gebhart/patrepeval huggingface dataset:
Complete mitochondrial genome of a Pleistocene jawbone unveils the origin of polar bear (2010)

The polar bear has become the flagship species in the climate-change discussion. However, little is known about how past climate impacted its evolution and persistence, given an extremely poor fossil record. Although it is undisputed from analyses of mitochondrial (mt) DNA that polar bears constitute a lineage within the genetic diversity of brown bears, timing estimates of their divergence have differed considerably. Using next-generation sequencing technology, we have generated a complete, high-quality mt genome from a stratigraphically validated 130,000- to 110,000-year-old polar bear jawbone. In addition, six mt genomes were generated of extant polar bears from Alaska and brown bears from the Admiralty and Baranof islands of the Alexander Archipelago of southeastern Alaska and Kodiak Island. We show that the phylogenetic position of the ancient polar bear lies almost directly at the branching point between polar bears and brown bears, elucidating a unique morphologically and molecularly documented fossil link between living mammal species. Molecular dating and stable isotope analyses also show that by very early in their evolutionary history, polar bears were already inhabitants of the Artic sea ice and had adapted very rapidly to their current and unique ecology at the top of the Arctic marine food chain. As such, polar bears provide an excellent example of evolutionary opportunism within a widespread mammalian lineage.
Surface Porosity of Lignin/PP Blend Carbon Fibers (2007)

Abstract The surface porosities of carbon fibers derived from the polymer blend fibers of hardwood kraft lignin, HKL and polypropylene, PP, were discussed using thermal analyses, FTIR, and nitrogen adsorption. HKL/PP carbon fibers were prepared by two‐step thermal processing, thermostabilization, and carbonization. During the thermostabilization process, pores are created by oxidative degradation of the PP component. After thermostabilization some crystalline and highly oxidized PP components remained in the blend fiber. These residual PP components were subsequently pyrolyzed during carbonization, and effectively created a porous structure in the resulting carbon fibers. N2 adsorption tests of the porous carbon fibers revealed the same type of adsorption/desorption isotherms as for activated carbon fiber. The internal surface area of the HKL/PP = 62.5/37.5 carbon fibers was calculated to be 499 m2 g−1. This value was lower than that for commercial activated carbon, 745 m2 g−1. However, these porous lignin‐based carbon fibers were not activated carbon fibers, which could be relatively easily done through steam activation. Thus, the HKL/PP blend carbon fibers appear to be promising precursors for activated carbon fibers.
Characterization of cDNA sequences corresponding to three distinct HMG-1 mRNA species in line CHO Chinese hamster cells and cell cycle expression of the HMG-1 gene (1987)

We have isolated cDNA clones encoding the high mobility group (HMG) protein HMG-1 in line CHO Chinese hamster cells. The cDNA clones correspond to the three HMG-1 mRNA species detected on Northern blots. Three different polyadenylation sites are found to be used. The three mRNA species of sizes 1.05, 1.45 and 2.45 kb are generated by differential polyadenylation at sites 115 nucleotides, 513 nucleotides and 1515 nucleotides downstream from the stop codon. A perfectly conserved putative poly(A) signal AAUAAA is present upstream of only one of the three poly(A) sites. Two homologous but imperfect sequences exist upstream from the other two poly(A) sites. All three HMG-1 mRNA species maintain significant levels throughout the M, G1 and S phases of the cell cycle and the rate of large HMG protein (HMG-1 and HMG-2) synthesis increases approximately two-fold from G1 to S phase.
Regulation of Secreted Frizzled-related Protein-1 by Heparin (2007)

Secreted Frizzled-related protein-1 (sFRP-1) belongs to a class of extracellular antagonists that modulate Wnt signaling pathways by preventing ligand-receptor interactions among Wnts and Frizzled membrane receptor complexes. sFRP-1 and Wnts are heparin-binding proteins, and their interaction can be stabilized by heparin in vitro. Here we report that heparin can specifically enhance recombinant sFRP-1 accumulation in a cell type-specific manner. The effect requires O-sulfation in heparin, and involves fibroblast growth factor-2 as well as fibroblast growth factor receptor-1. Interestingly, further investigation uncovers that heparin can also affect the post-translational modification of sFRP-1. We demonstrate that sFRP-1 is post-translationally modified by tyrosine sulfation at tyrosines 34 and 36, which is inhibited by the treatment of heparin. The results suggest that accumulation of sFRP-1 induced by heparin is in part due to the relative stabilization of unsulfated sFRP-1 and the direct stabilization by heparin. The study has revealed a multifaceted regulation on sFRP-1 protein by heparin.
Induction of Robust Diabetes Resistance and Prevention of Recurrent Type 1 Diabetes Following Islet Transplantation by Gene Therapy (2007)

We have previously shown that the development of type 1 diabetes (T1D) can be prevented in nonobese diabetic (NOD) mice by reconstitution with autologous hemopoietic stem cells retrovirally transduced with viruses encoding MHC class II I-A beta-chain molecules associated with protection from the disease. In this study we examined whether a blockade of the programmed death-1 (PD-1)-programmed death ligand-1 (PD-L1) pathway, a major pathway known to control diabetes occurrence, could precipitate T1D in young NOD mice following reconstitution with autologous bone marrow retrovirally transduced with viruses encoding protective MHC class II I-A beta-chain molecules. In addition, we examined whether the expression of protective MHC class II alleles in hemopoietic cells could be used to prevent the recurrence of diabetes in mice with pre-existing disease following islet transplantation. Protection from the occurrence of T1D diabetes in young NOD mice by the expression of protective MHC class II I-A beta-chain molecules in bone marrow-derived hemopoietic cells was resistant to induction by PD-1-PD-L1 blockade. Moreover, reconstitution of NOD mice with pre-existing T1D autologous hemopoietic stem cells transduced with viruses encoding protective MHC class II I-A beta-chains allowed for the successful transplantation of syngeneic islets, resulting in the long-term reversal of T1D. Reversal of diabetes was resistant to induction by PD-1-PDL-1 blockade and depletion of CD25(+) T cells. These data suggest that expression of protective MHC class II alleles in bone marrow-derived cells establishes robust self-tolerance to islet autoantigens and is sufficient to prevent the recurrence of autoimmune diabetes following islet transplantation.
Use of Phosphine as an n-Type Dopant Source for Vapor−Liquid−Solid Growth of Silicon Nanowires (2005)

Phosphine (PH3) was investigated as an n-type dopant source for Au-catalyzed vapor-liquid-solid (VLS) growth of phosphorus-doped silicon nanowires (SiNWs). Transmission electron microscopy characterization revealed that the as-grown SiNWs were predominately single crystal even at high phosphorus concentrations. Four-point resistance and gate-dependent conductance measurements confirmed that electrically active phosphorus was incorporated into the SiNWs during VLS growth. A transition was observed from p-type conduction for nominally undoped SiNWs to n-type conduction upon the introduction of PH3 to the inlet gas. The resistivity of the n-type SiNWs decreased by approximately 3 orders of magnitude as the inlet PH3 to silane (SiH4) gas ratio was increased from 2 x 10(-5) to 2 x 10(-3). These results demonstrate that PH3 can be used to produce n-type SiNWs with properties that are suitable for electronic and optoelectronic device applications.
Maternal serum levels of dimeric inhibin A in pregnancies affected by trisomy 21 in the first trimester (2001)

Dimeric inhibin A was measured in maternal serum samples from 45 pregnancies affected by trisomy 21 and 493 samples from unaffected pregnancies at 10-14 weeks of gestation. Inhibin A levels in affected pregnancies were compared with levels of free beta-hCG and PAPP-A in the same series. In the trisomy 21 group, the median multiple of the median (MoM) inhibin A was not significantly elevated (1.28 vs 1.00) with only 15.5% being above the 95th centile. In contrast, the median MoM free beta-hCG was significantly increased (2.05 vs 1.00) with 36% above the 95th centile and PAPP-A was significantly reduced (0.49 vs 1.00) with 42% below the 5th centile. Inhibin A levels in the trisomy 21 group were significantly correlated with gestational age such that median levels rose from 1.04 at 11 weeks to 1.30 at 12 weeks and 1.67 at 13 weeks. These findings suggest that first trimester biochemical screening for trisomy 21, which is currently optimised using maternal serum free beta-hCG and PAPP-A and fetal nuchal translucency, will not benefit from the inclusion of inhibin A.
Specific T-cell immunity against Ki-ras peptides in patients with pancreatic and colorectal cancers (2003)

Mutations of codon 12 in the Ki-ras gene are frequently found in pancreatic and colorectal cancers. It has been demonstrated that human T-cells have the potential to recognise tumours expressing mutated ras-derived peptides. However, it remains unclear whether T-cells from a given individual can recognise the mutant peptides, which are expressed in that individual's tumour tissues. Mutations of the Ki-ras oncogene were analysed by the mutant-allele-specific amplification (MASA) method in pancreatic and colorectal tumour tissues, and T-cell responses against mutated Ki-ras-derived peptides were measured by [(3)H]thymidine incorporation and IFN-gamma production assays. Specific T-cell responses against Ki-ras-products were found in cancer patients, whereas no immune response was observed in normal individuals (P<0.01). Six of the eight pancreatic cancer patients (75%) and nine of 26 colorectal cancer patients (35%) had T-cell responses to mutated Ki-ras-derived-peptides. T-cell response in a given individual cannot recognise the same mutated ras peptide, which is expressed in that individual's tumour tissues. However, pancreatic and colorectal cancer patients have T-cell immunity against Ki-ras-peptides, and this provides potential target for cancer immunotherapy.
Sox17 and β-catenin cooperate to regulate the transcription of endodermal genes (2004)

Recent studies have led to a model of the molecular pathway that specifies the endoderm during vertebrate gastrulation. The HMG box transcription factor Sox17 is a key component of this pathway and is essential for endoderm formation; however, the molecular events controlled by Sox17 are largely unknown. We have identified several direct transcriptional targets of Sox17, including Foxa1 and Foxa2. We show that beta-catenin, a component of Wnt signaling pathway, physically interacts with Sox17 and potentiates its transcriptional activation of target genes. We identify a motif in the C terminus of Sox17, which is conserved in all the SoxF subfamily of Sox proteins, and this motif is required for the ability of Sox17 to both transactivate target genes and bind beta-catenin. Nuclear beta-catenin is present in endoderm cells of the gastrula, and depletion of beta-catenin from embryos results in a repression of Sox17 target genes. These data suggest that in a mechanism analogous to Tcf/Lef interacting with beta-catenin, Sox17 and beta-catenin interact to transcribe endodermal target genes.
Effects of ospemifene on the female reproductive and urinary tracts (2014)

Available evidence indicates that ospemifene has unique effects on tissue, leading to a favorable long-term profile for the relief of vulvar and vaginal atrophy compared with other estrogen receptor agonists/antagonists (eg, tamoxifen, raloxifene, and bazedoxifene) with no short-term concerns about endometrial safety (based on endometrial hyperplasia, carcinoma, endometrial spotting, and endometrial bleeding).
Overview of Clostridium difficile infection: implications for China (2013)

The incidence and severity of Clostridium difficile infection (CDI) have dramatically increased in the Western world in recent years. In contrast, CDI is rarely reported in China, possibly due to under-diagnosis. This article briefly summarizes CDI incidence, management and preventive strategies. The authors intend to raise awareness of this disease among Chinese physicians and health workers, in order to minimize the medical and economic burden of a potential epidemic in the future.
Temperature Effect on Leaf Emergence and Phyllochron in Wheat and Barley (1989)

An understanding of the effect of environment on leaf emergence is necessary for modeling crop canopy growth. This study was to determine the effect of controlled temperature on leaf emergence rate and phyllochron in four winter wheat ( Triticum aestivum L.) and four spring barley ( Hordeum vulgare L.) genotypes. Nine experiments were conducted in growth chambers at constant temperatures between 7.5 to 25 °C. The number of leaves per culm was recorded daily from seedling emergence until the fourth leaf was mature. At a given temperature, the emergence of new leaves was a linear function of time for all genotypes, with R 2 values not less than 0.95. The slopes of the linear regressions, which are the leaf emergence rates (leaves/day), however, differed among genotypes and among temperatures within genotypes. For all genotypes, the leaf emergence rates increased parabolically with increasing temperature until an optimum temperature was reached and then declined. These responses could be described with quadratic polynomials with R 2 values greater than 0.96 for all genotypes. As temperature increased, the phyllochron (degree‐days/leaf) increased exponentially. The relationships between phyllochron and temperature fit exponential equations with R 2 0.97 or greater for all genotypes. The phyllochron ranged among the eight genotypes from 57.2 ± 5.2 degree‐days at 7.5 °C to 116.2 ± 7.1 degree‐days at 25 °C. These results suggest that the temperature effect must be considered in modeling phyllochron in wheat and barley.
92-kd type IV collagenase (matrix metalloproteinase-9) activity in human amniochorion increases with labor. (1995)

To determine whether specific collagenolytic enzymes are expressed in human fetal membranes with labor, we examined gelatinase activity in extracts of amniochorion by zymography. The 92-kd gelatinase (MMP-9) was barely detectable in extracts of fetal membranes before the onset of labor but was readily demonstrable in extracts prepared from membranes isolated from laboring women or membranes collected immediately after delivery. In contrast, the 72-kd gelatinase (MMP-2) was detectable in extracts from pre- and post-labor membranes. Ethylenediaminetetracetic acid and the tissue inhibitor of metalloproteinases, TIMP-1, inhibited the gelatinase activities detected by zymography, confirming that the enzymes are metalloproteinase. Assay of amniochorion gelatinase activity using a radiolabeled denatured collagen substrate revealed a more than twofold increase in activity comparing pre-labor with post-labor fetal membrane extracts. A function-blocking anti-MMP-9 monoclonal antibody inhibited pre-labor membrane gelatinase activity by approximately 11.5%, which was only slightly greater inhibition than observed with irrelevant monoclonal antibodies. However, post-labor membrane gelatinase activity was reduced by 53% by the function-blocking antibody, indicating that MMP-9 is a major contributor to the increased gelatinase activity extractable from post-labor membranes. Western blot analyses demonstrated increased MMP-9 protein in amniochorion extracts after onset of labor. MMP-9 protein and mRNA were co-localized in amnion epithelium, underlying macrophages and chorion laeve trophoblast and decidual cells after labor. We conclude that 1) MMP-9 activity and protein in human amniochorion increases with labor and 2) MMP-9 is expressed by amnion epithelium, macrophages and chorion laeve trophoblast and decidual cells. The increased expression of MMP-9 may result in degradation of the extracellular matrix of the fetal membranes and facilitate their rupture under both physiological and pathological conditions.
Hyperammonemia from a Urea Cycle Disorder Presenting in Adulthood (2009)

OBJECTIVE: The aim of this report is to describe a patient with late presentation of carbamyl phosphate synthetase I (CPS-I, EC 6.3.4.16) deficiency, a rare urea cycle deficiency, and to facilitate recognition and treatment of patients presenting with encephalopathy and hyperammonemia in a critical care setting. DESIGN: Case Report. SETTING: Intensive care unit of Saint Mary's Hospital, Mayo Clinic, Rochester, Minnesota. PATIENT: A 65-year-old woman admitted with progressive encephalopathy. INTERVENTIONS: Intubation and mechanical ventilation, protein-restricted parenteral nutrition, intravenous arginine, hemodiafiltration, and intravenous antibiotic therapy. MEASUREMENTS AND MAIN RESULTS: Serum ammonia and glutamine levels were elevated, but other laboratory and imaging investigations were unremarkable. Despite the above interventions, her mental status deteriorated. She developed ventilator associated pneumonia, which worsened despite antibiotic treatment. The family decided to withdraw care and the patient expired on hospital day 10. A postmortem enzyme assay on fresh-frozen liver tissue showed severely diminished CPS-I activity. CONCLUSIONS: To our knowledge, this is the oldest reported age at presentation of CPS-I deficiency. Urea cycle disorders should be part of the differential diagnosis of hyperammonemia regardless of age as early treatment may ameliorate mortality and morbidity in these patients.
SARS-CoV-2 viral load is associated with increased disease severity and mortality (2020)

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.
Tumor-associated MUC5AC stimulates in vivo tumorigenicity of human pancreatic cancer (2011)

MUC5AC, a high molecular weight glycoprotein, is overexpressed in the ductal region of human pancreatic cancer but is not detectable in the normal pancreas, suggesting its association with disease development. In the present study, we investigated the in vitro and in vivo effects of MUC5AC knockdown by short interfering RNA (siRNA) in the MUC5AC-overexpressing SW1990 and BxPC3 human pancreatic cancer cell lines in order to clarify its function. Significant decreases in the expression levels of MUC5AC mRNA and protein were observed in SW1990 and BxPC3 cells that had been stably transfected with a MUC5AC siRNA expression vector (SW1990/si-MUC5AC and BxPC3/si-MUC5AC cells) compared to those in cells transfected with an si-mock vector (SW1990/si-mock and BxPC3/si-mock cells). In in vitro studies, neither type of MUC5AC-knockdown cell showed any difference in cell survival, proliferation, or morphology from the si-mock cells or parental cells. However, in vivo xenograft studies demonstrated that MUC5AC knockdown significantly reduced the tumorigenicity and suppressed the tumor growth of si-MUC5AC cells compared to those of the si-mock cells. Immunohistochemical analysis revealed that CD45R/B220+ and Gr-1+ cells had infiltrated into the tumor tissue of the SW1990/si-MUC5AC cells. Furthermore, cancer-associated antigen specific antibodies were detected at high levels in the sera from the SW1990/si-MUC5AC cell-bearing mice. These results suggest that tumor-associated MUC5AC expressed on the surface of pancreatic cancer cells supports the escape of pancreatic cancer cells from immunosurveillance. The present findings highlight a new dimension of MUC5AC as a functional immunosuppressive agent and its important role in pancreatic cancer progression.
Interface-induced conversion of infrared to visible light at semiconductor interfaces (1996)

Efficient, low-temperature conversion of infrared light into visible light (red, orange, green) is reported at single heterojunctions and undoped quantum wells of GaAs and ordered ${\mathrm{Al}}_{x}{\mathrm{Ga}}_{1\ensuremath{-}x}\mathrm{In}{\mathrm{P}}_{2}$; an increase in photon energy of 700 meV is obtained. The signal originates from the high-band-gap layers and disappears only if the excitation energy is tuned below the GaAs band gap. The intensity of the up-converted photoluminescence (PL) is found to decrease significantly slower with increasing temperature than that of the regular PL and it remains observable up to 200 K. Interface-induced cold Auger processes along with the presence of trapped states for both electrons and holes in these ordered alloys account for this nonlinear mechanism. A colinear double-beam experiment confirms this.
Deletion of Cysteine Cathepsins B or L Yields Differential Impacts on Murine Skin Proteome and Degradome (2012)

Numerous studies highlight the fact that concerted proteolysis is essential for skin morphology and function. The cysteine protease cathepsin L (Ctsl) has been implicated in epidermal proliferation and desquamation, as well as in hair cycle regulation. In stark contrast, mice deficient in cathepsin B (Ctsb) do not display an overt skin phenotype. To understand the systematic consequences of deleting Ctsb or Ctsl, we determined the protein abundances of >1300 proteins and proteolytic cleavage events in skin samples of wild-type, Ctsb(-/-), and Ctsl(-/-) mice via mass-spectrometry-based proteomics. Both protease deficiencies revealed distinct quantitative changes in proteome composition. Ctsl(-/-) skin revealed increased levels of the cysteine protease inhibitors cystatin B and cystatin M/E, increased cathepsin D, and an accumulation of the extracellular glycoprotein periostin. Immunohistochemistry located periostin predominantly in the hypodermal connective tissue of Ctsl(-/-) skin. The proteomic identification of proteolytic cleavage sites within skin proteins revealed numerous processing sites that are underrepresented in Ctsl(-/-) or Ctsb(-/-) samples. Notably, few of the affected cleavage sites shared the canonical Ctsl or Ctsb specificity, providing further evidence of a complex proteolytic network in the skin. Novel processing sites in proteins such as dermokine and Notch-1 were detected. Simultaneous analysis of acetylated protein N termini showed prototypical mammalian N-alpha acetylation. These results illustrate an influence of both Ctsb and Ctsl on the murine skin proteome and degradome, with the phenotypic consequences of the absence of either protease differing considerably.