gebhart/patrepeval huggingface dataset:
RNA Interference-Based Cancer Drugs: The Roadblocks, and the “Delivery” of the Promise (2018)

Nucleic acid-based therapeutics like synthetic small interfering RNAs have been exploited to modulate gene function, taking advantage of RNA interference (RNAi), an evolutionally conserved biological process. Recently, the world's first RNAi drug was approved for a rare genetic disorder in the liver. However, there are significant challenges that need to be resolved before RNAi can be translated in other genetic diseases like cancer. Current drug delivery platforms for therapeutic silencing RNAs are tailored to hepatic targets. RNAi therapies for nonhepatic conditions are still at early clinical phases. In this study, we discuss the critical design considerations in anticancer RNAi drug development, insights gained from initial clinical trials, and new strategies that are entering clinical development, shaping the future of RNAi in cancer.
The 1986 Lake Nyos Gas Disaster in Cameroon, West Africa (1987)

The sudden, catastrophic release of gas from Lake Nyos on 21 August 1986 caused the deaths of at least 1700 people in the northwest area of Cameroon, West Africa. Chemical, isotopic, geologic, and medical evidence support the hypotheses that (i) the bulk of gas released was carbon dioxide that had been stored in the lake's hypolimnion, (ii) the victims exposed to the gas cloud died of carbon dioxide asphyxiation, (iii) the carbon dioxide was derived from magmatic sources, and (iv) there was no significant, direct volcanic activity involved. The limnological nature of the gas release suggests that hazardous lakes may be identified and monitored and that the danger of future incidents can be reduced.
Studies of aluminium mobilization in renal dialysis patients using the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one. (1994)

The oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1, deferiprone, CAS 30652-11-0) has been tested in 11 renal dialysis patients, 10 for aluminium and 1 for iron mobilization. L1 was administered just after the patients were placed on the haemodialyser and blood samples were collected before haemodialysis at 1 h and for some patients at longer intervals. Plasma aluminium levels before treatment ranged from 12 to 264 micrograms/l. A mean increase of 90% was observed within the first hour of oral administration in 6 patients who received a dose of L1 of 40-60 mg/kg. Plasma aluminium levels then progressively decreased after this period. Three patients with plasma aluminium of 30-66 micrograms/l who received a dose of L1 of less than 30 mg/kg had no significant changes in their plasma aluminium. In 2 other cases administration of L1 resulted in an over 30-fold increase of aluminium concentration in the dialysate of a continuous ambulatory peritoneal dialysis patient and of over 3 times the iron concentration in the dialysate of an iron loaded haemodialysis patient. In the last patient HPLC analysis of the dialysate samples obtained from the haemodialyser has shown complete clearance of L1 within 4 h but not of its glucuronide metabolite within 6.5 h of the L1 administration. No toxic side effects were observed in any of the 11 patients who received oral L1. These are the first clinical trials of an oral chelator in renal dialysis patients which suggest that oral L1 and possibly other alpha-ketohydroxypyridine chelators may have a use in the treatment of patients with aluminium overload.
Automated Forest Area Estimation Using Iterative Guided Spectral Class Rejection (2006)

USDA Forest Service Forest Inventory and Analysis (FIA) forest area estimates were derived from 4 Landsat ETMimages in Virginia and Minnesota classified using an automated hybrid classifier known as Iterative Guided Spectral Class Rejection (IGSCR). Training data were collected using region- growing initiated at random points within each image. The classified images were spatially post-processed using five different techniques. Image accuracy was assessed using the center land-use of all available FIA plots and subsets contain- ing plots with 50, 75 and 100 percent homogeneity. Overall accuracy (81.9 to 95.4 percent) increased with homogeneity of validation plots and decreased with frag- mentation (estimated by percent edge; r 2 = 0.932). Filter- ing effects were not consistently significant at the 95 per- cent level; however, the 3 � 3 majority filter significantly improved the accuracy of the most fragmented image. The now-automated IGSCR is a suitable candidate for operational forest area estimation, with strong potential for use in other application areas.
Generation of Stable Complex Gradients Across Two-Dimensional Surfaces and Three-Dimensional Gels (2007)

Many chemical and biological processes are dependent on molecular gradients. We describe a new microfluidic approach that can be used to produce spatiotemporal gradients across two-dimensional surfaces and three-dimensional gels under flow-free conditions. Free diffusion between dynamically replenished flow channels acting as a sink and source is utilized to give rise to stable steady-state gradient profiles. The gradient profile is dictated by the engineered design of the device's gradient-generating region. Different designs can yield both linear and non-linear gradients of varying profiles. More complex gradients can be made by juxtaposing different designs within a single gradient-generating region. By fabricating an array of designs along the gradient-generating region, different gradient profiles can be generated simultaneously, allowing for parallel analysis. Additionally, simple methods of localizing gels into microdevices are demonstrated. The device was characterized by experimentally obtained gradient profiles of fluorescent molecules that corroborated closely with a simulated finite element model.
A Peptide Mimic of a Protective Epitope of Respiratory Syncytial Virus Selected from a Combinatorial Library Induces Virus-Neutralizing Antibodies and Reduces Viral Load In Vivo (1998)

Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis and pneumonia in infants and young children worldwide. As yet, there is no effective vaccine against RSV infection, and previous attempts to develop a formalin-inactivated vaccine resulted in exacerbated disease in recipients subsequently exposed to the virus. In the work described here, a combinatorial solid-phase peptide library was screened with a protective monoclonal antibody (MAb 19) to identify peptide mimics (mimotopes) of a conserved and conformationally-determined epitope of RSV fusion (F) protein. Two sequences identified (S1 [HWYISKPQ] and S2 [HWYDAEVL]) reacted specifically with MAb 19 when they were presented as solid-phase peptides. Furthermore, after amino acid substitution analyses, three sequences derived from S1 (S1S [HWSISKPQ], S1K [KWYISKPQ], and S1P [HPYISKPQ]), presented as multiple antigen peptides (MAPs), also showed strong reactivity with MAb 19. The affinity constants of the binding of MAb 19, determined by surface plasmon resonance analyses, were 1.19 x 10(9) and 4.93 x 10(9) M(-1) for S1 and S1S, respectively. Immunization of BALB/c mice with these mimotopes, presented as MAPs, resulted in the induction of anti-peptide antibodies that inhibited the binding of MAb 19 to RSV and neutralized viral infection in vitro, with titers equivalent to those in sera from RSV-infected animals. Following RSV challenge of S1S mimotope-immunized mice, a 98.7% reduction in the titer of virus in the lungs was observed. Furthermore, there was a greatly reduced cell infiltration in the lungs of immunized mice compared to that in controls. These results indicate the potential of peptide mimotopes to protect against RSV infection without exacerbating pulmonary pathology.
Human Atherosclerotic Intima and Blood of Patients with Established Coronary Artery Disease Contain High Density Lipoprotein Damaged by Reactive Nitrogen Species (2004)

High density lipoprotein (HDL) is the major carrier of lipid hydroperoxides in plasma, but it is not yet established whether HDL proteins are damaged by reactive nitrogen species in the circulation or artery wall. One pathway that generates such species involves myeloperoxidase (MPO), a major constituent of artery wall macrophages. Another pathway involves peroxynitrite, a potent oxidant generated in the reaction of nitric oxide with superoxide. Both MPO and peroxynitrite produce 3-nitrotyrosine in vitro. To investigate the involvement of reactive nitrogen species in atherogenesis, we quantified 3-nitrotyrosine levels in HDL in vivo. The mean level of 3-nitrotyrosine in HDL isolated from human aortic atherosclerotic intima was 6-fold higher (619 +/- 178 micromol/mol Tyr) than that in circulating HDL (104 +/- 11 micromol/mol Tyr; p < 0.01). Immunohistochemical studies demonstrated striking colocalization of MPO with epitopes reactive with an antibody to 3-nitrotyrosine. However, there was no significant correlation between the levels of 3-chlorotyrosine, a specific product of MPO, and those of 3-nitrotyrosine in lesion HDL. We also detected 3-nitrotyrosine in circulating HDL, and linear regression analysis demonstrated a strong correlation between the levels of 3-chlorotyrosine and levels of 3-nitrotyrosine. These observations suggest that MPO promotes the formation of 3-chlorotyrosine and 3-nitrotyrosine in circulating HDL but that other pathways also produce 3-nitrotyrosine in atherosclerotic tissue. Levels of HDL isolated from plasma of patients with established coronary artery disease contained twice as much 3-nitrotyrosine as HDL from plasma of healthy subjects, suggesting that nitrated HDL might be a marker for clinically significant vascular disease. The detection of 3-nitrotyrosine in HDL raises the possibility that reactive nitrogen species derived from nitric oxide might promote atherogenesis. Thus, nitrated HDL might represent a previously unsuspected link between nitrosative stress, atherosclerosis, and inflammation.
Ge segregation in SiGe/Si heterostructures and its dependence on deposition technique and growth atmosphere (1993)

Ge segregation at SiGe/Si heterointerfaces has been studied for films deposited by atmospheric pressure chemical vapor deposition (APCVD), ultrahigh vacuum CVD (UHV/CVD) and molecular beam epitaxy (MBE). Profiles were taken by secondary-ion-mass-spectroscopy (SIMS) of samples grown with these techniques at the same growth temperatures and Ge concentrations. The MBE grown profiles are dominated by segregation of Ge into the Si top layer in the temperature range from 450 to 800 °C. SiGe/Si interfaces deposited by UHV/CVD at elevated temperatures are smeared, but at 515 °C and below the interfaces are abrupt within the resolution of the SIMS. Heterostructures grown by APCVD show abrupt interfaces and no indication of Ge segregation in the investigated temperature range from 600 to 800 °C. Surface passivation by hydrogen appears to be responsible for the suppression of the Ge segregation in CVD processes.
Coexistence in Wireless Networks: Challenges and System-Level Solutions in the Unlicensed Bands (2006)

The increasing popularity of wireless networks makes interference and cross-talk between multiple systems inevitable. This book describes techniques for quantifying this, and the effects on the performance of wireless networks operating in the unlicensed bands. It also presents a variety of system-level solutions, obviating the need for new hardware implementations. The book starts with basic concepts and wireless protocols before moving on to interference performance evaluation, interference modeling, coexistence solutions, and concluding with common misconceptions and pitfalls. The theory is illustrated by reference to real-world systems such as Bluetooth and WiFi. With a number of case studies and many illustrations, this book will be of interest to graduate students in electrical engineering and computer science, to practitioners designing new WLAN and WPAN systems or developing new techniques for interference supression, and to general users of merging wireless technologies
Attention-Based Models for Speech Recognition (2015)

Recurrent sequence generators conditioned on input data through an attention mechanism have recently shown very good performance on a range of tasks in- cluding machine translation, handwriting synthesis and image caption gen- eration. We extend the attention-mechanism with features needed for speech recognition. We show that while an adaptation of the model used for machine translation in reaches a competitive 18.7% phoneme error rate (PER) on the TIMIT phoneme recognition task, it can only be applied to utterances which are roughly as long as the ones it was trained on. We offer a qualitative explanation of this failure and propose a novel and generic method of adding location-awareness to the attention mechanism to alleviate this issue. The new method yields a model that is robust to long inputs and achieves 18% PER in single utterances and 20% in 10-times longer (repeated) utterances. Finally, we propose a change to the at- tention mechanism that prevents it from concentrating too much on single frames, which further reduces PER to 17.6% level.
The Biology and Taxonomy of the Solanaceae. (1980)

The Biology and taxonomy of the Solanaceae , The Biology and taxonomy of the Solanaceae , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Collision recovery receiver for EPC Gen2 RFID systems (2012)

In this paper, a multi-tag anti-collision method with collision signal recovery for UHF RFID systems is proposed. Signal recovery of 2 tags or 3 tags is adopted in the algorithm and the frame size is optimized accordingly. Simulation results show that the average system efficiency of the proposed anti-collision algorithm can be up to 67%, while the system efficiency of the algorithms without adopting collision recovery is no more than 36.8%. The influence of non-ideal parameters in different scenarios, such as signal-noise-ratio (SNR) and frequency of clustering, is discussed as well.
Pleiotropic resistance to DNA-interactive drugs is associated with increased expression of genes involved in DNA replication, repair, and stress response. (2000)

A combination of four genetic suppressor elements (GSEs), two of which are derived from putative transcriptional regulators, was previously found to increase resistance to drugs inhibiting DNA replication in HT1080 fibrosarcoma cells. In the present study, two GSE-transduced cell lines, isolated with and without cytotoxic selection, were found to be resistant to a diverse group of DNA-interactive agents, including aphidicolin, hydroxyurea, cytarabine, etoposide, doxorubicin, and mafosfamide. Changes in gene expression associated with GSE-induced drug resistance were analyzed by cDNA array hybridization and reverse transcription-PCR. Twenty genes were found to be up-regulated in both of the resistant cell lines. These include genes involved in DNA replication and repair (e.g., PCNA, XRCC1, B-MYB, and GADD45), transcriptional regulators associated with stress response, and cell cycle checkpoint control (e.g., YB-1, DBPA, and ATF4), and genes for signal transduction proteins (e.g., protein tyrosine phosphatase 1B and regulatory subunits alpha and beta of cAMP-dependent protein kinase). The observed changes in gene expression may play a role in pleiotropic resistance to different classes of DNA-targeting drugs.
Determining MHC Restriction of T-cell Responses (2008)

T-cell receptors (TcR) recognize short linear peptides (9-15 amino acid long), which have been processed by an 'antigen-presenting cell' and complexed to products of the major histocompatibility complex (MHC). Peptides of the appropriate shape and charge are able to bind within the groove of the MHC molecule and it is this complex which is recognized by the TcR. The MHC molecules are highly polymorphic, but each individual will only express one maternal and one paternal allele of HLA Class 1 molecule A, B, and C and HLA Class II DR, DP, and DQ. As a result of TcR specificity and MHC restriction, a clone of T cells will bear a specific receptor which has a very limited repertoire of targets (peptide-MHC complexes). When sufficient numbers of TcR are engaged on a T-cell surface, a cascade of signal transduction events is initiated which results in cellular activation. When investigating the immune response, it may be advantageous to be able to identify which MHC molecules bind a particular peptide well and give rise to a vigorous T-cell response. Such information may be useful in generating effective vaccines. In this chapter, we provide examples of Epstein-Barr virus-transformed lymphoid cell lines and fibroblast cell lines to determine MHC restriction elements.
공동주택 SYSTEM FORM 공사의 생산성 분석 및 향상방안 제안 (2001)

벽식 구조 공동주택(고층아파트)은 수평, 수직구조체가 동일하게 연속되므로 시스템거푸집 시공이 효율적이다. 그런데 현재 많은 고층 건축물 시공현장에서 사용되고 있는 시스템 거푸집은 전용횟수의 증대와 콘크리트 품질향상의 장점을 가지고 있지만, 공장 제작되어 현장 반입된 후 2차 조립 과정중의 공기지연 및 시공초기의 인력과다투입 등으로 초기 계획공정달성에 많은 애로점을 가지고 있다. 이러한 측면에서, 각각의 노무자들이 실제 생산적인 작업에 소비하는 시간 비율과 공사지연의 정도 및 원인 등을 평가대상으로 생산성 저하의 원인을 찾아내어 개선방안을 찾아보고자 한다. 본 연구는 시스템거푸집 공정을 수행하고 있는 아파트 신축현장을 선택하여, 다양한 생산성 분석방법 중의 하나인 워크샘플링(Work Sampling)를 통하여 생산성을 분석한 후, 크루발런스스터디(Crew Balance Study)를 통하여 생산성 향상방안을 현장조립공정과 내부 폼(form)작업, 외부 폼(form)작업으로 구분하여 제시하였다. 【Application of system form is very effective to continuous horizontal or vertical walls of the apartment housing. Though the system forms that are used in the construction field have the advantage of concrete quality improvement and increasing number of usages, there are some problems in reaching early planning scheduling goal due to schedule delay and low productivity. This study is initiated to solve the problem and suggest some improvements searching for reasons that diminish the productivity. A case study was done in apartment construction field where system form was used and the productivity is analyzed by work sampling. Finally, productivity improvements for assembly of the form, internal form and external form are suggested, respectively.】
Demand response by dynamic demand control using frequency linked real‐time prices (2010)

Purpose The purpose of this paper is to propose a novel demand response method for real‐time (RT) balancing markets, which relies on dynamic demand control (DDC) based on frequency linked RT prices. Design/methodology/approach A RT balancing market, where the RT price varies inversely with the system frequency, is described. In such a market, producers and consumers can get the RT price, simply by monitoring the frequency deviations themselves. Air conditioning load, the main contributor of summer peaks, is selected for DDC. A physically based model of air conditioner load is taken to simulate the load control. A smart load controller is proposed that changes the thermostat setting with deviations in grid frequency/RT price. Simple examples are simulated to show the load reductions achieved by DDC in a single air conditioner, a group of large number of air conditioners and a RT market consisting of four generation companies and four distribution companies. Findings The result of simulation on a single air conditioner shows that significant reduction in energy consumption can be achieved during severe frequency dips in a RT market. The results of simulation in an example of a RT market show that such load control not only results in better frequency control but also lowers the RT price of power. Practical implications The demand control mechanism suggested in this paper can be applied to Indian market setting but its applicability to other markets might be limited due to differing, reliability standards, market rules, and regulatory framework. Originality/value This paper finds that DDC by distribution companies based on RT price/frequency signal not only results in a significant benefit to these companies and consumers but also helps the system operator in frequency regulation. By making the demand‐side participate in frequency regulation, such control can potentially facilitate an increase in renewable energy portfolio.
Regulatory Effects of Interleukin (IL)-1, Interferon-β, and IL-4 on the Production of IL-1 Receptor Antagonist by Human Adipose Tissue (2004)

Adipose tissue is the source of production and site of action of several pro- and antiinflammatory cytokines. We have recently shown that white adipose tissue (WAT) is a major producer of the antiinflammatory IL-1 receptor antagonist (IL-1Ra). Because IL-1Ra serum levels are elevated 7-fold in human obesity and an excess of this protein has been implicated in the acquired resistance to leptin and insulin, we investigated the regulation of IL-1Ra in human WAT. We demonstrate that IL-1Ra is mainly produced by adipocytes, rather than the stromal fraction of WAT, and that IL-1alpha and beta, as well as interferon-beta (IFN-beta), strongly up-regulate the expression and secretion of IL-1Ra in WAT. Moreover, human WAT expresses the receptors and proteins known to be required for the action of IL-1 (IL-1 receptor type I, IL-1 receptor accessory protein) and IFN-beta (IFN-alpha/beta receptor subunits 1 and 2). Finally, human WAT actively secretes these regulatory cytokines, suggesting that they up-regulate IL-1Ra through a local autocrine/paracrine action, which is hypothesized to play a regulatory role in adipogenesis and metabolism.
Quantitative study of collagen and elastin of the optic nerve head and sclera in human and experimental monkey glaucoma (1991)

Quantitative studies of collagen density and fibril size distribution as well as elastin density were carried out in the optic nerve head and sclera of human and experimental monkey glaucoma eyes. The collagen fibrils of the normal lamina cribrosa are smaller and more uniform in size than those of the sclera. This feature may be an adaptation to maximize either elasticity or resistance to mechanical stress. In glaucomatous nerve heads, there is a major disruption of the structure of the lamina cribrosa beam structure, including a decrease in collagen density. The peripapillary sclera undergoes similar collagen density changes to those in the nerve head in human glaucoma eyes. Elastin fiber density is unchanged in the glaucomatous nerve heads that we studied.
Nicotine Protects Kidney from Renal Ischemia/Reperfusion Injury through the Cholinergic Anti-Inflammatory Pathway (2007)

Kidney ischemia/reperfusion injury (I/R) is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the alpha7nAChR, as attested by the absence of protection in alpha7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-alpha and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic alpha7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation.