gebhart/patrepeval huggingface dataset:
A Dap12-Mediated Pathway Regulates Expression of Cc Chemokine Receptor 7 and Maturation of Human Dendritic Cells (2001)

Gene targeting of the adaptor molecule DAP12 in mice caused abnormal distribution and impaired antigen presentation capacity of dendritic cells (DCs). However, the DAP12-associated receptors expressed on DCs and their functions have not been identified yet. Here we show that the triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12. TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase. In contrast to Toll-like receptor-mediated signaling, TREM2/DAP12 stimulation is independent of nuclear factor-kappaB and p38 stress-activated protein kinase. This novel DC activation pathway may regulate DC homeostasis and amplify DC responses to pathogens, explaining the phenotype observed in DAP12-deficient mice.
What Else Can CD39 Tell Us? (2017)

As the rate-limiting enzyme in ATP/ADP-AMP-adenosine pathway, CD39 would be a novel checkpoint inhibitor target in preventing adenosine-triggered immune-suppressive effect. In addition, CD39<sup>hi</sup> Tregs, but not CD25<sup>hi</sup> Tregs, exhibit sustained Foxp3 levels and functional abilities, indicating it could represent a new specific marker of Tregs. Similarly, inhibition of CD39 enzymatic function at the surface of tumor cells alleviates their immunosuppressive activity. Far from conclusive, present research revealed that CD39 also dephosphorylated and thus inactivated self- and pathogen-associated phosphoantigens of Vγ9Vδ2 T cells, which may be the most promising subpopulation for cellular vaccine. CD39 is also tightly related to Th17 cells and can be regarded as a Th17 cells marker. In this review, we focus on present research of CD39 ectoenzyme and provide insights into its clinical application.
CD22 Regulates B Cell Receptor-mediated Signals via Two Domains That Independently Recruit Grb2 and SHP-1 (2001)

Recognition of antigen by the B cell antigen receptor (BCR) determines the subsequent fate of a B cell and is regulated in part by the involvement of other surface molecules, termed coreceptors. CD22 is a B cell-restricted coreceptor that gets rapidly tyrosyl-phosphorylated and recruits various signaling molecules to the membrane following BCR ligation. Although CD22 contains three immunoreceptor tyrosine-based inhibitory motifs (ITIMs), only the two carboxyl-terminal ITIM tyrosines are required for efficient recruitment of the SHP-1 phosphatase after BCR ligation. Furthermore, Grb2 is inducibly recruited to CD22 in human and murine B cells. Unlike SHP-1, Grb2 recruitment to CD22 is not inhibited by specific doses of the Src family kinase-specific inhibitor PP1. The tyrosine residue in CD22 required for Grb2 recruitment (Tyr-828) is distinct and independent from the two ITIM tyrosines required for efficient SHP-1 recruitment (Tyr-843 and Tyr-863). Individually both Lyn and Syk are required for maximal phosphorylation of CD22 following ligation of the BCR, and together Lyn and Syk are required for all of the constitutive and induced tyrosine phosphorylation of CD22. We propose that the cytoplasmic tail of CD22 contains two domains that regulate signal transduction pathways initiated by the BCR and B cell fate.
The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models (2013)

Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein due to the functional loss of the SMN1 gene and the inability of its paralog, SMN2, to fully compensate due to reduced exon 7 splicing efficiency. Since SMA patients have at least one copy of SMN2, drug discovery campaigns have sought to identify SMN2 inducers. C5-substituted quinazolines increase SMN2 promoter activity in cell-based assays and a derivative, RG3039, has progressed to clinical testing. It is orally bioavailable, brain-penetrant and has been shown to be an inhibitor of the mRNA decapping enzyme, DcpS. Our pharmacological characterization of RG3039, reported here, demonstrates that RG3039 can extend survival and improve function in two SMA mouse models of varying disease severity (Taiwanese 5058 Hemi and 2B/- SMA mice), and positively impacts neuromuscular pathologies. In 2B/- SMA mice, RG3039 provided a >600% survival benefit (median 18 days to >112 days) when dosing began at P4, highlighting the importance of early intervention. We determined the minimum effective dose and the associated pharmacokinetic (PK) and exposure relationship of RG3039 and DcpS inhibition ex vivo. These data support the long PK half-life with extended pharmacodynamic outcome of RG3039 in 2B/- SMA mice. In motor neurons, RG3039 significantly increased both the average number of cells with gems and average number of gems per cell, which is used as an indirect measure of SMN levels. These studies contribute to dose selection and exposure estimates for the first studies with RG3039 in human subjects.
Ornithine decarboxylase and polyamines in familial adenomatous polyposis. (1997)

Familial adenomatous polyposis (FAP), due to germ-line mutation of the adenomatous polyposis coli (APC) gene, is characterized by development of colorectal adenomas and ultimately colorectal cancer. The usefulness of ornithine decarboxylase (ODC) activity and polyamine levels in normal-appearing colorectal mucosa to stratify risk for colorectal neoplasia by discriminating presymptomatic individuals with germ-line APC mutation (genotype-positive) from genotype-negative family controls was evaluated in 36 at-risk subjects undergoing endoscopic and genetic screening for FAP. ODC activity and levels of putrescine, spermidine, and spermine were significantly higher in presymptomatic genotype-positive patients compared to genotype-negative persons (P = 0.029, <0.001, 0.002, and <0.001, respectively). Moreover, a putrescine level with a cutoff point of 1.5 nmol/mg protein was the most accurate single discriminator of risk status. ODC activity and polyamine levels are significantly elevated in gene carriers of FAP before the development of polyposis, suggesting a role for these compounds in tumorigenesis of FAP. These assays may be useful in evaluating at-risk members of FAP families in which mutation of the APC gene cannot be found.
Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells (2013)

NCI (5R21CA115043-2), NHLBI (5R01HL103532-03), and Leukemia and Lymphoma Society Translational Research Program.
Development and characterisation of phosphate glasses for athermalisation (2004)

Lightwave devices such as gratings have a drawback where the central wavelength of the devices is sensitive to changes in temperature, which compromises their performance. This problem is particularly acute in systems that employ Wavelength Division Multiplexing (WDM), where the stability of wavelength with regards to temperature is essential. An athermal waveguide, which is inherently insensitive to temperature, is an ideal choice to solve this problem instead of using a passive temperature control unit, which could limit the optimum performance of a WDM system. &#13;\n&#13;\nGenerally, athermal glasses must exhibit negative refractive index change with temperature (dn/dT) to counter the effect of thermal expansion. Phosphate glasses are ideal candidates for athermalisation as they exhibit negative dn/dT. An interferometer set-up has been constructed to specifically measure dn/dT of the glasses. &#13;\n&#13;\nThree different phosphate glass families were prepared and characterised in terms of their optical and thermal properties. The properties of the potassium aluminophosphate glasses were strongly influenced by the strengthening effect of Al3+, the trend observed for the binary phosphate glasses depended on the availability of terminal oxygens to coordinate the cations while the change in the properties of borophosphate glasses depended on the effect and coordination number of B3+. Glasses with negative dn/dT have been achieved from the various compositions of glasses studied. The results showed that there was a minimum thermal expansion coefficient (α) for each glass system, beyond which α would overcome the effect of polarisability change with temperature so that the glasses exhibited negative dn/dT. Semi-empirical equations linking dn/dT and α have been defined, enabling the estimation of dn/dT of any glass within the same system. This research work represents the first comprehensive measurement of dn/dT of phosphate glasses. &#13;\n&#13;\nBoth fibre and planar waveguides were fabricated. Extrusion was used to prepare the preform for fibre drawing. The extrusion process used a two-die assembly to extrude dissimilar glasses, and is the first demonstration of its kind. The spin-coating process was used to deposit layers of glass on glass substrates to produce planar structures. The success of the extrusion and spin-coating work showed that these processes could be used for combinations of glasses with dissimilar thermal properties. Femtosecond writing was investigated on the phosphate glasses and channel waveguides have been successfully defined.
β-Carboline Compounds, Including Harmine, Inhibit DYRK1A and Tau Phosphorylation at Multiple Alzheimer's Disease-Related Sites (2011)

Harmine, a β-carboline alkaloid, is a high affinity inhibitor of the dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) protein. The DYRK1A gene is located within the Down Syndrome Critical Region (DSCR) on chromosome 21. We and others have implicated DYRK1A in the phosphorylation of tau protein on multiple sites associated with tau pathology in Down Syndrome and in Alzheimer's disease (AD). Pharmacological inhibition of this kinase may provide an opportunity to intervene therapeutically to alter the onset or progression of tau pathology in AD. Here we test the ability of harmine, and numerous additional β-carboline compounds, to inhibit the DYRK1A dependent phosphorylation of tau protein on serine 396, serine 262/serine 356 (12E8 epitope), and threonine 231 in cell culture assays and in vitro phosphorylation assays. Results demonstrate that the β-carboline compounds (1) potently reduce the expression of all three phosphorylated forms of tau protein, and (2) inhibit the DYRK1A catalyzed direct phosphorylation of tau protein on serine 396. By assaying several β-carboline compounds, we define certain chemical groups that modulate the affinity of this class of compounds for inhibition of tau phosphorylation.
Transcriptional gene silencing by short interfering RNAs. (2005)

Double-stranded RNA (dsRNA)-induced sequence-specific gene silencing in animals and plants is known as RNA interference. In mammalian cells, although long dsRNAs induce an interferon-mediated, non-specific gene silencing, short interfering RNAs (siRNAs) that are processed from long dsRNAs by Dicer can induce sequence-specific gene silencing. Since siRNAs can be designed for genes of interest, these molecules have great potential to be used as effective gene therapies. In plants, siRNAs targeted to CpG islands within a promoter can also induce RNA-directed DNA methylation. In addition, siRNAs have a role in heterochromatic gene silencing in fission yeasts, plants and animals. Recently, siRNAs were demonstrated to induce transcriptional gene silencing (TGS) via DNA methylation in human cells. This review will focus on TGS by siRNAs, such as DNA methylation and histone methylation.
Detecting driver phone use leveraging car speakers (2011)

This work addresses the fundamental problem of distinguishing between a driver and passenger using a mobile phone, which is the critical input to enable numerous safety and interface enhancements. Our detection system leverages the existing car stereo infrastructure, in particular the speakers and Bluetooth network. Our acoustic approach has the phone send a series of customized high frequency beeps via the car stereo. The beeps are spaced in time across the left, right, and if available, front and rear speakers. After sampling the beeps, we use a sequential change-point detection scheme to time their arrival, and then use a differential approach to estimate the phone's distance from the car's center. From these differences a passenger or driver classification can be made. To validate our approach, we experimented with two kinds of phones and in two different cars. We found that our customized beeps were imperceptible to most users, yet still playable and recordable in both cars. Our customized beeps were also robust to background sounds such as music and wind, and we found the signal processing did not require excessive computational resources. In spite of the cars' heavy multi-path environment, our approach had a classification accuracy of over 90%, and around 95% with some calibrations. We also found we have a low false positive rate, on the order of a few percent.
Role of Environmental Contamination as a Risk Factor for Acquisition of Vancomycin-Resistant Enterococci in Patients Treated in a Medical Intensive Care Unit (2003)

Among all other factors associated with VRE transmission, VRE acquisition may depend on room contamination, even after extensive cleaning. This study underscores the need for better cleaning and the role of the environment in transmission of VRE.
Fluorouracil plus Levamisole as Effective Adjuvant Therapy after Resection of Stage III Colon Carcinoma: A Final Report (1995)

Fluorouracil plus levamisole is tolerable adjuvant therapy to surgery; it has been confirmed to substantially increase cure rates for patients with high-risk (stage III) colon cancer. It should be considered standard treatment for all such patients not entered into clinical trials.
Selective Doped Polysilicon Growth: Effect of Carbon on the Selective Doped Silicon Film Growth (1987)

We have announced selective polysilicon growth technology based on selective epitaxial growth technology (1, 2). In this paper, we report the influence of on the crystallinity of silicon, the doping control with , and the selective growth of silicon. It has become possible to control the transition from epitaxial silicon to polysilicon and . By achieving a definite doping control, the resistivity can be lowered to . A combination of these technologies made it possible to grow selectively doped polysilicon with a flat surface.
Enzymatic Method of Preparation of Opticallly Active Trans-2-Amtno Cyclohexanol Derivatives (1999)

Abstract Supported Lipase Amano PS-D catalyzes the resolution of (±)-trans-2-tert butoxycarbonyl amino cyclohexanol by a selective acylation reaction. Using the supported enzyme gave a much faster reaction compared to existing methodology on similar substrates. A variety of acylating agents were investigated, with vinyl acetate providing the most practical and convenient procedure.
Sphingosine 1-phosphate antagonizes apoptosis of human leukemia cells by inhibiting release of cytochrome c and Smac/DIABLO from mitochondria (2001)

Sphingosine 1-phosphate (S-1P) has been implicated as a second messenger preventing apoptosis by counteracting activation of executioner caspases. Here it is reported that S-1P prevents apoptosis and executioner caspase-3 activation by inhibiting the translocation of cytochrome c and Smac/DIABLO from mitochondria to the cytosol induced by anti-Fas, tumor necrosis factor-alpha (TNF-alpha), serum deprivation, and cell-permeable ceramides in the human acute leukemia Jurkat, U937, and HL-60 cell lines. Furthermore, the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate, which stimulates sphingosine kinase, the enzyme responsible for S-1P production, also inhibits cytochrome c and Smac/DIABLO release. In contrast, dimethylsphingosine (DMS), a specific inhibitor of sphingosine kinase, sensitizes cells to cytochrome c and Smac/DIABLO release triggered by anti-Fas, TNF-alpha, serum deprivation, or ceramide. DMS-induced mitochondrial apoptogenic factor leakage can likewise be overcome by S-1P cotreatment. Hence, S-1P, likely generated through a protein kinase C- mediated activation of sphingosine kinase, inhibits the apoptotic cascade upstream of the release of the mitochondrial apoptogenic factors, cytochrome c, and Smac/DIABLO in human acute leukemia cells.
Agonist-induced Conformational Changes at the Cytoplasmic Side of Transmembrane Segment 6 in the β2 Adrenergic Receptor Mapped by Site-selective Fluorescent Labeling (2001)

The environmentally sensitive, sulfhydryl-reactive, fluorescent probe N,N'-dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) ethylene-diamine (IANBD) was used as a molecular reporter of agonist-induced conformational changes in the beta(2) adrenergic receptor, a prototype hormone-activated G protein-coupled receptor. In the background of a mutant beta(2) adrenergic receptor, with a minimal number of endogenous cysteine residues, new cysteines were introduced in positions 269(6.31), 270(6.32), 271(6.33), and 272(6.34) at the cytoplasmic side of transmembrane segment (TM) 6. The resulting mutant receptors were fully functional and bound both agonists and antagonist with high affinities also upon IANBD labeling. Fluorescence spectroscopy analysis of the purified and site-selectively IANBD-labeled mutants suggested that the covalently attached fluorophore was exposed to a less polar environment at all four positions upon agonist binding. Whereas evidence for only a minor change in the molecular environment was obtained for positions 269(6.31) and 270(6.32), the full agonist isoproterenol caused clear dose-dependent and reversible increases in fluorescence emission at positions 271(6.33) and 272(6.34). The data suggest that activation of G protein-coupled receptors, which are activated by "diffusible" ligands, involves a structural rearrangement corresponding to the cytoplasmic part of TM 6. The preferred conformations of the IANBD moiety attached to the inserted cysteines were predicted by employing a computational method that incorporated the complex hydrophobic/hydrophilic environment in which the cysteines reside. Based on these preferred conformations, it is suggested that the spectral changes reflect an agonist-promoted movement of the cytoplasmic part of TM 6 away from the receptor core and upwards toward the membrane bilayer.
Surface loss simulations of superconducting coplanar waveguide resonators (2011)

Losses in superconducting planar resonators are presently assumed to predominantly arise from surface-oxide dissipation, due to experimental losses varying with choice of materials. We model and simulate the magnitude of the loss from interface surfaces in the resonator and investigate the dependence on power, resonator geometry, and dimensions. Surprisingly, the dominant surface loss is found to arise from the metal-substrate and substrate-air interfaces. This result will be useful in guiding device optimization, even with conventional materials.
Epithelial to Mesenchymal Transition Is Mechanistically Linked with Stem Cell Signatures in Prostate Cancer Cells (2010)

These results suggest that miR-200 played a pivotal role in linking the characteristics of cancer stem-like cells with EMT-like cell signatures in PCa. Selective elimination of cancer stem-like cells by reversing the EMT phenotype to Mesenchymal-Epithelial Transition (MET) phenotype using novel agents would be useful for the prevention of tumor recurrence especially by eliminating those cells that are the "Root Cause" of tumor development and recurrence.
Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients (2015)

The analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for the assessment of solid tumors. Although its clinical potential has been increasingly recognized, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. With respect to the size profile of such plasma DNA molecules, a number of studies reported the finding of increased integrity of tumor-derived plasma DNA, whereas others found evidence to suggest that plasma DNA molecules released by tumors might be shorter. Here, we performed a detailed analysis of the size profiles of plasma DNA in 90 patients with hepatocellular carcinoma, 67 with chronic hepatitis B, 36 with hepatitis B-associated cirrhosis, and 32 healthy controls. We used massively parallel sequencing to achieve plasma DNA size measurement at single-base resolution and in a genome-wide manner. Tumor-derived plasma DNA molecules were further identified with the use of chromosome arm-level z-score analysis (CAZA), which facilitated the studying of their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of plasma mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These results have improved our understanding of the size profile of tumor-derived circulating cell-free DNA and might further enhance our ability to use plasma DNA as a molecular diagnostic tool.
Radio access for ultra-reliable and low-latency 5G communications (2015)

Fifth generation wireless networks are currently being developed to handle a wide range of new use cases. One important emerging area is ultra-reliable communication with guaranteed low latencies well beyond what current wireless technologies can provide. In this paper, we explore the viability of using wireless communication for low-latency, high-reliability communication in an example scenario of factory automation, and outline important design choices for such a system. We show that it is possible to achieve very low error rates and latencies over a radio channel, also when considering fast fading signal and interference, channel estimation errors, and antenna correlation. The most important tool to ensure high reliability is diversity, and low latency is achieved by using short transmission intervals without retransmissions, which, however, introduces a natural restriction on coverage area.
Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. (1992)

The mesolimbic dopaminergic system has been implicated in mediating the motivational effects of opioids and other drugs of abuse. The site of action of opioids within this system and the role of endogenous opioid peptides in modulating dopamine activity therein remain unknown. Employing the technique of in vivo microdialysis and the administration of highly selective opioid ligands, the present study demonstrates the existence of tonically active and functionally opposing mu and kappa opioid systems that regulate dopamine release in the nucleus accumbens, the major terminal area of A10 dopaminergic neurons. Thus, stimulation of mu-type receptors in the ventral tegmental area, the site of origin of A10 dopaminergic neurons, increases dopamine release whereas the selective blockade of this opioid receptor type results in a significant decrease in basal dopamine release. In contrast, stimulation of kappa-type receptors within the nucleus accumbens decreases dopamine release whereas their selective blockade markedly increases basal dopamine release. These data show that tonic activation of mu and kappa receptors is required for the maintenance of basal dopamine release in the nucleus accumbens. In view of the postulated role of the mesolimbic system in the mediation of drug-induced alterations in mood and affect, such findings may have implications for the treatment of opiate dependence and affective disorders.