gebhart/patrepeval huggingface dataset:
Mesodermal defects and cranial neural crest apoptosis in α5 integrin-null embryos (1997)

Alpha5beta1 integrin is a cell surface receptor that mediates cell-extracellular matrix adhesions by interacting with fibronectin. Alpha5 subunit-deficient mice die early in gestation and display mesodermal defects; most notably, embryos have a truncated posterior and fail to produce posterior somites. In this study, we report on the in vivo effects of the alpha5-null mutation on cell proliferation and survival, and on mesodermal development. We found no significant differences in the numbers of apoptotic cells or in cell proliferation in the mesoderm of alpha5-null embryos compared to wild-type controls. These results suggest that changes in overall cell death or cell proliferation rates are unlikely to be responsible for the mesodermal deficits seen in the alpha5-null embryos. No increases in cell death were seen in alpha5-null embryonic yolk sac, amnion and allantois compared with wild-type, indicating that the mutant phenotype is not due to changes in apoptosis rates in these extraembryonic tissues. Increased numbers of dying cells were, however, seen in migrating cranial neural crest cells of the hyoid arch and in endodermal cells surrounding the omphalomesenteric artery in alpha5-null embryos, indicating that these subpopulations of cells are dependent on alpha5 integrin function for their survival. Mesodermal markers mox-1, Notch-1, Brachyury (T) and Sonic hedgehog (Shh) were expressed in the mutant embryos in a regionally appropriate fashion. Both T and Shh, however, showed discontinuous expression in the notochords of alpha5-null embryos due to (1) degeneration of the notochordal tissue structure, and (2) non-maintenance of gene expression. Consistent with the disorganization of notochordal signals in the alpha5-null embryos, reduced Pax-1 expression and misexpression of Pax-3 were observed. Anteriorly expressed HoxB genes were expressed normally in the alpha5-null embryos. However, expression of the posteriormost HoxB gene, Hoxb-9, was reduced in alpha5-null embryos. These results suggest that alpha5beta1-fibronectin interactions are not essential for the initial commitment of mesodermal cells, but are crucial for maintenance of mesodermal derivatives during postgastrulation stages and also for the survival of some neural crest cells.
Expression of cancer cachexia-related factors in human cancer xenografts: an immunohistochemical analysis (2006)

We immunohistochemically evaluated the involvement of five cancer cachexia-related factors, including leukemia-inhibitory factor (LIF), zinc-α2-glycoprotein (ZAG), interleukin 6 (IL-6), proteolysis-inducing factor (PIF) and tumor necrosis factor α (TNF α) in causing cancer cachexia. Twenty-six xenografts implanted into mice were examined for the expression of the cancer cachexia-related factors, in relation to the body weight loss of the hosts. Five xenografts were categorized in the cachectic group, and the remaining 21 xenografts belonged to the non-cachectic group. LIF was extensively expressed in both the cachectic and non-cachectic groups. ZAG and IL-6 were expressed in one of the cachectic and some non-cachectic xenografts. PIF and TNF α were detected in one and two non-cachectic xenografts, respectively, but in none of the cachectic ones. Any of five factors examined were not conclusive for causing cancer cachexia in the murine xenograft model. Further analysis is needed in order to elucidate the mechanisms responsible for cancer cachexia.
WP-1034, a novel JAK-STAT inhibitor, with proapoptotic and antileukemic activity in acute myeloid leukemia (AML). (2005)

Cytokine stimulation induces proliferation and growth of acute myeloid leukemia (AML) blasts and high levels of cytokines have been associated with poor prognosis in AML. The Jak-Stat pathway constitutes a major mediator of cytokine activity. We investigated whether WP-1034, a novel Jak-Stat inhibitor, is active against AML blasts. OCIM2 and fresh AML cells were incubated with 1 to 6 microM WP-1034 to determine its effect on proliferation. WP-1034 effectively inhibited proliferation of OCIM2 cells and fresh AML samples. We then analyzed the expressions of Stat 1, 3, and 5, as well as Phospho-Stat 1, 3, and 5 by Western immunoblotting after incubation of OCIM2 cells without and with 1 to 10 microM WP-1034 for 2 hours, and at 5 microM from 20 minutes up to 4 hours and found that WP-1034 blocked Stat 3 and 5 activation. Analysis of cell cycle status by PI staining and flow cytometry showed that WP-1034 caused cell cycle arrest of OCIM2 cells in sub-Go phase. We then evaluated the induction of apoptosis of OCIM2 cells following incubation with WP-1034 at 3 to 6 microM by annexin V-CY5 assay and analyzed caspase 3 and PARP cleavage using Western immunoblotting. We found that WP-1034 induced apoptosis of OCIM2 cells and that induction of apoptosis involved cleavage of caspase 3 and the DNA repair enzyme poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP). Taken together, our data suggest that WP-1034 is a potent inhibitor of AML cell proliferation by inhibition of Stat 3 and 5 and induction of caspase-dependent apoptosis.
Head and neck cancer (2008)

Since the inception of this journal in 1948, the understanding of etiologic factors that contribute to and the treatment of head and neck cancer has evolved dramatically. Advances in surgery, radiation therapy, and chemotherapy have improved locoregional control, survival, and quality of life. The outcomes of these treatment modalities have shifted the focus of curative efforts from radical ablation to preservation and restoration of function. This evolution has been documented in the pages of Cancer for the past 6 decades. This review focuses on the evolution of treatment approaches for head and neck cancer and future directions while recognizing the historic contributions recorded within this journal.
Discrimination between Circulating Endothelial Cells and Blood Cell Populations with Overlapping Phenotype Reveals Distinct Regulation and Predictive Potential in Cancer Therapy (2011)

Flow cytometric CEC analysis based on CD45, CD31, and CD146 requires careful discrimination between blood cell populations with overlapping phenotype showing hallmarks of activated T cells and large platelets. However, these three cell populations show distinct regulation during cancer therapy, and their concomitant analysis may offer extended prognostic and predictive information.
Cellular mechanisms of low-power laser therapy (2003)

Cytochrome c oxidase is considered as the photoacceptor when eukaryotic cells are exposed to monochromatic red to near-IR radiation. Five primary mechanisms are discussed: changes in the redox properties of the respiratory chain components following photoexcitation of their electronic states, NO release from catalytic center of cytochrome c oxidase, generation of singlet oxygen, localized transient heating of absorbing chromophores, in creased superoxide anion production with a subsequent increase in the concentration of H<sub>2</sub>O<sub>2</sub>. A cascade of reactions related to the alteration of cellular homeostasis parameters (pH<sub>i</sub>, [Ca<sub>i</sub>], cAMP, Eh, [ATP] and some others) is considered as a photosignal transduction and amplification chain in a cell (secondary mechanisms).
Partial Cvi JI Digestion as an Alternative Approach to Generate Cosmid Sublibraries for Large-Scale Sequencing Projects (1996)

We demonstrate an alternative method for the generation of random subclones for large-scale shotgun human DNA sequencing projects. Miniprep DNA from a human cosmid clone was partially digested with CviJI, size-fractionated by agarose gel electrophoresis and cloned into bacteriophage M13. A library consisting of 10(5) subclones of 1.1 kb average size was recovered from one gel fraction containing approximately 300 ng of partially digested DNA. DNA sequences from an initial 103 subclones demonstrate that 100 of the subclones cover 90% of the cosmid, which is close to the 92% expected if the subclones were generated at random. DNA sequences from three of the subclones did not match the cosmid sequences, establishing that miniprep DNA can be used for library construction with little concern for contamination with genomic E. coli DNA. The use of CviJI to generate random DNA fragments thus offers a simple alternative to other commonly used fragmentation methods, such as shearing or sonication, for the generation of random sublibraries for large-scale human shotgun DNA sequencing projects.
Humidification and Secretion Volume in Mechanically Ventilated Patients (2009)

The volume of secretions appeared to be linked to humidification, as greater water vapor delivery measured in vitro was associated with greater secretion volume in vivo.
Requirement of glucose metabolism for regulation of glucose transporter type 2 (GLUT2) gene expression in liver (1996)

Previous studies have shown that glucose increases the glucose transporter (GLUT2) mRNA expression in the liver in vivo and in vitro. Here we report an analysis of the effects of glucose metabolism on GLUT2 gene expression. GLUT2 mRNA accumulation by glucose was not due to stabilization of its transcript but rather was a direct effect on gene transcription. A proximal fragment of the 5' regulatory region of the mouse GLUT2 gene linked to a reporter gene was transiently transfected into liver GLUT2-expressing cells. Glucose stimulated reporter gene expression in these cells, suggesting that glucose-responsive elements were included within the proximal region of the promoter. A dose-dependent effect of glucose on GLUT2 expression was observed over 10 mM glucose irrespective of the hexokinase isozyme (glucokinase K(m) 16 mM; hexokinase I K(m) 0.01 mM) present in the cell type used. This suggests that the correlation between extracellular glucose and GLUT2 mRNA concentrations is simply a reflection of an activation of glucose metabolism. The mediators and the mechanism responsible for this response remain to be determined. In conclusion, glucose metabolism is required for the proper induction of the GLUT2 gene in the liver and this effect is transcriptionally regulated.
Using and Managing PPP (1999)

From the Publisher:
In the last decade, the Internet has grown from a network that connected a few universities and research centers to a network that links many businesses and households all over the country. That expansion occurred for many reasons, but the technological advance that facilitated this growth was an obscure protocol called PPP. 
PPP isn't talked about as much as TCP and IP, but it plays a crucial role in extending networks into remote locations. The Point-to-Point Protocol enables telephone lines and other point-to-point connections to carry Internet traffic. It's the protocol that establishes and maintains the connection between your home and an Internet service provider. This book provides in-depth coverage of PPP for network administrators and others who are involved in the care and maintenance of PPP connections. It provides a thorough introduction to how PPP works, which will help you diagnose and troubleshoot problems. It discusses in detail how to set up dial-in and dial-out PPP on the most important platforms, including Windows, Linux, and Solaris. Whether you're a sophisticated user responsible for your own connection or a network administrator providing dial-up services for hundreds of remote users, you'll find this book an essential addition to your library. Covers:
PPP implementations in Windows 95/98/NT, Solaris, and Linux Authentication (CHAP, PAP, Microsoft variants, and other techniques) Virtual networks and tunnels, including PPTP Modems and serial lines Related technologies, including DNS and ARP Optimizing and customizing a connection Debugging techniques
Effect immunization with highly purified alpha- and beta-toxins on staphylococcal mastitis in rabbits (1977)

Experiments were carried out to determine whether immunization of female rabbits with highly purified staphylococcal alpha- or beta-toxins would protect them against intramammary challenge with staphylococci. High circulating anti-alpha-toxin titers reduced the lethal hemorrhagic edematous form of the disease ("blue-breast") produced by strains BB and Compton 201 to a localized chronic abscess form. No such protection was afforded by high anti-beta-toxin titers. Immunization with alpha- or beta-toxins produced no change in the clinical picture of the disease produced by CN.6708, a strain of Staphylococcus responsible for a natural outbreak of abscess-type rabbit mastitis. From these experiments it would appear that alpha-toxin is a key antigen in the blue-breast form of rabbit mastitis. Since the abscess form of the disease was not prevented by immunization with either alpha- or beta-toxin, other virulence factors must be acting to produce this more localized disease.
Prophylactic and Therapeutic Use of Antibodies for Protection against Respiratory Infection with Francisella tularensis (2007)

The role of Abs in protection against respiratory infection with the intracellular bacterium Francisella tularensis is not clear. To investigate the ability of Abs to clear bacteria from the lungs and prevent systemic spread, immune serum was passively administered i.p. to naive mice before intranasal F. tularensis live vaccine strain infection. It was found that immune serum treatment provided 100% protection against lethal challenge while normal serum or Ig-depleted immune serum provided no protection. Protective efficacy was correlated with increased clearance of bacteria from the lung and required expression of FcgammaR on phagocytes, including macrophages and neutrophils. However, complement was not required for protection. In vitro experiments demonstrated that macrophages were more readily infected by Ab-opsonized bacteria but became highly efficient in killing upon activation by IFN-gamma. Consistent with this finding, in vivo Ab-mediated protection was found to be dependent upon IFN-gamma. SCID mice were not protected by passive Ab transfer, suggesting that T cells but not NK cells serve as the primary source for IFN-gamma. These data suggest that a critical interaction of humoral and cellular immune responses is necessary to provide sterilizing immunity against F. tularensis. Of considerable interest was the finding that serum Abs were capable of conferring protection against lethal respiratory tularemia when given 24-48 h postexposure. Thus, this study provides the first evidence for the therapeutic use of Abs in Francisella-infected individuals.
Gene therapy vectors based on adeno-associated virus: characteristics and applications to acquired and inherited diseases (review). (2000)

Adeno-associated virus (AAV), a defective parvovirus, was discovered more than 30 years ago. Interest in this virus for human gene therapy applications focuses on its non-pathogenicity, broad tropism and infectivity, site-specific integration and long-term persistence. The field of rAAV research has considerably advanced: titers of 1014 p/ml have been achieved, plasmid systems devised to produce helper-free viruses, chimaeric vectors combining properties of rAAV ITRs and large sequence capacity from Ad/HS vectors in parallel with the revolutionary intron strategy based on heterodimerisation of the forming concatamers have expanded the vector capacity. Muscle cells and neurons (post-mitotic cells) are amongst the most efficient targets of rAAV delivery and AAV receptors and co-receptors have been identified. This review will describe advances in the field of rAAV technology that overcome certain limitations of the vector as a gene delivery system and overview applications involving these recombinant vectors for the treatment of acquired and inherited diseases.
A Strategy for Designing Inhibitors of β-Amyloid Toxicity (1996)

beta-Amyloid peptide is the major protein component of Alzheimer's plaques. When aggregated into amyloid fibrils, the peptide is toxic to neuronal cells. Here, an approach to the design of inhibitors of beta-amyloid toxicity is described; in this strategy, a recognition element, which interacts specifically with beta-amyloid, is combined with a disrupting element, which alters beta-amyloid aggregation pathways. The synthesis, biophysical characterization, and biological activity of such an inhibitor is reported. This prototype inhibitor is composed of residues 15-25 of beta-amyloid peptide, designed to function as the recognition element, linked to an oligolysine disrupting element. The inhibitor does not alter the apparent secondary structure of beta-amyloid nor prevent its aggregation; rather, it causes changes in aggregation kinetics and higher order structural characteristics of the aggregate. Evidence for these effects includes changes in fibril morphology and a reduction in thioflavin T fluorescence. In addition to its influence on the physical properties of beta-amyloid aggregates, the inhibitor completely blocks beta-amyloid toxicity to PC-12 cells. Together, these data suggest that this general strategy for design of beta-amyloid toxicity inhibitors is effective. Significantly, these results demonstrate that complete disruption of amyloid fibril formation is not necessary for abrogation of toxicity.
Janus: an Approach for Confinement of Untrusted Applications (1999)

Security is a serious concern on today&amp;apos;s computer networks. Many applications are not very good at resisting attack, and our operating systems are not very good at preventing the spread of any intrusions that may result. In this thesis, we propose to manage the risk of a security breach by confining these untrusted (and untrustworthy) applications in a carefully sanitized space. We design a secure environment for confinement of untrusted applications by restricting the program&amp;apos;s access to the operating system. In our prototype implementation, we intercept and filter dangerous system calls via the Solaris process tracing facility. This enables us to build a simple, clean, user-mode mechanism for con ning untrusted applications. Our implementation has negligible performance impact, and can protect pre-existing legacy code.
Short-term treatment of spontaneously hypertensive rats with liver growth factor reduces carotid artery fibrosis, improves vascular function, and lowers blood pressure (2005)

Short-term treatment with a low dose of LGF induced a large improvement in vascular structure and function and significantly reduced blood pressure in a rat model of essential hypertension. The present results could open future research to explore the vascular effects of this endogenous factor in order to determine its potential as an antifibrotic and antihypertensive agent in humans.
Novel Neurotensin Analogues for Radioisotope Targeting to Neurotensin Receptor-Positive Tumors (2009)

The increased expression of the neurotensin (NT) receptor NTS1 by different cancer cells, such as pancreatic adenocarcinoma and ductal breast cancer cells, as compared to normal epithelium, offers the opportunity to target these tumors with radiolabeled neurotensin analogues for diagnostic or therapeutic purposes. The aim of the present study was to design and synthesize new neurotensin radioligands and to select a lead molecule with high in vivo tumor selectivity for further development. Two series of neurotensin analogues bearing DTPA were tested: a series of NT(8-13) analogues, with DTPA coupled to the α-NH(2), sharing the same peptide sequence with analogues previously developed for radiolabeling with technetium or rhenium, as well as an NT(6-13) series in which DTPA was coupled to the ε-NH(2) of Lys(6). Changes were introduced to stabilize the bonds between Arg(8)-Arg(9), Pro(10)-Tyr(11), and Tyr(11)-Ile(12) to provide metabolic stability. Structure-activity studies of NT analogues have shown that the attachment of DTPA induces an important loss of affinity unless the distance between the chelator and the NT(8-13) sequence, which binds to the NTS1 receptor, is increased. The doubly stabilized DTPA-NT-20.3 exhibits a high affinity and an elevated stability to enzymatic degradation. It shows specific tumor uptake and high tumor to blood, to liver, and to intestine activity uptake ratios and affords high-contrast planar and SPECT images in an animal model. The DTPA-NT-20.3 peptide is a promising candidate for imaging neurotensin receptor-positive tumors, such as pancreatic adenocarcinoma and invasive ductal breast cancer. Analogues carrying DOTA are being developed for yttrium-90 or lutetium-177 labeling.
Diabetes and Atherosclerosis (2002)

Since most patients with diabetes die from complications of atherosclerosis, they should receive intensive preventive interventions proven to reduce their cardiovascular risk.
Nuclease Activity and Binding Characteristics of a Cationic “Manganese Porphyrin−Bis(benzimidazole) Dye (Hoechst 33258)” Conjugate (1997)

To increase the binding affinity and/or the sequence selectivity of the chemical nuclease manganese-(III) tetrakis(4-N-methylpyridiniumyl)porphyrin, we synthesized a conjugate molecule by associating a tris(4-N-methylpyridiniumyl)metalloporphyrin motif to Hoechst 33258 (H33258), a DNA minor groove binding dye known for its selective affinity for A-T tracts. Selected double-stranded (ds) 35-mer oligodeoxyribonucleotides have been used to probe DNA chain breakages induced by the managanese derivative of the conjugate after activation by potassium monopersulfate. Gel electrophoresis analyses show that DNA cuts were generated by the metalloporphyrin moiety of the hybrid molecule, with the H33258 entity interacting in two different possible orientations, upstream or downstream, with its preferred affinity site inside the minor groove. Also studied was the cleavage of a ds 29-mer oligodesoxyribonucleotide containing two stretches of A.T basepair (bp) which clearly showed that the hybrid can occupy the binding region at least in four preferred ways. These cleavage experiments support the strong and selective interaction of the metalloporphyrin-dye hybrid with DNA and allow the estimate of 10 bp as an average size for the affinity site of an isolated conjugate molecule. Further studies by UV-visible spectroscopy, DNA melting temperature determinations, and DNase I footprinting showed, for higher concentrations of H33258 conjugate, a preferential interaction of only the H33258 moiety with DNA (estimated binding site size 6-7 bp) with the porphyrin entity pushed out of the groove and, for the highest concentrations, self-aggregation of the H33258 conjugate all along the DNA strand in a nonselective mode.
[Expression of the glycoprotein in atrioventricular cell membrane of acute myocardial infarction in human]. (2003)

This experiment proved that atrioventricular cell membrane expressed D-galactose as same as myocardial cell membrane in the acute myocardial infarction.