gebhart/patrepeval huggingface dataset:
Molecular Architecture and Function of Polymeric Oriented Systems: Models for the Study of Organization, Surface Recognition, and Dynamics of Biomembranes (1988)

Abstract The Part and the Whole . The principle of self‐organization for the creation of functional units is not an invention of modern natural sciences. It was already a basic idea of the ancient philosophies in Asia and Europe: only the mutuality of the parts creates the whole and its ability to function. Translated into the language of chemistry this means: the self‐organization of molecules leads to supramolecular systems and is responsible for their functions. Thermotropic and lyotropic liquid crystals are such functional units, formed by self‐organization. As highly oriented systems, they exhibit new properties. The importance of lyotropic liquid crystals for the life sciences has been known for a long time. They are a prerequisite for the development of life and the ability of cells to function. In materials sciences this concept of function through organization led to the development of new liquid‐crystalline materials. From the point of view of macromolecular chemistry, this review tries to combine these two different fields and especially hopes to stimulate their interaction and joint treatment. To exemplify this, the molecular architecture of polymeric organized systems will be discussed. Polymeric liquid crystals combine the ability to undergo spontaneous self‐organization–typical of liquid‐crystalline phases–with the polymer‐specific property of stabilizing these ordered states. As new materials, polymeric liquid crystals have already been investigated intensively. As model systems for biomembranes as well as for the simulation of biomembrane processes, they so far have been little discussed. The intention of this review article is to show that polymer science is able to contribute to the simulation of cellular processes such as the stabilization of biomembranes, specific surface recognition, or even the “uncorking” of cells. Polymer science, having an old tradition as an inter‐disciplinary field, can no longer restrict itself to common plastics. Attempts to reach new horizons have already begun. The borderland between liquid crystals and cells will certainly play an important role. Basic requirements to work in this frontier area between organic chemistry, membrane biology, life science, and materials science will be the delight in scientific adventures as well as the courage to go ahead. The most important prerequisite will be the willingness to cooperate with disciplines which so far have not really accepted each other. From this point of view, this review does not aim at giving defined answers. It wants instead to encourage the scientific venture: too often we cling to painfully acquired knowledge, fearing adventures.
From Genetic Footprinting to Antimicrobial Drug Targets: Examples in Cofactor Biosynthetic Pathways (2002)

Novel drug targets are required in order to design new defenses against antibiotic-resistant pathogens. Comparative genomics provides new opportunities for finding optimal targets among previously unexplored cellular functions, based on an understanding of related biological processes in bacterial pathogens and their hosts. We describe an integrated approach to identification and prioritization of broad-spectrum drug targets. Our strategy is based on genetic footprinting in Escherichia coli followed by metabolic context analysis of essential gene orthologs in various species. Genes required for viability of E. coli in rich medium were identified on a whole-genome scale using the genetic footprinting technique. Potential target pathways were deduced from these data and compared with a panel of representative bacterial pathogens by using metabolic reconstructions from genomic data. Conserved and indispensable functions revealed by this analysis potentially represent broad-spectrum antibacterial targets. Further target prioritization involves comparison of the corresponding pathways and individual functions between pathogens and the human host. The most promising targets are validated by direct knockouts in model pathogens. The efficacy of this approach is illustrated using examples from metabolism of adenylate cofactors NAD(P), coenzyme A, and flavin adenine dinucleotide. Several drug targets within these pathways, including three distantly related adenylyltransferases (orthologs of the E. coli genes nadD, coaD, and ribF), are discussed in detail.
Vector Targeting for Therapeutic Gene Delivery (2002)

"...very informative and comprehensive...belongs on the shelf ofevery library and lab providing essential resources for research onvector design or delivery." -Cancer Biology and Therapy This comprehensive volume presents the most recent advances intarget definition technology and provides a detailed overview onthe rational design of targeted vectors for gene therapy. Atheoretical framework for advanced vector design is provided thatintegrates all of the allied sciences relevant to the study ofvector targeting. The text discusses the basic underlying scienceand then leads to discussions of the various viral vectors andmethods of defining targets. Finally, an expert outlook onpromising therapeutic applications is offered.
Irradiation of Polymeric Materials (1993)

The effects of radiation on polymer materials is an area of rapidly increasing interest. Several high technology industries require specialty polymers that exhibit a specific response upon exposure to radiation. For instance, the electronics industry requires materials that undergo radiation induced scission or crosslinking for resist applications, while aerospace and medical applications require highly radiation stable materials. The design and development of appropriate chemistry for these applications requires full understanding of the effects of radiation on polymer materials. It is through fundamental understanding of the radiation chemical processes occurring in polymers that the technological advances required by today's industries can be realized.
The Homeobox Gene ATH1 of Arabidopsis Is Derepressed in the Photomorphogenic Mutants cop1 and det1 (1995)

Nicolette Quaedvlieg, Jan Dockx, Fred Rook, Peter Weisbeek, Sjef Smeekens, The Homeobox Gene ATH1 of Arabidopsis Is Derepressed in the Photomorphogenic Mutants cop1 and det1, The Plant Cell, Vol. 7, No. 1 (Jan., 1995), pp. 117-129
Overlapped Operation with Microprogramming (1978)

This paper presents a system for parallel operation of functional units in a processor that is under microprogram control. Specifically, for a multiple functional unit computer this new technique allows concurrent operation of the functional units without requiring hardwired instructions. A new interlock system for ordering execution of instructions is also presented. Two applications are shown: one to a three functional unit serial processor and one to an array processor. The mechanism allows holding instructions until the data on which they are to operate are ready and is a microcode version of that used on the IBM 360/91 or on the CDC 6600. This concurrency can be under either hardware, firmware, or software control.
The use of whole genome amplification to study chromosomal changes in prostate cancer: insights into genome-wide signature of preneoplasia associated with cancer progression (2006)

An overall increase in chromosomal changes was seen in CaP compared to HPIN, suggesting a universal breakdown in chromosomal stability. The accumulation of CNAs, which occurs during this process is non-random and may indicate chromosomal regions important in tumourigenesis. It is therefore likely that the alterations in copy number are part of a programmed cycle of events that promote tumour development, progression and survival. The combination of LCM, MDA and gaCGH is ideally suited for the identification of CNAs from small cell clusters and may assist in the discovery of potential genomic markers for early diagnosis, or identify the location of tumour suppressor genes (TSG) or oncogenes previously unreported in HPIN and CaP.
Piezoelectric MEMS sensors: state-of-the-art and perspectives (2009)

Over the past two decades, several advances have been made in micromachined sensors and actuators. As the field of microelectromechanical systems (MEMS) has advanced, a clear need for the integration of materials other than silicon and its compounds into micromachined transducers has emerged. Piezoelectric materials are high energy density materials that scale very favorably upon miniaturization and that has led to an ever-growing interest in piezoelectric films for MEMS applications. At this time, piezoelectric aluminum-nitride-based film bulk acoustic resonators (FBAR) have already been successfully commercialized. Future innovations and improvements in inertial sensors for navigation, high-frequency crystal oscillators and filters for wireless applications, microactuators for RF applications, chip-scale chemical analysis systems and countless other applications hinge upon the successful miniaturization of components and integration of piezoelectrics and metals into these systems. In this article, a comprehensive review of micromachined piezoelectric transducer technology will be presented. Piezoelectric materials in bulk and thin film forms will be reviewed and fabrication techniques for the integration of these materials for microsensor applications will be presented. Recent advances in various piezoelectric microsensors will be presented through specific examples. This review will conclude with a critical assessment of the future trends and promise of this technology.
Immortalization of bipotential and plastic glio-neuronal precursor cells. (1990)

Permanent clonal cell lines from newborn mouse striatum have been established after transfer of the simian virus 40 large tumor oncogene by means of a retroviral vector. Some of the lines obtained displayed properties of bipotential and plastic glio-neuronal precursors. Depending on the culture conditions, these cells express either the glial fibrillary acidic protein or neurofilaments. In addition, the cells can display adrenergic, D1 and D2 dopaminergic, muscarinic, and 5-hydroxytryptamine type 2 serotoninergic receptors, which are coupled either to the adenylate cyclase or to the phosphatidylinositol signaling pathways. The panel of receptors for neurotransmitters exhibited by these lines closely resembles that of primary striatal neurons. Results suggest that plastic common precursors of astrocytes and neurons persist in the striatum at a late developmental stage. As these permanent cell lines constitute an unlimited source of homogenous cell material, we suggest that they should be useful for molecular and pharmacological studies on the mechanisms and regulation of signal transduction as well as the commitment, plasticity, and differentiation of neural cells.
Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models (2004)

The therapeutic efficacy of direct drug infusion into the brain, the target organ of transmissible spongiform encephalopathies, was assessed in transgenic mice intracerebrally infected with 263K scrapie agent. Pentosan polysulfate (PPS) gave the most dramatic prolongation of the incubation period, and amphotericin B had intermediate effects, but antimalarial drugs such as quinacrine gave no significant prolongation. Treatment with the highest dose of PPS at an early or late stage of the infection prolonged the incubation time by 2.4 or 1.7 times that of the control mice, respectively. PPS infusion decreased not only abnormal prion protein deposition but also neurodegenerative changes and infectivity. These alterations were observed within the brain hemisphere fitted with an intraventricular infusion cannula but not within the contralateral hemisphere, even at the terminal disease stage long after the infusion had ended. Therapeutic effects of PPS were also demonstrated in mice infected with either RML agent or Fukuoka-1 agent. However, at doses higher than that providing the maximal effects, intraventricular PPS infusion caused adverse effects such as hematoma formation in the experimental animals. These findings indicate that intraventricular PPS infusion might be useful for the treatment of transmissible spongiform encephalopathies in humans, providing that the therapeutic dosage is carefully evaluated.
Regulation of the Cell Cycle by Focal Adhesion Kinase (1998)

In this report, we have analyzed the potential role and mechanisms of integrin signaling through FAK in cell cycle regulation by using tetracycline-regulated expression of exogenous FAK and mutants. We have found that overexpression of wild-type FAK accelerated G1 to S phase transition. Conversely, overexpression of a dominant-negative FAK mutant DeltaC14 inhibited cell cycle progression at G1 phase and this inhibition required the Y397 in DeltaC14. Biochemical analyses indicated that FAK mutant DeltaC14 was mislocalized and functioned as a dominant-negative mutant by competing with endogenous FAK in focal contacts for binding signaling molecules such as Src and Fyn, resulting in a decreases of Erk activation in cell adhesion. Consistent with this, we also observed inhibition of BrdU incorporation and Erk activation by FAK Y397F mutant and FRNK, but not FRNKDeltaC14, in transient transfection assays using primary human foreskin fibroblasts. Finally, we also found that DeltaC14 blocked cyclin D1 upregulation and induced p21 expression, while wild-type FAK increased cyclin D1 expression and decreased p21 expression. Taken together, these results have identified FAK and its associated signaling pathways as a mediator of the cell cycle regulation by integrins.
A cone-beam reconstruction algorithm using shift-variant filtering and cone-beam backprojection (1994)

An exact inversion formula written in the form of shift-variant filtered-backprojection (FBP) is given for reconstruction from cone-beam data taken from any orbit satisfying H.K. Tuy's (1983) sufficiency conditions. The method is based on a result of P. Grangeat (1987), involving the derivative of the three-dimensional (3D) Radon transform, but unlike Grangeat's algorithm, no 3D rebinning step is required. Data redundancy, which occurs when several cone-beam projections supply the same values in the Radon domain, is handled using an elegant weighting function and without discarding data. The algorithm is expressed in a convenient cone-beam detector reference frame, and a specific example for the case of a dual orthogonal circular orbit is presented. When the method is applied to a single circular orbit (even though Tuy's condition is not satisfied), it is shown to be equivalent to the well-known algorithm of L.A. Feldkamp et al. (1984).
Algorithms for sequence analysis via mutagenesis (2004)

The essential idea of SAM is to infer the target sequence using the sequences of mutants derived from the target. We describe three algorithms used in this process. The first algorithm predicts the number of mutants that will be required to infer the target sequence with a desired level of accuracy. The second algorithm infers the target sequence itself, using the mutant sequences. The third algorithm assigns quality values to each inferred base. The algorithms are illustrated using mutant sequences generated in the laboratory.
Functional Consequences of the Human Leptin Receptor (LEPR) Q223R Transversion (2008)

Perturbations in the functional integrity of the leptin axis are obvious candidates for mediation of altered adiposity. In a large number of genetic association studies in humans, the nonconservative LEPR Q223R allele has been inconsistently associated with adiposity. Subtle, long-term effects of such genetic variants can be obscured by effects of the environment and other confounders that render definitive inferences difficult to reach. We directly assessed the biological effects of this variant in 129P3/J mice segregating for the humanized Lepr allele at codon 223. No effects of this allele were detected on body weight, composition, or energy expenditure in animals fed diets of varying fat content over periods as long as 235 days. In vitro, Q223R did not affect leptin signaling as reflected by activation of STAT3. We conclude that Q223R is unlikely to play a significant role in regulation of human adiposity. This approach to vetting of human allelic variation might be more widely used.
Abundance of SSR Motifs and Development of Candidate Polymorphic SSR Markers (BARCSOYSSR_1.0) in Soybean (2010)

ABSTRACT Simple sequence repeat (SSR) genetic markers, also referred to as microsatellites, function in map‐based cloning and for marker‐assisted selection in plant breeding. The objectives of this study were to determine the abundance of SSRs in the soybean genome and to develop and test soybean SSR markers to create a database of locus‐specific markers with a high likelihood of polymorphism. A total of 210,990 SSRs with di‐, tri‐, and tetranucleotide repeats of five or more were identified in the soybean whole genome sequence (WGS) which included 61,458 SSRs consisting of repeat units of di‐ (≥10), tri‐ (≥8), and tetranucleotide (≥7). Among the 61,458 SSRs, (AT)n, (ATT)n and (AAAT)n were the most abundant motifs among di‐, tri‐, and tetranucleotide SSRs, respectively. After screening for a number of factors including locus‐specificity using e‐PCR, a soybean SSR database (BARCSOYSSR_1.0) with the genome position and primer sequences for 33,065 SSRs was created. To examine the likelihood that primers in the database would function to amplify locus‐specific polymorphic products, 1034 primer sets were evaluated by amplifying DNAs of seven diverse Glycine max (L.) Merr. and one wild soybean ( Glycine soja Siebold &amp; Zucc.) genotypes. A total of 978 (94.6%) of the primer sets amplified a single polymerase chain reaction (PCR) product and 798 (77.2%) amplified polymorphic amplicons as determined by 4.5% agarose gel electrophoresis. The BARCSOYSSR1.0 SSR markers can be found in SoyBase ( http://soybase.org ; verified 21 June 2010) the USDA‐ARS Soybean Genome Database.
Synthetic peptide analogs to probe the immunological expression of the rat encephalitogenic neuropeptide (1987)

The rationale for designing and synthesizing 24 different peptide analogs and subpeptides of residues 69-84 of guinea pig myelin basic protein is presented. The encephalitogenic potential of 19 of these peptides in Lewis rats is also given.
Optical cross-connect architecture using free-space optical switches based on PI-LOSS topology (2002)

An optical cross-connect (OXC) system is an essential ingredient needed to create an optical transport network for B-ISDN. We propose an OXC architecture, incorporating failure restoration based on reserved wavelengths, which consists of a routing block and bypass block. We compare the number of required optical devices in our structure with a conventional structure. We also propose a polarization controlled free-space switch based on path-independent insertion loss (PI-LOSS) topology, adopt it to the routing block, and demonstrate a 4/spl times/4 prototype free-space switch.
Changes in physical fitness and all-cause mortality. A prospective study of healthy and unhealthy men (1995)

<h3>Objective.</h3> —To evaluate the relationship between changes in physical fitness and risk of mortality in men. <h3>Design.</h3> —Prospective study, with two clinical examinations (mean interval between examinations, 4.9 years) to assess change or lack of change in physical fitness as associated with risk of mortality during follow-up after the subsequent examination (mean follow-up from subsequent examination, 5.1 years). <h3>Setting.</h3> —Preventive medicine clinic. <h3>Study Participants.</h3> —Participants were 9777 men given two preventive medical examinations, each of which included assessment of physical fitness by maximal exercise tests and evaluation of health status. <h3>Main Outcome Measures.</h3> —All-cause (n=223) and cardiovascular disease (n=87) mortality. <h3>Results.</h3> —The highest age-adjusted all-cause death rate was observed in men who were unfit at both examinations (122.0/10 000 man-years); the lowest death rate was in men who were physically fit at both examinations (39.6/10000 man-years). Men who improved from unfit to fit between the first and subsequent examinations had an age-adjusted death rate of 67.7/10 000 man-years. This is a reduction in mortality risk of 44% (95% confidence interval, 25% to 59%) relative to men who remained unfit at both examinations. Improvement in fitness was associated with lower death rates after adjusting for age, health status, and other risk factors of premature mortality. For each minute increase in maximal treadmill time between examinations, there was a corresponding 7.9% (<i>P</i>=.001) decrease in risk of mortality. Similar results were seen when the group was stratified by health status, and for cardiovascular disease mortality. <h3>Conclusions.</h3> —Men who maintained or improved adequate physical fitness were less likely to die from all causes and from cardiovascular disease during follow-up than persistently unfit men. Physicians should encourage unfit men to improve their fitness by starting a physical activity program. (<i>JAMA</i>. 1995;273:1093-1098)
Germline mutations of BRCA1-associated RING domain (BARD1) gene in breast and/or ovarian families negative for BRCA1 and 2 alterations (2000)

While advances in science and technology have increased options for treating breast cancer, current social trends have changed the way people deal with this disease. Women in the United States are no longer simply passive patients, but rather they are survivors, advocates and activists who are speaking up for themselves and speaking out for issues relevant to the treatment and prevention of breast cancer.
Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation (2014)

The ability to control the movement of nanoparticles remotely and with high precision would have far-reaching implications in many areas of nanotechnology. We have designed a unique dynamic magnetic field (DMF) generator that can induce rotational movements of superparamagnetic iron oxide nanoparticles (SPIONs). We examined whether the rotational nanoparticle movement could be used for remote induction of cell death by injuring lysosomal membrane structures. We further hypothesized that the shear forces created by the generation of oscillatory torques (incomplete rotation) of SPIONs bound to lysosomal membranes would cause membrane permeabilization, lead to extravasation of lysosomal contents into the cytoplasm, and induce apoptosis. To this end, we covalently conjugated SPIONs with antibodies targeting the lysosomal protein marker LAMP1 (LAMP1-SPION). Remote activation of slow rotation of LAMP1-SPIONs significantly improved the efficacy of cellular internalization of the nanoparticles. LAMP1-SPIONs then preferentially accumulated along the membrane in lysosomes in both rat insulinoma tumor cells and human pancreatic beta cells due to binding of LAMP1-SPIONs to endogenous LAMP1. Further activation of torques by the LAMP1-SPIONs bound to lysosomes resulted in rapid decrease in size and number of lysosomes, attributable to tearing of the lysosomal membrane by the shear force of the rotationally activated LAMP1-SPIONs. This remote activation resulted in an increased expression of early and late apoptotic markers and impaired cell growth. Our findings suggest that DMF treatment of lysosome-targeted nanoparticles offers a noninvasive tool to induce apoptosis remotely and could serve as an important platform technology for a wide range of biomedical applications.