gebhart/patrepeval huggingface dataset:
Regulation of heme oxygenase gene expression by cobalt in rat liver and kidney (1990)

The effect of heavy metals such as cobalt chloride and the corresponding metalloporphyrin on the transcription of the heme oxygenase gene in tissues was examined using cDNA for rat heme oxygenase as the probe. An increase in heme oxygenase mRNA level was observed in response to cobalt chloride and cobalt protoporphyrin treatment in both liver and kidney. Quantitative evaluation of the heme oxygenase transcript was obtained by determining the intensity of mRNA bands by scanning densitometry, and indicated that cobalt chloride increased heme oxygenase mRNA by 40-60-fold after 2 h of metal exposure. Accumulation of heme oxygenase mRNA after cobalt chloride administration was prevented by co-administration of actinomycin D or cycloheximide. These results indicate that the increased expression of heme oxygenase by cobalt chloride required de novo protein synthesis and was regulated at the transcriptional level. The time course of heme oxygenase transcript accumulation following administration of cobalt protoporphyrin was different from that of cobalt chloride. There was a sharp increase in heme oxygenase mRNA after cobalt chloride administration at 2 h and cobalt protoporphyrin at 10 h. Heme, to which cobalt protoporphyrin is structurally analogous, acted as a potent inducer of heme oxygenase transcripts in both liver and kidney. Variation in heme oxygenase mRNA levels resulting from enhanced transcription of the heme oxygenase gene was evaluated by nuclear runoff assay using isolated rat liver nuclei after cobalt chloride administration. Quantification of specific nuclear RNAs labeled during the in vitro transcription revealed active heme oxygenase gene transcription in liver nuclei from cobalt-chloride-treated rats. Transcription of heme oxygenase is greatly increased within 1 h of administration of cobalt chloride in rat liver, as evidenced by the level of [alpha-32P]UTP incorporation into nuclear RNA. The transcription was increased by 40-fold after 3 h of cobalt chloride administration. The activation of the heme oxygenase gene by metal ions is the most rapid transcriptional response to heavy metals yet described and highlights the regulatory role of heme oxygenase in heme degradation during deviating environmental conditions. On the other hand, cobalt protoporphyrin and heme arginate increase transcription of the heme oxygenase gene in a similar pattern but at a slower rate than that of the heavy metal, suggesting that the heme oxygenase promotor region may contain additional elements conferring the inducing effect of these two agents.
Glycosides from Paeonia suffruticosa. (1999)

Four new glycosides, namely mudanpiosides-G, -H, -I and mudanoside-A together with three known compounds, gallic acid, adenosine and p-hydroxybenzoic acid were isolated from the root bark of Paeonia suffruticosa. Their structures have been determined on the basis of spectral evidence.
Molecular Mechanisms of Receptor-Mediated Endocytosis in the Renal Proximal Tubular Epithelium (2009)

Receptor-mediated endocytosis is a pivotal function of renal proximal tubule epithelial cells (PTECs) to reabsorb and metabolize substantial amounts of proteins and other substances in glomerular filtrates. The function accounts for the conservation of nutrients, including carrier-bound vitamins and trace elements, filtered by glomeruli. Impairment of the process results in a loss of such substances and development of proteinuria, an important clinical sign of kidney disease and a risk marker for cardiovascular disease. Megalin is a multiligand endocytic receptor expressed at clathrin-coated pits of PTEC, playing a central role in the process. Megalin cooperates with various membrane molecules and interacts with many intracellular adaptor proteins for endocytic trafficking. Megalin is also involved in signaling pathways in the cells. Megalin-mediated endocytic overload leads to damage of PTEC. Further studies are needed to elucidate the mechanism of megalin-mediated endocytosis and develop strategies for preventing the damage of PTEC.
High mesothelin expression in advanced lung adenocarcinoma is associated withKRASmutations and a poor prognosis (2015)

Mesothelin is a cell surface glycoprotein which is highly expressed in several epithelial cancers and may have a role in cell adhesion and metastases. In this study, we used prospectively obtained clinical and pathological data to characterize mesothelin expression in advanced lung adenocarcinoma. Tissue was obtained from patients who underwent molecular profiling of potentially actionable genes on a trial of molecular profiling and targeted therapies in advanced thoracic malignancies. We immunohistochemically evaluated the intensity, and the percentage of cells expressing mesothelin in 93 advanced lung adenocarcinomas. The evaluation was blinded for molecular data and outcome. Mutations of EGFR, KRAS, BRAF, AKT1, PIK3CA and HER2 were assessed by pyrosequencing; HER2 amplification and ALK translocation were assessed by fluorescence in situ hybridization. 53% of advanced lung adenocarcinomas expressed mesothelin to some degree; high mesothelin expression, defined as mesothelin positivity in more than 25% of cells, was found in 24% of patients. High mesothelin expression was associated with inferior survival (median 18.2 months vs. 32.9 months; P = 0.014). High mesothelin expression was strongly associated with mutant KRAS (P < 0.0001) and wild-type EGFR (P = 0.002). Our results provide strong rationale to explore anti-mesothelin targeted therapies in advanced lung adenocarcinoma especially in the KRAS-mutant subgroup.
Inducible DNA repair and differentiation in Bacillus subtilis: interactions between global regulons (1992)

The SOS response of Escherichia coli has become a paradigm for the study of inducible DNA repair and recombination processes in many different organisms. While these studies have demonstrated that the components of the SOS response appear to be highly conserved among bacterial species, as with most models, there are some significant variations. Perhaps the best example of this comes from an analysis of the SOS-like system of the developmental organism, Bacillus subtilis. Accordingly, the most striking difference is the complex developmental regulation of the SOS system as this organism differentiates into its competent state. In this review we have given an overview of the elements that comprise the SOS system of B. subtilis. Additionally, we have summarized our most recent findings regarding the regulation of this regulon. Using these results along with new findings from other laboratories we have provided provocative molecular models for the regulation of the B. subtilis SOS system in response to DNA damage and during competent cell formation.
Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children (1999)

We examined mRNA expression and internal tandem duplication of the Fms-like tyrosine kinase 3 (FLT3) gene in haematological malignancies by reverse transcriptase-polymerase chain reaction (RT-PCR) and genomic PCR followed by sequencing. By RT-PCR, expression of FLT3 was detected in 45/74 (61%) leukaemia cell lines and the frequency of expression of FLT3 was significantly higher in undifferentiated type (B-precursor acute lymphoblastic leukaemia; ALL) than in differentiated type cell lines (B-ALL) (P = 0.0076). Using the genomic PCR method, 194 fresh samples including 87 acute myeloid leukaemias, 60 ALLs, 32 myelodysplastic syndromes (MDSs) and 15 juvenile chronic myelogenous leukaemias (JCMLs) were examined. Tandem duplication was found in 12 (13.8%) AMLs and two (3.3%) ALLs. Sequence analyses of the 14 samples with the duplication revealed that eight showed a simple tandem duplication and six a tandem duplication with insertion. Most of these tandem duplications occurred within exon 11, and two duplications occurred from exon 11 to intron 11 and exon 12. No tandem duplications of FLT3 gene were detected in MDS or JCML. The frequency of tandem duplication of FLT3 gene in childhood AML was lower than that in adult AML so far reported. All of the 12 AML patients with the duplication died within 47 months after diagnosis, whereas two ALL patients with the duplication have survived 44 and 72 months, respectively. These two ALL patients expressed both lymphoid and myeloid antigens and were considered to have biphenotypic leukaemia. These results suggest that tandem duplication is involved in ALL in addition to AML, but not in childhood MDS or JCML, and that childhood AML patients with the tandem duplication have a poor prognosis.
DNA recognition properties of the N-terminal DNA binding domain within the large subunit of replication factor C (1998)

Replication Factor C (RFC) is a five-subunit protein complex required for eukaryotic DNA replication and repair. The large subunit within this complex contains a C-terminal DNA binding domain which provides specificity for PCNA loading at a primer-template and a second, N-terminal DNA binding domain of unknown function. We isolated the N-terminal DNA binding domain from Drosophila melanogaster and defined the region within this polypeptide required for DNA binding. The DNA determinants most efficiently recognized by both the Drosophila minimal DNA binding domain and the N-terminal half of the human large subunit consist of a double-stranded DNA containing a recessed 5' phosphate. DNA containing a recessed 5' phosphate was preferred 5-fold over hairpined DNA containing a recessed 3' hydroxyl. Combined with existing data, these DNA binding properties suggest a role for the N-terminal DNA binding domain in the recognition of phosphorylated DNA ends.
Genetic Variations of TAP1 Gene Exon 3 Affects Gene Expression and Escherichia coli F18 Resistance in Piglets (2014)

Firstly, our research group identified Sutai pigs’ phenotypes that exhibited extreme resistance and susceptibility to the Escherichia coli F18 respectively, and then eight ETEC (Enterotoxigenic Escherichia coli) F18-resistant piglets and eight ETEC F18-sensitive piglets were selected. Then, the TAP1 (Transporter associated with antigen processing) mRNA relative expression levels were analyzed in 11 tissues of the resistant and susceptible phenotypes. Simultaneously, we detected the genetic variations in exon 3 of the TAP1 gene and evaluated the TAP1 mRNA expression levels among the different genotype pigs to study the effects of the genetic variation on gene expression, and the E. coli F18 resistance. The results revealed higher expression levels in the resistant genotypes than that in the susceptible genotypes in 11 tissues, with significant differences in the spleen, lymph node, lung, thymus, duodenum and jejunum. Furthermore, a G729A mutation was identified in the TAP1 gene exon 3, and this mutation deviates from Hardy-Weinberg equilibrium (p &lt; 0.01). The TAP1 mRNA levels in GG genotype were significantly higher than that in the other two genotypes, with significant differences in the liver, lung, kidney, thymus, lymph node, duodenum and jejunum tissues. We speculated that high expression of the TAP1 gene might confer resistance against the E. coli F18, the G729A mutation had a significant effect on the mRNA expression, and individuals with the GG genotype possessed a stronger ability to resist the E. coli F18 infection.
Minimal ligand analysis of gastrin releasing peptide. Receptor binding and mitogenesis. (1988)

Gastrin releasing peptide (GRP) is a peptide hormone containing 27 amino acids which is structurally analogous to the amphibian peptide bombesin. GRP serves a variety of physiological functions and has been implicated in the pathophysiology of small cell lung cancer. Previous work has demonstrated that the modified C terminus of GRP, N-acetyl-GRP-20-27, exerts full agonist activity in a variety of assay systems. However, no systematic comparison of binding of GRP fragments to its receptor and mitogenic potency has been reported. To investigate whether smaller GRP fragments could bind to the GRP receptor without stimulating mitogenesis, we performed binding inhibition and thymidine uptake assays with Swiss 3T3 fibroblasts. These studies were facilitated by the development of a novel tritiated GRP-based radioligand, [3H-Phe15] GRP-15-27, which exhibits enhanced chemical stability compared to iodinated GRP derivatives. We examined a series of C-terminal GRP fragments, from the pentapeptide to the octapeptide, with both N-acetyl and free amine moieties at the N terminus. N-Acetylated derivatives were more potent than their primary amine counterparts in both assays. Deletion of N-terminal residues from GRP-20-27 resulted in significant loss of potency in both assays: the EC50 values of N-acetyl-GRP-21-27 were 10(2)-fold higher than N-acetyl-GRP-20-27, those of N-acetyl-GRP-22-27 were 10(4)-fold higher, and N-acetyl-GRP-23-27 showed minimal activity at concentrations below 100 microM. These results suggest that 1) both His20 and Trp21 play an important role in binding of GRP to the receptor, and 2) for this series of N-terminal deletions, binding to the receptor and mitogenic activity are tightly coupled.
The rationale for targeted therapies in medulloblastoma (2013)

Medulloblastoma (MB) is the most frequent malignant brain tumor in children. Patients with MB who are classified as having high-risk disease or those with recurrent disease respond poorly to current therapies and have an increased risk of MB-related mortality. Preclinical studies and molecular profiling of MB tumors have revealed upregulation or activation of several key signaling pathways such as the sonic hedgehog and WNT pathways. Although the exact mechanisms underlying MB tumorigenesis remain poorly understood, inhibiting these key pathways with molecularly targeted therapies represents an important approach to improving MB outcomes. Several molecularly targeted therapies are already under clinical investigation in MB patients. We discuss current preclinical and clinical data, as well as data from clinical trials of targeted therapies that are either ongoing or in development for MB.
Intratympanic Application of an Antiviral Agent for the Treatment of Ménière’s Disease (2008)

It has been suggested that Ménière's disease is part of a polyganglionitis in which symptoms result from the reactivation of neurotropic virus within the internal auditory canal, and that intratympanic applications of an antiviral agent might be an efficient therapy. In 2002, we performed a pilot study ending with encouraging results. Control of vertigo was achieved in 80% of the 17 patients included. We present here a prospective, double-blind study, with a 2-year follow-up, in 29 patients referred by ENT practitioners for a surgical treatment after failure of a medical therapy. The participation in the study was offered to patients prior to surgery. A solution of ganciclovir 50 mg/ml or of NaCl 9% was delivered for 10 consecutive days via a microwick inserted into the tympanic membrane in the direction of the round window or through a ventilation tube. One patient was withdrawn from the study immediately after the end of the injections. He could not complete the follow-up period, because of persisting vertigo. As he had received the placebo, he was then treated with the solution of ganciclovir. Symptoms persisted and he underwent a vestibular neurectomy. Among the remaining 28 patients, surgery could be postponed in 22 (81%). Surgery remained necessary to control vertigo in 3 patients from the group that received the antiviral agent, and in 3 from the control group. Using an analogical scale, patients of both groups indicated a similar improvement of their health immediately after the intratympanic injections. The scores obtained with a 36-item short-form health survey quality of life questionnaire and the Dizziness Handicap Inventory were also similar for both groups. In conclusion, most patients were improved after the intratympanic injections, but there was no obvious difference between the treated and control groups. The benefit might be due to the middle ear ventilation or reflect an improvement in the patients' emotional state.
Template Activating Factor-I Remodels the Chromatin Structure and Stimulates Transcription from the Chromatin Template (1998)

To study the mechanisms of replication and transcription on chromatin, we have been using the adenovirus DNA complexed with viral basic core proteins, called Ad core. We have identified template activating factor (TAF)-I from uninfected HeLa cells as the factor that stimulates replication and transcription from the Ad core. The nuclease sensitivity assays have revealed that TAF-I remodels the Ad core, thereby making transcription and replication apparatus accessible to the template DNA. To examine whether TAF-I remodels the chromatin consisting of histones, the chromatin structure was reconstituted on the DNA fragment with core histones by the salt dialysis method. The transcription from the reconstituted chromatin was completely repressed, while TAF-I remodeled the chromatin and stimulated the transcription. TAF-I was found to interact with histones. Furthermore, it was shown that TAF-I is capable not only of disrupting the chromatin structure but also of preventing the formation of DNA-histone aggregation and transferring histones to naked DNA. The possible function of TAF-I in conjunction with a histone chaperone activity is discussed.
Implantable selective stimulator to improve bladder voiding: design and chronic experiments in dogs (2000)

Among the treatments to enhance the bladder voiding, the sacral roots neurostimulation is one of the most promising techniques. The electrostimulation of sacral nerves provokes a simultaneous contraction of the detrusor muscle as well as the external urethral sphincter (EUS). A new simplified-architecture implantable stimulator with its wireless controller have been designed to investigate high-frequency inhibition stimulation strategies. This innovative technique based on high-frequency inhibition reduces sphincter activity during stimulation. Low-frequency current pulses also applied to the sacral roots induces contraction of the detrusor muscle resulting in low pressure voiding. Chronic experiments were carried out on ten male mongrel paraplegic dogs. One cuff electrode was implanted along with each stimulator for eight months. The animals were stimulated twice a day using the prototypes of our implantable selective stimulator while voided and residual urine volume were measured during the procedure. These experiments revealed that the proposed stimulation strategy enhances bladder voiding by more than 50% in comparison with low-frequency only stimulation. The residual urine volume was reduced to an average of 9% and low pressure micturition was achieved as shown by weekly cystourethrogram.
Scaling Up Concurrent Analytical Workloads on Multi-Core Servers (2016)

Today, an ever-increasing number of researchers, businesses, and data scientists collect and analyze massive amounts of data in database systems. The database system needs to process the resulting highly concurrent analytical workloads by exploiting modern multi-socket multi-core processor systems with non-uniform memory access (NUMA) architectures and increasing memory sizes. Conventional execution engines, however, are not designed for many cores, and neither scale nor perform efficiently on modern multi-core NUMA architectures. Firstly, their query-centric approach, where each query is optimized and evaluated independently, can result in unnecessary contention for hardware resources due to redundant work found across queries in highly concurrent workloads. Secondly, they are unaware of the non-uniform memory access costs and the underlying hardware topology, incurring unnecessarily expensive memory accesses and bandwidth saturation. In this thesis, we show how these scalability and performance impediments can be solved by exploiting sharing among concurrent queries and incorporating NUMA-aware adaptive task scheduling and data placement strategies in the execution engine. Regarding sharing, we identify and categorize state-of-the-art techniques for sharing data and work across concurrent queries at run-time into two categories: reactive sharing, which shares intermediate results across common query sub-plans, and proactive sharing, which builds a global query plan with shared operators to evaluate queries. We integrate the original research prototypes that introduce reactive and proactive sharing, perform a sensitivity analysis, and show how and when each technique benefits performance. Our most significant finding is that reactive and proactive sharing can be combined to exploit the advantages of both sharing techniques for highly concurrent analytical workloads. Regarding NUMA-awareness, we identify, implement, and compare various combinations of task scheduling and data placement strategies under a diverse set of highly concurrent analytical workloads. We develop a prototype based on a commercial main-memory column-store database system. Our most significant finding is that there is no single strategy for task scheduling and data placement that is best for all workloads. In specific, inter-socket stealing of memory-intensive tasks can hurt overall performance, and unnecessary partitioning of data across sockets involves an overhead. For this reason, we implement algorithms that adapt task scheduling and data placement to the workload at run-time. Our experiments show that both sharing and NUMA-awareness can significantly improve the performance and scalability of highly concurrent analytical workloads on modern multi-core servers. Thus, we argue that sharing and NUMA-awareness are key factors for supporting faster processing of big data analytical applications, fully exploiting the hardware resources of modern multi-core servers, and for more responsive user experience.
Mobility Based MIMO Link Adaptation in LTE-Advanced Cellular Networks (2010)

As the demand for mobile broadband services are growing, cellular networks are heading towards their fourth generation (4G). Long Term Evolution - Advanced (LTE-A) is emerging as a major candidate for 4G cellular networks. MIMO technology combined with OFDMA is a major technological change in 4G compared to their 3G counterparts. However various MIMO configurations and modulation/coding schemes(MCS) need to be carefully tuned to derive the promised gains of MIMO technology. In this paper we evaluate the performance of different MIMO configurations and MCSs in the downlink of LTE-based cellular networks. We propose a signal-to-noise-ratio(SNR) cum mobility based MIMO/MCS link adaptation to enhance the overall performance of the LTE downlink.
Common regions of deletion on chromosomes 5q, 6q, and 10q in renal cell carcinoma. (1991)

Relatively frequent losses of heterozygosity on chromosomes 5q, 6q, and 10q, in addition to loss of heterozygosity on the short arm of chromosome 3, have been observed in renal cell carcinomas. As the first step toward isolation of tumor suppressor genes on these three chromosomal arms, we used six restriction fragment length polymorphism markers for 5q, nine for 6q, and eight for 10q to identify regions commonly deleted in a panel of 64 renal cell carcinomas. Allelic losses were common at chromosome 5q21, the region where the MCC (mutated in colorectal cancer) gene was recently identified; at chromosome 6q27; and at chromosome 10q21-23. Furthermore, as association was observed between accumulation of allelic losses on these three chromosomal arms and progression of tumors. Loss of heterozygosity on chromosome 5 showed a correlation with the histopathological grade of a given tumor and the incidence of distant metastasis.