gebhart/patrepeval huggingface dataset:
Controlling Gene Expression through RNA Regulons: The Role of the Eukaryotic Translation Initiation Factor eIF4E (2007)

The eukaryotic translation initiation factor eIF4E is a potent oncogene. In fact, its overexpression in human cancer often correlates with poor prognosis. Traditionally, eIF4E plays a role in translation initiation where it binds the 5' m7G cap found on mRNAs. More recent studies indicate that a significant fraction of eIF4E (up to 68%) resides in the nucleus where it regulates the nuclear export of specific mRNAs. Additionally, eIF4E may play a role in mRNA sequestration and stability in cytoplasmic processing bodies (P-bodies). Our recent studies suggest that eIF4E governs cell cycle progression and cellular proliferation by coordinately orchestrating the expression of several genes at the post-transcriptional level. Hence, eIF4E functions as a central node of an RNA regulon (described below), which plays an essential role in normal differentiation and development and is frequently dysregulated in cancer. Several cellular factors, such as the promyelocytic leukemia protein PML, modulate the function of this regulon by altering the activity of eIF4E. Here, the physiological implications of these observations are described and the clinical implications of directly targeting eIF4E, and the related regulon, are discussed.
Epigenome-wide ovarian cancer analysis identifies a methylation profile differentiating clear-cell histology with epigenetic silencing of the HERG K+ channel (2013)

Ovarian cancer remains the leading cause of death in women with gynecologic malignancies, despite surgical advances and the development of more effective chemotherapeutics. As increasing evidence indicates that clear-cell ovarian cancer may have unique pathogenesis, further understanding of molecular features may enable us to begin to understand the underlying biology and histology-specific information for improved outcomes. To study epigenetics in clear-cell ovarian cancer, fresh frozen tumor DNA (n = 485) was assayed on Illumina Infinium HumanMethylation450 BeadChips. We identified a clear-cell ovarian cancer tumor methylation profile (n = 163) which we validated in two independent replication sets (set 1, n = 163; set 2, n = 159), highlighting 22 CpG loci associated with nine genes (VWA1, FOXP1, FGFRL1, LINC00340, KCNH2, ANK1, ATXN2, NDRG21 and SLC16A11). Nearly all of the differentially methylated CpGs showed a propensity toward hypermethylation among clear-cell cases. Several loci methylation inversely correlated with tumor gene expression, most notably KCNH2 (HERG, a potassium channel) (P = 9.5 × 10(-7)), indicating epigenetic silencing. In addition, a predicted methylation class mainly represented by the clear-cell cases (20 clear cell out of 23 cases) had improved survival time. Although these analyses included only 30 clear-cell carcinomas, results suggest that loss of expression of KCNH2 (HERG) by methylation could be a good prognostic marker, given that overexpression of the potassium (K(+)) channel Eag family members promotes increased proliferation and results in poor prognosis. Validation in a bigger cohort of clear-cell tumors of the ovary is warranted.
Control of microbial souring of oil in a porous media column (2015)

Oil reservoir souring is a major problem in industry due to H2S toxicity, corrosion, plugging and sulfide concentrations in natural gas.Reservoir souring was simulated in Berea sandstone columns and cores using native mixed microbial consortia from two oil fields.Similar souring activity (substrate preference, and rates of substrate consumption and H2S production) were seen with both consortia growing as a biofilm in columns and cores at 60C.Most of the souring activity occurred at the beginning of the columns.This simulated injection well souring, in which sulfate-reducing bacteria (SRB), sulfate and carbon sources are all available at the wellbore.Biomass and precipitated iron sulfide accumulated uniformly along the column length and caused plugging.More plugging was found in systems with lower initial permeabilities, and most of this plugging was due to iron sulfide precipitation.Several novel methods were discovered to inhibit souring in the columns and cores.Addition of ten ppm nitrate stimulated both native consortia to quickly and completely inhibit active souring, and five ppm maintained the inhibition.Nitrite was produced at 80-100% of the nitrate level added through incomplete denitrification by nitrate-reducing bacteria (NRB), and nitrite was determined to be the inhibitory agent.Direct continuous addition of 10-12 ppm nitrite also inhibited souring and pulse addition was found to be more effective than continuous addition at the same total addition rate.In the 20-hour residence time of the reactor, 10-20% of the nitrite was consumed.Nitrite addition appeared to decrease plugging in the core system.Removal of nitrate or nitrite allowed souring to resume after it had been inhibited for as long as three months.Nitrite was a more effective and longer-lasting inhibitor than was glutaraldehyde, a biocide routinely used in oil fields and other industrial applications.Initial attempts to model souring and nitrate reduction in a column using kinetics from batch studies yielded predictions that differed significantly from the experimental data.Biofilm thickness and K the Monod inhibition constant for nitrite acting against SRB, were found to be key parameters in the model and were thus adjusted.A final model captured the qualitative behavior of the system.
A Clinicopathologic Study of 100 Cases of Parkinson's Disease (1993)

The clinical details of 100 cases of histologically confirmed Parkinson's disease were examined and correlated with pathologic findings. Age at disease onset (mean, 62.4 years), disease duration (mean, 13.1 years), and age at death (mean, 75.5 years) were similar to those in previous smaller series. Asymmetric, tremulous onset was most common, although 23% of patients had no rest tremor. Motor fluctuations and dyskinesias occurred in 60% of levodopa-treated patients. All patients had clinical parkinsonism; however, 12 had atypical clinical features of Parkinson's disease, including severe early dementia, fluctuating confusional states, no response to levodopa, and early marked autonomic disturbance. Neuropathologic examination found coexistent Alzheimer-type change in 17 cases and striatal abnormality--mainly vascular--in 34 cases. Cortical Lewy bodies were present in all cases, but only four satisfied proposed criteria for diffuse Lewy body disease. Dementia occurred in 44% of cases; 29% had Alzheimer's disease, 10% had numerous cortical Lewy bodies, and 6% had a possible vascular cause; in 55% no definite pathologic cause was found. Nigral cell loss correlated with disease duration and severity. Although the general pattern of disease conformed to traditional descriptions, the findings broaden the present clinical and pathologic spectrum of Parkinson's disease.
CHANGES IN SKELETAL MUSCLE PO2 AFTER ADMINISTRATION OF ANTI-TNFα-ANTIBODY IN PATIENTS WITH SEVERE SEPSIS (1994)

In 20 patients with severe sepsis, skeletal muscle pO2 was continuously measured in order to assess whether a decrease of skeletal muscle pO2 was accompanied by an improvement of sepsis after repeated administration of F(ab')2 fragments of a murine anti-TNF alpha-antibody. Abnormally high skeletal muscle pO2 decreased from 43.5 +/- 10.9 mmHg (day 0) to 36.4 +/- 10.1 mmHg within 24 h after the first administration of anti-TNF alpha-antibody (day 1, p = .006, n = 20) and remained at 34.6 +/- 7.7 mmHg thereafter (mean day 2-7, p = .004). The decrease of skeletal muscle pO2 within 24 h exceeded 5 mmHg (-7 to -19 mmHg) in 11 patients in contrast to nine patients (-4 to +4 mmHg). Only in the patients showing a decrease of skeletal muscle pO2 did sepsis improve as determined by Elebute score, APACHE II score, and interleukin-6 serum levels. The change of skeletal muscle pO2 within 24 h was associated with a change of interleukin-6 serum levels within 24 h (r = .5, n = 20), with a change of Elebute score (r = .7, n = 20) and of APACHE II score (r = .62). These data suggest that a decrease of skeletal muscle pO2 might be an early indicator of improvement of sepsis after administration of anti-TNF alpha-antibodies.
Analysis of Cre1 binding sites in the Trichoderma reesei cbh1 upstream region (1996)

A 1.5-kb XbaI-SacII fragment containing the upstream region of the Trichoderma reesei cellobiohydrolase I gene (cbh1) has been sequenced. The 1.5-kb fragment contains eight 6-bp sites having an identical or similar sequence to the consensus sequence for binding a catabolite repressor, Aspergillus nidulans CreA. Results of binding assays with the maltose-binding protein: :Cre1(10–131) fusion protein (Cre1 is a catabolite repressor of T. reesei) and the cbhI upstream region revealed that a 504-bp XbaI-NspV fragment (nucleotide position − 1496 to − 993) bearing three 6-bp sites, Al, A2, and A3, and a 356-bp NspV-MunI fragment (nucleotide position −994 to −639) bearing three 6-bp sites, B1, B2, and B3, were shifted in the electrophoretic mobility shift assay. DNase I footprinting experiments showed that the 6-bp sites A2, B1, B2, and B3 were protected from DNase I digestion.
A Closed Form Solution to Natural Image Matting (2006)

Interactive digital matting, the process of extracting a foreground object from an image based on limited user input, is an important task in image and video editing. From a computer vision perspective, this task is extremely challenging because it is massively ill-posed - at each pixel we must estimate the foreground and the background colors, as well as the foreground opacity ("alpha matte") from a single color measurement. Current approaches either restrict the estimation to a small part of the image, estimating foreground and background colors based on nearby pixels where they are known, or perform iterative nonlinear estimation by alternating foreground and background color estimation with alpha estimation. In this paper we present a closed form solution to natural image matting. We derive a cost function from local smoothness assumptions on foreground and background colors, and show that in the resulting expression it is possible to analytically eliminate the foreground and background colors to obtain a quadratic cost function in alpha. This allows us to find the globally optimal alpha matte by solving a sparse linear system of equations. Furthermore, the closed form formula allows us to predict the properties of the solution by analyzing the eigenvectors of a sparse matrix, closely related to matrices used in spectral image segmentation algorithms. We show that high quality mattes can be obtained on natural images from a surprisingly small amount of user input.
A Reconfigurable Spiral Antenna for Adaptive MIMO Systems (2005)

We present a reconfigurable spiral antenna for use in adaptive MIMO systems. The antenna is capable of changing the sense of polarization of the radiated field. It is fabricated by using an RF-MEMS technology compatible with microwave laminate substrates developed within the author's group. The proposed antenna structure is built on a number of rectangular-shaped bent metallic strips interconnected to each other with RF-MEMS actuators. Two senses of polarization, RHCP and LHCP, are achieved by configuring the physical structure of the antenna, that is, by changing the winding sense of the spiral, through judicious activation of MEM actuators. The fabrication process for the monolithic integration of MEM actuators with bent microstrip pixels on RO4003-FR4 microwave laminate substrate is described. The measured and calculated radiation and impedance characteristics of the antenna are given. The operating frequency of the presented antenna design can easily be adjusted to be compatible with popular IEEE networking standards such as 802.11a.
Avoidance of Host Recognition by Alterations in the Repetitive and C-Terminal Regions of AvrXa7, a Type III Effector of Xanthomonas oryzae pv. oryzae (2005)

avrXa7 is a member of the avrBs3/pthA gene family. The gene is a critical type III effector in several strains of Xanthomonas oryzae pv. oryzae (virulence activity), and in the presence of the Xa7 host gene for resistance, controls the elicitation of resistance in rice (avirulence activity). The ability of strains containing avrXa7 to adapt to the presence of Xa7 in the host population is dependent, in part, on the genetic plasticity of avrXa7. The potential for the conversion of avrXa7 to a virulence effector without Xa7-dependent elicitor activity was examined. Internal reorganization of avrXa7 by artificially deleting a portion of the central repetitive region resulted in gene pthXo4, which retained virulence activity and lost Xa7-dependent avirulence activity. Similarly, spontaneous rearrangements between repetitive regions of avrXa7 during bacterial culture gave rise to gene pthXo5, which also had virulence activity without Xa7-dependent avirulence activity. pthXo5 appeared to be the result of recombination between avrXa7 and a related gene in the genome. Loss of avirulence activity and retention of virulence activity also resulted from replacement of a portion of the C-terminal coding region of avrXa7 with the corresponding sequence from avrBs3. The results demonstrated the potential for a critical virulence effector to lose avirulence activity while retaining effector function. The results also demonstrated that features of both repetitive and nonrepetitive C-terminal regions of AvrXa7 are involved in avirulence specificity.
Effect of Inserting Paramyxovirus Simian Virus 5 Gene Junctions at the HN/L Gene Junction: Analysis of Accumulation of mRNAs Transcribed from Rescued Viable Viruses (1999)

Simian parainfluenza virus 5 (SV5) is a prototype of the Paramyxoviridae family of nonsegmented negative-sense RNA viruses. The single-stranded RNA genomes of these viruses contain a series of tandemly linked genes separated by intergenic (IG) sequences flanked by gene-end (GE) and gene-start (GS) sequences. The viral RNA polymerase (vRNAP) complex is thought to enter the genome at its 3' end, and synthesis of mRNAs is thought to occur by a stop-start mechanism in a sequential and polar manner, with transcriptional attenuation occurring primarily at the intergenic regions. As a result, multiple nonoverlapping mRNA species are generated for each single entry of the vRNAP. To investigate the functions of GE, IG, and GS sequences in transcription, we constructed plasmids containing cDNAs of the full-length SV5 genome in which the gene junction sequences (GE, IG, and GS sequences) located between the hemagglutinin-neuraminidase (HN) and the polymerase (L) genes were replaced with the counterpart sequences from other gene junctions. By using reverse genetics, we recovered viable viruses from each cDNA construct, although their growth characteristics varied. Analysis of the HN and L mRNAs by quantitative RNase protection assay indicated that the ratios of HN to L mRNAs varied over a fourfold range. The alteration of the gene junction sequences also permitted examination of the hypothesized requirement for hexamer nucleotide position of the GS sites. The recovery of infectious viruses with transcription initiation sites that occurred at nucleotide positions 1, 2, 3, 5, and 6 of the hexamer suggest that the requirement is nonstringent.
Temporal and Spatial Pattern of Expression of the Pea Phenylalanine Ammonia-Lyase Genel Promoter in Transgenic Tobacco (1997)

Genes encoding phenylalanine ammonia-lyase (PAL) form a small multigene family with at least three members in pea. Tissue-specific expression of the promoter of a member of PAL gene family (PSPAL1) was investigated in the transgenic tobacco transformants carrying the different modes of chimeric fusion between the PSPAL1 promoter and a bacterial beta-glucuronidase (GUS) gene. In stems, at least, strict correlation was found between steady-state levels of Gus-mRNA and enzyme activity. Significantly high level of GUS activity was observed in roots, particularly in meristematic tissues and the pigmented region of petals of transgenic tobacco carrying the translational fusion type B (-1,394 to +140 of PSPAL1 connected to Gus), followed by moderately high level of GUS activity carrying the translational fusion type A (-1,394 to +117). GUS expression in tissues of mature leaves, however, was very low in these constructs. Extremely low GUS activity was observed in the transformants of transcriptional fusion type (-1,394 to +5), whilst no activity was detected carrying non-transcription fusion type (-1,394 to -27). Furthermore, the pattern of the PSPAL1 expression was characterized in response to pathogen ingress and woundings in transgenic tobacco carrying the translational fusion type B. Woundings itself triggered marked expression of PSPAL1-driven GUS expression at the wounded sites. Inoculation of nonpathogens, Phytophthora capsici, P. boehmeriae and Erisiphe graminis f. sp. hordei, both caused rapid and very clear GUS expression zone along with the development of hypersensitive cell death area where callose was accumulated, however, the inoculation of a pathogen, P.nicotiana caused slow and hazy GUS expression zone along with the lesion development. These results suggest that the expression of pea PSPAL1 promoter is regulated in a similar fashion, at least in a part, in pea and transgenic tobacco, under the plant development and various environmental cues.
Tissue-Specific and Hormonal Regulation of the Gene for Rat Prostatic Steroid-Binding Protein in Transgenic Mice (1989)

We investigated the tissue-specific and hormonal regulation of the gene for rat prostatic steroid-binding protein by introducing the C3(1) gene with 4-kilobase (kb) upstream and 2-kb downstream flanking sequences into transgenic mice. There was selective expression in the ventral prostate that was stimulated by testosterone, which indicated that the gene together with 6-kb flanking DNA contains the information required for prostate-specific and testosterone-regulated expression.
Complete nucleotide sequence and characterization of a cryptic plasmid from Lactobacillus helveticus subsp. jugurti (1989)

A small cryptic plasmid, pLJ1, was isolated from Lactobacillus helveticus subsp. jugurti and was cloned into Escherichia coli HB101 by using pBR329 as a vector. Plasmid pLJ1 was 3,292 base pairs long and had single restriction endonuclease sites for PvuII, KpnI, AvaII, Acci, HindIII, and EcoRI. In a maxicell system, pLJ1 produced a protein of about 41 kilodaltons.
Orally administeredLactobacillus plantarumreduces pro-inflammatory interleukin secretion in sera fromListeria monocytogenesinfected mice (2007)

Lactic acid bacteria have traditionally been thought to have immunomodulating effects. To verify this property, Lactobacillus plantarum was orally administered to mice (5 x 107 colony forming units (c.f.u.)), prior to infection with Listeria monocytogenes in order to evaluate the host resistance against an infectious micro-organism and to better define the influence of L. plantarum on such responses. Balb/c mice were treated daily with L. plantarum or received PBS (sham-treated mice as controls) for 4 weeks. Subsequently, mice were intravenously infected with a clinical isolate of L. monocytogenes. Our study revealed that the administration of L. plantarum did not significantly increase the survival (P = 0.13) of mice (fifteen in each group) after L. monocytogenes infection (106 c.f.u./ml), whereas a sub-lethal dose of L. monocytogenes (105 c.f.u./ml) was eliminated from liver and spleen 5 d after the challenge in both L. plantarum- and sham-treated mice (n 5). Nevertheless, the levels of IL-1beta and IL-6 from sera of orally administered L. plantarum were drastically reduced at 0, 4 (P < 0.01) and 6 d after L. monocytogenes infection, whereas TNF-alpha production was unaltered. In conclusion, administration of L. plantarum reduced pro-inflammatory IL production after challenge with L. monocytogenes, although it did not significantly impact the survival of mice. We speculate that L. plantarum could exert anti-inflammatory effects, which may represent an important model to reduce inflammatory disorders. Therefore, further studies in human subjects should determine the role of L. plantarum as an immunomodulatory micro-organism and its relationship in the host protection to pathogens.
Characterization of golimumab, a human monoclonal antibody specific for human tumor necrosis factor α (2010)

We prepared and characterized golimumab (CNTO148), a human IgG1 tumor necrosis factor alpha (TNFα) antagonist monoclonal antibody chosen for clinical development based on its molecular properties. Golimumab was compared with infliximab, adalimumab and etanercept for affinity and in vitro TNFα neutralization. The affinity of golimumab for soluble human TNFα, as determined by surface plasmon resonance, was similar to that of etanercept (18 pM versus 11 pM), greater than that of infliximab (44 pM) and significantly greater than that of adalimumab (127 pM, p=0.018). The concentration of golimumab necessary to neutralize TNFα-induced E-selectin expression on human endothelial cells by 50% was significantly less than those for infliximab (3.2 fold; p=0.017) and adalimumab (3.3-fold; p=0.008) and comparable to that for etanercept. The conformational stability of golimumab was greater than that of infliximab (primary melting temperature [Tm] 74.8 °C vs. 69.5 °C) as assessed by differential scanning calorimetry. In addition, golimumab showed minimal aggregation over the intended shelf life when formulated as a high concentration liquid product (100 mg/mL) for subcutaneous administration. In vivo, golimumab at doses of 1 and 10 mg/kg significantly delayed disease progression in a mouse model of human TNFα-induced arthritis when compared with untreated mice, while infliximab was effective only at 10 mg/kg. Golimumab also significantly reduced histological scores for arthritis severity and cartilage damage, as well as serum levels of pro-inflammatory cytokines and chemokines associated with arthritis. Thus, we have demonstrated that golimumab is a highly stable human monoclonal antibody with high affinity and capacity to neutralize human TNFα in vitro and in vivo.