gebhart/patrepeval huggingface dataset:
Absolute oxygen tension (pO2) in murine fatty and muscle tissue as determined by EPR (2005)

The absolute partial pressure of oxygen (pO(2)) in the mammary gland pad and femoral muscle of female mice was measured using EPR oximetry at 700 MHz. A small quantity of lithium phthalocyanine (LiPc) crystals was implanted in both mammary and femoral muscle tissue of female C3H mice. Subsequent EPR measurements were carried out 1-30 days after implantation with or without control of core body temperature. The pO(2) values in the tissue became stable 2 weeks after implantation of LiPc crystals. The pO(2) level was found to be higher in the femoral muscle than in the mammary tissue. However, the pO(2) values showed a strong dependence on the core body temperature of the mice. The pO(2) values were responsive to carbogen (95% O(2), 5% CO(2)) breathing even 44-58 days after the implantation of LiPc. The LiPc linewidth was also sensitive to changes in the blood supply even 60 days after implantation of the crystals. This study further validates the use of LiPc crystals and EPR oximetry for long-term non-invasive assessment of pO(2) levels in tissues, underscores the importance of maintaining normal body core temperature during the measurements, and demonstrates that mammary tissue functions at a lower pO(2) level than muscle in female C3H mice.
Recombinant Protein-co-PEG Networks as Cell-Adhesive and Proteolytically Degradable Hydrogel Matrixes. Part II:  Biofunctional Characteristics (2006)

We present here the biological performance in supporting tissue regeneration of hybrid hydrogels consisting of genetically engineered protein polymers that carry specific features of the natural extracellular matrix, cross-linked with reactive poly(ethylene glycol) (PEG). Specifically, the protein polymers contain the cell adhesion motif RGD, which mediates integrin receptor binding, and degradation sites for plasmin and matrix-metalloproteinases, both being proteases implicated in natural matrix remodeling. Biochemical assays as well as in vitro cell culture experiments confirmed the ability of these protein-PEG hydrogels to promote specific cellular adhesion and to exhibit degradability by the target enzymes. Cell culture experiments demonstrated that proteolytic sensitivity and suitable mechanical properties were critical for three-dimensional cell migration inside these synthetic matrixes. In vivo, protein-PEG matrixes were tested as a carrier of bone morphogenetic protein (rhBMP-2) to heal critical-sized defects in a rat calvarial defect model. The results underscore the importance of fine-tuning material properties of provisional therapeutic matrixes to induce cellular responses conducive to tissue repair. In particular, a lack of rhBMP or insufficient degradability of the protein-PEG matrix prevented healing of bone defects or remodeling and replacement of the artificial matrix. This work confirms the feasibility of attaining desired biological responses in vivo by engineering material properties through the design of single components at the molecular level. The combination of polymer science and recombinant DNA technology emerges as a powerful tool for the development of novel biomaterials.
USF1 Recruits Histone Modification Complexes and Is Critical for Maintenance of a Chromatin Barrier (2007)

The insulator element at the 5' end of the chicken beta-globin locus acts as a barrier, protecting transgenes against silencing effects of adjacent heterochromatin. We showed earlier that the transcription factor USF1 binds within the insulator and that this site is important for generating in adjacent nucleosomes histone modifications associated with active chromatin and, by inference, with barrier function. To understand the mechanism of USF1 action, we have characterized USF1-containing complexes. USF1 interacts directly with the histone H4R3-specific methyltransferase PRMT1. USF1, PRMT1, and the histone acetyltransferases (HATs) PCAF and SRC-1 form a complex with both H4R3 histone methyltransferase and HAT activities. Small interfering RNA downregulation of USF1 results in localized loss of H4R3 methylation, and other histone modifications associated with euchromatin, at the insulator. A dominant negative peptide that interferes with USF1 binding to DNA causes silencing of an insulated reporter construct, indicating abolition of barrier function. These results show that USF1 plays a direct role in maintaining the barrier, supporting a model in which the insulator works as a barrier by maintaining a local environment of active chromatin.
A rapid method for detection of putative RNAi target genes in genomic data (2003)

RNAi, inhibition of gene expression by double stranded RNA molecules, has rapidly become a powerful laboratory technique to study gene function. The effectiveness of the procedure raised the question of whether this laboratory technique may actually mimic a natural cellular control mechanism that works on similar principles. Indeed recent evidence is accumulating to suggest that RNAi is a natural control mechanism that might even serve as a primitive immune response against RNA viruses and retroposons. Three different interference scenarios seem to be utilized by various RNAi mechanisms. One of the mechanisms involves degradation of mRNA molecules. Here we suggest a method to systematically scan entire genomes simultaneously for RNAi elements and the presence of cellular genes that are degraded by these RNAi elements via exact short base-pair matching. The method is based on scanning the genomes using a suffix tree data structure that was specifically modified to identify sets of combinations of repeated and inverted repeated sequences of 20 bp or more. Initial scan suggest that a large number, about 7% of C.elegans and 3% of C.briggsae genes, have the potential to be subject to natural RNAi control. Two methods are proposed to further analyze these genes to select the cases that are more likely to be actual cases of RNAi control. One method involves looking for ESTs that can provide direct evidence that RNAi control element are indeed expressed. The other method looks for synteny between C.elegans and C.briggsae assuming that genes that might be under RNAi control in both organisms are more likely to be biological significant. Taken together, supportive evidence was found for about 70 genes to be under RNAi control. Among these genes are: transposase, hormone receptors, homeobox proteins, defensin, actins, and several types of collagens. While our method is not capable of detecting all cases of natural RNAi control, it points to a large number of potential cases that can be further verified by experimental work.
Glycosylation in Lepidopteran insect cells: identification of a β1→4-N-acetylgalactosaminyltransferase involved in the synthesis of complex-type oligosaccharide chains (1996)

The choice for a heterologous expression system to produce glycoprotein therapeutics highly depends on its potential to perform mammalian-like posttranslational modifications such as glycosylation. To gain more insight into the glycosylation potential of the baculovirus mediated insect cell expression system, we have studied the expression of glycosyltransferases involved in complex-type N-glycosylation. Lepidopteran insect cell lines derived from Trichoplusia ni, Spodoptera frugiperda, and Mamestra brassicae were found to express a beta 1-->4- N-acetylgalactosaminyltransferase (beta 4-GalNAcT) that catalyzes the transfer of GalNAc from UDP-GalNAc to oligosaccharides and glycoproteins carrying a terminal beta-linked GlcNAc residue. These results suggest that Lepidopteran insect cells are capable of synthesizing complex-type carbohydrate chains containing GalNAc beta 1-->4GlcNAc (LacdiNAc) units. Baculovirus infection of the cells, however, resulted in a decrease in the activity of beta 4-GalNAcT from 80 to <1 pmol.min-1 mg-1 protein within 48 h post infection. Furthermore, considerable beta-N-acetylgalactosaminidase and beta-N-acetylglucosaminidase activity was observed in insect cells, whether or not infected with baculovirus, as well as in the culture medium. These enzyme activities could be responsible for degradation of complex-type oligosaccharide chains containing LacdiNAc units. Our findings provide an enzymatic basis for the observation that most recombinant glycoproteins produced by baculovirus infected insect cells carry oligomannosidic-type N-linked glycans, in spite of the fact that uninfected insect cells have the potential for the synthesis of mammalian-like complex-type glycans.
Amino Acid Residues 721–729 are Required for Full Factor VIII Activity (1995)

Recombinant two-chain factor VIII, from which the B domain had been deleted, was expressed in Chinese hamster ovary cells. In addition to the major product, three minor factor VIII forms were isolated. The A2 domains generated by thrombin cleavage showed different electrophoretic mobilities. Peptide mapping of the A2 domains showed that two of the factor VIII forms had the expected C-terminus of the heavy chain at Arg740 [FVIII-(1-740)] and that the other factor VIII forms had C-termini at Tyr729 [FVIII-(1-729)] or Glu720 [FVIII-(1-720)]. The major FVIII-(1-740) form, FVIII-(1-729), and FVIII-(1-720) contained sulfated tyrosine residues at Tyr718, Tyr719 and Tyr723. The minor FVIII-(1-740) form was shown to lack sulfation at these positions. The specific clotting activity was approximately 1 x 10(4) U/mg for FVIII-(1-740) (both forms) and FVIII-(1-729), but twofold lower for FVIII-(1-720). A time study of thrombin activation showed that FVIII-(1-720) was activated slower than FVIII-(1-740), FVIII-(1-729) and plasma-derived factor VIII. Partially sulfated FVIII-(1-740) was activated at the same rate as the fully sulfated FVIII-(1-740). The equilibrium dissociation constant for binding of factor VIII to inactivated immobilized thrombin was the same for all factor VIII forms, showing that the slower activation of FVIII-(1-720) was not due to a lower affinity for the anion-binding exosite in thrombin.
Preparation of Highly Luminescent Nanocrystals and Their Application to Light‐Emitting Diodes (2007)

Core/multishell-structured semiconductor nanocrystals (NCs) are prepared in multigram amounts through a one-pot process without a core-separation step (see figure and cover). The NCs show a maximum quantum efficiency of 85 % at a controlled wavelength and strong photostability against UV-light bleaching. The NCs are applied as phosphors on UV-light-emitting diodes (390 nm source), which emit light at 620 nm with a 48 % power conversion efficiency. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2007/c2642_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Diagnosis of breast cancer by tear proteomic pattern. (2009)

In this study a biomarker panel in tear fluid was successfully generated to allow breast cancer patients to be discriminated from healthy women. The study suggests that the proteomic pattern of tear fluid may be useful in the diagnosis of breast cancer and for high-throughput biomarker discovery.
RAPID FREE FLOW ISOELECTRIC FOCUSING VIA NOVEL ELECTRODE STRUCTURES (2005)

This work presents the first implementation o fn a noporous and hydrogel materials as an electrical interface for micro free flow electrophoresis devices. Packed polymer beads or agar were used to isolate the sample from the electrochemical reactions at the metal electrode surface. These materials allow for applied voltages two order so f magnitude larger than what is possible with patterned metal electrodes. This versatility in voltage allows a wide variety of samples to be rapidly focused.
[A case of inoperable scirrhous gastric cancer that responded remarkably to a combination of TS-1+paclitaxel and showed complete loss of ascites]. (2004)

Complete loss of malignant ascites by combination chemotherapy of TS-1+paclitaxel was experienced. The case was a 56-year-old woman who was diagnosed with inoperable scirrhous gastric cancer with malignant ascites. The administered regimen of chemotherapy was TS-1 100 mg/day (80 mg/m2) for 2 weeks. Paclitaxel 60 mg/day (50 mg/m2) on day 1 and 8 of TS-1 intake, followed by 2-weeks rest. Partial response was confirmed by gastrography and gastrofiberscope after 3 courses were performed. Furthermore, computed tomography (CT) showed complete loss of malignant ascites. Adverse reactions were grade 3 leukopenia and grade 2 nausea, vomiting and diarrhea. This result indicates the possibility of combination chemotherapy of TS-1+paclitaxel becoming an effective option in treating inoperable scirrhous gastric cancer.
Growth Inhibition of Human Colorectal Carcinoma Cell Lines by Tumor Necrosis Factor-Alpha Correlates with Reduced Activity of pp60c-src (1992)

One molecular alteration that has been observed in the majority of colorectal carcinomas is the activation of pp60c-src kinase. To address the role of pp60c-src in growth control of colon carcinoma cell lines, the effects of the biologic response modifier, tumor necrosis factor (TNF)-alpha were studied on the established HT29 colorectal carcinoma cell line and two clonal variants derived from the parental line. In one clone, HT29-A34, approximately 55% growth inhibition was observed following a 120-h incubation period with 10(3) U/ml TNF. In this TNF-sensitive cell line, pp60c-src immune complex kinase activity was reduced 3.9-fold accompanied by only a slight reduction in pp60c-src protein levels. Growth inhibition and decreased pp60c-src kinase activity correlated in a dose-dependent manner. The HT29-A14 TNF-resistant clone was not growth-inhibited by TNF, and no changes in pp60c-src were observed following treatment. Growth inhibition also correlated with reduced pp60c-src kinase specific activity in a number of other established colon carcinoma cell lines that were TNF-sensitive. In TNF-resistant colon carcinoma cell lines, pp60c-src kinase activity and levels remained unchanged. When changes in specific activity of pp60c-src were observed in sensitive cells, they occurred after decreased [3H]-thymidine uptake was observed. Therefore, these changes in pp60c-src activity are not the earliest event in TNF-induced growth inhibition. Nevertheless, our results suggest that modulation of pp60c-src kinase activity may be important in growth control of colorectal carcinoma cell lines.
Mitochondrial and extramitochondrial apoptotic signaling pathways in cerebrocortical neurons (2000)

In cultured cerebrocortical neurons, mild excitotoxic insults or staurosporine result in apoptosis. We show here that N-methyl-d-aspartate (NMDA) receptor-mediated, but not staurosporine-mediated, apoptosis is preceded by depolarization of the mitochondrial membrane potential (Deltapsi(m)) and ATP loss. Both insults, however, release cytochrome c (Cyt c) into the cytoplasm. What prompts mitochondria to release Cyt c and the mechanism of release are as yet unknown. We examined the effect of inhibition of the adenine nucleotide translocator (ANT), a putative component of the mitochondrial permeability transition pore. Inhibition of the mitochondrial ANT with bongkrekic acid (BA) prevented NMDA receptor-mediated apoptosis of cerebrocortical neurons. Concomitantly, BA prevented Deltapsi(m) depolarization, promoted recovery of cellular ATP content, and blocked caspase-3 activation. However, in the presence of BA, Cyt c was still released. Because BA prevented NMDA-induced caspase-3 activation and apoptosis, the presence of Cyt c in the neuronal cytoplasm is not sufficient for the induction of caspase activity or apoptosis. In contrast to these findings, BA was ineffective in preventing staurosporine-induced activation of caspases or apoptosis. Additionally, staurosporine-induced, but not NMDA-induced, apoptosis was associated with activation of caspase-8. These results indicate that, in cerebrocortical cultures, excessive NMDA receptor activation precipitates neuronal apoptosis by means of mitochondrial dysfunction, whereas staurosporine utilizes a distinct pathway.
Intrinsic bias and public rearrangements in the human immunoglobulin Vλ light chain repertoire (2013)

The immunoglobulin lambda (IGL) repertoires from two unrelated human blood samples, three NOD-scid-IL2Rγ(null) mice engrafted with human hematopoietic stem cells and two pairs of monozygotic twin blood samples were determined by Roche 454 sequencing to generate a total of about 700 000 IGL sequences. We applied bioinformatic analysis to examine IGL repertoires wherein, surprisingly, 20% of CDR-L3 peptide sequences were 'public' (shared across individuals); moreover, full-length IGL protein sequences (VJ recombinants) were also present in the public domain. Subtle yet significant differences in CDR-L3 nontemplated nucleotide addition, IGL V-gene family usage, and amino-acid composition distinguished the public CDR-L3 groups from the private groups. These data suggest that public CDR-L3 intervals can arise by intrinsic genetic mechanisms irrespective of different B-cell developmental milieu (human versus humanized mouse). Furthermore, the occurrence of identical public IGL protein sequences indirectly suggest the positive selection (evolutionary, somatic or both) of particular IGL chains independent of the immunoglobulin heavy chain.
Supplementation of Iron in Pulmonary Hypertension: Rationale and Design of a Phase II Clinical Trial in Idiopathic Pulmonary Arterial Hypertension (2013)

Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy.
Magnetically-inducible optical contrast agents for optical coherence tomography (2002)

We present the development and use of sonochemically-generated microsphere contrast agents containing a suspension of iron-oxide particles. These microspheres represent a new class of magnetically-inducible optical contrast agents for diagnostic imaging techniques such as optical coherence tomography.
Preparation and characteristics of magnetite‐labelled antibody with the use of poly(ethylene glycol) derivatives (1995)

With a view to the application of magnetic particles in cancer thermotherapy (hyperthermia), methods of preparing a bio-applicable magnetite with targeting activity towards cancer cells were investigated, and the properties of the material examined. Poly(ethylene glycol) (PEG)-magnetite consisting of magnetite (Fe3O4) and PEG with terminal carboxy or amino groups was prepared. Monoclonal antibody was then immobilized covalently on to the PEG-magnetite. Among three different immobilization methods employed, the highest immobilization density of 492 mg of protein/g of PEG-magnetite was achieved by using water-soluble carbodi-imide. However, with respect to residual antibody activity, only the method in which IgG sugar chains were oxidized to give aldehyde groups for coupling to N-terminal PEG-magnetite was satisfactory, with about 60% of the activity surviving. The immobilization density by this method (109 mg of protein/g of PEG-magnetite) was also sufficiently high. The product, termed magnetite-labelled antibody, was of sub-micrometre size and showed easy magnetophoresis. It was further elucidated that cancer-specific magnetite-labelled antibody bound to cancer cells at an amount of 50 mg of magnetite/cm3 of cells. The PEG-magnetite generates heat at an evolution rate of 31.5 W/g, and the amount adsorbed to the cells was calculated to be high enough to heat a tumour 1 cm in diameter to more than 42 degrees C in 30 s under an alternating magnetic field [at an intensity of 572 Oe (approx. 45.5 kA/m) and a frequency of 240 kHz]. This magnetite-labelled antibody is expected to be applicable clinically as a therapeutic agent for the induction of hyperthermia.
Effect of Long-Term Administration of Prostaglandin I<sub>2</sub> in Incipient Diabetic Nephropathy (2002)

In this study, we found that the long-term 24-month administration of PGI(2) preparation, beraprost sodium, decreased albuminuria in patients of incipient diabetic nephropathy. The possible mechanisms are that the PGI(2) may have alleviated constriction effect of angiotensin II on efferent glomerular arteriole and attenuated glomerular hyperfiltration, and inhibited growth of mesangial cells by platelet-derived growth factor as well.
Hematopoietic Stem Cell Transplant into Non-Myeloablated W/W v Mice to Detect Steady-State Engraftment Defects (2008)

Hematopoietic stem cells (HSC) are capable of self-renewal and reconstitution of the lymphoid and myeloid lineages of transplant recipients. Classical assays for HSC function rely on lethal irradiation to prepare the host for donor engraftment. This assay destroys most of the hematopoietic tissue and the vasculature of the bone marrow space, leading to regeneration of the niche in which HSC are intimately dependent for their survival, self-renewal, and lineage differentiation. The non-ablated transplant setting provides a more physiological background for measuring HSC function during steady-state hematopoiesis. In this chapter, we describe methods for assaying HSC function during the steady-state using W/W ( v ) c-Kit mutant mice as recipients. Our previous studies have found that the competition from W/W ( v )allows an additional level of stringency that is not observed in limiting dilution assays of HSC number based on fully ablated recipient competition. The ease of this approach is an advantage, and this method may be particularly useful for teasing apart HSC engraftment phenotypes that are especially dependent on functions related to homing, adhesion, or migration into the niche.