gebhart/patrepeval huggingface dataset:
Three-Fold Induction of Renal 25-Hydroxyvitamin D3-24-Hydroxylase Activity and Increased Serum 24,25-Dihydroxyvitamin D3 Levels Are Correlated with the Healing Process After Chick Tibial Fracture (1997)

To investigate the possible biological actions of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), a tibial fracture-healing model was established in White Leghorn chicks. Three-week-old White Leghorn chicks fed a vitamin D3-replete diet were divided into four groups (control, anesthetized, sham, and fractured). On varying days after tibial fracture (F) or sham manipulation (S), renal 25(OH)D3-1 alpha-hydroxylase and 25(OH)D3-24-hydroxylase (24-hydroxylase) activities and serum Ca2+ concentrations were measured. Metofane anesthesia was found to have no effect on the activity of either of the hydroxylases; the activities of the hydroxylases in the control, anesthetized, and sham-operated birds were similar. By 10 days after tibial fracture, the renal 24-hydroxylase activity increased more than 3-fold in F (1.33 +/- 0.07 pmol/mg of protein) as compared with S (0.42 +/- 0.03 pmol/mg of protein) (p < 0.0001). A time-dependent study of the renal 24-hydroxylase activity during the fracture repair process revealed a slow increase from the first day after fracture, a higher activity at 8 days, which peaked at 10-11 days, which is consistent with the formation of the callus. The 24-hydroxylase activity then returned to the same level as the sham group 14 days after fracture. There was no significant difference in serum Ca2+ levels between the F and S groups over the 3-week postfracture period. Serum levels of vitamin D3 metabolites were also measured during the fracture healing process: a 3.4x increase of the 24,25(OH)2D3 level in the fractured group (3.64 +/- 1.16 nM) was observed as compared with the control groups (1.08 +/- 0.49 nM) at 10 days after fracture (p = 0.068). No significant differences were observed in the plasma levels of 25(OH)D3 or 1 alpha, 25(OH)2D3 between the group with a fracture and the controls. Exposure of primary chick kidney cells in culture to serum obtained from chicks with a tibial fracture for 20 h resulted in an approximately 40% increase in the activity of the 24-hydroxylase as compared with cells exposed to serum from control birds. These results suggest that 24,25(OH)2D3 is involved in the early process of fracture repair and that there is some form of physiological communication between the fractured bone and the kidney so as to increase the renal 24-hydroxylase and the circulating concentration of this metabolite.
An ingestible self-orienting system for oral delivery of macromolecules (2019)

Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise's ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator's safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasma levels comparable to those achieved with subcutaneous millipost administration.
Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury (2008)

Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury (SCI). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created within the extracellular spaces of the spinal cord by simply injecting a liquid. The molecules are designed to form cylindrical nanofibers that display to cells in the spinal cord the laminin epitope IKVAV at nearly van der Waals density. IKVAV PA nanofibers are known to inhibit glial differentiation of cultured neural stem cells and to promote neurite outgrowth from cultured neurons. In this work, in vivo treatment with the PA after SCI reduced astrogliosis, reduced cell death, and increased the number of oligodendroglia at the site of injury. Furthermore, the nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site. Treatment with the PA also resulted in significant behavioral improvement. These observations demonstrate that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces.
Electrochemical Detection of Single Molecules (1995)

The electrochemical behavior of a single molecule can be observed by trapping a small volume of a dilute solution of the electroactive species between an ultramicroelectrode tip with a diameter of approximately 15 nanometers and a conductive substrate. A scanning electrochemical microscope was used to adjust the tip-substrate distance ( approximately 10 nanometers), and the oxidation of [(trimethylammonio)methyl] ferrocene (Cp(2)FeTMA(+)) to Cp(2)FeTMA(2+) was carried out. The response was stochastic, and anodic current peaks were observed as the molecule moved into and out of the electrode-substrate gap. Similar experiments were performed with a solution containing two redox species, ferrocene carboxylate (Cp(2)FeCOO(-)) and Os(bpy)(3)(2+) (bpy is 2,2'-bipyridyl).
Coherent anti-Stokes Raman scattering spectral interferometry: determination of the real and imaginary components of nonlinear susceptibility χ^(3) for vibrational microscopy (2004)

We demonstrate coherent anti-Stokes Raman scattering (CARS) heterodyne spectral interferometry for retrieval of the real and imaginary components of the third-order nonlinear susceptibility (chi(3)) of molecular vibrations. Extraction of the imaginary component of chi(3) allows a straightforward reconstruction of the vibrationally resonant signal that is completely free of the electronic nonresonant background and resembles the spontaneous Raman spectrum. Heterodyne detection offers potential for signal amplification and enhanced sensitivity for CARS microscopy.
The cancer anorexia-cachexia syndrome. (1994)

The anorexia-cachexia syndrome is a common problem in advanced cancer. Although many possible etiologies have been investigated, the cause has not been determined. Appropriate clinical evaluation is necessary to identify those patients who may respond to available, symptomatic treatments.
Intracellular multiplication of Legionella pneumophila depends on host cell amino acid transporter SLC1A5 (2005)

The infectious agent of Legionnaires' disease, Legionella (L) pneumophila, multiplies intracellularly in eukaryotic cells. This study has been performed to explore the nutrient requirements of L. pneumophila during intracellular replication. In human monocytes, bacterial replication rate was reduced by 76% in defined medium lacking L-cysteine, L-glutamine or L-serine. SLC1A5 (hATB(0,+)), a neutral amino acid transporter, was upregulated in the host cells after infection with L. pneumophila. Inhibition of SLC1A5 by BCH, a competitive inhibitor of amino acid uptake as well as siRNA silencing of the slc1a5 gene blocked intracellular multiplication of L. pneumophila without compromising viability of host cells. These observations suggest that replication of L. pneumophila depends on the function of host cell SLC1A5.
Orthogonal Self-Assembly of Redox Active Molecules on Pt and Au: Selective Reaction of Disulfide with Au and Isonitrile with Pt (1992)

Surfaces of platinum and gold adsorb ferrocenyl-12-dodecyl isocyanide, I, and di(10-ferrocenecarbonyl-decyl) disulfide, II, and yield self-assembled, redox active monolayers incorporating ferrocene groups. The values of E 1/2 for alkyl ferrocenyl centers from I are approximately 300 mV more negative than acyl ferrocenyl centers from II. This difference allows easy electrochemical measurement of surface concentrations of ferrocene centers from I and II on Pt or Au. I adsorbs selectively on Pt or Au compared to II, but with different degrees of selectivity. Further, for Pt the selectivity depends on the surface pretreatment. The affinity of II for a Pt surface first exposed to an O2 plasma (oxidized Pt) is lower than that for a Pt surface exposed first to an O2 plasma and then to a H2 plasma (reduced Pt). The same two plasma treatments of Pt do not affect the binding of I on Pt. Thus, the selectivity of Pt for I vs. II is higher for the oxidized Pt approximately (200:1) compared to that for the reduced Pt approximately (20:1). The two plasma treatments of Au do not influence the selectivity for binding I vs. II; the selectivity for binding I vs II. on Au is approximately 8.1. By using the O2 plasma pretreatment and a 40:1 solution of II:I, orthogonal self-assembly of II onto Au and I onto Pt can be effected when the two samples are derivatized in the same solution.
Optimization of bioprocess conditions improves production of a CHO cell‐derived, bioengineered heparin (2015)

Heparin is the most widely used anticoagulant drug in the world today. Heparin is currently produced from animal tissues, primarily porcine intestines. A recent contamination crisis motivated development of a non-animal-derived source of this critical drug. We hypothesized that Chinese hamster ovary (CHO) cells could be metabolically engineered to produce a bioengineered heparin, equivalent to current pharmaceutical heparin. We previously engineered CHO-S cells to overexpress two exogenous enzymes from the heparin/heparan sulfate biosynthetic pathway, increasing the anticoagulant activity ∼100-fold and the heparin/heparan sulfate yield ∼10-fold. Here, we explored the effects of bioprocess parameters on the yield and anticoagulant activity of the bioengineered GAGs. Fed-batch shaker-flask studies using a proprietary, chemically-defined feed, resulted in ∼two-fold increase in integrated viable cell density and a 70% increase in specific productivity, resulting in nearly three-fold increase in product titer. Transferring the process to a stirred-tank bioreactor increased the productivity further, yielding a final product concentration of ∼90 μg/mL. Unfortunately, the product composition still differs from pharmaceutical heparin, suggesting that additional metabolic engineering will be required. However, these studies clearly demonstrate bioprocess optimization, in parallel with metabolic engineering refinements, will play a substantial role in developing a bioengineered heparin to replace the current animal-derived drug.
Prostate cancer: status of current treatments and emerging antisense-based therapies. (2002)

Prostate cancer, like most other solid tumors, represents a heterogeneous entity consisting of a mixture of androgen-dependent and androgen-independent cells. Although proliferation of prostate tumor cells is often initially androgen-dependent, the inevitable development of androgen-insensitivity in late-stage prostate cancer renders androgen-suppressing treatments ultimately ineffective. Non-hormonal chemotherapy induces apoptosis in actively proliferating cells and is typically of little value, since prostate cancer demonstrates very slow growth kinetics. Objective response rates of < 10% and no improved survival rates have been observed in several hundred clinical studies using both experimental and approved chemotherapeutic agents. An improved understanding of the molecular mechanisms responsible for the onset of the disease, as well as the factors that control the proliferation of prostate cancer cells, have identified key changes in gene expression during cancer progression, especially from androgen-dependent to androgen-independent status. Manipulation of the genes implicated in disease progression represent an important approach for therapeutic intervention. This review summarizes recent progress that has been made with the use of antisense technology with various chemistries to modify gene expression, a strategy that seems to hold great promise for prostate cancer therapy.
Identification of unique peanut and soy allergens in sera adsorbed with cross-reacting antibodies (1996)

Antigen-affinity chromatography is an effective method for removal of cross-reacting antibodies. We identified IgE antibody binding (with sera where cross-reacting antibodies were removed) to several unique antigenic fractions of peanut and soy. Further studies will determine the clinical significance of these fractions in IgE-mediated food hypersensitivity reactions.
The Effect of Weather on Headache (2004)

Our study supports the influence of weather variables on headache. We showed that patients are susceptible to multiple weather variables and that more patients thought weather was a trigger than was the case.
Total Synthesis of Everninomicin 13,384-1—Part 2: Synthesis of the FGHA2 Fragment (1999)

The powerful antibiotic everninomicin 13,384-1 (1, Ziracin) has been prepared for the first time through a total synthesis. The 1-->1'-disaccharide and the two orthoesters of this target molecule were introduced by new methodologies using a tin acetal and 1,2-phenylseleno migrations. The reaction sequence also relies on stereoselective glycosidations and subtle manipulations of protecting groups. In addition to the introduction of new synthetic methodologies, this total synthesis should allow the preparation of combinatorial libraries of semisynthetic analogues of this highly promising antibiotic for biological screening purposes.
WearIT@work: Toward Real-World Industrial Wearable Computing (2007)

The wearIT@work project, financed by the European Union, aims at facilitating real-life industrial deployment of wearable technology. With 42 partners, a project funding of 23.7 million, this consortium is the largest civilian wearable-computing effort worldwide. The project is organized around four pilot applications—aircraft maintenance, car production, healthcare, and emergency response—that drive the work in a bottom-up, user-centered approach.
Contactless measurement of thoracic conductivity changes by magnetic induction (2002)

A noninvasive technique of measuring thoracic conductivity changes caused by respiration and cardiac activity is described. Conductivity is measured with a hand-held sensor comprising a planar coil, a radio-frequency (RF) oscillator and a closed-loop control system to hold constant the amplitude of oscillations. This system automatically compensates for changes in the power dissipated by eddy-currents in the thorax by adjusting the RF current driven into the coil. This results in the control signal being proportional to the conductivity of the thorax. Simulations with a thorax model consisting of four eccentric spheres were used to determine the magnitude of changes for a range of tidal volumes and stroke volumes. The importance of tissue properties, such as lung conductivity and hematocrit was assessed. Finally, an example of signals recorded in-vivo with the sensor is presented. Use of this technique to monitor cardiac output would require a one-time measurement of geometrical data specific to the patient's thorax (e.g. the distance between the heart and the body-surface), in order to transform measured cardiosynchronous conductivity changes into stroke volume.
Increase in dNTP pool size during the DNA damage response plays a key role in spontaneous and induced-mutagenesis in Escherichia coli (2011)

Exposure of Escherichia coli to UV light increases expression of NrdAB, the major ribonucleotide reductase leading to a moderate increase in dNTP levels. The role of elevated dNTP levels during translesion synthesis (TLS) across specific replication-blocking lesions was investigated. Here we show that although the specialized DNA polymerase PolV is necessary for replication across UV-lesions, such as cyclobutane pyrimidine dimers or pyrimidine(6-4)pyrimidone photoproduct, Pol V per se is not sufficient. Indeed, efficient TLS additionally requires elevated dNTP levels. Similarly, for the bypass of an N-2-acetylaminofluorene-guanine adduct that requires Pol II instead of PolV, efficient TLS is only observed under conditions of high dNTP levels. We suggest that increased dNTP levels transiently modify the activity balance of Pol III (i.e., increasing the polymerase and reducing the proofreading functions). Indeed, we show that the stimulation of TLS by elevated dNTP levels can be mimicked by genetic inactivation of the proofreading function (mutD5 allele). We also show that spontaneous mutagenesis increases proportionally to dNTP pool levels, thus defining a unique spontaneous mutator phenotype. The so-called "dNTP mutator" phenotype does not depend upon any of the specialized DNA polymerases, and is thus likely to reflect an increase in Pol III's own replication errors because of the modified activity balance of Pol III. As up-regulation of the dNTP pool size represents a common physiological response to DNA damage, the present model is likely to represent a general and unique paradigm for TLS pathways in many organisms.
Hsp90 Regulates a von Hippel Lindau-independent Hypoxia-inducible Factor-1α-degradative Pathway (2002)

HIF-1 alpha is a normally labile proangiogenic transcription factor that is stabilized and activated in hypoxia. Although the von Hippel Lindau (VHL) gene product, the ubiquitin ligase responsible for regulating HIF-1 alpha protein levels, efficiently targets HIF-1 alpha for rapid proteasome-dependent degradation under normoxia, HIF-1 alpha is resistant to the destabilizing effects of VHL under hypoxia. HIF-1 alpha also associates with the molecular chaperone Hsp90. To examine the role of Hsp90 in HIF-1 alpha function, we used renal carcinoma cell (RCC) lines that lack functional VHL and express stable HIF-1 alpha protein under normoxia. Geldanamycin (GA), an Hsp90 antagonist, promoted efficient ubiquitination and proteasome-mediated degradation of HIF-1 alpha in RCC in both normoxia and hypoxia. Furthermore, HIF-1 alpha point mutations that block VHL association did not protect HIF-1 alpha from GA-induced destabilization. Hsp90 antagonists also inhibited HIF-1 alpha transcriptional activity and dramatically reduced both hypoxia-induced accumulation of VEGF mRNA and hypoxia-dependent angiogenic activity. These findings demonstrate that disruption of Hsp90 function 1) promotes HIF-1 alpha degradation via a novel, oxygen-independent E3 ubiquitin ligase and 2) diminishes HIF-1 alpha transcriptional activity. Existence of an Hsp90-dependent pathway for elimination of HIF-1 alpha predicts that Hsp90 antagonists may be hypoxic cell sensitizers and possess antiangiogenic activity in vivo, thus extending the utility of these drugs as therapeutic anticancer agents.
ChemInform Abstract: Synthesis, Crystal Chemistry, and Electrochemical Properties of Li7‐2xLa3Zr2‐xMoxO12 (x = 0.1—0.4): Stabilization of the Cubic Garnet Polymorph via Substitution of Zr4+ by Mo6+. (2015)

Abstract Li 7‐2x La 3 Zr 2‐x Mo x O 12 (x = 0.1—0.4) are prepared by calcining a stoichiometric mixture of Li 2 CO 3 , La 2 O 3 , ZrO 2 , and MoO 3 (850 °C, 4 h), followed by grinding and final sintering (1230 °C, 4 h).
The role of palmitoylation in regulating Ras localization and function (2013)

Ras GTPases are important regulators of pathways controlling proliferation, differentiation and transformation. Three ubiquitously expressed almost identical Ras genes are not functionally redundant; this has been attributed to their distinctive trafficking and localization profiles. A palmitoylation cycle controls the correct compartmentalization of H-Ras and N-Ras. We review recent data that reveal how this cycle can be regulated by membrane organization to influence the spatiotemporal signalling of Ras.
Accumulation of glycosphingolipids in human atherosclerotic plaque and unaffected aorta tissues (1997)

We have measured the levels of glycosphingolipids and the activity of glycosphingolipid glycosyltransferases in human aortic intima and media from patients who died of atherosclerosis. The effects of lactosylceramide (LacCer) and glucosylceramide (GlcCer) from plaque intima on smooth muscle cell proliferation were assessed. When the GlcCer data was expressed as (micrograms GlcCer/mg cholesterol and/mg total phospholipid, a 28-fold and 7-fold increase in plaque intima compared to normal intima was observed. Similarly, the level of LacCer was elevated 5-fold and 4-fold, respectively, compared to unaffected intima. The activity of UDP-GlcCer: ceramide beta 1-->4 glucosyltransferase (GlcT-1) was similar in unaffected tissue, fatty streaks, and plaques. However, the activity of UDP-galactose: GlcCer, beta 1-->4 galactosyltransferase (GalT-2) activity was moderately higher in plaque than in unaffected tissue. LacCer, but not GlcCer derived from plaque intima exerted a approximately 2.8-fold increase in the proliferation of human aortic smooth muscle cells grown in tissue culture compared to control presumably due to a marked increase in LacCer molecular species containing C16:0, C22:1, and C24:0 fatty acids in plaque intima compared to control. In sum, our findings provide an interesting and novel pathogenic mechanism of lactosylceramide mediated plaque formation via stimulation of aortic smooth muscle cell proliferation.
Purification and characterization of methylmalonyl-CoA epimerase from Propionibacterium shermanii (1981)

Methylmalonyl-CoA epimerase, which specifically interconverts the (2R)- and (2S)- epimers of methylmalonyl-CoA, was purified 95-fold from Propionibacterium shermanii by a new method that affords apparently homogeneous enzyme, in 80-100mg quantities, in yields representing about 40% of the activity in cell-free extracts. The specific activity of the purified enzyme, 10.1 mukat/mg, is much greater than previously reported. Native methylmalonyl-CoA epimerase has Mr about 33000, and apparently consists of two identical subunits. The purified enzyme is stable indefinitely when stored at -20 degrees C and pH 8.5, but contrary to previous reports it is not unusually acid-stable. The activity of methylmalonyl-CoA epimerase is increased by Co2+, and to a smaller extent by Ni2+, Mn2+ and Zn2+.
The Inducible Costimulator Augments Tc17 Cell Responses to Self and Tumor Tissue (2015)

The inducible costimulator (ICOS) plays a key role in the development of Th17 cells, but its role in the development and antitumor activity of IL-17-producing CD8(+) T cells (Tc17) remains unknown. We found that ICOS costimulation was important for the functional maintenance, but not differentiation, of Tc17 cells in vitro. Blocking the ICOS pathway using an antagonist mAb or by using recipient mice genetically deficient in the ICOS ligand reduced the antitumor activity of adoptively transferred Tc17 cells. Conversely, activating Tc17 cells with an ICOS agonist in vitro enhanced their capacity to eradicate melanoma and induce autoimmune vitiligo when infused into mice. However, ICOS stimulation did not augment the antitumor activity of IL-2 expanded T cells. Additional investigation revealed that ICOS stimulation not only increased IL-2Rα, CXCR3, and IL-23R expression on Tc17 cells, but also dampened their expression of suppressive molecule CD39. Although Tc17 cells activated with an ICOS agonist cosecreted heightened IL-17A, IL-9, and IFN-γ, their therapeutic effectiveness was critically dependent on IFN-γ production. Depletion of IL-17A and IL-9 had little impact on antitumor Tc17 cells activated with an ICOS agonist. Collectively, our work reveals that the ICOS pathway potentiates the antitumor activity of adoptively transferred Tc17 cells. This work has major implications for the design of vaccine, Ab and cell-based therapies for autoimmunity, infectious disease, and cancer.