gebhart/patrepeval huggingface dataset:
The Efficiency and Specificity of Apurinic/Apyrimidinic Site Bypass by Human DNA Polymerase η and Sulfolobus solfataricus Dpo4 (2003)

One of the most common DNA lesions arising in cells is an apurinic/apyrimidinic (AP) site resulting from base loss. Although a template strand AP site impedes DNA synthesis, translesion synthesis (TLS) DNA polymerases can bypass an AP site. Because this bypass is expected to be highly mutagenic because of loss of base coding potential, here we quantify the efficiency and the specificity of AP site bypass by two Y family TLS enzymes, Sulfolobus solfataricus DNA polymerase 4 (Dpo4) and human DNA polymerase eta (Pol eta). During a single cycle of processive DNA synthesis, Dpo4 and Pol eta bypass synthetic AP sites with 13-30 and 10-13%, respectively, of the bypass efficiency for undamaged bases in the same sequence contexts. These efficiencies are higher than for the A family, exonuclease-deficient Klenow fragment of Escherichia coli DNA polymerase I. We then determined AP site bypass specificity for complete bypass, requiring insertion or misalignment at the AP site followed by multiple incorporations using the aberrant primer templates. Although Dpo4, Pol eta, and Klenow polymerase have different fidelity when copying undamaged DNA, bypass of AP sites lacking A or G by all three polymerases is nearly 100% mutagenic. The majority (70-80%) of bypass events made by all three polymerases are insertion of dAMP opposite the AP site. Single base deletion errors comprise 10-25% of bypass events, with other base insertions observed at lower rates. Given that mammalian cells contain five polymerases implicated in TLS, and given that a large number of AP sites are generated per mammalian cell per day, even moderately efficient AP site bypass could be a source of substitution and frameshift mutagenesis in vivo.
The growth of cutaneous T-cell lymphoma is stimulated by immature dendritic cells (2002)

In the initial stage of cutaneous T-cell lymphoma (CTCL), proliferating CTCL cells are concentrated in the epidermis in close association with an immature dendritic cell (DC), the Langerhans cell. Because long-term in vitro culture of CTCL cells has proven difficult, the in vivo association with the major antigen-presenting cell (APC) of the epidermis has been postulated to play a role in directly stimulating the clonal T-cell proliferation. We report that CTCL cells can be reproducibly grown in culture for 3 months when cocultured with immature DCs. CTCL cells retain the phenotype and genotype of the initial malignant clone, whereas the APCs are a mixture of immature and mature DCs. CTCL cell and DC survival was dependent on direct membrane contact. Growth was inhibited by antibodies that bound to the T-cell receptor (TCR) or interfered with the interaction of CD40 with its ligand on the CTCL cell. Addition of antibody to CD3 or the clonotypic TCR caused rapid CTCL cell apoptosis followed by engulfment by avidly phagocytic immature DCs and subsequent DC maturation. The opportunity to study CTCL cells and immature DCs for prolonged periods will facilitate studies of tumor cell biology and will allow investigation of the intriguing hypothesis that CTCL cell growth is driven through TCR recognition of class II–presented self-peptides. In addition, the culture of CTCL cells will permit evaluation of therapies in vitro before clinical intervention, thereby improving safety and efficacy.
Ziracin, a Novel Oligosaccharide Antibiotic. (2000)

Ziracin is produced by Micromonospora carbonacea and is highly active against Gram-positive bacteria. In particular it is highly active against methicillin resistant staphylococci and vancomycin resistant enterococci. Ziracin, C71H97NO38Cl2, contains two orthoester linkages, a nitro sugar, a methylene dioxy group, two aromatic ester residues and thirty five centres of assymmetries. In this paper a brief description of the structural elucidation of ziracin is presented along with the chemical modification of the antibiotic which has led to the identification of several potent antibacterials.
Design and implementation of a caching system for streaming media over the Internet (2002)

Congested networks and overloaded servers resulting from the ever growing number of Internet users contribute to the lack of good quality video streaming over the Internet. We propose a design and implementation of a caching system for streaming media, which utilizes its local memory and disk resources to reduce network and server load, while also improving the video and audio quality perceived by end users. In particular, request aggregation, prefix caching and rate control mechanisms are used in the system design. The effectiveness of the system is validated through performance results from prototype implementation. As expected, the caching system reduces network and server load and improves client start-up latency.
Determination of the absolute configuration of a key tricyclic component of a novel vasopressin receptor antagonist by use of vibrational circular dichroism (2002)

We present the results of a study using vibrational circular dichroism (VCD) for (+)-1, which furnished an unambiguous determination of its absolute configuration as S. The most abundant conformation of (+)-1 in CDCl(3) solution was also established.
Modal expansions for resonance scattering phenomena (1965)

This paper very briefly reviews certain approaches commonly used to predict scattering in the region between those amenable to either high or low frequency approximations. As an alternative to extensions of such approximations into this so-called "resonance region," the suggestion is made that the concept of modal expansions of fields be investigated. The existence of such characteristic modes is reasoned heuristically and certain speculations are presented concerning their properties and their determination.
O6-(Alkyl/aralkyl)guanosine and 2‘-Deoxyguanosine Derivatives:  Synthesis and Ability To Enhance Chloroethylnitrosourea Antitumor Action (1997)

A series of O6-(alkyl/aralkyl)guanosines and 2'-deoxyguanosine analogs extended to peracetyl and N2-acetyl derivatives, potentially water soluble, was synthesized. Each was associated with N'-(2-chloroethyl)-N-[2-(methylsulfonyl)ethyl]-N'-nitrosourea for in vitro evaluation on M4Beu melanoma cells of their ability to enhance the cytotoxic effect of this chloroethylnitrosourea, which is frequently reduced by repairs performed by O6-alkylguanine-DNA-alkyltransferase. Structure-activity analysis revealed that (i) benzyl and 4-halobenzyl are the O6-substituents required to afford a significant activity, (ii) 2'-deoxyguanosine derivatives demonstrate greater potency than guanosine analogs, (iii) acetylation, especially at the N2 position, generally results in compounds with moderate ability but may prevent incorporation of such nucleosides into DNA. Accordingly, O6-(4-iodobenzyl)-N2-acetylguanosine (3b) and O6-benzylperacetyl-2'-deoxyguanosine (2a), as well as O6-benzyl-N2-acetylguanosine (1b) and O6-benzyl-N2-acetyl-2'-deoxyguanosine (2b), by far the most water soluble, exhibit a good profile for further in vivo trials by the intravenous route.
Escherichia coli S-adenosylhomocysteine/5′-methylthioadenosine nucleosidase. Purification, substrate specificity and mechanism of action (1985)

S-Adenosylhomocysteine/5'-methylthioadenosine nucleosidase (EC 3.2.2.9) was purified to homogeneity from Escherichia coli to a final specific activity of 373 mumol of 5'-methylthioadenosine cleaved/min per mg of protein. Affinity chromatography on S-formycinylhomocysteine-Sepharose is the key step of the purification procedure. The enzyme, responsible for the cleavage of the glycosidic bond of both S-adenosylhomocysteine and 5'-methylthioadenosine, was partially characterized. The apparent Km for 5'-methylthioadenosine is 0.4 microM, and that for S-adenosylhomocysteine is 4.3 microM. The maximal rate of cleavage of S-adenosylhomocysteine is approx. 40% of that of 5'-methylthioadenosine. Some 25 analogues of the two naturally occurring thioethers were studied as potential substrates or inhibitors of the enzyme. Except for the analogues modified in the 5'-position of the ribose moiety or the 2-position of the purine ring, none of the compounds tested was effective as a substrate. Moreover, 5'-methylthioformycin, 5'-chloroformycin, S-formycinylhomocysteine, 5'-methylthiotubercidin and S-tubercidinylhomocysteine were powerful inhibitors of the enzyme activity. The results obtained allow the hypothesis of a mechanism of enzymic catalysis requiring as a key step the protonation of N-7 of the purine ring.
Autodisplay: one-component system for efficient surface display and release of soluble recombinant proteins from Escherichia coli (1997)

The immunoglobulin A protease family of secreted proteins are derived from self-translocating polyprotein precursors which contain C-terminal domains promoting the translocation of the N-terminally attached passenger domains across gram-negative bacterial outer membranes. Computer predictions identified the C-terminal domain of the Escherichia coli adhesin involved in diffuse adherence (AIDA-I) as a member of the autotransporter family. A model of the beta-barrel structure, proposed to be responsible for outer membrane translocation, served as a basis for the construction of fusion proteins containing heterologous passengers. Autotransporter-mediated surface display (autodisplay) was investigated for the cholera toxin B subunit and the peptide antigen tag PEYFK. Up to 5% of total cellular protein was detectable in the outer membrane as passenger autotransporter fusion protein synthesized under control of the constitutive P(TK) promoter. Efficient presentation of the passenger domains was demonstrated in the outer membrane protease T-deficient (ompT) strain E. coli UT5600 and the ompT dsbA double mutant JK321. Surface exposure was ascertained by enzyme-linked immunosorbent assay, immunofluorescence microscopy, and immunogold electron microscopy using antisera specific for the passenger domains. In strain UT2300 (ompT+), the passenger domains were released from the cell surface by the OmpT protease at a novel specific cleavage site, R / V. Autodisplay represents a useful tool for future protein translocation studies with interesting biotechnological possibilities.
Learning Fast Approximations of Sparse Coding (2010)

In Sparse Coding (SC), input vectors are reconstructed using a sparse linear combination of basis vectors. SC has become a popular method for extracting features from data. For a given input, SC minimizes a quadratic reconstruction error with an L1 penalty term on the code. The process is often too slow for applications such as real-time pattern recognition. We proposed two versions of a very fast algorithm that produces approximate estimates of the sparse code that can be used to compute good visual features, or to initialize exact iterative algorithms. The main idea is to train a non-linear, feed-forward predictor with a specific architecture and a fixed depth to produce the best possible approximation of the sparse code. A version of the method, which can be seen as a trainable version of Li and Osher’s coordinate descent method, is shown to produce approximate solutions with 10 times less computation than Li and Osher’s for the same approximation error. Unlike previous proposals for sparse code predictors, the system allows a kind of approximate “explaining away ” to take place during inference. The resulting predictor is differentiable and can be included into globallytrained recognition systems. 1.
Engineering and optimising deaminase fusions for genome editing (2016)

Abstract Precise editing is essential for biomedical research and gene therapy. Yet, homology-directed genome modification is limited by the requirements for genomic lesions, homology donors and the endogenous DNA repair machinery. Here we engineered programmable cytidine deaminases and test if we could introduce site-specific cytidine to thymidine transitions in the absence of targeted genomic lesions. Our programmable deaminases effectively convert specific cytidines to thymidines with 13% efficiency in Escherichia coli and 2.5% in human cells. However, off-target deaminations were detected more than 150 bp away from the target site. Moreover, whole genome sequencing revealed that edited bacterial cells did not harbour chromosomal abnormalities but demonstrated elevated global cytidine deamination at deaminase intrinsic binding sites. Therefore programmable deaminases represent a promising genome editing tool in prokaryotes and eukaryotes. Future engineering is required to overcome the processivity and the intrinsic DNA binding affinity of deaminases for safer therapeutic applications.
Meiotic instability of the R-r complex arising from displaced intragenic exchange and intrachromosomal rearrangement. (1991)

The R complex of Zea mays encodes a tissue-specific transcriptional activator of the anthocyanin pigment biosynthetic pathway. Certain R alleles comprise two genetically distinct components that confer the plant (P) and seed (S) aspects of the pigmentation pattern. These alleles are meiotically unstable, losing (P) or (S) function, often accompanied by exchange of flanking markers. We show that the (P) component consists of a single gene within the R-r complex, whereas the (S) component is part of a more complex arrangement of multiple R genes or gene subfragments. A third, cryptic region of the complex, termed (Q), consists of a truncated R sequence. The analysis of R-r crossover derivative alleles shows they arise from unequal exchange between the (P) gene and one of several distinct regions of the R-r complex. Restriction site polymorphisms were used to show that most of these unequal exchanges are intragenic. The frequency of displaced intragenic recombination is comparable to previous estimates for intragenic recombination in maize involving genes that are not duplicated. These exchange events have been used to determine the arrangement of components within the complex and their orientation in the chromosome. We also show that localized rearrangements in the (P) or (S) components are responsible for noncrossover derivative alleles. The organization of R-r has implications for these noncrossover derivatives and models for their origin are discussed.
Comparison of Neisseria gonorrhoeae Multiantigen Sequence Typing and porB Sequence Analysis for Identification of Clusters of N. gonorrhoeae Isolates (2008)

porB DNA sequence analysis and Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) methods were compared for their abilities to discriminate strains and to identify epidemiologically congruent pairs of N. gonorrhoeae. Both methods provided high-level discrimination of strains. NG-MAST further differentiated large porB-based clusters. However, considerations of cost suggest that porB DNA sequence analysis is a useful tool for preliminary molecular analysis of the epidemiology of N. gonorrhoeae.
Pharmacology of Cl‐966: A potent GABA uptake inhibitor, in vitro and in experimental animals (1990)

Abstract Experiments were performed to assess the pharmacology of a novel inhibitor of GABA uptake, Cl‐966 ([1‐[2‐[bis 4‐(trifluoromethyl)phenyl]methoxy]ethyl]‐1,2,5,6‐tetrahydro‐3‐pyridinecarboxylic acid, HCl salt; the molecular weight of the free acid is 473.8). Cl‐966 potently inhibits tritiated GABA uptake into rat hippocampal slices in vitro (lC 50 = 304 nM). It has no appreciable effect on the uptake of other neurotransmitters tested (aspartate, dopamine, norepinephrine, serotonin) and has low activity in a broad range of neurotransmitter receptor binding assays. When given orally to mice, Cl‐966 prevents tonic extensor seizures from low‐intensity electroshock and prevents pentylenetetrazole‐induced clonic seizures (ED 50 = 0.4–1.0 mg/kg). In addition, the hippocampal afterdischarge threshold in kindled rats is increased markedly (ED 50 = 2.6 mg/kg p.o.). Despite anticonvulsant effects, higher doses of Cl‐966 reduce the intravenous dose of pentylenetetrazole needed to produce clonus in mice. In mice, rats, dogs, and monkeys, Cl‐966 interferes with normal behavior, causing ataxia, reduced responsivenes and myoclonus. In the hippocampus of anesthetized rats, Cl‐966 increases inhibition measured electrophysiologically. Overflow of endogenous GABA in the striatum (measured with in vivo microdialysis) was also increased. All of these observed effects with Cl‐966 may be explained by its inhibitory effect on GABA uptake.
Helper-dependent adenoviral vectors mediate therapeutic factor VIII expression for several months with minimal accompanying toxicity in a canine model of severe hemophilia A (2003)

Two helper-dependent (HD) adenoviral vectors encoding a canine factor VIII B-domain-deleted transgene (cFVIII) were constructed and evaluated in 4 hemophilia A dogs. One vector was regulated by the cytomegalovirus (CMV) promoter (HD-CMV-cFVIII), while the other vector contained a tissue-restricted promoter comprised of the human FVIII proximal promoter with an upstream concatemer of 5 hepatocyte nuclear factor 1 binding sites (HD-HNF-cFVIII). We detected no toxicity at low dose (5 x 10(11) vp/kg), but at higher vector doses (> 1 x 10(12) vp/kg) transient hepatotoxicity and thrombocytopenia were observed. Low-level increases in FVIII activity were detected in all 3 HD-HNF-cFVIII-treated dogs, which corresponded with decreased whole blood clotting times. None of the animals receiving the HD-HNF-cFVIII vector developed FVIII inhibitors, and in 1 of the 3 animals, FVIII activity was sustained for over 6 months after treatment. One animal, which received the HD-CMV-cFVIII vector, achieved peak levels of FVIII above 19 000 mU/mL, but FVIII activity disappeared within 1 week, coincident with the development of a potent anti-canine FVIII antibody response. This study supports previous demonstrations of improved safety using HD gene transfer and suggests that these vectors can provide transient FVIII expression with minimal, acute toxicity in the absence of inhibitor formation.
Paper‐Based Electrochemiluminescent 3D Immunodevice for Lab‐on‐Paper, Specific, and Sensitive Point‐of‐Care Testing (2012)

Recent research on microfluidic paper-based analytical devices (μPADs) has shown that paper has great potential for the fabrication of low-cost diagnostic devices for healthcare and environmental monitoring applications. Herein, electrochemiluminescence (ECL) was introduced for the first time into μPADs that were based on screen-printed paper-electrodes. To further perform high-specificity, high-performance, and high-sensitivity ECL on μPADs for point-of-care testing (POCT), ECL immunoassay capabilities were introduced into a wax-patterned 3D paper-based ECL device, which was characterized by SEM, contact-angle measurement, and electrochemical impedance spectroscopy. With the aid of a home-made device-holder, the ECL reaction was triggered at room temperature. By using a typical tris(bipyridine)ruthenium-tri-n-propylamine ECL system, this paper-based ECL 3D immunodevice was applied to the diagnosis of carcinoembryonic antigens in real clinical serum samples. This contribution further expands the number of sensitive and specific detection modes of μPADs.
Dual localization of neuropeptide FF receptors in the rat dorsal horn (2000)

Although neuropeptide FF (NPFF) is generally considered an anti-opioid, its intrathecal administration produces analgesia. In the present study, the stable analog 1DMe ([D.Tyr(1), (NMe)Phe(3)]neuropeptide FF) was used in quantitative autoradiographic experiments in combination with surgical and chemical lesions to precisely localize NPFF receptors in the rat spinal cord. Ligation of lumbar dorsal spinal roots revealed the presence of NPFF receptors in dorsal root fibers and it induced a significant accumulation of [(125)I]1DMe-specific binding on the side peripheral to the ligature, demonstrating that a population of NPFF receptors is synthesized in dorsal root ganglia and migrates anterogradely towards primary afferent nerve endings. Complete mid-thoracic spinal cord transection failed to modify the [(125)I]1DMe labeling density in the dorsal horn, indicating that NPFF receptors are not located on the descending fiber terminals. In contrast, unilateral microinjections of kainic acid into the dorsal horn dramatically reduced [(125)I]1DMe-specific binding in the superficial layers, revealing localization of a population of NPFF receptors on the spinal intrinsic neurons. NPFF receptor binding was not modified during the development of spinal opioid tolerance. The pre- and postsynaptic localization of spinal NPFF receptors provide further support for heterogeneity in the pain modulation by NPFF and related agonists.
Analog/Mixed-Signal Hardware Error Modeling for Deep Learning Inference (2019)

Analog/mixed-signal (AMS) computation can be more energy efficient than digital approaches for deep learning inference, but incurs an accuracy penalty from precision loss. Prior AMS approaches focus on small networks/datasets, which can maintain accuracy even with 2b precision. We analyze applicability of AMS approaches to larger networks by proposing a generic AMS error model, implementing it in an existing training framework, and investigating its effect on ImageNet classification with ResNet-50. We demonstrate significant accuracy recovery by exposing the network to AMS error during retraining, and we show that batch normalization layers are responsible for this accuracy recovery. We also introduce an energy model to predict the requirements of high-accuracy AMS hardware running large networks and use it to show that for ADC-dominated designs, there is a direct tradeoff between energy efficiency and network accuracy. Our model predicts that achieving < 0.4% accuracy loss on ResNet-50 with AMS hardware requires a computation energy of at least ~300 fJ/MAC. Finally, we propose methods for improving the energy-accuracy tradeoff.
Array-Based Binary Analysis for Bacterial Typing (2004)

An allele-specific oligonucleotide microarray was developed for rapid typing of pathogens based on analysis of genomic variations. Using a panel of Escherichia coli strains as a model system, selected loci were sequenced to uncover differences, such as single- or multiple-nucleotide polymorphisms as well as insertion/deletions (indels). While typical genomic profiling experiments employ specific sequences targeted to genomic DNA unique to a single strain or virulent gene, the present array is designed to type bacteria based on a patterned signature response across multiple loci. In the signature concept, all strains are interrogated by hybridizing their amplified DNA to an array containing multiple probe sequences. Allele-specific oligonucleotide probe sequences targeting each of these variable regions were synthesized and included in a custom fiber-optic array. For each locus, a set of specific probe sequences is selected, such that hybridization gives a binary signal/no signal response to each of the probes. Using this strategy for multiple loci, many pathogens or microorganisms could be classified using a limited number of probes. Because of the advantages of the fiber-optic array platform over other array formats, including sensitivity and speed, the platform described in this paper is capable of supporting a high-throughput diagnostic strategy.
MR vector sensor with trimmable sense axis direction (1989)

Magnetoresistive bridge sensors fabricated from thin-film Permalloy elements are biased by mutually opposing fields on adjacent arms of the bridge using integral thin-film bias magnets. The sensors have excellent vector response and good linearity in applied fields up to 1.5 Oe. It is shown both theoretically and experimentally that the axis of peak sensitivity is not aligned with any geometric edge of the sensor pattern but can be adjusted by varying the bias field. This ability to trim the sense-axis direction is discussed in relation to the production of three-axis sensor systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>