gebhart/patrepeval huggingface dataset:
Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing (2006)

DGCR8/Pasha is an essential cofactor for Drosha, a nuclear RNase III that cleaves the local hairpin structures embedded in long primary microRNA transcripts (pri-miRNAs) in eukaryotes. Although our knowledge of pri-miRNA processing has significantly advanced in recent years, the precise role of DGCR8 in this pathway remains unclear. In our present study, we dissect the domains in DGCR8 that contribute to the processing of pri-miRNAs and the subcellular localization of DGCR8. Drosha is stabilized through an interaction between its middle domain and the conserved C-terminal domain of DGCR8. Furthermore, DGCR8, but not Drosha, can directly and stably interact with pri-miRNAs, and the tandem dsRNA-binding domains (dsRBDs) in DGCR8 are responsible for this recognition. Moreover, the DGCR8 N-terminal region upstream of its dsRBDs is unnecessary for pri-miRNA processing but is critical for nuclear localization. Our study thus provides further insights into the mechanism of action of the Drosha-DGCR8 complex in pri-miRNA processing.
TAMMAC: An Adaptive Multi-Channel MAC Protocol for MANETs (2008)

The use of multiple channels in wireless networks could provide performance advantages in reducing collisions and enabling more concurrent transmissions. So et al. proposed a multi-channel MAC protocol, which uses a single transceiver and divides the beacon interval into two parts: channel negotiation and data transmission. However, the fixed length of channel negotiation interval limits the channel utilization. We propose a new single transceiver MAC protocol, named traffic aware multichannel medium access control (TAMMAC), that can exploit multiple channels with smart window increase and decrease rules to adjust the contention window size dynamically and properly. The simulation results show that the proposed protocol achieves higher aggregate network throughput than other schemes under various traffic loads.
High mobility group A2 protein and its derivatives bind a specific region of the promoter of DNA repair gene ERCC1 and modulate its activity (2003)

High mobility group A2 (HMGA2) chromosomal non-histone protein and its derivatives play an important role in development and progression of benign and malignant tumors, obesity and arteriosclerosis, although the underlying mechanisms of these conditions are poorly understood. Therefore, we tried to identify target genes for this transcriptional regulator and to provide insights in the mechanism of interaction to its target. Multiple genes have been identified by microarray experiments as being transcriptionally regulated by HMGA2. Among these we chose the ERCC1 gene, encoding a DNA repair protein, for this study. DNA-binding studies were performed using HMGA2 and C-terminally truncated DeltaHMGA2, a derivative that is frequently observed in a variety of tumors. A unique high affinity HMGA2 binding site was mapped to a specific AT-rich region located -323 to -298 upstream of the ERCC1 transcription start site, distinguishing it from other potential AT-rich binding sites. The observed 1:1 stoichiometry for the binding of wild-type HMGA2 to this region was altered to 1:2 upon binding of truncated DeltaHMGA2, causing DNA bending. Furthermore, the regulatory effect of HMGA2 was confirmed by luciferase promoter assays showing that ERCC1 promoter activity is down-regulated by all investigated HMGA2 forms, with the most striking effect exerted by DeltaHMGA2. Our results provide the first insights into how HMGA2 and its aberrant forms bind and regulate the ERCC1 promoter.
<title>IMM algorithm for tracking targets that maneuver through coordinated turns</title> (1992)

The interacting multiple model (IMM) algorithm uses multiple models that interact through state mixing to track a target maneuvering through an arbitrary trajectory. However, when a target maneuvers through a coordinated turn, the acceleration vector of the target changes magnitude and direction, and the maneuvering target models commonly used in the IMM (e.g., constant acceleration) can exhibit considerable model error. To address this problem an IMM algorithm that includes a constant velocity model, a constant speed model with the kinematic constraint for constant speed targets, and the exponentially increasing acceleration (EIA) model for maneuver response is proposed. The constant speed model utilizes a turning rate in the state transition matrix to achieve constant speed prediction. The turning rate is calculated from the velocity and acceleration estimates of the constant speed model. The kinematic constraint for constant speed targets is utilized as a pseudomeasurement in the filtering process with the constant speed model. Simulation results that demonstrate the benefits of the EIA model and the kinematic constraint to the IMM algorithm are given. The tracking performance of the proposed IMM algorithm is compared with that of an IMM algorithm utilizing constant velocity and constant turn rate models.
The Impact of Cell Dropping Policies in ATM Nodes (2001)

We consider policies for deciding which cells will be lost or dropped when losses occur at a finite buffer asynchronous transfer mode (ATM) node. The performance criteria of interest are the delay of transmitted (nonlost) cells, the jitter (or variability in the delay of transmitted cells), and the burstiness of lost cells. We analyze the performance trade-offs for various cell dropping policies. We show that “rear dropping,” in which cells that arrive to a full buffer are lost, stochastically maximizes delay, whereas “front dropping,” in which cells at the front of the buffer are lost, stochastically minimizes delay. On the other hand, rear dropping stochastically minimizes the jitter. We also propose policies that have both stochastically smaller delay and less lost cell burstiness in a stochastic majorization sense than the rear dropping policy.
Transcriptional regulation of solventogenesis in Clostridium acetobutylicum. (2002)

Solvent synthesis in Clostridium acetobutylicum is induced in concert with sporulation to counteract the dangerous effects of produced butyric and acetic acids and to provide the cell with sufficient time to complete endospore formation. Cardinal transcription units for butanol and acetone production are the sol and adc operons encoding butyraldehyde/butanol dehydrogenase and coenzyme A transferase as well as acetoacetate decarboxylase. Induction is achieved by a decreased level of DNA supercoiling and the transcription factor Spo0A, possibly in cooperation with other regulatory proteins. A number of other operons is also turned on during this metabolic switch, whose physiological relevance, however, is only partly understood. The recent completion of C. acetobutylicum genome sequencing will pave the way for transcriptional profiling and thus allow comprehension of the coherent regulatory networks of solventogenesis and sporulation.
Valproic Acid Enhanced Temozolomide-Induced Anticancer Activity in Human Glioma Through the p53–PUMA Apoptosis Pathway (2021)

Glioblastoma (GBM), the most lethal type of brain tumor in adults, has considerable cellular heterogeneity. The standard adjuvant chemotherapeutic agent for GBM, temozolomide (TMZ), has a modest response rate due to the development of drug resistance. Multiple studies have shown that valproic acid (VPA) can enhance GBM tumor control and prolong survival when given in conjunction with TMZ. However, the beneficial effect is variable. In this study, we analyzed the impact of VPA on GBM patient survival and its possible correlation with TMZ treatment and <i>p53</i> gene mutation. In addition, the molecular mechanisms of TMZ in combination with VPA were examined using both p53 wild-type and p53 mutant human GBM cell lines. Our analysis of clinical data indicates that the survival benefit of a combined TMZ and VPA treatment in GBM patients is dependent on their <i>p53</i> gene status. In cellular experiments, our results show that VPA enhanced the antineoplastic effect of TMZ by enhancing p53 activation and promoting the expression of its downstream pro-apoptotic protein, PUMA. Our study indicates that GBM patients with wild-type <i>p53</i> may benefit from a combined TMZ+VPA treatment.
Lightweight Deployable Booms: Design, Manufacture, Verification, and Smart Materials Application (2004)

Large and ultra-light space structures on base of deployable components will gain in importance for a row of future mission applications. The DLR Institute of Structural Mechanics is developing deployment concepts for ultra-light carbon-fibre reinforced struts (CFRP booms), which can be coiled around a hub for stowage within a very tight transportation volume. The development of cost-efficient and qualified production technologies for considerably long booms as well as the design verification including on-ground deployment tests are further tasks currently being worked out. Adaptive materials are efficient means to reduce the oscillations of the very large and flexible structures. They were successfully development tested and demonstrated in the framework of a boom test campaign on shortened samples. The deployable CFRP boom design is applied to a joint ESA/DLR Solar Sail in-orbit demonstration project. Four 14 meter long booms are designed, manufactured, verified, and finally integrated. The specific mass of the booms amounts to only 100 grams per meter for this application.
Lymphoid V(D)J recombination: nucleotide insertion at signal joints as well as coding joints. (1988)

The coding regions of antigen receptor genes assembled by variable-diversity-joining region [V(D)J] recombination are known in many cases to have undergone deletions of several nucleotides and also to contain insertions of noncoded nucleotides at the recombined junction (the coding joint). By using extrachromosomal recombination substrates to transfect lymphoid cell lines, we show that the signal joint (the fusion of the corresponding recognition signal sequences) can also contain insertions; however, nucleotide loss from the signals is very rare. The frequency of nucleotide addition varies among pre-B-cell lines in a manner proportional to their content of terminal deoxynucleotidyltransferase. We also find frequent nucleotide additions (and deletions) at coding joints, but in this case there is no strong correlation with the level of terminal deoxynucleotidyltransferase activity. Inserts at both signal and coding joints are rich in G + C, consistent with the base utilization preference of this enzyme.
Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach Cells (2008)

Induced pluripotent stem (iPS) cells have been generated from mouse and human fibroblasts by the retroviral transduction of four transcription factors. However, the cell origins and molecular mechanisms of iPS cell induction remain elusive. This report describes the generation of iPS cells from adult mouse hepatocytes and gastric epithelial cells. These iPS cell clones appear to be equivalent to embryonic stem cells in gene expression and are competent to generate germline chimeras. Genetic lineage tracings show that liver-derived iPS cells are derived from albumin-expressing cells. No common retroviral integration sites are found among multiple clones. These data suggest that iPS cells are generated by direct reprogramming of lineage-committed somatic cells and that retroviral integration into specific sites is not required.
Phase I Dose Escalation, Pharmacokinetic and Pharmacodynamic Study of Naptumomab Estafenatox Alone in Patients With Advanced Cancer and With Docetaxel in Patients With Advanced Non–Small-Cell Lung Cancer (2009)

ABR-217620 was well tolerated with evidence of immunological activity and antitumor activity.
Cell fate conversion by conditionally switching the signal‐transducing domain of signalobodies (2013)

Conditionally and strictly controlling cell fates is important for biomedical applications including cell therapies. Although previous studies have been based on regulating the expression or activation of signaling molecules, the techniques therein require improvement in terms of reducing leakiness and complexity. In this study, we propose a novel cell fate converting system using our previously developed antibody/receptor chimeras named "signalobodies" in combination with a Cre/loxP recombination system. We designed a "switch vector" where a growth signalobody gene was flanked by two loxP sites and a death signalobody gene was placed downstream of the floxed cassette. Cells transduced with the switch vector showed superior growth activity in the presence of a specific antigen. Subsequent expression of Cre induced the death signalobody, leading to conditional cell death. This technology could be applicable for other cell fate conversion systems including differentiation and migration, by using appropriate signal-transducing domains.
HIV‐1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells (2003)

Disruption of the blood-brain barrier (BBB) is widely believed to be the main route of human immunodeficiency virus (HIV) entry into the central nervous system (CNS). Although mechanisms of this process are not fully understood, alterations of tight junction protein expression can contribute, at least in part, to this phenomenon. Tight junctions are critical structural and functional elements of cerebral microvascular endothelial cells and the BBB. The aim of the present study was to examine the effects of HIV-1 Tat protein on expression of tight junction proteins. Primary cultures of brain microvascular endothelial cells (BMEC) were employed in these experiments. A 24-hr exposure of BMEC to Tat(1-72) resulted in a decrease of claudin-1, claudin-5, and zonula occludens (ZO)-2 expression, whereas total levels of occludin and ZO-1 remained unchanged. In addition, a short (3-hr) exposure of BMEC to Tat(1-72) induced cellular redistribution of claudin-5 immunoreactivity. Tat(1-72)-induced alterations of claudin-5 expression also were confirmed in vivo where Tat(1-72) was injected into the right hippocampus of mice. These findings indicate that HIV-1 Tat protein can markedly affect expression and distribution of specific tight junction proteins in brain endothelium. Alterations of only distinct tight junction proteins suggest a finely tuned effect of Tat(1-72) on the BBB. Because tight junction proteins are critical for the barrier function of the BBB, such alterations can lead to disturbances of the BBB integrity and contribute to HIV trafficking into the brain.
Design and fabrication of an integrated polarized light guide for liquid-crystal-display illumination (2004)

An integrated polarized light guide was designed and fabricated for use as a liquid-crystal backlight with emphasis on uniformity of the light and conversion of p-polarized to s-polarized light. Two different micro-optical structures were fabricated both on the top and the bottom surfaces of the light guide. On the top surface, a subwavelength grating separates s-polarized and p-polarized light to achieve a polarization-conversion efficiency of 69%. A 1.7 gain factor of polarization efficiency was obtained to increase the utility of light for liquid-crystal illumination.
Induction of CD4+T cell-dependent CD8+type 1 responses in humans by a malaria DNA vaccine (2001)

We assessed immunogenicity of a malaria DNA vaccine administered by needle i.m. or needleless jet injection [i.m. or i.m./intradermally (i.d.)] in 14 volunteers. Antigen-specific IFN-gamma responses were detected by enzyme-linked immunospot (ELISPOT) assays in all subjects to multiple 9- to 23-aa peptides containing class I and/or class II restricted epitopes, and were dependent on both CD8(+) and CD4(+) T cells. Overall, frequency of response was significantly greater after i.m. jet injection. CD8(+)-dependent cytotoxic T lymphocytes (CTL) were detected in 8/14 volunteers. Demonstration in humans of elicitation of the class I restricted IFN-gamma responses we believe necessary for protection against the liver stage of malaria parasites brings us closer to an effective malaria vaccine.
Bacterial start site prediction (1999)

With the growing number of completely sequenced bacterial genes, accurate gene prediction in bacterial genomes remains an important problem. Although the existing tools predict genes in bacterial genomes with high overall accuracy, their ability to pinpoint the translation start site remains unsatisfactory. In this paper, we present a novel approach to bacterial start site prediction that takes into account multiple features of a potential start site, viz., ribosome binding site (RBS) binding energy, distance of the RBS from the start codon, distance from the beginning of the maximal ORF to the start codon, the start codon itself and the coding/non-coding potential around the start site. Mixed integer programing was used to optimize the discriminatory system. The accuracy of this approach is up to 90%, compared to 70%, using the most common tools in fully automated mode (that is, without expert human post-processing of results). The approach is evaluated using Bacillus subtilis, Escherichia coli and Pyrococcus furiosus. These three genomes cover a broad spectrum of bacterial genomes, since B.subtilis is a Gram-positive bacterium, E.coli is a Gram-negative bacterium and P. furiosus is an archaebacterium. A significant problem is generating a set of 'true' start sites for algorithm training, in the absence of experimental work. We found that sequence conservation between P. furiosus and the related Pyrococcus horikoshii clearly delimited the gene start in many cases, providing a sufficient training set.
Genome‐wide analysis of DNA copy number alterations and gene expression in gastric cancer (2008)

Genomic copy number aberrations (CNAs) are believed to play a major role in the development and progression of human cancers. Although many CNAs have been reported in gastric cancer, their genome-wide transcriptional consequences are poorly understood. In this study, to reveal the impact of CNAs on genome-wide expression in gastric cancer, we analysed 30 cases of gastric cancers for their CNAs by array comparative genomic hybridization (array CGH) and 24 of these 30 cases for their expression profiles by oligonucleotide-expression microarray. We found that with the application of laser microdissection, most CNAs were detected at higher frequency than in previous studies. Notably, gain at 20q13 was detected in almost all cases (97%), suggesting that this may play an important role in the pathogenesis of gastric cancer. By comparing the array CGH data with expression profiles of the same samples, we showed that both genomic amplification and deletion strongly influence the expression of genes in altered genomic regions. Furthermore, we identified 125 candidate genes, consisting of 114 up-regulated genes located in recurrent regions (>10%) of amplification and 11 down-regulated genes located in recurrent regions of deletion. Up-regulation of several candidate genes, such as CDC6, SEC61G, ANP32E, BYSL and FDFT1, was confirmed by immunohistochemistry. Interestingly, some candidate genes were localized at genomic loci adjacent to well-known genes such as EGFR, ERBB2 and SMAD4, and concordantly deregulated by genomic alterations. Based on these results, we propose that our list of candidate genes may contain novel genes involved in the pathogenesis of advanced gastric cancer.
Modeling biomedical experimental processes with OBI (2010)

OBI is available at http://purl.obolibrary.org/obo/obi/2009-11-02/obi.owl.
Low-Dose Dopamine Agonist Administration Blocks Vascular Endothelial Growth Factor (VEGF)-Mediated Vascular Hyperpermeability without Altering VEGF Receptor 2-Dependent Luteal Angiogenesis in a Rat Ovarian Hyperstimulation Model (2006)

No specific treatment is available for ovarian hyperstimulation syndrome (OHSS), the most important complication in infertile women treated with gonadotropins. OHSS is caused by increased vascular permeability (VP) through ovarian hypersecretion of vascular endothelial growth factor (VEGF)-activating VEGF receptor 2 (VEGFR-2). We previously demonstrated in an OHSS rodent model that increased VP was prevented by inactivating VEGFR-2 with a receptor antagonist (SU5416). However, due to its toxicity (thromboembolism) and disruption of VEGFR-2-dependent angiogenic processes critical for pregnancy, this kind of compound cannot be used clinically to prevent OHSS. Dopamine receptor 2 (Dp-r2) agonists, used in the treatment of human hyperprolactinemia including pregnancy, inhibit VEGFR-2-dependent VP and angiogenesis when administered at high doses in animal cancer models. To test whether VEGFR-2-dependent VP and angiogenesis could be segregated in a dose-dependent fashion with the Dp-r2 agonist cabergoline, a well-established OHSS rat model supplemented with prolactin was used. A 100 microg/kg low-dose Dp-r2 agonist cabergoline reversed VEGFR-2-dependent VP without affecting luteal angiogenesis through partial inhibition of ovarian VEGFR-2 phosphorylation levels. No luteolytic effects (serum progesterone levels and luteal apoptosis unaffected) were observed. Cabergoline administration also did not affect VEGF/VEGFR-2 ovarian mRNA levels. Results in the animal model and the safe clinical profile of Dp-r2 agonists encouraged us to administer cabergoline to oocyte donors at high risk for developing the syndrome. Prophylactic administration of cabergoline (5-10 microg/kg x d) decreased the occurrence of OHSS from 65% (controls) to 25% (treatment). Therefore, a specific, safe treatment for OHSS is now available.
Analysis of clones carrying repeated DNA sequences in two YAC libraries of Arabidopsis thaliana DNA (1994)

YAC clones carrying repeated DNA sequences from the Arabidopsis thaliana genome have been characterized in two widely used Arabidopsis YAC libraries, the EG library and the EW library. Ribosomal, chloroplast and the paracentromeric repeat sequences are differentially represented in the two libraries. The coordinates of YAC clones hybridizing to these sequences are given. A high proportion of EG YAC clones were classified as containing chimaeric inserts because individual clones carried unique sequences and repetitive sequences originating from different locations in the genome. None of the EW YAC clones analysed were chimaeric in this way. YAC clones carrying tandemly repeated sequences, such as the paracentromeric or rDNA sequences, exhibited a high degree of instability. These observations need to be taken into account when using these libraries in the development of a physical map of the Arabidopsis genome and in chromosome walking experiments.