gebhart/patrepeval huggingface dataset:
The effect of resistance training on quadriceps muscle volume and some growth factors in elderly and young men. (2019)

Aging process is associated with loss of muscle mass, strength and growth factors dysfunction. Resistance training is one of the effective methods to overcome a decline in muscle mass, strength and also can modulate the level of myostatin, follistatin and insulin-like growth factor-1 (IGF-1) factors. The purpose of this study was to investigate the effect of 8 week resistance training on different anabolic factors which influence muscle hypertrophy in elderly and young men. Fifteen elderly and sixteen young men volunteered and participated in a periodized 3-day per week progressive resistance training program for a total of 8 weeks. Daily calorie intake, muscle volume, cross-sectional area (by computed tomography) and myostatin, follistatin, IGF-1, growth hormone (GH) and testosterone were calculated before and after the training protocol. At the end of the training period, the strength in the elderly group increased significantly compared to the young group (p<0,05); no differences of daily nutrient intake were found in both groups (p>0,05). Quadriceps muscle volume and cross-sectional area increased more in the younger group (p<0,05). Myostatin concentration significantly decreased in both groups (p<0,05), yet the amount of change was not different in either groups (p>0,05). Follistatin and testosterone increased in both groups (p<0,05), but growth hormone and IGF-1 increased in the younger group only (p<0,05). Resistance training improved hypertrophy and lead to anabolic conditions in elder and young subjects, but in different ways. In this regard, GH-IGF-1 axis and growth factors profile at the baseline had an important role in different age-related hypertrophy.
Regulation of human monocyte HLA-DR and CD4 antigen expression, and antigen presentation by 1,25-dihydroxyvitamin D3 (1990)

1,25-Dihydroxyvitamin D3 (1,25(OH)2-D) has been shown to be a macrophage-derived cytokine, capable of regulating myeloid differentiation and T-cell activation in vitro. Therefore, we examined the effects of 1,25(OH)2-D on the monocyte phenotype and function of human peripheral blood monocytes as an index of its biologic role at an inflammatory site. 1,25(OH)2-D treatment consistently and specifically reduced HLA-DR and CD4 expression by monocytes, while CD14 and class I HLA antigen expression were unaffected. Expression of Fc gamma R I-III on monocytes was variably modulated by 1,25(OH)2-D treatment, but no differences in antibody-dependent cell cytotoxicity (ADCC) were observed, measured using either ADCC or anti-Fc gamma R-antibody expressing hybridomas. In contrast, the ability of monocytes to induce antigen-dependent T-cell proliferation was markedly reduced by 1,25(OH)2-D pretreatment for as little as 6 hours. Addition of interleukin-1 (IL-1), IL-6, or indomethacin did not restore antigen- dependent T-cell proliferation, suggesting that this observation was not secondary to changes in IL-1, IL-6, or PGE2 production induced by 1,25(OH)2-D. These data suggest that 1,25(OH)2-D treatment specifically modulates human monocyte phenotype and function, altering HLA-DR antigen expression and antigen presentation, while leaving lytic function intact. These findings may be relevant to the immunobiologic role of 1,25(OH)2-D.
Summary of information on human CYP enzymes: human P450 metabolism data (2002)

This chapter is an update of the data on substrates, reactions, inducers, and inhibitors of human CYP enzymes published previously by Rendic and DiCarlo (1), now covering selection of the literature through 2001 in the reference section. The data are presented in a tabular form (Table 1) to provide a framework for predicting and interpreting the new P450 metabolic data. The data are formatted in an Excel format as most suitable for off-line searching and management of the Web-database. The data are presented as stated by the author(s) and in the case when several references are cited the data are presented according to the latest published information. The searchable database is available either as an Excel file (for information contact the author), or as a Web-searchable database (Human P450 Metabolism Database, www.gentest.com) enabling the readers easy and quick approach to the latest updates on human CYP metabolic reactions.
Foretinib Overcomes Entrectinib Resistance Associated with the NTRK1 G667C Mutation in NTRK1 Fusion–Positive Tumor Cells in a Brain Metastasis Model (2018)

<b>Purpose:</b> Rearrangement of the neurotrophic tropomyosin receptor kinase 1 (<i>NTRK1</i>) gene, which encodes tyrosine receptor kinase A (TRK-A), occurs in various cancers, including colon cancer. Although entrectinib is effective in the treatment of central nervous system (CNS) metastases that express <i>NTRK1</i> fusion proteins, acquired resistance inevitably results in recurrence. The CNS is a sanctuary for targeted drugs; however, the mechanism by which CNS metastases become entrectinib-resistant remains elusive and must be clarified to develop better therapeutics.<b>Experimental Design:</b> The entrectinib-resistant cell line KM12SM-ER was developed by continuous treatment with entrectinib in the brain metastasis-mimicking model inoculated with the entrectinib-sensitive human colon cancer cell line KM12SM, which harbors the <i>TPM3-NTRK1</i> gene fusion. The mechanism of entrectinib resistance in KM12SM-ER cells was examined by next-generation sequencing. Compounds that overcame entrectinib resistance were screened from a library of 122 kinase inhibitors.<b>Results:</b> KM12SM-ER cells, which showed moderate resistance to entrectinib <i>in vitro</i>, had acquired the G667C mutation in <i>NTRK1</i> The kinase inhibitor foretinib inhibited TRK-A phosphorylation and the viability of KM12SM-ER cells bearing the <i>NTRK1</i>-G667C mutation <i>in vitro</i> Moreover, foretinib markedly inhibited the progression of entrectinib-refractory KM12SM-ER-derived liver metastases and brain tumors in animal models, predominantly through inhibition of TRK-A phosphorylation.<b>Conclusions:</b> These results suggest that foretinib may be effective in overcoming entrectinib resistance associated with the <i>NTRK1</i>-G667C mutation in <i>NTRK1</i> fusion-positive tumors in various organs, including the brain, and provide a rationale for clinical trials of foretinib in cancer patients with entrectinib-resistant tumors harboring the <i>NTRK1</i>-G667C mutation, including patients with brain metastases. <i>Clin Cancer Res; 24(10); 2357-69. ©2018 AACR</i>.
Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications (2014)

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. Dimerization of the receptor results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways leading to cell proliferation and tumorigenesis. Amplification or overexpression of HER2 occurs in approximately 15-30% of breast cancers and 10-30% of gastric/gastroesophageal cancers and serves as a prognostic and predictive biomarker. HER2 overexpression has also been seen in other cancers like ovary, endometrium, bladder, lung, colon, and head and neck. The introduction of HER2 directed therapies has dramatically influenced the outcome of patients with HER2 positive breast and gastric/gastroesophageal cancers; however, the results have been proved disappointing in other HER2 overexpressing cancers. This review discusses the role of HER2 in various cancers and therapeutic modalities available targeting HER2.
Formation of elongated fascicle-inspired 3D tissues consisting of high-density, aligned cells using sacrificial outer molding (2014)

The majority of muscles, nerves, and tendons are composed of fiber-like fascicle morphology. Each fascicle has a) elongated cells highly aligned with the length of the construct, b) a high volumetric cell density, and c) a high length-to-width ratio with a diameter small enough to facilitate perfusion. Fiber-like fascicles are important building blocks for forming tissues of various sizes and cross-sectional shapes, yet no effective technology is currently available for producing long and thin fascicle-like constructs with aligned, high-density cells. Here we present a method for molding cell-laden hydrogels that generate cylindrical tissue structures that are ~100 μm in diameter with an extremely high length to diameter ratio (>100 : 1). Using this method we have successfully created skeletal muscle tissue with a high volumetric density (~50%) and perfect cell alignment along the axis. A new molding technique, sacrificial outer molding, allows us to i) create a long and thin cylindrical cavity of the desired size in a sacrificial mold that is solid at a low temperature, ii) release gelling agents from the sacrificial mold material after the cell-laden hydrogel is injected into fiber cavities, iii) generate a uniform axial tension between anchor points at both ends that promotes cell alignment and maturation, and iv) perfuse the tissue effectively by exposing it to media after melting the sacrificial outer mold at 37 °C. The effects of key parameters and conditions, including initial cavity diameter, axial tension, and concentrations of the hydrogel and gelling agent upon tissue compaction, volumetric cell density, and cell alignment are presented.
Fuel Oil Quality of Biomass Pyrolysis OilsState of the Art for the End Users (1999)

Biomass pyrolysis oils have potential to be used as a fuel oil substitute. Combustion tests have shown that the oils burn efficiently in standard or slightly modified boilers and engines with rates similar to those for commercial fuels. However, these tests also identified several challenges in bio-oils applications resulting from their properties. The oils have heating values of only 40−50% of that for hydrocarbon fuels. They have a high water content that is detrimental for ignition. Organic acids in the oils are corrosive to common construction materials. Solids (char) can block injectors or erode turbine blades. Over time, reactivity of some components in the oils leads to formation of larger molecules that results in high viscosity and in slower combustion. This paper discusses physical and chemical characteristics of bio-oils relevant to fuel applications as well as some low-cost methods for improvement of these properties. It also provides bio-oil specifications proposed by some industrial users and recommendations for storage and handling.
Silicon micromachined hollow microneedles for transdermal liquid transport (2003)

This paper presents a novel process for the fabrication of out-of-plane hollow microneedles in silicon. The fabrication method consists of a sequence of deep-reactive ion etching (DRIE), anisotropic wet etching and conformal thin film deposition, and allows needle shapes with different, lithography-defined tip curvature. In this study, the length of the needles varied between 150 and 350 micrometers. The widest dimension of the needle at its base was 250 μm. Preliminary application tests of the needle arrays show that they are robust and permit skin penetration without breakage. Transdermal water loss measurements before and after microneedle skin penetration are reported. Drug delivery is increased approximately by a factor of 750 in microneedle patch applications with respect to diffusion alone. The feasibility of using the microneedle array as a blood sampler on a capillary electrophoresis chip is demonstrated.
Multi-Heme Self-Assembly in Phospholipid Vesicles (1996)

The use of weak, intermolecular forces to orchestrate the contruction of multicomponent systems in membranes has significant implications in diverse areas of chemistry, biology, and medicine. We describe here the construction and characterization of multi-heme molecular ensembles in phospholipid vesicles. A trianionic zinc porphyrin was designed to bind cytochrome c at the membrane surface, while being anchored to a membrane spanning manganese porphyrin in the membrane interior via a terminal imidazole. The structure of the construct was probed by fluorescence and UV spectroscopy. Cytochrome c formed a stoichiometric 1:1 complex with the anionic porphyrin with a high binding constant (Ka ≈ 5 × 106 M-1). The ligation of the imidazole to the manganese porphyrin was confirmed by UV spectral changes. Large differences in the fluorescence quenching of Zn porphyrins with and without the terminal imidazole were observed upon their insertion into vesicles containing the Mn porphyrin. These spectroscopic observations were consistent with the formation of a ligated, ternary system consisting of the Mn(II) porphyrin, the imidazole-tailed zinc porphyrin acting as a bridge, and the surface associated cytochrome c. The nature of the binding of cytochrome c at the membrane−water interface was investigated by Langmuir−Blodgett (LB) and differential scanning calorimetric (DSC) techniques. The data obtained suggested that the protein was surface bound with minimal penetration into the membrane. LB studies were also used to probe the orientation of the trianionic porphyrin moiety at the membrane surface, and an edge-on orientation was inferred from the data. The formation of a stable vesicular system was confirmed by the formation of well-defined DSC thermograms. Phase separation was observed at high porphyrin:lipid ratios. Electron transfer from the Mn(II) in the membrane interior to the surface bound ferricytochrome c was investigated, as a probe both for spatial definition of the ensemble and for the elucidation of electron transfer mechanism in the genre of weakly coupled systems over large distances. Trianionic Zn porphyrins with varying tether lengths (12, 8, and 4 carbons) were used. The electron transfer rate was found to be first order and independent of the tether length, indicative of medium mediated electron transfer via multiple pathways. Comparison to similar systems in the literature yielded a predicted distance of ∼23 Å between the Mn and Fe centers in DMPC/DPPC vesicles. This distance suggested that the protein was surface bound to the membrane and separated from the Mn porphyrin by the thickness of one leaflet of the phospholipid bilayer. In thinner DLPC vesicles the predicted increase in the electron transfer rate was observed. Additionally, electron transfer was observed to be bimolecular in systems where trianionic porphyrins lacking the imidazole tether were used to recruit the cytochrome c.
Structure–activity Relationships of Amyloid Beta‐aggregation Inhibitors Based on Curcumin: Influence of Linker Length and Flexibility (2007)

Self-assembly of amyloid beta into fibrillar plaques is characteristic of Alzheimer's disease and oligomers of this peptide are believed to be involved in neurodegeneration. Natural organic dyes, such as congo red and curcumin, bind tightly to amyloid beta and, at higher concentrations, block its self-assembly. The ability of these molecules to prevent amyloid accumulation has generated interest in understanding which of their structural features contribute to inhibitory potency. In general, amyloid beta ligands tend to be flat, planar molecules with substituted aromatic end groups; however, a comprehensive structure-activity study has not been reported. To better understand these ligands, we surveyed the effect of three prominent features on inhibition of amyloid aggregation: the presence of two aromatic end groups, the substitution pattern of these aromatics, and the length and flexibility of the linker region. We found that modification of any one of the modules has profound effects on activity. Further, we report that the optimal length of the linker lies within a surprisingly narrow regime (6-19 A). These results offer insight into the key chemical features required for inhibiting amyloid beta aggregation. In turn, these findings help define the nature of the docking site for small molecules on the amyloid beta surface.
Stimulation of apical and basolateral VEGF-A and VEGF-C secretion by oxidative stress in polarized retinal pigment epithelial cells. (2006)

Our data show that oxidative stress to RPE from tBH upregulates secretion of both VEGF-A and C. The secretion to the apical side was higher than that of basolateral side for VEGF-A and C. Given the role of VEGF in choroidal neovascularization, these data may be of value in understanding pathogenic mechanisms and designing antiangiogenic therapies.
The efficacy of adenovirus-mediated gene therapy of ovarian cancer is enhanced by using the cytomegalovirus promoter. (1998)

The cytomegalovirus(CMV) promoter is considered one of the strongest positive regulators. In this study toxicity, cell killing efficacy and bystander effect of Rous Sarcoma Virus(RSV) driven herpes simplex thymidine kinase(TK) gene therapy was compared with CMV driven TK gene therapy in three ovarian cancer cell lines with different growth patterns using a 3-(4,5-dimethylthiazol)-2,5-diphenyl tetra-zolium bromide (MTT) based assay. ADV/CMV-TK was shown to be 2 to 10 times more effective in tumor cell killing than ADV/RSV-TK. The difference in cell killing efficacy between ADV/CMV-TK and ADV/RSV-TK was dependent on the individual cell line. A CMV promoter dependent eight to ten fold improvement in cell killing efficacy was observed in the relatively slow growing SKOV3 cell line which is not easily transducible, while only a 2 to 4 fold difference was observed in the easily transducible OV-CA-2774 and OV-CA-1225 cell lines. ADV/CMV-TK also showed a stronger bystander effect than ADV/RSV-TK in all three ovarian cancer cell lines. Our data demonstrated that the efficacy of adenovirus-mediated gene therapy of ovarian cancer can be enhanced by using the CMV promoter without increasing toxicity.
Generalized fisheye views (1986)

In many contexts, humans often represent their own “neighborhood” in great detail, yet only major landmarks further away. This suggests that such views (“fisheye views”) might be useful for the computer display of large information structures like programs, data bases, online text, etc. This paper explores fisheye views presenting, in turn, naturalistic studies, a general formalism, a specific instantiation, a resulting computer program, example displays and an evaluation.
Flexible Targeting of ErbB Dimers That Drive Tumorigenesis by Using Genetically Engineered T Cells (2012)

Pharmacological targeting of individual ErbB receptors elicits antitumor activity, but is frequently compromised by resistance leading to therapeutic failure. Here, we describe an immunotherapeutic approach that exploits prevalent and fundamental mechanisms by which aberrant upregulation of the ErbB network drives tumorigenesis. A chimeric antigen receptor named T1E28z was engineered, in which the promiscuous ErbB ligand, T1E, is fused to a CD28 + CD3ζ endodomain. Using a panel of ErbB-engineered 32D hematopoietic cells, we found that human T1E28z⁺ T cells are selectively activated by all ErbB1-based homodimers and heterodimers and by the potently mitogenic ErbB2/3 heterodimer. Owing to this flexible targeting capability, recognition and destruction of several tumor cell lines was achieved by T1E28⁺ T cells in vitro, comprising a wide diversity of ErbB receptor profiles and tumor origins. Furthermore, compelling antitumor activity was observed in mice bearing established xenografts, characterized either by ErbB1/2 or ErbB2/3 overexpression and representative of insidious or rapidly progressive tumor types. Together, these findings support the clinical development of a broadly applicable immunotherapeutic approach in which the propensity of solid tumors to dysregulate the extended ErbB network is targeted for therapeutic gain.
Splicing regulation: From a parts list of regulatory elements to an integrated splicing code (2008)

Alternative splicing of pre-mRNAs is a major contributor to both proteomic diversity and control of gene expression levels. Splicing is tightly regulated in different tissues and developmental stages, and its disruption can lead to a wide range of human diseases. An important long-term goal in the splicing field is to determine a set of rules or "code" for splicing that will enable prediction of the splicing pattern of any primary transcript from its sequence. Outside of the core splice site motifs, the bulk of the information required for splicing is thought to be contained in exonic and intronic cis-regulatory elements that function by recruitment of sequence-specific RNA-binding protein factors that either activate or repress the use of adjacent splice sites. Here, we summarize the current state of knowledge of splicing cis-regulatory elements and their context-dependent effects on splicing, emphasizing recent global/genome-wide studies and open questions.
Lymphatic endothelium (2003)

The lymphatic microvasculature is uniquely adapted for the continuous removal of interstitial fluid and proteins, and is an important point of entry for leukocytes and tumor cells. The traditional view that lymphatic capillaries are passive participants in these tasks is currently being challenged. This overview highlights recent advances in our understanding of the molecular mechanisms underlying the formation and function of lymphatic vessels.
Synthetic Protocells to Mimic and Test Cell Function (2009)

Synthetic protocells provide a new means to probe, mimic and deconstruct cell behavior; they are a powerful tool to quantify cell behavior and a useful platform to explore nanomedicine. Protocells are not simple particles; they mimic cell design and typically consist of a stabilized lipid bilayer with membrane proteins. With a finite number of well characterized components, protocells can be designed to maximize useful outputs. Energy conversion in cells is an intriguing output; many natural cells convert transmembrane ion gradients into electricity by membrane-protein regulated ion transport. Here, a synthetic cell system comprising two droplets separated by a lipid bilayer is described that functions as a biological battery. The factors that affect its electrogenic performance are explained and predicted by coupling equations of the electrodes, transport proteins and membrane behavior. We show that the output of such biological batteries can reach an energy density of 6.9 x 10(6) J m(-3), which is approximately 5% of the volumetric energy density of a lead-acid battery. The configuration with maximum power density has an energy conversion efficiency of 10%.