gebhart/patrepeval huggingface dataset:
Lgr proteins in epithelial stem cell biology (2013)

The ultimate success of global efforts to exploit adult stem cells for regenerative medicine will depend heavily on the availability of robust, highly selective stem cell surface markers that facilitate the isolation of stem cells from human tissues. Any subsequent expansion or manipulation of isolated stem cells will also require an intimate knowledge of the mechanisms that regulate these cells, to ensure maintenance of their regenerative capacities and to minimize the risk of introducing undesirable growth traits that could pose health risks for patients. A subclass of leucine-rich repeat-containing G-protein-coupled receptor (Lgr) proteins has recently gained prominence as adult stem cell markers with crucial roles in maintaining stem cell functions. Here, we discuss the major impact that their discovery has had on our understanding of adult stem cell biology in various self-renewing tissues and in accelerating progress towards the development of effective stem cell therapies.
RSK3 Encodes a Novel pp90 rsk Isoform with a Unique N-Terminal Sequence: Growth Factor-Stimulated Kinase Function and Nuclear Translocation (1995)

A novel pp90rsk Ser/Thr kinase (referred to as RSK3) was cloned from a human cDNA library. The RSK3 cDNA encodes a predicted 733-amino-acid protein with a unique N-terminal region containing a putative nuclear localization signal. RSK3 mRNA was widely expressed (but was predominant in lung and skeletal muscle). By using fluorescence in situ hybridization, the human RSK3 gene was localized to band q27 of chromosome 6. Hemagglutinin epitope-tagged RSK3 was expressed in transiently transfected COS cells. Growth factors, serum, and phorbol ester stimulated autophosphorylation of recombinant RSK3 and its kinase activity toward several protein substrates known to be phosphorylated by RSKs. However, the relative substrate specificity of RSK3 differed from that reported for other isoforms. RSK3 also phosphorylated potential nuclear target proteins including c-Fos and histones. Furthermore, although RSK3 was inactivated by protein phosphatase 2A in vitro, the enzyme was not activated by ERK2/mitogen-activated protein (MAP) kinase. In contrast, the kinase activity of another epitope-tagged RSK isoform (RSK-1) was significantly increased by in vitro incubation with ERK2/MAP kinase. Finally, we used affinity-purified RSK3 antibodies to demonstrate by immunofluorescence that endogenous RSK3 undergoes serum-stimulated nuclear translocation in cultured HeLa cells. These results provide evidence that RSK3 is a third distinct isoform of pp90rsk which translocates to the cell nucleus, phosphorylates potential nuclear targets, and may have a unique upstream activator. RSK3 may therefore subserve a discrete physiologic role(s) that differs from those of the other two known mammalian RSK isoforms.
Deep Boltzmann machines (2009)

We present a new learning algorithm for Boltz-mann machines that contain many layers of hid-den variables. Data-dependent expectations are estimated using a variational approximation that tends to focus on a single mode, and data-independent expectations are approximated us-ing persistent Markov chains. The use of two quite different techniques for estimating the two types of expectation that enter into the gradient of the log-likelihood makes it practical to learn Boltzmann machines with multiple hidden lay-ers and millions of parameters. The learning can be made more efficient by using a layer-by-layer “pre-training ” phase that allows variational in-ference to be initialized with a single bottom-up pass. We present results on the MNIST and NORB datasets showing that deep Boltzmann machines learn good generative models and per-form well on handwritten digit and visual object recognition tasks. 1
Demonstration of a narrowband Bragg-reflection filter in a single-mode fibre directional coupler (1986)

A narrowband wavelength-selective optical fibre directional coupler has been fabricated by etching a diffraction grating directly into the cladding region of a single-mode fibre. This device exhibits efficient (25%) interfibre Bragg reflection with a 6 Å bandwidth at 1.52 μm.
Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck Formation (2020)

<b>Rationale:</b> Caspase-1 is a zymogen whose activation predominantly depends upon the assembly of ASC monomers into insoluble prion-like polymers (specks). ASC polymers support caspase-1 dimer formation inducing a proximity mediated auto-activation of caspase-1. Therefore, the amount and nature of ASC monomers and polymers in lung bronchoalveolar lavage fluid (BALF) might serve as a marker of lung inflammasome activity. <b>Objectives:</b> To determine whether lung ASC concentrations or oligomerization status predicts lung function or activity of lung inflammation. <b>Methods:</b> BALF ASC amount and oligomerization status was studied in three distinct cohorts: (1) young healthy non-smokers, vapers and smokers; (2) healthy HIV+ smokers who underwent detailed lung function studies; and (3) hospitalized patients with suspected pneumonia. We quantified cell free BALF ASC levels by ELISA and immunoblot. Oligomers (i.e., ASC specks) were identified by chemical crosslinking and ability to sediment with centrifugation. <b>Measurement and Main Results:</b> ASC levels are significantly higher in lung lining fluid than in plasma as well as higher in smoker lungs compared to non-smoker lungs. In this context, ASC levels correlate with macrophage numbers, smoking intensity and loss of lung diffusion capacity in a well-characterized cohort of healthy HIV+ smokers. However, only monomeric ASC was found in our BALF samples from all subjects, including patients with lung infections. <b>Conclusions:</b> Even though, most, if not all, extracellular ASC in BALF exists in the soluble, monomeric form, monomeric ASC concentrations still reflect the inflammatory status of the lung microenvironment and correlate with loss of lung function.
A Current-Feedback Instrumentation Amplifier With a Gain Error Reduction Loop and 0.06% Untrimmed Gain Error (2011)

This paper presents a power-efficient current-feedback instrumentation amplifier (CFIA) with high gain accuracy. It is intended for interfacing precision bridge transducers and thermocouples that output mV-level signals. The gain accuracy of the CFIA is mainly limited by the mismatch of two transconductors. Applying dynamic element matching (DEM) to them ensures good gain accuracy, gain drift, and linearity. As a result, these transconductors can be implemented as simple differential pairs, resulting in significantly improved power efficiency when compared with the use of resistor-degenerated stages. To suppress the output ripple caused by DEM, an automatic gain error reduction loop dynamically nulls the G <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> mismatch of the input and feedback transconductors, thus eliminating the need for trimming. The prototype chip was realized in a 0.7-μm CMOS process. Measurement results show a maximum 0.06% untrimmed gain error and a 5-ppm INL at a gain of 100. This work also achieves an NEF of 11.2, a maximum input-referred offset of 3 μV, and a CMRR of 127 dB while consuming only 290 μA at a 5-V supply.
Interactional adjustments in humorous intercultural communication (2006)

Research has shown that native speakers (NSs) are generally capable of adjusting their language to make it appropriate for a non-native speaker (NNS) interlocutor's proficiency. Very little is known in general about humorous interaction in intercultural communication, and in particular little is known about whether, how, and what types of conversational adjustments are made during such interaction. The research presented here suggests that the adjustments made by NSs during conversational humor often may not be appropriate for the NNS. In fact, in this type of communication, NSs who do not have experience in intercultural communication may actually overestimate the amount and types of adjustments that are necessary, thus underestimating the second language (L2) user's proficiency. The result is that the L2 user sometimes gets marginalized and constructed as less than competent during playful interaction. This paper reports on a case study of one L2 user who, due to the interactional adjustments that were made when humor was used, was often positioned in marginalizing ways by interlocutors who were inexperienced in intercultural communication.
The architecture of eNVy, a non-volatile, main memory storage system (1994)

NSS is a feasible safe procedure that could be done with acceptable complications. It provides a good solution for patients with bilateral benign tumors and early localized RCC.
Estrogen-Progestogen Combinations for Contraception (1966)

The growing acceptance of various steroid compounds as contraceptive agents has been attended by extensive controversy concerning both the immediate and delayed effects of these preparations. This communication aims to identify certain questions which merit consideration and to appraise the currently available data bearing on these problems. Such a discussion is imperative because of piecemeal and inadequate treatment of these matters in the lay and scientific press. Meanwhile, the distribution of steroid compounds as contraceptives has become an accepted function of numerous public health agencies despite the lack of appropriately designed epidemiologic studies concerning many of their important potential effects. The following problems are selected for discussion because they exemplify the unmet need for more comprehensive epidemiologic analysis: (1) Will the prolonged use of steroid contraceptives affect the incidence or the pathogenesis of such malignant tumors as cancer of the breast, endometrium, or cervix? (2) Do these substances increase the
Relative Contribution of VEGF and TNF-α in the Cynomolgus Laser-Induced CNV Model: Comparing the Efficacy of Bevacizumab, Adalimumab, and ESBA105 (2010)

TNF-alpha contributes to laser-induced CNV formation, and its inhibition can be a new therapeutic target for CNV. This study suggests TNF-alpha as another therapeutic target for the prevention and treatment of CNV and adds to the emerging clinical data suggesting the therapeutic value of TNF-alpha inhibitors in age-related macular degeneration (AMD). Further, this study shows that topical therapy with suitable antibody fragments has the potential of being introduced to retinal disease treatment regimens.
Macrocyclic chelates of radiometals for diagnosis and therapy. (1990)

Monoclonal antibody technology allows the specificity of an antibody for its antigen to be used in targeting cancer cells. Stable attachment of metal ions to antibodies by means of 'bifunctional' chelating agents can add the nuclear, physical and chemical properties of the metallic elements to these target-selective proteins. The conjugation of metals--particularly radionuclides--to monoclonal antibodies results in agents for radioimmunotherapy and other medical applications. Chelators that can hold radiometals with high stability under physiological conditions are essential to avoid excessive radiation damage to non-target cells. Derivatives of polyazamacrocycles (bearing a C-substituted functional group for antibody attachment) can exhibit remarkable kinetic inertness. We have developed a new synthetic route these macrocycles via peptide synthesis and intramolecular tosylamide ring closure. Incubation of the yttrium complex of 2-p-nitrobenzyl-1,4,7,10-tetraazacyclododecane-N,N1N",N'"-te traacetic acid (nitrobenzyl-DOTA) for 18 days in serum results in loss of so little yttrium from the complex (less than 0.5%) that the rate of loss cannot be measured under these conditions. In animal models, conjugates of this chelate with monoclonal antibodies show much lower levels of yttrium in the bone than are found with DTPA chelates prepared from the cyclic anhydride. The rates of loss of indium and cobalt from nitrobenzyl-DOTA in serum are slower than from previously studied chelates. Preliminary clinical imaging studies of 111In-labeled monoclonal antibody conjugates of DOTA show highly encouraging results.
A W148R mutation in the human FOXD4 gene segregating with dilated cardiomyopathy, obsessive-compulsive disorder, and suicidality (2007)

The forkhead/winged helix box (FOX) gene family comprises at least 43 different genes encoding transcriptional factors with a highly conserved DNA-binding domain. To date, mutations in members of the FOX gene family have been causally linked to a variety of different human diseases. We describe a three-generation Albanian pedigree in which a complex phenotype consisting of dilated cardiomyopathy, obsessive-compulsive disorder, and suicidality is segregated with a missense mutation (W148R) in the human FOXD4 gene. This mutation disrupts an extremely highly conserved tryptophan residue in the forkhead domain of FOXD4, possibly resulting in reduced DNA binding capacity and altered transcriptional activity. Our present findings widen the spectrum of diseases associated with genetic aberrations in the forkhead gene family.
Effect of Mechanical Loading on Electrical Conductivity in Human Intervertebral Disk (2009)

The intervertebral disk (IVD), characterized as a charged, hydrated soft tissue, is the largest avascular structure in the body. Mechanical loading to the disk results in electromechanical transduction phenomenon as well as altered transport properties. Electrical conductivity is a material property of tissue depending on ion concentrations and diffusivities, which are in turn functions of tissue composition and structure. The aim of this study was to investigate the effect of mechanical loading on electrical behavior in human IVD tissues. We hypothesized that electrical conductivity in human IVD is strain-dependent, due to change in tissue composition caused by compression, and inhomogeneous, due to tissue structure and composition. We also hypothesized that conductivity in human annulus fibrosus (AF) is anisotropic, due to the layered structure of the tissue. Three lumbar IVDs were harvested from three human spines. From each disk, four AF specimens were prepared in each of the three principal directions (axial, circumferential, and radial), and four axial nucleus pulposus (NP) specimens were prepared. Conductivity was determined using a four-wire sense-current method and a custom-designed apparatus by measuring the resistance across the sample. Resistance measurements were taken at three levels of compression (0%, 10%, and 20%). Scanning electron microscopy (SEM) images of the human AF tissue were obtained in order to correlate tissue structure with conductivity results. Increasing compressive strain significantly decreased conductivity for all groups (p<0.05, analysis of variance (ANOVA)). Additionally, specimen orientation significantly affected electrical conductivity in the AF tissue, with conductivity in the radial direction being significantly lower than that in the axial or circumferential directions at all levels of compressive strain (p<0.05, ANOVA). Finally, conductivity in the NP tissue was significantly higher than that in the AF tissue (p<0.05, ANOVA). SEM images of the AF tissues showed evidence of microtubes orientated in the axial and circumferential directions, but not in the radial direction. This may suggest a relationship between tissue morphology and the anisotropic behavior of conductivity in the AF. The results of this investigation demonstrate that electrical conductivity in human IVD is strain-dependent and inhomogeneous, and that conductivity in the human AF tissue is anisotropic (i.e., direction-dependent). This anisotropic behavior is correlated with tissue structure shown in SEM images. This study provides important information regarding the effects of mechanical loading on solute transport and electrical behavior in IVD tissues.
The Peptides ADNF-9 and NAP Increase Survival and Neurite Outgrowth of Rat Retinal Ganglion Cells In Vitro (2005)

Both peptides, ADNF-9 and NAP, not only increase RGC survival in vitro but also support neurite outgrowth in retinal explants. These peptides deserve further attention as potential neuroprotective compounds in retinal and optic nerve diseases.
Specific Monoclonal Antibody Raised Against the p33ING1 Tumor Suppressor (1997)

An IgG1 mouse monoclonal antibody (CAb1) was produced against human recombinant p33ING1. The antibody is able to recognize native and denatured antigen in ELISA and Western blot protocols, respectively. CAb1 can be used to specifically detect the p33ING1 protein in dot blot and Western immunoblot protocols of both human and mouse cell lysates. In addition, this antibody is also useful for cellular localization of native and ectopically overexpressed p33ING1 protein by indirect immunofluorescence.
CXCL8/IL8 Stimulates Vascular Endothelial Growth Factor (VEGF) Expression and the Autocrine Activation of VEGFR2 in Endothelial Cells by Activating NFκB through the CBM (Carma3/Bcl10/Malt1) Complex (2008)

Vascular endothelial growth factor (VEGF) is a potent mitogen and permeability factor for endothelial cells that plays a central role in angiogenesis, vascular maintenance, inflammation, and cancer. VEGF also mediates the homeostatic adaptation to hypoxic conditions by promoting an increase in vascular density to compensate for decreased oxygenation. This process is triggered by an oxygen-sensitive transcription factor, hypoxia-inducible factor-1 (HIF1alpha), which becomes active in hypoxic tissues, leading to the synthesis and secretion of VEGF. The role of HIF1alpha in other processes that involve angiogenesis such as in inflammation is less clear. Of interest, endothelial cells not only respond to but also store and secrete VEGF, which is required for the maintenance of the integrity of the vascular system. How this intracellular pool of VEGF is regulated is still not understood. Here, we found that CXCL8/IL8, a potent proangiogenic and inflammatory chemokine, up-regulates VEGF mRNA and protein levels in endothelial cells by acting on its cognate receptor, CXCR2, and that this results in the autocrine activation of VEGFR2. Surprisingly, this process does not involve HIF1alpha but instead requires the activation of the transcription factor NFkappaB. Furthermore, we identified the components of the CBM complex, Carma3, Bcl10, and Malt1, as key mediators of the CXCL8/IL8-induced NFkappaB activation and VEGF up-regulation. Together, these findings support the existence of an NFkappaB-mediated pathway by which the proinflammatory chemokine CXCL8/IL8 controls the expression of VEGF in endothelial cells, thereby promoting the activation of VEGF receptors in an autocrine fashion.
Rescue of Cardiac Defects in Id Knockout Embryos by Injection of Embryonic Stem Cells (2004)

We report that Id knockout mouse embryos display multiple cardiac defects, but mid-gestation lethality is rescued by the injection of 15 wild-type embryonic stem (ES) cells into mutant blastocysts. Myocardial markers altered in Id mutant cells are restored to normal throughout the chimeric myocardium. Intraperitoneal injection of ES cells into female mice before conception also partially rescues the cardiac phenotype with no incorporation of ES cells. Insulin-like growth factor 1, a long-range secreted factor, in combination with WNT5a, a locally secreted factor, likely account for complete reversion of the cardiac phenotype. Thus, ES cells have the potential to reverse congenital defects through Id-dependent local and long-range effects in a mammalian embryo.
Oligodeoxynucleoside phosphoramidates and phosphorothioates as inhibitors of human immunodeficiency virus. (1988)

Modified oligodeoxynucleotides complementary to RNA of human immunodeficiency virus 1 (HIV-1) were tested for their ability to inhibit virally induced syncytium formation and expression of viral p24 protein. The modifications of oligomers include replacement of backbone phosphodiester groups with phosphorothioates and various phosphoramidates. All oligomers were found to be active. Oligomers with complete replacement of phosphodiesters with phosphoramidate or phosphorothioate groups were more active at the micromolar range than were unmodified oligomers of the same sequence. In addition, modified and unmodified homooligonucleotides also showed inhibition of HIV-1 replication. It is suggested that different classes of oligonucleotides may inhibit HIV replication by different mechanisms.
Induction of surfactin production in Bacillus subtilis by gsp, a gene located upstream of the gramicidin S operon in Bacillus brevis (1994)

The deduced amino acid sequence of the gsp gene, located upstream of the 5' end of the gramicidin S operon (grs operon) in Bacillus brevis, showed a high degree of similarity to the sfp gene product, which is located downstream of the srfA operon in B. subtilis. The gsp gene complemented in trans a defect in the sfp gene (sfpO) and promoted production of the lipopeptide antibiotic surfactin. The functional homology of Gsp and Sfp and the sequence similarity of these two proteins to EntD suggest that the three proteins represent a new class of proteins involved in peptide secretion, in support of a hypothesis published previously (T. H. Grossman, M. Tuckman, S. Ellestad, and M. S. Osburne, J. Bacteriol. 175:6203-6211, 1993).
Runx2/Cbfa1: A Multifunctional Regulator of Bone Formation (2003)

Runx2/Cbfa/AML3 is a member of the runt homology domain family of transcription factors, essential for osteoblast differentiation and bone formation. Defining the molecular mechanisms by which Runx2 can function as a master regulatory gene for activating the program of osteoblastogenesis has provided novel insights for transcriptional regulation of tissue-specific genes. Regulation of Runx expression has the potential to serve as a basis for the design of novel therapeutic strategies for promoting bone formation. Here we review the unique properties of Runx2 that mediate several key functions necessary for regulating skeletogenesis, controlling osteoblast growth and differentiation, and integrating the complex pathways required for bone formation and turnover.
Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors. (2002)

The human oncofetal antigen 5T4 (h5T4) is a transmembrane glycoprotein overexpressed by a wide spectrum of cancers, including colorectal, ovarian, and gastric, but with a limited normal tissue expression. Such properties make 5T4 an excellent putative target for cancer immunotherapy. The murine homologue of 5T4 (m5T4) has been cloned and characterized, which allows for the evaluation of immune intervention strategies in "self-antigen" in vivo tumor models. We have constructed recombinant vaccinia viruses based on the highly attenuated and modified vaccinia virus ankara (MVA strain), expressing h5T4 (MVA-h5T4), m5T4 (MVA-m5T4), and Escherichia coli LacZ (MVA-LacZ). Immunization of BALB/c and C57BL/6 mice with MVA-h5T4 and MVA-m5T4 constructs induced antibody responses to human and mouse 5T4, respectively. C57BL/6 and BALB/c mice vaccinated with MVA-h5T4 were challenged with syngeneic tumor line transfectants, B16 melanoma, and CT26 colorectal cells that express h5T4. MVA-h5T4-vaccinated mice showed significant tumor retardation compared with mice vaccinated with MVA-LacZ or PBS. In active treatment studies, inoculation with MVA-h5T4 was able to treat established CT26-h5T4 lung tumor and to a lesser extent B16.h5T4 s.c. tumors. Additionally, when C57BL/6 mice vaccinated with MVA-m5T4 were challenged with B16 cells expressing m5T4, resulting growth of the tumors was significantly retarded compared with control animals. Furthermore, mice vaccinated with MVA-m5T4 showed no signs of autoimmune toxicity. These data support the use of MVA-5T4 for tumor immunotherapy.