gebhart/patrepeval huggingface dataset:
A murine skeletal adaptation that significantly increases cortical bone mechanical properties. Implications for human skeletal fragility. (1993)

Mov13 mice carry a provirus that prevents transcription initiation of the alpha 1(I) collagen gene. Mutant mice homozygous for the null mutation produce no type I collagen and die at mid-gestation, whereas heterozygotes survive to adulthood. Dermal fibroblasts from heterozygous mice produce approximately 50% less type I collagen than normal littermates, and the partial deficiency in collagen production results in a phenotype similar to osteogenesis imperfecta type I (an inherited form of skeletal fragility). In this study, we have identified an adaptation of Mov13 skeletal tissue that significantly improves the bending strength of long bone. The adaptive response occurred over a 2-mo period, during which time a small number of newly proliferated osteogenic cells produced a significant amount of matrix components and thus generated new bone along periosteal surfaces. New bone deposition resulted in a measurable increase in cross-sectional geometry which, in turn, led to a dramatic increase in long bone bending strength.
Signal Transduction of Mechanical Stresses in the Vascular Wall (1998)

The vascular wall is constantly subjected to a variety of mechanical forces in the form of stretch (tensile stress), due to blood pressure, and shear stress, due to blood flow. Alterations in either of these stresses are known to result in vascular remodeling, an adaptation characterized by modified morphology and function of the blood vessels, allowing the vessels to cope with physiological or pathological conditions. The processes involved in vascular remodeling include cellular hypertrophy and hyperplasia, as well as enhanced protein synthesis or extracellular matrix protein reorganization. In vitro studies using vascular cells have attempted to identify the mechanisms behind structural alterations. Possible pathways include ion channels, integrin interaction between cells and the extracellular matrix, activation of various tyrosine kinases (such as c-Src, focal adhesion kinase, and mitogen-activated protein kinases), and autocrine production and release of growth factors. These pathways lie upstream of de novo synthesis of immediate response genes and total protein synthesis, both of which are likely to be involved in the process of vascular remodeling.
Predicting Hematologic Toxicity in Patients Undergoing Radioimmunotherapy with 90Y-Ibritumomab Tiuxetan or 131I-Tositumomab (2010)

The elapsed time since the last chemotherapy can be used to predict hematologic toxicity and customize the current dosing method in radioimmunotherapy.
Synthesis and transformations of stereoisomeric ethyl 2‐isothiocyanato‐1‐cyclopentanecarboxylatesm (2000)

Abstract Ethyl vis ‐ and trans ‐2‐isothiocyanato‐1‐cyclopentanecarboxylates 2 and 7 were prepared by the reaction of the corresponding alicyclic ethyl 2‐amino‐1‐carboxylates and thiophosgene. The cis ‐isothiocyanato compound 2 underwent ring closure with amines in one or two steps, resulting in 3‐substituted‐ cis ‐2‐thioxocyclopenta[ d ]pyrimidin‐4‐ones 3a‐g. The trans isomer 7 failed to cyclize, but gave carboxamide 8a,b or thiourea ester derivatives 9a,b.
Specific Intermolecular Interaction of Carbon Dioxide with Polymers (1996)

Fourier transform IR spectroscopy has been used to investigate the interaction of carbon dioxide with polymers. IR transmission and attenuated total reflectance spectra were obtained for CO2 impregnated into polymer films. It has been shown that the polymers possessing electron-donating functional groups (e.g., carbonyl groups) exhibit specific interactions with CO2, most probably of Lewis acid−base nature. An unusual aspect is the use of the bending mode (ν2) of CO2 to probe polymer−CO2 interactions. The evidence of the interaction is the observation of the splitting of the band corresponding to the CO2 ν2 mode. This splitting indicates that the double degeneracy of the ν2 mode is removed due to the interaction of electron lone pairs of the carbonyl oxygen with the carbon atom of the CO2 molecule. This splitting has not been observed for polymers lacking electron-donating functional groups (e.g., poly(ethylene)). In contrast, the ν3 mode shows little if any sensitivity to this interaction, which is in accordance with the interaction where CO2 molecule acts as an electron acceptor. Finally, the chemical and engineering implications of this type of specific interaction of CO2 with polymers are discussed; perhaps the changes in spectra of CO2 incorporated into polymers might serve as a basis for prediction of the solubility of CO2 in polymers.
Alzheimer’s-specific effects of soluble β-amyloid on protein kinase C-α and -γ degradation in human fibroblasts (1998)

Alzheimer's disease (AD) is a multifactorial disease in which beta-amyloid peptide (betaAP) plays a critical role. We report here that the soluble fraction 1-40 of betaAP differentially degrades protein kinase C-alpha and -gamma (PKCalpha and PKCgamma) isoenzymes in normal (age-matched controls, AC) and AD fibroblasts most likely through proteolytic cascades. Treatment with nanomolar concentrations of betaAP(1-40) induced a 75% decrease in PKCalpha, but not PKCgamma, immunoreactivity in AC fibroblasts. In the AD fibroblasts, a 70% reduction of the PKCgamma, but not PKCalpha, immunoreactivity was observed after betaAP treatment. Preincubation of AC or AD fibroblasts with 50 microM lactacystine, a selective proteasome inhibitor, prevented beta-AP(1-40)-mediated degradation of PKCalpha in the AC cells, and PKCgamma in the AD fibroblasts. The effects of betaAP(1-40) on PKCalpha in AC fibroblasts were prevented by inhibition of protein synthesis and reversed by PKC activation. A 3-hr treatment with 100 nM phorbol 12-myristate 13-acetate restored the PKCalpha signal in treated AC cells but it did not reverse the effects of betaAP(1-40) on PKCgamma in the AD fibroblasts. Pretreatment with the protein synthesis inhibitor, cycloheximide (CHX, 100 microM), inhibited the effects of betaAP(1-40) on PKCalpha and blocked the rescue effect of phorbol 12-myristate 13-acetate in AC fibroblasts but did not modify PKCgamma immunoreactivity in AD cells. These results suggest that betaAP(1-40) differentially affects PKC regulation in AC and AD cells via proteolytic degradation and that PKC activation exerts a protective role via de novo protein synthesis in normal but not AD cells.
Adaptive signal processing in mixed-signal VLSI with anti-Hebbian learning (2006)

We describe analog and mixed-signal primitives for implementing adaptive signal-processing algorithms in VLSI based on anti-Hebbian learning. Both on-chip calibration techniques and the adaptive nature of the algorithms allow us to compensate for the effects of device mismatch. We use our primitives to implement a linear filter trained with the least-mean squares (LMS) algorithm and an adaptive decorrelation network that improves the convergence of LMS. When applied to an adaptive code-division multiple-access (CDMA) despreading application, our system, without the need for power control, achieves more than 100× improvement in the bit-error ratio in the presence of high interference between users. Our 64-tap linear filter uses 0.25mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> of die area and dissipates 200μW in a 0.35μm CMOS process.
Human Body Temperature and Controlled Cold Exposure during Moderate and Severe Experimental Alcohol‐Intoxication (1981)

In an attempt to obtain more conclusive data, especially concerning the condition in many cases of very high alcohol concentration, two groups of healthy volunteers were exposed to controlled cold surroundings in a climate chamber after i.v. infusion of 96% ethyl alcohol, 1-2 1/2 ml per kg bodyweight, supplemented with alcohol perorally; the maximum blood alcohol concentration measured was 57 mmol/l, corresponding to 2.62%. One group was not habituated to drinking; the other group was habituated to heavy drinking, but functioned well socially. During the stay in a neutral environment, the alcohol infusion caused a rapid elevation of skin temperature with a short, but significant delay in temperature elevation in the alcohol-habituated group. After controlled exposure to cold, a rapid fall in surface temperature back to pre-alcoholic infusion values was seen in both groups. During cold exposure, core temperature remained unchanged in both groups. No changes in plasma catecholamines were found. A 12-18% increase in metabolic rate was seen in both groups during cold exposure, probably as an expression of the specific dynamic effect of alcohol. That the observed vasoconstriction was sufficient to prevent an undue fall in core temperature is further supported by the fact that neither shivering, nor non-shivering thermogenesis was activated, as no visible shivering occurred and no rise in plasma catecholamines was seen.
Multi-Scale Interactive Network for Salient Object Detection (2020)

Deep-learning based salient object detection methods achieve great progress. However, the variable scale and unknown category of salient objects are great challenges all the time. These are closely related to the utilization of multi-level and multi-scale features. In this paper, we propose the aggregate interaction modules to integrate the features from adjacent levels, in which less noise is introduced because of only using small up-/down-sampling rates. To obtain more efficient multi-scale features from the integrated features, the self-interaction modules are embedded in each decoder unit. Besides, the class imbalance issue caused by the scale variation weakens the effect of the binary cross entropy loss and results in the spatial inconsistency of the predictions. Therefore, we exploit the consistency-enhanced loss to highlight the fore-/back-ground difference and preserve the intra-class consistency. Experimental results on five benchmark datasets demonstrate that the proposed method without any post-processing performs favorably against 23 state-of-the-art approaches. The source code will be publicly available at https://github.com/lartpang/MINet.
Multi-label learning with incomplete class assignments (2011)

We consider a special type of multi-label learning where class assignments of training examples are incomplete. As an example, an instance whose true class assignment is (c <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> , c <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> , c <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> ) is only assigned to class c <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> when it is used as a training sample. We refer to this problem as multi-label learning with incomplete class assignment. Incompletely labeled data is frequently encountered when the number of classes is very large (hundreds as in MIR Flickr dataset) or when there is a large ambiguity between classes (e.g., jet vs plane). In both cases, it is difficult for users to provide complete class assignments for objects. We propose a ranking based multi-label learning framework that explicitly addresses the challenge of learning from incompletely labeled data by exploiting the group lasso technique to combine the ranking errors. We present a learning algorithm that is empirically shown to be efficient for solving the related optimization problem. Our empirical study shows that the proposed framework is more effective than the state-of-the-art algorithms for multi-label learning in dealing with incompletely labeled data.
Update on Novo Nordisk's clinical trial programme on NovoSeven® (2003)

Recombinant coagulation factor VIIa (rFVIIa; Novoseven, Novo Nordisk A/S, Bagsvaerd, Denmark) is registered in most regions of the world for the treatment of bleeding episodes in haemophilia patients with inhibitors to factor VIII or IX. Since its initial availability, there have been several case stories on the investigational use of rFVIIa as a haemostatic agent in a variety of bleeding patients. Novo Nordisk recognizes the need to establish clinical guidance, and when possible, regulatory approvals for indications with bleeding episodes of various aetiologies. Currently, the safety and efficacy of rFVIIa is being investigated in 11 multinational, phase II trials, involving more than 1500 patients. Most of these trials have been designed to establish the efficacy of rFVIIa as a rescue treatment in episodes of severe life-threatening (upper gastrointestinal bleeding, stem cell transplantation, intra-cerebral haemorrhage and trauma). The remaining focus is on the prophylactic use of rFVIIa to improve haemostasis during surgery (orthotopic liver transplantation and liver resection), with the aim of avoiding or reducing the need for blood transfusions. In addition, Novo Nordisk is also continuing studies in haemophilia patients with inhibitors to increase therapeutic knowledge within this indication. Studies addressing dosages and regimens in subpopulations are presently ongoing.
The Basic Research on Physiological Property of Functionalized Hyaluronan (II): Effect of Sulfated Hyaluronan on Histamine Release from the Mast Cell (2004)

Hyaluronan (HA) is one of polysaccharides in living body that is found widely in connective tissue of the mammals. It has no sulfate group but high molecular weight in comparison with other glycosaminoglycans (GAGs). We synthesized sulfated HA (S-HA) with various degrees of substitution (D.S.) in order to give HA new biological functions, since GAGs with sulfate groups interact with various biocomponents to express some specific biofunctions. Moreover in order to develop biomedical polymers, immunological response against artificial polymer matrices must be evaluated. So we measured histamine release from the mast cell and discussed the effect of S-HA on the immunological response. It was confirmed that they could be used as biomedical materials with immunological safety. And S-HA inhibited the histamine release that was induced by compound 48/80 from the mast cell. The inhibitory effect of S-HA was seemed to be due to such various factors as D.S., molecular weight, substitution site of the sulfate group and the structure of a polysaccharide chain.
RNA Interference-Mediated Gene Silencing of Pleiotrophin Through Polyethylenimine-Complexed Small Interfering RNAs In Vivo Exerts Antitumoral Effects in Glioblastoma Xenografts (2006)

RNA interference (RNAi) is a powerful strategy to inhibit gene expression through specific mRNA degradation mediated by small interfering RNAs (siRNAs). In vivo, however, the application of siRNAs is severely limited by their instability and poor delivery into target cells and target tissues. Glioblastomas are the most frequent and malignant brain tumors with, so far, limited treatment options. To develop novel and more efficacious therapies, advanced targeting strategies against glioblastoma multiforme (GBM)-relevant target genes must be established in vivo. Here we use RNAi-based targeting of the secreted growth factor pleiotrophin (PTN), employing a polyethylenimine (PEI)/siRNA complex strategy. We show that the complexation of chemically unmodified siRNAs with PEI leads to the formation of complexes that condense and completely cover siRNAs as determined by atomic force microscopy (AFM). On the efficient cellular delivery of these PEI/siRNA complexes, the PTN downregulation in U87 glioblastoma cells in vitro results in decreased proliferation and soft agar colony formation. More importantly, in vivo treatment of nude mice through systemic application (subcutaneous or intraperitoneal) of PEI-complexed PTN siRNAs leads to the delivery of intact siRNAs into subcutaneous tumor xenografts and a significant inhibition of tumor growth without a measurable induction of siRNA-mediated immunostimulation. Likewise, in a clinically more relevant orthotopic mouse glioblastoma model with U87 cells growing intracranially, the injection of PEI-complexed PTN siRNAs into the CNS exerts antitumoral effects. In conclusion, we present the PEI complexation of siRNAs as a universally applicable platform for RNAi in vitro and in vivo and establish, also in a complex and relevant orthotopic tumor model, the potential of PEI/siRNA-mediated PTN gene targeting as a novel therapeutic option in GBM.
Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice (2006)

The farnesoid X receptor (FXR) controls the synthesis and transport of bile acids (BAs). Mice lacking expression of FXR, designated Fxr-null, have elevated levels of serum and hepatic BAs and an increase in BA pool size. Surprisingly, at 12 months of age, male and female Fxr-null mice had a high incidence of degenerative hepatic lesions, altered cell foci and liver tumors including hepatocellular adenoma, carcinoma and hepatocholangiocellular carcinoma, the latter of which is rarely observed in mice. At 3 months, Fxr-null mice had increased expression of the proinflammatory cytokine IL-1beta mRNA and elevated beta-catenin and its target gene c-myc. They also had increased cell proliferation as revealed by increased PCNA mRNA and BrdU incorporation. These studies reveal a potential role for FXR and BAs in hepatocarcinogenesis.
The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice (2015)

LG101506 was originally synthesized to overcome some of the undesirable side effects of rexinoids. We compared the anticarcinogenic action of LG101506 and LG100268 and for the first time showed that both drugs are useful for prevention of lung cancer in A/J mice. These molecules markedly reduced tumor number, tumor size, and total tumor burden, when chronically administered to A/J mice that had been initiated with the mutagenic carcinogen, vinyl carbamate. Moreover, LG100268 synergized with the histone deacetylase inhibitor, vorinostat, for prevention of experimental lung cancer and enhanced the effect of carboplatin/paclitaxel for treatment of experimental lung cancer. Both rexinoids diminished the percentage of high-grade, highly malignant adenocarcinomas found at autopsy. In cell culture studies, the rexinoids exhibited potent anti-inflammatory properties at nanoMolar concentrations. These drugs suppressed the ability of lipopolysaccharide to stimulate the synthesis and secretion of nitric oxide and inflammatory cytokines and chemokines, such as IL6, IL1β, CXCL2, and CSF3, in macrophage-like RAW264.7 cells. The present results suggest that LG100268, LG101506, or a related rexinoid may have useful clinical applications in the field of oncology.
Overexpression of Aurora-A Contributes to Malignant Development of Human Esophageal Squamous Cell Carcinoma (2004)

The findings presented in this report show that Aurora-A expression is elevated in human esophageal squamous cell carcinoma and is possibly associated with tumor invasion, indicating that overexpression of Aurora-A may contribute to ESCC occurrence and progression.
Assembly, processing, and infectivity of human immunodeficiency virus type 1 gag mutants (1993)

We studied the effects of gag mutations on human immunodeficiency virus type 1 (HIV-1) assembly, processing, and infectivity by using a replication-defective HIV expression system. HIV mutants were screened for infectivity by transduction of a selectable marker and were examined for assembly by monitoring particle release from transfected cells. Gag protein processing and reverse transcriptase activities of mutant particles were also assayed. Surprisingly, most Gag protein mutants were assembled and processed. The two exceptions to this rule were a myristylation-minus mutant, and one gag matrix domain mutant which expressed proteins that were trapped intracellularly. Interestingly, a mutant with a 56-amino-acid deletion within the HIV gag capsid domain still could assemble and process virus particles, exhibited a wild-type retrovirus particle density, and had wild-type reverse transcriptase activity. Indeed, although most HIV-1 gag mutants were noninfectious or poorly infectious, they produced apparently normal particles which possessed significant reverse transcriptase activities. These results strongly support the notion that the HIV-1 Gag proteins are functionally involved in post-assembly, postprocessing stages of virus infectivity.
Comparison of auranofin, methotreaxate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial (1992)

Both combination therapy and MTX alone were superior to therapy with AZA alone for active RA but were not statistically different in their effect on outcome assessment.
The GAATTC triplet repeat expanded in Friedreich's ataxia impedes transcription elongation by T7 RNA polymerase in a length and supercoil dependent manner (2000)

Large expansions of the trinucleotide repeat GAA*TTC within the first intron of the X25 (frataxin) gene cause Friedreich's ataxia, the most common inherited ataxia. Expansion leads to reduced levels of frataxin mRNA in affected individuals. Here we show that GAA*TTC tracts, in the absence of any other frataxin gene sequences, can reduce the amount of GAA-containing transcript produced in a defined in vitro transcription system. This effect is due to an impediment to elongation that forms in the GAA*TTC tract during transcription, a phenomenon that is exacerbated by both superhelical stress and increased tract length. On supercoiled templates the major truncations of the GAA-containing transcripts occur in the distal (3') end of the GAA repeat. To account for these observations we present a model in which an RNA polymerase advancing within a long GAA*TTC tract initiates the transient formation of an R*R*Y intramolecular DNA triplex. The non-template (GAA) strand folds back creating a loop in the template strand, and the polymerase is paused at the distal triplex-duplex junction.
Partial Purification and Characterization of Hydroxycinnamoyl-Coenzyme A:Tyramine Hydroxycinnamoyltransferase from Cell Suspension Cultures of Solanum tuberosum (1995)

A pathogen elicitor-inducible soluble acyltransferase (tyramine hydroxycinnamoyltransferase [THT], EC 2.3.1), which catalyzes the transfer of hydroxycinnamic acids from hydroxycinnamoyl-coenzyme A (CoA) esters to tyramine in the formation of N-hydroxycinnamoyltyramine, was partially purified with a 380-fold enrichment and a 6% recovery from cell-suspension cultures of potato (Solanum tuberosum L. cv Datura). The enzyme showed specific activities of 33 mkat (kg protein)-1 (formation of feruloyltyramine). The apparent native Mr was found to be approximately 49,000. Highest activity was at pH 6.8 in K-phosphate. The isoelectric point of the enzyme was approximately pH5.2. The apparent energy of activation was calculated to be 96 kJ mol-1. The enzyme activity was stimulated more than 5-fold by 10 mM Ca2+ or Mg2+. The apparent Km values were 36 [mu]M for feruloyl-CoA and 85 and 140 [mu]M for cinnamoyl- and 4-coumaroyl-CoA, respectively. The Km value for tyramine in the presence of feruloyl-CoA was 22 [mu]M. In the presence of 4-coumaroyl-CoA, however, the Km for tyramine increased to about 230 [mu]M. The mode of action was an iso-ordered bi bi mechanism in which A, B, P, and Q equal hydroxycinnamoyl-CoA, tyramine, N-hydroxycinnamoyltyramine, and CoA, respectively. Thus, the reaction occurred in a ternary complex of the enzyme and substrates. The equilibrium constant of the reaction was determined to be 1.3 x 104. This gave a [delta]G[deg][prime] eq value of -23.5 kJ mol-1.
Parkinson's disease: clinical features and diagnosis (2008)

A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.