gebhart/patrepeval huggingface dataset:
In silicodissection of cell-type-associated patterns of gene expression in prostate cancer (2004)

Prostate tumors are complex entities composed of malignant cells mixed and interacting with nonmalignant cells. However, molecular analyses by standard gene expression profiling are limited because spatial information and nontumor cell types are lost in sample preparation. We scored 88 prostate specimens for relative content of tumor, benign hyperplastic epithelium, stroma, and dilated cystic glands. The proportions of these cell types were then linked in silico to gene expression levels determined by microarray analysis, revealing unique cell-specific profiles. Gene expression differences for malignant and nonmalignant epithelial cells (tumor versus benign hyperplastic epithelium) could be identified without being confounded by contributions from stroma that dominate many samples or sacrificing possible paracrine influences. Cell-specific expression of selected genes was validated by immunohistochemistry and quantitative PCR. The results provide patterns of gene expression for these three lineages with relevance to pathogenetic, diagnostic, and therapeutic considerations.
Polymorphic transitions in single crystals: A new molecular dynamics method (1981)

A new Lagrangian formulation is introduced. It can be used to make molecular dynamics (MD) calculations on systems under the most general, externally applied, conditions of stress. In this formulation the MD cell shape and size can change according to dynamical equations given by this Lagrangian. This new MD technique is well suited to the study of structural transformations in solids under external stress and at finite temperature. As an example of the use of this technique we show how a single crystal of Ni behaves under uniform uniaxial compressive and tensile loads. This work confirms some of the results of static (i.e., zero temperature) calculations reported in the literature. We also show that some results regarding the stress-strain relation obtained by static calculations are invalid at finite temperature. We find that, under compressive loading, our model of Ni shows a bifurcation in its stress-strain relation; this bifurcation provides a link in configuration space between cubic and hexagonal close packing. It is suggested that such a transformation could perhaps be observed experimentally under extreme conditions of shock.
Human primary osteoclasts: in vitro generation and applications as pharmacological and clinical assay (2004)

Osteoclasts are cells of hematopoietic origin with a unique property of dissolving bone; their inhibition is a principle for treatment of diseases of bone loss. Protocols for generation of human osteoclasts in vitro have been described, but they often result in cells of low activity, raising questions on cell phenotype and suitability of such assays for screening of bone resorption inhibitors. Here we describe an optimized protocol for the production of stable amounts of highly active human osteoclasts. Mononuclear cells were isolated from human peripheral blood by density centrifugation, seeded at 600,000 cells per 96-well and cultured for 17 days in alpha-MEM medium, supplemented with 10% of selected fetal calf serum, 1 microM dexamethasone and a mix of macrophage-colony stimulating factor (M-CSF, 25 ng/ml), receptor activator of NFkappaB ligand (RANKL, 50 ng/ml), and transforming growth factor-beta1 (TGF-beta1, 5 ng/ml). Thus, in addition to widely recognized osteoclast-generating factors M-CSF and RANKL, other medium supplements and lengthy culture times were necessary. This assay reliably detected inhibition of osteoclast formation (multinucleated cells positive for tartrate-resistant acid phosphatase) and activity (resorbed area and collagen fragments released from bone slices) in dose response curves with several classes of bone resorption inhibitors. Therefore, this assay can be applied for monitoring bone-resorbing activity of novel drugs and as an clinical test for determining the capacity of blood cells to generate bone-resorbing osteoclasts. Isolation of large quantities of active human osteoclast mRNA and protein is also made possible by this assay.
Immigrants into Citizens: a UK Case Study for the Classroom (2008)

How do you become a British citizen? Apart from finding yourself one, as an accident of birth, you can choose to become one. This paper looks at that process, because it reveals much about British government assumptions about the community, the role of the citizen, and appropriate education for citizenship. This in turn raises questions about how far these are appropriate assumptions for a country which aspires to be a democracy. I suggest at the end of the paper that studying the concrete example of the British process of becoming a citizen (i.e., naturalisation) may be a good route for school students into understanding the complexities of immigration and possible democratic responses. It will be very much a case of schooling as if democracy matters.
Inhibition of transcription in somatic cells by microinjection of antibodies to chromosomal proteins. (1983)

The in vivo function of defined chromosomal proteins was examined by microinjecting purified antibody and antibody fragments into living fibroblasts. The involvement of histones and chromosomal high mobility group proteins HMG-1, 2, and 17 in transcription was visualized by studying the [3H]uridine incorporation in KD human fibroblasts after microinjection of fluoresceinated antibodies to these proteins. Nuclear uridine incorporation was not affected by microinjection of control antibodies or by the presence of immune complexes formed after microinjection of antibodies to chromosomal proteins that are not involved in transcription. In contrast, injection of anti-histone IgG, F(ab')2, or Fab and anti-HMG-17 IgG causes a significant reduction in transcription. The reduction is proportional to the amount of antibody introduced into the cell. We conclude that histones and protein HMG-17 are present on transcribed regions of the genome and that passage of RNA polymerase along the chromatin fiber is prevented by antibody binding to these proteins.
Efficient N*N star couplers using Fourier optics (1989)

A technique for constructing an efficient N*N star coupler with large N at optical frequencies is described. The coupler is realized in free space using two arrays, each connected to N single-mode fibers. The highest efficiencies are obtained using a planar arrangement of two linear arrays separated by a dielectric slab serving as free-space region. The coupler is suitable for mass production in integrated form, with efficiencies exceeding 35%.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring (1999)

Although cancer classification has improved over the past 30 years, there has been no general approach for identifying new cancer classes (class discovery) or for assigning tumors to known classes (class prediction). Here, a generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case. A class discovery procedure automatically discovered the distinction between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) without previous knowledge of these classes. An automatically derived class predictor was able to determine the class of new leukemia cases. The results demonstrate the feasibility of cancer classification based solely on gene expression monitoring and suggest a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge.
Structurally Selective Imaging Mass Spectrometry by Imaging Ion Mobility-Mass Spectrometry (2010)

This chapter describes the utility of structurally based separations combined with imaging mass spectrometry (MS) by ion mobility-MS (IM-MS) approaches. The unique capabilities of combining rapid (mus-ms) IM separations with imaging MS are detailed for an audience ranging from new to potential practitioners in IM-MS technology. Importantly, imaging IM-MS provides the ability to rapidly separate and elucidate various types of endogenous and exogenous biomolecules (e.g., nucleotides, carbohydrates, peptides, and lipids), including isobaric species. Drift tube and traveling wave IM-MS instrumentation are described and specific protocols are presented for calculating ion-neutral collision cross sections (i.e., apparent ion surface area or structure) from experimentally obtained IM-MS data. Special emphasis is placed on the use of imaging IM-MS for the analysis of samples in life sciences research (e.g., thin tissue sections), including selective imaging for peptide/protein and lipid distributions. Future directions for rapid and multiplexed imaging IM-MS/MS are detailed.
Immunopathological characterization of selected mouse models of inflammatory bowel disease: Comparison to human disease (2014)

Inflammatory bowel diseases (IBD) are chronic, relapsing conditions of multifactorial etiology. The two primary diseases of IBD are Crohn's disease (CD) and ulcerative colitis (UC). Both entities are hypothesized to occur in genetically susceptible individuals due to microbial alterations and environmental contributions. The exact etiopathogenesis, however, is not known for either disease. A variety of mouse models of CD and UC have been developed to investigate the pathogenesis of these diseases and evaluate treatment modalities. Broadly speaking, the mouse models can be divided into 4 categories: genetically engineered, immune manipulated, spontaneous and erosive/chemically induced. No one mouse model completely recapitulates the immunopathology of CD or UC, however each model possesses particular similarities to human IBD and offers advantageous for specific details of IBD pathogenesis. Here we discuss the more commonly used models in each category and critically evaluate how the immunopathology induced compares to CD or UC, as well as the advantages and disadvantages associated with each model.
Wide local excision in carcinoma of the breast (1990)

We would like to reply to the letter from Dawson et al.The limit of 30 days was selected to allow a relatively close range of duration of occlusions; this then provides efficient lysis in comparable patients.We fully agree that lesions of longer duration can be treated, albeit with a longer duration of lysis, and hence a tendency to a higher haemorrhagic complication risk.As experience with new agents such as r-TPA increases, more mature lesions will undoubtedly be accepted for lysis.Peripheral arterial graft thromboses can be lysed even in the early postoperative period, the fresh intraluminal thrombus being more susceptible to lysis than the 'mature' (cross-linked) anastomotic and wound thrombus/fibrin.However, the longer the infusion continues, the higher the risk of this also being lysed and hence causing haemorrhage.In the periphery, this risk can be monitored, and if necessary controlled by pressure whilst other specific measures are introduced.However, following intra-abdominal, intrathoracic, or intracerebral surgery this presents an unacceptable risk.Postlysis anticoagulation rather than low-dose platelets was chosen following the occurrence of early rethromboses on patients only given aspirin in earlier work.These patients were successfully relysed and their patency has been maintained on warfarin.All patients are anticoagulated for 3 months and then transferred to low-dose aspirin.
Selective hydrolysis of cellulose into glucose over solid acid catalysts (2008)

The mildly hydrothermal method using solid acid catalysts for the glucose production from cellulose can be one of the key technologies for a future sustainable society using cellulose biomass. This article is the first to indicate solid acid catalysis for the hydrolysis of cellulose with β-1,4-glycosidic bonds into glucose selectively higher than 90 C-%. Among the solid acid catalysts we tested, such as the H-form zeolite catalysts and the sulfated and sulfonated catalysts, a sulfonated activated-carbon catalyst showed a remarkably high yield of glucose, which was due to the high hydrothermal stability and the excellent catalytic property attributed to the strong acid sites of SO3H functional groups and the hydrophobic planes.
Effect of Coenzyme Q10 on ischemia and neuronal damage in an experimental traumatic brain-injury model in rats (2011)

Neuronal degenerative findings and the secondary brain damage and ischemia caused by oxidative stress are decreased by CoQ₁₀ use in rats with traumatic brain injury.
The Kerberos Network Authentication Service (V5) (1993)

5 of the protocol for the Kerberos network authentication system.Version 4, described elsewhere [1,2], is presently in production use at MIT's Project Athena, and at other Internet sites.
Persistent abnormality detected in the non-ictal electroencephalogram in primary generalised epilepsy (2002)

Increased gamma EEG is probably a marker of the underlying ion channel or neurotransmitter receptor dysfunction in primary generalised epilepsies and may also be a pathophysiological prerequisite for the development of seizures. The finding provides a new diagnostic approach and also links the pathophysiology of generalised epilepsies to emerging concepts of neuronal correlates of consciousness.
Successful Integration of Informal Learning in Engineering Education (2012)

Abstractâ?? Research suggests that an emerging environment of ubiquitous information technology affords seamless movement between formal learning, informal learning, and the workplace. This paper reviews research data from one successful teaching and learning methodology that leverages seamless movements between informal and formal learning in engineering education. The research is an ongoing pilot study at the University of Hartford using data from selected technical mathematics and communication electronics courses. The research data suggests that clearly defined academic jurisdictions have a positive correlation with successful integration of formal learning, informal learning, and the workplace. However, themes from the data also suggest that crossing academic boundaries involves more than technology issues and could raise the specter of unintended social-dramas. One theme suggests that, in a seamless environment without clearly defined academic jurisdictions, opportunities for collaboration could be misinterpreted as encroachments. To mitigate issues of competing jurisdictional interests this study employs Learner Agent Objects (LAO) individual portfolios. LAO portfolios are collections of evidence-based artifacts representing a learner's academic experience that independently moves with the learner as data network nodes between jurisdictions in engineering education and the workplace.
Genomewide view of gene silencing by small interfering RNAs (2003)

RNA interference (RNAi) is an evolutionarily conserved mechanism in plant and animal cells that directs the degradation of messenger RNAs homologous to short double-stranded RNAs termed small interfering RNA (siRNA). The ability of siRNA to direct gene silencing in mammalian cells has raised the possibility that siRNA might be used to investigate gene function in a high throughput fashion or to modulate gene expression in human diseases. The specificity of siRNA-mediated silencing, a critical consideration in these applications, has not been addressed on a genomewide scale. Here we show that siRNA-induced gene silencing of transient or stably expressed mRNA is highly gene-specific and does not produce secondary effects detectable by genomewide expression profiling. A test for transitive RNAi, extension of the RNAi effect to sequences 5' of the target region that has been observed in Caenorhabditis elegans, was unable to detect this phenomenon in human cells.
QSAR in grossly underdetermined systems: Opportunities and issues (2001)

Regression in grossly underdetermined systems has emerged as an important means for understanding molecular activity via comparative molecular field analysis (CoMFA) and other quantitative structure activity relationship (QSAR) studies. But this methodology has applications in much broader areas; for example, near-infrared spectroscopy, mutational enzyme activity studies including protein folding rates to determine which sites are important for determining conformation, and analyses of gene expression data from chip arrays. An error analysis which answers questions concerning the quality of the predictivity, the relative importance of each descriptor, the quality of the estimates of the contribution by each descriptor, and the number of independent components expressed by the associated data is indispensable in understanding whether some particular set of structure variables is important in defining the mechanisms driving the chemical or biological activities. This paper reviews opportunities for QSAR stu dies. It also considers the analytical aspects of error analysis in least-squares regression, and contrasts principal component regression (PCR) and partial least-squares (PLS) procedures with cross-validation on the issues of error analysis (e.g., the quality of the contribution estimates for each structure descriptor). Further, a methodology for selecting optimal subsets of components in PCR is presented.
Protease-based synthetic sensing and signal amplification (2014)

The bottom-up design of protein-based signaling networks is a key goal of synthetic biology; yet, it remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Here, we report a generic approach for the construction of protein-based molecular switches based on artficially autoinhibited proteases. Using structure-guided design and directed protein evolution, we created signal transducers based on artificially autoinhibited proteases that can be activated following site-specific proteolysis and also demonstrate the modular design of an allosterically regulated protease receptor following recombination with an affinity clamp peptide receptor. Notably, the receptor's mode of action can be varied from >5-fold switch-OFF to >30-fold switch-ON solely by changing the length of the connecting linkers, demonstrating a high functional plasticity not previously observed in naturally occurring receptor systems. We also create an integrated signaling circuit based on two orthogonal autoinhibited protease units that can propagate and amplify molecular queues generated by the protease receptor. Finally, we present a generic two-component receptor architecture based on proximity-based activation of two autoinhibited proteases. Overall, the approach allows the design of protease-based signaling networks that, in principle, can be connected to any biological process.
Connexin 30 is expressed in the mouse sino-atrial node and modulates heart rate (2009)

Cx30 is functionally expressed, in low abundance, in the SA node of the adult mouse heart where it participates in HR regulation.
Dual myristylation and palmitylation of Src family member p59fyn affects subcellular localization (1994)

The Src family consists of nine related tyrosine protein kinases with a common domain structure, including a myristylated N-terminal glycine residue. In this report, we identify cysteine residues within the N-terminal region of the Src family member Fyn which serve as sites for palmitylation. To facilitate detection of protein fatty acylation, p59fyn was overexpressed in COS cells and incubated with radioiodinated fatty acid analogs of myristate (IC13) or palmitate (IC16). Incorporation of both fatty acids into p59fyn was readily observed. Acylation with the palmitate analog was prevented when Gly-2 was mutated to alanine, implying that N-myristylation is required for palmitylation, and when either Cys-3 or Cys-6 was mutated to serine. Palmitylation was shown to alter the distribution of p59fyn between membrane-bound and soluble fractions. In contrast, no incorporation of the palmitate analog into pp60v-src, which lacks N-terminal cysteine residues, was observed. Mutation of Ser-3 of Src to cysteine, but not Ser-6, resulted in incorporation of the palmitate analog. These results serve to delineate sequence elements important for dual acylation of proteins, and further illustrate the utility of radioiodinated fatty acid analogs for studies of protein fatty acid acylation.
Binding of DNA Oligonucleotides to Sequences in the Promoter of the Human bcl-2 Gene (1996)

Duplex DNA recognition by oligonucleotide-directed triple helix formation is being explored as a highly specific approach to artificial gene repression. We have identified two potential triplex target sequences in the promoter of the human bcl-2 gene, whose product inhibits apoptosis. Oligonucleotides designed to bind these target sequences were tested for their binding affinities and specificities under pseudo-physiological conditions. Electrophoretic mobility shift and dimethyl sulfate footprinting assays demonstrated that an oligonucleotide designed for simultaneous recognition of homopurine domains on alternate duplex DNA strands had the highest affinity of any oligonucleotide tested. Modifications to render this oligonucleotide nuclease-resistant did not reduce its binding affinity or specificity. In additional studies under various pH conditions, pyrimidine motif complexes at these target sequences were found to be stable at pH 8.0, despite the presumed requirement for protonation of oligonucleotide cytidines. In contrast, purine motif complexes, typically considered to be pH independent, were highly destabilized at decreasing pH values. These results indicate that a natural sequence in the human bcl-2 promoter can form a stable triplex with a synthetic oligonucleotide under pseudo-physiological conditions, and suggest that triple helix formation might provide an approach to the artificial repression of bcl-2 transcription.
Remodeling of Cardiolipin by Phospholipid Transacylation (2003)

Mitochondrial cardiolipin (CL) contains unique fatty acid patterns, but it is not known how the characteristic molecular species of CL are formed. We found a novel reaction that transfers acyl groups from phosphatidylcholine or phosphatidylethanolamine to CL in mitochondria of rat liver and human lymphoblasts. Acyl transfer was stimulated by ADP, ATP, and ATP gamma S, but not by other nucleotides. Coenzyme A stimulated the reaction only in the absence of adenine nucleotides. Free fatty acids were not incorporated into CL under the same incubation condition. The transacylation required addition of exogenous CL or monolyso-CL, whereas dilyso-CL was not a substrate. Transacylase activity was decreased in lymphoblasts from patients with Barth syndrome (tafazzin deletion), and this was accompanied by drastic changes in the molecular composition of CL. In rat liver, where linoleic acid was the most abundant residue of CL, only linoleoyl groups were transferred into CL, but not oleoyl or arachidonoyl groups. We demonstrated complete remodeling of tetraoleoyl-CL to tetralinoleoyl-CL in rat liver mitochondria and identified the intermediates linoleoyl-trioleoyl-CL, dilinoleoyl-dioleoyl-CL, and trilinoleoyl-oleoyl-CL by high-performance liquid chromatography. The data suggest that CL is remodeled by acyl specific phospholipid transacylation and that tafazzin is an acyltransferase involved in this mechanism.