gebhart/patrepeval huggingface dataset:
Adult Human Mesenchymal Stem Cell Differentiation to the Osteogenic or Adipogenic Lineage Is Regulated by Mitogen-activated Protein Kinase (2000)

Adult human mesenchymal stem cells are primary, multipotent cells capable of differentiating to osteocytic, chondrocytic, and adipocytic lineages when stimulated under appropriate conditions. To characterize the molecular mechanisms that regulate osteogenic differentiation, we examined the contribution of mitogen-activated protein kinase family members, ERK, JNK, and p38. Treatment of these stem cells with osteogenic supplements resulted in a sustained phase of ERK activation from day 7 to day 11 that coincided with differentiation, before decreasing to basal levels. Activation of JNK occurred much later (day 13 to day 17) in the osteogenic differentiation process. This JNK activation was associated with extracellular matrix synthesis and increased calcium deposition, the two hallmarks of bone formation. Inhibition of ERK activation by PD98059, a specific inhibitor of the ERK signaling pathway, blocked the osteogenic differentiation in a dose-dependent manner, as did transfection with a dominant negative form of MAP kinase kinase (MEK-1). Significantly, the blockage of osteogenic differentiation resulted in the adipogenic differentiation of the stem cells and the expression of adipose-specific mRNAs peroxisome proliferator-activated receptor gamma2, aP2, and lipoprotein lipase. These observations provide a potential mechanism involving MAP kinase activation in osteogenic differentiation of adult stem cells and suggest that commitment of hMSCs into osteogenic or adipogenic lineages is governed by activation or inhibition of ERK, respectively.
pathChirp: Efficient Available Bandwidth Estimation for Network Paths (2003)

This paper presents pathChirp, a new active probing tool for estimating the available bandwidth on a communication network path. Based on the concept of ''self-induced congestion,'' pathChirp features an exponential flight pattern of probes we call a chirp. Packet chips offer several significant advantages over current probing schemes based on packet pairs or packet trains. By rapidly increasing the probing rate within each chirp, pathChirp obtains a rich set of information from which to dynamically estimate the available bandwidth. Since it uses only packet interarrival times for estimation, pathChirp does not require synchronous nor highly stable clocks at the sender and receiver. We test pathChirp with simulations and Internet experiments and find that it provides good estimates of the available bandwidth while using only a fraction of the number of probe bytes that current state-of-the-art techniques use.
Maturation and Pro-peptide Cleavage of β-Secretase (2000)

Amyloid beta-peptide is generated by two sequential proteolytic cleavages mediated by beta-secretase (BACE) and gamma-secretase. BACE was recently identified as a membrane-associated aspartyl protease. We have now analyzed the maturation and pro-peptide cleavage of BACE. Pulse-chase experiments revealed that BACE is post-translationally modified during transport to the cell surface, which can be monitored by a significant increase in the molecular mass. The increase in molecular mass is caused by complex N-glycosylation. Treatment with tunicamycin and N-glycosidase F led to a BACE derivative with a molecular weight corresponding to an unmodified version. In contrast, the mature form of BACE was resistant to endoglycosidase H treatment. The cytoplasmic tail of BACE was required for efficient maturation and trafficking through the Golgi; a BACE variant lacking the cytoplasmic tail undergoes inefficient maturation. In contrast a soluble BACE variant that does not contain a membrane anchor matured more rapidly than full-length BACE. Pro-BACE was predominantly located within the endoplasmic reticulum. Pro-peptide cleavage occurred immediately before full maturation and trafficking through the Golgi.
Innate immunity based cancer immunotherapy: B16-F10 murine melanoma model (2016)

An efficient cancer treatment results from the combination of Toll-like receptor agonists and phagocytosis stimulating ligands bound to the tumor cells.
"To Lay and Collect Taxes": The Constitutional Case for Progressive Taxation (1999)

For centuries, people have debated whether the wealthy should pay more taxes than the poor, and if so, how much more. These issues have never been resolved, and solutions that will satisfy everyone seem unlikely to emerge. In this nation, the notion of "progressive" taxation sparked one of the early battles over tax distribution. Supporters of progressive taxation favored a graduated tax structure, where the tax rate would increase with the taxpayer's income. Opponents of progressive taxation believed that a person should not pay a higher tax rate just because he or she earned a higher income. For most of the nineteenth century, however, this country did not collect an income tax at all.
Culture parameters for stable expansion, genetic modification and germline transmission of rat pluripotent stem cells (2011)

The ability of cultured pluripotent cells to contribute to the germline of chimaeric animals is essential to their utility for genetic manipulation. In the three years since rat embryonic stem (ES) cells were first reported the anticipated proliferation of genetically modified rat models from this new resource has not been realised. Culture instability, karyotypic anomalies, and strain variation are postulated to contribute to poor germline colonisation capacity. The resolution of these issues is essential to bring pluripotent cell-based genetic manipulation technology in the rat to the level of efficiency achieved in the mouse. Recent reports have described various alternative methods to maintain rat ES cells that include provision of additional small molecules and selective passaging methods. In contrast, we report that euploid, germline competent rat ES and embryonic germ (EG) cell lines can be maintained by simple adherent culture methods in defined medium supplemented with the original two inhibitors (2i) of the mitogen-activated protein kinase (ERK1/2) cascade and of glycogen synthase kinase 3, in combination with the cytokine leukaemia inhibitory factor (LIF). We demonstrate genetic modification, clonal expansion and transmission through the germline of rat ES and EG cell lines. We also describe a marked preference for full-term chimaera contribution when SD strain blastocysts are used as recipients for either DA or SD pluripotent stem cells.
Primary Carnitine Deficiency Due to a Failure of Carnitine Transport in Kidney, Muscle, and Fibroblasts (1988)

CARNITINE (β-hydroxy-γ-trimethylaminobutyric acid) is an essential cofactor for the oxidation of fatty acids by mitochondria. It serves to carry long-chain fatty acids in the form of their acyl-carnitine esters across the barrier of the inner mitochondrial membrane before β-oxidation. Since 1973,1 a total of 46 patients have been described with evidence of impaired fatty acid oxidation associated with reduced levels of carnitine.2 These patients have been divided into a group with a "systemic carnitine deficiency," which presents in infancy or early childhood with recurrent episodes of coma and hypoglycemia, and a group with a "muscle carnitine deficiency," which presents later . . .
Liver Toxicities Typically Induced by First-Generation Adenoviral Vectors Can Be Reduced by Use of E1, E2b-Deleted Adenoviral Vectors (2003)

Adenoviral vectors from which the E1 region has been deleted ([E1(-)] Ad) are known to induce strong immune responses after systemic delivery. In this study we have evaluated liver toxicities in mice after intravenous injection with high doses of [E1(-)] or modified [E1(-), E2b(-)] Ad vectors (both expressing the bacterial beta-galactosidase [lacZ] marker gene) in C57BL/6, BALB/c, and SCID mice. Our data demonstrate a marked reduction in maximal liver toxicities and pathologies (typically noted at 21 days postinjection) with the use of the [E1(-), E2b(-)] modified vector in all strains of mice tested. Our data also demonstrated that despite the use of the [E1(-), E2b(-)] Ad vector, significant liver toxicities were still observed. To address this issue and the fact that the lacZ gene was perceived as a foreign antigen in the immune-competent C57BL/6 and BALB/c mice, we similarly injected mice tolerant of LacZ (lacZ-TG). In contrast to our studies in C57BL/6 and BALB/c mice, LacZ-TG mice exhibited virtually no evidence of hepatotoxicity after intravenous injection with the [E1(-), E2b(-)] vector, in contrast to use of the [E1(-)] Ad vector. Our results demonstrate that the [E1(-), E2b(-)] Ad vector class can reduce liver toxicities typically ascribed to Ad vector-mediated gene transfer after transfer of a highly immunogenic or foreign gene, whereas transfer of a transgene that is perceived as nonforeign by the host can be delivered with virtually no evidence of toxicity. On the basis of a careful review of the literature, these improvements in vector safety rival those noted with other, more significantly modified Ad vectors described to date.
Learning Optimization Updates for Multimodal Registration (2016)

We address the problem of multimodal image registration using a supervised learning approach. We pose the problem as a regression task, whose goal is to estimate the unknown geometric transformation from the joint appearance of the fixed and moving images. Our method is based on (i) context-aware features, which allow us to guide the registration using not only local, but also global structural information, and (ii) regression forests to map the very large contextual feature space to transformation parameters. Our approach improves the capture range, as we demonstrate on the publicly available IXI dataset. Furthermore, it can also handle difficult settings where other similarity metrics tend to fail; for instance, we show results on the deformable registration of Intravascular Ultrasound (IVUS) and Histology images.
The influence of genetic background on spontaneous and genetically engineered mouse models of complex diseases. (2001)

In recent years, the use of genetically altered mice as models of complex human disease has revolutionized biomedical research into the genetics of disease pathogenesis and potential therapeutic interventions. Whether a mouse expresses a spontaneous or induced mutation, it is critical to remember that the observed phenotype is not always the direct result of the genetic alteration. The author points out the importance of considering the genetic background of the strain used to create these important models.
Radicals from Aldehydes: A Convergent Access to Dienes and δ-Lactones (2006)

International audience
Corneal Wound Healing After Ultraviolet-A/Riboflavin Collagen Cross-Linking: A Rabbit Study (2010)

Riboflavin+UVA CXL triggers more anterior keratocyte apoptosis than corneal scrape with UVA alone or riboflavin alone. Inflammation monitored by the monocyte marker CD11b was present, but not statistically different among the three groups. Very little myofibroblast generation could be detected after UVA+riboflavin CXL, indicating that the mild stromal haze associated with this procedure is normally related to transient corneal fibroblast generation rather than more persistent haze due to generation of myofibroblasts.
Synthesis and biological activity of novel anti-juvenile hormone agents (2008)

Ethyl 4-[2-(tert-butylcarbonyloxy)butoxy]benzoate (ETB) is a partial juvenile hormone (JH) antagonist which targets larval epidermis. We converted ETB to ethyl 4-(2-substituted alkyloxy)benzoates. These compounds induced precocious metamorphosis in the silkworm, Bombyx mori, which is a clear sign of JH deficiency, and their activity was completely counteracted by the simultaneous application of a JH agonist, methoprene. Among these novel compounds, ethyl 4-(2-benzylhexyloxy)benzoate (KF-13) showed high precocious metamorphosis-inducing activity at low doses, but its activity decreased with increasing dose, probably due to their JH-like activity. KF-13 is an enantiomeric compound. The (S)-enatiomer of KF-13 was more active than the (R)-enantiomer at low doses, but at high doses the activity was reversed (R>S). Hemolymph JH esterase activity, which is indispensable for the initiation of pupation in normal last-instar larvae, was induced in 4th-instar larvae by treatment with KF-13. 2-(6-Methyl-3-pyridyloxy)hexyl and 2-phenoxyhexyl analogs showed JH activity when topically applied to allatechtomized 4th-instar larvae.
Decreased cardiac activity of AMP deaminase in subjects with the AMPD1 mutation—A potential mechanism of protection in heart failure (2003)

Our findings indicate that the C34T mutation of AMPD1 leads to a decrease in cardiac enzyme activity of AMP-deaminase without changes in any other adenosine-regulating enzymes, highlighting the importance of local cardiac metabolic changes. Systemic (blood) changes in adenosine concentration were apparent only in homozygous subjects and therefore may play a relatively small part in cardio-protection.
LT codes (2003)

We introduce LT codes, the first rateless erasure codes that are very efficient as the data length grows.
Demonstration of Biofilm in Human Bacterial Chronic Rhinosinusitis (2005)

Biofilms are refractory to antibiotics and often only cured by mechanical debridement. We believe this is the first TEM documentation of bacterial biofilms in CRS in humans.
Increased lymphocyte trafficking to colonic microvessels is dependent on MAdCAM-1 and C-C chemokine mLARC/CCL20 in DSS-induced mice colitis (2005)

Although enhanced lymphocyte trafficking is associated with colitis formation, little information about its regulation is available. The aim of this study was to examine how the murine liver and activation-regulated chemokine (mLARC/CCL20) contributes to lymphocyte recruitment in concert with vascular adhesion molecules in murine chronic experimental colitis. T and B lymphocytes isolated from the spleen were fluorescence-labelled and administered to recipient mice. Lymphocyte adhesion to microvessels of the colonic mucosa and submucosa was observed with an intravital microscope. To induce colitis, the mice received two cycles of treatment with 2% dextran sodium sulphate (DSS). In some of the experiments antibodies against the adhesion molecules or anti-mLARC/CCL20 were administered, or CC chemokine receptor 6 (CCR6) of the lymphocytes was desensitized with excess amounts of mLARC/CCL20. Significant increases in T and B cell adhesion to the microvessels of the DSS-treated mucosa and submucosa were observed. In chronic colitis, the accumulation of lymphocytes was significantly inhibited by anti-mucosal addressin cell adhesion molecule (MAdCAM)-1 mAb, but not by anti-vascular cell adhesion molecule-1. In DSS-treated colonic tissue, the expression of mLARC/CCL20 was significantly increased, the blocking of mLARC/CCL20 by monoclonal antibody or the desensitization of CCR6 with mLARC/CCL20 significantly attenuated the DSS-induced T and B cell accumulation. However, the combination of blocking CCR6 with MAdCAM-1 did not further inhibit these accumulations. These results suggest that in chronic DSS-induced colitis, both MAdCAM-1 and mLARC/CCL20 may play important roles in T and B lymphocyte adhesion in the inflamed colon under flow conditions.
Beneficial Effect of Coenzyme Q10 on Increased Oxidative and Nitrative Stress and Inflammation and Individual Metabolic Components Developing in a Rat Model of Metabolic Syndrome (2008)

Metabolic syndrome (MetS) is a group of cardiovascular risk factors, including visceral obesity, glucose intolerance, hypertension, and dyslipidemia. Increased oxidative and nitrative stress and inflammation and decreased endothelial function occur in an animal model of metabolic syndrome, SHR/NDmcr-cp (SHR/cp) rats. The present study investigated the effects of coenzyme Q10 (CoQ10), one of the important antioxidants, on the abnormal oxidative condition and characteristic components of metabolic syndrome in SHR/cp rats by maintaining them on a diet supplemented with 0.07% - 0.7% CoQ10 for 26 weeks. We determined serum levels of oxidatively modified low-density lipoprotein (Ox-LDL) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as oxidative stress markers, 3-nitrotyrosine as a nitrative stress marker, 3-chlorotyrosine as a marker of myeloperoxidase (MPO)-catalyzed oxidation and high-sensitivity C-reactive protein (hsCRP) as an inflammatory marker. The administration of CoQ10 significantly attenuated the increase of oxidative and nitrative stress markers and inflammatory markers in a dose-dependent manner. CoQ10 prevented the elevated serum insulin levels, although it did not affect the elevated glucose level and dyslipidemia. CoQ10 also reduced elevated blood pressure, but did not affect body weight gain. In addition, CoQ10 improved endothelial dysfunction in the mesenteric arteries. These findings suggest that the antioxidant properties of CoQ10 can be effective for ameliorating cardiovascular risk in MetS.
Hypothermia Therapy after Traumatic Brain Injury in Children (2008)

In children with severe traumatic brain injury, hypothermia therapy that is initiated within 8 hours after injury and continued for 24 hours does not improve the neurologic outcome and may increase mortality. (Current Controlled Trials number, ISRCTN77393684 [controlled-trials.com].).
Prevalence and Incidence of Antimicrobial‐Resistant Organisms among Hospitalized Inflammatory Bowel Disease Patients (2013)

This particular population of hospitalized IBD patients was not shown to have a higher prevalence or incidence of ARO colonization or infection compared with non-IBD inpatients.
G-CSF receptor truncations found in SCN/AML relieve SOCS3-controlled inhibition of STAT5 but leave suppression of STAT3 intact (2004)

Truncated granulocyte colony-stimulating factor receptors (G-CSF-Rs) are implicated in severe congenital neutropenia (SCN) and the consecutive development of acute myeloid leukemia (AML). Mice expressing G-CSF-R truncation mutants (gcsfr-d715) show defective receptor internalization, an increased signal transducer and activator of transcription 5 (STAT5)/STAT3 activation ratio, and hyperproliferative responses to G-CSF treatment. We determined whether a lack of negative feedback by suppressor of cytokine signaling (SOCS) proteins contributes to the signaling abnormalities of G-CSF-R-d715. Expression of SOCS3 transcripts in bone marrow cells from G-CSF-treated gcsfr-d715 mice was approximately 60% lower than in wild-type (WT) littermates. SOCS3 efficiently suppressed STAT3 and STAT5 activation by WT G-CSF-R in luciferase reporter assays. In contrast, while SOCS3 still inhibited STAT3 activation by G-CSF-R-d715, STAT5 activation was no longer affected. This was due mainly to loss of the SOCS3 recruitment site Tyr729, with an additional contribution of the internalization defects of G-CSF-R-d715. Because Tyr729 is also a docking site for the Src homology 2-containing protein tyrosine phosphatase-2 (SHP-2), which binds to and inactivates STAT5, we suggest a model in which reduced SOCS3 expression, combined with the loss of recruitment of both SOCS3 and SHP-2 to the activated receptor complex, determine the increased STAT5/STAT3 activation ratio and the resulting signaling abnormalities projected by truncated G-CSF-R mutants.
The resistance of varroa mites (Acari: Varroidae) to acaricides and the presence of esterase (2005)

Abstract Varroa mites (Varroa destructor Anderson and Trueman, 2000) are becoming resistant to acaricide treatments via metabolic and/or target site desensitivity. Results of a survey of mites from the Carl Hayden AZ lab and from cooperators in five locations (Arizona, California, Florida, Maine, North Dakota) showed that some mites were susceptible to all three acaricides (Amitraz, Coumaphos, Fluvalinate) in the spring of 2003, but by fall most mites were resistant. Mites were resistant to all chemicals, even from beekeepers that do not treat colonies with acaricides. We used esterase native activity gels to test for the presence of specific esterases which might be involved in pesticide resistance in varroa. All mites tested had positive bands for esterase, even those exhibiting susceptibility to some acaricides. Based on the differences between the esterase activity gel profile of the susceptible and cross-resistant V. destructor, it is possible that an esterase-mediated resistance mechanism is operative in the population of the mites we analyzed. However, a combination of other resistance mechanisms may be present which make the esterase activity gel method unreliable for use in identifying varroa mites with multiple resistance.
Spontaneous flux and magnetic-interference patterns in 0-πJosephson junctions (1997)

The spontaneous flux generation and magnetic field modulation of the critical current in a 0-$\ensuremath{\pi}$ Josephson junction are calculated for different ratios of the junction length $L$ to the Josephsen penetration depth ${\ensuremath{\lambda}}_{J},$ and different ratios of the $0$-junction length to the $\ensuremath{\pi}$-junction length. These calculations apply to a Pb-YBa${}_{2}$Cu${}_{3}$O${}_{7\ensuremath{-}\ensuremath{\delta}}$ (YBCO) $c$-axis-oriented junction with one YBCO twin boundary, as well as other experimental systems. Measurements of such a junction can provide information on the nature of the $c$-axis Josephson coupling and the symmetry of the order parameter in YBCO. We find spontaneous flux even for very short symmetric 0-$\ensuremath{\pi}$ junctions, but asymmetric junctions have qualitatively different behavior.
In vivo suppression of early experimental osteoarthritis by interleukin‐1 receptor antagonist using gene therapy (1997)

This study showed that a local increase in IL-1Ra production in OA knee joints by intraarticular injection of transduced synovial cells can reduce the progression of experimentally induced lesions.
Profiles of cytokine production in relation with susceptibility to cerebral malaria. (1993)

Infection with Plasmodium berghei ANKA (PbA) leads, in susceptible strains of mice, to the development of cerebral malaria (CM), a lethal syndrome that reproduces some features of human CM. To study a possible relationship between genetic susceptibility to CM and the cytokine expression pattern, we quantitatively evaluated gene expression on RNA extracted from various organs of malaria-infected mice, using strains that are susceptible and resistant to CM. Northern blot analysis and semi-quantitative PCR showed that CM is associated with an increased TNF-alpha mRNA accumulation in the brain of mice developing the neurologic complications of CM. An increased IFN-gamma mRNA accumulation and a decreased expression of IL-4 and TGF-beta genes were also observed in mice susceptible to CM. In vitro restimulation studies using crude malarial Ag showed that lymphoid cell proliferation was higher in CM-susceptible than in CM-resistant infected mice. Moreover, susceptible mice produced large amounts of IFN-gamma, in a dose-dependent manner, in response to PbA Ag, whereas cells from resistant mice failed to produce significant amounts of this cytokine. Conversely, IL-2 and IL-4 production was significantly higher in infected CM-resistant mouse cells. No difference was seen in the production of IL-3 and IL-5 between resistant and susceptible PbA-infected mice. Upon stimulation with various malarial Ag, comparable amounts of TNF-alpha were produced by macrophages of either strain of mice. Taken together, these findings indicate that susceptibility to CM resides at the level of T cells rather than macrophages. Furthermore, the cytokine production profile is consistent with a predominant Th1-like response in mice developing cerebral complications of malaria.