gebhart/patrepeval huggingface dataset:
TGF-β inhibitors for the treatment of cancer (2005)

Advances in understanding the role of transforming growth factor (TGF)-beta in tumorigenesis have led to the development of TGF-beta inhibitors for cancer treatment. Three platforms of TGF-beta inhibitors have evolved: antisense oligonucleotides, monoclonal antibodies and small molecules. In this review, the current stage of development of each known TGF-beta inhibitor will be discussed. As part of the risk/benefit assessment of TGF-beta inhibitors, the known effects of TGF-beta deficiency in mice, non-clinical toxicology studies with TGF-beta inhibitors in rats, and the clinical studies with monoclonal antibodies against TGF-beta will be summarised.
Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. (1999)

This randomized, double-blind study was undertaken to compare the efficacy and tolerability of policosanol (10 mg/day) and lovastatin (20 mg/day) in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. After 6 weeks on a lipid lowering diet, 53 patients were randomized to receive either policosanol or lovastatin tablets that were taken o.i.d. for 12 weeks under double-blind conditions. Both groups were similar at randomization. Policosanol significantly (p < 0.001) lowered low-density lipoprotein (LDL)-cholesterol (20.4%), total cholesterol (14.2%) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (23.7%). Lovastatin significantly (p < 0.01) lowered LDL-cholesterol (16.8%), total cholesterol (14.0%) and the ratio (p < 0.05) of LDL-cholesterol to HDL-cholesterol (14.9%). Triglyceride levels did not significantly change after therapy. Policosanol, but not lovastatin, significantly increased (p < 0.01) levels of HDL-cholesterol (7.5%). Comparison between groups showed that changes in HDL-cholesterol induced by policosanol were significantly greater (p < 0.01) than those induced by lovastatin. Both treatments were safe and well tolerated. Lovastatin moderately but significantly (p < 0.05) increased levels of aspartate aminotransferase, creatine phosphokinase and alkaline phosphatase. Adverse reactions were more frequent in the lovastatin group (p < 0.01) than in the policosanol group. In conclusion, policosanol administered at 10 mg/day produces more advantageous changes in HDL-cholesterol and has a better safety and tolerability profile than lovastatin 20 mg/day.
Cloning, chromosomal mapping and characterization of the human metal-regulatory transcription factor MTF-1 (1994)

Metallothioneins (MTs) are small cysteine-rich proteins that bind heavy metal ions such as zinc, cadmium and copper with high affinity, and have been functionally implicated in heavy metal detoxification and radical scavenging. Transcription of metallothioneins genes is induced by exposure of cells to heavy metals. This induction is mediated by metal-responsive promoter elements (MREs). We have previously cloned the cDNA of an MRE-binding transcription factor (MTF-1) from the mouse. Here we present the human cDNA equivalent of this metal-regulatory factor. Human MTF-1 is a protein of 753 amino acids with 93% amino acid sequence identity to mouse MTF-1 and has an extension of 78 amino acids at the C-terminus without counterpart in the mouse. The factors of both species have the same overall structure including six zinc fingers in the DNA binding domain. We have physically mapped the human MTF-1 gene to human chromosome 1 where it localizes to the short arm in the region 1p32-34, most likely 1p33. Both human and mouse MTF-1 when produced in transfected mammalian cells strongly bind to a consensus MRE of metallothionein promoters. However, human MTF-1 is more effective than the mouse MTF-1 clone in mediating zinc-induced transcription.
A developmentally inspired combined mechanical and biochemical signaling approach on zonal lineage commitment of mesenchymal stem cells in articular cartilage regeneration (2014)

Articular cartilage is organized into multiple zones including superficial, middle and calcified zones with distinct cellular and extracellular components to impart lubrication, compressive strength, and rigidity for load transmission to bone, respectively. During native cartilage tissue development, changes in biochemical, mechanical, and cellular factors direct the formation of stratified structure of articular cartilage. The objective of this work was to investigate the effect of combined gradients in cell density, matrix stiffness, and zone-specific growth factors on the zonal organization of articular cartilage. Human mesenchymal stem cells (hMSCs) were encapsulated in acrylate-functionalized lactide-chain-extended polyethylene glycol (SPELA) gels simulating cell density and stiffness of the superficial, middle and calcified zones. The cell-encapsulated gels were cultivated in a medium supplemented with growth factors specific to each zone and the expression of zone-specific markers was measured with incubation time. Encapsulation of 60 × 10(6) cells per mL hMSCs in a soft gel (80 kPa modulus) and cultivation with a combination of TGF-β1 (3 ng mL(-1)) and BMP-7 (100 ng mL(-1)) led to the expression of markers for the superficial zone. Conversely, encapsulation of 15 × 10(6) cells per mL hMSCs in a stiff gel (320 MPa modulus) and cultivation with a combination of TGF-β1 (30 ng mL(-1)) and hydroxyapatite (3%) led to the expression of markers for the calcified zone. Further, encapsulation of 20 × 10(6) cells per mL hMSCs in a gel with 2.1 MPa modulus and cultivation with a combination of TGF-β1 (30 ng mL(-1)) and IGF-1 (100 ng mL(-1)) led to up-regulation of the middle zone markers. Results demonstrate that a developmental approach with gradients in cell density, matrix stiffness, and zone-specific growth factors can potentially regenerate zonal structure of the articular cartilage.
Bulk Viscosity: Past to Present (1999)

A review of the concept of a bulk viscosity coefficient β is presented, involving a discussion of theoretical approaches and a summary of existing experimental data. Two independent viscosity coefficients μ and A are obtained in the viscous stress tensor as a result of the isotropic Newtonian assumption. Hence, all solutions of the Navier-Stokes equations must make an assumption regarding the functional form of A. With β=λ+2/3μ by definition, the assumption is often arbitrarily made that the two viscosity coefficients are not independent, with β =0. This assumption has been shown to be valid only for dilute monatomic gases and is equivalent to stating that dilatational flowfield effects are not significant. Theoretical approaches for quantifying β are classified according to whether the subject fluid is dilute or dense. Experimental methods used to estimate bulk viscosity are described. Existing experimental data are summarized for each fluid classification, and issues related to using these data for dilatational flows in local thermodynamic equilibrium are addressed
MHC class I‐deficient metastatic tumor variants immunoselected by T lymphocytes originate from the coordinated downregulation of APM components (2003)

Previous reports from our group indicated that the MHC class I phenotype of metastatic lung colonies produced by a mouse fibrosarcoma tumor clone (B9) were, depending on the immune status of the host, MHC class I negative in immunocompetent mice and MHC class I positive in immunodeficient athymic nude/nude mice. Now we report the identification of the molecular alterations responsible for the changes of MHC class I molecules in both situations. Metastatic nodes were analyzed for the mRNA level of H-2 class I and beta2-microglobulin genes, and several gene components of the major histocompatibility complex (MHC) class I antigen-processing machinery (APM). These included the genes coding for the low-molecular-weight proteins LMP2, LMP7, LMP10, the transporter associated with antigen processing (TAP-1, TAP-2), and calnexin, calreticulin, tapasin, PA-28-alpha, PA-28-beta, ERP-59 and ER-60. Analyses with RT-PCR showed that TAP-1, TAP2, LMP-2, LMP7, LMP10, tapasin and calnexin mRNA specific for these genes was absent in metastases produced in immunocompetent mice. In contrast, similar techniques with mRNA preparations obtained from metastatic nodes from immunodeficient mice showed that the mRNA expression level of these genes was highly positive. Interestingly, the MHC class I-positive or negative phenotypes of the metastatic colonies correlated with in vivo immunogenicity. H-2 positive metastasis grew more slowly than the H-2 negative ones when injected intrafootpat in syngeneic immunocompetent animals and were finally rejected. These results provide evidence of the role of T cells in immune surveillance against tumors and identify a mechanism targeted by antitumor T lymphocytes to generate MHC class I-negative tumor escape variants.
The effect of high-index liquids on PS-OCT imaging of dental caries (2005)

The aim of this study was to investigate the effects of high refractive index liquids on PS-OCT imaging of dental enamel. Several biocompatible agents such as propylene glycol and glycerol that have been proposed or utilized for soft tissue OCT experiments (skin and GI mucosa) were applied to the occlusal surfaces of sound and carious teeth. This study determined that the application of high refractive index liquids increased penetration depth in sound enamel to a greater degree than dried or water moistened samples. The results also demonstrated that image contrast between sound and carious enamel is dependent on the viscosity of the liquid and the degree of porosity of the carious lesion. The use of liquid agents with different viscositites in PS-OCT imaging may help determine the severity and depth of caries lesions in the occlusal pits and fissures.
Computational epidemiology (2014)

As recent pandemics such as SARS and the Swine Flu outbreak have shown, diseases spread very fast in today's interconnected world, making public health an important research area. Some of the basic questions are: How can an outbreak be contained before it becomes an epidemic, and what disease surveillance strategies should be implemented? These problems have been studied traditionally using differential equation methods, which are amenable to analysis and closed form solutions. However, these models are based on complete mixing assumptions, which do not hold for realistic populations, thereby limiting their utility.
Polymer–Clay Nanocomposite Foams Prepared Using Carbon Dioxide (2003)

Poly(methylmethacrylate) and polystyrene–clay nanocomposites have been synthesized and exfoliated clay dispersion has been achieved (see Figure). Nanocomposite foams have been prepared using CO 2 as the foaming agent. Orders of magnitude increase in nucleation efficiency was accomplished by manipulation of clay dispersion and polymer–clay–CO 2 interaction.
Infrared Spectra of Methanol and Deuterated Methanols in Gas, Liquid, and Solid Phases (1961)

The infrared spectra of CH3OH, CH3OD, CD3OH, and CD3OD in the five phases gas, liquid, vitreous solid, α-crystal, and (except perhaps for CD3OH and CD3OD for which the solid-solid transitions have not been studied) β-crystal have been recorded in the range 4000 to 300 cm−1. The Raman spectrum of liquid CD3OH has been recorded. A complete assignment of the internal modes is given, which differs somewhat from previous assignments for the CH3 bending and rocking vibrations. No significant difference in spectrum occurred between the α-crystal and β-crystal phases. Under the full symmetry of the β-phase determined by x-ray diffraction only one OH out-of-plane bending band should occur. Two bands are observed, and it is concluded that the carbon and oxygen atoms in one chain are not coplanar, as is required by the symmetry determined by x-ray diffraction [K. J. Tauer and W. N. Lipscomb, Acta Cryst. 5, 606 (1952)], but that the chains are puckered and the x-ray symmetry arises because the puckered chains are irregularly distributed, a structure that had been previously suggested by Tauer and Lipscomb tentatively on the basis of high apparent thermal amplitudes. Bands occur in the crystal spectra near 500 cm−1 and 340 cm−1 at −180°C. These are interpreted as lattice modes, probably the two infrared-active modes that involve translations of the molecules.
Multiple Combination Therapies Involving Blockade of ICOS/B7RP-1 Costimulation Facilitate Long-Term Islet Allograft Survival (2004)

In recent years a series of novel costimulatory molecules have been identified, including inducible costimulator (ICOS). In a fully major histocompatibility complex (MHC)-mismatched mouse model of islet transplantation, we demonstrate that while monotherapy with CTLA4-Ig, CD40 ligand monoclonal antibody (CD40L mAb) or rapamycin each improves islet allograft survival, graft rejection eventually develops. Immunohistologic analysis of rejected grafts revealed increased ICOS expression, suggesting a role for this costimulatory molecule as an alternate pathway for T-cell activation. The combination of a blocking anti-ICOS mAb with each of the above therapies resulted in significantly improved islet allograft survival, confirming the importance of ICOS signaling in islet allograft rejection. Mechanistic studies conducted in mice treated with anti-ICOS mAb and rapamycin demonstrated a lack of donor-specific immunological tolerance and an absence of regulatory T-cell activity. However, a dramatic effect was seen on acute anti-donor responses whereby anti-ICOS mAb and rapamycin significantly reduced the initial expansion and function of alloreactive T cells. These data demonstrate that blockade of the ICOS/B7RP-1 pathway has potential therapeutic benefit given its role in enhancing islet allograft survival and regulating acute alloresponses in vivo.
Simple and mild preparation of silica-enzyme composites from silicic acid solution (2009)

Silica-enzyme composite materials including nanoparticles are formed readily from silicic acid and some hydrolase enzymes under mild conditions when the enzyme pI is greater than about 10.
Role of the latent TGF-beta binding protein in the activation of latent TGF-beta by co-cultures of endothelial and smooth muscle cells. (1993)

Transforming growth factor beta (TGF-beta) is released from cells in a latent form consisting of the mature growth factor associated with an aminoterminal propeptide and latent TGF-beta binding protein (LTBP). The endogenous activation of latent TGF-beta has been described in co-cultures of endothelial and smooth muscle cells. However, the mechanism of this activation remains unknown. Antibodies to native platelet LTBP and to a peptide fragment of LTBP inhibit in a dose-dependent manner the activation of latent TGF-beta normally observed when endothelial cells are cocultured with smooth muscle cells. Inhibition of latent TGF-beta activation was also observed when cells were co-cultured in the presence of an excess of free LTBP. These data represent the first demonstration of a function for the LTBP in the extracellular regulation of TGF-beta activity and indicate that LTBP participates in the activation of latent TGF-beta, perhaps by concentrating the latent growth factor on the cell surface where activation occurs.
Orteronel for the Treatment of Prostate Cancer (2014)

Orteronel (also known as TAK-700) is a novel hormonal therapy that is currently in testing for the treatment of prostate cancer. Orteronel inhibits the 17,20 lyase activity of the enzyme CYP17A1, which is important for androgen synthesis in the testes, adrenal glands and prostate cancer cells. Preclinical studies demonstrate that orteronel treatment suppresses androgen levels and causes shrinkage of androgen-dependent organs, such as the prostate gland. Early reports of clinical studies demonstrate that orteronel treatment leads to reduced prostate-specific antigen levels, a marker of prostate cancer tumor burden, and more complete suppression of androgen synthesis than conventional androgen deprivation therapies that act in the testes alone. Treatment with single-agent orteronel has been well tolerated with fatigue as the most common adverse event, while febrile neutropenia was the dose-limiting toxicity in a combination study of orteronel with docetaxel. Recently, the ELM-PC5 Phase III clinical trial in patients with advanced-stage prostate cancer who had received prior docetaxel was unblinded as the overall survival primary end point was not achieved. However, additional Phase III orteronel trials are ongoing in men with earlier stages of prostate cancer.
Convolutional Patch Networks with Spatial Prior for Road Detection and Urban Scene Understanding (2015)

Classifying single image patches is important in many different applications, such as road detection or scene understanding. In this paper, we present convolutional patch networks, which are convolutional networks learned to distinguish different image patches and which can be used for pixel-wise labeling. We also show how to incorporate spatial information of the patch as an input to the network, which allows for learning spatial priors for certain categories jointly with an appearance model. In particular, we focus on road detection and urban scene understanding, two application areas where we are able to achieve state-of-the-art results on the KITTI as well as on the LabelMeFacade dataset. Furthermore, our paper offers a guideline for people working in the area and desperately wandering through all the painstaking details that render training CNs on image patches extremely difficult.
Interleukin‐4 and interleukin‐10 are chondroprotective and decrease mononuclear cell recruitment in human rheumatoid synovium in vivo (1998)

We used the severe combined immunodeficient (SCID) mouse model to assess the effect of interleukin-4 (IL-4) or IL-10 injection on cartilage degradation and mononuclear cell (MNC) recruitment to human rheumatoid synovium in vivo. Human rheumatoid synovium and cartilage from five rheumatoid arthritis patients, obtained after joint replacement surgery, were engrafted subcutaneously to 6-8-week-old SCID CB17 mice. Synovial tissues were injected with recombinant human IL-4 (rhIL-4, 100 ng; rhIL-10, 100 ng), both cytokines, or tumour necrosis factor-alpha (TNF-alpha) (1000 U), or phosphate-buffered saline twice a week for 4 weeks. The graft was removed and immunochemical analysis was carried out to assess intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression. Moreover, cartilage degradation was assessed through the quantification of the erosion surface on a computerized image of the engrafted cartilage at high power view. MNC recruitment in the synovial tissue was determined by labelling blood MNC with indium-111 before their intraperitoneal injection. The activity obtained in the region of the graft were determined with a gamma camera 72 hr postinjection. The results are expressed as a percentage of initial injected activity. After 4 weeks we observed a decrease of cartilage area in controls (77 +/- 8%), inhibited after injection of IL-4, IL-10, or both cytokines (90 +/- 3%, 89.1 +/- 4%, 89.2 +/- 5% respectively), and 57 +/- 17% after TNF-alpha injection. The % MNC activity in the graft decreased to 77 +/- 81% (NS), 9 +/- 4% (P < 0.003) and 19 +/- 6% (P < 0.007) compared with untreated synovial tissue after treatment with IL-4, IL-10, or both cytokines, respectively. Moreover, IL-10 but not IL-4 decreased the expression of ICAM-1 but not VCAM-1 or E-selectin by synovial cells. These results suggest that IL-10 and IL-4 could have chondroprotective properties, and that IL-10 but not IL-4 inhibits MNC traffic towards the synovial tissue efficiently.
A Novel Mannose-binding Lectin/Ficolin-associated Protein Is Highly Expressed in Heart and Skeletal Muscle Tissues and Inhibits Complement Activation (2010)

The human lectin complement pathway involves circulating complexes consisting of mannose-binding lectin (MBL) or three ficolins (ficolin-1, -2, and -3) in association with three MBL/ficolin-associated serine proteases (MASP) (MASP-1, -2, and -3) and a nonenzymatic sMAP. MASP-1 and MASP-3 (MASP1 isoforms 1 and 2, respectively) are splice variants of the MASP1 gene, whereas MASP-2 and sMAP are splice variants of the MASP2 gene. We have identified a novel serum protein of 45 kDa that is associated with MBL and the ficolins. This protein is named MBL/ficolin-associated protein 1 (MAP-1 corresponding to MASP1 isoform 3). The transcript generating MAP-1 (MASP1_v3) contains exons 1-8 and a novel exon encoding an in-frame stop codon. The corresponding protein lacks the serine protease domains but contains most of the common heavy chain of MASP-1 and MASP-3. Additionally MAP-1 contains 17 unique C-terminal amino acids. By use of quantitative PCR and MAP-1-specific immunohistochemistry, we found that MAP-1 is highly expressed in myocardial and skeletal muscle tissues as well as in liver hepatocytes with a different expression profile than that observed for MASP-1 and MASP-3. MAP-1 co-precipitated from human serum with MBL, ficolin-2, and ficolin-3, and recombinant MAP-1 was able to inhibit complement C4 deposition via both the ficolin-3 and MBL pathway. In conclusion we have identified a novel 45-kDa serum protein derived from the MASP1 gene, which is highly expressed in striated muscle tissues. It is found in complex with MBL and ficolins and may function as a potent inhibitor of the complement system in vivo.
Developing a vaccine against Zika (2016)

We’ve made a good start but substantial challenges remain
Sjögren's syndrome associated with systemic lupus erythematosus: Clinical and laboratory profiles and comparison with primary Sjögren's syndrome (2004)

SLE-SS appears to constitute a subgroup of patients with distinct clinical, serologic, pathologic, and immunogenetic features, in whom SS is expressed as an overlapping entity and is largely similar to primary SS.
Radiolabeled Peptides and Proteins in Cancer Therapy (2007)

With the advances in genomics, molecular biology including gene vector technologies today's molecular imaging modalities have strongly been improved. The major progress is based on peptide and antibody targeting vectors. When labeled with beta(-)-emitting radioisotopes these agents are applicable for endoradiotherapy and exploit the targeting potential for highly specific therapeutic applications. This novel class of pharmaceuticals offers the potential to develop patient specific therapies and might provide the means to go beyond the possibilities of current chemotherapy and radiation therapy. In this review the basic principles of endoradiotherapeutics based on peptides and proteins are presented. Several of these drugs such as (90)Y-rituximab (Zevalin), (131)I-tositumomab (Bexxar) and the somatostatin receptor binding (90)Y-DOTATOC that are nowadays successfully applied in oncological therapy are discussed. Future generations of endoradiopharmaceuticals will address yet unknown targets which might be identified by screening techniques such as ribosome and phage display peptide libraries.