gebhart/patrepeval huggingface dataset:
Characterization of canine osteosarcoma by array comparative genomic hybridization and RT‐qPCR: Signatures of genomic imbalance in canine osteosarcoma parallel the human counterpart (2011)

Osteosarcoma (OS) is the most commonly diagnosed malignant bone tumor in humans and dogs, characterized in both species by extremely complex karyotypes exhibiting high frequencies of genomic imbalance. Evaluation of genomic signatures in human OS using array comparative genomic hybridization (aCGH) has assisted in uncovering genetic mechanisms that result in disease phenotype. Previous low-resolution (10-20 Mb) aCGH analysis of canine OS identified a wide range of recurrent DNA copy number aberrations, indicating extensive genomic instability. In this study, we profiled 123 canine OS tumors by 1 Mb-resolution aCGH to generate a dataset for direct comparison with current data for human OS, concluding that several high frequency aberrations in canine and human OS are orthologous. To ensure complete coverage of gene annotation, we identified the human refseq genes that map to these orthologous aberrant dog regions and found several candidate genes warranting evaluation for OS involvement. Specifically, subsequenct FISH and qRT-PCR analysis of RUNX2, TUSC3, and PTEN indicated that expression levels correlated with genomic copy number status, showcasing RUNX2 as an OS associated gene and TUSC3 as a possible tumor suppressor candidate. Together these data demonstrate the ability of genomic comparative oncology to identify genetic abberations which may be important for OS progression. Large scale screening of genomic imbalance in canine OS further validates the use of the dog as a suitable model for human cancers, supporting the idea that dysregulation discovered in canine cancers will provide an avenue for complementary study in human counterparts.
An Enhanced Packaging System for Helper-Dependent Herpes Simplex Virus Vectors (1998)

Helper-dependent herpes simplex virus (HSV) vectors (amplicons) show considerable promise to provide for long-term transduced-gene expression in most cell types. The current packaging system of choice for these vectors involves cotransfection with a set of five overlapping cosmids that encode the full HSV type 1 (HSV-1) helper virus genome from which the packaging (pac) elements have been deleted. Although both the helper virus and the HSV amplicon can replicate, only the latter is packaged into infectious viral particles. Since the titers obtained are too low for practical application, an enhanced second-generation packaging system was developed by modifying both the helper virus and the HSV amplicon vector. The helper virus was reverse engineered by using the original five cosmids to generate a single HSV-bacterial artificial chromosome (BAC) clone in Escherichia coli from which the pac elements were deleted to generate a replication-proficient but packaging-defective HSV-1 genome. The HSV amplicon was modified to contain the simian virus 40 origin of replication, which acts as an HSV-independent replicon to provide for the replicative expansion of the vector. The HSV amplicon is packaged into infectious particles by cotransfection with the HSV-BAC helper virus into the 293T cell line, and the resulting cell lysate is free of detectable helper virus contamination. The combination of both modifications to the original packaging system affords an eightfold increase in the packaged-vector yield.
Sacral neuromodulation: Therapy evolution (2010)

Our understanding of SNM, as well as technological advances in therapy delivery, expands the pool of patients for which this form of therapy may prove beneficial. Less invasive instrumentation may even make this form of therapy appealing to patients without refractory symptoms.
Continuum crowds (2006)

We present a real-time crowd model based on continuum dynamics. In our model, a dynamic potential field simultaneously integrates global navigation with moving obstacles such as other people, efficiently solving for the motion of large crowds without the need for explicit collision avoidance. Simulations created with our system run at interactive rates, demonstrate smooth flow under a variety of conditions, and naturally exhibit emergent phenomena that have been observed in real crowds.
Molecular characterization of a gene from Saccharopolyspora erythraea (Streptomyces erythraeus) which is involved in erythromycin biosynthesis (1989)

A 7.3 kbp DNA fragment, encompassing the erythromycin (Em) resistance gene (ermE) and a portion of the gene cluster encoding the biosynthetic genes for erythromycin biosynthesis in Saccharopolyspora erythraea (formerly Streptomyces erythraeus) has been cloned in Streptomyces lividans using the plasmid vector pIJ702, and its nucleotide sequence has been determined using a modified dideoxy chain-termination procedure. In particular, we have examined the region immediately 5' of the resistance determinant, where the tandem promoters for ermE overlap the promoters for a divergently transcribed coding sequence (ORF). Disruption of this ORF using an integrational pIJ702-based plasmid vector gave mutants which were specifically blocked in erythromycin biosynthesis, and which accumulated 3-O-alpha-L-mycarosylerythronolide B: this behaviour is identical to that of previously described eryC1 mutants. The eryC1-gene product, a protein of subunit Mr 39,200, is therefore involved either as a structural or as a regulatory gene in the formation of the deoxyamino-sugar desosamine or in its attachment to the macrolide ring.
Ultrastructure of the Surface of Rickettsia prowazeki and Rickettsia akari (1974)

Negative-contrast electron microscopy revealed that the outer layer of the envelope of rickettsiae is composed of a matrix of tetragonally arranged subunits. The layer projects approximately 7 nm from the cell wall. It is suggested that this outer layer is analogous to the structure considered capsule-like in morphology.
A method for attachment of peptides to a solid surface with enhanced immunoreactivity. (1992)

Another method has been developed to attach synthetic peptides to solid supports for use in enzyme immunoassays. The method is based on passively adsorbing a synthetic peptide to a solid-phase support, then further attaching more of the same peptide by means of cross-linking to the previously adsorbed peptide. This method results in highly enhanced peptide immunoreactivity compared with that obtained with standard methodologies.
Shield (2004)

Software patching has not been effective as a first-line defense against large-scale worm attacks, even when patches have long been available for their corresponding vulnerabilities. Generally, people have been reluctant to patch their systems immediately, because patches are perceived to be unreliable and disruptive to apply. To address this problem, we propose a first-line worm defense in the network stack, using shields -- vulnerability-specific, exploit-generic network filters installed in end systems once a vulnerability is discovered, but before a patch is applied. These filters examine the incoming or outgoing traffic of vulnerable applications, and correct traffic that exploits vulnerabilities. Shields are less disruptive to install and uninstall, easier to test for bad side effects, and hence more reliable than traditional software patches. Further, shields are resilient to polymorphic or metamorphic variations of exploits [43].In this paper, we show that this concept is feasible by describing a prototype Shield framework implementation that filters traffic above the transport layer. We have designed a safe and restrictive language to describe vulnerabilities as partial state machines of the vulnerable application. The expressiveness of the language has been verified by encoding the signatures of several known vulnerabilites. Our evaluation provides evidence of Shield's low false positive rate and small impact on application throughput. An examination of a sample set of known vulnerabilities suggests that Shield could be used to prevent exploitation of a substantial fraction of the most dangerous ones.
A Cholesteryl Ester Transfer Protein Inhibitor from an Insect-associated Fungus. (1996)

Atherosclerosis is caused by the deposition of lipids, especially cholesterol, on to arterial walls, and continued
Modeling of In-Situ Stress Change Due to Cold Fluid Injection (1991)

ABSTRACT In hydraulic fracturing, the temperature for the treating fluid usually differs from the initial temperature reservoir. Because of fluid migration and heat transfer in the reservoir, such differential temperature induces thermal stresses. This paper presents a computational model, adaptive to hydraulic fracturing simulators, for calculating these thermoelastic changes in the in-situ stress distribution.
Phase control of a two-photon transition with shaped femtosecond laser-pulse sequences (2004)

Phase effects in a quantum control experiment on the two-photon transition $4s\phantom{\rule{0.3em}{0ex}}\ensuremath{\leftarrow}\ensuremath{\leftarrow}\phantom{\rule{0.3em}{0ex}}3s$ of atomic sodium are studied. In our experiment, we combine the generation of phase-locked interferometrically generated pulses with pulse-shaping techniques to study in detail the interplay of optical and quantum-mechanical phases. Subtle differences in the physical realization of the pulse sequences produce large difference in the control objective---the $4s$ population. The control mechanisms of more complex pulse sequences generated by periodic and discontinuous phase-modulation functions are investigated systematically and analyzed on the basis of quantum-mechanical interference.
Design and Structure of Peptide and Peptidomimetic Antagonists of Protein- Protein Interaction (2005)

Peptides based on the amino acid sequences found at protein-protein interaction sites make excellent leads for antagonist development. A statistical picture of amino acids involved in protein-protein interactions indicates that proteins recognize and interact with one another through the restricted set of specialized interface amino acid residues, Pro, Ile, Tyr, Trp, Asp and Arg. These amino acids represent residues from each of the three classes of amino acids, hydrophobic, aromatic and charged, with one anionic and one cationic residue at neutral pH. The use of peptides as drug leads has been successfully used to search for antagonists of cell-surface receptors. Peptide, peptidomimetic, and non-peptide organic inhibitors of a class of cell surface receptors, the integrins, currently serve as therapeutic and diagnostic imaging agents. In this review, we discuss the structural features of protein-protein interactions as well as the design of peptides, peptidomimetics, and small organic molecules for the inhibition of protein-protein interactions. Information gained from studying inhibitors of integrin functions is now being applied to the design and testing of inhibitors of other protein-protein interactions. Most drug development progress in the past several decades has been made using the enzyme binding-pocket model of drug targets. Small molecules are designed to fit into the substrate-binding pockets of proteins based on a lock-and-key, induced-fit, or conformational ensemble model of the protein binding site. Traditionally, enzymes have been used as therapeutic drug targets because it was easier to develop rapid, sensitive screening assays, and to find low molecular weight inhibitors that blocked the active site. However, for proteins which interact with other proteins, rather than with small substrate molecules, the lack of binding pockets means that this approach will not generally succeed. There exist many diseases in which the inhibition of protein-protein interactions would provide therapeutic benefit, but there are no general methods available to address such problems. The focus of the first part of this review is to discuss the features of protein-protein interactions which may serve as general guidelines for the development and design of inhibitors for protein-protein interactions. In the second part we focus on the design of peptides (lead compounds) and their conversion into peptidomimetics or small organic molecules for the inhibition of protein-protein interactions. We draw examples from the important and emerging area of integrin-based cell adhesion and show how the principles of protein-protein interactions are followed in the discovery, optimization and usage of specific protein interface peptides as drug leads.
TSPAN2 Is Involved in Cell Invasion and Motility during Lung Cancer Progression (2014)

In lung cancer progression, p53 mutations are more often observed in invasive tumors than in noninvasive tumors, suggesting that p53 is involved in tumor invasion and metastasis. To understand the nature of p53 function as a tumor suppressor, it is crucial to elucidate the detailed mechanism of the alteration in epithelial cells that follow oncogenic KRAS activation and p53 inactivation. Here, we report that KRAS activation induces epithelial-mesenchymal transition and that p53 inactivation is required for cell motility and invasiveness. Furthermore, TSPAN2, a transmembrane protein, is responsible for cell motility and invasiveness elicited by p53 inactivation. TSPAN2 is highly expressed in p53-mutated lung cancer cells, and high expression of TSPAN2 is associated with the poor prognosis of lung adenocarinomas. TSPAN2 knockdown suppresses metastasis to the lungs and liver, enabling prolonged survival. TSPAN2 enhances cell motility and invasiveness by assisting CD44 in scavenging intracellular reactive oxygen species.
Optimal Vibrotactile Stimulation Activates the Parasympathetic Nervous System (2012)

We currently live in an environment that has become more and more stressful. Escaping from the stress in society through various activities (e.g., acupuncture, massage, listening to classic music or natural sounds, etc.) is important for our mental health. We previously re‐ ported that optimal facial vibrotactile stimulation (i.e., 89 Hz frequency and 1.9 μm ampli‐ tude [89 Hz-S]) might activate the parasympathetic nervous system (Hiraba et al. 2008, 2011). Specifically, we showed that 89 Hz-S stimulation of the face led to increased saliva‐ tion and a feeling of mental well-being through parasympathetic activity based on function‐ al near-infrared spectroscopy (fNIRS) oxyhaemoglobin (oxyHb) activity. Namely, brain blood flow (BBF) oxyHb in the frontal cortex was near zero (Hiraba et al. 2011). We investi‐ gated adaptation to the continuous use of vibrotactile stimuli for 4 or 5 days in the same subjects to determine whether this resulted in decreased salivation (Despopoulos and Silber‐ nagel, 2003; Principles of Neural Science, 2000a). Then, we compared resting and stimulated salivation and investigated the most effective frequency for increasing salivary secretion. In‐ creased salivation in normal subjects was defined as a difference between resting and stimu‐ lated salivation (Hiraba et al. 2011).
TREM-1 Expression in Tumor-associated Macrophages and Clinical Outcome in Lung Cancer (2007)

Cancer cells can directly up-regulate TREM-1 expression in patients' macrophages. TREM-1 expression in tumor-associated macrophages is associated with cancer recurrence and poor survival of patients with NSCLC. TREM-1 and the inflammatory response may play an important role in cancer progression.
Intratumoral IGF-I protein expression is selectively upregulated in breast cancer patients with BRCA1/2 mutations (2007)

BRCA1/2 mutations predispose to early onset breast and ovarian cancers. The phenotypic expression of mutant alleles, however, is thought to be modified by factors that are also involved in the pathogenesis of sporadic breast cancer. One such protein is IGF-I, one of the strongest mitogens to breast cancer cells in vitro. We have utilized immunohistochemistry to compare the intratumoral IGF-I and IGF-I receptor (IGF-IR) protein expression in 57 BRCA1/2 mutation carriers and 102 matched breast cancer patients without a family history in a nested case-control study. BRCA1 silencing by siRNA was used to investigate the effect of BRCA mutations on IGF-I protein expression. IGF-I protein expression was detected in tumoral epithelium and surrounding stroma, and was significantly upregulated in tumors of BRCA mutation carriers when compared with matched sporadic tumors (epithelial: 87.7% vs 61.8%, P=0.001; stromal: 73.7% vs 34.3%, P<0.001). By contrast, IGF-IR protein expression was confined to malignant epithelium and was unchanged in mutation carriers (52.6% vs 39.2%, P=0.310). While in mutation carriers IGF-IR protein expression was significantly correlated with both epithelial (P=0.003) and stromal IGF-I (P=0.02), this association was less pronounced in sporadic breast cancer (P=0.02 respectively). siRNA-mediated downregulation of BRCA1 in primary human mammary gland cells triggered upregulation of endogenous intracellular IGF-I in vitro. The increased intratumoral IGF-I protein expression in BRCA mutation carriers suggests an involvement of the IGF-I/IGF-IR axis in the biological behavior of breast cancers in this population and could define a potential therapeutic target.
Cloning and complete nucleotide sequence of human 5'-alpha-globin gene. (1980)

We have cloned one of the two human alpha-globin genes and report its complete nucleotide sequence. The gene is 832 base pairs (bp) long from the 5'-cap site to the 3'-polyadenylylation site. The amino acid coding sequences are separated into three segments (exons) by two short (117 and 140 bp) intervening sequences. Highly conserved regions are identified in the 5'-flanking region, intron-exon junctions, and 3' noncoding regions that may have functional significance.
Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist (2005)

Improving approaches for hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) mobilization is clinically important because increased numbers of these cells are needed for enhanced transplantation. Chemokine stromal cell derived factor-1 (also known as CXCL12) is believed to be involved in retention of HSCs and HPCs in bone marrow. AMD3100, a selective antagonist of CXCL12 that binds to its receptor, CXCR4, was evaluated in murine and human systems for mobilizing capacity, alone and in combination with granulocyte colony-stimulating factor (G-CSF). AMD3100 induced rapid mobilization of mouse and human HPCs and synergistically augmented G-CSF-induced mobilization of HPCs. AMD3100 also mobilized murine long-term repopulating (LTR) cells that engrafted primary and secondary lethally-irradiated mice, and human CD34(+) cells that can repopulate nonobese diabetic-severe combined immunodeficiency (SCID) mice. AMD3100 synergized with G-CSF to mobilize murine LTR cells and human SCID repopulating cells (SRCs). Human CD34(+) cells isolated after treatment with G-CSF plus AMD3100 expressed a phenotype that was characteristic of highly engrafting mouse HSCs. Synergy of AMD3100 and G-CSF in mobilization was due to enhanced numbers and perhaps other characteristics of the mobilized cells. These results support the hypothesis that the CXCL12-CXCR4 axis is involved in marrow retention of HSCs and HPCs, and demonstrate the clinical potential of AMD3100 for HSC mobilization.
Visual attribute transfer through deep image analogy (2017)

We propose a new technique for visual attribute transfer across images that may have very different appearance but have perceptually similar semantic structure. By visual attribute transfer, we mean transfer of visual information (such as color, tone, texture, and style) from one image to another. For example, one image could be that of a painting or a sketch while the other is a photo of a real scene, and both depict the same type of scene. Our technique finds semantically-meaningful dense correspondences between two input images. To accomplish this, it adapts the notion of "image analogy" [Hertzmann et al. 2001] with features extracted from a Deep Convolutional Neutral Network for matching; we call our technique deep image analogy. A coarse-to-fine strategy is used to compute the nearest-neighbor field for generating the results. We validate the effectiveness of our proposed method in a variety of cases, including style/texture transfer, color/style swap, sketch/painting to photo, and time lapse.
A transient entanglement coupling mechanism for DNA separation by capillary electrophoresis in ultradilute polymer solutions (1994)

Using capillary electrophoresis, large DNA molecules (2.0-23.1 kbp) may be rapidly separated in ultradilute polymer solutions (< 0.002% w/w) under a high-voltage, steady field (265 V/cm). At this polymer concentration, the separation mechanism appears to be significantly different from that postulated to occur in crosslinked gels. Based on experimental results obtained with DNA restriction fragments and with negatively charged latex microspheres, we conclude that the Ogston and reptation models typically used to describe gel electrophoresis are not appropriate for DNA separations in such dilute polymer solutions. Electrophoresis experiments employing solutions of both small and large hydroxyethyl cellulose polymers highlight the importance of polymer length and concentration for the optimum resolution of DNA fragments varying in size from 72 bp to 23.1 kbp. A transient entanglement coupling mechanism for DNA separation in dilute polymer solutions is developed, which suggests that there is no a priori upper size limit to DNA that can be separated by capillary electrophoresis in a constant field.
Remodeling of gp41-C34 Peptide Leads to Highly Effective Inhibitors of the Fusion of HIV-1 with Target Cells We thank Dr. Terrence R. Burke, Jr., NCI, NIH, Frederick, MD 21702-1201, for proofreading the manuscript and providing useful comments. This research was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, the Japan Society for the Promotion of Science, and the Japan Health Science Foundation. (2002)

Substitution in the outer surface of the six-helix peptide bundle improved the solubility and enhanced the anti-HIV-1 activity of SC peptides. The E and K residues at positions b, c, f, and g (see scheme) stabilize the α-helix conformation critical to inhibition; the Z residues at positions a, d, and e interact with the inner strand.
Isolation and Characterization of Herbicide Resistant Mutants in the Cyanobacterium Synechococcus R2 (1987)

Department of Genetics, The Hebrew University of Jerusalem. Jerusalem. A variety of mutants which are resistant to triazine - and urea - classes of herbicides have been isolated in the cyanobacterium Synechococcus R2. All the mutants that have been analyzed, show some cross-resistance to different herbicides suggesting that these herbicides share a common binding site in photosystem II. Three psbA genes have been identified in Synechococcus R2. The psbA-copy I gene was cloned from three mutants and used in DNA-mediated genetic transformation. It was found that in all three mutants this gene could transfer the mutation for herbicide resistance indicating that this gene codes for the herbicide resistant protein.
An Antigen Produced by Splicing of Noncontiguous Peptides in the Reverse Order (2006)

CD8-positive T lymphocytes recognize peptides that are usually derived from the degradation of cellular proteins and are presented by class I molecules of the major histocompatibility complex. Here we describe a human minor histocompatibility antigen created by a polymorphism in the SP110 nuclear phosphoprotein gene. The antigenic peptide comprises two noncontiguous SP110 peptide segments spliced together in reverse order to that in which they occur in the predicted SP110 protein. The antigenic peptide could be produced in vitro by incubation of precursor peptides with highly purified 20S proteasomes. Cutting and splicing probably occur within the proteasome by transpeptidation.
Soluble Endoglin and Other Circulating Antiangiogenic Factors in Preeclampsia (2006)

Rising circulating levels of soluble endoglin and ratios of sFlt1:PlGF herald the onset of preeclampsia.