gebhart/patrepeval huggingface dataset:
無限趨近：論柯慈《麥可•K的生命與時代》中的遁逃路線 (2012)

This thesis aims to investigate the possible way out of the state of exception in JM Coetzee’s Life & Times of Michael K. From an Agambenian perspective on bio- and theo-political dimensions, I attempt to analyze how the protagonist brings about the messianic redemption via his radical passivity. I rethink the political significations in Michael K by deeming him as a weak Messiah. The thesis begins with a description of Michael K’s escape. As the medical officer at Kenilworth describes, the garden Michael K hides in is nowhere and everywhere. This peculiar escape has parallels to the concept of “the line of the flight” by Deleuze and Guattari. The Italian philosopher Giorgio Agamben appropriates it as “a flight with no elsewhere.” Following the movement of his thought from Homo Sacer, through Potentialities to The Time That Remains, I attempt to argue Agamben implicates this line of flight full of revolutionary potential could be a response to the present political situation. And I apply it to analyze the text. This strategic reading subverts the early biased and reductionistic phrasings of Michael K. Yet this alternative approach also goes against the mainstream that focuses on the political futurity. I employ Agamben’s interpretation of the Pauline idea of “the time of now,” as well as “the chips of messianic time” in Walter Benjamin. I argue Michael K as a great escape artist does not wait for the coming of the Messiah. Instead, he participates in the political interventions, in which the internal power structures are transformed. 

Chapter One examines the intertextuality between the fiction and the theory. Agamben’s topological rendering of the state of exception constructs the solid ground for my proposition: Michael K’s line of flight is on a biopolitical Mobius strip, which involves the complexity of the relation of law to life. In Chapter Two, I introduce the mathematical concept, asymptote. In light of its principle, I argue Michael K does not simply dwell on his pure potentiality (potentiality not to-be), but rather, he moves in the mode of always almosting (potentiality always not yet to-be). Chapter Three discusses the concept of inoperativity, or desœuvrement. I observe how Michael K lives “as not” (Hōs mē) Michael K. By making small adjustments, he reverses the state of exception to the messianic horizon. Discussion also centers around Michael K’s radical passivity, by means of which the law is fulfilled in its suspension. The final chapter reiterates the necessity to undo the set categories of representation. Agamben’s assertion to destabilize the arbitrary linkage echoes Jacques Derrida’s ethical concern in his “being-with” politics.
Statin Therapy, LDL Cholesterol, C-Reactive Protein, and Coronary Artery Disease (2005)

For patients with coronary artery disease, the reduced rate of progression of atherosclerosis associated with intensive statin treatment, as compared with moderate statin treatment, is significantly related to greater reductions in the levels of both atherogenic lipoproteins and CRP.
Enzymatic Depletion of Tumor Hyaluronan Induces Antitumor Responses in Preclinical Animal Models (2010)

Hyaluronan (HA) is a glycosaminoglycan polymer that often accumulates in malignancy. Megadalton complexes of HA with proteoglycans create a hydrated connective tissue matrix, which may play an important role in tumor stroma formation. Through its colloid osmotic effects, HA complexes contribute to tumor interstitial fluid pressure, limiting the effect of therapeutic molecules on malignant cells. The therapeutic potential of enzymatic remodeling of the tumor microenvironment through HA depletion was initially investigated using a recombinant human HA-degrading enzyme, rHuPH20, which removed HA-dependent tumor cell extracellular matrices in vitro. However, rHuPH20 showed a short serum half-life (t(1/2) < 3 minutes), making depletion of tumor HA in vivo impractical. A pegylated variant of rHuPH20, PEGPH20, was therefore evaluated. Pegylation improved serum half-life (t(1/2) = 10.3 hours), making it feasible to probe the effects of sustained HA depletion on tumor physiology. In high-HA prostate PC3 tumors, i.v. administration of PEGPH20 depleted tumor HA, decreased tumor interstitial fluid pressure by 84%, decreased water content by 7%, decompressed tumor vessels, and increased tumor vascular area >3-fold. Following repeat PEGPH20 administration, tumor growth was significantly inhibited (tumor growth inhibition, 70%). Furthermore, PEGPH20 enhanced both docetaxel and liposomal doxorubicin activity in PC3 tumors (P < 0.05) but did not significantly improve the activity of docetaxel in low-HA prostate DU145 tumors. The ability of PEGPH20 to enhance chemotherapy efficacy is likely due to increased drug perfusion combined with other tumor structural changes. These results support enzymatic remodeling of the tumor stroma with PEGPH20 to treat tumors characterized by the accumulation of HA.
Chelating DTPA amphiphiles: ion-tunable self-assembly structures and gadolinium complexes (2012)

A series of chelating amphiphiles and their gadolinium (Gd(III)) metal complexes have been synthesized and studied with respect to their neat and lyotropic liquid crystalline phase behavior. These amphiphiles have the ability to form ion-tunable self-assembly nanostructures and their associated Gd(III) complexes have potential as magnetic resonance imaging (MRI) contrast enhancement agents. The amphiphiles are composed of diethylenetriaminepentaacetic acid (DTPA) chelates conjugated to one or two oleyl chain(s) (DTPA-MO and DTPA-BO), or isoprenoid-type chain(s) of phytanyl (DTPA-MP and DTPA-BP). The thermal phase behavior of the neat amphiphiles was examined by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and cross polarizing optical microscopy (POM). Self-assembly of neat amphiphiles and their associated Gd complexes, as well as their lyotropic phase behavior in water and sodium acetate solutions of different ionic strengths, were examined by POM and small and wide angle X-ray scattering (SWAXS). All neat amphiphiles exhibited lamellar structures. The non-complexed amphiphiles showed a variety of lyotropic phases depending on the number and nature of the hydrophobic chain in addition to the ionic state of the hydration. Upon hydration with increased Na-acetate concentration and the subtle changes in the effective headgroup size, the interfacial curvature of the amphiphile increased, altering the lyotropic liquid crystalline structures towards higher order mesophases such as the gyroid (Ia3d) bicontinuous cubic phase. The chelation of Gd with the DTPA amphiphiles resulted in lamellar crystalline structures for all the neat amphiphiles. Upon hydration with water, the Gd-complexed mono-conjugates formed micellar or vesicular self-assemblies, whilst the bis-conjugates transformed only partially into lyotropic liquid crystalline mesophases.
Manipulating the Stereoselectivity of Limonene Epoxide Hydrolase by Directed Evolution Based on Iterative Saturation Mutagenesis (2010)

Limonene epoxide hydrolase from Rhodococcus erythropolis DCL 14 (LEH) is known to be an exceptional epoxide hydrolase (EH) because it has an unusual secondary structure and catalyzes the hydrolysis of epoxides by a rare one-step mechanism in contrast to the usual two-step sequence. From a synthetic organic viewpoint it is unfortunate that LEH shows acceptable stereoselectivity essentially only in the hydrolysis of the natural substrate limonene epoxide, which means that this EH cannot be exploited as a catalyst in asymmetric transformations of other substrates. In the present study, directed evolution using iterative saturation mutagenesis (ISM) has been tested as a means to engineer LEH mutants showing broad substrate scope with high stereoselectivity. By grouping individual residues aligning the binding pocket correctly into randomization sites and performing saturation mutagenesis iteratively using a reduced amino acid alphabet, mutants were obtained which catalyze the desymmetrization of cyclopentene−oxide with stereoselective formation of either the (R,R)- or the (S,S)-diol on an optional basis. The mutants prove to be excellent catalysts for the desymmetrization of other meso-epoxides and for the hydrolytic kinetic resolution of racemic substrates, without performing new mutagenesis experiments. Since less than 5000 tranformants had to be screened for achieving these results, this study contributes to the generalization of ISM as a fast and reliable method for protein engineering. In order to explain some of the stereoselective consequences of the observed mutations, a simple model based on molecular dynamics simulations has been proposed.
Estimation of dietary flavonoid intake and major food sources of Korean adults (2015)

Epidemiological studies have suggested that flavonoids exhibit preventive effects on degenerative diseases. However, lack of sufficient data on flavonoid intake has limited evaluating the proposed effects in populations. Therefore, we aimed to estimate the total and individual flavonoid intakes among Korean adults and determine the major dietary sources of these flavonoids. We constructed a flavonoid database of common Korean foods, based on the food list reported in the 24-h recall of the Korea National Health and Nutrition Examination Survey (KNHANES) 2007-2012, using data from the Korea Functional Food Composition Table, US Department of Agriculture flavonoid database, Phenol-Explorer database and other analytical studies. This database, which covers 49 % of food items and 76 % of food intake, was linked with the 24-h recall data of 33 581 subjects aged ≥19 years in the KNHANES 2007-2012. The mean daily intake of total flavonoids in Korean adults was 318·0 mg/d, from proanthocyanidins (22·3%), flavonols (20·3%), isoflavones (18·1%), flavan-3-ols (16·2%), anthocyanidins (11·6%), flavanones (11·3%) and flavones (0·3%). The major contributing food groups to the flavonoid intake were fruits (54·4%), vegetables (20·5%), legumes and legume products (16·2%) and beverages and alcohols (3·1%), and the major contributing food items were apples (21·9%), mandarins (12·5%), tofu (11·5%), onions (9·6%) and grapes (9·0%). In the regression analysis, the consumption of legumes and legume products, vegetables and fruits predicted total flavonoid intake the most. The findings of this study could facilitate further investigation on the health benefits of flavonoids and provide the basic information for establishing recommended flavonoid intakes for Koreans.
Regeneration of the Infarcted Heart With Stem Cells Derived by Nuclear Transplantation (2004)

Nuclear transfer techniques have been proposed as a strategy for generating an unlimited supply of rejuvenated and histocompatible stem cells for the treatment of cardiac diseases. For this purpose, c-kit-positive fetal liver stem cells obtained from cloned embryos were injected in the border zone of infarcted mice to induce tissue reconstitution. Cloned embryos were derived from somatic cell fusion between nuclei of cultured LacZ-positive fibroblasts and enucleated oocytes of a different mouse strain. We report that regenerating myocardium replaced 38% of the scar at 1 month. The rebuilt tissue expressed LacZ and was composed of myocytes and vessels connected with the coronary circulation. Myocytes were functionally competent and expressed contractile proteins, desmin, connexin43, and N-cadherin. These structural characteristics indicated that the new myocytes were electrically and mechanically coupled. Similarly, the formed coronary arterioles and capillary structures contained blood and contributed, therefore, to tissue oxygenation. Cardiac replacement resulted in an improvement of ventricular hemodynamics and in a reduction of diastolic wall stress. These beneficial effects were obtained by stem cell transdifferentiation and commitment to the cardiac cell lineages. Myocardial growth was independent from fusion of the injected stem cells with preexisting partner cells. In conclusion, c-kit-positive stem cells derived by nuclear transfer cloning restore infarcted myocardium. Although problems currently plague nuclear transplantation, including the potential for epigenetic and imprinting abnormalities, stem cells derived from cloned embryos are sufficiently normal to repair damaged tissue in vivo. Importantly, the magnitude of myocardial regeneration obtained in this study is significantly superior to that achieved with adult bone marrow cells.
The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report (1993)

Animal research suggests that moderate therapeutic hypothermia may improve outcome after a severe head injury, but its efficacy has not been established in humans. The authors randomly assigned 40 consecutively treated patients with a severe closed head injury (Glasgow Coma Scale score 3 to 7) to either a hypothermia or a normothermia group. Using cooling blankets and cold saline gastric lavage, patients in the hypothermia group were cooled to 32 degrees to 33 degrees C (brain temperature) within a mean of 10 hours after injury, maintained at that temperature for 24 hours, and rewarmed to 37 degrees to 38 degrees C over 12 hours. Patients in the normothermia group were maintained at 37 degrees to 38 degrees C during this time. Deep-brain temperatures were monitored directly and used for all temperature determinations. Intracranial pressure (ICP), cerebral blood flow (CBF), and cerebral metabolic rate for oxygen (CMRO2) were measured serially for all patients. Hypothermia significantly reduced ICP (40%) and CBF (26%) during the cooling period, and neither parameter showed a significant rebound increase after patients were rewarmed. Compared to the normothermia group, the mean CMRO2 in the hypothermia group was lower during cooling and higher 5 days after injury. Three months after injury, 12 of the 20 patients in the hypothermia group had moderate, mild, or no disabilities; eight of the 20 patients in the normothermia group had improved to the same degree. Both groups had a similar incidence of systemic complications, including cardiac arrhythmias, coagulopathies, and pulmonary complications. It is concluded that therapeutic moderate hypothermia is safe and has sustained favorable effects on acute derangements of cerebral physiology and metabolism caused by severe closed head injury. The trend toward better outcome with hypothermia may indicate that its beneficial physiological and metabolic effects limit secondary brain injury.
Coexpression of the KCNA3BGene Product with Kv1.5 Leads to a Novel A-type Potassium Channel (1998)

Shaker-related voltage-gated potassium (Kv) channels may be heterooligomers consisting of membrane-integral alpha-subunits associated with auxiliary cytoplasmic beta-subunits. In this study we have cloned the human Kvbeta3.1 subunit and the corresponding KCNA3B gene. Identification of sequence-tagged sites in the gene mapped KCNA3B to band p13.1 of human chromosome 17. Comparison of the KCNA1B, KCNA2B, and KCNA3B gene structures showed that the three Kvbeta genes have very disparate lengths varying from >/=350 kb (KCNA1B) to approximately 7 kb (KCNA3B). Yet, the exon patterns of the three genes, which code for the seven known mammalian Kvbeta subunits, are very similar. The Kvbeta1 and Kvbeta2 splice variants are generated by alternative use of 5'-exons. Mouse Kvbeta4, a potential splice variant of Kvbeta3, is a read-through product where the open reading frame starts within the sequence intervening between Kvbeta3 exons 7 and 8. The human KCNA3B sequence does not contain a mouse Kvbeta4-like open reading frame. Human Kvbeta3 mRNA is specifically expressed in the brain, where it is predominantly detected in the cerebellum. The heterologous coexpression of human Kv1.5 and Kvbeta3.1 subunits in Chinese hamster ovary cells yielded a novel Kv channel mediating very fast inactivating (A-type) outward currents upon depolarization. Thus, the expression of Kvbeta3.1 subunits potentially extends the possibilities to express diverse A-type Kv channels in the human brain.
Interleukin-1β and the treatment of auto-inflammatory diseases (ML12) (2010)

Chronic inflammatory diseases fall into two categories: either “autoimmune” or “auto-inflammatory”. Although nearly all autoimmune diseases have an inflammatory component as in rheumatoid arthritis, in autoimmune diseases, the auto-reactive T-cell is dysfunctional. The cytokines to block are TNFα, IFNγ and similar Th1 cytokines as well as IL-12/23 and IL-17. The “Auto-inflammatory Diseases” encompass several local and systemic diseases due to monocyte dysfunction, each responsive to blocking interleukin-beta (IL-1β). “Auto-inflammatory Diseases” include type 2 diabetes and gout and new data suggest that smoldering myeloma and heart failure are also auto-inflammatory diseases. The best example is Familial Mediterranean Fever since the manifestations of this disease include fever, inflamed serosal and synovial tissues, biochemical markers of systemic inflammation and hematological responses of leukocytosis. The co-cytokine in auto-inflammatory diseases is IL-6 as this cytokine drive CRP, thrombocytosis and polyclonal B-cell activation. Some of the syndromes have mutations in the protein “cryopyrin” and are called “cryopyrinopathies”; the same syndromes are also termed “Cryopyrin Associated Periodic Syndromes” (CAPS); however, identical biochemical, hematological and clinical disease is also observed in patients without mutations. What is the common link? The common link is dysregulation of the tight control over the processing and secretion of IL-1β from the activated monocyte. The processing and secretion of IL-1β is a function of the IL-1β/caspase-1 “inflammasome”, a complex of intracellular proteins that results in the secretion of IL-1β. The auto-inflammatory diseases are examples in cytokine biology that reveal a causative the role of a specifc cytokine in a disease process.
Pharmacokinetic interactions between HIV‐protease inhibitors in rats (1999)

The interactions of four HIV-protease inhibitors, ritonavir (RIT), saquinavir (SAQ), indinavir (IND) and nelfinavir (NEL), were examined by in vitro metabolic studies using rat liver microsomal fractions. The substrate concentrations employed were 0.75∼12 μM, and the inhibitor concentrations were 2.5∼60 μM. The metabolic clearance rates of SAQ, NEL and IND as determined by Vmax/Km were 170.9±10.9, 126.0±4.4 and 73.0±2.0 μL/min/mg protein, respectively. RIT was a potent inhibitor of the other three protease inhibitors, and the inhibition constants (Ki) were 1.64 μM for SAQ, 0.95 μM for IND and 1.01 μM for NEL. NEL was the second strongest inhibitor with a Ki for NEL inhibition of IND metabolism of 2.14 μM. IND was the third strongest inhibitor with Kis of 2.76 μM for inhibition of NEL and 3.55 μM for inhibition of SAQ. As SAQ has the highest metabolic clearance rate, the Ki for the SAQ inhibition of IND metabolism was high, 9.50 μM. Based on these in vitro results, drug interactions between NEL and IND or RIT were studied after oral administration to rats where the dose of each drug was 20 mg/kg. The Cmax and AUC of NEL were increased 3.6- and 8.5-fold by the co-administration with RIT. However, in contrast to co-administration of NEL and RIT, the effect of IND on the pharmacokinetics of NEL was negligible and the t1/2 of NEL was not significantly increased by IND. Therefore, the combination of NEL and IND is recommended as a combination therapy for AIDS patients. Copyright © 1999 John Wiley & Sons, Ltd.
Antigen-Specific Therapy of Murine Lupus Nephritis Using Nucleosomal Peptides: Tolerance Spreading Impairs Pathogenic Function of Autoimmune T and B Cells (1999)

In the (SWR x NZB)F1 mouse model of lupus, we previously localized the critical autoepitopes for nephritogenic autoantibody-inducing Th cells in the core histones of nucleosomes at aa positions 10-33 of H2B and 16-39 and 71-94 of H4. A brief therapy with the peptides administered i.v. to 3-mo-old prenephritic (SWR x NZB)F1 mice that were already producing pathogenic autoantibodies markedly delayed the onset of severe lupus nephritis. Strikingly, chronic therapy with the peptides injected into 18-mo-old (SWR x NZB)F1 mice with established glomerulonephritis prolonged survival and even halted the progression of renal disease. Remarkably, tolerization with any one of the nucleosomal peptides impaired autoimmune T cell help, inhibiting the production of multiple pathogenic autoantibodies. However, cytokine production or proliferative responses to the peptides were not grossly changed by the therapy. Moreover, suppressor T cells were not detected in the treated mice. Most interestingly, the best therapeutic effect was obtained with nucleosomal peptide H416-39, which had a tolerogenic effect not only on autoimmune Th cells, but autoimmune B cells as well, because this peptide contained both T and B cell autoepitopes. These studies show that the pathogenic T and B cells of lupus, despite intrinsic defects in activation thresholds, are still susceptible to autoantigen-specific tolerogens.
Polyvinyl Alcohol Membrane Permeability Characteristics of 5-Fluorouracil (1988)

5-fluorouracil is a useful new treatment modality in the difficult glaucoma filtering patient. However, its use is attended by a high incidence of complications principally involving the corneal epithelium. The pharmacokinetics of this drug suggest that a sustained release delivery system might avoid many of these problems if it could produce therapeutic levels in the subconjunctival space while avoiding toxic levels in the cornea and other ocular structures. In vitro studies of release rates for polyvinyl alcohol membranes suggest that this material could form the basis of such a delivery system.
Technique for Primate Heterotopic Cardiac Xenotransplantation (1985)

Heterotopic cardiac transplantation in the primate is a valuable method for the evaluation of immuno-suppressive regimens. This report describes our technique for heterotopic transplantation of cardiac grafts into the neck of baboons. Preliminary experience with cross-genus cardiac transplantation in the nonhuman primate is discussed.
The leucine metabolite 3‐hydroxy‐3‐methylbutyrate (HMB) modifies protein turnover in muscles of laboratory rats and domestic chickensin vitro (2000)

This study was conducted to assess the in vitro effects of leucine and 3‐hydroxy‐3‐methylbutyrate (HMB) on protein synthesis and degradation in isolated rat and chick muscles. Isolated muscles — extensor digitorum longus (EDL) and soleus (S) in rats and EDL and tibialis anterior (TA) in chicks — were taken out intact and incubated in Krebs—Henseleit buffer with [ 14 C]phenylalanine. Protein synthesis was then determined by measuring [ 14 C]phenylalanine incorporation into protein and protein breakdown was estimated by net release of tyrosine from muscle proteins. In all muscles investigated leucine stimulated protein synthesis (average 20%; p &lt; 0.05 versus control) but only slightly reduced proteolysis (average 8%, NS). In contrast, HMB had no significant effect on protein synthesis but consistently decreased protein degradation in the range from −29% (p &lt; 0.01 versus control) in rat extensor digitorus longus to −5% (NS) in rat soleus muscles. HMB appeared to suppress protein degradation more in white muscle fibres than in red muscle fibres (at least in the rat). These data support observations in humans indicating that HMB decreases muscle proteolysis. It is suggested that metabolism of leucine to HMB could be responsible for the reported suppressive effects of leucine on protein breakdown.