gebhart/patrepeval huggingface dataset:
Transplanted cord blood–derived endothelial precursor cells augment postnatal neovascularization (2000)

Endothelial precursor cells (EPCs) have been identified in adult peripheral blood. We examined whether EPCs could be isolated from umbilical cord blood, a rich source for hematopoietic progenitors, and whether in vivo transplantation of EPCs could modulate postnatal neovascularization. Numerous cell clusters, spindle-shaped and attaching (AT) cells, and cord-like structures developed from culture of cord blood mononuclear cells (MNCs). Fluorescence-trace experiments revealed that cell clusters, AT cells, and cord-like structures predominantly were derived from CD34-positive MNCs (MNC(CD34+)). AT cells and cell clusters could be generated more efficiently from cord blood MNCs than from adult peripheral blood MNCs. AT cells incorporated acetylated-LDL, released nitric oxide, and expressed KDR, VE-cadherin, CD31, and von Willebrand factor but not CD45. Locally transplanted AT cells survived and participated in capillary networks in the ischemic tissues of immunodeficient nude rats in vivo. AT cells thus had multiple endothelial phenotypes and were defined as a major population of EPCs. Furthermore, laser Doppler and immunohistochemical analyses revealed that EPC transplantation quantitatively augmented neovascularization and blood flow in the ischemic hindlimb. In conclusion, umbilical cord blood is a valuable source of EPCs, and transplantation of cord blood-derived EPCs represents a promising strategy for modulating postnatal neovascularization.
DFT study of the mechanism for methane hydroxylation by soluble methane monooxygenase (sMMO): effects of oxidation state, spin state, and coordination number (2012)

The exact structure of the active site of intermediate Q, the methane-oxidizing species of soluble methane monooxygenase (sMMO), and the reaction mechanism of Q with methane molecule are still not fully clear. To gain further insights into the structure and reaction mechanism, five diiron models of Q that differ in shape, oxidation state, spin state, and coordination number of the two iron centers are studied. Different mechanisms in different spin states were explored. Density functional theory (DFT) calculations show that Fe(III)Fe(IV)(μ-O)(μ-OH) is more reactive than Fe(IV)(2)(μ-O)(2) in the oxygen-rich environment and that the reactivity of the active core of sMMO-Q is not enhanced by converting its oxo bridge into a terminal ligand. A four-coordinated diiron model is the most effective for methane hydroxylation. Both radical and non-radical intermediates are involved in the reactions for the four-coordinated diiron model.
Flow velocity in the superficial lymphatic network of the mouse tail (1994)

The present study had two goals: 1) to establish an animal model in which a large network of the initial lymphatics of the skin can be investigated in vivo and 2) to measure effective flow velocity (defined as axial component of the flow velocity) in the lymph capillary network of the skin for the first time. A fluorescence microlymphography technique was used to stain the lymph capillaries in the superficial layer of the skin of the nude mouse tail in 10 female animals (mean age 45.8 +/- 2.4 days; mean wt 21.2 +/- 0.8 g). With the use of densitometric image analysis, effective flow velocity along the tail was measured. The network consisted of a honeycomb-like layer of hexagonally shaped meshes that could be stained in all animals. Effective lymph flow velocities were in the range of 1.4-20.4 microns/s with a mean value of 7.7 +/- 5.9 microns/s; median value was 6.2 microns/s (4.5-10.5; 25 and 75% percentiles). This new animal model allows studies of a large network of lymph capillaries in the skin and should provide new insight into the physiology and pathophysiology of the initial lymphatics.
Analysis and enhancement of videos of electronic slide presentations (2003)

This paper presents a new approach to indexing videos of presentations which use electronic slides. By determining the images of slides in the video frames, and then matching the video sequences to the original electronic slides, the video can be indexed and searched, and the visual appearance of the segments can be improved. We first detect the "content area" in video frames using a color similarity weighted least square method. By monitoring the frame-to-frame "content difference", we then temporally segment the video into sequences which display the same slide. Since this differencing removes low-level imaging effects, we can then relate the video segments to slides by matching the content differences of adjacent video segments to the content differences of all possible slide pairs. By defining the transition probabilities of video segments, we are able to solve this matching efficiently in two steps, first by finding high likelihood matches, and then by using dynamic programming for the unmatched remainder. Once matched, the correspondence to the original slides can be used to enhance the presentation video quality in the content area, and can also be used for indexing and summarization. Experiments show high performance of segmentation and matching on several presentation videos which vary considerably in color and background style.
Botulinum toxin type A: fine-tuning treatment of facial nerve injury. (2004)

Treatment of patients following facial nerve injury can be daunting. A multitude of procedures have been developed to treat the paralyzed face. As patients recover from facial nerve injuries, a variety of asymmetries from nerve hypofunction (paresis or paralysis) or hyperfunction (synkinesis or spasm) often persist. Careful use of botulinum toxin type A can be very useful in improving symmetry in acute or chronic facial nerve abnormality by treating the relatively hyperfunctional side.
The effect of cigarette smoke on adherence of respiratory pathogens to buccal epithelial cells (1999)

Smoking is associated with an increased risk of respiratory tract infection in adults. In children, exposure to cigarette smoke is a risk factor for respiratory tract infection and bacterial meningitis: Active smoking and passive exposure to cigarette smoke is also associated with carriage of some potentially pathogenic species of bacteria in both adults and children. The aims of the study were to determine the effect of active smoking on: (1) bacterial binding to epithelial cells; (2) expression of host cell antigens that act as receptors for some species; and (3) the effects of passive exposure to water-soluble components of cigarette smoke on bacterial binding. Flow cytometry was used to assess binding to buccal epithelial cells of the following species labelled with fluorescein isothiocyanate: Neisseria meningitidis, Neisseria lactamica, Streptococcus pneumoniae, Bordetella pertussis, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus. Flow cytometry was also used to assess expression of host cell antigens which have been identified as bacterial receptors. For each species, binding to cells of smokers was significantly higher than to cells of non-smokers; however, expression of host cell antigens was similar on epithelial cells of both groups. Non-dilute cigarette smoke extract reduced binding of bacteria to epithelial cells, but dilutions between 1 in 10 and 1 in 320 enhanced binding. We conclude that smokers might be more densely colonised by a variety of potentially pathogenic bacteria. The enhanced bacterial binding to epithelial cells of smokers is not related to enhanced expression of host cell antigens that can act as receptors for some species, but possibly to components in the smoke that alter charge or other properties of the epithelial cell surface. Passive coating of mucosal surfaces with components of cigarette smoke might enhance binding of potentially pathogenic bacteria.
A Direct Method for the Fabrication of Macro‐Porous SiOC Ceramics from Preceramic Polymers (2008)

Cellular SiOC ceramics having a complex morphology were produced using two silicone precursors. Linear PDMS and two different silsesquioxanes (containing either methyl or methyl-phenyl side groups) were mixed, crosslinked and pyrolyzed at 1200 °C, resulting in the formation of macroporous ceramic components. Pore formation was attributed to the different behavior of the precursors upon pyrolysis. The amount of porosity depended on the amount of PDMS, which acted as a “sacrificial filler”, leading to the formation of pores ranging from a few microns to a few hundred microns.
Nitric oxide-induced cellular stress and p53 activation in chronic inflammation (2002)

Free radical-induced cellular stress contributes to cancer during chronic inflammation. Here, we investigated mechanisms of p53 activation by the free radical, NO. NO from donor drugs induced both ataxia-telangiectasia mutated (ATM)- and ataxia-telangiectasia mutated and Rad3-related-dependent p53 posttranslational modifications, leading to an increase in p53 transcriptional targets and a G(2)M cell cycle checkpoint. Such modifications were also identified in cells cocultured with NO-releasing macrophages. In noncancerous colon tissues from patients with ulcerative colitis (a cancer-prone chronic inflammatory disease), inducible NO synthase protein levels were positively correlated with p53 serine 15 phosphorylation levels. Immunostaining of HDM-2 and p21(WAF1) was consistent with transcriptionally active p53. Our study highlights a pivotal role of NO in the induction of cellular stress and the activation of a p53 response pathway during chronic inflammation.
Mono- and bispecific single-chain antibody fragments for cancer therapy. (1996)

Especially when dealing with solid cancers, single-chain antibody fragments (scFvs) have a lot of advantages. Due to their small size (27 kDa), these proteins clear more rapidly from the blood, and penetrate faster and deeper into tissues, than whole antibodies. Furthermore, the lack of constant regions ensures that they are not retained in tissues such as the liver and kidney. This reduces possible toxic side-effects. Single-chain construction is normally done by polymerase chain reaction (PCR). To decrease the overall cost of oligonucleotide primer synthesis, time-consuming primer design, multiple PCR reactions and individual PCR optimization, we designed a universal single-step overlap extension PCR protocol using hybridoma cDNA as a template. To overcome the lack of effector function, bispecific scFvs, consisting of an scFv produced against a tumour-associated antigen fused to a T cell marker-specific scFv, are being created, starting from already assembled scFv, by means of two additional PCR reactions. In this paper we describe both PCR methods that were successfully used to create scFvs against the human transferrin receptor, the human interleukin-2 receptor, the human CD3 molecule, a breast tumour-associated antigen and an anti-transferrin-anti-CD3 bispecific scFv.
A prototype bioreductive DNA groove binding ligand. (1991)

Molecular mechanics calculations have been used to evaluate the potential bioreductive behaviour of several DNA minor groove binding ligands containing quinone/hydroquinone redox systems. The proposed structures are analogues of the Hoechst 33258 molecule with modifications of the benzimidazole rings. Binding energies of simple analogues indicate the reduced forms bind more strongly to the DNA minor groove. N-methylation of the imidazole ring(s) produces structures which can form extended quinone methides. These also show stronger binding in the reduced form and it is speculated that such structures might provide a basis for the design of groove binding ligands which will act as bioreductive alkylating agents.
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism, present strategies and future perspectives of therapies (2006)

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which manifests as non-cardiogenic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.
The effect of dietary α‐tocopherol supplementation and antioxidant spraying on colour stability and lipid oxidation of turkey meat (1994)

Abstract Vitamin E was supplemented in the diet (250 mg kg −1 ) of turkeys or sprayed directly on turkey meat. Turkey breast muscles were cut into 1.5 cm slices, wrapped with oxygen‐permeable film and stored at 2–4°C for 1 week. Colour coordinates ( L *, a *, b *), pH and reflectance values between 630 and 580 nm were determined at various times post mortem , TBARS (thiobarbituric acid‐reactive substances) values and vitamin E content were assessed immediately after slaughter and at 7 days post mortem for vitamin E‐supplemented, sprayed and control groups. Vitamin E supplementation or antioxidant spraying resulted in a lower myoglobin oxidation ( P &lt; 0.05) and a higher a * value at day 2, but not thereafter. No differences in TBARS values and ultimate pH were detected. When peroxidation was induced experimentally by addition of an activated mixture, vitamin E supplemented or antioxidant‐sprayed samples exhibited lower TBARS values than the controls. Vitamin E supplementation in the diet or antioxidant spraying of meat produced a temporary delay in the rate of discoloration of turkey meat.
Human Apolipoprotein A-IV (1980)

The role of the human intestine has been explored as a site of synthesis of apoA-IV, a major apoprotein of human intestinal triglyceride-rich lipoproteins. Intestinal biopsies were performed on normal volunteers while fasting and after lipid ingestion. Indirect immunofluorescence demonstrated a marked increase in immunofluorescence for apoA-IV during lipid absorption consistent with an increased intracellular content. ApoA-IV comprised 10-13% of chylomicron apoprotein and 24-30% of intestinal very low density lipoprotein (VLDL) as assessed by densitometry of sodium dodecyl sulfate gels of lipoproteins from chylous urine (mesenteric lymphatic-urinary fistula) and thoracic duct lymph (postoperative fistula). After one subject with chyluria ingested 40 g of corn oil, triglyceride excretion in urine was accompanied by an increased excretion of apoA-IV. 11.5 g of triglyceride and 81 mg of apoA-IV were recovered in the urine. In chylous urine 56% of apoA-IV was in the triglyceride-rich lipoproteins (chylomicrons and intestinal VLDL) and 44% in the d > 1.006-g/ml fraction. Normal plasma apoA-IV was 15.7+/-0.9 mg/dl (n = 14) whereas four subjects with abetalipoproteinemia had reduced levels 1.2, 7.6, 9.6, and 8.3 mg/dl, respectively. Lipid feeding in normal volunteers resulted in a rise in plasma apoA-IV (16.1+/-0.7 mg/dl to 18.5+/-0.7 mg/dl, n = 5, P < 0.01). In fasting plasma, 98% of apoA-IV was in the d > 1.21-g/ml fraction. In lipemic plasma, 10% of apoA-IV was associated with triglyceride-rich lipoproteins and 90% with the d > 1.21-g/ml fraction. Agarose column chromatography of fasting plasma confirmed that the bulk of plasma apoA-IV is free, unassociated with lipoproteins. These results demonstrate that apoA-IV is present in human intestinal epithelial cells and is secreted as a chylomicron and VLDL apoprotein. Within fasting plasma most of the apoA-IV is found free, unassociated with lipoproteins. After lipid ingestion apoA-IV is also found in plasma chylomicrons indicating that some apoA-IV remains associated with chylomicrons in plasma during chylomicron metabolism, although some may be transferred from the chylomicron surface.
Oral Delivery of Glutamic Acid Decarboxylase (GAD)-65 and IL10 byLactococcus lactisReverses Diabetes in Recent-Onset NOD Mice (2014)

Growing insight into the pathogenesis of type 1 diabetes (T1D) and numerous studies in preclinical models highlight the potential of antigen-specific approaches to restore tolerance efficiently and safely. Oral administration of protein antigens is a preferred method for tolerance induction, but degradation during gastrointestinal passage can impede such protein-based therapies, reducing their efficacy and making them cost-ineffective. To overcome these limitations, we generated a tolerogenic bacterial delivery technology based on live Lactococcus lactis (LL) bacteria for controlled secretion of the T1D autoantigen GAD65370-575 and the anti-inflammatory cytokine interleukin-10 in the gut. In combination with short-course low-dose anti-CD3, this treatment stabilized insulitis, preserved functional β-cell mass, and restored normoglycemia in recent-onset NOD mice, even when hyperglycemia was severe at diagnosis. Combination therapy did not eliminate pathogenic effector T cells, but increased the presence of functional CD4(+)Foxp3(+)CD25(+) regulatory T cells. These preclinical data indicate a great therapeutic potential of orally administered autoantigen-secreting LL for tolerance induction in T1D.
The Flavoring Agent Dihydrocoumarin Reverses Epigenetic Silencing and Inhibits Sirtuin Deacetylases (2005)

Sirtuins are a family of phylogenetically conserved nicotinamide adenine dinucleotide-dependent deacetylases that have a firmly established role in aging. Using a simple Saccharomyces cerevisiae yeast heterochromatic derepression assay, we tested a number of environmental chemicals to address the possibility that humans are exposed to sirtuin inhibitors. Here we show that dihydrocoumarin (DHC), a compound found in Melilotus officinalis (sweet clover) that is commonly added to food and cosmetics, disrupted heterochromatic silencing and inhibited yeast Sir2p as well as human SIRT1 deacetylase activity. DHC exposure in the human TK6 lymphoblastoid cell line also caused concentration-dependent increases in p53 acetylation and cytotoxicity. Flow cytometric analysis to detect annexin V binding to phosphatidylserine demonstrated that DHC increased apoptosis more than 3-fold over controls. Thus, DHC inhibits both yeast Sir2p and human SIRT1 deacetylases and increases p53 acetylation and apoptosis, a phenotype associated with senescence and aging. These findings demonstrate that humans are potentially exposed to epigenetic toxicants that inhibit sirtuin deacetylases.
Shaped, Stratified, Scaffold-free Grafts for Articular Cartilage Defects (2008)

One goal of treatment for large articular cartilage defects is to restore the anatomic contour of the joint with tissue having a structure similar to native cartilage. Shaped and stratified cartilaginous tissue may be fabricated into a suitable graft to achieve such restoration. We asked if scaffold-free cartilaginous constructs, anatomically shaped and targeting spherically-shaped hips, can be created using a molding technique and if biomimetic stratification of the shaped constructs can be achieved with appropriate superficial and middle/deep zone chondrocyte subpopulations. The shaped, scaffold-free constructs were formed from the alginate-released bovine calf chondrocytes with shaping on one (saucer), two (cup), or neither (disk) surfaces. The saucer and cup constructs had shapes distinguishable quantitatively (radius of curvature of 5.5 +/- 0.1 mm for saucer and 2.8 +/- 0.1 mm for cup) and had no adverse effects on the glycosaminoglycan and collagen contents and their distribution in the constructs as assessed by biochemical assays and histology, respectively. Biomimetic stratification of chondrocyte subpopulations in saucer- and cup-shaped constructs was confirmed and quantified using fluorescence microscopy and image analysis. This shaping method, combined with biomimetic stratification, has the potential to create anatomically contoured large cartilaginous constructs.
Cleavage of single-stranded DNA by plasmid pT 181-encoded RepC protein (1987)

RepC protein encoded by plasmid pT181 has single-stranded endonuclease and topoisomerase-like activities. These activities may be involved in the initiation (and termination) of pT181 replication by a rolling circle mechanism. RepC protein cleaves the bottom strand of DNA within the origin of replication at a single, specific site when the DNA is in the supercoiled or linear (double or single-stranded) form. We have found that RepC protein will also cleave single-stranded DNA at sites other than the origin of replication. We have mapped the secondary cleavage sites on pT181 DNA. When the DNA is in the supercoiled, or linear, double-stranded form, only the primary site within the origin is cleaved. However, when the DNA is present in the single-stranded form, several strong and weak cleavage sites are observed. The DNA sequence at these cleavage sites shows a strong similarity with the primary cleavage site. The presence of Escherichia coli SSB protein inhibited cleavage at all of the secondary nick sites while the primary nick site remained susceptible to cleavage.
Converting an AEG Cyclotron to H[sup −] Acceleration and Extraction (2009)

Clinical Trials are under way to evaluate agents labeled with the nuclide 225Ac and its decay product 213Bi, in targeted alpha‐immuno‐therapy [1]. 225Ac can be produced on a medium‐energy cyclotron via the nuclear reaction 226Ra(p,n)225Ac. To demonstrate proof‐of‐principle, a vintage AEG cyclotron, Model E33 [2], with an internal target, had been employed in a pilot production program at the Technical University of Munich (TUM). To enhance production capability and further support the clinical studies, the TUM facility has recently been refurbished and upgraded, adding a new external beam‐line, automated target irradiation and transport systems, new laboratories, hot cells, etc. [3]. An improved high‐power rotating target has been built and installed [4]. The AEG cyclotron itself has also been modified and upgraded to accelerate and extract H− ions. We have designed, built, and tested a new axial Penning‐type ion source which is optimized for the production of H− ions. The ion source has continued to evolve through experiment and experience. Steady improvements in materials and mechanics have led to enhanced source stability, life‐time, and H− production. We have also designed and built a precision H− charge‐exchange beam‐extraction system which is equipped with a vacuum lock. To fit within the tight mechanical constraint imposed by the narrow magnet gap, the system incorporates a novel chain‐drive foil holder and foil‐changer mechanism. The reconfigured cyclotron system has now been in operation for more than 1 year. Three long‐duration target irradiations have been conducted. The most recent bombardment ran 160 continuous hours at a beam on target of ∼80 microamperes for a total yield of ∼70 milli‐curies of 225Ac.