gebhart/patrepeval huggingface dataset:
[Removal of the 3'- and 5'-untranslated region amplifies expression of the erythropoietin gene in mammalian cells]. (2001)

The effect of the 5T- and 3T-untranslated regions (UTR) of human erythropoietin gene (gEpo) on its expression in mammalian cells was investigated. 5T-UTR-deleted, 3T-UTR-deleted, and 5T,3T-UTR-deleted gEpos were transfected into COS-7 cells, and the amount of transiently expressed Epo was measured. Cells transfected with the 5T,3T-UTR-deleted gEpo showed the highest expression, 2.6 times that with wild-type gEpo. Northern blot analysis indicated that the enhanced expression of 5T,3T-UTR-deleted gEpo might be related with the transcription efficiency.
Patterned growth of neonatal rat heart cells in culture. Morphological and electrophysiological characterization. (1991)

A culture method was developed that permits patterning of the growth of ventricular myocytes of neonatal rats. Regions were created on the culture substrate that either prevented (photoresist coat) or supported (glass surface) attachment of cells. In this way the geometry of interconnecting growth channels could be specified. Single-layered myocyte strands of variable length and with widths of as little as 65 micron (three to four cells wide) were obtained. The shape and orientation of the individual myocytes were a function of growth-channel width: the narrower the channel, the more elongated the cells and the more likely was the long axis to be oriented along the channel axis. In channels with width of 100 micron or less, cells were aligned longitudinally and cross-striated as in vivo. A high degree of morphological cell differentiation required the presence of contractile activity. Maximal diastolic potential (-71 mV), action potential amplitude (93 mV), and maximal upstroke velocity (140 V/sec) did not change with increasing culture age. Mean longitudinal conduction velocity was 0.39 m/sec. No electrophysiological or morphological evidence of photoresist toxicity was seen, and the data indicate a high degree of cell differentiation in the patterned cell cultures. The method thus is suitable for the study of the relation between impulse propagation and structure at a cellular level in artificial networks of predefined shape.
Multiple Rh messenger RNA isoforms are produced by alternative splicing (1992)

Three Rh-related cDNAs have been isolated from a human bone marrow cDNA library and by polymerase chain reaction (PCR) amplification of human bone marrow and erythroblast mRNAs. They potentially encode a family of Rh protein isoforms that exhibit several unexpected structural properties as compared with the Rh polypeptide encoded by the cDNA clone identified previously. These modifications include several peptide deletions, the predicted alteration of Rh protein topology within the cell membrane, variations in the number and surface exposition of cysteine residues, and the generation of new C-terminal polypeptide segments caused by frameshift mutations. The four Rh mRNAs now described correspond to different splicing isoforms transcribed from the same Rh gene, and all exist in the same cell lineage (erythroid). Moreover, PCR experiments indicated that at least three of these RNA species exist in reticulocytes from donors with different commonly expressed Rh phenotypes. Although the translated proteins have not yet been characterized, these results suggest that the two genes at the RH locus may direct the synthesis of several protein species possibly corresponding to different Rh antigenic variants.
Three-Dimensional-Engineered Matrix to Study Cancer Stem Cells and Tumorsphere Formation: Effect of Matrix Modulus (2012)

Maintenance of cancer stem cells (CSCs) is regulated by the tumor microenvironment. Synthetic hydrogels provide the flexibility to design three-dimensional (3D) matrices to isolate and study individual factors in the tumor microenvironment. The objective of this work was to investigate the effect of matrix modulus on tumorsphere formation by breast cancer cells and maintenance of CSCs in an inert microenvironment without the interference of other factors. In that regard, 4T1 mouse breast cancer cells were encapsulated in inert polyethylene glycol diacrylate hydrogels and the effect of matrix modulus on tumorsphere formation and expression of CSC markers was investigated. The gel modulus had a strong effect on tumorsphere formation and the effect was bimodal. Tumorsphere formation and expression of CSC markers peaked after 8 days of culture. At day 8, as the matrix modulus was increased from 2.5 kPa to 5.3, 26.1, and 47.1 kPa, the average tumorsphere size changed from 37±6 μm to 57±6, 20±4, and 12±2 μm, respectively; cell number density in the gel changed from 0.8±0.1×10⁵ cells/mL to 1.7±0.2×10⁵, 0.4±0.1×10⁵, and 0.2±0.1×10⁵ cells/mL after initial encapsulation of 0.14×10⁵ cells/mL; and the expression of CD44 breast CSC marker changed from 17±4-fold to 38±9-, 3±1-, and 2±1-fold increase compared with the initial level. Similar results were obtained with MCF7 human breast carcinoma cells. Mouse 4T1 and human MCF7 cells encapsulated in the gel with 5.3 kPa modulus formed the largest tumorspheres and highest density of tumorspheres, and had highest expression of breast CSC markers CD44 and ABCG2. The inert polyethylene glycol hydrogel can be used as a model-engineered 3D matrix to study the role of individual factors in the tumor microenvironment on tumorigenesis and maintenance of CSCs without the interference of other factors.
Evaluation of [(111/114m)In]CHX-A''-DTPA-ZHER2:342, an affibody ligand coniugate for targeting of HER2-expressing malignant tumors. (2007)

[(111)In]CHX-A''-DTPA-Z(HER2:342) is a promising candidate for the visualization of HER2 expression in malignant tumors. Labeled with (114m)In it could also be used for locoregional treatment of HER2 expressing tumors.
Antimicrobial peptides of phagocytes and epithelia. (1997)

Human and other vertebrate leukocytes contain multiple distinct antimicrobial (poly)peptides. Of these, BPI is a LPB protein active against gram-negative bacteria, PLA2 specifically cleaves bacterial phospholipids, while defensins and cathelicidins are broad spectrum antimicrobials that preferentially permeabilize microbial membranes. These and other polypeptides function in both phagocytic and extracellular killing of microbes, attacking multiple molecular targets to cooperatively penetrate and disrupt the microbial surfaces and membrane barriers. Such antimicrobial substances are of interest not only for students of phagocytic and epithelial host defenses but may lead to the development of novel pharmaceuticals for the treatment of infections and their sequellae.
Effect of increased glycogen synthase kinase-3 activity upon the maturation of the amyloid precursor protein in transfected cells (1997)

Aberrant control of protein phosphorylation is an important feature in Alzheimer's disease pathology. The action of glycogen synthase kinase-3 beta (GSK-3 beta) on the maturation and phosphorylation of an amyloid precursor protein-reporter construct (APP-REP) was studied in transfected COS-7 cells. Elevation of GSK-3 beta activity by enzyme over-expression resulted in an increase in the level of mature forms of co-expressed APP-REP. This effect was not associated with an increased level of APP-REP phosphorylation at Thr743, an in vitro GSK-3 beta phosphorylation site. These findings suggest that GSK-3 beta activity may indirectly increase cellular maturation of APP, which may subsequently result in altered production of beta-amyloid protein.
Autonomic effects of refractory epilepsy on heart rate variability in children: influence of intermittent vagus nerve stimulation (2011)

Heart rate variability is affected in children with refractory epilepsy, and changes after implantation of VNS. The observed changes could be of importance in the cardiac complications of individuals with epilepsy and should be explored in more detail.
Mammalian chromatin substructure studies with the calcium–magnesium endonuclease and two-dimensional polyacrylamide-gel electrophoresis (1974)

The basic regularity of chromatin substructure that has been reported in rat liver chromatin (Hewish & Burgoyne, 1973b) was also detected in mouse chromatin. The regular series of DNA fragments produced by the action of Ca-Mg endonuclease on rat chromatin were studied further. The smallest single-stranded class has a molecular weight of approx. 45000-63000 and the smallest double-stranded class has a molecular weight of approx. 120000-150000. Studies of the substructure of the DNA fragments produced by the Ca-Mg endonuclease have shown that the regular series of double-stranded fragments have regular series of single-stranded fragments within them. It was concluded that the regular series of double-stranded fragments was probably a consequence of the regular series of single-stranded fragments. Digestion time-courses are presented for mouse and rat nuclear DNA.
Understanding Leukemias, Lymphomas and Myelomas (2005)

A practical and highly illustrated guide to the hematologic cancers, Understanding Leukemias, Lymphomas and Myelomas is an invaluable primer for everyone involved with these conditions, from specialists in training to interested patients. Using straightforward terminology and extensive color figures to describe and illustrate the current procedures
Visualization of scalar data defined on a structured grid-applications to petroleum research (1990)

We will describe in this article some simple visualization techniques that may be used to explore dynamic 3D scalar fields in an interactive way. Scalar data are assumed to have been already computed, and graphic manipulations are done afterwards on a graphics workstation. Structured grids (finite difference grids) are used, leading to an easy and fast exploration of the interior of a volume. Smooth animation and simultaneous visualization of two or three scalar fields are also described. We have tested our methods on various types of data issuing from different fields of petroleum engineering, i.e. oil reservoir simulation, geophysics, geology and combustion engine simulations.A demonstration videotape is available.
Antitumor Activity of Targeted and Cytotoxic Agents in Murine Subcutaneous Tumor Models Correlates with Clinical Response (2012)

On the basis of these analyses, agents that led to greater than 60% TGI in preclinical models, at clinically relevant exposures, are more likely to lead to responses in the clinic. A proposed strategy for the use of murine subcutaneous models for compound selection in anticancer drug discovery is discussed.
Primary prophylaxis in children with haemophilia. (2008)

Starting from the clinical observations that moderate haemophiliacs experienced only few bleeding episodes and rarely developed significant joint deterioration (haemophilic arthropathy), and the pioneer experience in Sweden, prophylaxis (i.e. the regular and long-term administration of clotting factor concentrate in order to prevent bleeding) has been practiced for more than forty years in severe haemophilia and is currently recommended as the first choice of treatment by the World Health Organisation and World Federation of Hemophilia and by many national medical/scientific organizations. Observational studies clearly established the superiority of prophylaxis over on-demand treatment in reducing the risk of arthropathy, also showing that starting prophylaxis earlier in life and after very few joint bleeds was associated with better joint outcomes, and led to the current definitions of primary (started before the age of 2 yrs and after no more than one joint bleed) and secondary prophylaxis. More recently, evidences from randomized trials, which were previously lacking in this setting, were also provided. This review summarizes available data from which current clinical practice of primary (and early secondary) prophylaxis in children with severe haemophilia was drawn. Open issues concerning optimal regimens and barriers to the implementation of prophylaxis are also discussed.
Video-bandwidth compression: a study in tradeoffs (1979)

Discusses the image compression technology where the aim is to narrow the transmitted band-width as much as possible. Such compression reduces the cost of transmission and for military use it reduces the susceptibility to interference, but the problem is that the higher the compression, the greater the loss of image quality.
Overexpression of the MarA positive regulator is sufficient to confer multiple antibiotic resistance in Escherichia coli (1993)

A genetic approach was undertaken to identify normal bacterial genes whose products function to limit the effective concentration of antibiotics. In this approach, a multicopy plasmid library containing cloned Escherichia coli chromosomal sequences was screened for transformants that showed increased resistance to a number of unrelated antibiotics. Three such plasmids were identified, and all contained sequences originating from the mar locus. DNA sequence analysis of the minimal complementation unit revealed that the resistance phenotype was associated with the presence of the marA gene on the plasmids. The putative marA gene product is predicted to contain a helix-turn-helix DNA binding domain that is very similar to analogous domains found in three other E. coli proteins. One such similarity was to the SoxS gene product, the elevated expression of which has previously been associated with the multiple antibiotic resistance (Mar) phenotype. Constitutive expression of marA conferred antibiotic resistance even in cells carrying a deletion of the chromosomal mar locus. We have also found that transformants bearing marA plasmids show a significant reduction in ompF translation but not transcription, similar to previously described mar mutants. However, this reduction in ompF expression plays only a minor role in the resistance mechanism, suggesting that functions encoded by genes unlinked to mar must be affected by marA. These results suggest that activation of marA is the ultimate event that occurs at the mar locus during the process that results in multiple antibiotic resistance.
Tandem Binding of Six OmpR Proteins to the ompF Upstream Regulatory Sequence of Escherichia coli (1995)

OmpR is a transcription factor in Escherichia coli whose function is modulated by phosphorylation in the presence of phosphorylated EnvZ, a transmembrane protein histidine kinase involved in osmosensing. Using a protein S-OmpR hybrid protein, we demonstrated that six OmpR molecules bind tandemly to the -100 to -39 sequence of ompF. This sequence consists of three 20-base pair units: F1, F2, and F3, each of which is bound by two OmpR proteins. Polymerase chain reaction selection of nine randomized base pairs within the F1 sequence revealed highly conserved C residues spaced 10 base pairs apart. Further mutational analysis of conserved bases indicated that two OmpR molecules bind tandemly to two direct repeats. Mobility shift assays showed that cooperative interactions play a role in enhancing binding of OmpR to lower affinity F2 and F3 sites. Activation and repression of ompF expression are thus regulated by a total of eight OmpR molecules, including two molecules that bind to a distal site (-380 to -361). OmpR is a transcription factor in Escherichia coli whose function is modulated by phosphorylation in the presence of phosphorylated EnvZ, a transmembrane protein histidine kinase involved in osmosensing. Using a protein S-OmpR hybrid protein, we demonstrated that six OmpR molecules bind tandemly to the -100 to -39 sequence of ompF. This sequence consists of three 20-base pair units: F1, F2, and F3, each of which is bound by two OmpR proteins. Polymerase chain reaction selection of nine randomized base pairs within the F1 sequence revealed highly conserved C residues spaced 10 base pairs apart. Further mutational analysis of conserved bases indicated that two OmpR molecules bind tandemly to two direct repeats. Mobility shift assays showed that cooperative interactions play a role in enhancing binding of OmpR to lower affinity F2 and F3 sites. Activation and repression of ompF expression are thus regulated by a total of eight OmpR molecules, including two molecules that bind to a distal site (-380 to -361).
Back-gate forward bias method for low-voltage CMOS digital circuits (1996)

The back-gate forward bias method suitable for present standard bulk CMOS processes has been promoted for low-voltage digital circuit application. A CMOS inverter employing the method has experimentally exhibited the ability of electrically adjusting the transition region of the dc voltage transfer characteristics. Transient measurement has further shown that the inverter with a back-gate forward bias of 0.4 V can operate at low supply voltages down to 0.6 V without significant loss in switching speed. Guidelines for ensuring proper implementation of the method in a bulk CMOS process have been set up against latch-up, parasitic bipolar, impact ionization, and stand by current. Following these guidelines, a cost-effective low power, low-voltage, high-density mixed mode CMOS analog/digital integrated circuits chip with both reasonable speed and improved precision has been projected for the first time.
Review article: visceral hypersensitivity in irritable bowel syndrome: molecular mechanisms and therapeutic agents (2009)

It is anticipated that with advancing molecular understanding of the basis of visceral hypersensitivity, the next decade will see accelerated development of new molecules for treatment of functional bowel diseases.
Aortic and hepatic contrast medium enhancement at CT. Part I. Prediction with a computer model. (1998)

A computer-based, physiologic model that may help predict organ-specific CT contrast medium enhancement for different injection protocols was developed. Such a physiologic model may have many clinical applications.
Co-clustering directed graphs to discover asymmetries and directional communities (2016)

In directed graphs, relationships are asymmetric and these asymmetries contain essential structural information about the graph. Directed relationships lead to a new type of clustering that is not feasible in undirected graphs. We propose a spectral co-clustering algorithm called di-sim for asymmetry discovery and directional clustering. A Stochastic co-Blockmodel is introduced to show favorable properties of di-sim To account for the sparse and highly heterogeneous nature of directed networks, di-sim uses the regularized graph Laplacian and projects the rows of the eigenvector matrix onto the sphere. A nodewise asymmetry score and di-sim are used to analyze the clustering asymmetries in the networks of Enron emails, political blogs, and the <i>Caenorhabditis</i><i>elegans</i> chemical connectome. In each example, a subset of nodes have clustering asymmetries; these nodes send edges to one cluster, but receive edges from another cluster. Such nodes yield insightful information (e.g., communication bottlenecks) about directed networks, but are missed if the analysis ignores edge direction.
Recognizing Insufficiently Supported Arguments in Argumentative Essays (2017)

In this paper, we propose a new task for assessing the quality of natural language arguments. The premises of a well-reasoned argument should provide enough evidence for accepting or rejecting its claim. Although this criterion, known as sufficiency, is widely adopted in argumentation theory, there are no empirical studies on its applicability to real arguments. In this work, we show that human annotators substantially agree on the sufficiency criterion and introduce a novel annotated corpus. Furthermore, we experiment with feature-rich SVMs and convolutional neural networks and achieve 84% accuracy for automatically identifying insufficiently supported arguments. The final corpus as well as the annotation guideline are freely available for encouraging future research on argument quality. 1
Induction of apoptosis by beta-lapachone in human prostate cancer cells. (1995)

beta-Lapachone, a plant product, has been shown to be a novel inhibitor of DNA topoisomerase I, with a mode of action different from camptothecin and a chemical structure distinct from those of current anti-cancer drugs. We observed that beta-lapachone, at concentrations of less than 8 microM, induces cell death with characteristics of apoptosis in human prostate cancer cell lines. This effect of beta-lapachone was also observed in a human promyelocytic leukemia cell line (HL-60). beta-Lapachone-induced apoptosis is independent of p53 expression, and ectopic overexpression of bcl-2 did not confer significant resistance to beta-lapachone. Among other human carcinoma and adenoma cell lines tested, human breast and ovary carcinoma showed sensitivity to the cytotoxic effect of beta-lapachone without manifesting signs of apoptosis. These results suggest that beta-lapachone is a potential compound to be added to cancer chemotherapy, particularly for prostate cancer.
When your cap matters: structural insights into self vs non-self recognition of 5′ RNA by immunomodulatory host proteins (2016)

Cytosolic recognition of viral RNA is important for host innate immune responses. Differential recognition of self vs non-self RNA is a considerable challenge as the inability to differentiate may trigger aberrant immune responses. Recent work identified the composition of the RNA 5', including the 5' cap and its methylation state, as an important determinant of recognition by the host. Recent studies have advanced our understanding of the modified 5' RNA recognition and viral antagonism of RNA receptors. Here, we will discuss RIG-I and IFIT proteins as examples of host proteins that detect dsRNA and ssRNA, respectively.
Synthesis and cellular activity of stereochemically-pure 2′-O-(2-methoxyethyl)-phosphorothioate oligonucleotides (2016)

Stereochemically-pure 2'-O-(2-methoxyethyl)-phosphorothioate (PS-MOE) oligonucleotides were synthesized from new chiral oxazaphospholidine-containing nucleosides. Thermal stability studies showed that the incorporation of Rp-PS linkages increased RNA-binding affinity. In cells, a full Rp-PS-MOE splice-switching oligonucleotide targeting part of the ferrochelatase gene was more potent than its Sp-PS counterpart, but of similar potency to the stereorandom PS-parent sequence.
Immunologic Recognition of a Shared p53 Mutated Neoantigen in a Patient with Metastatic Colorectal Cancer (2019)

Adoptive cell therapy (ACT) with T cells targeting neoantigens can mediate durable responses in patients with metastatic cancer. Cell therapies targeting common shared antigens for epithelial cancers are not yet broadly available. Here, we report the identification and characterization in one patient of T-cell receptors (TCRs) recognizing mutated p53 p.R175H, which is shared among a subset of patients with cancer. Tumor-infiltrating lymphocytes were screened for recognition of mutated neoantigens in a patient with metastatic colorectal cancer. HLA-A*0201-restricted recognition of mutated p53 p.R175H was identified, and the minimal peptide epitope was HMTEVVR<u>H</u>C. Reactive T cells were isolated by tetramer sorting, and three TCRs were identified. These TCRs mediated recognition of commercially available ovarian cancer, uterine carcinoma, and myeloma cell lines, as well as an NIH patient-derived esophageal adenocarcinoma line that endogenously expressed p53 p.R175H and HLA-A*0201. They also mediated recognition of p53 p.R175H<sup>+</sup> colon, breast, and leukemia cell lines after transduction with a retrovirus encoding HLA-A*0201. This work demonstrates that common shared mutated epitopes such as those found in p53 can elicit immunogenic responses and that the application of ACT may be extended to patients with any cancer histology that expresses both HLA-A*0201 and the p53 p.R175H mutation.