gebhart/patrepeval huggingface dataset:
The herpes simplex virus 1 protein kinase U S 3 is required for protection from apoptosis induced by the virus (1997)

An earlier report showed that a disabled mutant lacking both copies of the major regulatory gene (alpha4) of herpes simplex virus 1 induced DNA degradation characteristic of apoptosis in infected cells, whereas the wild-type virus protected cells from apoptosis induced by thermal shock. More extensive analyses of the disabled mutant revealed a second mutation which disabled US3, a viral gene encoding a protein kinase known to phosphorylate serine/threonine within a specific arginine-rich consensus sequence. Analyses of cells infected with a viral mutant carrying a wild-type alpha4 gene but from which the US3 gene had been deleted showed that it induced fragmentation of cellular DNA, whereas a recombinant virus in which the deleted sequences of the US3 gene had been restored did not cause the cellular DNA to fragment. These results point to the protein kinase encoded by the US3 gene as the principal viral product required to block apoptosis.
Using EC and ES cell culture to study early development: recent observations on Indian hedgehog and Bmps (1998)

Despite great technological advances in the study of mammalian development in the past two decades, certain problems in early development, such as how the extraembryonic lineages are established, have remained intractable. We suggest that teratocarcinoma (EC) and embryonic stem cells (ES) remain useful in vitro tools for studying some of these problems. We present a continuation of our studies on the role of IHH-based signaling in early development and demonstrate that the IHH N-peptide is expressed in the outer visceral endoderm cells of both the EC and ES-derived embryoid body. We also show that Bmp2 is upregulated and Bmp4 downregulated during the differentiation of F9 EC cells into embryoid bodies, whereas both genes are upregulated when J7 ES cells differentiate into embryoid bodies. We also examine the spatial localization of Ihh, Bmp2, and Bmp4 in day 6.5-7.0 and 7.5-8.0 embryos by in situ hybridization analysis. These data support the EC temporal expression data in that all 3 genes are expressed in visceral endoderm. Bmp4 expression appears to be limited to extraembryonic regions, where mesoderm as well as visceral endoderm are stained. Ihh and Bmp2 are expressed in extraembryonic tissues and the embryo proper. Functional roles for the observed expression patterns are discussed.
Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus (2000)

Although hepatitis C virus (HCV) infection is very common, identification of patients during acute infection is rare. Consequently, little is known about the immune response during this critical stage of the disease. We analyzed the T lymphocyte response during and after acute resolving HCV infection in three persons, using interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) and human histocompatibility leukocyte antigen (HLA) peptide tetramer assays. Acute infection was associated with a broadly directed T helper and cytotoxic T lymphocyte (CTL) response, which persisted after resolution of clinical hepatitis and clearance of viremia. At the earliest time point studied, highly activated CTL populations were observed that temporarily failed to secrete IFN-gamma, a "stunned" phenotype, from which they recovered as viremia declined. In long-term HCV-seropositive persons, CTL responses were more common in persons who had cleared viremia compared with those with persistent viremia, although the frequencies of HCV-specific CTLs were lower than those found in persons during and after resolution of acute HCV infection. These studies demonstrate a strong and persistent CTL response in resolving acute HCV infection, and provide rationale to explore immune augmentation as a therapeutic intervention in chronic HCV infection.
Cytometry of cell cycle regulatory proteins. (2003)

Immunocytochemical detection of cyclins, inhibitors of cyclin-dependent kinases and other cell cycle regulatory proteins, combined with analysis of cell cycle position (DNA content) by multiparameter cytometry offers unique analytical possibilities. This review focuses on applications of the methodology that yield information on the abundance, modification or interactions of these proteins in relation to cell cycle progression that cannot be obtained by other methods. Particular attention is given to the use of multiparameter cytometry in analysis of the mechanism by which antitumor drugs affect cell cycle progression and induce cell cycle phase-specific apoptosis.
MagicBrush (2013)

In this paper, we showcase the MagicBrush system, a novel painting-based image search engine. This system enables users to draw a color sketch as a query to find images. Different from existing works on sketch-based image retrieval, most of which focus on matching the shape structure without carefully considering other important visual modalities, MagicBrush takes into account the indispensable value of "color" related to "shape", and explores to make use of both the shape and color expectations that users usually have when they're imaging or searching for an image. To achieve this, we 1) develop a user-friendly interface to allow users to easily "paint out" their colorful visual expectations; 2) design a compact feature "color-edge word" to encode both shape and color information in a organic way; and 3) develop a novel matching and index structure to support a real-time response in 6.4 million images. By taking into account both shape and color information, the MagicBrush system helps users to vividly present what they are imagining, and retrieve images in a more natural way.
Genetically Encoded Short Peptide Tags for Orthogonal Protein Labeling by Sfp and AcpS Phosphopantetheinyl Transferases (2007)

Short peptide tags S6 and A1, each 12 residues in length, were identified from a phage-displayed peptide library as efficient substrates for site-specific protein labeling catalyzed by Sfp and AcpS phosphopantetheinyl transferases (PPTases), respectively. S6 and A1 tags were selected for useful levels of orthogonality in reactivities with the PPTases: the catalytic efficiency, kcat/Km of Sfp-catalyzed S6 serine phosphopantetheinylation was 442-fold greater than that for AcpS. Conversely, the kcat/Km of AcpS-catalyzed A1 labeling was 30-fold higher than that for Sfp-catalyzed A1 labeling. S6 and A1 peptide tags can be fused to N- or C-termini of proteins for orthogonal labeling of target proteins in cell lysates or on live cell surfaces. The development of the orthogonal S6 and A1 tags represents a significant enhancement of PPTase-catalyzed protein labeling, allowing tandem or iterative covalent attachment of small molecules of diverse structures to the target proteins with high efficiency and specificity.
Clinically Meaningful Change Estimates for the Six-Minute Walk Test and Daily Activity in Individuals With Chronic Heart Failure (2013)

Purpose: The purpose of the present pilot study was to provide a preliminary estimate of the minimum detectable difference (MDD) and minimum clinically important difference (MCID) of the six-minute walk test (6MWT) and daily activity in outpatients with chronic heart failure (CHF). Methods: A convenience sample of 22 adults with stable New York Heart Association Functional Class II and III CHF performed two baseline 6MWTs separated by 30 minutes of rest. Subjects then wore a triaxial accelerometer for 7 days to monitor daily activity. After 7 weeks of usual care, subjects again wore the accelerometer for 7 days and then returned to the clinic to complete the Global Rating of Change Scale (GRS) with regard to their heart disease and perform another set of 6MWTs. For the 6MWT, the MDD was calculated using the two baseline 6MWT distances. For daily activity, the MDD was calculated using two methods: (1) day-to-day test-retest reliability during baseline monitoring, and (2) baseline to follow-up test-retest reliability in those who reported no change on the GRS. The MCID for the 6MWT and daily activity was calculated using the mean and 95% confidence interval (CI95%) for those subjects who reported ‘improvement’ on the GRS. Results: The MDD at the CI95% for the 6MWT was 32.4 meters. The MCID for the 6MWT was 30.1 (CI95% 20.8, 39.4) meters. The MDD for daily activity was 5,909 vector magnitude units (VMU·hr.-1) The MCID for daily activity was 1,337 VMU·hr.-1 There was good alignment of the MDD and MCID for the 6MWT, suggesting that clinically meaningful change is approximately 32 meters. However, the calculated MCID was substantially less than measurement error as represented by the MDD, indicating that the MCID was underestimated in this sample or that daily activity may be robust to change in overall disease status.
Influence of body size and gender on control of ventilation (1986)

Hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses are influenced by both metabolic activity and hormonal factors. By studying 67 subjects of both sexes, including those at the extremes of stature, we examined the influence of gender, CO2 production (VCO2), O2 consumption (VO2), body surface area (BSA), and vital capacity (VC) on resting ventilation (VE), HVR, and HCVR. We measured resting VE, VO2, and VCO2 and then performed isocapnic progressive hypoxic and hypercapnic ventilatory responses. The effect of stature was reflected in higher VE and metabolic rate (both P less than 0.001) in tall men compared with short men that was ablated by correction for BSA. Perhaps because their heights vary less than those of the men, tall women were not statistically distinguishable from short women in any of these measured parameters. Tall men tended to have greater hypoxic chemosensitivity than short men but this was not significantly different (P = 0.07). Gender affected the control of ventilation in a number of ways. Men had higher VE (P less than 0.05) and metabolic rate (P less than 0.001) than women. Even after correction for BSA men still had higher metabolic rates. Women had higher VE/VCO2 than men (P less than 0.05) and lower resting end-tidal Pco2 (PETCO2) values (P less than 0.05). Both A, the shape parameter of the hyperbolic HVR curve, and HVR determined from mouth occlusion pressure (AP) were greater in women than in men, although only AP reached statistical significance. However, corrections of A for BSA (P less than 0.05), VCO2 (P less than 0.01), and VC (P less than 0.001) amplified these differences.(ABSTRACT TRUNCATED AT 250 WORDS)
Robust estimation of a single complex sinusoid in white noise-H/sub ∞/ filtering approach (1999)

A novel robust estimator is proposed for extracting a single complex sinusoid and its parameter (frequency) from measurements corrupted by white noise. This estimator is called an H/sub /spl infin// sinusoidal estimator (HSE), which is derived by applying an H/sub /spl infin// filter to a noisy sinusoidal model with the state-space representation. Simulations demonstrate that the HSE is more robust to the nature of observation noise {v/sub k/} than the Kalman sinusoidal estimator (KSE), which is an improved version of the nonlinear filter previously proposed by the author.
Frequency shifts of the magnetic-resonance spectrum of mixtures of nuclear spin-polarized noble gases and vapors of spin-polarized alkali-metal atoms (1989)

We report the first quantitative theoretical and experimental studies of frequency shifts of nuclear-magnetic-resonance (NMR) lines of noble-gas atoms and the corresponding frequency shifts of electron-paramagnetic-resonance (EPR) lines of alkali-metal atoms in mixtures of nuclear spin-polarized noble gases and vapors of spin-polarized alkali-metal atoms. The shifts are primarily due to the Fermi-contact hyperfine interaction. For the heavier noble gases there can be relatively large (\ensuremath{\approxeq}10%) contributions to the shifts from van der Waals molecules. The NMR frequencies of polarized $^{83}\mathrm{Kr}$ and $^{129}\mathrm{Xe}$ were measured in a vapor of spin-polarized alkali-metal atoms oriented parallel and antiparallel to the external magnetic field. The shift in the EPR frequency of the alkali-metal vapor due to the polarized noble-gas nuclei was measured simultaneously, thus providing a measurement of the absolute noble-gas nuclear polarization. The frequency shifts can be used as a convenient way to measure the absolute nuclear spin polarization of noble gases.
Mitomycin C and airway surgery: How well does it work? (2008)

The majority of the published literature individually suggests the use of topical MMC improves airway surgery outcomes. However, heterogeneity within the clinical studies, the lack of controlled data, and the lack of significance in the pooled animal data (other than histologic outcomes) suggest that the utility of MMC is still undetermined.
Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti–PD-1 treatment (2018)

In a large proportion of cancer patients, CD8 T cells are excluded from the vicinity of cancer cells. The inability of CD8 T cells to reach tumor cells is considered an important mechanism of resistance to cancer immunotherapy. We show that, in human lung squamous-cell carcinomas, exclusion of CD8 T cells from tumor islets is correlated with a poor clinical outcome and with a low lymphocyte motility, as assessed by dynamic imaging on fresh tumor slices. In the tumor stroma, macrophages mediate lymphocyte trapping by forming long-lasting interactions with CD8 T cells. Using a mouse tumor model with well-defined stromal and tumor cell areas, macrophages were depleted with PLX3397, an inhibitor of colony-stimulating factor-1 receptor (CSF-1R). Our results reveal that a CSF-1R blockade enhances CD8 T cell migration and infiltration into tumor islets. Although this treatment alone has minor effects on tumor growth, its combination with anti-PD-1 therapy further increases the accumulation of CD8 T cells in close contact with malignant cells and delays tumor progression. These data suggest that the reduction of macrophage-mediated T cell exclusion increases tumor surveillance by CD8 T cells and renders tumors more responsive to anti-PD-1 treatment.
Breast cell invasive potential relates to the myoepithelial phenotype (2003)

On the basis of marker profile, the majority of breast carcinomas are thought to be derived from luminal epithelial cells; however, a subgroup of tumours with more mesenchymal characteristics are associated with a worse prognosis. The hypothesis of our study is that some breast carcinomas exhibit myoepithelial rather than pure mesenchymal differentiation and that acquisition of myoepithelial characteristics confers an aggressive phenotype. Pure luminal epithelial cells and fibroblasts are readily distinguished by many markers but distinguishing between myoepithelial and fibroblast cell lineages is more problematic. The markers found to be most discriminating in our study were CK14, alpha6beta4 integrin and the myoepithelial-associated desmosomal cadherin DSg3. These markers were applied to a series of breast cell lines and purified normal breast cell populations and the expression profile related to in vitro invasive behaviour. This demonstrated that expression of one or more myoepithelial markers by tumour cells (MDA MB 231, MDA MB 468, MDA MB 436) was associated with a high invasive capacity compared with cells with a pure luminal phenotype (MCF-7, T47D, ZR75). To address why myoepithelial characteristics are associated with higher invasion, the in vitro behaviour of normal myoepithelial cells and two other nontumourigenic breast cell lines (MCF-10A, HBL100) was also analysed. Primary myoepithelial cells from normal human breast exhibit a high invasive capacity when grown at low density, suggesting that invasive capacity is part of the myoepithelial phenotype. In keeping with this, both nontumourigenic cell lines exhibited features of the myoepithelial phenotype and a high invasive capacity. These results suggest that tumours that exhibit a myoepithelial phenotype may be clinically more aggressive because a high invasive capacity is intrinsic to the myoepithelial phenotype.
Selective reduction of cis-diamminedichloroplatinum(II) nephrotoxicity by ebselen. (1990)

2-Phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) is classified as a relatively nontoxic selenium compound, probably because of its bound selenium moiety. In thiol-rich tissues, such as the kidneys, ebselen is converted into selenol intermediates. Selenols are nucleophilic agents which might be able to react with platinum compounds. The influence of ebselen on cis-diamminedichloroplatinum(II) (cisplatin)-induced nephrotoxicity in mice was assessed, using single doses of both compounds. Ebselen prevented cisplatin-induced elevations of blood urea nitrogen and serum creatinine levels and morphological kidney damage in BALB/c mice. This protective effect of ebselen was dose dependent: at a cisplatin dose of 14.5 mg/kg, maximal protection was achieved when a single dose of 10 mg of ebselen/kg was administered 1 h before cisplatin. Administration of ebselen, 10 mg/kg, 1 h after cisplatin also protected against severe nephrotoxicity. Treatment with ebselen did not reduce the antitumor activity of cisplatin against MPC 11 plasmacytoma or Prima breast tumor in BALB/c mice. However, this reduction of cisplatin-induced nephrotoxicity would be of little clinical value if it was achieved at toxic doses of ebselen. Ebselen, 10 mg/kg, did not induce blood urea nitrogen, serum creatinine, serum glutamic pyruvate transaminase, or serum glutamic oxalate elevations in the mice. These results are in agreement with the reported low toxicity of ebselen, which is now in Phase I clinical trials as an antiinflammatory drug. The present results indicate that ebselen may provide protection against cisplatin-induced nephrotoxicity, when it is given before or after cisplatin. This might open new perspectives in cancer chemotherapy.
De novo assembly and phasing of a Korean human genome (2016)

Advances in genome assembly and phasing provide an opportunity to investigate the diploid architecture of the human genome and reveal the full range of structural variation across population groups. Here we report the de novo assembly and haplotype phasing of the Korean individual AK1 (ref. 1) using single-molecule real-time sequencing, next-generation mapping, microfluidics-based linked reads, and bacterial artificial chromosome (BAC) sequencing approaches. Single-molecule sequencing coupled with next-generation mapping generated a highly contiguous assembly, with a contig N50 size of 17.9 Mb and a scaffold N50 size of 44.8 Mb, resolving 8 chromosomal arms into single scaffolds. The de novo assembly, along with local assemblies and spanning long reads, closes 105 and extends into 72 out of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously intractable sequence. High concordance between the assembly and paired-end sequences from 62,758 BAC clones provides strong support for the robustness of the assembly. We identify 18,210 structural variants by direct comparison of the assembly with the human reference, identifying thousands of breakpoints that, to our knowledge, have not been reported before. Many of the insertions are reflected in the transcriptome and are shared across the Asian population. We performed haplotype phasing of the assembly with short reads, long reads and linked reads from whole-genome sequencing and with short reads from 31,719 BAC clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs assembled from single-molecule real-time reads assigned to haplotypes on phased blocks covered 89% of genes. The haplotigs accurately characterized the hypervariable major histocompatability complex region as well as demonstrating allele configuration in clinically relevant genes such as CYP2D6. This work presents the most contiguous diploid human genome assembly so far, with extensive investigation of unreported and Asian-specific structural variants, and high-quality haplotyping of clinically relevant alleles for precision medicine.
Analysis of Adaptive Neural Networks for Helicopter Flight Control (1997)

The design of online adaptive neural networks for use in a nonlinear helicopter e ight control architecture is treated. Emphasis is given to network architecture and the effect that varying the adaptation gain has on performance. Conclusionsarebasedon asix-degree-of-freedom nonlinearevaluation model ofan attackhelicopter and ametricthatmeasuresthenetwork’ sability tocancel theeffectofmodeling errorsforacomplicated maneuver. Thenetwork isshownto providenearlyperfecttracking in thefaceofsignie cantmodelingerrorsand,additionally, to cancel the model inversion error after a short initial period of learning. Furthermore, it is shown that the performance varies gracefully and monotonically improves as the adaptation gain parameter is increased. The effect on control effort is modest and is mainly perceptible only during a short training episode that can be associated with transition from hover to forward e ight.
Reactivation of p53 by Inhibiting Mdm2 E3 Ligase: A Novel Antitumor Approach (2011)

The p53 tumor suppressor has been pursued as a cancer therapeutic target based on its ability to induce cell cycle arrest and apoptosis. Reactivation of p53 in the approximately 50% of tumors that retain a functional p53 has served as potential approach in the development of cancer drug therapy. Mdm2 is a major negative regulator of p53 and has long been thought to inhibit p53 in two ways: through ubiquitination of p53, signaling for its degradation by the proteasome, and through directly binding to p53, masking its transactivation domain. Research on Mdm2 E3 function and regulation has important implications for the feasibility of targeting Mdm2 in cancer treatment. By targeting Mdm2 in cancers, especially those harboring wild-type p53, it may be possible to restore p53 function to control tumor growth. Several inhibitors for Mdm2 have been developed and have shown promise in restoring p53 function. This review will summarize the current progress of targeting Mdm2 in cancer treatment with a focus on regulating Mdm2 E3 ubiquitin ligase activity via a number of small Mdm2 binding proteins and the post-translational modification of Mdm2 itself. The potential of inhibitors of Mdm2 E3 ligase as a new novel class of anticancer drugs will also be discussed.
Distinguishing Eosinophilic Esophagitis in Pediatric Patients (2007)

We demonstrate that school-aged children, particularly boys, who complain of dysphagia should raise the index of suspicion for EE. We also suggest that EE-associated strictures are more common than peptic strictures in children.
A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer (2006)

Large numbers of gene-modified tumor-reactive T cells can be safely given to patients, but these cells do not persist in large numbers long term. Future studies need to employ strategies to extend T cell persistence. This report is the first to document the use of genetically redirected T cells for the treatment of ovarian cancer.
IncBricks (2017)

The emergence of programmable network devices and the increasing data traffic of datacenters motivate the idea of in-network computation. By offloading compute operations onto intermediate networking devices (e.g., switches, network accelerators, middleboxes), one can (1) serve network requests on the fly with low latency; (2) reduce datacenter traffic and mitigate network congestion; and (3) save energy by running servers in a low-power mode. However, since (1) existing switch technology doesn't provide general computing capabilities, and (2) commodity datacenter networks are complex (e.g., hierarchical fat-tree topologies, multipath communication), enabling in-network computation inside a datacenter is challenging.