gebhart/patrepeval huggingface dataset:
Dissolution of Pristine Single Walled Carbon Nanotubes in Superacids by Direct Protonation (2004)

Strong tube−tube van der Waal attractions that hinder the dissolution of single walled carbon nanotubes (SWNTs) as individuals have been overcome by the direct protonation of the tubes by superacids. The pristine nanotubes disperse as individuals in 100% H2SO4, oleum, trifluromethanesulfonic acid, and chlorosulfonic acid to varying solubility levels. Optically homogeneous solutions with concentration as high as 45 g/L (2.5 wt %) at room temperature have been observed in the case of chlorosulfonic acid, the strongest among the series of superacids investigated. A dissolution model is proposed wherein the solubilized tubes exist as protonated polycarbocations, charge balanced by corresponding conjugate base anions. The removal of electrons from the SWNT, leading to a fractional positive charge on the carbons in the protonated state, is reversible upon deprotonation. With increasing concentration of the solubilized nanotubes, anion-mediated attractions at lower concentrations and spatial constraints at high concentrations guide the transformation of the SWNT−acid system into a nematic mesophase. Highly anisotropic, nematic mesophases formed in the dissolution process are promising precursors for the fabrication of macroscopic forms of SWNTs with high alignment of the carbon nanotubes.
The demonstration of αKlotho deficiency in human chronic kidney disease with a novel synthetic antibody (2014)

αKlotho is the prototypic member of the Klotho family and is most highly expressed in the kidney. αKlotho has pleiotropic biologic effects, and in the kidney, its actions include regulation of ion transport, cytoprotection, anti-oxidation and anti-fibrosis. In rodent models of chronic kidney disease (CKD), αKlotho deficiency has been shown to be an early biomarker as well as a pathogenic factor. The database for αKlotho in human CKD remains controversial even after years of study. We used a synthetic antibody library to identify a high-affinity human antigen-binding fragment that recognizes human, rat and mouse αKlotho primarily in its native, rather than denatured, form. Using an immunoprecipitation–immunoblot (IP-IB) assay, we measured both serum and urinary levels of full-length soluble αKlotho in humans and established that human CKD is associated with αKlotho deficiency in serum and urine. αKlotho levels were detectably lower in early CKD preceding disturbances in other parameters of mineral metabolism and progressively declined with CKD stages. We also found that exogenously added αKlotho is inherently unstable in the CKD milieu suggesting that decreased production may not be the sole reason for αKlotho deficiency. Synthetic antibody libraries harbor tremendous potential for a variety of biomedical and clinical applications. Using such a reagent, we furnish data in support of αKlotho deficiency in human CKD, and we set the foundation for the development of diagnostic and therapeutic applications of anti-αKlotho antibodies.
Chimeric Human Calcitonin and Glucagon Receptors Reveal Two Dissociable Calcitonin Interaction Sites (1995)

Two chimeric receptors were constructed by transposing the coding regions for the putative N-terminal domains of the human calcitonin (hCTR) and glucagon (hGGR) receptors. These receptors were stably expressed as glycosylated proteins with molecular masses of 80 kDa for the calcitonin receptor N-terminus chimera (NtCTr) and 65 kDa for the glucagon receptor N-terminus chimera (NtGGr). The NtCTr chimera binds salmon calcitonin (sCT) with an apparent Kd of 12 nM relative to 0.3 nM for the native hCTR. However, this chimera does not mediate a cAMP response even with a transfectant expressing 1.8 x 10(6) cell surface receptors. Stable transfectants expressing the NtGGr chimera show no detectable binding of 125I-sCT or 125I-human glucagon. Surprisingly, adenylate cyclase is activated through the NtGGr chimera by sCT, pCT, and hCT with half-maximal activation at 2.2 +/- 0.6, 5.8 +/- 2.1, and 810 +/- 151 nM, respectively, and the maximum response is similar to that induced by 25 microM forskolin. The rank-order of competition for sCT binding to the NtCTr chimera is similar to the hCTR (sCT > pCT > hCT), but the concentrations required for half-maximal competition are 100- to > 2000-fold higher. In addition, salmon calcitonin binds with a much more rapid on-rate and off-rate to the NtCTr chimera relative to the hCTR which binds hormone irreversibly. Cross-linking of 125I-sCT to the NtCTr chimera with bis(sulfosuccinimidyl) suberate is much greater than to the hCTR, suggesting unique conformations for the two receptor-hormone complexes.(ABSTRACT TRUNCATED AT 250 WORDS)
Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response (2000)

Human HtrA2 is a novel member of the HtrA serine protease family and shows extensive homology to the Escherichia coli HtrA genes that are essential for bacterial survival at high temperatures. HumHtrA2 is also homologous to human HtrA1, also known as L56/HtrA, which is differentially expressed in human osteoarthritic cartilage and after SV40 transformation of human fibroblasts. HumHtrA2 is upregulated in mammalian cells in response to stress induced by both heat shock and tunicamycin treatment. Biochemical characterization of humHtrA2 shows it to be predominantly a nuclear protease which undergoes autoproteolysis. This proteolysis is abolished when the predicted active site serine residue is altered to alanine by site-directed mutagenesis. In human cell lines, it is present as two polypeptides of 38 and 40 kDa. HumHtrA2 cleaves beta-casein with an inhibitor profile similar to that previously described for E. coli HtrA, in addition to an increase in beta-casein turnover when the assay temperature is raised from 37 to 45 degrees C. The biochemical and sequence similarities between humHtrA2 and its bacterial homologues, in conjunction with its nuclear location and upregulation in response to tunicamycin and heat shock suggest that it is involved in mammalian stress response pathways.
Chemical Synthesis of a Glycoprotein Having an Intact Human Complex-Type Sialyloligosaccharide under the Boc and Fmoc Synthetic Strategies (2007)

The chemical synthesis of complex glycoproteins is an ongoing challenge in protein chemistry. We have examined the synthesis of a single glycoform of monocyte chemotactic protein-3 (MCP-3), a CC-chemokine that consists of 76 amino acids and one N-glycosylation site. A three-segment native chemical ligation strategy was employed using unprotected peptides and glycopeptide. Importantly, the synthesis required the development of methods for the generation of sialylglycopeptide-alphathioesters. For the sialylglycopeptide-alphathioester segment, we examined and successfully implemented approaches using Fmoc-SPPS and Boc-SPPS. To avoid use of hydrogen fluoride, the Boc approach utilized minimal side chain protection and direct thiolysis of the resin bound peptide. Using these strategies, we successfully synthesized a glycoprotein having an intact and homogeneous complex-type sialyloligosaccharide.
A New Look at Viruses in Type 1 Diabetes (2004)

Type 1 diabetes results from the destruction of pancreatic beta cells. Genetic factors are believed to be a major component for the development of type 1diabetes, but the concordance rate for the development of diabetes in identical twins is only about 40%, suggesting that non-genetic factors play an important role in the expression of the disease. Viruses are one environmental factor that is implicated in the pathogenesis of type 1 diabetes. To date, 14 different viruses have been reported to be associated with the development of type 1 diabetes in humans and animal models. Viruses may be involved in the pathogenesis of type 1 diabetes in at least two distinct ways: by inducing beta cell-specific autoimmunity, with or without infection of the beta cells, (e.g. Kilham rat virus) and by cytolytic infection and destruction of the beta cells (e.g. encephalomyocarditis virus in mice). With respect to virus-mediated autoimmunity, retrovirus, reovirus, Kilham rat virus, bovine viral diarrhoea-mucosal disease virus, mumps virus, rubella virus, cytomegalovirus and Epstein-Barr virus are discussed. With respect to the destruction of beta cells by cytolytic infection, encephalomyocarditis virus, mengovirus and Coxsackie B viruses are discussed. In addition, a review of transgenic animal models for virus-induced autoimmune diabetes is included, particularly with regard to lymphocytic choriomeningitis virus, influenza viral proteins and the Epstein-Barr viral receptor. Finally, the prevention of autoimmune diabetes by infection of viruses such as lymphocytic choriomeningitis virus is discussed.
Novel Aqueous Aluminum/Sulfur Batteries (1993)

Aluminum sulfur batteries based on concentrated polysulfide catholytes and an alkaline aluminum anode are introduced and investigated. The new battery is expressed by aluminum oxidation and aqueous sulfur reduction for an overall battery discharge consisting of
Predictive model representation and comparison: Towards data and predictive models governance (2010)

The increasing variety of data mining tools offers a large palette of types and representation formats for predictive models. Managing the models becomes then a big challenge, as well as reusing the models and keeping the consistency of model and data repositories because of the lack of an agreed representation across the models. The flexibility of XML representation makes it easier to provide solutions for Data and Model Governance (DMG) and support data and model exchange. We choose Predictive Toxicology as an application field to demonstrate our approach to represent predictive models linked to data for DMG. We propose an original structure: Predictive Toxicology Markup Language (PTML) offers a representation scheme for predictive toxicology data and models generated by data mining tools. We also show how this representation offers possibilities to compare models by similarity using our Distance Models Comparison technique. This work is ongoing and first encouraging results for calculating PTML distance are reported hereby.
Differential Display of Eukaryotic Messenger RNA by Means of the Polymerase Chain Reaction (1992)

Effective methods are needed to identify and isolate those genes that are differentially expressed in various cells or under altered conditions. This report describes a method to separate and clone individual messenger RNAs (mRNAs) by means of the polymerase chain reaction. The key element is to use a set of oligonucleotide primers, one being anchored to the polyadenylate tail of a subset of mRNAs, the other being short and arbitrary in sequence so that it anneals at different positions relative to the first primer. The mRNA subpopulations defined by these primer pairs were amplified after reverse transcription and resolved on a DNA sequencing gel. When multiple primer sets were used, reproducible patterns of amplified complementary DNA fragments were obtained that showed strong dependence on sequence specificity of either primer.
Search for energetic-charged-particle emission from deuterated Ti and Pd foils (1989)

Searching for evidence of ``cold'' nuclear fusion in deuterium-loaded Ti and Pd foils with plastic track detectors, we detected the emission of \ensuremath{\alpha} particles from trace-heavy-element decay, but found no evidence of dd fusion. Cycling ${\mathrm{TiD}}_{2}$ and ${\mathrm{PdD}}_{&gt;0.4}$, in high-pressure ${\mathrm{D}}_{2}$ cells between 1 and 15 bars and 77 and 300 K, gave an upper bound of 0.7 ${\mathrm{cm}}^{\mathrm{\ensuremath{-}}3}$ ${\mathrm{s}}^{\mathrm{\ensuremath{-}}1}$ for the mean rate of dd${\ensuremath{\rightarrow}}^{3}$He+n fusion. For electrolytically deuterated ${\mathrm{PdD}}_{0.8}$ our upper bound is 0.0018 ${\mathrm{cm}}^{\mathrm{\ensuremath{-}}3}$ ${\mathrm{s}}^{\mathrm{\ensuremath{-}}1}$ for the mean rate of dd\ensuremath{\rightarrow}p+t. This is \ensuremath{\sim}1.5\ifmmode\times\else\texttimes\fi{}${10}^{6}$ and 180 times lower than ``cold''-fusion rates reported by Fleischmann, Pons, and Hawkins and Jones et al., respectively.
Integration of Microfabricated Devices to Capillary Electrophoresis−Electrospray Mass Spectrometry Using a Low Dead Volume Connection: Application to Rapid Analyses of Proteolytic Digests (1999)

This report describes the development of a compact and versatile, micromachined chip device enabling the efficient coupling of capillary electrophoresis to electrospray mass spectrometry (CE-ESMS). On-chip separation provides a convenient means of achieving rapid sample cleanup and resolution of multicomponent samples (typically 2-5 min) prior to mass spectral analysis. A low dead volume connection facilitating the coupling of microfabricated devices to CE-ESMS was evaluated using two different interfaces. The first configuration used disposable nanoelectrospray emitters directly coupled to the chip device via this low dead volume junction, thereby providing rapid separation of complex protein digests. The performance of this interface was compared with that of more traditional configurations using a sheath flow CE-ESMS arrangement where a fused-silica capillary of varying length enabled further temporal resolution of the multicomponent samples. The sensitivity and analytical characteristics of these interfaces were investigated in both negative and positive ion modes using standard peptide mixtures. The separation performance for synthetic peptides using a chip coated with amine reagent ranged from 26,000 to 58,000 theoretical plates for a sheath flow CE-ESMS interface comprising a 15-cm CE column. Replicate injections of a dilution series of peptide standards provided detection limits of 45-400 nM without the use of on-line preconcentration devices. The reproducibility of migration time ranged from 0.9 to 1.5% RSD whereas RSDs of 5-10% were observed on peak areas. The application of these devices for the analysis of protein digests was further evaluated using on-line tandem mass spectrometry.
Toward a detailed computational model for the mammalian circadian clock (2003)

We present a computational model for the mammalian circadian clock based on the intertwined positive and negative regulatory loops involving the Per, Cry, Bmal1, Clock, and Rev-Erb alpha genes. In agreement with experimental observations, the model can give rise to sustained circadian oscillations in continuous darkness, characterized by an antiphase relationship between Per/Cry/Rev-Erbalpha and Bmal1 mRNAs. Sustained oscillations correspond to the rhythms autonomously generated by suprachiasmatic nuclei. For other parameter values, damped oscillations can also be obtained in the model. These oscillations, which transform into sustained oscillations when coupled to a periodic signal, correspond to rhythms produced by peripheral tissues. When incorporating the light-induced expression of the Per gene, the model accounts for entrainment of the oscillations by light-dark cycles. Simulations show that the phase of the oscillations can then vary by several hours with relatively minor changes in parameter values. Such a lability of the phase could account for physiological disorders related to circadian rhythms in humans, such as advanced or delayed sleep phase syndrome, whereas the lack of entrainment by light-dark cycles can be related to the non-24h sleep-wake syndrome. The model uncovers the possible existence of multiple sources of oscillatory behavior. Thus, in conditions where the indirect negative autoregulation of Per and Cry expression is inoperative, the model indicates the possibility that sustained oscillations might still arise from the negative autoregulation of Bmal1 expression.
The Receptor Interacting Protein 1 Inhibits p53 Induction through NF-κB Activation and Confers a Worse Prognosis in Glioblastoma (2009)

Nuclear factor-kappaB (NF-kappaB) activation may play an important role in the pathogenesis of cancer and also in resistance to treatment. Inactivation of the p53 tumor suppressor is a key component of the multistep evolution of most cancers. Links between the NF-kappaB and p53 pathways are under intense investigation. In this study, we show that the receptor interacting protein 1 (RIP1), a central component of the NF-kappaB signaling network, negatively regulates p53 tumor suppressor signaling. Loss of RIP1 from cells results in augmented induction of p53 in response to DNA damage, whereas increased RIP1 level leads to a complete shutdown of DNA damage-induced p53 induction by enhancing levels of cellular mdm2. The key signal generated by RIP1 to up-regulate mdm2 and inhibit p53 is activation of NF-kappaB. The clinical implication of this finding is shown in glioblastoma, the most common primary malignant brain tumor in adults. We show that RIP1 is commonly overexpressed in glioblastoma, but not in grades II and III glioma, and increased expression of RIP1 confers a worse prognosis in glioblastoma. Importantly, RIP1 levels correlate strongly with mdm2 levels in glioblastoma. Our results show a key interaction between the NF-kappaB and p53 pathways that may have implications for the targeted treatment of glioblastoma.
Isolation and characterization of the lower portion of the thin limb of Henle in primary culture (1998)

To further characterize cells of the lower portion of the thin limb of Henle (TLH1p) under defined conditions in vitro, we developed a technique to enrich this cell population in suspension. TLH1p cells were isolated by enzymatic digestion of rat inner medulla, elimination of collecting ducts by lectin-coated beads, and differential centrifugation. Immunohistochemical staining of primary cultures of TLH1p cells with various markers revealed the preparations to be > 90% pure. The hormonal stimulation pattern of PGE2 and cAMP production by arginine vasopressin, angiotensin II, and dopamine in the isolated cells also argued against significant contamination by other cell types. Staining with an antibody against the aquaporin-1 water channel showed the distribution of cells from the ascending and descending limbs to be approximately equal in the isolated population. This technique allows the enrichment of cells from the lower portion of the thin limb of Henle in suspension to a very high degree of purity with the option to start primary cultures. Because these segments of the tubular system in particular are relatively inaccessible for microdissection, the presented method renders the possibility of addressing new questions regarding these tubular segments under defined conditions in vitro.
High-Gradient Magnetic Capture of Ferrofluids: Implications for Drug Targeting and Tumor Embolization (2001)

One of the perspective methods of cancer chemotherapy is magnetic targeting of drugs to tumors. This task is usually accomplished using small permanent magnets attached near the desired sites. In this study a new much more effective approach is proposed which is based on a strong magnetic gradient using a ferromagnetic wire placed in a strong magnetic field. Feasibility of this approach has been evaluated by the formation of ferrofluid seals and measurement of maximum pressure the formed seal can resists. Using this method it is possible to capture even superparamagnetic particles with nanosize dimensions, therefore the method may have an interesting applications in biomedical sciences.
Intratumoral injection of interferon‐α and systemic delivery of agonist anti‐CD137 monoclonal antibodies synergize for immunotherapy (2010)

CD137 artificial costimulation results in complete tumor rejection in several mouse models. Type I interferons (IFN) exert antitumor effects through an array of molecular functions on malignant cells, tumor stroma and immune system cells. The fact that agonist anti-CD137 mAb induce tumor regressions in mice deficient in the unique receptor for Type I IFNs (IFNAR(-/-) ) indicated potential for treatment combinations. Indeed, combination of intratumor injections of mouse IFN-α and intraperitoneal injections of anti-CD137 mAb synergized as seen on subcutaneous lesions derived from the MC38 colon carcinoma, which is resistant to each treatment if given separately. Therapeutic activity was achieved both against lesions directly injected with IFN-α and against distant concomitant tumors. Experiments in bone marrow chimeras prepared with IFNAR(-/-) and WT mice concluded that expression of the receptor for Type I interferons is mainly required on cells of the hematopoietic compartment. Synergistic effects correlated with a remarkable cellular hyperplasia of the tumor draining lymph nodes (TDLNs). Enlarged TDLNs contained more plasmacytoid and conventional dendritic cells (DC) that more readily cross-presented. Importantly, numbers of both DC subtypes inversely correlated with the tumor size. Numbers of CD8 T cells specific for a dominant tumor antigen were increased at TDLNs by each separate treatment but only with slight augments due to the combination. Combined antitumor effects of the therapeutic strategy were also seen on subcutaneous TC-1 tumors established for 24 days before treatment onset. The described strategy is realistic because (i) agents of each kind are clinically available and (ii) equivalent procedures in humans are feasible.
An evaluation of sequential model-based optimization for expensive blackbox functions (2013)

We benchmark a sequential model-based optimization procedure, SMAC-BBOB, on the BBOB set of blackbox functions. We demonstrate that with a small budget of 10xD evaluations of D-dimensional functions, SMAC-BBOB in most cases outperforms the state-of-the-art blackbox optimizer CMA-ES. However, CMA-ES benefits more from growing the budget to 100xD, and for larger number of function evaluations SMAC-BBOB also requires increasingly large computational resources for building and using its models.
Celecoxib suppresses hepatoma stemness and progression by up-regulating PTEN (2013)

Celecoxib, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, can prevent several types of cancer, including hepatocellular carcinoma (HCC). Here we show that celecoxib suppressed the self-renewal and drug-pumping functions in HCC cells. Besides, celecoxib depleted CD44+/CD133+ hepatic cancer stem cells (hCSC). Prostaglandin E2 (PGE2) and CD133 overexpression did not reverse the celecoxib-induced depletion of hCSC. Also, celecoxib inhibited progression of rat Novikoff hepatoma. Moreover, a 60-day celecoxib program increased the survival rate of rats with hepatoma. Histological analysis revealed that celecoxib therapy reduced the abundance of CD44+/CD133+ hCSCs in hepatoma tissues. Besides, the hCSCs depletion was associated with elevated apoptosis and blunted proliferation and angiogenesis in hepatoma. Celecoxib therapy activated peroxisome proliferator-activated receptor γ (PPARγ) and up-regulated PTEN, thereby inhibiting Akt and disrupting hCSC expansion. PTEN gene delivery by adenovirus reduced CD44/CD133 expression in vitro and hepatoma formation in vivo. This study suggests that celecoxib suppresses cancer stemness and progression of HCC via activation of PPARγ/PTEN signaling.