gebhart/patrepeval huggingface dataset:
Antiapoptotic Signalling by the Insulin-Like Growth Factor I Receptor, Phosphatidylinositol 3-Kinase, and Akt (1997)

We have found that insulin-like growth factor I (IGF-I) can protect fibroblasts from apoptosis induced by UV-B light. Antiapoptotic signalling by the IGF-I receptor depended on receptor kinase activity, as cells overexpressing kinase-defective receptor mutants could not be protected by IGF-I. Overexpression of a kinase-defective receptor which contained a mutation in the ATP binding loop functioned as a dominant negative and sensitized cells to apoptosis. The antiapoptotic capacity of the IGF-I receptor was not shared by other growth factors tested, including epidermal growth factor (EGF) and thrombin, although the cells expressed functional receptors for all the agonists. However, EGF was antiapoptotic for cells overexpressing the EGF receptor, and expression of activated pp60v-src also was protective. There was no correlation between protection from apoptosis and activation of mitogen-activated protein kinase, p38/HOG1, or p70S6 kinase. On the other hand, protection by any of the tyrosine kinases against UV-induced apoptosis was blocked by wortmannin, implying a role for phosphatidylinositol 3-kinase (PI3 kinase). To test this, we transiently expressed constitutively active or kinase-dead PI3 kinase and found that overexpression of activated phosphatidylinositol 3-kinase (PI3 kinase) was sufficient to provide protection against apoptosis. Because Akt/PKB is believed to be a downstream effector for PI3 kinase, we also examined the role of this serine/threonine protein kinase in antiapoptotic signalling. We found that membrane-targeted Akt was sufficient to protect against apoptosis but that kinase-dead Akt was not. We conclude that the endogenous IGF-I receptor has a specific antiapoptotic signalling capacity, that overexpression of other tyrosine kinases can allow them also to be antiapoptotic, and that activation of PI3 kinase and Akt is sufficient for antiapoptotic signalling.
Radar target scattering matrix measurement through orthogonal signals (1993)

A method recently proposed for the simultaneous measurement of all four elements of the target scattering matrix in polarimetric radars is considered and analysed. The method makes use of pulse signal coding and is theoretically based on the simultaneous independent transmission of two orthogonal signals on two orthogonally polarised channels feeding the same antenna. The elements of the target scattering matrix are retrieved by correlating the received signal on each orthogonally polarised channel with both the transmitted waveforms. The potential advantages offered by this measurement method are discussed, with particular reference to the accuracy of the scattering matrix measurement in the presence of point targets. Related radar system implications and improvements are discussed, and applications of different types of transmission waveforms are considered.
An information-bearing seed for nucleating algorithmic self-assembly (2009)

Self-assembly creates natural mineral, chemical, and biological structures of great complexity. Often, the same starting materials have the potential to form an infinite variety of distinct structures; information in a seed molecule can determine which form is grown as well as where and when. These phenomena can be exploited to program the growth of complex supramolecular structures, as demonstrated by the algorithmic self-assembly of DNA tiles. However, the lack of effective seeds has limited the reliability and yield of algorithmic crystals. Here, we present a programmable DNA origami seed that can display up to 32 distinct binding sites and demonstrate the use of seeds to nucleate three types of algorithmic crystals. In the simplest case, the starting materials are a set of tiles that can form crystalline ribbons of any width; the seed directs assembly of a chosen width with >90% yield. Increased structural diversity is obtained by using tiles that copy a binary string from layer to layer; the seed specifies the initial string and triggers growth under near-optimal conditions where the bit copying error rate is <0.2%. Increased structural complexity is achieved by using tiles that generate a binary counting pattern; the seed specifies the initial value for the counter. Self-assembly proceeds in a one-pot annealing reaction involving up to 300 DNA strands containing >17 kb of sequence information. In sum, this work demonstrates how DNA origami seeds enable the easy, high-yield, low-error-rate growth of algorithmic crystals as a route toward programmable bottom-up fabrication.
The putative serine/threonine kinase gene STK15 on chromosome 20q13.2 is amplified in human gliomas (2003)

Searching for amplifications in low grade and high grade gliomas we observed an interesting correlation between the recurrence and progression of astrocytic low grade gliomas and the amplification of the STK15 gene located in the chromosomal region 20q13. Chromosome copy gains in this region have been reported previously in astrocytic gliomas and glioma cell lines and in many cancer types including breast, colorectal and ovarian cancers. The putative serine/threonine kinase STK15 has been reported to be amplified and overexpressed in breast cancer cell lines and colorectal cancer. Another candidate gene located in this region is PTPN1, a protein tyrosine phosphatase non-receptor type 1 that might play a role in cell cycle control. We used comparative PCR for quantitative DNA analysis to search for STK15 and PTPN1 amplification in gliomas previously characterized by CGH. Five out of 16 tumors (31%) of different WHO grade (1x grade II, 1x grade III, 3x grade IV) showed DNA amplification of STK15 whereas we did not detect amplification of PTPN1. We hypothesize that amplification of the STK15 gene may be a non-random genetic alteration in human gliomas playing a role in the genetic pathways of tumorigenesis.
Detrimental Effect of Formaldehyde on Plasma RNA Detection (2005)

Recent studies have shown that detection of fetal DNA or RNA in maternal plasma is useful for prenatal investigation of certain fetal genetic traits (1)(2) or pregnancy-associated complications (3)(4). Fetal DNA has been shown to amount to 3.4%–6.2% of the total DNA in maternal plasma (5). Thus, the reliability of circulating fetal nucleic acids analysis is dependent on the ability to sensitively and specifically detect and distinguish such fetal molecules from a background of maternal nucleic acids. Hence, methods that enable enrichment of the proportion of fetal nucleic acids in maternal plasma would, in theory, facilitate robust analysis of circulating fetal nucleic acids. Dhallan et al. (6) recently explored the use of formaldehyde for the enrichment of circulating fetal DNA. The authors reported marked increases in the proportion of fetal DNA in maternal blood samples preserved with formaldehyde. Although controversies exist regarding the …
Characteristics of pyridoxine overdose neuropathy syndrome (1987)

A newly recognised neurotoxic syndrome due to pyridoxine (B6) overdose is described. It is the largest series of B6 intoxication hitherto reported. A raised serum B6 level was present in 172 women of whom 60% had neurological symptoms, which disappeared when B6 was withdrawn and reappeared in 4 cases when B6 was restarted. The mean dose of B6 in the 103 women with neurological symptoms was 117 +/- 92 mgs, compared with 116.2 +/- 66 mgs in the control group. There was a significant difference (P less than 0.01) in the average duration of ingestion of B6 in the neurotoxic group of 2.9 +/- 1.9 years compared with 1.6 +/- 2.1 years in controls. The symptoms were paraesthesia, hyperaesthesia, bone pains, muscle weakness, numbness and fasciculation, most marked on the extremities and predominantly bilateral unless there was a history of previous trauma to the limb. These women were taking a lower dose of B6 than previously described (1,2), which may account for the complete recovery within 6 months of stopping B6.
Spontaneous Formation of Nucleic Acid-based Nanoparticles Is Responsible for High Interferon-α Induction by CpG-A in Plasmacytoid Dendritic Cells (2005)

Plasmacytoid dendritic cells (PDC) represent a highly specialized immune cell subset that produces large quantities of the anti-viral cytokines type I interferons (IFN-alpha and IFN-beta) upon viral infection. PDC employ a member of the family of toll-like receptors, TLR9, to detect CpG motifs (unmethylated CG dinucleotides in certain base context) present in viral DNA. A certain group of CpG motif-containing oligodeoxynucleotides (CpG ODN), CpG-A, was the first synthetic stimulus available that induced large amounts of interferon-alpha (IFN-alpha) in PDC. However, the mechanism responsible for this activity remained elusive. CpG-A is characterized by a central palindrome and poly(G) at the 5' and 3' end. Here we demonstrate that CpG-A self-assembles to higher order tertiary structures via G-tetrad formation of their poly(G) motifs. Spontaneous G-tetrad formation of CpG-A required the palindrome sequence allowing structure formation in a physiological environment. Once formed, G-tetrad-linked structures were stable even under denaturing conditions. Atomic force microscopy revealed that the tertiary structures formed by CpG-A represent nucleic acid-based nanoparticles in the size range of viruses. Similarly sized preformed polystyrene nanoparticles loaded with a CpG ODN that is otherwise weak at inducing IFN-alpha (CpG-B) gained the potency of CpG-A to induce IFN-alpha. Higher ODN uptake in PDC was not responsible for the higher IFN-alpha-inducing activity of CpG-A or of CpG-B-coated nanoparticles as compared with CpG-B. Based on these results we propose a model in which the spatial configuration of CpG motifs as particle is responsible for the virus-like potency of CpG-A to induce IFN-alpha in PDC.
Identification of functional domains in Arabidopsis thaliana mRNA decapping enzyme (AtDcp2) (2007)

The Arabidopsis thaliana decapping enzyme (AtDcp2) was characterized by bioinformatics analysis and by biochemical studies of the enzyme and mutants produced by recombinant expression. Three functionally significant regions were detected: (i) a highly disordered C-terminal region with a putative PSD-95, Discs-large, ZO-1 (PDZ) domain-binding motif, (ii) a conserved Nudix box constituting the putative active site and (iii) a putative RNA binding domain consisting of the conserved Box B and a preceding loop region. Mutation of the putative PDZ domain-binding motif improved the stability of recombinant AtDcp2 and secondary mutants expressed in Escherichia coli. Such recombinant AtDcp2 specifically hydrolysed capped mRNA to produce 7-methyl GDP and decapped RNA. AtDcp2 activity was Mn(2+)- or Mg(2+)-dependent and was inhibited by the product 7-methyl GDP. Mutation of the conserved glutamate-154 and glutamate-158 in the Nudix box reduced AtDcp2 activity up to 400-fold and showed that AtDcp2 employs the catalytic mechanism conserved amongst Nudix hydrolases. Unlike many Nudix hydrolases, AtDcp2 is refractory to inhibition by fluoride ions. Decapping was dependent on binding to the mRNA moiety rather than to the 7-methyl diguanosine triphosphate cap of the substrate. Mutational analysis of the putative RNA-binding domain confirmed the functional significance of an 11-residue loop region and the conserved Box B.
Space–time mapping and tiling: a helpful combination: Research Articles (2004)

Tiling is a well-known technique for sequential compiler optimization, as well as for automatic program parallelization. However, in the context of parallelization, tiling should not be considered as a stand-alone technique, but should be applied after a dedicated parallelization phase, in our case after space–time mapping. We show how tiling can benefit from space–time mapping, and we derive an algorithm for computing tiles which can minimize the number of communication startups, taking the number of physically available processors into account. We also present how the use of a simple cost model reduces real execution time. Copyright © 2004 John Wiley & Sons, Ltd.
APC‐dependent regulation of ornithine decarboxylase in human colon tumor cells (2002)

Mutation/deletion of the adenomatous polyposis coli (APC) tumor suppressor gene in germline cells of rodents and humans is associated with increased intestinal activity of ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, and intestinal neoplasia. To study the role of APC in signaling ODC expression, we used the human colon tumor cell line HT29 (wtAPC-/-), which has been stably transfected with a zinc-inducible wild-type APC gene. The addition of ZnCl(2) to HT29-APC cells increased wild-type APC protein and Mad1 RNA and protein and decreased levels of c-myc and ODC RNA and protein, relative to these parameters in HT29 cells transfected with the same plasmid containing the beta-galactosidase gene in place of APC. Upon induction of APC expression, ODC promoter activity and RNA levels were suppressed. When the e-box domain in the 5' flanking region of the ODC gene was mutated, ODC promoter activity was unaffected by wild-type APC expression. Antisense, but not missense, c-myc oligonucleotides decreased ODC activity in HT29 cells expressing mutant APC. These results demonstrated that wild-type APC suppressed c-myc and activated Mad1 expression in HT29 colon-derived cells. These proteins, in turn, regulated the transcription of target genes, including ODC. The data presented indicate that ODC is a modifier of APC-dependent signaling in intestinal cells and tissues.
Role of Gangliosides in Active Immunotherapy with Melanoma Vaccine (1991)

Among various tumor associated cell surface antigens, gangliosides, the glycosphingolipids that contain sialic acids, offer a variety of epitopes, some of which are preferentially expressed on melanoma cells. These surface components of the bilayered lipid membrane of tumor cells are the targets of active immunotherapy with melanoma vaccine. Purified gangliosides in aqueous solution form micelles and, at high density, form lactones. Their antigenic expression (physical conformation and orientation) on the cell surface is governed by the nature of the sphingosine and the fatty acids they contain. Evidence is accruing to show that the nature of the fatty acid moiety of gangliosides differs in normal and neoplastic cells. Gangliosides per se are not immunogenic and require extrinsic adjuvanticity. Preparation of a melanoma cell vaccine for active immunotherapy requires an understanding of the ganglioside profile of melanoma, the ganglioside-associated heterogeneity of melanoma, and the role of shed melanoma gangliosides in the immunosuppression of cell mediated and humoral immunity. In addition, the role of some of the anti-ganglioside antibodies in the elimination of shed gangliosides, the cytotoxic killing of tumor cells, as well as in the down-regulation of lymphocyte functions must be considered in the formulation of vaccine. Different strategies for augmenting the immunogenicity of melanoma associated gangliosides with melanoma vaccine are evaluated.
Many yeast chromosomes lack the telomere-specific Y' sequence. (1989)

Chromosomal DNAs of 26 different strains representing Saccharomyces species were analyzed by pulsed-field gel electrophoresis and subsequent hybridization to Y' telomere DNA. Hybridization to Y' was found exclusively in Saccharomyces cerevisiae strains, and among these strains, Y' sequences were found to be lacking in small, middle-sized, and large chromosomes.
Multi-GSPS all-optical ADC for direct digital receivers (2006)

Multi-beam phased array antennas are employed in wireless communications, where RF direct down-conversion, timing synchronization, and analog-to-digital are of important functions. Design of a novel all-optical ADC using spectral technique is presented, where sampling speeds as high as 40 GSPS with 6 bits of resolution is attainable.
A cost-effective portable telemedicine kit for use in Developing countries (2000)

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2000.
Quantitative and Qualitative Analysis of Type III Antifreeze Protein Structure and Function (1999)

Some cold water marine fishes avoid cellular damage because of freezing by expressing antifreeze proteins (AFPs) that bind to ice and inhibit its growth; one such protein is the globular type III AFP from eel pout. Despite several studies, the mechanism of ice binding remains unclear because of the difficulty in modeling the AFP-ice interaction. To further explore the mechanism, we have determined the x-ray crystallographic structure of 10 type III AFP mutants and combined that information with 7 previously determined structures to mainly analyze specific AFP-ice interactions such as hydrogen bonds. Quantitative assessment of binding was performed using a neural network with properties of the structure as input and predicted antifreeze activity as output. Using the cross-validation method, a correlation coefficient of 0.60 was obtained between measured and predicted activity, indicating successful learning and good predictive power. A large loss in the predictive power of the neural network occurred after properties related to the hydrophobic surface were left out, suggesting that van der Waal's interactions make a significant contribution to ice binding. By combining the analysis of the neural network with antifreeze activity and x-ray crystallographic structures of the mutants, we extend the existing ice-binding model to a two-step process: 1) probing of the surface for the correct ice-binding plane by hydrogen-bonding side chains and 2) attractive van der Waal's interactions between the other residues of the ice-binding surface and the ice, which increases the strength of the protein-ice interaction.
Hematopoiesis, including lymphocyte development and maturation (2006)

Hematopoiesis is the production of blood cells, that includes the generation of ERYTHROCYTES, THROMBOCYTES and white blood cells (GRANULOCYTES, LYMPHOCYTES and MONOCYTES). The major site of HEMATOPOIESIS is the BONE MARROW, but it can occur at other (extramedullary) locations as well. Hematopoiesis includes the generation of most cells involved in immune reactions, including LYMPHOCYTES carrying the specificity in these reactions, and accessory cells in the induction phase (DENDRITIC CELLS with antigen-presenting function) and effector phase (GRANULOCYTES and MONOCYTES/MACROPHAGES involved in, e.g., PHAGOCYTOSIS). Regarding LYMPHOCYTES, the pluripotent hematopoietic STEM CELL first develops into a common lymphoid progenitor cell, which subsequently develops in either T (thymusdependent) or B lymphoid progenitors. Subsequently these cells rearrange the genes encoding antigen receptors (TCR, Ig) and express these receptors on the cell surface. In a next phase the cells go through a process of positive and negative selection that has been well established for the T LYMPHOCYTE lineage and occurs within the thymic microenvironment. This selection process is relevant in shaping the antigen- recognition REPERTOIRE and avoids the generation of auto-reactive cells. Since basic cellular processes are similar for HEMATOPOIESIS, including lymphocyte development and reactions of mature LYMPHOCYTES (i.e., cellular proliferation, response to CYTOKINES), pharmacological agents affecting mature LYMPHOCYTES can also affect the development and maturation of these cells. For example, immunosuppressants with an antiproliferative mode of action can show BONE MARROW depression as an adverse side-effect.
Cytotoxicity of iron oxide nanoparticles made from the thermal decomposition of organometallics and aqueous phase transfer with Pluronic F127 (2010)

Magnetic nanoparticles are promising molecular imaging agents due to their relatively high relaxivity and the potential to modify surface functionality to tailor biodistribution. In this work we describe the synthesis of magnetic nanoparticles using organic solvents with organometallic precursors. This method results in nanoparticles that are highly crystalline and have uniform size and shape. The ability to create a monodispersion of particles of the same size and shape results in unique magnetic properties that can be useful for biomedical applications with MR imaging. Before these nanoparticles can be used in biological applications, however, means are needed to make the nanoparticles soluble in aqueous solutions and the toxicity of these nanoparticles needs to be studied. We have developed two methods to surface modify and transfer these nanoparticles to the aqueous phase using the biocompatible co-polymer, Pluronic F127. Cytotoxicity was found to be dependent on the coating procedure used. Nanoparticle effects on a cell-culture model were quantified using concurrent assaying: a lactate dehydrogenase assay to determine cytotoxicity and a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay to determine viability for a 24 h incubation period. Concurrent assaying was done to insure that nanoparticles did not interfere with the colorimetric assay results. This report demonstrates that a monodispersion of nanoparticles of uniform size and shape can be manufactured. Initial cytotoxicity testing of new molecular imaging agents needs to be carefully constructed to avoid interference and erroneous results.
Mild Cognitive Impairment (2009)

Mild Cognitive Impairment Concerns about memory, word-finding, or other cognitive (mental function) problems are common among older adults.A mild cognitive problem is different from dementia, however, because dementia is diagnosed only when both memory and another cognitive function are each affected severely enough to interfere with a person' s ability to carry out routine daily activities.Dementia is much more severe than a mild memory problem such as difficulty recalling names.The July 22/29, 2009, issue of JAMA includes an article about mild cognitive impairment.This Patient Page is based on one published in the October 1, 2008, issue.
Persistent spectral hole burning for R’ color centers in LiF crystals: Statics, dynamics, and external-field effects (1986)

The persistent spectral hole-burning properties of R' color centers in pure and doped LiF single crystals at liquid-helium temperatures are described and analyzed. Using frequency-modulation spectroscopy and precision ratiometric transmission spectroscopy, a satellite hole structure has been observed which varies with position in the inhomogeneous line due to excited-state splittings. Transient effects in the optical absorption indicate that an intermediate state with millisecond lifetimes is involved in hole formation. The persistent holes have been observed to grow as the logarithm of time and the logarithm of burning intensity in certain regimes, and a phenomenological tunneling model has been used to explain the time and intensity dependence. The results suggest that R' centers interact via tunneling and local strains with a quasi-random distribution of nearby traps which may be other color centers in the host material. A linear Stark effect has been observed in agreement with earlier measurements. This work illustrates the power of hole-burning spectroscopy to uncover static and dynamic interactions normally hidden by inhomogeneous broadening.