gebhart/patrepeval huggingface dataset:
What are good apertures for defocus deblurring? (2009)

In recent years, with camera pixels shrinking in size, images are more likely to include defocused regions. In order to recover scene details from defocused regions, deblurring techniques must be applied. It is well known that the quality of a deblurred image is closely related to the defocus kernel, which is determined by the pattern of the aperture. The design of aperture patterns has been studied for decades in several fields, including optics, astronomy, computer vision, and computer graphics. However, previous attempts at designing apertures have been based on intuitive criteria related to the shape of the power spectrum of the aperture pattern. In this paper, we present a comprehensive framework for evaluating an aperture pattern based on the quality of deblurring. Our criterion explicitly accounts for the effects of image noise and the statistics of natural images. Based on our criterion, we have developed a genetic algorithm that converges very quickly to near-optimal aperture patterns. We have conducted extensive simulations and experiments to compare our apertures with previously proposed ones.
Matrix Metalloproteinases and Abdominal Aortic Aneurysms: A Potential Therapeutic Target (1998)

Abdominal aortic aneurysm (AAA) is a leading cause of death in the United States, and there is no effective treatment in the early course of disease. Therapy to retard or reverse aneurysmal growth requires an understanding of the underlying vascular pathology. Recent research has indicated that enzymatic degradation of structural matrix proteins plays a large role in the formation of AAAs. Specifically, many studies have implicated a family of matrix degrading enzymes, known as matrix metalloproteinases (MMPs), as vital factors in the disease. Although AAA was once thought to be purely secondary to atherosclerosis, investigators have demonstrated various differences between the diseases in both levels and distribution of MMPs, suggesting independent mechanisms. Experimental models have shown that inhibition of these proteinases may slow aortic wall matrix breakdown. The purpose of this article is to review the current literature regarding the role of individual MMPs in AAA, including their complex regulatory mechanisms and possible cellular sources, the importance of MMPs as a potential therapeutic target in the prevention and treatment of AAA, and their inhibition using novel pharmacologic interventions in animal models.
A New Class of Ruthenium Carbene Complexes: Synthesis and Structures of Highly Efficient Catalysts for Olefin Metathesis (1999)

Cationic Ru<sup>II</sup> carbene complexes with tBu<sub>2</sub> PCH<sub>2</sub> PtBu<sub>2</sub> (dtbpm) as a chelating ligand, which are accessible by chloride abstraction from neutral precursors [(κ<sup>2</sup> -dtbpm)Cl<sub>2</sub> Ru=CHR] with trimethylsilyl triflate, are established as highly efficient ring opening metathesis polymerization catalysts (see scheme). Solv=solvent.
Role of Asparagine-linked Oligosaccharides in Protein Folding, Membrane Targeting, and Thyrotropin and Autoantibody Binding of the Human Thyrotropin Receptor (1998)

The amino-terminal ectodomain of thyrotropin (TSH) receptor (TSHR) is heavily glycosylated with asparagine-linked (N-linked) oligosaccharides. The present studies were designed to evaluate how acquisition and processing of N-linked oligosaccharides play a role in the functional maturation of human TSHR. A glycosylation inhibitor tunicamycin, which inhibits the first step of N-linked glycosylation (acquisition of N-linked oligosaccharides), and a series of mutant Chinese hamster ovary (CHO)-Lec cells defective in the different steps of glycosylation processing were used. Inhibition of acquisition of N-linked oligosaccharides by tunicamycin treatment in CHO cells stably expressing TSHR produced nonglycosylated TSHR, which was totally nonfunctional. In contrast, all of the TSHRs synthesized in mutant CHO-Lec1, 2, and 8 cells (mannose-rich, sialic acid-deficient, and galactose-deficient oligosaccharides, respectively) bound TSH and produced cAMP in response to TSH with an affinity and an EC50 similar to those in TSHR expressed in parental CHO cells (CHO-TSHR; sialylated oligosaccharides). However, Lec1-TSHR and Lec2-TSHR were not efficiently expressed on the cell surface, whereas the expression levels of Lec8-TSHR and CHO-TSHR were essentially identical. All of the TSHRs expressed in CHO-Lec cells cleaved into two subunits. Finally, anti-TSHR autoantibodies from Graves' patients interacted with all of the TSHRs harboring different oligosaccharides to a similar extent. These data demonstrate that acquisition and processing of N-linked oligosaccharides of TSHR appear to be essential for correct folding in the endoplasmic reticulum and for cell surface targeting in the Golgi apparatus. We also show that complex type carbohydrates are not crucially involved in the interaction of TSHR with TSH and anti-TSHR autoantibodies.
Efficient coding of LPC parameters by temporal decomposition (2005)

This paper describes a method for efficient coding of LPC log area parameters. It is now well recognized that sample-by-sample quantization of LPC parameters is not very efficient in minimizing the bit rate needed to code these parameters. Recent methods for reducing the bit rate have used vector and segment quantization methods. Much of the past work in this area has focussed on efficient coding of LPC parameters in the context of vocoders which put a ceiling on achievable speech quality. The results from these studies cannot be directly applied to synthesis of high quality speech. This paper describes a different approach to efficient coding of log area parameters. Our aim is to determine the extent to which the bit rate of LPC parameters can be reduced without sacrificing speech quality. Speech events occur generally at non-uniformly spaced time intervals. Moreover, some speech events are slow while others are fast. Uniform sampling of speech parameters is thus not efficient. We describe a non-uniform sampling and interpolation procedure for efficient coding of log area parameters. A temporal decomposition technique is used to represent the continuous variation of these parameters as a linearly-weighted sum of a number of discrete elementary components. The location and length of each component is automatically adapted to speech events. We find that each elementary component can be coded as a very low information rate signal.
Nanomaterials‐based electrochemical immunosensors for proteins (2012)

For this special issue on 90 years of polarography, the following personal account describes how my early research in electrochemistry and polarography in the laboratory of Prof. Petr Zuman led to a major research effort in the determination of proteins for cancer detection and monitoring. It reviews the very recent history of nanoparticle labels and multiplexed detection in protein immunosensors. It then describes our journey of discovery that has led to ultrasensitive protein immunosensors achieved by combining nanostructured electrodes with particles labeled with up to ½ million enzymes that can detect down to as little as 1 fg mL(-1) protein in diluted serum. Our most mature multiple protein detection system is a microfluidic device with eight sensors coated with 5-nm gold nanoparticles that uses off-line protein detection with heavily labeled magnetic particles. This approach has led to reliable sub pg mL(-1) detection limits for multiple proteins, provides excellent correlation with referee ELISA methods, and is currently being used for validation of panels of biomarkers for oral and prostate cancer. The article ends with a section on future perspectives.
Inhibition of rat cervical epithelial cell growth by heparin and its reversal by EGF (1985)

The effects of heparin on the in vitro growth of rat cervical epithelial cells were examined. Heparin was found to inhibit in a dose dependent fashion the log-phase growth of rat cervical epithelial cells (RCEC) grown in the absence of medium supplements. An inhibition of growth is observed at concentrations as low as 500 ng/ml and 50% inhibition of growth occurs at a concentration of 5 micrograms/ml. The growth inhibitory activity of heparin is independent of anticoagulant activity since three separate non-anticoagulant preparations of heparin all inhibit growth. Other glycosaminoglycans including chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, hyaluronic acid, and keratin sulfate do not inhibit the growth of rat cervical epithelial cells. The ability of heparin to inhibit the log-phase growth of rat cervical epithelial cells is dependent on the composition of the medium in which the cells are grown. The addition of greater than or equal to 7.5 ng/ml epidermal growth factor to epithelial cultures blocks the growth inhibitory activity of heparin. These results suggest that components of the extracellular matrix modulate the growth responses of epithelial cells and may be important in regulating cellular proliferation in normal and pathological states.
Restriction of plasmid DNA during transformation but not conjugation in Neisseria gonorrhoeae (1988)

Neisseria gonorrhoeae strains WR302 and PGH3-2 were characterized with respect to their restriction-modification phenotype. WR302 DNA was cleaved by HaeIII, indicating the lack of methylation at the GGCC sequence. PGH3-2 produced NgoSI (an isoschizomer of NgoII). WR302 produced a restriction enzyme with a recognition sequence different from that of NgoI, NgoII, or NgoIII. Plasmid pFT180 isolated from WR302 was unable to transform PGH3-2, whereas plasmid pFT180 isolated from PGH3-2 was able to transform PGH3-2 at a very high frequency. When plasmid pFT180 isolated from WR302 was methylated in vitro with meth M. HaeIII, this plasmid was able to transform PGH3-2. NgoSI was able to restrict WR302 DNA in vitro, whereas it was incapable of restricting PGH3-2 DNA in vitro. When the self-transmissible R factor pFT6 was mobilized from WR302 to PGH3-2 by conjugation, a 1-order-of-magnitude difference in transfer frequencies was observed, as compared with an isogenic cross. The data indicate that host-mediated restriction can prevent the gonococcus from acquiring DNA via transformation but not via conjugation.
Studies of respiratory disease in random-source laboratory dogs: viral infections in unconditioned dogs. (1979)

A prospective study was conducted to identify the viruses causing respiratory diseases in unconditioned, random-source dogs. During the quarantine period, respiratory disease occurred in 86 of 167 (52%) dogs, and 34 (21%) died. Most affected dogs had a distemper-like illness which required extensive and prolonged care. Histopathologic studies confirmed the diagnosis of canine distemper in 10 of 12 (83%) fatal infections examined. Sixty-seven of 91 (74%) dogs which arrived without canine distemper antibody became ill, and 30 (32%) died. In contrast, only 16 of 67 (24%) dogs with canine distemper antibody had respiratory disease, and only 3 (4%) died. Parainfluenza SV5 and canine adenovirus--type II were recovered from 27 of 54 and 22 of 54 sick dogs, respectively. Canine herpesviruses, canine coronaviruses, and canine parvoviruses were less frequently isolated. Increased antibody titers to SV5 were found consistently, and rises in titer to the other viruses were demonstrated. Many of the sick dogs were infected with two or more viruses. Although several viral agents were detected during these epizootics, prevention of canine distemper appeared to be the key to controlling severe, prolonged, and often fatal respiratory disease.
Efficient recovery of dysferlin deficiency by dual adeno-associated vector-mediated gene transfer (2010)

Deficiency of the dysferlin protein presents as two major clinical phenotypes: limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Dysferlin is known to participate in membrane repair, providing a potential hypothesis to the underlying pathophysiology of these diseases. The size of the dysferlin cDNA prevents its direct incorporation into an adeno-associated virus (AAV) vector for therapeutic gene transfer into muscle. To bypass this limitation, we split the dysferlin cDNA at the exon 28/29 junction and cloned it into two independent AAV vectors carrying the appropriate splicing sequences. Intramuscular injection of the corresponding vectors into a dysferlin-deficient mouse model led to the expression of full-length dysferlin for at least 1 year. Importantly, systemic injection in the tail vein of the two vectors led to a widespread although weak expression of the full-length protein. Injections were associated with an improvement of the histological aspect of the muscle, a reduction in the number of necrotic fibers, restoration of membrane repair capacity and a global improvement in locomotor activity. Altogether, these data support the use of such a strategy for the treatment of dysferlin deficiency.
Modulation of neuroblastoma cell differentiation by the extracellular matrix (1992)

The effect of a complex in vitro synthesized extracellular matrix (ECM) and its components on growth and phenotypical differentiation of a human neuroblastoma (NB) cell line (HTLA230) was investigated. Rat smooth-muscle-cell (R22CIF)-derived ECM composed of collagen, glycoproteins, and glycosaminoglycans (GAGs) promoted spontaneous neurite outgrowth of HTLA230 cells but did not alter their growth kinetic or cloning efficiency as compared with cells seeded onto gelatin-coated dishes. The matrix significantly enhanced, quantitatively and qualitatively, the responsiveness of HTLA230 cells to retinoic acid (RA), and a substantially reduced growth rate was observed in the presence of RA with cells grown on the ECM. Biochemical modification of the composition of the R22CIF-matrix by trypsin digestion and/or high-salt extraction (4 M guanidinium) demonstrated that the ratio of chondroitin sulfate to hyaluronic acid (HA) present in the ECM determines the capacity of the matrix to promote NB differentiation. A human fibroblast (T-1)-derived ECM, which has a biochemical composition of the GAG component similar to that of the trypsinized R22CIF-matrix, but which has a high amount of glycoproteins, confirmed these results. Nerve-growth-factor (NGF)-induced differentiation in a variant HTLA 230 cell line was inhibited when cells were grown on an ECM with a low ratio of chondroitin sulfate/HA. The composition of the ECM thus modulates the responsiveness to various differentiation-inducing agents and alters the phenotype of NB cells.
Improving the DNA specificity and applicability of base editing through protein engineering and protein delivery (2017)

We recently developed base editing, a genome-editing approach that enables the programmable conversion of one base pair into another without double-stranded DNA cleavage, excess stochastic insertions and deletions, or dependence on homology-directed repair. The application of base editing is limited by off-target activity and reliance on intracellular DNA delivery. Here we describe two advances that address these limitations. First, we greatly reduce off-target base editing by installing mutations into our third-generation base editor (BE3) to generate a high-fidelity base editor (HF-BE3). Next, we purify and deliver BE3 and HF-BE3 as ribonucleoprotein (RNP) complexes into mammalian cells, establishing DNA-free base editing. RNP delivery of BE3 confers higher specificity even than plasmid transfection of HF-BE3, while maintaining comparable on-target editing levels. Finally, we apply these advances to deliver BE3 RNPs into both zebrafish embryos and the inner ear of live mice to achieve specific, DNA-free base editing in vivo.
Ten-year outcome of patients with advanced epithelial ovarian carcinoma treated with cisplatin-based multimodality therapy. (1992)

Our multimodality treatment program was noncurative for the majority of the patients. Innovative therapies are needed before we can hope to cure such disease.
Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin (2015)

The 30-item revised Mystical Experience Questionnaire (MEQ30) was previously developed within an online survey of mystical-type experiences occasioned by psilocybin-containing mushrooms. The rated experiences occurred on average eight years before completion of the questionnaire. The current paper validates the MEQ30 using data from experimental studies with controlled doses of psilocybin. Data were pooled and analyzed from five laboratory experiments in which participants (n=184) received a moderate to high oral dose of psilocybin (at least 20 mg/70 kg). Results of confirmatory factor analysis demonstrate the reliability and internal validity of the MEQ30. Structural equation models demonstrate the external and convergent validity of the MEQ30 by showing that latent variable scores on the MEQ30 positively predict persisting change in attitudes, behavior, and well-being attributed to experiences with psilocybin while controlling for the contribution of the participant-rated intensity of drug effects. These findings support the use of the MEQ30 as an efficient measure of individual mystical experiences. A method to score a "complete mystical experience" that was used in previous versions of the mystical experience questionnaire is validated in the MEQ30, and a stand-alone version of the MEQ30 is provided for use in future research.
Telomere Length in Epidemiology: A Biomarker of Aging, Age-Related Disease, Both, or Neither? (2013)

Telomeres are nucleoprotein caps flanking DNA. They are shortened by cell division and oxidative stress and are lengthened by the enzyme telomerase and DNA exchange during mitosis. Short telomeres induce cellular senescence. As an indicator of oxidative stress and senescence (2 processes thought to be fundamental to aging), telomere length is hypothesized to be a biomarker of aging. This hypothesis has been tested for more than a decade with epidemiologic study methods. In cross-sectional studies, researchers have investigated whether leukocyte telomere length (LTL) is associated with demographic, behavioral, and health variables. In prospective studies, baseline LTL has been used to predict mortality and occasionally other adverse health outcomes. Conflicting data have generated heated debate about the value of LTL as a biomarker of overall aging. In this review, we address the epidemiologic data on LTL and demonstrate that shorter LTL is associated with older age, male gender, Caucasian race, and possibly atherosclerosis; associations with other markers of health are equivocal. We discuss the reasons for discrepancy across studies, including a detailed review of methods for measuring telomere length as they apply to epidemiology. Finally, we conclude with questions about LTL as a biomarker of aging and how epidemiology can be used to answer these questions.
CPPsite: a curated database of cell penetrating peptides (2012)

Delivering drug molecules into the cell is one of the major challenges in the process of drug development. In past, cell penetrating peptides have been successfully used for delivering a wide variety of therapeutic molecules into various types of cells for the treatment of multiple diseases. These peptides have unique ability to gain access to the interior of almost any type of cell. Due to the huge therapeutic applications of CPPs, we have built a comprehensive database 'CPPsite', of cell penetrating peptides, where information is compiled from the literature and patents. CPPsite is a manually curated database of experimentally validated 843 CPPs. Each entry provides information of a peptide that includes ID, PubMed ID, peptide name, peptide sequence, chirality, origin, nature of peptide, sub-cellular localization, uptake efficiency, uptake mechanism, hydrophobicity, amino acid frequency and composition, etc. A wide range of user-friendly tools have been incorporated in this database like searching, browsing, analyzing, mapping tools. In addition, we have derived various types of information from these peptide sequences that include secondary/tertiary structure, amino acid composition and physicochemical properties of peptides. This database will be very useful for developing models for predicting effective cell penetrating peptides. Database URL: http://crdd.osdd.net/raghava/cppsite/.
Challenges and opportunities in the targeting of fibroblast growth factor receptors in breast cancer (2012)

Activation of the fibroblast growth factor receptor pathway is a common event in many cancer types. Here we review the role of fibroblast growth factor receptor signalling in breast cancer, from SNPs in FGFR2 that influence breast cancer risk and SNPs in FGFR4 that associate with breast cancer prognosis, and potential therapeutic targets such as receptor amplification and aberrant autocrine and paracrine ligand expression. We discuss the multiple therapeutic strategies in preclinical and clinical development and the current and future challenges to successfully targeting this pathway in cancer.
Isolation and characterization of a second RNase H (RNase HII) of Escherichia coli K-12 encoded by the rnhB gene. (1990)

An additional RNase H (EC 3.1.26.4), RNase HII, has been isolated from Escherichia coli K-12. By screening a library of E. coli DNA for clones that suppressed RNase H deficiency of an E. coli rnh mutant, a clone was obtained that produced a protein with RNase H activity. The overexpressed RNase HIII protein in E. coli was purified to near homogeneity and exhibited a strong preference for the ribonucleotide moiety of RNA-DNA hybrid as substrate. The terminal 11 amino acids were determined and were identical to those predicted from the nucleotide sequence. The rnhB gene, which encodes RNase HII, was distinct from rnhA by its map position (4.5 min on E. coli genetic map, between lpxB and dnaE) and by the lack of significant amino acid sequence similarity. The presence of a second RNase H in E. coli indicates that multiple RNase H genes per genome is a general feature of a general feature of a wide variety of organisms.
Oltipraz: Clinical opportunities for cancer chemoprevention (1995)

Oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione], originally developed as an antischistosomal agent, protects against chemical carcinogenesis in lung, trachea, forestomach, small intestine, colon, breast, skin, liver and urinary bladder in rodents. Oltipraz induces electrophile detoxication enzymes, resulting in diminished carcinogen-DNA adduct formation and reduced cytotoxicity, an important component of anticarcinogenic actions. Phase I trials of this drug have been recently conducted in the United States and indicate that the maximum tolerated dose is about 125 mg/day over a six-month period. Grade I/II dose-limiting toxicities included photosensitivity/heat intolerance, gastrointestinal, and neurologic toxicities. Ongoing studies are monitoring relationships between dose scheduling, drug plasma concentrations and pharmacodynamic action. Subsequent trials with this agent might most appropriately target individuals at high risk for occupational or environmental exposures to genotoxic carcinogens. Towards this end, a randomized, placebo-controlled Phase II study is planned for people at high risk for exposure to aflatoxins and development of hepatocellular carcinoma. Modulation of biomarkers reflecting the biologically effective dose of aflatoxin will serve as study endpoints.