gebhart/patrepeval huggingface dataset:
Multichannel dc Josephson effect in ballistic point contacts (1997)

Mesoscopic Josephson junctions of small diameter are expected to display universal behavior of the critical current if the junction is short enough so that only one bound Andreev state per transverse channel contributes to the current. For example, the critical current of a clean superconducting--normal-metal--superconducting (SNS) junction is supposed to increase stepwise with the number N of filled transverse channels in the junction, in units of e${\mathrm{\ensuremath{\Delta}}}_{0}$/\ensuremath{\hbar}. The critical current then is independent of the specific junction geometry. We investigate the robustness of this universal behavior for heterogeneous clean metallic ${\mathrm{S}}_{1}$${\mathrm{NS}}_{3}$ junctions. For this purpose, we present the current-phase relationship in terms of the ratio ${\mathrm{\ensuremath{\Delta}}}_{1}$/${\mathrm{\ensuremath{\Delta}}}_{3}$ for the single-particle s-wave energy gaps of the two superconductors, and in terms of the junction length L and temperature T. If L=0 still holds, finite T and finite asymmetry ${\mathrm{\ensuremath{\Delta}}}_{1}$/${\mathrm{\ensuremath{\Delta}}}_{3}$1 reduce the step height of the critical current steps but preserve the sharp step edges. The step behavior is however smeared due to finite L/\ensuremath{\xi}, where \ensuremath{\xi} is the coherence length of the superconductor with the larger gap. The steps are blurred even more at finite temperature, even though L/\ensuremath{\xi}\ensuremath{\ll}1 may still hold. On the other hand, junction asymmetry may reduce this smearing for fixed L/\ensuremath{\xi} and T considerably. The limit of a smoothly increasing ${\mathrm{I}}_{\mathrm{c}}$(N) is recovered for N&gt;${\mathrm{N}}_{\mathrm{c}}$, where ${\mathrm{N}}_{\mathrm{c}}$=min[(1/2)(\ensuremath{\pi}\ensuremath{\xi}/L${)}^{2}$(1+${\mathrm{\ensuremath{\Delta}}}_{3}$/${\mathrm{\ensuremath{\Delta}}}_{1}$${)}^{2}$,(1/2)\ensuremath{\pi}${\mathrm{k}}_{\mathrm{F}}$\ensuremath{\xi}] for T=0 and L/\ensuremath{\pi}\ensuremath{\xi}\ensuremath{\ll}1.
β2-Microglobulin Induces Epithelial to Mesenchymal Transition and Confers Cancer Lethality and Bone Metastasis in Human Cancer Cells (2011)

Bone metastasis is one of the predominant causes of cancer lethality. This study demonstrates for the first time how β2-microglobulin (β2-M) supports lethal metastasis in vivo in human prostate, breast, lung, and renal cancer cells. β2-M mediates this process by activating epithelial to mesenchymal transition (EMT) to promote lethal bone and soft tissue metastases in host mice. β2-M interacts with its receptor, hemochromatosis (HFE) protein, to modulate iron responsive pathways in cancer cells. Inhibition of either β2-M or HFE results in reversion of EMT. These results demonstrate the role of β2-M in cancer metastasis and lethality. Thus, β2-M and its downstream signaling pathways are promising prognostic markers of cancer metastases and novel therapeutic targets for cancer therapy.
Thermoelectric properties of semimetallic (Zr, Hf)CoSb half-Heusler phases (2000)

Unlike semiconducting TiCoSb, ZrCoSb and HfCoSb half-Heusler phases are semimetallic below room temperature and exhibit small Seebeck coefficients of ∼−10 μV/K at 300 K. However, upon substituting (doping) the Co and Sb sites with Pt and Sn, respectively, much larger thermopowers (S) are obtained. For ZrCoSb, S reaches −110 and +130 μV/K while resistivity ρ decreases from ∼5×104 μΩ cm in the undoped phase to 1–2×103 μΩ cm in the substituted phases at 300 K. The lowest thermal conductivity obtained in the substituted alloys is ∼3.0 W/m K at 300 K, which is among the lowest reported for this class of structural phases. There are indications that the thermoelectric properties have not been optimized in these multinary alloys.
Panitumumab: A Fully Human Monoclonal Antibody with Activity in Metastatic Colorectal Cancer (2007)

Panitumumab is a fully human monoclonal antibody with promising activity in treatment of patients with metastatic colorectal cancer who have failed previous therapy, offering a favorable safety profile.
NF-κB: a key role in inflammatory diseases (2001)

Activation of the NF-B/Rel transcription family, by nuclear translocation of cytoplasmic complexes, plays a central role in inflammation through its ability to induce transcription of proinflammatory genes (1). This pathway is activated upon appropriate cellular stimulation, most often by signals related to pathogens or stress. Here we will discuss the specificity of various NF-B proteins, their role in inflammatory disease, the regulation of NF-B activity by IB proteins and IB kinase (IKK), and the development of therapeutic strategies aimed at inhibition of NF-B.
Cutting Edge: Natalizumab Blocks Adhesion but Not Initial Contact of Human T Cells to the Blood-Brain Barrier In Vivo in an Animal Model of Multiple Sclerosis (2009)

The humanized anti-alpha(4) integrin Ab Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis. Natalizumab is thought to exert its therapeutic efficacy by blocking the alpha(4) integrin-mediated binding of circulating immune cells to the blood-brain barrier (BBB). As alpha(4) integrins control other immunological processes, natalizumab may, however, execute its beneficial effects elsewhere. By means of intravital microscopy we demonstrate that natalizumab specifically inhibits the firm adhesion but not the rolling or capture of human T cells on the inflamed BBB in mice with acute experimental autoimmune encephalomyelitis (EAE). The efficiency of natalizumab to block T cell adhesion to the inflamed BBB was found to be more effective in EAE than in acute systemic TNF-alpha-induced inflammation. Our data demonstrate that alpha(4) integrin-mediated adhesion of human T cells to the inflamed BBB during EAE is efficiently blocked by natalizumab and thus provide the first direct in vivo proof of concept of this therapy in multiple sclerosis.
Temperature Receptors in the Central Nervous System (1986)

For half a century, it has been known that thermo sensitive regions of the rostral brain stem are important in thermoregulation (61). Figure 1 indicates that a variety of thermoregulatory responses can be elicited by changing the tempera­ ture of the preoptic area and anterior hypothalamus (POI AH). POI AH warming evokes heat-loss responses, and POIAH cooling evokes heat-production re­ sponses. If POIAH temperature is changed slightly above or below normal, there are changes in heat-retention responses such as skin blood flow and thermoregulatory behavior. Figure 1 also describes the synaptic organization of POI AH thermosensitive neurons (4). While most neurons are temperature insensitive, warm-sensitive neurons have firing rates that increase with warm­ ing or decrease with cooling. Conversely, the firing rates of cold-sensitive neurons increase with cooling or decrease with warming. Many central thermo­ sensitive neurons also receive synaptic inputs from skin and spinal thermore­ ceptive pathways (4, 7). This indicates that such neurons are capable of thermal integration, and it increases the likelihood that these neurons function in thermoregulation. As summarized in Figure 1, the evidence for central thermosensitivity comes from thermoregulatory studies during thermal stimulation of discrete neural areas and from electrophysiological studies of temperature-sensitive neurons. In this review, these studies are presented first as an overview of the comparative aspects of central thermo sensitivity in vertebrates. The second half of this review focuses on the properties and synaptic organization of POIAH thermosensitive neurons.
Profiling of Glycans in Serum for the Discovery of Potential Biomarkers for Ovarian Cancer (2006)

A glycomic approach is developed to identify oligosaccharide markers for ovarian cancer by rapidly profiling globally released oligosaccharides. Glycoproteins shed by cancer cells are found in the supernatant (or conditioned media) of cultured cells. In this approach, shed glycoproteins are profiled for their oligosaccharide content using beta-elimination conditions. Changes in glycosylation are monitored by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR-MS). Because shed glycoproteins would also be found in serum, similar glycan profiling was performed to observe potential oligosaccharide markers. Oligosaccharide profiling data on a limited set of patient and normal serum samples were studied to determine potential glycan markers in ovarian cancer. We were able to demonstrate the presence of at least 15 unique serum glycan markers in all patients but absent in normal individuals. To determine the structure of the glycan biomarkers, a number of the ions were isolated and further analyzed using infrared multiphoton dissociation (IRMPD). One major advantage of this approach is that glycans are examined directly from patient sera without the need to obtain cancer biopsy specimens or to purify glycosylated proteins from these specimens.
Detection of Chromosome 21-encoded mRNA of Placental Origin in Maternal Plasma (2003)

The detection of chromosome 21-encoded mRNA of placental origin in maternal plasma during the first trimester may allow development of plasma-RNA-based strategies for prenatal prediction of Down syndrome. LOC90625 is a candidate gene for this purpose.
Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family. (1991)

Interleukin 6 (IL-6) signal is transduced through gp130 that associates with a complex of IL-6 and IL-6 receptor. Truncations or amino acid substitutions offe introduced in the cytoplasmic region of human gp130, and the mutant cDNAs were transfected into murine interleukin 3-dependent cells to determine amino acid residues critical for generating the IL-6-mediated growth signal. In the 277-amino acid cytoplasmic region of gp130, a 61-amino acid region proximal to the transmembrane domain was sufficient for generating the growth signal. In this region, two short segments were significantly homologous with other cytokine-receptor family members. One segment is conserved in almost all members of the family, and the other is found especially in granulocyte colony-stimulating factor receptor, interleukin 2 receptor beta chain, erythropoietin receptor, KH97 (a granulocyte/macrophage colony-stimulating factor receptor-associated molecule), and interleukin 3 receptor. gp130 molecules with mutations in either of these two segments could not transduce growth signal. Loss of signal-transducing ability of gp130 with such a mutation coincided with disappearance of IL-6-induced tyrosine phosphorylation of gp130.
Differentially private data cubes (2011)

Data cubes play an essential role in data analysis and decision support. In a data cube, data from a fact table is aggregated on subsets of the table's dimensions, forming a collection of smaller tables called cuboids. When the fact table includes sensitive data such as salary or diagnosis, publishing even a subset of its cuboids may compromise individuals' privacy. In this paper, we address this problem using differential privacy (DP), which provides provable privacy guarantees for individuals by adding noise to query answers. We choose an initial subset of cuboids to compute directly from the fact table, injecting DP noise as usual; and then compute the remaining cuboids from the initial set. Given a fixed privacy guarantee, we show that it is NP-hard to choose the initial set of cuboids so that the maximal noise over all published cuboids is minimized, or so that the number of cuboids with noise below a given threshold (precise cuboids) is maximized. We provide an efficient procedure with running time polynomial in the number of cuboids to select the initial set of cuboids, such that the maximal noise in all published cuboids will be within a factor (ln|L| + 1)^2 of the optimal, where |L| is the number of cuboids to be published, or the number of precise cuboids will be within a factor (1 - 1/e) of the optimal. We also show how to enforce consistency in the published cuboids while simultaneously improving their utility (reducing error). In an empirical evaluation on real and synthetic data, we report the amounts of error of different publishing algorithms, and show that our approaches outperform baselines significantly.
The role of interleukin‐1 and tumour necrosis factor‐α in human multiple myeloma (1990)

This study investigates the capacity of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) to induce interleukin-6 (IL-6) production in freshly isolated myeloma cells (MC) and bone marrow-derived stromal cells (MSC). Recombinant human (rh) IL-1 alpha, IL-1 beta and TNF-alpha augmented production of IL-6 in human MC. IL-6 was determined on a factor-dependent Cess cell line. This activity was completely abrogated by anti-IL-6 antibodies. Prior incubation of IL-1 alpha, IL-1 beta and TNF-alpha with their respective antibodies inactivated the ability of recombinant cytokines to stimulate the release of IL-6 from myeloma cells. IL-1 alpha, IL-1 beta and TNF-alpha enhanced 3H-TdR uptake in myeloma cells through IL-6, as antibodies to IL-6 completely abolished the DNA synthesis induced by culture supernatants of MC exposed to these cytokines. rhIL-6 reversed the inhibitory action of anti-IL-6 antibodies and reinduced DNA synthesis in MC. Next we found that IL-1 alpha, IL-1 beta and TNF-alpha induced MSC to produce IL-6. In contrast, supernatants of unstimulated MSC did not contain detectable IL-6 biologic activity. Further data demonstrated that human MC were able to induce IL-6 production in MSC. The stimulatory activities of MC appeared to be mediated through endogenously released IL-1, as the addition of antibodies towards IL-1 at the initiation of cocultures completely abrogated the IL-6 production. We conclude from our data that IL-1 and TNF-alpha may play an important role in the pathogenesis of human multiple myeloma.
Structural analysis of lipooligosaccharide produced by Neisseria gonorrhoeae, strain MS11mk (variant A): a precursor for a gonococcal lipooligosaccharide associated with virulence (1992)

We studied the structure of the lipooligosaccharide (LOS) that is produced by a variant A of strain MS11mk. This variant produces a single LOS that is recognized by monoclonal antibody (MAb) 2-1-L8. In a recent study of the pathogenesis of Neisseria gonorrhoeae in male volunteers, variant A gave rise to other phase variants that produce higher molecular weight LOSs, and these LOS were associated with virulence. Definition of the structure of the variant A LOS is important to understand the biosynthesis of LOS and its expression in vivo. The dephosphorylated oligosaccharide (OS) structure derived from the variant A LOS was analyzed by two-dimensional NMR and methylation analysis. The OS structure was found to be a truncated form of the LOS produced by strain F62 [Yamasaki et al. (1991) Biochemistry 30, 10566-10575]; the variant A OS is a hexamer, a beta-lactosyl residue linked to a tetrasaccharide: Gal beta 1-->4Glc beta 1-->4[GlcNAc alpha 1-->2Hep alpha 1-->3]Hep alpha 1-->KDO. We determined that the variant A LOS is a precursor for the synthesis of higher MW LOS. We also studied expression of the MAb 2-1-L8-defined epitope present on the variant A LOS. Our data indicate that the MAb-defined epitope is not a linear beta-lactosyl residue but its specificity is directed toward the phosphorylated GlcNAc-Hep-Hep residue. Since this MAb binds to gonococci, at least part of the phosphorylated diheptose area is exposed on the gonococcal surface.
Heparanase induces tissue factor pathway inhibitor expression and extracellular accumulation in endothelial and tumor cells (2008)

Heparanase activity is implicated in cell invasion, tumor metastasis and angiogenesis. Recently, we have reported that heparanase stimulates tissue factor (TF) expression in endothelial and cancer cells, resulting in elevation of coagulation activity. We hypothesized that heparanase regulates other coagulation modulators, and examined the expression and localization of tissue factor pathway inhibitor (TFPI) following heparanase over-expression or exogenous addition. Primary human umbilical vein endothelial cells (HUVEC) and human tumor-derived cell lines were incubated with heparanase, or were stably transfected with heparanase gene-constructs, and TFPI expression and secretion were examined. Heparanase over-expression or exogenous addition stimulated TFPI expression by 2-3 folds. TFPI accumulation in the cell culture medium exceeded in magnitude the observed induction of TFPI gene transcription reaching 5- to 6-fold increase. Extracellular accumulation of TFPI was evident already 60 min following heparanase addition, prior to TFPI protein induction, and correlated with increased coagulation activity. This effect was found to be independent of heparanase enzymatic activity and interaction with heparan-sulfate, and correlated with reduced TFPI levels on the cell surface. Data were verified in heparanase transgenic mice tissues and plasma. Interaction between heparanase and TFPI was evident by co-immunoprecipitation. Interaction of heparanase with TFPI resulted in its displacement from the surface of the vascular endothelium and in increased pro-coagulant activity. Thus, heparanase facilitates blood coagulation on the cell surface by two independent mechanisms: dissociation of TFPI from the vascular surface shortly after local elevation of heparanase levels, and subsequent induction of TF expression.
Extraordinarily low density of hepatitis C virus estimated by sucrose density gradient centrifugation and the polymerase chain reaction (1992)

The genomic RNA of hepatitis C virus (HCV) in the plasma of volunteer blood donors was detected by using the polymerase chain reaction in a fraction of density 1.08 g/ml from sucrose density gradient equilibrium centrifugation. When the fraction was treated with the detergent NP40 and recentrifuged in sucrose, the HCV RNA banded at 1.25 g/ml. Assuming that NP40 removed a lipid-rich surface coat from HCV, the 1.08 g/ml and 1.25 g/ml HCV RNA may correspond to intact HCV virions and nucleocapsids, respectively. The extraordinarily low density of the virion is unusual in comparison to the density of classified viruses.
A shift in the balance of inhibitory and activating Fcγ receptors on monocytes toward the inhibitory Fcγ receptor IIb is associated with prevention of monocyte activation in rheumatoid arthritis (2004)

The altered balance of FcgammaR in favor of activating receptors in RA may contribute to increased activation of monocyte/macrophages. A change in the FcgammaR balance toward the inhibitory FcgammaRIIb may offer a novel treatment strategy for preventing the pleiotropic activity of FcgammaR-triggered macrophages.
Deep Image Harmonization (2017)

Compositing is one of the most common operations in photo editing. To generate realistic composites, the appearances of foreground and background need to be adjusted to make them compatible. Previous approaches to harmonize composites have focused on learning statistical relationships between hand-crafted appearance features of the foreground and background, which is unreliable especially when the contents in the two layers are vastly different. In this work, we propose an end-to-end deep convolutional neural network for image harmonization, which can capture both the context and semantic information of the composite images during harmonization. We also introduce an efficient way to collect large-scale and high-quality training data that can facilitate the training process. Experiments on the synthesized dataset and real composite images show that the proposed network outperforms previous state-of-the-art methods.
A novel myelin P0–specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy (2009)

Autoimmune-prone nonobese diabetic mice deficient for B7-2 spontaneously develop an autoimmune peripheral neuropathy mediated by inflammatory CD4(+) T cells that is reminiscent of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. To determine the etiology of this disease, CD4(+) T cell hybridomas were generated from inflamed tissue-derived CD4(+) T cells. A majority of T cell hybridomas were specific for myelin protein 0 (P0), which was the principal target of autoantibody responses targeting nerve proteins. To determine whether P0-specific T cell responses were sufficient to mediate disease, we generated a novel myelin P0-specific T cell receptor transgenic (POT) mouse. POT T cells were not tolerized or deleted during thymic development and proliferated in response to P0 in vitro. Importantly, when bred onto a recombination activating gene knockout background, POT mice developed a fulminant form of peripheral neuropathy that affected all mice by weaning age and led to their premature death by 3-5 wk of age. This abrupt disease was associated with the production of interferon gamma by P0-specific T cells and a lack of CD4(+) Foxp3(+) regulatory T cells. Collectively, our data suggest that myelin P0 is a major autoantigen in autoimmune peripheral neuropathy.
Regulation of T‐cell survival and mitochondrial homeostasis by TSC1 (2011)

The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and metabolism. It associates with multiple proteins and forms two distinct signaling complexes, mTORC1 and mTORC2. Accumulating evidence has revealed critical roles for intact mTOR signaling during T-cell activation and responses to microbial infection. However, the importance of mTOR regulation in T cells has yet to be explored. The TSC1/TSC2 complex has been shown to inhibit mTORC1 signaling in cell line models. We show here that deletion of TSC1 in the murine T-cell lineage results in a dramatic reduction of the peripheral T-cell pool, correlating with increased cell death. While mTORC1 is constitutively activated, mTORC2 signaling, reflected by Akt phosphorylation and activity, is decreased in TSC1-deficient T cells. Furthermore, TSC1-deficient T cells contain elevated reactive oxygen species (ROS) and exhibit decreased mitochondrial content and membrane potential, which is correlated with the activation of the intrinsic death pathway. Overall, our results demonstrate that TSC1 differentially regulates mTORC1 and mTORC2 activity, promotes T-cell survival, and is critical for normal mitochondrial homeostasis in T cells.