gebhart/patrepeval huggingface dataset:
Covalent Organic Frameworks with High Charge Carrier Mobility (2011)

Two types (imine and boronate) of covalent organic frameworks (COFs) having a porphyrin unit have been synthesized. The two highly crystalline porphyrin COFs (COF-366 and COF-66) display excellent chemical and thermal stability and are permanently porous. Two-dimensional extended layered structures of the two COFs demonstrate very high charge carrier mobility values (8.1 cm2 V−1 s−1).
Pitch ranking with nonsimultaneous dual-electrode electrical stimulation of the cochlea (1994)

It has already been established that simultaneous activation of two intracochlear electrodes can evoke a pitch percept which is intermediate to that of either electrode when activated by itself. In the present study, this result has been extended to nonsimultaneous activation of nearby electrodes. Pitch perception was investigated for electric stimuli presented on one or two intracochlear electrode pairs. All stimuli were pulse trains of period 4 ms. In the dual-electrode stimuli, each period contained two biphasic pulses, separated by 0.4 ms, with one pulse for each electrode pair. These stimuli were compared with loudness-balanced single-electrode stimuli, having one pulse per period, generated on the same electrode pairs. Their pitches were ranked in a two-alternative forced-choice procedure by five experienced users of the 22-electrode implant manufactured by Cochlear Pty Limited. The studies showed that the pitch of a dual-electrode stimulus was intermediate to, and moved monotonically between, those of the component electrode pairs as the relative currents were altered in an orderly fashion. Intermediate pitches were achieved in all subjects at a range of cochlear positions, for electrode separations generally up to 3 mm. In half the cases a significantly different intermediate pitch could be created between adjacent electrodes. Further studies are necessary to establish whether intermediate pitches can be obtained at larger separations, as for simultaneous stimulation, and how they are affected by other factors such as the time between pulses or the spatial extent of the stimulation.
Saccharomyces cerevisiae HOC1, a Suppressor of pkc1, Encodes a Putative Glycosyltransferase (1997)

The Saccharomyces cerevisiae gene PKC1 encodes a protein kinase C isozyme that regulates cell wall synthesis. Here we describe the characterization of HOC1, a gene identified by its ability to suppress the cell lysis phenotype of pkc1-371 cells. The HOC1 gene (Homologous to OCH1) is predicted to encode a type II integral membrane protein that strongly resembles Och 1p, an alpha-1,6-mannosyltransferase. Immunofluorescence studies localized Hoc1p to the Golgi apparatus. While overexpression of HOC1 rescued the pkc1-371 temperature-sensitive cell lysis phenotype, disruption of HOC1 lowered the restrictive temperature of the pkc1-371 allele. Disruption of HOC1 also resulted in hypersensitivity to Calcofluor White and hygromycin B, phenotypes characteristic of defects in cell wall integrity and protein glycosylation, respectively. The function of HOC1 appears to be distinct from that of OCH1. Taken together, these results suggest that HOC1 encodes a Golgi-localized putative mannosyltransferase required for the proper construction of the cell wall.
Optical Limiting and Switching of Ultrashort Pulses in Nonlinear Photonic Band Gap Materials (1994)

We numerically investigate nonlinear propagation of ultrashort pulses in a one-dimensional photonic band gap structure. We find that, near the band edge, nonlinear effects cause a dynamical shift in the location of the band gap. We demonstrate that this nonlinear mechanism can induce intensity-dependent pulse transmission and reflections. In addition, pulse reshaping and pulse generation is observed. This phenomenon has important new applications in both optical limiting and optical switching.
Mdx mice inducibly expressing dystrophin provide insights into the potential of gene therapy for Duchenne muscular dystrophy (2000)

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by the lack of expression of the dystrophin protein in muscle tissues. We genetically engineered a mouse model (mdx) of DMD that allowed for the high level and inducible transcription of a dystrophin mini-gene. This was achieved via the tetracycline-responsive transactivator (tTA) system. Multiple analyses confirmed that dystrophin expression in the mice was: (i) tTA dependent; (ii) correctly localized to the sarcolemmal membranes; (iii) capable of preventing the onset of dystrophy; and (iv) effectively blocked by the oral administration of tetracyclines. The model allowed us to somatically extinguish or induce dystrophin gene transcription. Somatic induction of dystrophin transcription prevented the onset of muscular dystrophy in some muscle groups. The levels of phenotypic rescue were influenced, however, by the age of the animals at the time of dystrophin induction. We also found that despite somatic termination of dystrophin gene transcription, the dystrophin protein was found to be associated with the sarcolemmal membrane for at least 26 weeks. Persistent detection of dystrophin was also accompanied by a prolonged protection of the muscle cells from the onset of dystrophy. The findings demonstrated that somatic transfer of the dystrophin gene not only may allow for the prevention of muscular dystrophy in multiple muscle groups, but also may be accompanied by persistent efficacy, secondary to the long-term functional stability of the dystrophin protein in vivo. This model should be useful in future studies concerning the potential of genetic therapy for DMD, as well as other muscle disorders.
Expression of katG in Mycobacterium tuberculosis Is Associated with Its Growth and Persistence in Mice and Guinea Pigs (1998)

The molecular mechanisms associated with the pathogenesis of tuberculosis are not well understood. The present study evaluated the role of catalase-peroxidase as a potential virulence factor for Mycobacterium tuberculosis. Growth and persistence of M. tuberculosis H37Rv in intravenously infected BALB/ c mice were compared with katG-deleted, isoniazid-resistant M. tuberculosis H37RVINHR. Transformation of M. tuberculosis H37Rv (TBkatG) or Mycobacterium intracellulare (MACkatG) genes into M. tuberculosis H37RvINHR restored its catalase-peroxidase activities and the ability of the recombinants to persist in spleens of mice and guinea pigs. Transformation with the TBkatG gene with the codon 463 R-->L mutation also restored catalase-peroxidase activity and enhanced persistence. However, transformants with the codon 275 T-->P mutant expressed low levels of enzymatic activity and failed to persist in guinea pig spleen, although they did survive in mouse tissues. These results indicate that KatG contributes to the ability of M. tuberculosis to grow and survive within the infected host tissues.
Differentiation of Human Embryonic Stem Cells After Transplantation in Immune‐Deficient Mice (2005)

Our current knowledge of how human tissues grow and develop is limited. We need to increase our understanding of tissue formation if we are to fully realize the potential of stem cells as a source of material for research into health and disease and possible therapeutic applications. Transplanted pluripotent human embryonic stem cells (hESCs) provide a potential system to model and investigate cell differentiation in humans. hESCs transplanted into immune-deficient mice form complex teratomas consisting of a range of differentiated somatic tissues, some of which appear highly organized and resemble structures normally identified in the embryo and adult. Analysis of such tumors may provide a unique opportunity to study organogenesis and lead to novel approaches in bioengineering and the growth of functioning structures composed of a range of alternative cell types. However, little has been done to characterize the developmental potential of hESCs after transplantation. This concise review presents evidence for the ability of hESCs to differentiate in vivo and highlights some of the prominent questions that need to be addressed if transplantation is to be used as a research tool to study hESC differentiation.
Quo Vadis Printed (Circuit) Board? (1989)

Printed (circuit) boards have been used in the electronics industry for the past 25 years and more. The technology used to design and manufacture PCBs is well known and accepted. Recently, however, designers of electronic equipment have shown that the use of newer materials and systems, such as flexible and moulded circuits, hybrid circuits, or a combination of these, can significantly improve the cost/performance ratio for electronic interconnects. This paper examines some of the many possibilities open to electronics designers and how these new opportunities can improve the economics and performance of electronic equipment.
Notes on the History of Cellular Uptake and Deiodination of Thyroid Hormone (2005)

In this mini review on the history of the research devoted to thyroid hormone metabolism two pathways are discussed, i.e. uptake and subsequent deiodination in cells and tissues. In the 1950's the investigations of these processes were greatly stimulated when 131I became available for research purposes. The true nature of both mechanisms surfaced in the 1970's when it became apparent that transport of thyroid hormones into cells was a regulated carrier mediated process, while deiodination appeared to be catalyzed by different types of enzymes. Kinetic data indicated that these processes were of great importance in the ultimate regulation of thyroid hormone bio-availability.
Chimeric Granulocyte/Macrophage Colony-stimulating Factor/Transforming Growth Factor-β (TGF-β) Receptors Define a Model System for Investigating the Role of Homomeric and Heteromeric Receptors in TGF-β Signaling (1996)

Transforming growth factor-beta (TGF-beta) belongs to a family of ligands that regulate cell growth and differentiation. The most commonly observed receptors are referred to as the type I, type II, and type III (betaglycan) TGF-beta receptors. Two receptor models have been presented to account for the various cellular responses to TGF-beta. The first proposes that all TGF-beta signaling results from the formation of a heteromeric type I/type II complex, while the second suggests that distinct type I or type II TGF-beta receptor combinations mediate aspects of TGF-beta signaling. We have addressed this general question relating to TGF-beta signaling by constructing chimeric receptors consisting of the extracellular domain of the granulocyte/macrophage colony-stimulating factor (GM-CSF) alpha or beta receptor fused to the transmembrane and cytoplasmic domain of the type I or type II TGF-beta receptor. Since high affinity GM-CSF binding requires dimerization of the alpha and beta ligand binding subunits, the response elicited by defined type I and/or type II TGF-beta receptor cytoplasmic domain homomers or heteromers can be examined. We show in mesenchymal AKR-2B cells that while TGF-beta-dependent transient luciferase activity, endogenous gene activity, and long-term biological responses are similarly induced by activating the chimeric heteromeric receptors with GM-CSF as the endogenous TGF-beta receptor, chimeric homomeric type I/type I or type II/type II receptors are signaling-incompetent.
Inclusion-induced anisotropy of fatigue crack growth in steel (1986)

Experiments on a free–machining steel have been undertaken to elucidate the role of non–metallic inclusions in fatigue crack growth. In the mid–to–high stress intensity range ∆K of the crack growth date da/dN versus ∆K curve inclusions are found to influence fatigue crack growth rates by plastic strain intensification. High crack growth rates are associated with testing orientations which exhibit low initiation values of fracture toughness. In the low growth rate regime, orientations which exhibit low values of fracture toughness give high threshold values of ∆K. Crack growth behaviour in this regime is strongly influenced by crack closure phenomena.MST/318
Evidence that the UV endonuclease activity induced by bacteriophage T4 contains both pyrimidine dimer-DNA glycosylase and apyrimidinic/apurinic endonuclease activities in the enzyme molecule (1981)

We performed experiments to determine whether the phage T4-induced UV endonuclease activity is a single protein containing both pyrimidine dimer-DNA glycosylase and apyrimidinic endonuclease activities. The UV endonuclease activity is induced by the denV gene and codes for the glycosylase activity. We obtained several kinds of evidence that the protein containing the glycosylase activity also contains the apyrimidinic endonuclease activity. After chromatography on DEAE-cellulose, the two activities copurified during phosphocellulose chromatography and Sephadex G-100 chromatography, with a constant ratio of activities across the activity peaks. On Sephadex G-100 columns the molecular weights of the two activities agreed within 2,500 or less. When an extract of cells infected with the T4 V1 mutant was purified in exactly the same way as an extract of cells infected with T4 V1+, neither glycosylase nor apyrimidinic endonuclease activity was detected in the normal elution position of the T4 UV endonuclease activity. The glycosylase and apyrimidinic endonuclease activities were induced with similar kinetics, which were characteristic of immediate early rather than delayed early enzymes. This correlated well with the presumed major role of these activities in repairing thymine dimers in parental DNA before DNA replication begins. Finally, glycosylase and apyrimidinic endonuclease activities were lost in parallel during incubation of the enzyme at 46 degree C. Our results indicated that both of these enzyme activities are contained in the same enzyme molecule and, probably, in the same polypeptide.
Bacteriophage lambda as a cloning vector (1992)

Extensive research has been directed toward the development of multipurpose lambda vectors for cloning ever since the potential of using coliphage lambda as a cloning vector was recognized in the late 1970s. An understanding of the intrinsic molecular organization and of the genetic events which determine lysis or lysogeny in lambda has allowed investigators to modify it to suit the specific requirements of gene manipulations. Unwanted restriction sites have been altered and arranged together into suitable polylinkers. The development of a highly efficient in vitro packaging system has permitted the introduction of chimeric molecules into hosts. Biological containment of recombinants has been achieved by introducing amber mutations into the lambda genome and by using specific amber suppressor hosts. Taking advantage of the limited range of genome size (78 to 105% of the wild-type size) for its efficient packaging, an array of vectors has been devised to accommodate inserts of a wide size range, the limit being 24 kbp in Charon 40. The central dispensable fragment of the lambda genome can be replaced by a fragment of heterologous DNA, leading to the construction of replacement vectors such as Charon and EMBL. Alternatively, small DNA fragments can be inserted without removing the dispensable region of the lambda genome, as in lambda gt10 and lambda gt11 vectors. In addition, the introduction of many other desirable properties, such as NotI and SfiI sites in polylinkers (e.g., lambda gt22), T7 and T3 promoters for the in vitro transcription (e.g., lambda DASH), and the mechanism for in vivo excision of the intact insert (e.g., lambda ZAP), has facilitated both cloning and subsequent analysis. In most cases, the recombinants can be differentiated from the parental phages by their altered phenotype. Libraries constructed in lambda vectors are screened easily with antibody or nucleic acid probes since several thousand clones can be plated on a single petri dish. Besides the availability of a wide range of lambda vectors, many related techniques such as rapid isolation of lambda DNA, a high efficiency of commercially available in vitro packaging extracts, and in vitro amplification of DNA via the polymerase chain reaction have collectively contributed to lambda's becoming one of the most powerful and popular tools for molecular cloning.
Circulating angiopoietin‐1 to angiopoietin‐2 ratio is an independent prognostic factor for survival in newly diagnosed patients with multiple myeloma who received therapy with novel antimyeloma agents (2011)

The circulating levels of several angiogenic cytokines [angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), angiogenin and basic fibroblast growth factor (bFGF)] were evaluated in 174 consecutive patients with newly diagnosed, symptomatic, multiple myeloma (MM). Circulating levels of Ang-1/Ang-2 were reduced in myeloma patients compared to controls, whereas VEGF and angiogenin levels were increased. Reduced angiopoietin-1/angiopoietin-2 ratio correlated with advanced disease features including international staging system (ISS)-3 stage, renal impairment and extensive bone disease. Based on immunohistochemical results in 20 patients (10 with the higher and 10 with the lower values of circulating angiopoietin-2) we found that angiopoietin-2 is expressed by myeloma cells and correlates with increased microvessel density in subsets of patients. Furthermore, Ang-1/Ang-2 ratio correlated with survival. Patients with circulating Ang-1/Ang-2 below or equal to the median value (6.03) had a median survival of 26.3 months compared to 53 months of all others (p = 0.002). Interestingly, this was mainly observed in patients who received first-line therapy with novel agent-based regimens (65% of our patients). Furthermore, a subset of ISS-3 patients with serum Ang-1/Ang-2 above the median value had favourable prognosis (median survival: 45 months versus 17 months of all others; p = 0.0001). The multivariate analysis revealed that low Ang-1/Ang-2 ratio could independently predict for inferior survival in our cohort of patients (relative risk (RR) 2.07, 95% CI 1.50-2.42; p < 0.001). These results highlight the role of angiopoietins pathway in the biology of MM and reveal novel targets for the development of antimyeloma agents.
Presence of bone marrow–derived circulating progenitor endothelial cells in the newly formed lymphatic vessels (2005)

Bone marrow (BM)-derived circulating endothelial precursor cells (CEPCs) have been reported to incorporate into newly formed blood vessels under physiologic and pathologic conditions. However, it is unknown if CEPCs contribute to lymphangiogenesis. Here we show that in a corneal lymphangiogenesis model of irradiated mice reconstituted with enhanced green fluorescent protein (EGFP)-positive donor bone marrow cells, CEPCs are present in the newly formed lymphatic vessels. Depletion of bone marrow cells by irradiation remarkably suppressed lymphangiogenesis in corneas implanted with fibroblast growth factor-2 (FGF-2). Further, transplantation of isolated EGFP-positive/vascular endothelial growth factor receptor-3-positive (EGFP+/VEGFR-3+) or EGFP+/VEGFR-2+ cell populations resulted in incorporation of EGFP+ cells into the newly formed lymphatic vessels. EGFP+/CEPCs were also present in peritumoral lymphatic vessels of a fibrosarcoma. These data suggest that BM-derived CEPCs may play a role in "lymphvasculogenesis."
一个马克思主义者无权成为悲观主义者——与J．-M．帕尔米尔的谈话 (2007)

本文追溯了布洛赫从求学到流亡，从东德到西德的生活经历，描述了他与卢卡奇、海德格尔、马尔库塞、萨特等同时代人的关系。第一次世界大战期间，布洛赫是一个和平主义者，他的哲学思想深受表现主义的影响。1938年布洛赫流亡美国，1949年回到东德。1956年以后，布洛赫受到东德当局的批判，被指控为“偏离分子和修正主义者”。1961年布洛赫移居西德。布洛赫承认深受黑格尔哲学和宗教的影响，但他强调自己是完全站在马克思立场上的马克思主义哲学家。在他看来，乌托邦理论在马克思那里就已经出现，而他只是从马克思主义立场出发，发展了马克思的乌托邦概念而已。乌托邦不仅是哲学一艺术范畴，也是我们时代的政治范畴。乌托邦并不意味着逃避现实，而是意味着探索现实事物的客观可能性，并为其实现而奋斗。具体的乌托邦导向一种更美好的未来、一个人道的世界。一个马克思主义者无权成为悲观主义者。
The Molecular Target of Rapamycin (mTOR) as a Therapeutic Target Against Cancer (2003)

The molecular target of rapamycin (mTOR), which is a member of the phosphoinositide 3-kinase related kinase (PIKK) family and a central modulator of cell growth, is a prime strategic target for anti-cancer therapeutic development. mTOR plays a critical role in transducing proliferative signals mediated through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway, principally by activating downstream protein kinases that are required for both ribosomal biosynthesis and translation of key mRNAs of proteins required for G(1) to S phase traverse. By targeting mTOR, the immunsuppressant and antiproliferative agent rapamycin (RAP) inhibits signals required for cell cycle progression, cell growth, and proliferation. RAP, a complex macrolide and highly potent fungicide, immunosuppressant, and anti-cancer agent, is a highly specific inhibitor of mTOR. In essence, RAP gains function by binding to the immunophilin FK506 binding protein 12 (FKBP12) and the resultant complex inhibits the activity of mTOR. Since mTOR activates both the 40S ribosomal protein S6 kinase ((p)70(s6k)) and the eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), RAP blocks activation of these downstream signaling elements, which results in cell cycle arrest in the G1 arrest. RAP also prevents cyclin-dependent kinase (cdk) activation, inhibits retinoblastoma protein ((p)Rb) phosphorylation, and accelerates the turnover of cyclin D1 that leads to a deficienciy of active cdk4/cyclin D1 complexes, all of which potentially contribute to the prominent inhibitory effects of RAP at the G(1)/S phase transition. Both RAP and several RAP analogs with more favorable pharmaceutical properties have demonstrated prominent growth inhibitory effects against a broad range of human cancers in both preclinical and early clinical evaluations. This review will summarize the principal mechanisms of action of RAP and RAP derivatives and their potential utility of these agents as anti-cancer therapeutics. The preliminary results of early clinical evaluations with RAP analogs and the unique developmental challenges that lie ahead will also be discussed.
AN EVIDENCE‐BASED APPROACH TO ANAEMIA MANAGEMENT IN PREDIALYSIS CHRONIC KIDNEY DISEASE (2009)

The use of Evidence-based practice (EBP) is a decision-making process, which integrates the best available research, clinician expertise, and client characteristics, integrating quality patient care in terms of clinical outcomes and cost-effectiveness. This paper describes the application of EBP to an outpatient intravenous (IV) iron clinic for patients with predialysis chronic kidney disease (CKD). There has been an increasing focus on managing anaemia in patients with predialysis CKD. Along with the use of erythropoiesis stimulating agents, there has been an emerging interest in the use of IV iron preparations to treat anaemia in this patient population. Using EBP, we introduced a single dose preparation Ferinject to replace our original IV iron protocol using Venofer. As a test dose of Ferinject is not required, it is extremely appropriate for use in busy nurse-led IV iron clinics. Based upon the evidence generated from our initial trial of using Ferinject, and our clinical experience of using this preparation, we have now converted our IV iron protocol to Ferinject. Although the evaluation of Ferinject in our predialysis population is ongoing, we are continuing to observe the benefits of using this preparation, both in terms of patient outcome and cost-effectiveness. We consider that the use of Ferinject has reduced waiting time and waiting list pressure, and also reduced material and hospital transport costs, which are significant due to the large geographical area covered by our CKD service.
Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells (2004)

These findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free) for the treatment of anaplastic human thyroid tumours.