gebhart/patrepeval huggingface dataset:
TONOGRAPHIC METHOD FOR MEASURING THE FACILITY AND RATE OF AQUEOUS FLOW IN HUMAN EYES (1950)

THE PURPOSE of this preliminary report is to describe a manner of utilizing the Schiøtz tonometer to obtain a measure of the patency of the channels of aqueous humor outflow and of the steady state net rate of aqueous humor flow. It is believed that the method described here provides a means of discerning in what measure changes in intraocular pressure are due to change in facility of outflow or to change in net rate of aqueous humor formation. A subsequent report will describe the alterations in these factors which are effected in normal and in glaucomatous eyes by various medical and surgical influences. The electronic Schiøtz tonometer is electrically connected to an amplifier and recording galvanometer in such a manner that all measurements made by the tonometer are continuously and automatically recorded on a moving paper strip, such as is employed in electrocardiography. The apparatus is pictured in figure
Hydraulic Fracture Propagation in Layered Rock: Experimental Studies of Fracture Containment (1984)

Abstract Fracture geometry is an important concern in the design of a massive hydraulic fracture for improved natural gas recovery from low-permeability reservoirs. Determination of the extent of vertical fracture growth and containment in layered rock, a priori, requires an improved understanding of the parameters that may control fracture growth across layer interfaces. We have conducted laboratory hydraulic fracture experiments and elastic finite element studies that show that at least two distinct geologic conditions can inhibit or contain the vertical growth of hydraulic fractures in layered rock: (1) a weak interfacial shear strength of the layers and (2) an increase in the minimum horizontal compressive stress in the bounding layer. The second condition is more important and more likely to occur at depth. Differences in elastic properties within a layered rock mass may be important—not as a containment barrier per se, but in the manner in which variations in elastic properties affect the vertical distribution of the minimum horizontal stress magnitude. These results suggest that improved fracture treatment designs and an assessment of the potential success of stimulations in low-permeability reservoirs can be made by determining the in-situ stress state in the producing interval and bounding formations before stimulation. If the bounding formations have a higher minimum horizontal stress, then one can optimize the fracture treatment and maximize the ratio of productive formation fracture area to volume of fluid pumped by limiting bottomhole pressures to that of the bounding formation.
Danazol, Premenstrual Tension, and Uveitis (1989)

<h3>To the Editor.</h3> —It is known that the menstrual cycle may be associated with eye symptoms. Danazol is a weakly androgenic 2,3-isoxazol derivative of 17 x-ethyl testosterone and is used to treat various disorders, including premenstrual tension. In this report, the role of danazol in the treatment of a patient suffering from premenstrual tension and acute iridocyclitis secondary to ankylosing spondylitis is reported. <h3>Report of a Case.</h3> —A healthy 30-year-old woman first presented with severe acute iridocyclitis, secondary glaucoma, and sterile hypopyon in the right eye, which responded favorably to treatment with topical steroids and mydriatic agents. She was also found to be HLA-B27 positive and was suffering from ankylosing spondylitis. Over the following three years, she suffered nine acute attacks of iridocyclitis in the same eye, four of which required systemically administered steroids in addition to topical treatment to induce remission. Rarely was she not receiving treatment, and over
Gastrointestinal spread of oral prolonged‐release mesalazine microgranules (Pentasa) dosed as either tablets or sachet (2000)

Pentasa sachets 1 g unit dose offers the same release of mesalazine as Pentasa 500 mg tablets. Drug release occurs throughout the gastrointestinal tract from stomach to colon, with the advantage of fewer oral doses and ease of swallowing.
The safety of ustekinumab treatment in patients with moderate-to-severe psoriasis and latent tuberculosis infection (2012)

Across five trials of ustekinumab-treated patients with psoriasis, no cases of LTBI reactivation were observed in patients receiving concomitant INH prophylaxis for LTBI. INH prophylaxis was generally well tolerated by these patients with psoriasis.
Computer vision for detecting and quantifying gamma-ray sources in coded-aperture images (2002)

We report the development of an automatic image analysis system that detects gamma-ray source regions in images obtained from a coded aperture, gamma-ray imager. The number of gamma sources in the image is plot known prior to analysis. The system counts the number (K) of gamma sources detected in the image and estimates the lower bound for the probability that the number of sources in the image is K. The system consists of a two-stage pattern classification scheme in which the probabilistic neural network is used in the supervised learning mode. The algorithms were developed and tested using real gamma-ray images from controlled experiments in which the number and location of depleted uranium source disks in the scene are known.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Studies on DNA-cleaving agents: computer modeling analysis of the mechanism of activation and cleavage of dynemicin-oligonucleotide complexes. (1991)

Dynemicin A is a recently identified antitumor antibiotic. Upon activation, dynemicin is reported to cause double-stranded cleavage of DNA, putatively through the intermediacy of a diradical. Computer modeling of this activation and cleavage process is described herein as part of an effort to establish a structural hypothesis for this mechanistic sequence and for the design of simple analogues. Intercalation complexes of duplex dodecamers [d(CGCGAATTCGCG)]2 and [d(GC)6]2 with both enantiomers of dynemicin and of all related mechanistic intermediates are evaluated. Examination of these structures shows that cycloaromatization of dynemicin to a diradical intermediate results in the rotation of the diradical-forming subunit with respect to the intercalation plane that is of an opposite sense for the two dynemicin enantiomers. In addition, the activation of the (2S) enantiomer of dynemicin occurs by a less restricted approach trajectory than the corresponding (2R) enantiomer. In all complexes, the 5'-3' strand is at least 1 A closer than the 3'-5' strand to the diyl intermediate. As a result, complexes are produced in which the diyl moiety is aligned along [(2S)] or across [(2R)] the minor groove, leading to different predictions for the selectivity of radical-initiated, oxidative lesion of DNA. Molecular dynamics simulations are found to support these predictions, including the 3-base-pair offset cleavage reported for dynemicin.
Tumor Rejection and Immune Memory Elicited by Locally Released LEC Chemokine Are Associated with an Impressive Recruitment of APCs, Lymphocytes, and Granulocytes (2000)

The human beta chemokine known as LEC (also called NCC-4, HCC-4, or LMC) displays chemotactic activity for monocytes and dendritic cells. The possibility that its local presence increases tumor immunogenicity is addressed in this paper. TSA parental cells (TSA-pc) are poorly immunogenic adenocarcinoma cells that grow progressively, kill both nu/nu and syngeneic BALB/c mice, and give rise to lung metastases. TSA cells engineered to release LEC (TSA-LEC) are still able to grow in nu/nu mice, but are promptly rejected and display a marginal metastatic phenotype in BALB/c mice. Rejection is associated with a marked T lymphocyte and granulocyte infiltration, along with extensive macrophage and dendritic cell recruitment. NK cells and CD4+ T lymphocytes are uninfluential in TSA-LEC cell rejection, whereas both CD8+ lymphocytes and polymorphonuclear leukocytes play a major role. An antitumor immune memory is established very quickly after rejection, since 6 days later 75% of BALB/c mice were already resistant to a TSA-pc challenge. Spleen cells from rejecting mice display specific cytotoxic activity against TSA-pc and secrete IFN-gamma and IL-2 when restimulated by TSA-pc. The ability of LEC to markedly improve recognition of poorly immunogenic cells by promoting APC-T cell cross-talk suggests that it could be an effective component of antitumor vaccines.
Leucine alters hepatic glucose/lipid homeostasis via the myostatin-AMP-activated protein kinase pathway - potential implications for nonalcoholic fatty liver disease (2014)

Collectively, our observations suggest leucine may be both 'friend' and 'foe' in the context of metabolic syndrome, promoting glucose sequestration and driving lipid accumulation in liver cells. These observations provide insight into the clinical consequences of excess plasma leucine, particularly for hyperglycemia, IR and nonalcoholic fatty liver disease (NAFLD).
The Measurement of Preoperative Anxiety (1988)

Preoperative anxiety was assessed using the hospital anxiety and depression (HAD) scale, multiple affect adjective check list (MAACL) and linear analogue anxiety scale (LAAS) in 100 consecutive day case patients undergoing termination of pregnancy. The HAD scale, a recently introduced self assessment scale comprising 7 multiple choice questions, was readily accepted and easily understood by patients. There was a high degree of correlation between the HAD scale and both the MAACL (correlation coefficient 0.74) and the LAAS (correlation coefficient 0.67). There was only a moderate degree of correlation between the HAD scale and the anaesthetist's assessment of anxiety (correlation coefficient 0.46). The HAD scale is a useful method of subjective measurement of preoperative anxiety.
Staphylococcal Protein A Deletes B-1a and Marginal Zone B Lymphocytes Expressing Human Immunoglobulins: An Immune Evasion Mechanism (2005)

Protein A (SpA) of Staphylococcus aureus is endowed with the capacity to interact with the H chain variable region (V(H)) of human Abs and to target >40% of B lymphocytes. To investigate whether this property represents a virulence factor and to determine the in vivo consequences of the confrontation of SpA with B lymphocytes, we used transgenic mice expressing fully human Abs. We found that administration of soluble SpA reduces B-1a lymphocytes of the peritoneal cavity and marginal zone B lymphocytes of the spleen, resulting in a markedly deficient type 2 humoral response. Single-cell PCR analysis and sequencing of the Ab V(H) gene repertoire revealed a significant reduction of V(H)3+ marginal zone B cells. Since the two B lymphocyte subsets targeted are involved in innate immune functions, our data suggest that crippling of humoral immunity by S. aureus represents an immune evasion mechanism that may aggravate recurrent infections.
A 160-MHz, 32-b, 0.5-W CMOS RISC microprocessor (1996)

This paper describes a 160 MHz 500 mW 32 b StrongARM(R) microprocessor designed for low-power, low-cost applications. The chip implements the ARM(R) V4 instruction set and is bus compatible with earlier implementations. The pin interface runs at 3.3 V but the internal power supplies can vary from 1.5 to 2.2 V, providing various options to balance performance and power dissipation. At 160 MHz internal clock speed with a nominal Vdd of 1.65 V, it delivers 185 Dhrystone 2.1 MIPS while dissipating less than 450 mW. The range of operating points runs from 100 MHz at 1.65 V dissipating less than 300 mW to 200 MHz at 2.0 V for less than 900 mW. An on-chip PLL provides the internal clock based on a 3.68 MHz clock input. The chip contains 2.5 million transistors, 90% of which are in the two 16 kB caches. It is fabricated in a 0.35-/spl mu/m three-metal CMOS process with 0.35 V thresholds and 0.25 /spl mu/m effective channel lengths. The chip measures 7.8 mm/spl times/6.4 mm and is packaged in a 144-pin plastic thin quad flat pack (TQFP) package.
mRNA display selection of a high‐affinity, Bcl‐X L ‐specific binding peptide (2010)

Bcl-X(L), an antiapoptotic member of the Bcl-2 family, is a mitochondrial protein that inhibits activation of Bax and Bak, which commit the cell to apoptosis, and it therefore represents a potential target for drug discovery. Peptides have potential as therapeutic molecules because they can be designed to engage a larger portion of the target protein with higher specificity. In the present study, we selected 16-mer peptides that interact with Bcl-X(L) from random and degenerate peptide libraries using mRNA display. The selected peptides have sequence similarity with the Bcl-2 family BH3 domains, and one of them has higher affinity (IC(50)=0.9 microM) than Bak BH3 (IC(50)=11.8 microM) for Bcl-X(L) in vitro. We also found that GFP fusions of the selected peptides specifically interact with Bcl-X(L), localize in mitochondria, and induce cell death. Further, a chimeric molecule, in which the BH3 domain of Bak protein was replaced with a selected peptide, retained the ability to bind specifically to Bcl-X(L). These results demonstrate that this selected peptide specifically antagonizes the function of Bcl-X(L) and overcomes the effects of Bcl-X(L) in intact cells. We suggest that mRNA display is a powerful technique to identify peptide inhibitors with high affinity and specificity for disease-related proteins.
Store, Forget, and Check: Using Algebraic Signatures to Check Remotely Administered Storage (2006)

The emerging use of the Internet for remote storage and backup has led to the problem of verifying that storage sites in a distributed system indeed store the data; this must often be done in the absence of knowledge of what the data should be. We use m/n erasure-correcting coding to safeguard the stored data and use algebraic signatures hash functions with algebraic properties for verification. Our scheme primarily utilizes one such algebraic property: taking a signature of parity gives the same result as taking the parity of the signatures. To make our scheme collusionresistant, we blind data and parity by XORing them with a pseudo-random stream. Our scheme has three advantages over existing techniques. First, it uses only small messages for verification, an attractive property in a P2P setting where the storing peers often only have a small upstream pipe. Second, it allows verification of challenges across random data without the need for the challenger to compare against the original data. Third, it is highly resistant to coordinated attempts to undetectably modify data. These signature techniques are very fast, running at tens to hundreds of megabytes per second. Because of these properties, the use of algebraic signatures will permit the construction of large-scale distributed storage systems in which large amounts of storage can be verified with minimal network bandwidth.
HIV Experts vs. Sequencers in Patent Race (1997)

Half a dozen groups are vying for priority on CCR5—the receptor HIV uses to enter cells early in an infection—and many are filing patents. But these competitors may themselves be surprised to learn that a company that was not directly involved in these HIV studies—Human Genome Sciences of Rockville, Maryland—appears to have beaten everyone to the patent office.
Development of TLR inhibitors for the treatment of autoimmune diseases (2008)

The innate immune system is a critical element of protection from invading pathogens. The specific receptors that recognize various components of the pathogens trigger signals that result in the production of proinflammatory cytokines as well as the activation of antigen-presenting cells, which activate the adaptive immune system. The discovery of the Toll-like receptors (TLRs) as important components of pathogen recognition has brought new understanding of the key signaling molecules involves in innate immune activation. Interestingly, it appears that most TLRs can recognize self-ligands as well and that mechanisms are required to discriminate between self and non-self ligands. One of these mechanisms is the expression of all the nucleic acid-specific TLR in endosomal compartments and not on the cell surface. Inappropriate activation of TLRs by self-components can result in sterile inflammation or autoimmunity. For example, TLR7 and TLR9 activation by endogenous RNA and DNA, transported to the endosomes in the form of immune complexes or non-covalently associated with cationic peptides, could be an important mechanism involved in promoting diseases such as systemic lupus erythematosus and psoriasis. In this review, we discuss the rationale for self-recognition by TLR7 and TLR9 as an important part of the development of lupus and other autoimmune diseases. We describe novel inhibitors of these receptors and provide evidence to support their use as novel therapeutic agents for autoimmunity.
The CIRCE Element and Its Putative Repressor Control Cell Cycle Expression of the Caulobacter crescentus groESL Operon (1998)

The groESL operon is under complex regulation in Caulobacter crescentus. In addition to strong induction after exposure to heat shock, under physiological growth conditions, its expression is subject to cell cycle control. Transcription and translation of the groE genes occur primarily in predivisional cells, with very low levels of expression in stalked cells. The regulatory region of groESL contains both a sigma32-like promoter and a CIRCE element. Overexpression of C. crescentus sigma32 gives rise to higher levels of GroEL and increased levels of the groESL transcript coming from the sigma32-like promoter. Site-directed mutagenesis in CIRCE has indicated a negative role for this cis-acting element in the expression of groESL only at normal growth temperatures, with a minor effect on heat shock induction. Furthermore, groESL-lacZ transcription fusions carrying mutations in CIRCE are no longer cell cycle regulated. Analysis of an hrcA null strain, carrying a disruption in the gene encoding the putative repressor that binds to the CIRCE element, shows constitutive synthesis of GroEL throughout the Caulobacter cell cycle. These results indicate a negative role for the hrcA gene product and the CIRCE element in the temporal control of the groESL operon.
CRISPR/Cas9-Mediated Gene Knock-Down in Post-Mitotic Neurons (2014)

The prokaryotic adaptive immune system CRISPR/Cas9 has recently been adapted for genome editing in eukaryotic cells. This technique allows for sequence-specific induction of double-strand breaks in genomic DNA of individual cells, effectively resulting in knock-out of targeted genes. It thus promises to be an ideal candidate for application in neuroscience where constitutive genetic modifications are frequently either lethal or ineffective due to adaptive changes of the brain. Here we use CRISPR/Cas9 to knock-out Grin1, the gene encoding the obligatory NMDA receptor subunit protein GluN1, in a sparse population of mouse pyramidal neurons. Within this genetically mosaic tissue, manipulated cells lack synaptic current mediated by NMDA-type glutamate receptors consistent with complete knock-out of the targeted gene. Our results show the first proof-of-principle demonstration of CRISPR/Cas9-mediated knock-down in neurons in vivo, where it can be a useful tool to study the function of specific proteins in neuronal circuits.
Broad Wavelength Range Metal-Enhanced Fluorescence Using Nickel Nanodeposits (2009)

We describe the use of surface-deposited nickel nanoparticles to enhance the fluorescence signatures of fluorophores. Different density Ni nanoparticulate substrates were fabricated and characterized using both AFM and optical absorption techniques. When fluorophores were placed in close proximity to the substrates, metal-enhanced fluorescence (MEF) was observed. The wavelength dependence of the metal-enhanced fluorescence corresponded with numerical finite-difference time-domain simulations also showing a broad range (500−800 nm) for the enhanced electric field of Ni nanoparticles as compared with traditionally ≈400 to 500 nm for the widely used Ag nanoparticles. This broad wavelength range for an enhanced electric field enables nickel nanoparticles to enhance near-field dipoles in the visible to the infrared region. In addition, the decay times of fluorophores were also reduced near the Ni substrates, suggesting both an enhanced electric field and a plasmon-coupling component are the mechanisms for fluorescence enhancement, similar to MEF substrates made from silver, copper, and gold nanoparticles. Our results show that nickel nanoparticles are suitable for enhancing near-infrared fluorescence, to a similar degree as Ag nanoparticles, and, therefore, are particularly applicable to the many whole blood biological assays in use today.
A Novel and Rapid Encoding Method Based on Mass Spectrometry for “One-Bead-One-Compound” Small Molecule Combinatorial Libraries (2003)

A novel and efficient encoding method based on mass spectrometry for "one-bead-one-compound" small molecule combinatorial libraries has been developed. The topologically segregated bifunctional resin beads with orthogonal protecting groups in the outer and inner regions are first prepared according to our previously published procedure. Prior to library synthesis, the inner core of each bead is derivatized with 3-4 different coding blocks on a cleavable linker. Each functional group on the scaffold is encoded by an individual coding block containing a functional group with the same chemical reactivity. During the library synthesis, the same chemical reactions take place on the scaffold (outer layer of the bead) and coding blocks (inner core of the bead) concurrently. After screening, the coding tags in the positive beads are released, followed by molecular mass determination using matrix-assisted laser desorption ionization Fourier transform mass spectrometry. The chemical structure of library compounds can be readily identified according to the molecular masses of the coding tags. The feasibility and efficiency of this approach were demonstrated by the synthesis and screening of a model small molecule library containing 84 672 member compounds, with a model receptor, streptavidin. Streptavidin binding ligands with structural similarity (17) were identified. The decoding results were clear and unambiguous.
Reduced subcutaneous tissue distribution of cefazolin in morbidly obese versus non-obese patients determined using clinical microdialysis (2013)

This study shows that cefazolin tissue distribution is lower in morbidly obese patients and reduces with increasing body weight, and that dose adjustments are required in this patient group.
ChemInform Abstract: A SHORT AND EFFICIENT SYNTHESIS OF C‐NOR‐DIHYDROCODEINONE ‐ THE ANTIPODE OF GOTO′S SINOMENILONE (1983)

Abstract Die aus Dihydrocodeinon (Ia) erhaltene Bromverbindung (Ib) wird durch alkalische Umlagerung zu (11), Decarboxylierung zu (IIIa) und hydrierende Debromierung in das Nor‐dihydrocodeinon (IIIb) übergeführt.
Peptides bound to proteosomes via hydrophobic feet become highly immunogenic without adjuvants. (1988)

Addition of either a lauroyl or a pentapeptide (FLLAV) hydrophobic foot to the NH2 terminus of a small, synthetic peptide allowed the peptide to hydrophobically complex to meningococcal outer membrane protein proteosomes by simple dialysis. Both conventional and LPS-hyporesponsive mice immunized with these complexes without any adjuvants developed high-titered and persistent anti-peptide IgG. Since proteosomes have been safely given to many people and since important antigenic determinants are generally hydrophilic, this system should be widely applicable to the development of peptide vaccines for human use.