gebhart/patrepeval huggingface dataset:
Non-DNA-binding platinum anticancer agents: Cytotoxic activities of platinum–phosphato complexes towards human ovarian cancer cells (2008)

DNA is believed to be the molecular target for the cytotoxic activities of platinum (Pt) anticancer drugs. We report here a class of platinum(II)- and platinum(IV)-pyrophosphato complexes that exhibit cytotoxicity comparable with and, in some cases, better than cisplatin in ovarian cell lines (A2780, A2780/C30, and CHO), yet they do not show any evidence of covalent binding to DNA. Moreover, some of these compounds are quite effective in cisplatin- and carboplatin-resistant cell line A2780/C30. The lack of DNA binding was demonstrated by the absence of a detectable Pt signal by atomic absorption spectroscopy using isolated DNA from human ovarian cells treated with a platinum(II)-pyrophosphato complex, (trans-1,2-cyclohexanediamine)(dihydrogen pyrophosphato) platinum(II), (pyrodach-2) and from NMR experiments using a variety of nucleotides including single- and double-stranded DNA. Furthermore, pyrodach-2 exhibited reduced cellular accumulations compared with cisplatin in cisplatin- and carboplatin-resistant human ovarian cells, yet the IC(50) value for the pyrophosphato complex was much less than that of cisplatin. Moreover, unlike cisplatin, pyrodach-2 treated cells overexpressed fas and fas-related transcription factors and some proapoptotic genes such as Bak and Bax. Data presented in this report collectively indicate that pyrodach-2 follows different cytotoxic mechanisms than does cisplatin. Unlike cisplatin, pyrodach-2 does not undergo aquation during 1 week and is quite soluble and stable in aqueous solutions. Results presented in this article represent a clear paradigm shift not only in expanding the molecular targets for Pt anticancer drugs but also in strategic development for more effective anticancer drugs.
Synthesis of Heterotelechelic Poly(ethylene glycol) Macromonomers. Preparation of Poly(ethylene glycol) Possessing a Methacryloyl Group at One End and a Formyl Group at the Other End (1997)

Poly(ethylene glycol) (PEG) having a polymerizable methacryloyl group at one end and an aldehyde group at the other end was quantitatively synthesized. Potassium 3,3-diethoxy-1-propanoxide initiated the anionic polymerization of ethylene oxide to form an acetal-ended PEG having potassium alkolate at the ω chain end. By adding methacrylic anhydride to the reaction mixture, the ω end was quantitatively converted to the methacryloxy group. When the PEG with an acetal group at one end and a methacryloyl group at the other end was treated with 90% acetic acid solution, the hydrolysis of the acetal end group proceeded to form a PEG macromonomer possessing an aldehyde end group. The end groups were characterized by 1H NMR and MALDI-TOF-MS spectroscopies. Copolymerization of the aldehyde-PEG macromonomer with methacrylate monomers quantitatively gave the PEG graft polymer with an aldehyde group at the free end of the graft chain.
Regulation of polyamine transport in Chinese hamster ovary cells (1990)

Control Chinese hamster ovary (CHO) cells and mutant CHO cells lacking ornithine decarboxylase activity (CHODC-) were used to study the regulation of polyamine uptake. It was found that the transport system responsible for this uptake was regulated by intracellular polyamine levels and that this regulation was responsible for the maintenance of physiological intracellular levels under extreme conditions such as polyamine deprivation or exposure to exogenous polyamines. Polyamine transport activity was enhanced by decreases in polyamine content produced either by inhibition of ornithine decarboxylase with alpha-difluoromethylornithine in CHO cells or via polyamine starvation of CHODC- cells. The provision of exogenous polyamines resulted in rapid and large increases in intracellular polyamine content followed by decreased polyamine transport activity. Soon after this decrease in uptake activity, intracellular polyamine levels then fell to near control values. Cells grown in the presence of exogenous polyamines maintained intracellular polyamine levels at values similar to those of control cells. Protein synthesis was necessary for the increase in transport in response to polyamine depletion, but appeared to play no role in decreasing polyamine transport. Bis(ethyl) polyamine analogues mimicked polyamines in the regulation of polyamine transport but this process was relatively insensitive to regulation by methylglyoxal bis(guanylhydrazone), a spermidine analogue known to enter cells via this transport system and to accumulate to very high levels.
Studies of Inositol Phospholipid-Specific Phospholipase C (1989)

Inositol phospholipid-specific phospholipase C is the enzyme that generates phosphoinositide-derived messenger molecules. Mammalian cells contain at least five immunologically distinct phospholipase C enzymes that appear to be separate gene products. Complete amino acid sequences of four of these isozymes have been established. The overall sequence similarity is surprisingly low for enzymes catalyzing the same chemical reaction: three of them show limited amino acid sequence similarity to each other in two narrow regions, and the fourth enzyme is completely different. The diversity in primary structure together with different regional and cellular expression of the isozymes suggests that each isozyme has a defined function in processing the physiological response of different cell types to a variety of external stimuli and that each is regulated differently.
Growth-regulated expression of rhoG, a new member of the ras homolog gene family. (1992)

Cellular transition from the resting state to DNA synthesis involves master switches genes encoding transcriptional factors (e.g., fos, jun, and egr genes), whose targets remain to be fully characterized. To isolate coding sequences specifically accumulated in late G1, a differential screening was performed on a cDNA library prepared from hamster lung fibroblasts stimulated for 5 h with serum. One of the positive clones which displayed a sevenfold induction, turned out to code for a protein sharing homology to Ras-like products. Cloning and sequence analysis of the human homolog revealed that this putative new small GTPase, referred to as rhoG, is more closely related to the rac, CDC42, and TC10 members of the rho (ras homolog) gene family and might have diverged very early during evolution. rhoG mRNA accumulates in proportion to the mitogenic strength of various purified growth factors used for the stimulation, as a consequence of transcriptional activation. G1-specific RNA accumulation is impaired upon addition of antimitogenic cyclic AMP and is enhanced when protein synthesis is inhibited, mainly as a result of RNA stabilization. rhoG mRNA expression is observed in a wide variety of human organs but reaches a particularly high level in lung and placental tissues.
Effects of the Interest Rate and Reserve Requirement Ratio on Bank Risk in China: A Panel Smooth Transition Regression Approach (2015)

This paper applies the Panel Smooth Transition Regression (PSTR) model to simulate the effects of the interest rate and reserve requirement ratio on bank risk in China. The results reveal the nonlinearity embedded in the interest rate, reserve requirement ratio, and bank risk nexus. Both the interest rate and reserve requirement ratio exert a positive impact on bank risk for the low regime and a negative impact for the high regime. The interest rate performs a significant effect while the reserve requirement ratio shows an insignificant effect on bank risk on a statistical basis for both the high and low regimes.
Tracking recorded fires using charcoal morphology from the sedimentary sequence of Prosser Lake, British Columbia (Canada) (2006)

Abstract Quantitative analyses of variations in morphological features of charcoal were undertaken in a 210 Pb-dated sediment core from Prosser Lake (British Columbia, Canada). Seven morphological types of charcoal were defined by particle shape, major–minor axis ratio, apparent porosity and progradation to unburned material. The distribution of morphotypes and total charcoal abundances were assessed as a proxy for fire events recorded between 1919 and 2000 and to subsequent mechanisms of transportation–sedimentation to lake sediments. Charcoal morphotypes showed distinct relationships to recorded area burned by fires. Fragile charcoal fragments with highly irregular porosity (termed Type M) displayed the strongest correlation to burned area ( r 2 = 0.51; P = 0.0001) and did not produce any false-positive signal for fires recorded within a radius of 20 km around the lake. We infer that high porosity and low density Type M fragments are aerially transported and directly deposited on the lake, and that the fragility of Type M charcoal prevents significant quantities from being secondarily transported and incorporated into the sedimentary record. We propose that charcoal morphology is an important but underutilized technique that can yield important insights into fire type, proximity and transportation–sedimentation processes.
Clinical trials in systemic lupus erythematosus (SLE): lessons from the past as we proceed to the future – the EULAR recommendations for the management of SLE and the use of end-points in clinical trials (2008)

Among rheumatic diseases, lupus, especially nephritis, has been more extensively studied with several controlled clinical trials as reported in the literature. The large number of studies on the diagnosis and management of the disease have created a plethora of data that need to be systemically reviewed and formulated in recommendations to be used in daily practice. Moreover, the increasing number of new agents holding the promise of improved efficacy and safety profiles over traditional treatments in systemic lupus erythematosus (SLE) has provided the impetus for optimal design of clinical trials. To this end, and under the auspices of European League Against Rheumatism (EULAR), we developed recommendations for the management of SLE and for points to consider in the design of SLE trials. These recommendations were developed using a combination of research-based evidence following a systematic literature search of trials and cohort studies, and expert consensus. Twelve statements concerning the management of SLE and points regarding the eligibility criteria and outcome measures to be included in trials were developed and are briefly reviewed here. The literature search showed that there have been few high quality Randomized controlled trails (RCTs) in SLE, particularly for manifestations other than nephritis and thus, several important issues have not been adequately addressed. Importantly, end-points currently used in SLE trials have not actually been validated in clinical trials. These findings underscore the need to establish international networks to facilitate clinical trials addressing these issues and testing new therapies.
Synthetic Molecular Motors and Mechanical Machines (2006)

The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.
STATE-OF-THE-ART OF OPTICAL FIBERS, FIBER CABLES AND THEIR TECHNOLOGIES (1990)

In this paper, state-of-the-art of optical fibers (centering on the wholly synthesized VAD fiber), fiber cables (including comparison of fiber cables), fiber amplifiers and their accessories concerned are reviewed.
Some new recorded plants from Shandong Province (1997)

4 species, 2 varieties and 1 form collected from Shandong are reported as new records to this province. All the voucher specimens are preserved in herbaria of Shandong Agricultural University and Nanjing Forestry University.
Defensins and Host Defense (1999)

Defensins are antimicrobial peptides produced by cells as part of the host9s immune defense system against invading pathogens. A Perspective by
 Tomas Ganz
 highlights three papers that provide new insights into the structure and function of vertebrate defensins. In mice, a-defensins produced by the Paneth cells of the small intestine help defend the host against invasion by intestinal pathogens such as
 Escherichia coli
 and
 Salmonella
 (
 Wilson
 et al.). Two human b-defensins have been shown to act as chemoattractants for dendritic cells and memory T cells (
 Yang
 et al.), and a new cyclic q-defensin identified in monkeys has powerful antimicrobial activity and may be a molecular template for designing new antibiotics (
 Tang
 et al.).
Promotion of estrogen-induced mammary gland carcinogenesis by androgen in the male Noble rat: probable mediation by steroid receptors (1998)

Both endogenous and exogenous estrogen exposure is associated with an increased breast cancer risk. In some studies, elevated serum testosterone levels have also been linked to an increased breast cancer risk. Estrogen alone or combined with progesterone induces high mammary tumor incidences in various strains of both male and female rats. Mammary gland ductal adenocarcinomas were induced after 17beta-estradiol (E2) and testosterone propionate (TP) treatment in male Noble rats. Tumor incidence was 100% after 8-9 months of treatment. Such neoplasms were not detected after either estrogen or androgen exposure alone within this time period. TP alone caused disruption of mammary gland ducts and proliferation of stromal tissue, while E2 treatment alone induced both ductal epithelial growth and nodular atypical hyperplasia. To study the interaction of these hormones in mammary tumorigenesis, sex hormone receptors were characterized in mammary glands of Noble rats. Estrogen receptor-alpha (ER) was detected in age-matched, untreated mammary gland epithelium; in most early atypical hyperplastic lesions appearing after E2 and E2 + TP treatment and in E2 + TP-induced mammary tumors. Two major ER putative isoforms, 116 and 120 kDa, were detected in E2- and E2 + TP-treated mammary glands, and in the induced tumors. A 54 kDa ER protein was found in untreated and TP-treated mammary glands, and in the induced tumors. Both progesterone receptor-B (PR-B) and PR-A2, as well as androgen receptor-B (AR-B) and AR-A isoforms were markedly elevated in all E2 + TP-induced mammary tumors. However, the levels of both PR and AR were very low in mammary glands of E2- and E2 + TP-treated male rats. Low and moderate levels of AR and PR, respectively, were detected in most atypical hyperplastic lesions induced by E2- and E2 + TP-treated mammary glands. These results suggest that androgens may interact with either AR or PR, and perhaps both receptors, in E2 + TP-induced mammary glands and the induced tumors to effect the reduction in latency period, enhance tumor size, and increase incidence to 100%.
Strategies for the identification of inhibitors of West Nile virus and other flaviviruses. (2002)

The recent outbreaks of West Nile virus (WNV) and other emerging and re-emerging flaviviruses, have made prevention and treatment of flavivirus infections a global public health priority. No inhibitor is currently available for use as an antiflavivirus therapy. In this communication, I review (i) stages of flavivirus replication representing potential targets for antiviral drug discovery; (ii) strategies for identification of flavivirus inhibitors; and (iii) existing antiviral inhibitors reported to have anti-WNV or other antiflavivirus activities. Flaviviruses share conserved nucleotide elements and amino acid sequences, and have similar genome organization and replication strategies. As such, it is hoped that broad spectrum flavivirus inhibitors could be identified through screening of compound libraries.
Covalent Layer‐by‐Layer Assembly of Conjugated Polymers and CdSe Nanoparticles: Multilayer Structure and Photovoltaic Properties (2005)

Abstract Hybrid thin films of conjugated polymers and CdSe nanoparticles have been fabricated by using a layer‐by‐layer (LbL) approach driven by covalent coupling reactions. This method permits facile covalent crosslinking of the polymer/nanoparticle interlayers in common organic solvents, which provides a general route for preparing robust and uniform functional thin films. The deposition process is linearly related to the number of bilayers as monitored by UV‐vis absorption spectroscopy and ellipsometry. Characterization of the multilayer structures has been carried out by fluorescence spectroscopy, X‐ray photoelectron spectroscopy (XPS), and grazing‐angle Fourier‐transform infrared spectroscopy (FTIR). Techniques such as atomic force microscopy (AFM) and scanning electron microscopy (SEM) have also been used. A preliminary application of the hybrid films in the development of organic photovoltaics is presented. Upon illumination with white light at 10 mW cm –2 , the self‐assembled multilayer films exhibit steady photocurrent responses with an overall optical‐to‐electrical power conversion efficiency of 0.71 %.
Cross‐presentation of NY‐ESO‐1 cytotoxic T lymphocyte epitope fused to human heat shock cognate protein 70 by dendritic cells (2007)

The cancer-testis antigen NY-ESO-1 has been implicated as one of the most attractive candidates for a cancer vaccine. However, a protein vaccine generally meets inefficient antigen presentation to CD8(+) T cells, which could be overcome by combination with an appropriate adjuvant. Heat shock protein is a natural adjuvant and activates the antigen-presenting cells to channel exogenous antigens into the classical major histocompatibility complex class I antigen-processing pathway (cross-presentation). Therefore, we genetically fused a minigene encompassing the NY-ESO-1 cytotoxic T lymphocyte (CTL) epitope 157-165 (ESO p157-165) to the human heat shock cognate protein 70 (hsc70) and expressed the resulting fusion proteins in Escherichia coli. By using a human leukocyte antigen-A*0201-restricted NY-ESO-1-specific CTL clone, the cross-presentation of ESO p157-165 by monocyte-derived dendritic cells (mo-DC) pulsed with the fusion protein was evaluated. The fusion protein-pulsed mo-DC activates the CTL clone much more efficiently than the free NY-ESO-1 protein-pulsed mo-DC. Moreover, the magnitude of the CTL activity was comparable between ESO p157-165 and the fusion protein of hsc70 and ESO p157-165 (hsc70-ESO p157-165 fusion protein). In addition, the CTL activation induced by the fusion protein, but not by the epitope, was inhibited by paraformaldehyde fixation of the mo-DC and by treatment with lactacystin, a specific inhibitor for the proteasome. Finally, the hsc70-ESO p157-165 fusion protein-pulsed DC was able to induce an antigen-specific T-cell response. These results suggest that the hsc70-ESO p157-165 fusion protein is therefore considered to be a promising candidate as a cancer vaccine.
1/f noise in passive CMOS mixers for low and zero IF integrated receivers (2001)

Passive mixers are generally thought attractive as having no 1/f noise sources when used in AC coupled configurations, in contrast to the conventional «Gilbert» type circuit. In this paper, we show that not only does this type of mixer exhibit internal 1/f noise, but with a poor choice of device sizes, one can magnify the noise of a subsequent amplifier stage. The mechanisms underlying these phenomena are examined, and some design recommendations offered.
Changes in Cortical and Striatal Neurons Predict Behavioral and Electrophysiological Abnormalities in a Transgenic Murine Model of Huntington's Disease (2001)

Neurons in Huntington's disease exhibit selective morphological and subcellular alterations in the striatum and cortex. The link between these neuronal changes and behavioral abnormalities is unclear. We investigated relationships between essential neuronal changes that predict motor impairment and possible involvement of the corticostriatal pathway in developing behavioral phenotypes. We therefore generated heterozygote mice expressing the N-terminal one-third of huntingtin with normal (CT18) or expanded (HD46, HD100) glutamine repeats. The HD mice exhibited motor deficits between 3 and 10 months. The age of onset depended on an expanded polyglutamine length; phenotype severity correlated with increasing age. Neuronal changes in the striatum (nuclear inclusions) preceded the onset of phenotype, whereas cortical changes, especially the accumulation of huntingtin in the nucleus and cytoplasm and the appearance of dysmorphic dendrites, predicted the onset and severity of behavioral deficits. Striatal neurons in the HD mice displayed altered responses to cortical stimulation and to activation by the excitotoxic agent NMDA. Application of NMDA increased intracellular Ca(2+) levels in HD100 neurons compared with wild-type neurons. Results suggest that motor deficits in Huntington's disease arise from cumulative morphological and physiological changes in neurons that impair corticostriatal circuitry.
A median peak detecting analog signal processor for hard disk drive servo (1995)

An analog signal processor for hard disk drive servo is described. It performs servo demodulation by means of median peak defection which provides immunity against additive as well as multiplicative noise from the medium, unlike conventional methods. A novel circuit configuration has been employed to implement the median peak detector in an area and power efficient manner. The entire servo processor that includes the demodulator and 10 b A/D and D/A converters has been integrated into a single CMOS integrated circuit.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>