gebhart/patrepeval huggingface dataset:
Cyclin-Dependent Kinase Inhibitors as Anticancer Drugs (2010)

Poor therapeutic outcomes and serious side effects, together with acquired resistance to multiple drugs, are common problems of current cancer therapies. Therefore, there is an urgent need for new cancer-targeted drugs, which has led (inter alia) to the development of molecules that can specifically inhibit cyclin-dependent kinases (CDKs). In addition to their cell cycle regulatory functions, CDKs, especially CDK7 and CDK9, play important roles in the regulation of RNA polymerase II-mediated transcription. Here, we report on progress in the preclinical development of CDK inhibitors and their anticancer activities. Special attention is paid to the action mechanisms of the pan-specific CDK inhibitors flavopiridol and roscovitine, which have already entered phase II clinical trials as treatments for various tumours. The links between their ability to inhibit transcription and sensitisation of some types of cancer to apoptosis, mechanisms leading to p53 activation, and their synergistic cooperation with common DNA damaging drugs are also discussed. It has been demonstrated that drug-resistant cancer cells can arise during therapeutic application of small molecule protein kinase inhibitors. Clinical resistance to CDK inhibitors has not yet been described, but by comparing CDKs to other kinases, and CDK inhibitors to other clinically used protein kinase inhibitors, we also discuss possible mechanisms that could lead to resistance to CDK inhibitors.
Single nucleotide polymorphism discrimination assisted by improved base stacking hybridization using oligonucleotide microarrays (2003)

Efficiencies of mismatch discrimination using size-varied capture probes were examined at various hybridization temperatures. The probes were 17, 15, 13, 11, 9, and 7 nucleotides long and contained single-base mismatches at their 3' ends. The optimal signal intensity and efficiency of base stacking hybridization on mismatch discrimination were observed for capture probes with a melting temperature (Tm) value of 36 degrees C, in the detection of DNA sequence variations at 40 degrees C. We employed asymmetric PCR to prepare single-stranded target DNA labeled with a fluorescent dye, and the PCR product was hybridized on the DNA microarray with no further purification. Our efforts have enhanced the sensitivity and simplified the procedures of base stacking hybridization on mismatch discrimination. As a model experiment, this improved technology was used to identify plasmid templates of human leukocyte antigen (HLA)-A alleles 2601, 2902, and 0206 on oligonucleotide microarrays. It is now possible to apply this simple, rapid, sensitive, and reliable base stacking hybridization technology to detect DNA sequence variations on microarrays in clinical diagnosis and other applications.
A proteolytic fragment of Trypanosoma cruzi trans-sialidase lacking the carboxyl-terminal domain is active, monomeric, and generates antibodies that inhibit enzymatic activity. (1994)

trans-Sialidase isolated from trypomastigote forms of Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, is multimeric and heterogeneous in size. We show here that limited proteolysis of tans-sialidase with papain yields a single monomeric polypeptide chain of 70 kDa that conserves full enzymatic activity on soluble and membrane-bound substrates. The papain fragment lacks most of the 12-amino acid repeats of the carboxyl-terminal domain that comprises about 50% of the native trans-sialidase. When injected into rabbits, the papain-generated fragment induces antibodies that inhibit trans-sialidase activity and trypomastigote sialylation. The repeats are also not required for the stability of the enzyme or for the correct folding during the biosynthesis in Escherichia coli, but seem essential for trans-sialidase oligomerization. We conclude that trans-sialidase is composed of two structurally and functionally independent domains.
Cisco Router Firewall Security (2004)

Harden perimeter routers with Cisco firewall functionality and features to ensure network security Detect and prevent denial of service (DoS) attacks with TCP Intercept, Context-Based Access Control (CBAC), and rate-limiting techniques Use Network-Based Application Recognition (NBAR) to detect and filter unwanted and malicious traffic Use router authentication to prevent spoofing and routing attacks Activate basic Cisco IOS filtering features like standard, extended, timed, lock-and-key, and reflexive ACLs to block various types of security threats and attacks, such as spoofing, DoS, Trojan horses, and worms Use black hole routing, policy routing, and Reverse Path Forwarding (RPF) to protect against spoofing attacks Apply stateful filtering of traffic with CBAC, including dynamic port mapping Use Authentication Proxy (AP) for user authentication Perform address translation with NAT, PAT, load distribution, and other methods Implement stateful NAT (SNAT) for redundancy Use Intrusion Detection System (IDS) to protect against basic types of attacks Obtain how-to instructions on basic logging and learn to easily interpret results Apply IPSec to provide secure connectivity for site-to-site and remote access connections Read about many, many more features of the IOS firewall for mastery of router securityThe Cisco IOS firewall offers you the feature-rich functionality that you've come to expect from best-of-breed firewalls: address translation, authentication, encryption, stateful filtering, failover, URL content filtering, ACLs, NBAR, and many others. Cisco Router Firewall Security teaches you how to use the Cisco IOS firewall to enhance the security of your perimeter routers and, along the way, take advantage of the flexibility and scalability that is part of the Cisco IOS Software package.Each chapter in Cisco Router Firewall Security addresses an important component of perimeter router security. Author Richard Deal explains the advantages and disadvantages of all key security features to help you understand when they should be used and includes examples from his personal consulting experience to illustrate critical issues and security pitfalls. A detailed case study is included at the end of the book, which illustrates best practices and specific information on how to implement Cisco router security features.Whether you are looking to learn about firewall security or seeking how-to techniques to enhance security in your Cisco routers, Cisco Router Firewall Security is your complete reference for securing the perimeter of your network.This book is part of the Networking Technology Series from Cisco Press, which offers networking professionals valuable information for constructing efficient networks, understanding new technologies, and building successful careers.
Composition and in vitro Anticancer Activities of the Leaf Essential Oil of Neolitsea variabillima from Taiwan (2013)

This study investigated the chemical composition and in vitro anticancer activities of the essential oil isolated from the leaf of Neolitsea variabillima. The essential oil was isolated using hydrodistillation in a Clevenger-type apparatus, and characterized by GC-FID and GC-MS. Sixty-seven compounds were identified, representing 100% of the oil. The main components identified were trans-beta-ocimene (13.4%), alpha-cadinol (10.5%), terpinen-4-ol (9.3%), tau-cadinol (9.2%), beta-caryophyllene (8.8%), and sabinene (6.7%). The anticancer activities of oil were evaluated. The results showed that the oil exhibited cytotoxic activity against human oral, liver, lung, colon, melanoma, and leukemic cancer cells. The presence of beta-caryophyllene, tau-cadinol, and alpha-cadinol significantly contributed to the anticancer activities of N. variabillima leaf oil.
Novel, Potent Anti-Androgens of Therapeutic Potential: Recent Advances and Promising Developments (2010)

The beneficial effect of androgen ablation has been well established in prostate cancer therapy. Despite the initial response, patients typically relapse with a more aggressive form described as castration-resistant prostate cancer (CRCP), driven by continued androgen receptor (AR) signaling. This review details the current state of anti-androgen therapy, mainly for CRPC, with major emphasis on the most potent and promising compounds under development. Anti-androgen failure has been linked to elevated AR expression, increased expression of coactivator proteins, AR mutations, ligand-independent AR activation and persistent intraprostatic androgens. MDV3100, BMS-641988 and VN/124-1 were developed to overcome these mechanisms. In CRCP, prostate cancer cells still rely on intracellular androgens and, to a greater extent, on active AR for growth and survival. Therefore, potent anti-androgens that efficiently disrupt the functions (signaling) of AR are envisioned to be effective drugs for all types of prostate cancers.
Adenovirus and Adeno-Associated Virus Vectors (2002)

Recombinant adenovirus (rAd) and recombinant adeno-associated virus (rAAV) are among the most extensively used vectors in gene therapy studies to date. These two vectors share some similar features such as a broad host range and ability to infect both proliferating and quiescent cells. However, they also possess their own unique set of properties that render them particularly attractive for gene therapy applications. rAd vectors can accommodate larger inserts, mediate transient but high levels of protein expression, and can be easily produced at high titers. Development of gutted rAd vectors has further increased the cloning capacity of these vectors. The gaining popularity of rAAV use in gene therapy can be attributed to its lack of pathogenicity and added safety due to its replication defectiveness, and its ability to mediate long-term expression in a variety of tissues. Site-specific integration, as occurs with wild-type AAV, will be a unique and valuable feature if incorporated into rAAV vectors, further improving their safety. This paper describes these properties of rAd and rAAV vectors, and discusses further development and vector improvements that continue to extend the utility of these vectors, such as cell retargeting by capsid modification, differential transduction by use of serotypes, and extension of the cloning capacity of rAAV vectors by dual vector heterodimerization.
Activation of proto-oncogenes in human and mouse lung tumors. (1991)

Lung cancer is a leading cause of cancer-related deaths in several nations. Epidemiological studies have indicated that 85% of all lung cancer deaths and 30% of all cancer deaths in the U.S. are associated with tobacco smoking. Various chemicals in tobacco smoke are thought to react with DNA and to ultimately yield heritable mutations. In an effort to understand the molecular mechanisms involved in lung tumorigenesis, we have analyzed proto-oncogene activation in a series of human lung tumors from smokers and spontaneously occurring and chemically induced lung tumors in mice. Approximately 86% of the human lung tumors and greater than 90% of the mouse lung tumors were found to contain activated oncogenes. ras Oncogenes activated by point mutations were detected in many of the human lung adenocarcinomas and virtually all of the mouse lung adenomas and adenocarcinomas. The mutation profiles of the activated K-ras genes detected in the chemically induced mouse lung tumors suggest that the observed mutations result from genotoxic effects of the chemicals. Comparison of the K-ras mutations observed in the human lung adenocarcinomas with mutation profiles observed in the mouse lung tumors suggest that bulky hydrophobic DNA adducts may be responsible for the majority of the mutations observed in the activated human K-ras genes. Other data indicate that approximately 20% of human lung tumors contain potentially novel transforming genes that may also be targets for mutagens in cigarette smoke.
Solution–Liquid–Solid Growth of Soluble GaAs Nanowires (2003)

GaAs nanowires exhibiting narrow diameter distributions and small diameters within and near the strong‐confinement regime can be generated using the solution–liquid–solid (SLS) mechanism (see Figure for 5.99 nm diameter wires). A relationship between the mean diameters of the nanowires and the indium catalyst nanoparticles from which the nanowires are grown is furthermore established.
The aryl hydrocarbon receptor in inflammatory bowel disease (2012)

These novel findings may help explain how environmental factors may regulate mucosal immune responses.
Natural history of woodchuck hepatitis virus infections during the course of experimental viral infection: molecular virologic features of the liver and lymphoid tissues (1989)

In this study, the kinetic patterns of woodchuck hepatitis virus (WHV) infection were monitored in the liver and the five primary components of the lymphoid system (peripheral blood lymphocytes, lymph nodes, bone marrow, spleen, and thymus). Groups of woodchucks experimentally infected with a standardized inoculum of WHV were sacrificed at different times over a 65-week period beginning in the preacute phase of viral infection and continuing to the period of serologic recovery or the establishment of chronic infections and subsequent hepatocellular carcinoma. Infection by WHV was not limited to the liver but involved the major components of the lymphoid system during all stages of virus infection. A complex series of kinetic patterns was observed for the appearance of WHV DNA in the different lymphoid compartments and the liver during the entire course of viral infection. A progressive evolution of different WHV genomic forms related to the replicative state of WHV was also observed. Lymphoid cells of the bone marrow were the first cells in which WHV DNA was detected, followed in order by the liver, the spleen, peripheral blood lymphocytes, lymph nodes, and finally the thymus. Several differences were observed in the cellular WHV DNA patterns between woodchucks that developed chronic WHV infections and those that serologically recovered from acute WHV infections. The observations compiled in this study indicate that the host lymphoid system is intimately involved in the natural history of hepadnavirus infections from the earliest stages of virus entry.
Allelic exchange in Escherichia coli using the Bacillus subtilis sacB gene and a temperature‐sensitive pSC101 replicon (1991)

To facilitate efficient allelic exchange of genetic information into a wild-type strain background, we improved upon and merged approaches using a temperature-sensitive plasmid and a counter-selectable marker in the chromosome. We first constructed intermediate strains of Escherichia coli K12 in which we replaced wild-type chromosomal sequences, at either the fimB-A or lacZ-A loci, with a newly constituted DNA cassette. The cassette consists of the sacB gene from Bacillus subtilis and the neomycin (kanamycin) resistance gene of Tn5, but, unlike another similar cassette, it lacks IS1 sequences. We found that sucrose sensitivity was highly dependent on incubation temperature and sodium chloride concentration. The DNA to be exchanged into the chromosome was first cloned into derivatives of plasmid pMAK705, a temperature-sensitive pSC101 replicon. The exchanges were carried out in two steps, first selecting for plasmid integration by standard techniques. In the second step, we grew the plasmid integrates under non-selective conditions at 42 degrees C, and then in the presence of sucrose at 30 degrees C, allowing positive selection for both plasmid excision and curing. Despite marked locus-specific strain differences in sucrose sensitivity and in the growth retardation due to the integrated plasmids, the protocol permitted highly efficient exchange of cloned DNA into either the fim or lac chromosomal loci. This procedure should allow the exchange of any DNA segment, in addition to the original or mutant allelic DNA, into any non-essential parts of the E. coli chromosome.
Iodination, radioiodination and spectroscopic identification of β-carboline derivatives (1999)

The synthesis and spectral properties (MS, and NMR) of radioiodinated β-carbolines: 6-(I) and 8-(II) [131I]-iodo-1-methyl-7-methoxy-β-carboline([131I]-iodo-harmine), 6-(III) and 8-(IV) [131I]-iodo-1-methyl-β-carboline-7-ol([131I]-iodo-harmol), 8-[131I]-iodo-1-methyl-7-methoxy-3,4-dihydro-β-carboline(8-[131I]-iodo-harmaline) (V), 8-[131I]-iodo-3,4-dihydro-1-methyl-β-carboline-7-ol(8-[131I]-iodo-harmalol) (VI), 6-[131I]-iodo-1-methyl-β-carboline(6-[131I]-iodo-harmane) (VII) are described. These are compounds of biological importance and can be used for brain mapping with SPECT technology. Copyright © 1999 John Wiley & Sons, Ltd.
Involvement of αvβ5 integrin–mediated activation of latent transforming growth factor β1 in autocrine transforming growth factor β signaling in systemic sclerosis fibroblasts (2005)

Up-regulated expression of alphavbeta5 contributes to the establishment of autocrine TGFbeta signaling in SSc fibroblasts through activation of endogenous latent TGFbeta1.
Skin and Soft Tissue Infections (2009)

This chapter contains sections titled: Introduction and epidemiology Impetigo Blistering skin diseases Folliculitis, furuncles, and carbuncles Abscesses Cellulitis Necrotizing fasciitis Pyomyositis Mastitis Hidradenitis suppurativa Botryomycosis Skin and soft tissue infections caused by coagulase-negative staphylococci Colonization, outbreaks, and recurrent infection Antibacterial therapy Acknowledgments References
Cell behaviour on micropatterned substrata: limits of extracellular matrix geometry for spreading and adhesion (2003)

Cell adhesion, spreading and migration require the dynamic formation and dispersal of contacts with the extracellular matrix (ECM). In vivo, the number, availability and distribution of ECM binding sites dictate the shape of a cell and determine its mobility. To analyse the geometrical limits of ECM binding sites required for cell attachment and spreading, we used microcontact printing to produce regular patterns of ECM protein dots of defined size separated by nonadhesive regions. Cells cultured on these substrata adhere to and spread on ECM regions as small as 0.1 microm2, when spacing between dots is less than 5 microm. Spacing of 5-25 microm induces a cell to adapt its shape to the ECM pattern. The ability to spread and migrate on dots > or =1 microm2 ceases when the dot separation is > or =30 microm. The extent of cell spreading is directly correlated to the total substratum coverage with ECM-proteins, but irrespective of the geometrical pattern. An optimal spreading extent is reached at a surface coating above 15%. Knowledge of these geometrical limits is essential for an understanding of cell adhesion and migration, and for the design of artificial surfaces that optimally interact with cells in a living tissue.
CT Angiography for Safe Discharge of Patients with Possible Acute Coronary Syndromes (2012)

A CCTA-based strategy for low-to-intermediate-risk patients presenting with a possible acute coronary syndrome appears to allow the safe, expedited discharge from the emergency department of many patients who would otherwise be admitted. (Funded by the Commonwealth of Pennsylvania Department of Health and the American College of Radiology Imaging Network Foundation; ClinicalTrials.gov number, NCT00933400.).
Compressive light transport sensing (2009)

In this article we propose a new framework for capturing light transport data of a real scene, based on the recently developed theory of compressive sensing. Compressive sensing offers a solid mathematical framework to infer a sparse signal from a limited number of nonadaptive measurements. Besides introducing compressive sensing for fast acquisition of light transport to computer graphics, we develop several innovations that address specific challenges for image-based relighting, and which may have broader implications. We develop a novel hierarchical decoding algorithm that improves reconstruction quality by exploiting interpixel coherency relations. Additionally, we design new nonadaptive illumination patterns that minimize measurement noise and further improve reconstruction quality. We illustrate our framework by capturing detailed high-resolution reflectance fields for image-based relighting.
[Dexamethasone and vorinostat cooperatively promote differentiation and apoptosis in Kasumi-1 leukemia cells through ubiquitination and degradation of AML1-ETO]. (2013)

The results indicated that DEX and vorinostat could synergistically inhibit the Kasumi-1 cells proliferation, induce Kasumi-1 cells differentiation and apoptosis through ubiquitination and degradation of AML1-ETO.
Pharmacological actions of the atypical antipsychotic drug clozapine: A review (1996)

Clozapine [8-chloro- 11-(4-methyl- 1-piperazinyl)-3H-dibenzo (b,e)(1,4) diazepine], or clozaril, is a member of the dibenazepine class of antipsychotic drugs. Initially, studies in animals using a number of neurochemical, biochemical, electrophysiological, and behavioral paradigms indicated that clozapine was markedly different from various typical antipsychotic drugs such as haloperidol and chlorpromazine. Subsequently, clinical studies have shown that clozapine is effective in ameliorating the core symptoms, as well as the negative symptoms, in schizophrenia. However, clozapine has a much lower propensity for inducing neurological side effects after acute or repeated administration compared to various typical neuroleptics. Furthermore, clozapine is therapeutically effective in treating about 30% of schizophrenic patients who are resistant to standard antipsychotic drugs. Based on the above information, clozapine has been designated an atypical antipsychotic drug. However, at this time, it is not entirely clear why clozapine is such a unique antipsychotic drug. To date, there has not been a comprehensive review regarding clozapine's pharmacological profile. Therefore, we will review clozapine's profile in the following areas: 1) affinity for neurotransmitter receptors in the brain; 2) electrophysiology (in vivo, single-cell recording and iontophoresis; in vitro studies); 3) in vivo microdialysis and voltammetry; 4) monoamine turnover or metabolism; 5) intermediate early gene expression; 6) positron emission tomography studies; and 7) molecular biological studies. We will also compare and contrast clozapine's acute and chronic effects, and discuss the merits of various hypotheses that have been put forward to explain clozapine's unique profile.
Selection and Characterization of an RNA Decoy for Transcription Factor NF-κB (1999)

Despite their chemical similarity, DNA and RNA sequences typically adopt very different structures within cells and are recognized by different proteins. However, a few interesting examples of proteins with dual specificity for DNA and RNA have previously been noted. These observations raise the possibility that RNA surrogates might be identified for many transcription factors that normally bind DNA. As an initial test of this novel concept, we used in vitro selection to isolate a small RNA aptamer that binds with nanomolar affinity to human transcription factor NF-kappa B, a key regulator of inflammation, HIV-1 gene expression, and apoptosis. Selected RNAs contain a 31-nucleotide core domain that was shown by mutation and deletion analyses to be necessary and sufficient for NF-kappa B binding. Neither DNA nor 2'-O-methyl RNA analogues of the aptamer bound NF-kappa B. The results of competition experiments demonstrate that binding of the RNA aptamer blocks the ability of NF-kappa B to bind duplex DNA. Expression of this aptamer structure within heterologous nuclear RNA transcripts may provide a new strategy to inhibit NF-kappa B function in vivo. Aptamers that inhibit transcription factors might be useful in a variety of applications.