gebhart/patrepeval huggingface dataset:
Liposomal Tumor Targeting in Drug Delivery Utilizing MMP-2- and MMP-9-Binding Ligands (2010)

Nanotechnology offers an alternative to conventional treatment options by enabling different drug delivery and controlled-release delivery strategies. Liposomes being especially biodegradable and in most cases essentially nontoxic offer a versatile platform for several different delivery approaches that can potentially enhance the delivery and targeting of therapies to tumors. Liposomes penetrate tumors spontaneously as a result of fenestrated blood vessels within tumors, leading to known enhanced permeability and subsequent drug retention effects. In addition, liposomes can be used to carry radioactive moieties, such as radiotracers, which can be bound at multiple locations within liposomes, making them attractive carriers for molecular imaging applications. Phage display is a technique that can deliver various high-affinity and selectivity peptides to different targets. In this study, gelatinase-binding peptides, found by phage display, were attached to liposomes by covalent peptide-PEG-PE anchor creating a targeted drug delivery vehicle. Gelatinases as extracellular targets for tumor targeting offer a viable alternative for tumor targeting. Our findings show that targeted drug delivery is more efficient than non-targeted drug delivery.
The Wisconsin Wind Tunnel (1993)

We have developed a new technique for evaluating cache coherent, shared-memory computers. The Wisconsin Wind Tunnel (WWT) runs a parallel shared-memory program on a parallel computer (CM-5) and uses execution-driven, distributed, discrete-event simulation to accurately calculate program execution time. WWT is a virtual prototype that exploits similarities between the system under design (the target) and an existing evaluation platform (the host). The host directly executes all target program instructions and memory references that hit in the target cache. WWT's shared memory uses the CM-5 memory's error-correcting code (ECC) as valid bits for a fine-grained extension of shared virtual memory. Only memory references that miss in the target cache trap to WWT, which simulates a cache-coherence protocol. WWT correctly interleaves target machine events and calculates target program execution time. WWT runs on parallel computers with greater speed and memory capacity than uniprocessors. WWT's simulation time decreases as target system size increases for fixed-size problems and holds roughly constant as the target system and problem scale.
Basic science and inherited retinal disease . Tumors (1989)

VOLUME I: BASIC SCIENCE INHERITED RETINAL DISEASE AND TUMORS PART 1 BASIC SCIENCE AND INHERITED RETINAL DISEASE Section 1 Anatomy and physiology Section 2 Virtual psychophysics Section 3 Ocular immunology Section 4 Evaluation Section 5 Genetics Section 6 Retinal degenerations and dystrophies Section 7 Principles of vitreoretinal therapy PART 2 TUMORS OF THE RETINA, CHOROID, AND VITREOUS Section 1 Tumors of the retina Section 2 Tumors of the retinal pigment Epithelium Section 3 Choroidal melanoma and related issues Section 4 Other tumors of the choroid Section 5 Intraocular lymphoid tumors Section 6 Tumors of the vitreous VOLUME II: MEDICAL RETINA Section 1 Normal retinal anatomy and function Section 2 Pathologic responses Section 3 Treatment principles Section 4 Macular disease Section 5 Retinal vascular diseases Section 6 Inflammatory disease Section 7 Other disease Section 8 Optic nerve VOLUME III: SURGICAL RETINA Section 1 What normally keeps the retina attached? Section 2 Retinal reattachments: Surgical principles and techniques Section 3 Special adjuncts to treatment Section 4 Complicated forms of retinal detachment Section 5 Vitreous surgery additional applications
DNA sequences and expression in Streptomyces lividans of an exoglucanase gene and an endoglucanase gene from Thermomonospora fusca (1993)

Two genes encoding cellulases E1 and E4 from Thermomonospora fusca have been cloned in Escherichia coli, and their DNA sequences have been determined. Both genes were introduced into Streptomyces lividans, and the enzymes were purified from the culture supernatants of transformants. E1 and E4 were expressed 18- and 4-fold higher, respectively, in S. lividans than in E. coli. Thin-layer chromatography of digestion products showed that E1 digests cellotriose, cellotetraose, and cellopentaose to cellobiose and a trace of glucose. E4 is poor at degrading cellotriose and cleaves cellopentaose to cellotetraose and glucose or cellotriose and cellobiose. It readily cleaves cellotetraose to cellobiose. E1 shows 59% identity to Cellulomonas fumi CenC in a 689-amino-acid overlap, and E4 shows 80% identity to the N terminus of C. fimi CenB in a 441-amino-acid overlap; all of these proteins are members of cellulase family E. Alignment of the amino acid sequences of Clostridium thermocellum celD, E1, E4, and four other members of family E demonstrates a clear relationship between their catalytic domains, although there is as little as 25% identity between some of them. Residues in celD that have been identified by site-directed mutagenesis and chemical modification to be important for catalytic activity are conserved in all seven proteins. The catalytic domains of E1 and E4 are not similar to those of T. fusca E2 or E5, but all four enzymes share similar cellulose-binding domains and have the same 14-bp inverted repeat upstream of their initiation codons. This sequence has been identified previously as the binding site for a protein that regulates induction.
Novel Peptide Inhibitors of Human Kallikrein 2 (2006)

Human kallikrein 2 (hK2) is a serine protease produced by the secretory epithelial cells in the prostate. Because hK2 activates several factors participating in proteolytic cascades that may mediate metastasis of prostate cancer, modulation of the activity of hK2 is a potential way of preventing tumor growth and metastasis. Furthermore, specific ligands for hK2 are potentially useful for targeting and imaging of prostate cancer and for assay development. We have used enzymatically active recombinant hK2 captured by a monoclonal antibody exposing the active site of the enzyme to screen phage display peptide libraries. Using libraries expressing 10 or 11 amino acids long linear peptides, we identified six different peptides binding to hK2. Three of these were shown to be specific and efficient inhibitors of the enzymatic activity of hK2 toward a peptide substrate. Furthermore, the peptides inhibited the activation of the proform of prostate-specific antigen by hK2. Amino acid substitution analyses revealed that motifs of six amino acids were required for the inhibitory activity. These peptides are potentially useful for treatment and targeting of prostate cancer.
Polymer Imprint Lithography with Molecular-Scale Resolution (2004)

We show that small diameter, single-walled carbon nanotubes can serve as templates for performing polymer imprint lithography with feature sizes as small as 2 nm − comparable to the size of an individual molecule. The angstrom level uniformity in the critical dimensions of the features provided by this unusual type of template provides a unique ability to investigate systematically the resolution of imprint lithography at this molecular scale. Collective results of experiments with several polymer formulations for the molds and the molded materials suggest that the density of cross-links is an important molecular parameter that influences the ultimate resolution in this process. Optimized materials enable reliable, repetitive patterning in this single nanometer range.
A Study of Rat Epididymal Sperm Adenosine 3′,5′-Monophosphate-Dependent Protein Kinases: Maturation Differences and Cellular Location (1985)

The photoaffinity analog [32P]8-N3 cAMP (8-azido adenosine 3',5'-monophosphate was used to analyze the membrane sidedness of rat sperm cAMP binding proteins during epididymal maturation. Evidence is presented here which supports the hypothesis that 35-45% of the regulatory subunits of the Type I and Type II cAMP-dependent protein kinases are readily available to externally added cyclic nucleotide. It was observed by sodium dodecyl sulfate gel electrophoresis (SDS-PAGE) and autoradiography that only two rat sperm proteins (Mr = 49K and 55K) were photolabeled which comigrated on gels with partially purified Type I and Type II regulatory subunits, respectively. Both of these photolabeled epididymal sperm proteins were saturated at physiological titers of [32P]8-N3cAMP and photoincorporation of [32P]8-N3 cAMP was specific since other SDS-resolvable sperm proteins did not photoincorporate the analog. Caput and cauda sperm protein photoincorporation could be effectively blocked by low levels of cAMP, but not by cGMP, ATP or GTP. Sperm epididymal maturation coincided with changes in the cAMP-dependent protein kinase subunits since cauda sperm contained more available Type II than did caput sperm. A subcellular analysis of cAMP-dependent protein kinase regulatory subunit in head and tail fractions was done for caput and cauda sperm and demonstrated that the tail fractions showed more photo-labeling of both Type I and II regulatory subunits than did the head fractions.
Slow Electron Cooling in Colloidal Quantum Dots (2008)

Hot electrons in semiconductors lose their energy very quickly (within picoseconds) to lattice vibrations. Slowing this energy loss could prove useful for more efficient photovoltaic or infrared devices. With their well-separated electronic states, quantum dots should display slow relaxation, but other mechanisms have made it difficult to observe. We report slow intraband relaxation (>1 nanosecond) in colloidal quantum dots. The small cadmium selenide (CdSe) dots, with an intraband energy separation of approximately 0.25 electron volts, are capped by an epitaxial zinc selenide (ZnSe) shell. The shell is terminated by a CdSe passivating layer to remove electron traps and is covered by ligands of low infrared absorbance (alkane thiols) at the intraband energy. We found that relaxation is markedly slowed with increasing ZnSe shell thickness.
Comparison of Two Methods for Estimating Absolute Risk of Prostate Cancer Based on Single Nucleotide Polymorphisms and Family History (2010)

Disease risk-associated single nucleotide polymorphisms (SNP) identified from genome-wide association studies have the potential to be used for disease risk prediction. An important feature of these risk-associated SNPs is their weak individual effect but stronger cumulative effect on disease risk. Several approaches are commonly used to model the combined effect in risk prediction, but their performance is unclear. We compared two methods to model the combined effect of 14 prostate cancer risk-associated SNPs and family history for the estimation of absolute risk for prostate cancer in a population-based case-control study in Sweden (2,899 cases and 1,722 controls). Method 1 weighs each risk allele equally using a simple method of counting the number of risk alleles, whereas method 2 weighs each risk SNP differently based on its odds ratio. We found considerable differences between the two methods. Absolute risk estimates from method 1 were generally higher than those of method 2, especially among men at higher risk. The difference in the overall discriminative performance, measured by area under the curve of the receiver operating characteristic, was small between method 1 (0.614) and method 2 (0.618), P = 0.20. However, the performance of these two methods in identifying high-risk individuals (2- or 3-fold higher than average risk), measured by positive predictive values, was higher for method 2 than for method 1. These results suggest that method 2 is superior to method 1 in estimating absolute risk if the purpose of risk prediction is to identify high-risk individuals.
Gateable Nanofluidic Interconnects for Multilayered Microfluidic Separation Systems (2003)

The extension of microfluidic devices to include three-dimensional fluidic networks allows complex fluidic and chemical manipulations but requires innovative methods to interface fluidic layers. Externally controllable interconnects, employing nuclear track-etched polycarbonate membranes containing nanometer-diameter capillaries, are described that produce hybrid three-dimensional fluidic architectures. Controllable nanofluidic transfer is achieved by controlling applied bias, polarity, and density of the immobile nanopore surface charge and the impedance of the nanocapillary array relative to the microfluidic channels. Analyte transport between vertically separated microchannels has three stable transfer levels, corresponding to zero, reverse, and forward bias. The transfer can even depend on the properties of the analyte being transferred such as the molecular size, illustrating the flexible character of the analyte transfer. In a specific analysis implementation, nanochannel array gating is applied to capillary electrophoresis separations, allowing selected separated components to be isolated for further manipulation, thereby opening the way for preparative separations at attomole analyte mass levels.
Circularly Polarized Electroluminescence from Liquid-Crystalline Chiral Polyfluorenes (2000)

Circularly polarized electroluminescence (CPEL) has potential application in optical data storage and processing. It was recently discovered that CPEL could be generated from chiral-substituted, conjugated polymers. These authors have synthesized a range of polyfluorenes (e.g., see Figure) that form liquid crystals and emit bluish light with a significant (200 times greater than in the first report) circularly polarized component.
Production planning in flexible manufacturing systems using an expert system (1994)

This paper deals with generating a near optimal production plan for Flexible Manufacturing Systems (FMS). The production plan is one of the most important aspects for the efficient operation of FMS. First, we define the scope of the production planning problem. Then we develop a set of production rules to be used in an expert system approach to the problem. The expert system has been implemented in Guru 2.0, an expert system development tool. The performance of this expert system is evaluated using a set of small to medium-size problem data. Based on the test results, the expert system approach to the solution of the production planning problem appears to be an efficient method.
Determination of trace-gas amounts in plumes by the use of orthogonal digital filtering of thermal-emission spectra (1996)

The thermal emission of gases in a plume can be measured by a Fourier-transform spectrometer that is located some distance from the plume. In order to measure quantitatively the amount of a particular gas of interest, in general a large spectrally structured background must be removed. Differencing techniques, in which a measured background spectrum is subtracted from a measured spectrum believed to contain a target, often do not remove background spectral features adequately. The inadequacy of two-spectrum differencing techniques is due to the spatial and the temporal variations in a scene. We present a method by which to reduce spatial and temporal spectral clutter to instrument random noise, allowing the measurement of gas amounts in an effluent plume. The method is applied to simulated data and field data to show its effectiveness.
Application of repeated measures designs in environmental impact and monitoring studies (1993)

Abstract Traditional environmental studies have employed sampling at different times, but based on re‐randomized ‘replicate’ samples taken at each time. For example, in a 4 year monitoring study of near‐shore marine benthic communities there might be three box cores collected annually at each of three depths along each of three transects. Repeated measures designs, long used in medicine and the social sciences, are based on resampling replicates (e.g. sites) at a series of times. In such designs spatial sampling variability is not used for tests of environmental impact. Error for such tests is based on variability of time trends among similar sites (similar with respect to impact). For example in a tropical oil spill study five oiled and five unoiled coral reefs were studied over 5 years. Error for tests of oil impact was based on variability among reefs (within degree‐of‐oiling category) in the year‐to‐year trends of biological response variables. It was not based on variability among field samples within reefs at given times. The two approaches (univariate and multivariate) to repeated measures analysis of variance are described. The pros and cons of each are discussed, as are the assumptions and consequences of their violations. Emphasis is especially placed on the adequacy of error degrees of freedom in the two approaches, and some exploration of power to detect impact is presented. Examples of application of repeated measures designs to various impact and monitoring studies are presented and discussed, including (i) interpretation of significant effects; (ii) decomposition of effects by contrasts (e.g. before vs after impact); and (iii) modelling time trends by polynomial and cosine functions.
Antibody library selection by the β-lactamase protein fragment complementation assay (2008)

Protein fragment complementation assay (PCA) is based on the interaction between two protein partners (e.g. target antigen and antibody), which are genetically fused to the two halves of a dissected marker protein. Binding of the two partners reassembles the marker protein and hence reconstitutes its activity. In this work we have developed the first application of beta-lactamase-based PCA for the isolation of single chain Fv fragments (scFvs) binding to the human receptor RON from a naïve library. Specific scFvs with the ability to immunoprecipitate could be isolated after a single round of PCA selection from an scFv repertoire previously pre-selected by phage display. Furthermore, the PCA was used to successfully map the epitopes recognized by the selected scFvs by screening them against a small library of random RON fragments.
Psychological effects of a drug that facilitates brain AMPA receptors (1996)

The effects of 1-(quinoxalin-6-ylcarbonyl)piperidine (CX516), a centrally active compound that facilitates AMPA receptor-mediated synaptic responses, were tested in human subjects. Separate tests of delayed recall were given prior to and nearly 3 h after administration of placebo (n = 12) or drug (n = 36). Control subjects exhibited poorer performance in the second session than in the first while subjects given 600-1200 mg of the drug did not. There were no pre- vs post-treatment differences in immediate recall in either group. The drug did not reliably affect self-assessment scores for any of several psychological variables but did disrupt the normally present correlations for within-subject changes in the variables. These results suggest that AMPA receptor modulators may (1) improve memory under some circumstances and (2) produce psychological effects that are subtle or not related to specific mood states.
Natural-Fracture Reactivation in Shale Gas Reservoir and Resulting Microseismicity (2015)

Summary A geomechanical and fluid-flow coupled model was developed to simulate natural-fracture-network reactivation during hydraulic-fracturing treatments in shale gas reservoirs. The fractures were modelled using the continuum approach in a commercial finite-difference code, labeled the “softening ubiquitous joints” model, with randomly distributed strength parameters to describe heterogeneity along the fracture plane. The models allow for intersecting fractures to represent realistic scenarios. The permeability values in the fractures are dynamically updated during the simulations together with the reversible tensile opening because of elastic response and irreversible shear opening caused by plastic deformations. The reactivation of the fracture network resulted in high permeability along these fracture planes. The developed model can predict microseismic events caused by slip on the fracture planes. The magnitude levels of these microseismic events are comparable with the levels observed in events monitored by use of geophone arrays during hydraulic-fracturing treatments for different shale gas reservoirs.
Childhood adversity and adult psychiatric disorder in the US National Comorbidity Survey (1997)

The existence of strong clustering among childhood adversities and lifetime co-morbidity among adult disorders means that caution is needed in interpreting the results of previous single-adversity single-disorder studies as documenting unique effects of specific childhood adversities on specific adult disorders. Future studies need to assess a broader range of adversities and disorders and to explore the existence and effects of commonly occurring adversity clusters. Replication is needed to verify that the effects of childhood adversities are mostly on first onset rather than on the creation of vulnerabilities that lead to increased risk of persistence.
Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes (2002)

Recent investigation has focused on identifying signaling pathways that inhibit cardiac hypertrophy, a major risk factor for cardiovascular morbidity and mortality. In this context, nitric oxide (NO), signaling via cGMP and cGMP-dependent protein kinase type I (PKG I), has been recognized as a negative regulator of cardiac myocyte (CM) hypertrophy. However, the underlying mechanisms are poorly understood. Here, we show that PKG I inhibits CM hypertrophy by targeting the calcineurin-NFAT signaling pathway. Calcineurin, a Ca2+-dependent phosphatase, promotes hypertrophy in part by activating NFAT transcription factors which induce expression of hypertrophic genes, including brain natriuretic peptide (BNP). Activation of PKG I by NO/cGMP in CM suppressed NFAT transcriptional activity, BNP induction, and cell enlargement in response to alpha(1)-adrenoreceptor stimulation but not in response to adenoviral expression of a Ca2+-independent, constitutively active calcineurin mutant, thus demonstrating NO-cGMP-PKG I inhibition of calcineurin-NFAT signaling upstream of calcineurin. PKG I suppressed single L-type Ca2+-channel open probability, [Ca2+]i transient amplitude, and, most importantly, L-type Ca2+-channel current-induced NFAT activation, indicating that PKG I targets Ca2+-dependent steps upstream of calcineurin. Adenoviral expression of PKG I enhanced NO/cGMP inhibitory effects upstream of calcineurin, confirming that PKG I mediates NO/cGMP inhibition of calcineurin-NFAT signaling. In CM overexpressing PKG I, NO/cGMP also suppressed BNP induction and cell enlargement but not NFAT activation elicited by constitutively active calcineurin, which is consistent with additional, NFAT-independent inhibitory effect(s) of PKG I downstream of calcineurin. Inhibition of calcineurin-NFAT signaling by PKG I provides a framework for understanding how NO inhibits cardiac myocyte hypertrophy.