gebhart/patrepeval huggingface dataset:
Intra-lymphatic administration of interleukin-2 (IL-2) in cancer patients: a pilot study. (1988)

Seven patients suffering from advanced metastatic tumours, unresponsive to standard therapies, were treated with 3 to 5 intra-lymphatic injections of interleukin-2 (IL-2) and IL-2-activated-peripheral blood lymphocytes (PBL). A partial (50-70%) regression was obtained in three of the patients, and complete regression in the other four. It thus seems that intra-lymphatic injections of IL-2 and PBL can be used for the treatment of certain solid tumours (e.g., hypernephroma, adenocarcinoma, seminoma, epidermoid carcinoma) without noticeable side effects. This method could advantageously replace intravenous IL-2 administration and warrants further investigation.
Molecular basis for the high-affinity binding and stabilization of firefly luciferase by PTC124 (2010)

Firefly luciferase (FLuc), an ATP-dependent bioluminescent reporter enzyme, is broadly used in chemical biology and drug discovery assays. PTC124 (Ataluren; (3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid) discovered in an FLuc-based assay targeting nonsense codon suppression, is an unusually potent FLuc-inhibitor. Paradoxically, PTC124 and related analogs increase cellular FLuc activity levels by posttranslational stabilization. In this study, we show that FLuc inhibition and stabilization is the result of an inhibitory product formed during the FLuc-catalyzed reaction between its natural substrate, ATP, and PTC124. A 2.0 A cocrystal structure revealed the inhibitor to be the acyl-AMP mixed-anhydride adduct PTC124-AMP, which was subsequently synthesized and shown to be a high-affinity multisubstrate adduct inhibitor (MAI; K(D) = 120 pM) of FLuc. Biochemical assays, liquid chromatography/mass spectrometry, and near-attack conformer modeling demonstrate that formation of this novel MAI is absolutely dependent upon the precise positioning and reactivity of a key meta-carboxylate of PTC124 within the FLuc active site. We also demonstrate that the inhibitory activity of PTC124-AMP is relieved by free coenzyme A, a component present at high concentrations in luciferase detection reagents used for cell-based assays. This explains why PTC124 can appear to increase, instead of inhibit, FLuc activity in cell-based reporter gene assays. To our knowledge, this is an unusual example in which the "off-target" effect of a small molecule is mediated by an MAI mechanism.
Scalable Monocular SLAM (2006)

Localization and mapping in unknown environments becomes more difficult as the complexity of the environment increases. With conventional techniques, the cost of maintaining estimates rises rapidly with the number of landmarks mapped. We present a monocular SLAM system that employs a particle filter and top-down search to allow realtime performance while mapping large numbers of landmarks. To our knowledge, we are the first to apply this FastSLAM-type particle filter to single-camera SLAM. We also introduce a novel partial initialization procedure that efficiently determines the depth of new landmarks. Moreover, we use information available in observations of new landmarks to improve camera pose estimates. Results show the system operating in real-time on a standard workstation while mapping hundreds of landmarks.
Cloning and nucleotide sequence of the leucyl-tRNA synthetase gene of Bacillus subtilis (1992)

The leucyl-tRNA synthetase gene (leuS) of Bacillus subtilis was cloned and sequenced. A mutation in the gene, leuS1, increases the transcription and expression of the ilv-leu operion, permitting monitoring of leuS alleles. The leuS1 mutation was mapped to 270 degrees on the chromosome. Sequence analysis showed that the mutation is a single-base substitution, possibly in a monocistronic operon. The leader mRNA predicted by the sequence would contain a number of possible secondary structures and a T box, a sequence observed upstream of leader mRNA terminators of Bacillus tRNA synthetases and the B. subtilis ilv-leu operon. The DNA of the B. subtilis leuS open reading frame is 48% identical to the leuS gene of Escherichia coli and is predicted to encode a polypeptide with 46% identity to the leucyl-tRNA synthetase of E. coli.
Functional Role of Adult Hippocampal Neurogenesis as a Therapeutic Strategy for Mental Disorders (2012)

Adult neurogenesis, the process of generating new neurons from neural stem cells, plays significant roles in synaptic plasticity, memory, and mood regulation. In the mammalian brain, it continues to occur well into adulthood in discrete regions, namely, the hippocampus and olfactory bulb. During the past decade, significant progress has been made in understanding the mechanisms regulating adult hippocampal neurogenesis and its role in the etiology of mental disorders. In addition, adult hippocampal neurogenesis is highly correlated with the remission of the antidepressant effect. In this paper, we discuss three major psychiatric disorders, depression, schizophrenia, and drug addiction, in light of preclinical evidence used in establishing the neurobiological significance of adult neurogenesis. We interpret the significance of these results and pose questions that remain unanswered. Potential treatments which include electroconvulsive therapy, deep brain stimulation, chemical antidepressants, and exercise therapy are discussed. While consensus lacks on specific mechanisms, we highlight evidence which indicates that these treatments may function via an increase in neural progenitor proliferation and changes to the hippocampal circuitry. Establishing a significant role of adult neurogenesis in the pathogenicity of psychiatric disorders may hold the key to potential strategies toward effective treatment.
In Vitro Activities of Terbinafine against Cutaneous Isolates ofCandida albicansand Other Pathogenic Yeasts (1998)

Terbinafine is active in vitro against a wide range of pathogenic fungi, including dermatophytes, molds, dimorphic fungi, and some yeasts, but earlier studies indicated that the drug had little activity against Candida albicans. In contrast, clinical studies have shown topical and oral terbinafine to be active in cutaneous candidiasis and Candida nail infections. In order to define the anti-Candida activity of terbinafine, we tested the drug against 350 fresh clinical isolates and additional strains by using a broth dilution assay standardized according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) M27-A assay. Terbinafine was found to have an MIC of 1 microg/ml for reference C. albicans strains. For 259 clinical isolates, the MIC at which 50% of the isolates are inhibited (MIC50) of terbinafine was 1 microg/ml (fluconazole, 0.5 microg/ml), and the MIC90 was 4 microg/ml (fluconazole, 1 microg/ml). Terbinafine was highly active against Candida parapsilosis (MIC90, 0.125 microg/ml) and showed potentially interesting activity against isolates of Candida dubliniensis, Candida guilliermondii, Candida humicola, and Candida lusitaniae. It was not active against the Candida glabrata, Candida krusei, and Candida tropicalis isolates in this assay. Cryptococcus laurentii and Cryptococcus neoformans were highly susceptible to terbinafine, with MICs of 0.06 to 0.25 microg/ml. The NCCLS macrodilution assay provides reproducible in vitro data for terbinafine against Candida and other yeasts. The MICs for C. albicans and C. parapsilosis are compatible with the known clinical efficacy of terbinafine in cutaneous infections, while the clinical relevance of its activities against the other species has yet to be determined.
Interleukin-4-deficient BALB/c mice develop an enhanced Th1-like response but control cardiac inflammation following Borrelia burgdorferi infection (2000)

Interleukin-4 has been reported to critically modulate Borrelia burgdorferi infection and Lyme arthritis in experimental murine models. To determine the in vivo role of IL-4 in controlling Lyme carditis, we compared immunological responses and the severity of cardiac inflammation in wild-type BALB/c (IL-4 +/+) and IL-4 deficient BALB/c (IL-4 −/−) mice infected with B. burgdorferi by tick-bite. At day 15 and 30 post-infection IL-4 −/− mice produced significantly greater titers of spirochete-specific IgG2a than the wild-type IL-4 +/+ mice, which produced significantly more spirochete-specific IgG1. Following in vitro antigenic stimulation with B. burgdorferi antigen, splenocytes from infected IL-4 −/− and IL-4 +/+ mice displayed similar magnitudes of proliferative responses at day 15 and 30 post-infection. At day 30 antigen-stimulated splenocytes from infected IL-4 −/− mice, however, produced significantly more IFN-γ than those derived from similarly infected IL-4 +/+ mice, suggesting that Th1-influenced responses predominated in IL-4 −/− mice. Moreover, inflamed hearts from IL-4 −/− mice displayed higher levels of IFN-γ and TNF-α transcripts as compared to IL-4 +/+ mice. At both time points antigen-stimulated splenocytes from IL-4 +/+ and IL-4 −/− mice produced significant amounts of IL-10 but those from IL-4 +/+ mice produced either no or little IL-4. Histopathology demonstrated typical Lyme carditis in both IL-4 +/+ and IL-4 −/− mice at day 15 and day 30. Although Borrelia-infected IL-4 −/− mice developed a more severe carditis on day 30, the carditis resolved by day 50, as it did in IL4 +/+ mice. These results indicate that although IL-4 may help limit the severity of Lyme carditis, its absence does not preclude resolution of cardiac lesions.
Video streaming using a location-based bandwidth-lookup service for bitrate planning (2012)

A lot of people around the world commute using public transportation and would like to spend this time viewing streamed video content such as news or sports updates. However, mobile wireless networks typically suffer from severe bandwidth fluctuations, and the networks are often completely unresponsive for several seconds, sometimes minutes. Today, there are several ways of adapting the video bitrate and thus the video quality to such fluctuations, for example, using scalable video codecs or segmented adaptive HTTP streaming that switches between nonscalable video streams encoded in different bitrates. Still, for a better long-term video playout experience that avoids disruptions and frequent quality changes while using existing video adaptation technology, it is desirable to perform bandwidth prediction and planned quality adaptation. This article describes a video streaming system for receivers equipped with a GPS. A receiver's download rate is constantly monitored, and periodically reported back to a central database along with associated GPS positional data. Thus, based on the current location, a streaming device can use a GPS-based bandwidth-lookup service in order to better predict the near-future bandwidth availability and create a schedule for the video playout that takes likely future availability into account. To create a prototype and perform initial tests, we conducted several field trials while commuting using public transportation. We show how our database has been used to predict bandwidth fluctuations and network outages, and how this information helps maintain uninterrupted playback with less compromise on video quality than possible without prediction.
Advantages of the Circular Dumbbell Decoy in Gene Therapy and Studies of Gene Regulation (2003)

Decoy oligodeoxynucleotides (ODN) that can reduce the trans-activity of transcription factors may be highly useful in gene therapy and the study of transcriptional regulation. Several different types of these double-stranded DNA decoys have been developed, including unmodified oligonucleotide duplexes, alphabeta-anomeric oligonucleotides, and oligonucleotide duplexes with methylphosphonate- and phosphorothioate-modified linkages. The latter ODNs have been particularly extensively studied but suffer from a number of limitations, including their insensitivity to polymerases, their lack of sequence specificity, and their tendency to activate immune responses. To resolve these problems, circular dumbbell (CD) double-stranded ODNs were developed. These CD ODNs are constructed by the circularization of the 3' and 5' ends of the oligonucleotides and enzymatic ligation. They exhibit high resistance to nucleases, are easily taken up by cells, and have a nontoxic unmodified backbone that resembles natural DNA. In this article, we review the method of constructing CD ODNs and their advantages compared to other modified ODNs for use as transcription decoys.
Complement Contributes to Inflammatory Tissue Destruction in a Mouse Model of Ross River Virus-Induced Disease (2007)

Arthritogenic alphaviruses, including Ross River virus (RRV) and chikungunya virus, are mosquito-borne viruses that cause significant human disease worldwide, including explosive epidemics that can result in thousands to millions of infected individuals. Similar to infection of humans, infection of C57BL/6 mice with RRV results in severe monocytic inflammation of bone, joint, and skeletal muscle tissues. We demonstrate here that the complement system, an important component of the innate immune response, enhances the severity of RRV-induced disease in mice. Complement activation products were detected in the inflamed tissues and in the serum of RRV-infected wild-type mice. Furthermore, mice deficient in C3 (C3(-/-)), the central component of the complement system, developed much less severe disease signs than did wild-type mice. Complement-mediated chemotaxis is essential for many inflammatory arthritides; however, RRV-infected wild-type and C3(-/-) mice had similar numbers and composition of inflammatory infiltrates within hind limb skeletal muscle tissue. Despite similar inflammatory infiltrates, RRV-infected C3(-/-) mice exhibited far less severe destruction of skeletal muscle tissue. In addition to these studies, complement activation was also detected in synovial fluid from RRV-infected patients. Taken together, these findings indicate that complement activation occurs in the tissues of humans and mice infected with RRV and suggest that complement plays an essential role in the effector phase, but not the inductive phase, of RRV-induced arthritis and myositis.
A simple concealment for ATM bursty cell loss (1993)

In the ATM (asynchronous transfer mode) network, a fixed-length packet (cell) which contains a header and an information field is used to provide integrated services, but bit error and cell loss error are inevitable. In order to cope with cell loss, pixel arrangement (PR) and block rearrangement (BR) are presented. The PR and BR are used for the concealment of ATM cell loss. This scheme is able to reduce the blocking effects and restore the sequential burst cell loss errors. Computer simulation shows that the concealment of even the burst cell loss improves the image quality.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Differential genomic alterations in normal and cancerous lung cells in response to chronic inflammation (2013)

Although chronic inflammation increases the risk of carcinogenesis, there have been few reports of genome-wide screening for chromosomal alterations and DNA damage, such as mutations and strand breaks, induced by chronic inflammation. This study utilized high-resolution comparative genomic hybridization to detect copy number variations (CNVs) between normal and cancerous lung cells treated with tumor necrosis factor-alpha (TNF-α) for 24 weeks to induce chronic inflammation. Ingenuity Pathway Analysis was used to analyze the functions of genes located at the common CNV regions that were induced by chronic inflammation. The results shown that TNF-α induced more CNVs in normal lung cells than in cancerous lung cells. Moreover, Ingenuity Pathway Analysis was used to analyze the function of genes located at the common CNV regions get involved in cancer progression, DNA repair and inflammatory disease. In conclusion, chronic inflammation might be one of a set of factors which transform normal lung cells into tumor cells.
Distribution, detection of enterotoxigenic strains and antimicrobial drug susceptibility patterns of Bacteroides fragilis group in diarrheic and non-diarrheic feces from Brazilian infants (2010)

Despite the importance of gastrointestinal diseases and their global distribution, affecting millions of individuals around the world, the role and antimicrobial susceptibility patterns of anaerobic bacteria such as those in the Bacteroides fragilis group (BFG) are still unclear in young children. This study investigated the occurrence and distribution of species in the BFG and enterotoxigenic strains in the fecal microbiota of children and their antimicrobial susceptibility patterns. Diarrheic (n=110) and non-diarrheic (n=65) fecal samples from children aged 0-5 years old were evaluated. BFG strains were isolated and identified by conventional biochemical, physiological and molecular approaches. Alternatively, bacteria and enterotoxigenic strains were detected directly from feces by molecular biology. Antimicrobial drug susceptibility patterns were determined by the agar dilution method according to the guidelines for isolated bacteria. BFG was detected in 64.3% of the fecal samples (55% diarrheic and 80.4% non-diarrheic), and 4.6% were enterotoxigenic. Antimicrobial resistance was observed against ampicillin, ampicillin/sulbactam, piperacillin/tazobactam, meropenem, ceftriaxone, clindamycin and chloramphenicol. The data show that these bacteria are prevalent in fecal microbiota at higher levels in healthy children. The molecular methodology was more effective in identifying the B. fragilis group when compared to the biochemical and physiological techniques. The observation of high resistance levels stimulates thoughts about the indiscriminate use of antimicrobial drugs in early infancy. Further quantitative studies are needed to gain a better understanding of the role of these bacteria in acute diarrhea in children.
Microheterogeneity of plasma albumins. V. Permutations in disulfide pairings as a probable source of microheterogeneity in bovine albumin (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMicroheterogeneity of plasma albumins. V. Permutations in disulfide pairings as a probable source of microheterogeneity in bovine albuminMasaru Sogami, H. August Petersen, and Joseph F. FosterCite this: Biochemistry 1969, 8, 1, 49–58Publication Date (Print):January 1, 1969Publication History Published online1 May 2002Published inissue 1 January 1969https://pubs.acs.org/doi/10.1021/bi00829a008https://doi.org/10.1021/bi00829a008research-articleACS PublicationsRequest reuse permissionsArticle Views76Altmetric-Citations64LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Plasminogen activator and metalloprotease activities of Du-145, PC-3, and 1-LN-PC-3-1A human prostate tumors grown in nude mice: correlation with tumor invasive behavior. (1993)

Proteolytic enzymes are required to mediate tumor cell invasion of adjacent tissues and spread of primary tumors to distant sites. Our objective was to examine the activities and molecular forms of plasminogen activator (PA) and matrix metalloproteases (MP) in primary and secondary growths of SC tumors of three human prostatic cell lines (Du-145, PC-3, and 1-LN-PC-3-1A [1-LN], a subline of PC-3) grown in nude mice. The plasminogen activator activities were 1.7 +/- 1.3 (+/- SD), 6.2 +/- 2.8, and 11.5 +/- 4.2 for Du-145, PC-3, and 1-LN in primary SC tumors, respectively. Urokinase was the predominant molecular form of PA found in each tumor as determined from its molecular size (predominantly 54 kDa with a minor activity of 33 kDa) and sensitivity to amiloride. Prominent MP activities of approximately 68, 76, and 96 kDa as well as lesser activities of about 56, 59, 63, 84, 165, and 180 kDa were found in 1-LN tumors, whereas only less active MP of 59, 68, and 96 kDa were detected in the parental PC-3 cells. Du-145 tumors expressed MP activities of 59 and 96 kDa. Treatment of 1-LN tumor extracts with p-aminophenylmercuric acetate (APMA) significantly reduced the MP activities of 76 and 165 kDa while increasing activities of 56, 59, 65, 68, and 84 kDa. The 76 and 165 kDa MP activities thus appear to be prominent proenzyme forms of MP expressed in the 1-LN tumor. Secondary growths of tumor were subsequently found near the site of initial injection of PC-3 and 1-LN cells following removal of the primary tumor. There was a 42% increase in PA activity in the PC-3 secondary tumors, but only an 8% increase in 1-LN secondary tumors. However, there was no difference in the activities or number of molecular forms of MP in extracts of PC-3 or 1-LN primary or secondary tumors. The substantial expression of MP activities in the more aggressive 1-LN subline of the human prostatic PC-3 cell line indicates that induction of certain MP may be an important regulatory event in prostate tumor progression.
Photoaffinity Analogues of Farnesyl Pyrophosphate Transferable by Protein Farnesyl Transferase (2002)

Farnesylation is a posttranslational lipid modification in which a 15-carbon farnesyl isoprenoid is linked via a thioether bond to specific cysteine residues of proteins in a reaction catalyzed by protein farnesyltransferase (FTase). We synthesized analogues (3-6) of farnesyl pyrophosphate (FPP) to probe the range of modifications possible to the FPP skeleton which allow for efficient transfer by FTase. Photoaffinity analogues of FPP (5, 6) were prepared by substituting perfluorophenyl azide functional groups for the omega-terminal isoprene of FPP. Substituted anilines replace the omega-terminal isoprene in analogues 3 and 4. Compounds 3-5 were prepared by reductive amination of the appropriate anilines with 8-oxo-geranyl acetate, followed by ester hydrolysis, chlorination, and pyrophosphorylation. Additional substitution of three methylenes for the beta-isoprene of FPP gave photoprobe 6 in nine steps. Preparation of the analogues required TiCl(4)-mediated imine formation prior to NaBH(OAc)(3) reduction for anilines with a pK(a) < 1. The azide moiety was not affected by Ph(3)PCl(2) conversion of allylic alcohols 13-16 into corresponding chlorides 17-20. Analogues 3-6 are efficiently transferred to target N-dansyl-GCVLS peptide substrate by mammalian FTase. Comparison of analogue structures and kinetics of transfer to those of FPP reveals that ring fluorination and para substituents have little effect on the affinity of the analogue pyrophosphate for FTase and its transfer efficiency. These results are also supported with models of the analogue binding modes in the active site of FTase. The transferable azide photoprobe 5 photoinactivates FTase. Transferable analogues 5 and 6 allow the formation of appropriately posttranslationally modified photoreactive peptide probes of isoprene function.