gebhart/patrepeval huggingface dataset:
Learning Deep Representation for Imbalanced Classification (2016)

Data in vision domain often exhibit highly-skewed class distribution, i.e., most data belong to a few majority classes, while the minority classes only contain a scarce amount of instances. To mitigate this issue, contemporary classification methods based on deep convolutional neural network (CNN) typically follow classic strategies such as class re-sampling or cost-sensitive training. In this paper, we conduct extensive and systematic experiments to validate the effectiveness of these classic schemes for representation learning on class-imbalanced data. We further demonstrate that more discriminative deep representation can be learned by enforcing a deep network to maintain both intercluster and inter-class margins. This tighter constraint effectively reduces the class imbalance inherent in the local data neighborhood. We show that the margins can be easily deployed in standard deep learning framework through quintuplet instance sampling and the associated triple-header hinge loss. The representation learned by our approach, when combined with a simple k-nearest neighbor (kNN) algorithm, shows significant improvements over existing methods on both high-and low-level vision classification tasks that exhibit imbalanced class distribution.
Drug-Inducible Gene Recombination by the Dppa3-MER Cre MER Transgene in the Developmental Cycle of the Germ Cell Lineage in Mice1 (2011)

Germ cells ensure the diversification and totipotency of genetic information via the elaborate genetic and epigenetic regulation of the genome architecture during their development. To understand the mechanism underlying the regulation of genome function in germ cells, it is of primary importance to develop systems in which gene function can be regulated at desired time points during their development. Here, we report the generation of transgenic strains that express Cre recombinase flanked by the ligand-binding domains of murine estrogen receptor (MER Cre MER [MCM]) under the control of the regulatory elements of the Dppa3 (also known as Stella or Pgc7) gene. On the administration of 4-hydroxytamoxifen (4-OHT), the Dppa3-MCM strains recombined the sequence flanked by the loxP elements (the floxed sequence) specifically in primordial germ cells as early as Embryonic Day (E) 7.0, and this recombination became robust after E9.5. Furthermore, these strains exhibited efficient and specific recombination of the floxed sequence during the growth of oocytes and in preimplantation embryos in the 4-OHT-dependent manner. Thus, these Dppa3-MCM strains offer valuable opportunities to explore gene function in both loss-of-function and gain-of-function experiments at a variety of time points during germ cell development.
Cystic Fibrosis Transmembrane Conductance Regulator–associated ATP Release Is Controlled by a Chloride Sensor (1998)

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is defective in cystic fibrosis, and has also been closely associated with ATP permeability in cells. Using a Xenopus oocyte cRNA expression system, we have evaluated the molecular mechanisms that control CFTR-modulated ATP release. CFTR-modulated ATP release was dependent on both cAMP activation and a gradient change in the extracellular chloride concentration. Activation of ATP release occurred within a narrow concentration range of external Cl- that was similar to that reported in airway surface fluid. Mutagenesis of CFTR demonstrated that Cl- conductance and ATP release regulatory properties could be dissociated to different regions of the CFTR protein. Despite the lack of a need for Cl- conductance through CFTR to modulate ATP release, alterations in channel pore residues R347 and R334 caused changes in the relative ability of different halides to activate ATP efflux (wtCFTR, Cl >> Br; R347P, Cl >> Br; R347E, Br >> Cl; R334W, Cl = Br). We hypothesize that residues R347 and R334 may contribute a Cl- binding site within the CFTR channel pore that is necessary for activation of ATP efflux in response to increases of extracellular Cl-. In summary, these findings suggest a novel chloride sensor mechanism by which CFTR is capable of responding to changes in the extracellular chloride concentration by modulating the activity of an unidentified ATP efflux pathway. This pathway may play an important role in maintaining fluid and electrolyte balance in the airway through purinergic regulation of epithelial cells. Insight into these molecular mechanisms enhances our understanding of pathogenesis in the cystic fibrosis lung.
Putative protein markers in the sera of men with prostatic neoplasms (2003)

These proteins, particularly the 15.9 kDa one, may be used for the diagnosis or monitoring of prostate cancer and differentiation from BPH, and have the potential for antibody-based chip SELDI-TOF technology. Identified proteins may be targets for immunotherapy.
Nitrogen-doped graphene and its electrochemical applications (2010)

Nitrogen-doped graphene (N-graphene) is obtained by exposing graphene to nitrogen plasma. N-graphene exhibits much higher electrocatalytic activity toward oxygen reduction and H2O2 reduction than graphene, and much higher durability and selectivity than the widely-used expensive Pt for oxygen reduction. The excellent electrochemical performance of N-graphene is attributed to nitrogen functional groups and the specific properties of graphene. This indicates that N-graphene is promising for applications in electrochemical energy devices (fuel cells, metal–air batteries) and biosensors.
Blockade of the type I IGF receptor expression in human prostate cancer cells inhibits proliferation and invasion, up‐regulates IGF binding protein‐3, and suppresses MMP‐2 expression (2003)

The type I insulin-like growth factor receptor (IGF-IR) is involved in tumour cell proliferation, invasion, and cancer cell survival. Several studies indicate that the IGF axis contributes to prostate cancer pathogenesis, but there is no consensus regarding the relative expression of the IGF-IR in benign and malignant prostate epithelium. In this study, endogenous IGF-IR gene expression was reduced in stably transfected PC-3 cells by employing an antisense RNA strategy which resulted in significant suppression of both PC-3 cell invasion and proliferation in vitro. Furthermore, it was demonstrated that a direct correlation exists between the inhibition of IGF-IR gene expression and either up-regulation of IGF binding protein (BP)-3 or down-regulation of matrix metalloproteinase (MMP)-2 expression in androgen-independent PC-3 cells. Moreover, inhibition of IGF-IR gene expression in transfected PC-3 cells leads to an enhanced rate of spontaneous apoptosis. In addition, expression analyses by quantitative RT-PCR on RNA from laser microdissected matched normal prostate and prostate tumour samples revealed that IGF-IR gene expression was up-regulated in nine of 12 prostate cancers, whereas IGFBP-3 gene expression was down-regulated in all 12 prostate carcinomas analysed. These results indicate an important role for IGF-IR and IGFBP-3 in the homeostasis of prostate carcinoma cells and provide a further basis for targeting IGF-IR or IGFBP-3 gene expression in order to improve understanding of the IGF-IR-activated signalling pathways and as a potential treatment for prostate cancer.
The Optimiazation of Knowledgebase for Swimming Pool Temperature Control Systems using Genetic Algorithms (1994)

Automatic control has been for the most part applied to linear systems where ti can be approximately formalized. In case that it is not definitely established the mathematical modelling to control objects, it requires manual control strategies which put under the human rule. In this paper, it constructs an FLC (Fuzzy Logic Controller) in order to turn a hand control into an automatic control in the domain of swimming pool that has been almost absolutely dependant on a skilled worker's experience. Genetic algorithms upgrade the knowledge which is acquired from human expert, using by FLC, so as to maintain knowledge in the very optimal way. It also designs an algorithm that modifies the rule base and the membership function at the same time, and ultimately will show that it can get better result than human controllers.
Systemic Increase in the Ratio between Foxp3+ and IL-17-Producing CD4+ T Cells in Healthy Pregnancy but Not in Preeclampsia (2009)

Preeclampsia is the leading cause of morbidity and mortality in pregnancy. Although the etiology of preeclampsia is still unclear, it is believed to involve rejection of the fetus, possibly due to an imbalance between regulatory (Treg) and effector T cells. To test this, we compared the frequencies of circulating CD4(+) T cells expressing Foxp3, IFN-gamma, IL-10, or IL-17 at the end of the third trimester of healthy and preeclamptic pregnancies. The size of the Treg cell compartment, defined by the frequency of CD4(+)CD25(high), CD4(+)CD127(low)CD25(+), and CD4(+)Foxp3(+) cells was significantly higher in normal compared with preeclamptic pregnancies. CD4(+)CD25(high) and CD4(+)CD127(low)CD25(+) populations in preeclampsia were not significantly different from those in nonpregnant controls, whereas CD4(+)Foxp3(+) cells numbersre slightly lower in preeclampsia. The suppressive activity of ex vivo-sorted CD4(+)CD127(low)CD25(+) Treg cells was not significantly different between the three study groups. The percentage of CD4(+)IL-17-producing T cells decreased significantly in healthy compared with preeclamptic pregnancies and nonpregnant controls, whereas CD4(+)IL-10- and CD4(+)IFN-gamma-producing cells remained unchanged. Consequently, the ratio of Foxp3(+) Treg to IL-17-expressing CD4(+) T cells was significantly increased in healthy but not in preeclamptic pregnancies. Thus, preeclampsia is associated with the absence of normal systemic skewing away from IL-17 production toward Foxp3(+) expression. Finally, preeclamptic women had significantly higher levels of soluble endoglin, an inhibitor of TGF-beta receptor signaling, which may bias toward IL-17 production. These results suggest that homeostasis between regulatory and proinflammatory CD4(+) T cells might be pivotal for the semiallogeneic fetus to be tolerated within the maternal environment.
Complement activation in patients at risk of developing the adult respiratory distress syndrome. (1984)

In this prospective study of 50 patients, 36 of whom developed the adult respiratory distress syndrome (ARDS), early and intense complement activation was demonstrated. These patients were at risk of the ARDS because of multiple injuries, major abdominal surgery, acute pancreatitis, severe burns, or disseminated intravascular coagulation. Abnormal C3 consumption (as measured by the C3d/C3 ratio) and elevated plasma C5a-like activity (as measured by a leukocyte aggregation assay) were associated with, respectively, 84 and 86% of cases of ARDS. Both tests were more sensitive indicators of complement consumption than were assays of total hemolytic complement activity (CH50) or total C3. The C3d/C3 ratio showed a close, inverse correlation with CH50 in 47 healthy subjects, and was increased in 12 control patients after minor surgery. The C5a-like activity was found only in patients at risk of ARDS; it was highly associated with clinical conditions that predispose to the ARDS, but it cannot be considered as a real predictor of ARDS occurrence in these patients. Sequential samples from both sides of the pulmonary circulation showed initial pulmonary clearance followed by the release of C5a-like activity. No simultaneous changes in C3 levels were found, suggesting the possible presence of modulating factors. These observations suggest that other factors (e.g., hypoxia and metabolic cascades) may influence the development of ARDS.
Structural Characterization of Human Recombinant and Bone-derived Bone Sialoprotein (2001)

Human bone sialoprotein (BSP) comprises 15% of the total noncollagenous proteins in bone and is thought to be involved in bone mineralization and remodeling. Recent data suggest a role for BSP in breast cancer and the development of bone metastases. We have produced full-length recombinant BSP in a human cell line and purified the protein from human bone retaining the native structure with proper folding and post-translational modifications. Mass spectrometry of bone-derived BSP revealed an average mass of 49 kDa and for recombinant BSP 57 kDa. The post-translational modifications contribute 30-40%. Carbohydrate analysis revealed 10 different complex-type N-glycans on both proteins and eight different O-glycans on recombinant BSP, four of those were found on bone-derived BSP. We could identify eight threonines modified by O-glycans, leaving the C terminus of the protein free of glycans. The recombinant protein showed similar secondary structures as bone-derived BSP. BSP was visualized in electron microscopy as a globule linked to a thread-like structure. The affinity for hydroxyapatite was higher for bone-derived BSP than for recombinant BSP. Cell adhesion assays showed that the binding of BSP to cells can be reversibly diminished by denaturation.
Phase II Trial of Autologous Tumor Vaccination, Anti-CD3-Activated Vaccine-Primed Lymphocytes, and Interleukin-2 in Stage IV Renal Cell Cancer (2003)

The treatment protocol resulted in durable tumor responses in patients with advanced RCC. The ratio of IFNgamma and IL-10 cytokines released in response to tumor by the VPLN cells was a significant correlate with tumor response.
Brain magnetic resonance imaging with contrast dependent on blood oxygenation. (1990)

Paramagnetic deoxyhemoglobin in venous blood is a naturally occurring contrast agent for magnetic resonance imaging (MRI). By accentuating the effects of this agent through the use of gradient-echo techniques in high fields, we demonstrate in vivo images of brain microvasculature with image contrast reflecting the blood oxygen level. This blood oxygenation level-dependent (BOLD) contrast follows blood oxygen changes induced by anesthetics, by insulin-induced hypoglycemia, and by inhaled gas mixtures that alter metabolic demand or blood flow. The results suggest that BOLD contrast can be used to provide in vivo real-time maps of blood oxygenation in the brain under normal physiological conditions. BOLD contrast adds an additional feature to magnetic resonance imaging and complements other techniques that are attempting to provide positron emission tomography-like measurements related to regional neural activity.
Inhibition of muscle fibrosis and improvement of muscle histopathology in dysferlin knock-out mice treated with halofuginone. (2013)

Absence of, or loss-of-function mutations in the dysferlin gene (dysf) result in dysferlinopathy, characterized by increased muscle inflammation, collagen deposition and deterioration in muscle function. We evaluated halofuginone efficacy in improving muscle histopathology in mice with deleted dysf transmembrane domain. Quadriceps sublumbar and longissimus muscles of 9-month-old dysf-/- mice treated with halofuginone for 4 months exhibited a reduction in centrally-nucleated myofibers, inflammatory infiltrates and collagen content. Late onset of dysferlinopathy makes it ideal for evaluating the efficacy of early treatments on late outcome. The dysf-/- mice were treated with halofuginone for 3 to 4 months starting at 1, 5 or 9 months of age, and quadricep muscle histopathology was evaluated at 12 months. Collagen content and number of centrally nucleated myofibers decreased after early halofuginone treatment, administered when myofibers with central nuclei and inflammatory infiltrates are evident, but there was almost no fibrosis. When administered at the beginning of fibrosis it resulted in a further decrease in the number of centrally-nucleated myofibers with no additional decrease in collagen levels. Cardiac fibrosis was almost completely abolished following early halofuginone treatment. Halofuginone inhibited Smad3 phosphorylation and its translocation to the nucleus and increased the activity of matrix metalloproteinases 9 and 2 responsible for resolution of pre-existing collagen. Macrophage and myofibroblast invasion into the dystrophic muscle at the site of myofibers with central nuclei was inhibited by halofuginone. These results suggest that early halofuginone treatment can prevent the late outcome of dysferlinopathy and can cause resolution of the established fibrosis when administered at later stages.
High-density microprojection array delivery to rat skin of low doses of trivalent inactivated poliovirus vaccine elicits potent neutralising antibody responses (2017)

To secure a polio-free world, the live attenuated oral poliovirus vaccine (OPV) will eventually need to be replaced with inactivated poliovirus vaccines (IPV). However, current IPV delivery is less suitable for campaign use than OPV, and more expensive. We are progressing a microarray patch delivery platform, the Nanopatch, as an easy-to-use device to administer vaccines, including IPV. The Nanopatch contains an ultra-high density array (10,000/cm<sup>2</sup>) of short (~230 μm) microprojections that delivers dry coated vaccine into the skin. Here, we compare the relative immunogenicity of Nanopatch immunisation versus intramuscular injection in rats, using monovalent and trivalent formulations of IPV. Nanopatch delivery elicits faster antibody response kinetics, with high titres of neutralising antibody after just one (IPV2) or two (IPV1 and IPV3) immunisations, while IM injection requires two (IPV2) or three (IPV1 and IPV3) immunisations to induce similar responses. Seroconversion to each poliovirus type was seen in 100% of rats that received ~1/40th of a human dose of IPV delivered by Nanopatch, but not in rats given ~1/8th or ~1/40th dose by IM injection. Ease of administration coupled with dose reduction observed in this study suggests the Nanopatch could facilitate inexpensive IPV vaccination in campaign settings.
Primary amyloidosis associated with a novel heavy‐chain fragment (AH amyloidosis) (1994)

Primary or AL amyloidosis occurs in patients with monoclonal plasma cell-related disorders and is typically associated with the systemic deposition as amyloid fibrils of the light-chain portion of the immunoglobulin molecule. Recently, the discovery that heavy chains could be involved in amyloid formation led to the designation of this type of disease process as AH amyloidosis. We have now identified a second example of heavy chain-associated amyloidosis in a patient (MAD) who had a serum IgG monoclonal gammopathy and Bence Jones proteinuria. In this case, the renal and splenic amyloid deposits consisted solely of the VH-D-encoded portion of the heavy polypeptide chain, in contrast to the first case, where the amyloid contained an immunoglobulin component composed of the entire heavy-chain variable and third constant domains. In this respect, the chemical composition of the amyloid protein MAD differed not only from that of the first reported case of AH amyloidosis but from all other structurally abnormal components found in patients with heavy chain-associated disease. The discovery that certain forms of heavy chains, as well as light chains, can form amyloid provides further information on the chemical basis of amyloidogenicity and the diverse nature of this disease.
Tumores carcinoides bronquiales: estudio retrospectivo de nuestra casuística (1997)

Desde 1970 a 1994 hemos revisado 47 pacientes intervenidos de tumor carcinoide bronquial. La edad media fue de 45 anos. 36 fueron carcinoides tipicos y 11 atipicos, con un 5 y 54% de casos de invasion regional linfatica, respectivamente. La distribucion por estadios en los carcinoides atipicos fue: 45,4% en estadio I, 18,1 % en estadio II y 36,3 % en estadio Illa. En los tipicos el 94,5% correspondio al estadio I y el 5,5% al estadio II. La clinica mas frecuente fueron episodios de neumonia recurrentes en 26 casos y sindrome de irritacion bronquial con hemoptisis y tos seca en 12. En dos pacientes aparecio sintomatologia endocrina paraneoplasica. En ningun caso sindrome carcinoide. En todos los pacientes se realizo endoscopia preoperatoria, objetivandose signos directos de neoplasia en el 85%, siendo la biopsia bronquial positiva para carcinoide en un 56%. La exeresis quirurgica fue el tratamiento aplicado en todos los pacientes, con reseccion completa de la tumoracion y linfadenectomia regional. Se realizaron 10 neumectomias, 5 bilobectomias, 28 lobectomias, 2 broncotomias, y 2 resecciones atipicas. Todos los enfermos han sido revisados posteriormente, siendo la supervivencia a los 5 y 10 anos de un 97 y 93 %, respectivamente para los carcinoides tipicos, y de un 72 y 58% para los atipicos.
The “On–Off” Phenomenon in Parkinson’s Disease (1984)

To determine whether the oscillating clinical response to levodopa in Parkinson's disease (the "on-off" phenomenon) reflects fluctuations in absorption and transport of the drug, we investigated this phenomenon in nine patients with an oscillating motor state. We studied the response to continuous infusion of levodopa and the effects of meals on the plasma levodopa concentrations and on the clinical response during oral and intravenous administration of the drug. Meals reduced peak plasma levodopa concentrations by 29 per cent and delayed absorption by 34 minutes. Bypassing absorption by constant infusion of the drug produced a stable clinical state lasting for 12 hours in all of six patients and for up to 36 hours in some. High-protein meals or oral phenylalanine, leucine, or isoleucine (100 mg per kilogram of body weight) reversed the therapeutic effect of infused levodopa without reducing plasma levodopa concentrations. Glycine and lysine at identical doses had no effect. We conclude that interference with absorption of levodopa by food and by competition between large neutral amino acids and levodopa for transport from plasma to the brain may be partly responsible for the fluctuating clinical response in patients with Parkinson's disease.
Expression of Oligodendroglial and Astrocytic Lineage Markers in Diffuse Gliomas (2006)

The phenotypic heterogeneity of astrocytic and oligodendroglial tumor cells complicates establishing accurate diagnostic criteria, and lineage-specific markers would facilitate diagnosis of glioma subtypes. Based on data from the literature and from expression microarrays, we selected molecules relevant to gliogenesis and glial lineage specificity and then used immunohistochemistry to assess expression of these molecules in 55 diffuse gliomas, including 8 biphasic oligoastrocytomas, 21 oligodendrogliomas (all with 1p/19qloss), 21 astrocytomas, and 5 glioblastomas. For the astrocytic lineage markers (GFAP, YKL-40, and ApoE), GFAP expression was significantly higher in the astrocytic component of oligoastrocytomas compared with the oligodendroglial part; similar patterns were detected for YKL-40 and ApoE, although the differences were not significant. GFAP, YKL-40, and ApoE reliably distinguished grade II-III oligodendrogliomas from grade II-IV astrocytomas (p < 0.0001, p = 0.002, and p < 0.0001, respectively). Among the oligodendroglial lineage markers (Olig2, Sox10, ASCL1, and NKX2-2), ASCL1 and NKX2-2 displayed significantly different immunostaining between oligodendrogliomas and astrocytomas (p = 0.017 and 0.004, respectively), but none clearly differentiated between the 2 glial populations of oligoastrocytomas. In addition to GFAP, therefore, YKL-40, ApoE, ASCL1, and NKX2-2 represent promising tumor cell markers to distinguish oligodendrogliomas from astrocytomas.