene which augments expression from the ER promoter. This region contains two binding sites for a protein, estrogen receptor factor 1 (ERF-1), which is expressed in ER-positive breast carcinomas. A concatenated ERF-1 binding site probe identified a 30,000-Da protein. Low-level ERF-1 expression was detected in normal human mammary epithelial cells. Abundant ERF-1 expression was also found in endometrial carcinoma cell lines that express the ER-positive phenotype. These results indicate that ERF-1 expression represents a common mechanism of ER regulation in hormonally responsive carcinomas.
Immunoliposomes bearing polyethyleneglycol‐coupled Fab′ fragment show prolonged circulation time and high extravasation into targeted solid tumors in vivo (1997)

We have developed a new type of long-circulating immunoliposome (Fab'-PEG immunoliposomes) which is efficiently extravasated into the targeted solid tumor in vivo. Small unilamellar liposomes (100-130 nm in diameter) were prepared from distearoylphosphatidylcholine (DSPC), cholesterol (CHOL) and a dipalmitoylphosphatidylethanolamine derivative of PEG with a terminal maleimidyl group (DPPE-PEG-Mal), and conjugated Fab' fragment of antibody. Inclusion of DPPE-PEG-Mal and linkage of the Fab' fragment instead of intact antibody to PEG terminals allowed the liposomes to evade RES uptake and remain in the circulation for a long time, resulting in enhanced accumulation of the liposomes in the solid tumor. Because of the ability of such Fab'-PEG immunoliposomes to target solid tumors, they appear highly attractive as carriers of not only chemotherapeutic agents, but also of macromolecular drugs.
The Prognostic Significance of IRF8 Transcripts in Adult Patients with Acute Myeloid Leukemia (2013)

Interferon regulatory factor 8 (IRF8) is a transcription factor that plays a critical role in normal hematopoiesis, such that disruption of IRF8 activity promotes leukemogenesis. We and others have identified aberrant expression of IRF8 transcripts, including novel splice variants, in acute myeloid leukemia (AML), but studies have not investigated the prognostic significance of these transcripts. Therefore, we developed and optimized quantitative expression assays for both, the wild type, or the reference sequence (WT-IRF8) and novel splice variants (SV-IRF8). These assays were used to quantify IRF8 transcript levels in 194 adult patients with AML, and multivariate analyses investigated the prognostic significance of these expression levels. After adjusting for known prognostic factors, expression levels of WT- or SV-IRF8 transcripts were not significantly associated with complete responses or overall survival. However, increased expression of WT-IRF8 was associated with decreased relapse-free survival (RFS) in both univariate (P = 0.010) and multivariate (P = 0.019) analyses. Similarly, increased expression of SV-IRF8 was associated with a decreased RFS (univariate, P = 0.026 and multivariate, P = 0.021). These studies show for the first time that WT-IRF8 and SV-IRF8 are independent adverse prognostic factors for patients with AML. Additional studies are planned to examine the prognostic significance of IRF8 transcripts in other populations of AML patients.
Selective Activation of peripheral nerve fibre groups of different diameter by triangular shaped stimulus pulses. (1977)

1. The differential block of cutaneous nerve fibres has been achieved with a simple method of electrical stimulation, employing a single pair of active electrodes. 2. The method allows the selective activation of 95% of small myelinated (delta) axons, without activation of the larger (beta) ones; and activation of unmyelinated (C) fibres, without A fibre activation. Asynchronous firing of myelinated axons was absent in the majority of the experiments. 3. The method employs triangularly shaped electrical pulses, with a steep rise front and a slow exponential decay. The outward flow of current at the cathode fires conducted impulses in both larger and smaller axons, and the inward flow inactivates differentially the conduction in the smaller ones. 4. The differential effect of anodal currents rests upon the greater internal conductance and greater conduction velocity of larger fibres. 5. The method has the advantage over the conventional polarization block of simpler surgical preparation, longer nerve survival and minimal latency distortion. However, it cannot be applied in experiments requiring physiological stimulation of peripheral receptors.