gebhart/patrepeval huggingface dataset:
Anticancer Activity of Iridium(III) Complexes Based on a Pyrazole-Appended Quinoline-Based BODIPY (2017)

A pyrazole-appended quinoline-based 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (L1, BODIPY) has been synthesized and used as a ligand for the preparation of iridium(III) complexes [Ir(phpy)<sub>2</sub>(L1)]PF<sub>6</sub> (1; phpy = 2-phenylpyridine) and [(η<sup>5</sup>-C<sub>5</sub>Me<sub>5</sub>)Ir(L1)Cl]PF<sub>6</sub> (2). The ligand L1 and complexes 1 and 2 have been meticulously characterized by elemental analyses and spectral studies (IR, electrospray ionization mass spectrometry, <sup>1</sup>H and <sup>13</sup>C NMR, UV/vis, fluorescence) and their structures explicitly authenticated by single-crystal X-ray analyses. UV/vis, fluorescence, and circular dichroism studies showed that complexes strongly bind with calf-thymus DNA and bovine serum albumin. Molecular docking studies clearly illustrated binding through DNA minor grooves via van der Waals forces and their electrostatic interaction and occurrence in the hydrophobic cavity of protein (subdomain IIA). Cytotoxicity, morphological changes, and apoptosis have been explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst 33342 staining. IC<sub>50</sub> values for complexes (1, 30 μM; 2, 50 μM) at 24 h toward the human cervical cancer cell line (HeLa) are as good as that of cisplatin (21.6 μM) under analogous conditions, and their ability to kill cancer cells lies in the order 1 > 2. Because of the inherent emissive nature of the BODIPY moiety, these are apt for intracellular visualization at low concentration and may find potential applications in cellular imaging and behave as a theranostic agent.
Strategies and Progress Towards the Ideal Orally Active Thrombin Inhibitor (1999)

Thrombin plays a key role in the control of thrombus formation, for which reason its inhibition has become a target for new antithrombotics. Important issues in the profile of the ideal thrombin inhibitor are: potency, selectivity, oral bioavailability, half-life in the circulatory system and safety. Although many potent direct inhibitors of thrombin have been discovered, most of these inhibitors lack sufficient oral bioavailability. This is often associated with the presence of highly basic functionalities such as guanidine or amidine. These basic functionalities in the P1 moiety are preferred by thrombin and are present in the first generation of thrombin inhibitors. Recently, several orally active direct thrombin inhibitors have been disclosed. Most of these inhibitors originate from leads of the first generation. Two major optimization strategies could be identified to further improve these leads: A: maintain the highly basic P1 moiety and compensate its negative effects, and B: reduce the basicity of the P1 moiety and compensate for the decrease in inhibitory activity. The progress made using these strategies is evaluated. In addition, screening large sets of compounds yielded new structures that provide useful starting points for optimization. The optimization strategy used to convert leads from screening into potent orally active thrombin inhibitors is also be evaluated.
Self-rolled-up microtube ring resonators: a review of geometrical and resonant properties (2011)

Strain-induced self-rolled-up microtubes, a category of recently discovered tubular structure with ultrathin walls, have been demonstrated to be unique ring resonators. Recent development in their geometrical and resonant properties are reviewed.
Erythroferrone contributes to recovery from anemia of inflammation (2014)

Erythroferrone (ERFE) is an erythropoiesis-driven regulator of iron homeostasis. ERFE mediates the suppression of the iron-regulatory hormone hepcidin to increase iron absorption and mobilization of iron from stores. We examined the role of ERFE in the recovery from anemia of inflammation (AI) induced by injection of heat-killed Brucella abortus. B abortus-treated wild-type mice developed a moderate anemia and reached nadir hemoglobin 14 days after injection and partially recovered by 28 days. We observed that Erfe expression in the bone marrow and the spleen was greatly increased during anemia and peaked at 14 days after injection, a time course similar to serum erythropoietin. To determine whether ERFE facilitates the recovery from anemia, we analyzed Erfe-deficient mice injected with B abortus. Compared with wild-type mice, Erfe-deficient mice exhibited a more severe anemia, had higher hepcidin levels and consequently lower serum iron concentration on days 14 and 21, and manifested impaired mobilization of iron from stores (liver and spleen). Erfe(-/-) mice eventually compensated by further stimulating erythropoiesis and reticulocyte production. Thus, ERFE contributes to the recovery from AI by suppressing hepcidin and increasing iron availability.
Improving Cache Management Policies Using Dynamic Reuse Distances (2012)

Cache management policies such as replacement, bypass, or shared cache partitioning have been relying on data reuse behavior to predict the future. This paper proposes a new way to use dynamic reuse distances to further improve such policies. A new replacement policy is proposed which prevents replacing a cache line until a certain number of accesses to its cache set, called a Protecting Distance (PD). The policy protects a cache line long enough for it to be reused, but not beyond that to avoid cache pollution. This can be combined with a bypass mechanism that also relies on dynamic reuse analysis to bypass lines with less expected reuse. A miss fetch is bypassed if there are no unprotected lines. A hit rate model based on dynamic reuse history is proposed and the PD that maximizes the hit rate is dynamically computed. The PD is recomputed periodically to track a program's memory access behavior and phases. Next, a new multi-core cache partitioning policy is proposed using the concept of protection. It manages lifetimes of lines from different cores (threads) in such a way that the overall hit rate is maximized. The average per-thread lifetime is reduced by decreasing the thread's PD. The single-core PD-based replacement policy with bypass achieves an average speedup of 4.2% over the DIP policy, while the average speedups over DIP are 1.5% for dynamic RRIP (DRRIP) and 1.6% for sampling dead-block prediction (SDP). The 16-core PD-based partitioning policy improves the average weighted IPC by 5.2%, throughput by 6.4% and fairness by 9.9% over thread-aware DRRIP (TA-DRRIP). The required hardware is evaluated and the overhead is shown to be manageable.
The use of glycerol intercalates in the exchange of CO32−with SO42−, NO3−or Cl−in pyroaurite-type compounds (1991)

Abstract Strongly held carbonates anions in the interlayer region of pyroaurite-type compounds, [ Ml II 1− x M2 III x (OH) 2 ] x + [(CO 3 ) x /2 y H 2 O] x − ( x = 0·15−0·44), can be relatively easily exchanged by other anions such as NO 3 − , Cl − or SO 4 2− dissolved in heated glycerol. Some Fe(III) of pyroaurite is reduced to Fe(II) by the glycerol treatment. If pyroaurite is treated with glycerol in the absence of dissolved anions or with glycerol vapour at 120°C, glycerol becomes intercalated in the interlayers. In all examples the interlayer CO 3 2− is partially or completely lost as CO 2 . In aqueous salt solutions a glycerol intercalated form allows other anions to substitute in the interlayer. Expansion in the c -axis direction following glycerol treatment depends on (1) the method of glycerol treatment, (2) the trivalent metal in the octahedral sheet, and (3) the interlayer anions. Heated glycerol causes a different expansion to that produced by its vapour phase at 120°C. The variation in d (003) follows the series: hydrotalcite vap . &gt; pyroaurite vap. &gt; hydrotalcite liquid &gt; pyroaurite liquid &gt; SO 4 2− -pyroaurite vap . &gt; SO 4 2− -hydrotalcite vap. , where liquid refers to glycerol used at 160–180°C and vap. refers to glycerol vapour at 120°C Carbonate-free, glycerol-intercalated pyroaurite compounds may serve as re-usable anion absorbers. Glycerol intercalates of pyroaurite-type compounds may also be useful to study and identify stacking sequences and interlayer compositions in these minerals.
Experimental Use of Murine Lupus Models (2004)

SummaryMurine models of systemic lupus erythematosus provide fertile research systems for the pathogenesis and therapy of systemic autoimmune disease. Their phenotypes span the broad range of clinical manifestations of human lupus and consist of both spontaneous and experimentally induced disease in both inbred and targeted mutant animals. This chapter contrasts the clinical characteristics of these various models, providing an outline for the use and analysis of these in vivo autoimmune systems.
Conventional treatment of Crohn's disease: Objectives and outcomes (2001)

Despite conventional medical and/or surgical intervention, endoscopic and symptomatic relapse is common among individuals with Crohn's disease (CD). Treatment goals have therefore been refocused to include achieving control of active disease and maintaining remission with agents associated with a minimum of toxic adverse effects. Conventional treatment regimens have been used with varying success in regard to these therapeutic goals. Traditionally, aminosalicylates have been considered effective in inducing a response in some patients with mild-to-moderate CD but have demonstrated little or no long-term benefit in controlled clinical trials. Glucocorticosteroid therapy is associated with higher rates of response in patients with active CD; however, clinical benefits are frequently offset by the common occurrence of corticosteroid-related toxicity. Oral controlled-release budesonide has demonstrated comparable efficacy to prednisolone with less risk for adverse effects, although many questions remain regarding the long-term use of this agent. Response to standard immunosuppressive agents such as azathioprine and 6-mercaptopurine in patients with active disease may require 3 to 6 months from initiation of treatment. These agents are therefore considered most valuable as maintenance therapy, providing consistent long-term benefit in patients with chronic refractory or corticosteroid-dependent disease. Although the incidence of allergic adverse effects is relatively low with azathioprine/6-mercaptopurine, more serious adverse effects, including bone marrow suppression, hepatotoxicity, pancreatitis, and infectious complications, can occur. Limited success in the treatment of perianal disease has been achieved with antibiotics such as metronidazole and the immunosuppressives cyclosporine and azathioprine/6-mercaptopurine. Although broader use of immunosuppressive agents has allowed improvement in the maintenance of remission in patients with CD, long-term safety data with these agents are lacking, concerns about toxicity and the potential risk for neoplasia remain, and attenuation of response with chronic immunosuppressive use can occur. Therefore, innovative therapeutic approaches are needed to meet key treatment goals often not addressed by conventional therapies.
Characterization of an extracellular protease inhibitor of Bacillus brevis HPD31 and nucleotide sequence of the corresponding gene (1992)

A novel proteinaceous protease inhibitor was isolated from the culture supernatant of Bacillus brevis HPD31. The protease inhibitor of B. brevis (designated BbrPI) was produced extracellularly in multiple forms having at least three different molecular weights. One of them, BbrPI-a, was purified to near homogeneity and only showed inhibitory activity toward serine proteases, such as trypsin, chymotrypsin, and subtilisin. BbrPI was presumed to form a trypsin-inhibitor complex in a molar ratio of 1:1. The inhibitor was found to be heat resistant at neutral and acidic pHs. The gene coding for BbrPI was cloned into Escherichia coli, and its nucleotide sequence was determined. The sequence suggested that BbrPI is produced with a signal peptide of 24 amino acid residues. The amino acid sequence of the protein deduced from the DNA sequence contained the amino acid sequences of amino termini of the inhibitors, a, b, and c, and their putative precursor determined chemically. The molecular weight of the precursor was about 33,000, and the molecular weights of inhibitors a, b, and c were about 22,000, 23,500, and 24,000, respectively. It is presumed that the secreted precursor protein, which is probably inactive, is cleaved by protease into several active protease inhibitor molecules. BbrPI shows no significant homology to the protease inhibitors described previously and is unique in not having any cysteine residues in its molecule.
Computer aided modelling of an interdigitated microelectrode array impedance biosensor for the detection of bacteria (2009)

Electrostatic finite element modelling software and an ac equivalent circuit model have been used to investigate an impediometric microelectrode array biosensor for the detection of bacteria. The electrostatic model showed the capacitance of the biosensor to decrease with increasing numbers of bacteria trapped on the sensor's surface in a suspension of relatively high dielectric permittivity. Optimization of the model suggests that reducing the spatial wavelength of the biosensor's electrodes either through a decrease in electrode width or gap will improve the sensor's sensitivity. In addition, the model confirmed that the permittivity of the external medium had a significant effect on detection efficiency. Increased sensitivity in suspensions of lower relative dielectric permittivity was observed. The equivalent circuit model (ECM) was used to analyze the effect of high levels of immobilized bacteria at fixed signal frequencies (100 Hz and 1 MHz). It has been shown that the ECM discussed in this paper is able to successfully model the experimental data for the actual sensor in the low frequency ranges, allowing prediction of the sensor response and analysis of its performance. Overall, the modelling results obtained in the present paper are in general agreement with those from other published data and can be used in the development and optimization of impediometric biosensors for rapid and reliable detection of pathogenic bacteria.
[The significance of intestinal decompression and lavage in the treatment of ileus and peritonitis]. (2007)

The results of treatment of 67 patients, admitted to the hospital clinic for the spread peritonitis and ileus were studied. In 37 of them (main group) the intestinal decompression and hypothermic lavage was performed, in 30 (control group)--intestinal decompression only. The operation character and intensive therapy volume in patients of both groups were similar. In conduction of hypothermic intestinal lavage the accelerated restoration of intestinal peristalsis was noted, as well as the peritonitis and intoxication symptoms elimination. Duration of treatment of patients in stationary in the main and control groups had constituted, accordingly (11.6 +/- 0.73) and (16.8 +/- 1.03) days, lethality--8.1 and 13.8, frequency of complications--10.8 and 30%.
CNTF Protection of Oligodendrocytes Against Natural and Tumor Necrosis Factor-Induced Death (1993)

A proportion of developing oligodendrocytes undergo natural cell death by apoptosis, and mature oligodendrocytes die, either by apoptosis or necrosis, in response to injurious signals such as cytotoxic cytokines and complement. Ciliary neurotrophic factor (CNTF), a trophic factor found in astrocytes in the central nervous system (CNS), promoted the survival and maturation of cultured oligodendrocytes. This trophic factor also protected oligodendrocytes from death induced by tumor necrosis factors (apoptosis) but not against complement (necrosis). These results suggest that CNTF functions in the survival of oligodendrocytes during development and may lead to therapeutic approaches for degenerative diseases of the CNS that involve oligodendrocyte destruction.
Differential killing efficacy of twenty antitumor drugs on proliferating and nonproliferating human tumor cells. (1981)

The lethal effects of a 1-hr treatment with 20 antitumor drugs on proliferating and nonproliferating cultured human colon carcinoma cells (line LoVo) were analyzed quantitatively by the colony-forming technique. Proliferating cells were obtained from exponentially growing cultures, while nonproliferating cells were from cultures in a stationary phase of growth. The 1-hr treatment was intended to approximate serum peak levels after bolus administration. Two agents, cis-platinum and vindesine, were more effective on nonproliferating than on proliferating cells. Mitomycin C, nitrosourea, and dihydroxybisalkylanthracenedione were equally effective on proliferating and nonproliferating cells. The low lethal activity (less than 1 log) of methylglyoxal bis(guanylhydrazone), hycanthone, and vinblastine was similar in proliferating and nonproliferating cells. For most drugs (Adriamycin, rubidazone, bleomycin, maytansine, vincristine, epipodophyllotoxin, fluorouracil, hydroxyurea, methotrexate, and transplantinum) cytotoxicity was significantly less pronounced (or even totally absent) in nonproliferating than in proliferating cells. These results demonstrate the significance of cellular proliferation kinetics in determining sensitivity to antitumor therapy. Nonproliferating human cells have decreased sensitivity to most antitumor agents. An occasional agent may present increased activity to nonproliferating cells; but at best, few agents can be expected to be as effective on nonproliferating as on proliferating cells.
Register integration (2000)

Register integration (or simply integration) is a mechanism for incorporating speculative results directly into a sequential execution using data-dependence relationships. In this paper we use integration to implement squash reuse, the salvaging of instruction results that were needlessly discarded during the course of sequential recovery from a control- or datamis-speculation. To implement integration, we first allow the results of squashed instructions to remain in the physical register file past mis-speculation recovery. As the processor re-traces portions of the squashed path, integration logic examines each instruction as it is being renamed. Using an auxiliary table, this circuit searches the physical register file for the physical register belonging to the corresponding squashed instance of the instruction. If this register is found, integration succeeds and the squashed result is re-validated by a simple update of the rename table. Once integrated, an instruction is complete and may bypass the out-of-order core of the machine entirely. Integration reduces contention for queuing and execution resources, collapses dependent chains of instructions and accelerates the resolution of branches. It achieves this using only rename-table manipulations; no additional values are read from or written to the physical registers. Our preliminary evaluation shows that a minimal integration configuration can provide performance improvements of up to 8% when applied to current-generation micro-architectures and up to 11.5% when applied to more aggressive microarchitectures. Integration also reduces the amount of wasteful speculation in the machine, cutting the number of instructions executed by up to 15% and the number of instructions fetched along mis-speculated paths by as much as 6%.
Biosynthesis and turnover of O-acetyl and N-acetyl groups in the gangliosides of human melanoma cells. (1990)

We and others previously described the melanoma-associated oncofetal glycosphingolipid antigen 9-O-acetyl-GD3, a disialoganglioside O-acetylated at the 9-position of the outer sialic acid residue. We have now developed methods to examine the biosynthesis and turnover of disialogangliosides in cultured melanoma cells and in Golgi-enriched vesicles from these cells. O-Acetylation was selectively expressed on di- and trisialogangliosides, but not on monosialogangliosides, nor on glycoprotein-bound sialic acids. Double-labeling of cells with [3H]acetate and [14C]glucosamine introduced easily detectable labels into each of the components of the ganglioside molecules. Pulse-chase studies of such doubly labeled molecules indicated that the O-acetyl groups turn over faster than the parent molecule. When Golgi-enriched vesicles from these cells were incubated with [acetyl-3H]acetyl-coenzyme A, the major labeled products were disialogangliosides. [Acetyl-3H]O-acetyl groups were found at both the 7- and the 9-positions, indicating that both 7-O-acetyl GD3 and 9-O-acetyl GD3 were synthesized by the action of O-acetyltransferase(s) on endogenous GD3. Analysis of the metabolically labeled molecules confirmed the existence of both 7- and 9-O-acetylated GD3 in the intact cells. Surprisingly, the major 3H-labeled product of the in vitro labeling reaction was not O-acetyl-GD3, but GD3, with the label exclusively in the sialic acid residues. Fragmentation of the labeled sialic acids by enzymatic and chemical methods showed that the 3H-label was exclusively in [3H]N-acetyl groups. Analyses of the double-labeled sialic acids from intact cells also showed that the 3H-label from [3H]acetate was exclusively in the form of [3H]N-acetyl groups, whereas the 14C-label was at the 4-position. Pulse-chase analysis of the 3H/14C ratio showed that the N-acetyl groups of both GD3 and of the monosialoganglioside GM3 were turning over faster than the parent molecules. Selective periodate oxidation showed that both the inner and outer sialic acid residues of GD3 incorporated 3H-label in the in vitro reaction, and showed similar turnover of N-acetylation in the pulse-chase study. Taken together, these results indicate that both the O- and N-acetyl groups of the sialic acid residues of gangliosides turn over faster than the parent molecules. They also demonstrate a novel re-N-acetylation reaction that predicts the existence of de-N-acetyl gangliosides in melanoma cells.
Systemic Human CR2-Targeted Complement Alternative Pathway Inhibitor Ameliorates Mouse Laser-Induced Choroidal Neovascularization (2012)

Systemic administration of TT30 was found to reduce CNV pathology. These data may open new avenues for novel systemic AMD treatment strategies.