gebhart/patrepeval huggingface dataset:
Antibodies to IFN-gamma prevent immunologically mediated intestinal damage in murine graft-versus-host reaction. (1989)

We have tested the hypothesis that interferon-gamma (IFN-gamma) plays a role in the enteropathy of graft-versus-host reaction (GVHR) by treating host mice with a monoclonal antibody directed at this mediator. Two models of GVHR were examined. In the mild proliferative GVHR, which occurs in adult unirradiated (CBA x BALB/c)F1 mice given parental spleen cells, anti-IFN-gamma slightly inhibited the development of splenomegaly and the activation of natural killer (NK) cells in GVHR. Anti-IFN-gamma had no effect on splenomegaly or generation of anti-host cytotoxic T lymphocytes (CTL) during the more severe GVHR in adult BDF hosts, but inhibited the weight loss and mortality normally found in this GVHR. Despite these variable effects on systemic GVHR, anti-IFN-gamma treatment abolished the crypt hyperplasia and increased counts of intraepithelial lymphocytes (IEL) normally found in the jejunum of (CBA X BALB/c)F1 mice with GVHR. In parallel, anti-IFN-gamma-treated BDF1 mice with GVHR did not develop the villus atrophy and intense crypt hyperplasia found in untreated GVHR hosts. These results support the view that IFN-gamma is essential for the development of enteropathy in GVHR and we propose that this mediator may also be involved in the pathogenesis of clinical enteropathies in man.
K-RasG12D expression induces hyperproliferation and aberrant signaling in primary hematopoietic stem/progenitor cells (2006)

Defining how cancer-associated mutations perturb signaling networks in stem/progenitor populations that are integral to tumor formation and maintenance is a fundamental problem with biologic and clinical implications. Point mutations in RAS genes contribute to many cancers, including myeloid malignancies. We investigated the effects of an oncogenic Kras(G12D) allele on phosphorylated signaling molecules in primary c-kit(+) lin(-/low) hematopoietic stem/progenitor cells. Comparison of wild-type and Kras(G12D) c-kit(+) lin(-/low) cells shows that K-Ras(G12D) expression causes hyperproliferation in vivo and results in abnormal levels of phosphorylated STAT5, ERK, and S6 under basal and stimulated conditions. Whereas Kras(G12D) cells demonstrate hyperactive signaling after exposure to granulocyte-macrophage colony-stimulating factor, we unexpectedly observe a paradoxical attenuation of ERK and S6 phosphorylation in response to stem cell factor. These studies provide direct biochemical evidence that cancer stem/progenitor cells remodel signaling networks in response to oncogenic stress and demonstrate that multi-parameter flow cytometry can be used to monitor the effects of targeted therapeutics in vivo. This strategy has broad implications for defining the architecture of signaling networks in primary cancer cells and for implementing stem cell-targeted interventions.
Regional Accelerated Phenomenon in the Mandible Following Mucoperiosteal Flap Surgery (1994)

Striking remodeling activity occurs adjacent to the site of injury in orthopedic surgery. This reaction has been described as regional accelerated phenomenon (RAP), as it speeds up the healing stage. The phenomenon is a transient burst of localized remodeling process following surgical wounding of cortical bone. We explored whether RAP occurs following mucoperiosteal flap surgery in the jaw bone. Mucoperiosteal flaps were performed on 60 Wistar rats, either only on the buccal aspect or both on buccal and lingual aspects of the mandible. The surgical procedure lasted an average of 30 seconds and the flap was readapted without sutures. The rats were sacrificed at 3, 7, 10, 14, 21, and 120 days. High resolution x-ray microradiography of 1 to 1.5 mm thick ground sections between premolar and molar regions of the mandible were analyzed and revealed large areas of radiolucency which correlated to massive resorption of the alveolar bone, as well as areas in the bone proper. The RAP was observed as early as 10 days in the treated side group. Striking resorption of the cortical bone, both on the surface and the bone proper, occurred on the periodontal aspect of the crestal bone leading to widening of the periodontal ligament space, where a mucoperiosteal flap was performed on the buccal aspect. The resorption was more prominent when a mucoperiosteal flap was performed both on the lingual and buccal aspect. The alveolar bone recovered almost to control levels 120 days after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Introduction of the QF‐PCR analysis for the purposes of prenatal diagnosis in Bulgaria—estimation of applicability of 6 STR markers on chromosomes 21 and 18 (2004)

QF-PCR analysis could be an applicable alternative in prenatal and postnatal diagnosis in cases with a strong suspicion for particular autosomal aneuploidies (including chromosomes 21, 18, and 13) in small countries with limited resources like Bulgaria.
Is it still possible to extend TCP? (2011)

We've known for a while that the Internet has ossified as a result of the race to optimize existing applications or enhance security. NATs, performance-enhancing-proxies,firewalls and traffic normalizers are only a few of the middleboxes that are deployed in the network and look beyond the IP header to do their job. IP itself can't be extended because "IP options are not an option". Is the same true for TCP?
Nonsteroidal Antiinflammatory Agents, XVIII: C‐5 Functionalized 6,7‐Diphenyl‐2,3‐dihydro‐1<i>H</i>‐pyrrolizines as Inhibitors of Bovine Cyclooxygenase and 5‐Lipoxygenase (1994)

6-(4-Chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizines with functional groups at position 5 of the heterocyclic moiety were synthesized and tested. To determine their antiinflammatory activity bovine blood was used as enzyme source for the cyclooxygenase and 5-lipoxygenase, respectively. The iminoxy acetic acid derivative and the iminotetrazole selectively inhibit the 5-lipoxygenase, all the other compounds show medium or low affinity to the active sites of cyclooxygenase and 5-lipoxygenase. In general all compounds inhibit 5-lipoxygenase more effectively than cyclooxygenase. Concerning the inhibition of 5-lipoxygenase the most active compounds found are equipotent to the corresponding propionic acid compounds, but they aren't well balanced dual inhibitors as shown for the carboxylic derivatives. A structure activity relationship and the enzyme selectivity are discussed.
In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury (2015)

The pathophysiological mechanism involved in side effects of radiation therapy, and especially the role of the endothelium remains unclear. Previous results showed that plasminogen activator inhibitor-type 1 (PAI-1) contributes to radiation-induced intestinal injury and suggested that this role could be driven by an endothelium-dependent mechanism. We investigated whether endothelial-specific PAI-1 deletion could affect radiation-induced intestinal injury. We created a mouse model with a specific deletion of PAI-1 in the endothelium (PAI-1KO(endo)) by a Cre-LoxP system. In a model of radiation enteropathy, survival and intestinal radiation injury were followed as well as intestinal gene transcriptional profile and inflammatory cells intestinal infiltration. Irradiated PAI-1KO(endo) mice exhibited increased survival, reduced acute enteritis severity and attenuated late fibrosis compared with irradiated PAI-1(flx/flx) mice. Double E-cadherin/TUNEL labeling confirmed a reduced epithelial cell apoptosis in irradiated PAI-1KO(endo). High-throughput gene expression combined with bioinformatic analyses revealed a putative involvement of macrophages. We observed a decrease in CD68(+)cells in irradiated intestinal tissues from PAI-1KO(endo) mice as well as modifications associated with M1/M2 polarization. This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis.
Tracking tumor growth rates in patients with malignant gliomas: a test of two algorithms. (2001)

The nearest-neighbor tissue segmentation algorithm provides significant power in quantifying tumor volume and in tracking growth rates of contrast-enhancing tissue in patients with GBM. The surface modeling algorithm is able to quantify tumor volume reliably as well.
Macrophages from motheaten and viable motheaten mutant mice show increased proliferative responses to GM-CSF: detection of potential HCP substrates in GM-CSF signal transduction. (1997)

Loss of functional hematopoietic cell phosphatase (HCP) underlies severe hematopoietic and immunologic abnormalities in mice homozygous for the motheaten and viable motheaten mutations. These mice die from pulmonary accumulation of macrophages that are regulated by macrophage colony-stimulating factor (M-CSF) and granulocyte (G)-M-CSF. We determined the growth response of motheaten macrophages to the two growth factors and looked for potential HCP substrates in these cells. Motheaten macrophages showed increased proliferative responses to GM-CSF but not to M-CSF, demonstrating that HCP plays a critical role in downregulating GM-CSF mitogenic signaling. Despite the heightened growth responses of the motheaten macrophages to GM-CSF, there were no marked differences between motheaten macrophages and normal controls in GM-CSF-induced phosphorylation of GM-CSFR beta, Jak2, STAT5 and MAPK, indicating that these molecules are not major HCP substrates in GM-CSF signaling. Interestingly, several markedly hyperphosphorylated proteins were detected in the motheaten macrophages, including a novel 126-kDa phosphotyrosine protein that associated with the phosphatase via its SH2 domains, suggesting that these proteins depend on HCP for dephosphorylation and may mediate the heightened growth responses to GM-CSF. Our data indicate that macrophage hypersensitivity to GM-CSF may be a major factor in motheaten pathogenesis and that HCP may dephosphorylate novel substrates critical in GM-CSF mitogenic signaling.
Optical fiber long-period grating sensors (1996)

We present a novel class of highly sensitive sensors based on long-period fiber gratings that can be implemented with simple and inexpensive demodulation schemes. Temperature, strain, and refractive-index resolutions of 0.65 °C, 65.75 μ∈, and 7.69 × 10−5, respectively, are demonstrated for gratings fabricated in standard telecommunication fibers.
Cathepsins Are Upregulated by IFN-γ/STAT1 in Human Muscle Culture: A Possible Active Factor in Dermatomyositis (2001)

The aim of this work was to study which genes upregulated by the IFN-gamma/STAT1 system in human muscle might be involved in the process of muscle fiber atrophy in dermatomyositis (DM). These proteins included proteases (cathepsins B and L, calpain), proteins implicated in apoptosis and cell cycle (Bcl-x(l), Fas, p21), structural proteins (beta-actin, utrophin, desmin), and other proteins whose expression is known to be modified by IFN-gamma (neural cell adhesion molecule (N-CAM), major histocompatibility complex-I (MHC-I)). We performed immunocytochemistry, Western blot, and semiquantitative reverse transcriptase-polymerase chain reaction using human muscle cultures. We found upregulation of cathepsins B and L, bcl-x(l) and p21 while N-CAM, calpain, utrophin, desmin, beta-actin and Fas remained at basal levels. Immunohistochemistry on frozen sections from biopsies of patients with different muscle diseases showed upregulation of cathepsin L and calpain in perifascicular muscle fibers in DM. In view of these results, the increased expression of cathepsins L and B after IFN-gamma stimulation in muscle cultures and its inhibition using fludarabine, a STAT1 blocker, further support our previous studies and suggest that the increased expression of cathepsins detected in perifascicular muscle fibers in DM is mediated by IFN-gamma/STAT1 and contributes to their atrophy.
Conversion of Spinosyn A and Spinosyn D to Their Respective 9- and 17-Pseudoaglycones and Their Aglycones. (1998)

Forosamine at the 17-position of spinosyns A and D was hydrolyzed under mild acidic conditions to give the corresponding 17-pseudoaglycones. The tri-O-methylrhamnose at the 9-position of the 17-pseudoaglycone of spinosyn A was hydrolyzed under more vigorous acidic conditions to give the aglycone of spinosyn A. However, these conditions led to decomposition of the 17-pseudoaglycone of spinosyn D, presumably due to more facile protonation of the 5,6-double bond to produce a tertiary carbonium ion which undergoes further rearrangements. Spinosyns J and L (3'-O-demethyl spinosyn A and D, respectively) obtained from fermentation of biosynthetically-blocked mutant strains of Saccharopolyspora spinosa, were oxidized to give the corresponding 3'-keto-derivatives and the resultant keto-sugars were then beta-eliminated under basic conditions to give the 9-pseudoaglycones of spinosyns A and D respectively. Forosamine at the 17-position of the 9-pseudoaglycone of spinosyn D was then readily hydrolyzed to yield the aglycone of spinosyn D.
Overcoming the restriction barrier to plasmid transformation and targeted mutagenesis in <i>Bifidobacterium breve</i> UCC2003 (2008)

In silico analysis of the Bifidobacterium breve UCC2003 genome predicted two distinct loci, which encode three different restriction/modification systems, each comprising a modification methylase and a restriction endonuclease. Based on sequence homology and observed protection against restriction we conclude that the first restriction endonuclease, designated BbrI, is an isoschizomer of BbeI, the second, BbrII, is a neoschizomer of SalI, while the third, BbrIII, is an isoschizomer of PstI. Expression of each of the B. breve UCC2003 methylase-encoding genes in B. breve JCM 7017 established that BbrII and BbrIII are active and restrict incoming DNA. By exploiting knowledge on restriction/modification in B. breve UCC2003 we successfully increased the transformation efficiency to a level that allows the reliable generation of mutants by homologous recombination using a non-replicative plasmid.
Reperfusion injury to endothelial cells after cold storage of rat livers: protection by mildly acidic pH and lack of protection by antioxidants (1995)

Lethal reperfusion injury to sinusoidal endothelial cells occurs after cold ischemic storage of livers and may be responsible for liver graft failure from storage injury. Here, we evaluated potential mechanisms underlying this reperfusion injury. In rat livers stored in Euro-Collins solution for 24 h and reperfused with Krebs-Henseleit bicarbonate buffer, nonparenchymal cell killing showed periportal predominance as assessed by nuclear staining with trypan blue. In livers reperfused in the retrograde direction, the lobular distribution of cell killing was reversed, indicating that cell killing was more rapid in oxygen-rich upstream regions. However, antioxidants, including allopurinol, desferrioxamine, catalase, superoxide dismutase, superoxide dismutase plus catalase, and U74006F, did not reduce cell killing. Similarly, reperfusion with anoxic buffer did not prevent lethal injury. Antioxidants and anoxic reperfusion also did not improve cell viability in livers stored in UW solution. Nevertheless, superoxide generation, as identified by formazan formation from nitroblue tetrazolium, was increased in Kupffer cells after lives storage and reperfusion as compared to unstored livers. Acidification of the reperfusion buffer from pH 7.4 to pH 7.15 reduced overall nonparenchymal cell killing from about 40% to 10%. Moreover, a pH gradient developed across the liver lobule during reperfusion with the effluent 0.2-0.4 pH units more acidic than the influent. This intralobular pH gradient appears to account for the relative sparing of cells in more acidic downstream regions of the lobule. Lower temperatures of reperfusion also reduced lethal injury. In conclusion, Kupffer cells generated superoxide after perfusion of stored rat livers, but formation of oxygen free radicals did not appear to contribute to lethal reperfusion injury to endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Structural Health Monitoring Using Frequency Response Functions and Sparse Measurements (1998)

The accuracy of damage detection techniques that are based on using vibration response measurements depends on the number of measurements that are taken over the surface of the structure. This paper examines the accuracy of locating structural damage using the damage vector method and a sparse distribution of sensors over the structure. An analytical beam model is used to compare the accuracy of locating damage using partial and full measurements. It is shown that damage can be located with a spatial resolution equal to the distance between the sensors on the structure. The technique requires measurement of rotational and translation frequency response functions, and that the excitation force be applied at a point on the structure where the response is measured. Experimentation is underway to determine the feasibility of the technique.
Potential of integrated field spectroscopy and spatial analysis for enhanced assessment of soil contamination: A prospective review (2014)

There are tens of millions of contaminated soil sites in the world, and with an increasing population and associated risk there is a growing pressure to remediate them. A barrier to remediation is the lack of cost-effective approaches to assessment. Soil contaminants include a wide range of natural and synthetic metallic and organic compounds and minerals thus making analytical costs potentially very large. Further, soil contaminants show a large degree of spatial variation which increases the burden on sampling costs. This paper reviews potentially cost-effective methods for measurement, sampling design, and assessment. Current tiered investigation approaches and sampling strategies can be improved by using new technologies such as proximal sensing. Design of sampling can be aided by on-the-go proximal soil sensing; and expedited by subsequent adaptive spatially optimal sampling and prediction procedures enabled by field spectroscopic methods and advanced geostatistics. Field deployment of portable Visible & Near Infrared [wavelength 400–2500 nm] (Vis-NIR) and X-ray fluorescence (PXRF) spectroscopies will require special calibration approaches but show huge potential for synergistic use. The use of mid-infrared spectroscopy [wavelength 2500–25,000 nm, wavenumber 4000–400 cm− 1] (MIR) for field implementation requires further adaptive research. We propose an integrated field-deployable methodology as a basis for further developments.
Temperature Dependence of Order, Disorder, and Defects in Laterally Confined Diblock Copolymer Cylinder Monolayers (2005)

Monolayer arrays of polystyrene−poly(2-vinylpyridine) diblock copolymer cylinders with excellent orientational order and a very low density of dislocations are prepared by cooling slowly from above the bulk order−disorder temperature (ODT) ∼212 °C within silicon oxide channels one cylinder spacing a in depth and 2 μm in width. The translational order of this array, however, is short range with a correlation length of ∼12a. If such an array is heated to a temperature above the glass transition temperature of the block copolymer (100 °C) but well below the ODT, a finite density of thermally generated dislocations is observed, which leads to a decrease in the translational correlation length and an appearance of quasi-long-range orientational order such that the orientational correlation function g2(r) decays as a power law, i.e., g2(r) ≈ (r/a)-η2(T). The state of disorder at any given temperature appears to be an equilibrium one since cylinder arrays with similar dislocation densities and correlation functions can be obtained either by heating from the well-ordered state or by cooling slowly directly to the final temperature and holding at that temperature for a sufficient time. Above a temperature of 195 °C, the orientational order becomes short range (g2(r) decaying exponentially with r), and a large density of disclinations is observed in addition to the dislocations. The cylinder array becomes isotropic above this temperature, which is ∼20 °C below the bulk ODT. These results are in qualitative agreement with the theory of Toner and Nelson1 which describes the thermal generation of disorder and ultimate melting of a two-dimensional smectic.
The Avian Eggshell Extracellular Matrix as a Model for Biomineralization (1996)

The avian eggshell is a complex, extracellularly assembled structure which contains both mineralized and non-mineralized regions. The composition of the hen eggshell organic matrix was examined by immunohistochemistry with antibodies to different extracellular matrix molecules. Type I collagen is found in the shell membranes, but only after treatment of the tissue sections with pepsin. When incomplete eggshells are removed from the oviduct and immunostained, type I collagen can be detected in the shell membranes without pepsin treatment. The shell membranes, which are non-mineralized, also contain type X collagen, and this immunostaining does not require pepsin treatment. The occurrence of type X collagen in the shell membranes is surprising, since this collagen has not been found in any tissue other than hypertrophic cartilage. Immunostaining for various glycosaminoglycans shows the presence of keratan sulfate and dermatan sulfate. Several different antibodies to keratan sulfate stain different regions of the eggshell; one keratan sulfate epitope is prominent in the calcium reserve assemblies. Dermatan sulfate staining is very intense in the palisade region. Demineralized matrix from the palisade region was extracted with guanidine and fractionated by ion exchange chromatography. A approximately 200-kDa dermatan sulfate proteoglycan is found in these extracts, along with a number of protein components. This preparation was tested for its ability to affect calcium carbonate crystal formation in vitro. Pieces of demineralized shell membranes were used as a substrate for crystal formation and various amounts of the palisade matrix dermatan sulfate proteoglycan preparation were added to the solution from which the crystals were formed. This material causes a concentration-dependent change in crystal morphology to one in which the crystals are smaller and more rounded, which more closely approximates the crystals normally observed in eggshells. These results suggest that the dermatan sulfate proteoglycans may be important in modulating crystal morphology in the hen eggshell and correlate with mineralization-modulating biomolecules from other calcified tissue, which are generally anionic.