gebhart/patrepeval huggingface dataset:
Quantitative and qualitative normal regulatory T cells are not capable of inducing suppression in SLE patients due to T-cell resistance (2008)

Previous reports have suggested that regulatory T cells (Treg) are abnormal in patients with systemic lupus erythematosus (SLE). In the present work, we quantified CD4+FOXP3+ Treg cells in patients with SLE and found no quantitative alterations. However, we found a clear defect in suppression assays. Surprisingly, SLE-derived Treg cells exhibited a normal phenotype and functional capacity. Conversely, SLE-derived CD4+CD25(-) effector T cells resisted suppression by autologous and allogeneic regulatory cells. Our findings strongly suggest that the defect in T-cell suppression observed in SLE is because of effector cell resistance and not because of an abnormal regulatory function.
Characterization of avirulent mutant Legionella pneumophila that survive but do not multiply within human monocytes. (1987)

Legionella pneumophila, the causative agent of Legionnaires' disease, is a Gram-negative bacterium and a facultative intracellular parasite that multiplies in human monocytes and alveolar macrophages. In this paper, mutants of L. pneumophila avirulent for human monocytes were obtained and extensively characterized. The mutants were obtained by serial passage of wild-type L. pneumophila on suboptimal artificial medium. None of 44 such mutant clones were capable of multiplying in monocytes or exerting a cytopathic effect on monocyte monolayers. Under the same conditions, wild-type L. pneumophila multiplied 2.5-4.5 logs, and destroyed the monocyte monolayers. The basis for the avirulent phenotype was an inability of the mutants to multiply intracellularly. Both mutant and wild-type bacteria bound to and were ingested by monocytes, and both entered by coiling phagocytosis. Thereafter, their intracellular destinies diverged. The wild-type formed a distinctive ribosome-lined replicative phagosome, inhibited phagosome-lysosome fusion, and multiplied intracellularly. The mutant did not form the distinctive phagosome nor inhibit phagosome-lysosome fusion. The mutant survived intracellularly but did not replicate in the phagolysosome. In all other respects studied, the mutant and wild-type bacteria were similar. They had similar ultrastructure and colony morphology; both formed colonies of compact and diffuse type. They had similar structural and secretory protein profiles and LPS profile by PAGE. Both the mutant and wild-type bacteria were completely resistant to human complement in the presence or absence of high titer anti-L. pneumophila antibody. The mutant L. pneumophila have tremendous potential for enhancing our understanding of the intracellular biology of L. pneumophila and other parasites that follow a similar pathway through the mononuclear phagocyte. Such mutants also show promise for enhancing our understanding of immunity to L. pneumophila, and they may serve as prototypes in the development of safe and effective vaccines against intracellular pathogens.
Low threshold half-wave vertical-cavity lasers (1994)

Data are presented characterising half-wavelength vertical-cavity surface-emitting lasers defined by a native-oxide ring in which the native oxide is 200 Å from the single quantum well. The lowest threshold is achieved with a 2 µm square active region, with a minimum threshold current of 91 µA continuous-wave at room temperature.
Carcinoembryonic Antigen (CEA) Inhibits NK Killing via Interaction with CEA-Related Cell Adhesion Molecule 1 (2005)

The NK killing activity is regulated by activating and inhibitory NK receptors. All of the activating ligands identified so far are either viral or stress-induced proteins. The class I MHC proteins are the ligands for most of the inhibitory NK receptors. However, in the past few years, several receptors have been identified that are able to inhibit NK killing independently of class I MHC recognition. We have previously demonstrated the existence of a novel inhibitory mechanism of NK cell cytotoxicity mediated by the homophilic carcinoembryonic Ag (CEA)-related cell adhesion molecule 1 (CEACAM1) interactions. In this study, we demonstrate that CEACAM1 also interacts heterophilically with the CEA protein. Importantly, we show that these heterophilic interactions of CEA and CEACAM1 inhibit the killing by NK cells. Because CEA is expressed on a wide range of carcinomas and commonly used as tumor marker, these results represent a novel role for the CEA protein enabling the escape of tumor cells from NK-mediated killing. We further characterize, for the first time, the CEACAM1-CEA interactions. Using functional and binding assays, we demonstrate that the N domains of CEACAM1 and CEA are crucial but not sufficient for both the CEACAM1-CEACAM1 homophilic and CEACAM1-CEA heterophilic interactions. Finally, we suggest that the involvement of additional domains beside the N domain in the heterophilic and homophilic interactions is important for regulating the balance between cis and trans interactions.
The Human Nuclear Xenobiotic Receptor PXR: Structural Determinants of Directed Promiscuity (2001)

The human nuclear pregnane X receptor (hPXR) activates cytochrome P450-3A expression in response to a wide variety of xenobiotics and plays a critical role in mediating dangerous drug-drug interactions. We present the crystal structures of the ligand-binding domain of hPXR both alone and in complex with the cholesterol-lowering drug SR12813 at resolutions of 2.5 and 2.75 angstroms, respectively. The hydrophobic ligand-binding cavity of hPXR contains a small number of polar residues, permitting SR12813 to bind in three distinct orientations. The position and nature of these polar residues were found to be critical for establishing the precise pharmacologic activation profile of PXR. Our findings provide important insights into how hPXR detects xenobiotics and may prove useful in predicting and avoiding drug-drug interactions.
Longitudinal Profile of Retinal Ganglion Cell Damage after Optic Nerve Crush with Blue-Light Confocal Scanning Laser Ophthalmoscopy (2008)

The longitudinal profile of RGC degeneration after optic nerve crush is characterized by a two-phase exponential decay model. bCSLO imaging provides an efficient and noninvasive approach to the longitudinal study of progressive RGC damage.
Ependymin, a Brain Extracellular Glycoprotein, and CNS Plasticitya (1991)

Ependymin, a glycoprotein of the brain ECF, has been implicated in the neurochemistry of memory and neuronal regeneration. Three behavioral experiments (swimming with a float, avoidance conditioning, and classical conditioning) in the goldfish and one in the mouse (T-maze learning) indicate that ependymin has a role in the synaptic changes that take place in the consolidation step of memory formation and the activity-dependent phase of sharpening of goldfish retinotectal connections during neuronal regeneration. The ECF concentration of the protein was found to decrease after the goldfish learned to associate a light stimulus (CS) with the subsequent arrival of a shock (US): paired CS-US gave changes whereas an unpaired presentation of CS-US gave no changes relative to the unstimulated controls. Ependymin is present in ECF as a mixture of three disulfide-linked dimers of two acidic (alpha and beta) polypeptide chains (37 kDa and 31 kDa). Upon removal of its N-linked glycan fragment by N-glycosidase F, the beta chain yields gamma-ependymin (26 kDa). Determinations of the amino acid sequence of gamma-ependymin indicate that it is a unique protein with no long sequence homologies to any known polypeptide. There are, however, small segments (5-7 amino acids long) with homologies to fibronectin, laminin, and tubulin. Ependymin has the capacity to polymerize into FIP (after activation by phosphorylation) in response to events that deplete ECF calcium. FIP is insoluble in 2% SDS in 6 M urea, 10 mM Ca2+Ac2, 100% acetic acid, chloroform/methanol (2/1), saturated KCNS, and even 100% trifluoroacetic acid. FIP was found to be present in goldfish brain and to be formed as a labeled product in vivo. Ependymin's FIP-forming property was used to propose a molecular hypothesis for generating synaptic changes in response to local extracellular depletions of calcium at sites of "associating inputs." The model assumes that, following NMDA receptor stimulation, the translocated PKC that is generated activates extracellular ependymin by converting it to its phosphorylated form using presynaptically released ATP. The hypothesis was tested in studies of LTP of rat hippocampal slices at CA1. After LTP, new sites that stained with antisera to ependymin, visible at 100x, were obtained in its potentiated radiatum in the CA1 region but not in the unpotentiated CA3. Electron microscopic studies showed that the horseradish peroxidase reaction product obtained was localized at synaptic clefts and postsynaptic regions. The results suggest that FIP may be formed at extracellular and postsynaptic loci where multiple associating inputs interact at CA1.
Quenching investigation on new erbium doped fibers using MCVD nanoparticle doping process (2010)

Ever demanding network implementations brought new requirements to be addressed to offer cost effective and power efficient solutions with smaller footprints. This general trend together with the constant need to improve L-band optical amplification efficiency account for the renewed interest on highly doped Erbium fibers. Erbium doped fiber amplifiers (EDFAs) performance degradation with Er<sup>3+</sup> concentration increase has extensively been studied1 and is attributed to additional losses due to energy transfers between neighbouring ions. Experimental observations have been interpreted by the homogeneous up-conversion (HUC) and pair-induced quenching (PIQ) models, which account for pump power penalty and unsaturable absorption respectively. For a given Er3+ concentration, studies have also showed that both fiber manufacturing process and core matrix composition have a strong impact on quenching parameters. In 2009, we introduced a new doping concept involving Al<sub>2</sub>O<sub>3</sub>Er nanoparticles (NP) in a MCVD-compatible process showing improved performances in terms of erbium homogeneity along the fiber length for standard doping levels.<sup>2</sup> In this paper, we address our most recent work on concentration quenching encountered in both standard and NP Erbium doped fibers.
A study of salivary secretion in Parkinson's disease. (1999)

Hypersialorrhea is frequently reported in patients with idiopathic Parkinson's Disease (PD). Excessive production of saliva, swallowing difficulties, or both could explain this complaint. Dopamine (DA) has been shown to modulate salivary secretion in a number of vertebrate and invertebrate species. The present study was performed to compare the unstimulated salivary flow in 83 patients with PD (8 untreated and 75 treated with levodopa + DA agonist) and in 65 age- and sex-matched control subjects. The Mann-Whitney U-test showed a significantly lower salivary flow in treated patients with PD (535 +/- 42 mg/2 min) (p < 0.002) and de novo patients (447 +/- 141) (p < 0.03) compared to controls (834 +/- 68 mg/2 min) with no relation with age or sex. Finally, the present study of reduced salivary flow in PD suggests that complaints of hypersialorrhea are not caused by a salivary defect, but could be explained by difficulties in swallowing. The decrease in salivary flow could be explained by autonomic dysfunction in PD.
Expression of the period clock gene within different cell types in the brain of Drosophila adults and mosaic analysis of these cells' influence on circadian behavioral rhythms (1992)

The product of the period (per) gene of Drosophila melanogaster is continuously required for the functioning of the circadian pacemaker of locomotor activity. We have used internally marked mosaics to determine the anatomical locations at which per expression is required for adult rhythmicity, and thus where the fly's circadian pacemaker is likely located in this holometabolous insect. We first provide a detailed description of the distribution and nature of per-expressing cells in the fly's CNS. Using an antibody to the per gene product, or to that of a reporter of per expression, in conjunction with an antibody to the embryonic lethal-abnormal visual system (elav) gene product--which is used as a marker of neuronal identity--we have experimentally confirmed previously proposed assignments of per-expressing cells to the neuronal and glial classes. Thus, we found that per expression and elav immunoreactivity colocalized in large cells located in the lateral cortex of the central brain, as well as in more dorsally located cells in the posterior central brain. In contrast, we found that cells located at the margins of the cortex and the neuropil, and within the neuropil, as well as smaller cortical cells found throughout the brain's cortex, were elav negative, supporting the notion that they are glial in nature. Using internally marked mosaics, we find that the pacemaker is located in brain but is not exclusive to the eyes, the ocelli, or the optic lobes, which is consistent with previous reports obtained in this and other insects of this class. Although the pacemaker may be a paired structure, we show that the functioning of one of them is sufficient for rhythmicity. Finally, we report that glial expression is sufficient for some behavioral rhythmicity to be manifest. However, the rhythmicities of animals for which per expression was confined to glia were weak, suggesting that neuronal per expression as well may be required for normal pacemaker function.
Single-Molecule Detection and Probe Strategies for Rapid and Ultrasensitive Genomic Detection (2005)

This paper reviews the current state-of-the-art development of single-molecule detection (SMD)-based methods for ultrasensitive and specific analysis of genomic sequences. We first discuss several newly devised single fluorescent probe strategies that allow separation-free detection of low-abundance DNA sequences, such as quantum dot (QD)-mediated fluorescence resonance energy transfer (FRET) technology and dual-color fluorescence coincidence and colocalization analysis. Various schemes toward single DNA sizing and sequencing in solutions or on surfaces are also reviewed. In the end, we summarize the different microfluidic approaches developed for use with SMD to facilitate rapid, low-volume and quantitative analysis, such as electrokinetic and hydrodynamic single-molecule manipulation techniques.
Automatic Variable-Width Routing for VLSI (1983)

Some of the essentials for layout of complex VLSI circuits are hierarchical design based on macrocells of arbitrary size and shape, power nets with local varying width, signal nets with individual width and very compacted layouts which still have to guarantee all geometrical design rules. This paper is devoted to the problem of automatic routing with real geometries. VWROUT, a Variable Width Routing System is presented. This includes planar power net routing with variable width on a single layer, loose and final routing of signal nets with variable width on two layers (H-V routing), and layout compaction with design-rule verification. Though automatic routing systems have been developed successfully, the intention of this paper is to demonstrate that layout programs of today have not yet become perfect. A lot of effort in software development is necessary in order that automatic layouts can compared with manual designs.
Diabroticite Beetle Responses to Cucurbitacin Kairomones in Cucurbita Hybrids1 (1980)

Abstract Two hybrid cucurbits were produced that combined the genetic production of cucurbitacins as found in the wild bitter gourds, Cucurbita andreana Naud and C. texana Gray, with the high fruit yields characteristic of the domesticated cultivars of C. maxima Duchesne and C. pepo L. Both the C. andreana × C. maxima and C. texana × C. pepo hybrids produced relatively high yields of fruit with high cucurbitacin content. Both hybrids showed promise as attractants for population estimation of corn rootworm beetles ( Diabrotica undecimpunctata howardi Barber and D. virgifera LeConte) or for use in poisoned baits using methomyl or trichlorfon with the bitter cut fruits or fruit homogenates.
CD44+ cancer cells express higher levels of the anti-apoptotic protein Bcl-2 in breast tumours. (2009)

Breast tumours consist of phenotypically diverse populations of breast cancer cells of which only a minority has the ability to form new tumours. The capacity for breast tumour development has been shown to be restricted to breast cancer stem cells with the CD44+/CD24(-/low) phenotype. These cells can resist apoptosis through mechanisms such as the regulation of Bcl-2. Identification of this population of cells is important because of its implication in the development of new therapeutic strategies. One hundred and forty-six primary operable breast cancer patients were investigated in order to identify the population of CD44+ and Bcl-2+ cells in paraffin-embedded tissues by immunohistochemistry. The prevalence of these phenotypes was then correlated with clinicopathological features. CD44 and Bcl-2 expression was detected in 86% and 82% of breast tumours, respectively. There was no significant correlation between CD44+ tumour cell prevalence and tumour characteristics, whereas the prevalence of CD44+ cells was associated with higher levels of Bcl-2 expression (P = 0.004). In univariate analysis, Bcl-2 expression was correlated with breast tumours of lower grade (P < 0.001) and fewer lymphatic metastases (P < 0.05). Our findings suggest that the prevalence of CD44+ tumour cells as a subpopulation of breast cancer stem cells was of no clinicopathological significance, but was correlated with higher Bcl-2 expression. This population of tumour cells may thus be more resistant to apoptosis. Targeting these cells in combination with current treatments may be more effective in treating breast cancer patients.
Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis (2011)

In this large cohort of patients with histologically documented ASH early after admission and no sepsis, liver biopsy identified marked intraparenchymal cholestasis as an independent predictor of poor short term outcome together with age and the Maddrey's score. It may be hypothesized that incorporation of this particular variable into existing disease severity scores for ASH would improve their performance.
Cell‐free circulating tumour DNA as a liquid biopsy in breast cancer (2015)

Recent developments in massively parallel sequencing and digital genomic techniques support the clinical validity of cell-free circulating tumour DNA (ctDNA) as a 'liquid biopsy' in human cancer. In breast cancer, ctDNA detected in plasma can be used to non-invasively scan tumour genomes and quantify tumour burden. The applications for ctDNA in plasma include identifying actionable genomic alterations, monitoring treatment responses, unravelling therapeutic resistance, and potentially detecting disease progression before clinical and radiological confirmation. ctDNA may be used to characterise tumour heterogeneity and metastasis-specific mutations providing information to adapt the therapeutic management of patients. In this article, we review the current status of ctDNA as a 'liquid biopsy' in breast cancer.
Behavior-based formation control for multirobot teams (1998)

New reactive behaviors that implement formations in multirobot teams are presented and evaluated. The formation behaviors are integrated with other navigational behaviors to enable a robotic team to reach navigational goals, avoid hazards and simultaneously remain in formation. The behaviors are implemented in simulation, on robots in the laboratory and aboard DARPA's HMMWV-based unmanned ground vehicles. The technique has been integrated with the autonomous robot architecture (AuRA) and the UGV Demo II architecture. The results demonstrate the value of various types of formations in autonomous, human-led and communications-restricted applications, and their appropriateness in different types of task environments.
Analysis of STAT4 expression in cutaneous T-cell lymphoma (CTCL) patients and patient-derived cell lines (2014)

Deregulation of STAT signaling has been implicated in the pathogenesis for a variety of cancers, including CTCL. Recent reports indicate that loss of STAT4 expression is an important prognostic marker for CTCL progression and is associated with the acquisition of T helper 2 cell phenotype by malignant cells. However, little is known about the molecular mechanism behind the downregulation of STAT4 in this cancer. In the current work we test the expression of STAT4 and STAT6 via RT-PCR and/or Western Blot in CTCL lesional skin samples and in immortalized patient-derived cell lines. In these malignant cell lines we correlate the expression of STAT4 and STAT6 with the T helper (Th) phenotype markers and test the effect of Histone Deacetylase (HDAC) inhibitors and siRNA-mediated knock down of miR-155 on STAT4 expression. Our findings demonstrate that STAT4 expression correlates with Th1 phenotype, while STAT6 is associated with the Th2 phenotype. Our results further document that STAT4 and STAT6 genes are inversely regulated in CTCL. Treatment with HDAC inhibitors upregulates STAT4 expression, while at the same time decreases STAT6 expression in MyLa cells. Also, siRNA-mediated knock down of miR-155 leads to upregulation in STAT4 expression in MyLa cells. In summary, our results suggest that loss of STAT4 expression and associated switch to Th2 phenotype during Mycosis Fungoides progression may be driven via aberrant histone acetylation and/or upregulation of oncogenic miR-155 microRNA.
Binding of Ovarian Cancer Antigen CA125/MUC16 to Mesothelin Mediates Cell Adhesion (2004)

Mesothelin is a glycosylphosphatidylinositol-linked cell surface molecule expressed in the mesothelial lining of the body cavities and in many tumor cells. Based on the finding that a soluble form of mesothelin specifically binds to ovarian carcinoma cell line OVCAR-3, we isolated cDNAs encoding a mesothelin-binding protein by expression cloning. The polypeptides encoded by the two cloned cDNA fragments matched to portions of CA125, an ovarian cancer antigen and a giant mucin-like glycoprotein present at the surface of tumor cells. By flow cytometric analysis and immunoprecipitation, we demonstrate that CA125 binds to mesothelin in a specific manner. Binding of CA125 to membrane-bound mesothelin mediates heterotypic cell adhesion as anti-mesothelin antibody blocks binding of OVCAR-3 cells expressing CA125 to an endothelial-like cell line expressing mesothelin. Finally, we show that CA125 and mesothelin are co-expressed in advanced grade ovarian adenocarcinoma. Taken together, our data indicate that mesothelin is a novel CA125-binding protein and that CA125 might contribute to the metastasis of ovarian cancer to the peritoneum by initiating cell attachment to the mesothelial epithelium via binding to mesothelin.