gebhart/patrepeval huggingface dataset:
Equine infectious anemia virus utilizes a YXXL motif within the late assembly domain of the Gag p9 protein (1997)

We have previously demonstrated that the Gag p9 protein of equine infectious anemia virus (EIAV) is functionally homologous with Rous sarcoma virus (RSV) p2b and human immunodeficiency virus type 1 (HIV-1) p6 in providing a critical late assembly function in RSV Gag-mediated budding from transfected COS-1 cells (L. J. Parent et al., J. Virol. 69:5455-5460, 1995). In light of the absence of amino acid sequence homology between EIAV p9 and the functional homologs of RSV and HIV-1, we have now designed an EIAV Gag-mediated budding assay to define the late assembly (L) domain peptide sequences contained in the EIAV p9 protein. The results of these particle budding assays revealed that expression of EIAV Gag polyprotein in COS-1 cells yielded extracellular Gag particles with a characteristic density of 1.18 g/ml, while expression of EIAV Gag polyprotein lacking p9 resulted in a severe reduction in the release of extracellular Gag particles. The defect in EIAV Gag polyprotein particle assembly could be corrected by substituting either the RSV p2b or HIV-1 p6 protein for EIAV p9. These observations demonstrated that the L domains of EIAV, HIV-1, and RSV were interchangeable in mediating assembly of EIAV Gag particles in the COS-1 cell budding assay. To localize the L domain of EIAV p9, we next assayed the effects of deletions and site-specific mutations in the p9 protein on its ability to mediate budding of EIAV Gag particles. Analyses of EIAV Gag constructs with progressive N-terminal or C-terminal deletions of the p9 protein identified a minimum sequence of 11 amino acids (Q20N21L22Y23P24D25L26S27E28I29K30) capable of providing the late assembly function. Alanine scanning studies of this L-domain sequence demonstrated that mutations of residues Y23, P24, and L26 abrogated the p9 late budding function; mutations of other residues in the p9 L domain did not substantially affect the level of EIAV Gag particle assembly. These data indicate that the L domain in EIAV p9 utilizes a YXXL motif which we hypothesize may interact with cellular proteins to facilitate virus particle budding from infected cells.
DNA Replication Licensing and Progenitor Numbers Are Increased by Progesterone in Normal Human Breast (2009)

Proliferation in the nonpregnant human breast is highest in the luteal phase of the menstrual cycle when serum progesterone levels are high, and exposure to progesterone analogues in hormone replacement therapy is known to elevate breast cancer risk, yet the proliferative effects of progesterone in the human breast are poorly understood. In a model of normal human breast, we have shown that progesterone increased incorporation of 5-bromo-2'-deoxyuridine and increased cell numbers by activation of pathways involved in DNA replication licensing, including E2F transcription factors, chromatin licensing and DNA replication factor 1 (Cdt1), and the minichromosome maintenance proteins and by increased expression of proteins involved in kinetochore formation including Ras-related nuclear protein (Ran) and regulation of chromosome condensation 1 (RCC1). Progenitor cells competent to give rise to both myoepithelial and luminal epithelial cells were increased by progesterone, showing that progesterone influences epithelial cell lineage differentiation. Therefore, we have demonstrated that progesterone augments proliferation of normal human breast cells by both activating DNA replication licensing and kinetochore formation and increasing bipotent progenitor numbers.
Identification of genes and gene products necessary for bacterial bioluminescence. (1984)

Expression of luminescence in Escherichia coli was recently achieved by cloning genes from the marine bacterium Vibrio fischeri. One DNA fragment on a hybrid plasmid encoded regulatory functions and enzymatic activities necessary for light production. We report the results of a genetic analysis to identify the luminescence genes (lux) that reside on this recombinant plasmid. lux gene mutations were generated by hydroxylamine treatment, and these mutations were ordered on a linear map by complementation in trans with a series of polar transposon insertions on other plasmids. lux genes were defined by complementation of lux gene defects on pairs of plasmids in trans in E. coli. Hybrid plasmids were also used to direct the synthesis of polypeptides in the E. coli minicell system. Seven lux genes and the corresponding gene products were identified from the complementation analysis and the minicell programing experiments. These genes, in the order of their position on a linear map, and the apparent molecular weights of the gene products are luxR (27,000), luxI (25,000), luxC (53,000), luxD (33,000), luxA (40,000), luxB (38,000), and luxE (42,000). From the luminescence phenotypes of E. coli containing mutant plasmids, functions were assigned to these genes: luxA, luxB, luxC, luxD, and luxE encode enzymes for light production and luxR and luxI encode regulatory functions.
Lattice match: An application to heteroepitaxy (1984)

We define the concept of lattice match for any pair of crystal lattices in any given crystal direction, allowing for a periodic reconstruction of the interface. An algorithm for a systematic search for all possible matches is developed, and some examples of nonstandard lattice matches are given for CdTe on GaAs and sapphire to illustrate the method. For the case of CdTe on GaAs, our results agree with published results, both with respect to growth plane and orientation for CdTe(111) on GaAs(100). For CdTe on sapphire, our results agree with published results with respect to growth plane.
Dimeric Cinchona alkaloids (2015)

Nature is full of dimeric alkaloids of various types from many plant families, some of them with interesting biological properties. However, dimeric Cinchona alkaloids were not isolated from any species but were products of designed partial chemical synthesis. Although the Cinchona bark is amongst the sources of oldest efficient medicines, the synthetic dimers found most use in the field of asymmetric synthesis. Prominent examples include the Sharpless dihydroxylation and aminohydroxylation ligands, and dimeric phase transfer catalysts. In this article the syntheses of Cinchona alkaloid dimers and oligomers are reviewed, and their structure and applications are outlined. Various synthetic routes exploit reactivity of the alkaloids at the central 9-hydroxyl group, quinuclidine, and quinoline rings, as well as 3-vinyl group. This availability of reactive sites, in combination with a plethora of linker molecules, contributes to the diversity of the products obtained.
The Tumor Microenvironment: Key to Early Detection (2006)

The tumor microenvironment plays an important role equal to the tumor cell population in the progression of cancer. Consisting of stromal fibroblasts, inflammatory cells, components of the vasculature, normal epithelia, and extracellular matrix, the surrounding environment interacts or "cross-talks" with tumor cells through the release of growth factors, cytokines, proteases, and other bioactive molecules. Tumor growth, formation of new vascular networks, evasion of the host immune system, and invasion and metastasis are processes that co-evolve and become finely optimized and regulated within the tumor microenvironment. However, relatively recent reports on three areas of study have come together to add new levels of complexity to the tumor microenvironment. These include ectodomain shedding of proteins, shedding of membrane-derived vesicles, and novel roles for phospholipids. These dynamic changes that take place in the tumor microenvironment provide new avenues for study and for the early detection of cancer, whereas proteomic technologies provide the means to detect these unique proteins and lipids. Here we review the evolving concepts of the tumor microenvironment that, together with advances in proteomic technologies, hold the promise to facilitate the detection of early-stage cancer.
Uncoupled Cardiac Nitric Oxide Synthase Mediates Diastolic Dysfunction (2010)

Cardiac oxidation, independently of vascular changes, can lead to uncoupled cardiac NOS and diastolic dysfunction. BH(4) may represent a possible treatment for diastolic dysfunction.
DNA Translocation through Graphene Nanopores (2010)

Nanopores--nanosized holes that can transport ions and molecules--are very promising devices for genomic screening, in particular DNA sequencing. Solid-state nanopores currently suffer from the drawback, however, that the channel constituting the pore is long, approximately 100 times the distance between two bases in a DNA molecule (0.5 nm for single-stranded DNA). This paper provides proof of concept that it is possible to realize and use ultrathin nanopores fabricated in graphene monolayers for single-molecule DNA translocation. The pores are obtained by placing a graphene flake over a microsize hole in a silicon nitride membrane and drilling a nanosize hole in the graphene using an electron beam. As individual DNA molecules translocate through the pore, characteristic temporary conductance changes are observed in the ionic current through the nanopore, setting the stage for future single-molecule genomic screening devices.
A 5′ stem–loop and ribosome binding but not translation are important for the stability of Bacillus subtilis aprE leader mRNA (2002)

The Bacillus subtilis aprE leader is a determinant of extreme mRNA stability. The authors examined what properties of the aprE leader confer stability on an mRNA. The secondary structure of the aprE leader mRNA was analysed in vitro and in vivo, and mutations were introduced into different domains of an aprE leader-lacZ fusion. The half-lives of the corresponding transcripts were determined and beta-galactosidase activities were measured. Removal of a stem-loop structure at the 5' end or diminishing the strength of the RBS reduced the half-lives from more than 25 min to about 5 min. Interfering with translation by abolishing the start codon or creating an early stop codon had no or little effect on mRNA stability. The authors conclude that a 5' stem-loop and binding of ribosomes are necessary for the stability of aprE leader mRNA. The present results, together with a number of other data, suggest that translation of a B. subtilis mRNA is generally not important for its stability; the situation seems different in Escherichia coli. It is further concluded that the calculated strength of a B. subtilis RBS cannot be used to predict the stability of the corresponding transcript.
A Template‐Mediated Click–Click Reaction: PNA–DNA, PNA–PNA (or Peptide) Ligation, and Single Nucleotide Discrimination (2010)

A highly efficient chemical ligation was developed for quantitative conjugation of PNA with DNA (PNA or peptide) using the copper-catalyzed azide-alkyne cycloaddition reaction. While PNAs with an alkyne at the C-terminus and an azide at the N-terminus have been used, an efficient click-click reaction occurs. The PNA click ligation is sequence-specific and capable of single nucleotide discrimination.
Cross-Talk in the Innate Immune System: Neutrophils Instruct Recruitment and Activation of Dendritic Cells during Microbial Infection (2003)

Type I inflammatory cytokines are essential for immunity to many microbial pathogens, including Toxoplasma gondii. Dendritic cells (DC) are key to initiating type 1 immunity, but neutrophils are also a source of chemokines and cytokines involved in Th1 response ignition. We found that T. gondii triggered neutrophil synthesis of CC chemokine ligand (CCL)3, CCL4, CCL5, and CCL20, chemokines that were strongly chemotactic for immature DC. Moreover, supernatants obtained from parasite-stimulated polymorphonuclear leukocytes induced DC IL-12(p40) and TNF-alpha production. Parasite-triggered neutrophils also released factors that induced DC CD40 and CD86 up-regulation, and this response was dependent upon parasite-triggered neutrophil TNF-alpha production. In vivo evidence that polymorphonuclear leukocytes exert an important influence on DC activation was obtained by examining splenic DC cytokine production following infection of neutrophil-depleted mice. These animals displayed severely curtailed splenic DC IL-12 and TNF-alpha production, as revealed by ex vivo flow cytometric analysis and in vitro culture assay. Our results reveal a previously unrecognized regulatory role for neutrophils in DC function during microbial infection, and suggest that cross-talk between these cell populations is an important component of the innate immune response to infection.
Expression Cloning and Characterization of Oxidative 17β- and 3α-Hydroxysteroid Dehydrogenases from Rat and Human Prostate (1997)

Intracellular levels of active steroid hormones are determined by their relative rates of synthesis and breakdown. In the case of the potent androgen dihydrotestosterone, synthesis from the precursor testosterone is mediated by steroid 5alpha-reductase, whereas breakdown to the inactive androgens 5alpha-androstane-3alpha, 17beta-diol (3alpha-adiol), and androsterone is mediated by reductive 3alpha-hydroxysteroid dehydrogenases (3alpha-HSD) and oxidative 17beta-hydroxysteroid dehydrogenases (17beta-HSD), respectively. We report the isolation by expression cloning of a cDNA encoding a 17beta-HSD6 isozyme that oxidizes 3alpha-adiol to androsterone. 17beta-HSD6 is a member of the short chain dehydrogenase/reductase family and shares 65% sequence identity with retinol dehydrogenase 1 (RoDH1), which catalyzes the oxidation of retinol to retinal. Expression of rat and human RoDH cDNAs in mammalian cells is associated with the oxidative conversion of 3alpha-adiol to dihydrotestosterone. Thus, 17beta-HSD6 and RoDH play opposing roles in androgen action; 17beta-HSD6 inactivates 3alpha-adiol by conversion to androsterone and RoDH activates 3alpha-adiol by conversion to dihydrotestosterone. The synthesis of an active steroid hormone by back conversion of an inactive metabolite represents a potentially important mechanism by which the steady state level of a transcriptional effector can be regulated.
Unsupervised Learning of Invariant Feature Hierarchies with Applications to Object Recognition (2007)

We present an unsupervised method for learning a hierarchy of sparse feature detectors that are invariant to small shifts and distortions. The resulting feature extractor consists of multiple convolution filters, followed by a feature-pooling layer that computes the max of each filter output within adjacent windows, and a point-wise sigmoid non-linearity. A second level of larger and more invariant features is obtained by training the same algorithm on patches of features from the first level. Training a supervised classifier on these features yields 0.64% error on MNIST, and 54% average recognition rate on Caltech 101 with 30 training samples per category. While the resulting architecture is similar to convolutional networks, the layer-wise unsupervised training procedure alleviates the over-parameterization problems that plague purely supervised learning procedures, and yields good performance with very few labeled training samples.
Generalized methods and strategies for modeling and optimizing the optics of 3D head-mounted light field displays (2019)

An integral-imaging based light field head-mounted display, which typically renders a 3D scene by reconstructing the directional light rays apparently emitted by the scene via an array optics, is potentially capable of rendering correct or nearly correct focus cues and therefore solving the well-known vergence-accommodation conflict problem plaguing conventional stereoscopic displays. Its true 3D image formation nature, however, imposes significant complications and the well-established optical design process for conventional head-mounted displays becomes inadequate to address the design challenges. To our best knowledge, there are no existing methods or framework that have been previously proposed or demonstrated to address the challenges of modeling and optimizing an optical system for this type of display systems. In this paper, we present novel and generalizable methodology and framework for designing and optimizing the optical performance of integral-imaging based light field head-mounted displays, including methods of system configurations, user-defined metrics for characterizing the performance of such systems, and optimization strategies unique in light field displays. A design example is further given based on the proposed design methodology for the purpose of validating the proposed design method and framework.
Overlapping pools for high-throughput targeted resequencing (2009)

Resequencing genomic DNA from pools of individuals is an effective strategy to detect new variants in targeted regions and compare them between cases and controls. There are numerous ways to assign individuals to the pools on which they are to be sequenced. The naïve, disjoint pooling scheme (many individuals to one pool) in predominant use today offers insight into allele frequencies, but does not offer the identity of an allele carrier. We present a framework for overlapping pool design, where each individual sample is resequenced in several pools (many individuals to many pools). Upon discovering a variant, the set of pools where this variant is observed reveals the identity of its carrier. We formalize the mathematical framework for such pool designs and list the requirements from such designs. We specifically address three practical concerns for pooled resequencing designs: (1) false-positives due to errors introduced during amplification and sequencing; (2) false-negatives due to undersampling particular alleles aggravated by nonuniform coverage; and consequently, (3) ambiguous identification of individual carriers in the presence of errors. We build on theory of error-correcting codes to design pools that overcome these pitfalls. We show that in practical parameters of resequencing studies, our designs guarantee high probability of unambiguous singleton carrier identification while maintaining the features of naïve pools in terms of sensitivity, specificity, and the ability to estimate allele frequencies. We demonstrate the ability of our designs in extracting rare variations using short read data from the 1000 Genomes Pilot 3 project.
Ribonuclease inhibitor from human placenta. Purification and properties. (1977)

A soluble ribonuclease inhibitor from the human placenta has been purified 4000-fold by a combination of ion exchange and affinity chromatography. The inhibitor has been isolated in 45% yield (about 2 mg/placenta) as a protein that is homogeneous by sodium dodecyl sulfate-gel electrophoresis. In common with the inhibitors of pancreatic ribonuclease from other tissues that have been studied earlier, the placental inhibitor is an acidic protein of molecular weight near 50,000; it forms a 1:1 complex with bovine pancreatic RNase A and is a noncompetitive inhibitor of the pancreatic enzyme, with a Ki of 3 X 10(-10) M. The amino acid composition of the protein has been determined. The protein contains 30 half-cystine plus cysteine residues determined as cysteic acid after performic acid oxidation. At pH 8.6 the nondenatured protein alkylated with iodoacetic acid in the presence of free thiol has 8 free sulfhydryl groups. The inhibitor is irreversibly inactivated by sulfhydryl reagents and also by removal of free thiol from solutions of the protein. Inactivation by sulfhydryl reagents causes the dissociation of the RNase - inhibitor complex into active RNase and inactive inhibitor.
Grid information services for distributed resource sharing (2002)

Grid technologies enable large-scale sharing of resources within formal or informal consortia of individuals and/or institutions: what are sometimes called virtual organizations. In these settings, the discovery, characterization, and monitoring of resources, services, and computations are challenging problems due to the considerable diversity; large numbers, dynamic behavior, and geographical distribution of the entities in which a user might be interested. Consequently, information services are a vital part of any Grid software infrastructure, providing fundamental mechanisms for discovery and monitoring, and hence for planning and adapting application behavior. We present an information services architecture that addresses performance, security, scalability, and robustness requirements. Our architecture defines simple low-level enquiry and registration protocols that make it easy to incorporate individual entities into various information structures, such as aggregate directories that support a variety of different query languages and discovery strategies. These protocols can also be combined with other Grid protocols to construct additional higher-level services and capabilities such as brokering, monitoring, fault detection, and troubleshooting. Our architecture has been implemented as MDS-2, which forms part of the Globus Grid toolkit and has been widely deployed and applied.
High resolution calorimetric sensing based on Aluminum Nitride MEMS resonant thermal detectors (2014)

This paper presents a high temperature resolution (994.5 μK/Hz <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sup> in a 50 Hz measurement bandwidth) micro-calorimetric sensor based on a high frequency (134.5 MHz) Aluminum Nitride (AlN) nano-plate resonator (NPR) overlapped by a freestanding reaction chamber separated by a micro-scale air gap (~50 μm). For the first time, the unique thermal detection capabilities of the AlN NPR technology are exploited to devise a calorimetric sensor with superior performance. Efficient heat transfer from the reaction chamber to the thermal detector is achieved by scaling the air gap between them. By taking advantage of the large thermal resistance (2.64 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> K/W) of the AlN NPR and the reduced air gap, high heat transfer efficiency (ratio between the temperature of the resonator and the one of the reaction chamber) of 33% is achieved. The effectiveness of the fabricated prototype is experimentally verified by monitoring an exothermic reaction between Hydrochloric Acid (HCl) and Ammonium Hydroxide (NH <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> OH). A high sensitivity of 9.62 kHz/M and detection limit of ~120 μM/Hz <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sup> are achieved for the first device prototype.
Spiking Neurons Can Learn to Solve Information Bottleneck Problems and Extract Independent Components (2008)

Independent component analysis (or blind source separation) is assumed to be an essential component of sensory processing in the brain and could provide a less redundant representation about the external world. Another powerful processing strategy is the optimization of internal representations according to the information bottleneck method. This method would allow extracting preferentially those components from high-dimensional sensory input streams that are related to other information sources, such as internal predictions or proprioceptive feedback. However, there exists a lack of models that could explain how spiking neurons could learn to execute either of these two processing strategies. We show in this article how stochastically spiking neurons with refractoriness could in principle learn in an unsupervised manner to carry out both information bottleneck optimization and the extraction of independent components. We derive suitable learning rules, which extend the well-known BCM rule, from abstract information optimization principles. These rules will simultaneously keep the firing rate of the neuron within a biologically realistic range.