gebhart/patrepeval huggingface dataset:
Direct probing: covalent attachment of probe DNA to double-stranded target DNA (1998)

We report a novel procedure, which can be applied to probing of specific DNA, for covalently attaching probe DNA to complementary sequences in double-stranded target DNA. Employing hairpin-like oligonucleotide probes in combination with successive use of recA protein and DNA ligase, probes can be attached directly to target DNA molecules without dissociation of the DNA. The hairpin-like structure of the probes was designed so that the terminus of the probe oligonucleotide can be brought into close stereochemical proximity to the terminus of the complementary strand of target DNA for ligation. Because of the elimination of the DNA dissociation and subsequent hybridization (and washing) steps in the currently employed method, the probing process has become greatly simplified and more efficient and may lead to development of fully automated probing systems.
Ambipolar light-emitting organic field-effect transistor (2004)

We demonstrate a light-emitting organic field-effect transistor (OFET) with pronounced ambipolar current characteristics. The ambipolar transport layer is a coevaporated thin film of α-quinquethiophene (α-5T) as hole-transport material and N,N′-ditridecylperylene-3,4,9,10-tetracarboxylic diimide (P13) as electron-transport material. The light intensity is controlled by both the drain–source voltage VDS and the gate voltage VG. Moreover, the latter can be used to adjust the charge-carrier balance. The device structure serves as a model system for ambipolar light-emitting OFETs and demonstrates the general concept of adjusting electron and hole mobilities by coevaporation of two different organic semiconductors.
Beta‐sheet breaker strategy for the treatment of Alzheimer's disease (2002)

Abstract Alzheimer's disease is a degenerative disorder of the brain for which there is no cure or effective treatment. Recent studies suggest that cerebral amyloid plaques play a central role in the pathogenesis of the disease. An attractive therapeutic strategy for Alzheimer's disease is to block the early steps of misfolding and aggregation of the soluble amyloid‐beta peptide. We have engineered synthetic β‐sheet breaker peptides to bind amyloid‐β peptide, stabilize the normal conformation, and destabilize the β‐sheet rich structure that leads to the formation of amyloid plaques. Results in vitro, in cell culture, and in vivo suggest that β‐sheet breaker peptide may be useful for blocking the process of cerebral amyloid deposition. Chemical modifications were introduced into the active peptides to improve their pharmacological properties. It remains to be proved that inhibition of the pathway leading to amyloid plaque deposition could be beneficial for the therapeutic treatment of Alzheimer's disease. Drug Dev. Res. 56:184–193, 2002. © 2002 Wiley‐Liss, Inc.
Duqu: Analysis, Detection, and Lessons Learned (2012)

In September 2011, a European company sought our help to investigate a security incident that happened in their IT system. During the investigation, we discovered a new malware that was unknown to all mainstream anti-virus products, however, it showed striking similarities to the infamous Stuxnet worm. We named the new malware Duqu, and we carried out its first analysis. Our findings led to the hypothesis that Duqu was probably created by the same people who developed Stuxnet, but with a different purpose: unlike Stuxnet whose mission was to attack industrial equipment, Duqu is an information stealer rootkit. Nevertheless, both pieces of malware have a modular structure, and they can be re-configured remotely from a Command and Control server to include virtually any kind of functionality. In this paper, we present an abridged version of our initial Duqu analysis, which is available in a longer format as a technical report. We also describe the Duqu detector toolkit, a set of heuristic tools that we developed to detect Duqu and its variants. Finally, we discuss a number of issues that we learned, observed, or identified during our Duqu analysis project concerning the problems of preventing, detecting, and handling targeted malware attacks; we believe that solving these issues represents a great challenge to the system
Kappa B-Specific DNA Binding Proteins: Role in the Regulation of Human Interleukin-2 Gene Expression (1989)

Transcriptional activation of the human interleukin-2 (IL-2) gene, like induction of the IL-2 receptor alpha (IL-2R alpha) gene and the type 1 human immunodeficiency virus (HIV-1), is shown to be modulated by a kappa B-like enhancer element. Mutation of a kappa B core sequence identified in the IL-2 promoter (-206 to -195) partially inhibits both mitogen- and HTLV-I Tax-mediated activation of this transcription unit and blocks the specific binding of two inducible cellular factors. These kappa B-specific proteins (80 to 90 and 50 to 55 kilodaltons) similarly interact with the functional kappa B enhancer present in the IL-2R alpha promoter. These data suggest that these kappa B-specific proteins have a role in the coordinate regulation of this growth factor-growth factor receptor gene system that controls T cell proliferation.
Deep bi-directional recurrent networks over spectral windows (2015)

Long short-term memory (LSTM) acoustic models have recently achieved state-of-the-art results on speech recognition tasks. As a type of recurrent neural network, LSTMs potentially have the ability to model long-span phenomena relating the spectral input to linguistic units. However, it has not been clear whether their observed performance is actually due to this capability, or instead if it is due to a better modeling of short term dynamics through the recurrence. In this paper. we answer this question by applying a windowed (truncated) LSTM to conversational speech transcription, and find that a limited context is adequate, and that it is not necessaary to scan the entire utterance. The sliding window approach allows not only incremental (online) recognition with a bidirectional model, but also frame-wise randomization (as opposed to utterance randomization), which results in faster convergence. On the SWBD/Fisher corpus, applying bidirectional LSTM RNNs to spectral windows of about 0.5s improves WER on the Hub5'00 benchmark set by 16% relative compared to our best sequence-trained DNN. On an extended 3850h training set that that also includes lectures, the relative gain becomes 28% (Hub5'00 WER 9.2%). In-house conversational data improves by 12 to 17% relative.
Endogenous endostatin inhibits choroidal neovascularization (2007)

Endostatin, a fragment of the basement membrane component collagen XVIII, exhibits antiangiogenic properties in vitro and in vivo when high doses are administered. It is not known whether endogenous endostatin at physiological levels has a protective role as an inhibitor of pathological angiogenesis, such as choroidal neovascularization (CNV) in age-related macular degeneration. Using a laser injury model, we induced CNV in mice lacking collagen XVIII/endostatin and in control mice. CNV lesions in mutant mice were approximately 3-fold larger than in control mice and showed increased vascular leakage. These differences were independent of age-related changes at the choroid-retina interface. Ultrastructural analysis of the choroidal vasculature in mutant mice excluded morphological vascular abnormalities as a cause for the larger CNV lesions. When recombinant endostatin was administered to collagen XVIII/endostatin-deficient mice, CNV lesions were similar to those seen in control mice. In control mice treated with recombinant endostatin, CNV lesions were almost undetectable. These findings demonstrate that endogenous endostatin is an inhibitor of induced angiogenesis and that administration of endostatin potently inhibits CNV growth and vascular leakage. Endostatin may have a regulatory role in the pathogenesis of CNV and could be used therapeutically to inhibit growth and leakage of CNV lesions.
Neutral Lipid Bodies in Prokaryotes: Recent Insights into Structure, Formation, and Relationship to Eukaryotic Lipid Depots (2005)

Many prokaryotes are able to accumulate large amounts of lipophilic compounds as inclusion bodies in the cytoplasm. Members of most genera synthesize polymeric lipids such as poly(3-hydroxybutyrate) (PHB) or other polyhydroxyalkanoates (PHAs) (125), whereas accumulation of triacylglycerols (TAGs) and wax esters (WEs) in intracellular lipid-bodies is a property of only a few prokaryotes (10). Like the formation of PHAs, TAG and WE biosynthesis is also promoted in response to stress imposed on the cells and during imbalanced growth, for example by nitrogen limitation, if an abundant carbon source is present at the same time. All these lipids act as storage compounds for energy and carbon needed for maintenance of metabolism and synthesis of cellular metabolites during starvation and in particular if growth resumes. Although neutral lipid metabolism in bacteria, especially WE biosynthesis, has attracted increasing biotechnological interest, there has so far been little interest in medical research in the formation of prokaryotic lipid bodies. However, recent findings suggest that lipid body formation and accumulation of TAGs play an important role in the metabolism of the pathogenic bacteria like Mycobacterium tuberculosis (37, 52).

In contrast to the restricted occurrence of storage TAGs in prokaryotes, intracellular TAGs are widespread in many eukaryotes (34, 35, 40, 53, 65, 106, 112, 132, 133). In eukaryotes, storage lipids are also deposited as lipid bodies. Their structure and formation have recently been reviewed in detail by several authors, but additional information on prokaryotic lipid-bodies has been only superficial (98, 100, 151). In contrast, intracellular accumulation of WEs as a storage lipid is a great exception in eukaryotes and occurs only in jojoba (Simmondsia chinensis) (147), and PHAs are not at all synthesized as a storage compound in eukaryotes.

The number of studies investigating the enzymatic and structural fundamentals of storage lipid metabolism in bacteria has increased drastically in the last years, providing the knowledge that storage lipids in bacteria have a similar important metabolic function like in eukaryotes. This review will focus on prokaryotic neutral lipid bodies in comparison with the currently discussed models for lipid body structure and their formation in eukaryotes and with PHA inclusions in prokaryotes.
Pharmacogenetic Analysis of Clinically Relevant Genetic Polymorphisms (2003)

With the recent publication of the human genome sequence, there has been an expanse of publicly available resources for pharmacogenomics research. Early estimates predicted that over 3 million single nucleotide polymorphisms (SNPs) are present in the human genome, with over 1.42 million already deposited in the public databases (1). SNPs in coding and control regions of genes can cause significant inter-individual variation in the resulting protein function and activity, leading to important differences in disease susceptibility and drug metabolism. This expansion in valuable SNPs has stimulated the development of a number of detection methods (2). We describe protocols for three distinct methods (allele-specific polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and Pyrosequencing) as examples of ways to assay clinically relevant polymorphisms.
The relationship between accessibility and usability of websites (2007)

Accessibility and usability are well established concepts for user interfaces and websites. Usability is precisely defined, but there are different approaches to accessibility. In addition, different possible relationships could exist between problems encountered by disabled and non-disabled users, yet little empirical data have been gathered on this question. Guidelines for accessibility and usability of websites provide ratings of the importance of problems for users, yet little empirical data have been gathered to validate these ratings. A study investigated the accessibility of two websites with 6 disabled (blind) and 6 non-disabled (sighted) people. Problems encountered by the two groups comprised two intersecting sets, with approximately 15% overlap. For one of the two websites, blind people rated problems significantly more severely than sighted people. There was high agreement between participants as to the severity of problems, and agreement between participants and researchers. However, there was no significant agreement between either participants or researchers and the importance/priority ratings provided by accessibility and usability guidelines. Practical and theoretical implications of these results are discussed.
Functional Expression and Mutations of c-Met and Its Therapeutic Inhibition with SU11274 and Small Interfering RNA in Non–Small Cell Lung Cancer (2005)

Non-small cell lung cancer (NSCLC) is a difficult disease to treat. The c-Met receptor is an attractive potential target for novel therapeutic inhibition in human cancers. We provide strong evidence that c-Met is overexpressed, activated, and sometimes mutated in NSCLC cell lines and tumor tissues. Expression of c-Met was found in all (100%) of the NSCLC tumor tissues examined (n = 23) and most (89%) of the cell lines (n = 9). Sixty-one percent of tumor tissues strongly expressed total c-Met, especially adenocarcinoma (67%). Specific expression of phospho-Met (p-Met) [Y1003] and [Y1230/1234/1235] was seen by immunohistochemistry. p-Met expression was preferentially observed at the NSCLC tumor invasive fronts. c-Met alterations were identified within the semaphorin domain (E168D, L299F, S323G, and N375S) and the juxtamembrane domain (R988C, R988C + T1010I, S1058P, and alternative splice product skipping entire juxtamembrane domain) of a NSCLC cell line and adenocarcinoma tissues. We validated c-Met as potential therapeutic target using small interfering RNA down-regulation of the receptor expression by 50% to 60% in NSCLC cells. This led to inhibition of p-Met and phospho-AKT and up to 57.1 +/- 7.2% cell viability inhibition at 72 hours. The selective small molecule inhibitor of c-Met SU11274 inhibited cell viability in c-Met-expressing NSCLC cells. SU11274 also abrogated hepatocyte growth factor-induced phosphorylation of c-Met and its downstream signaling. Here, we provide first direct evidence by small interfering RNA targeting and small molecule inhibitor that c-Met is important in NSCLC biology and biochemistry. These results indicate that c-Met inhibition will be an important therapeutic strategy against NSCLC to improve its clinical outcome.
Measuring color breakup of stationary images in field‐sequential‐color displays (2005)

Abstract— Color breakup is an artifact perceivable on field‐sequential‐color (FSC) displays, both in stationary and in moving images. In this work, a unique device and a method for measuring color breakup on stationary images is proposed. Rotating the field of view of a high‐speed measurement camera in milliseconds simulates saccadic behavior. The target can be a virtual display, a direct‐view display or a projector image. Captured images can be used for quantifying the color breakup of a target display. The results along with an exploration of their application to breakup characterization will be presented.
Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL (2004)

The mechanisms underlying the autonomous accumulation of malignant B cells remain elusive. We show in this study that non-Hodgkin's lymphoma (NHL) B cells express B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL), two powerful B cell-activating molecules usually expressed by myeloid cells. In addition, NHL B cells express BAFF receptor, which binds BAFF, as well as transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation Ag (BCMA), which bind both BAFF and APRIL. Neutralization of endogenous BAFF and APRIL by soluble TACI and BCMA decoy receptors attenuates the survival of NHL B cells, decreases activation of the prosurvival transcription factor NF-kappaB, down-regulates the antiapoptotic proteins Bcl-2 and Bcl-x(L), and up-regulates the proapoptotic protein Bax. Conversely, exposure of NHL B cells to recombinant or myeloid cell-derived BAFF and APRIL attenuates apoptosis, increases NF-kappaB activation, up-regulates Bcl-2 and Bcl-x(L), and down-regulates Bax. In some NHLs, exogenous BAFF and APRIL up-regulate c-Myc, an inducer of cell proliferation; down-regulate p53, an inhibitor of cell proliferation; and increase Bcl-6, an inhibitor of B cell differentiation. By showing that nonmalignant B cells up-regulate BAFF and APRIL upon stimulation by T cell CD40 ligand, our findings indicate that NHL B cells deregulate an otherwise physiological autocrine survival pathway to evade apoptosis. Thus, neutralization of BAFF and APRIL by soluble TACI and BCMA decoy receptors could be useful to dampen the accumulation of malignant B cells in NHL patients.
Biologically Active Polymers from Spontaneous Carotenoid Oxidation: A New Frontier in Carotenoid Activity (2014)

In animals carotenoids show biological activity unrelated to vitamin A that has been considered to arise directly from the behavior of the parent compound, particularly as an antioxidant. However, the very property that confers antioxidant activity on some carotenoids in plants also confers susceptibility to oxidative transformation. As an alternative, it has been suggested that carotenoid oxidative breakdown or metabolic products could be the actual agents of activity in animals. However, an important and neglected aspect of the behavior of the highly unsaturated carotenoids is their potential to undergo addition of oxygen to form copolymers. Recently we reported that spontaneous oxidation of ß-carotene transforms it into a product dominated by ß-carotene-oxygen copolymers. We now report that the polymeric product is biologically active. Results suggest an overall ability to prime innate immune function to more rapidly respond to subsequent microbial challenges. An underlying structural resemblance to sporopollenin, found in the outer shell of spores and pollen, may allow the polymer to modulate innate immune responses through interactions with the pattern recognition receptor system. Oxygen copolymer formation appears common to all carotenoids, is anticipated to be widespread, and the products may contribute to the health benefits of carotenoid-rich fruits and vegetables.
A digital phase-locked loop with calibrated coarse and stochastic fine TDC (2012)

A coarse-fine time-to-digital converter (TDC) is presented with a calibrated course stage followed by a stochastic fine stage. On power-up, calibration algorithm based on a code density test is used to minimize nonlinearities in the coarse TDC. By using a balanced mean method, the number of registers required for calibration algorithm is a reduced by 30%. Based upon the coarse TDC resuls, the appropriate clock signals are multiplexed into a stochastic fine TDC. The TDC is incorporated into a 1.9-2.54 GHz digital phase locked loop (DPLL) in 0.13 μm CMOS. The DPLL consumes a total of 15.2 mW of which 4.4 mW are consumed in the TDC. Measurements show an in-band phase noise of -107 dBc/Hz which is equivalent to 4 ps TDC resolution, approximately an order of magnitude better than an inverter delay in this process technology. The integrated random jitter is 213 fs. The calibration reduces worst-case spurs by 16 dB.
Potentiation of Endothelial Cell Proliferation by Fibrin(ogen)-bound Fibroblast Growth Factor-2 (1999)

Endothelial cell growth is stimulated by fibroblast growth factor-2 (FGF-2), and both adhesion and proliferation are modulated by interactions with fibrinogen and fibrin. Previous evidence indicates that FGF-2 binds specifically and with high affinity to fibrinogen and fibrin, suggesting that their effects on endothelial cells may be coordinated. In this study, we have, therefore, investigated the ability of FGF-2 bound to fibrinogen and fibrin to stimulate proliferation of endothelial cells. Human umbilical vein endothelial cells were cultured in the presence of FGF-2 with or without fibrinogen, and proliferation was assessed by microscopic examination of cultures, incorporation of [3H]thymidine and by cell counting. Cells cultured in the presence of both FGF-2 and fibrinogen proliferated more rapidly than those with FGF-2 alone and exhibited a decreased population doubling time. At concentrations of FGF-2 up to 150 ng/ml, there was greater endothelial cell proliferation in the presence of fibrinogen than in its absence with the most pronounced effect below 1 ng/ml. The maximum effect of fibrinogen was observed at a molar ratio of fibrinogen to FGF-2 of 2:1, corresponding to the maximum molar binding ratio. Endothelial cells proliferated when plated on fibrin or surface-immobilized fibrinogen with FGF-2, indicating that FGF-2 bound to surface-associated fibrin(ogen) retained activity. We conclude that fibrinogen- or fibrin-bound FGF-2 is able to support endothelial cell proliferation and that fibrinogen potentiates the proliferative capacity of FGF-2.
[Effect of minoxidil on DNA synthesis in cultured fibroblasts from healthy skin or keloids]. (1990)

A potential therapeutic role of minoxidil in fibrotic or sclerotic conditions, such as keloids, has been suggested on the basis of its reported ability to inhibit the proliferation of human dermal fibroblasts. We have studied the effect of minoxidil on 3H-deoxythymidine uptake in cultures of human dermal fibroblasts derived from lesional and non-lesional skin from patients with keloids. The effect of the addition of fetal bovine serum, plasma and growth factors (insulin, EGF, PDGF, FGF and beta-TGF) to the medium has also been studied. Minoxidil, at concentrations ranging from 500 to 1,000 microM., caused an increase in DNA synthesis, which was proportional to the initial degree of fibroblast activation. Concentrations higher than 1,000 microM. caused a cytotoxic effect. Some reservations arise on the potential therapeutic use of minoxidil in conditions characterized by increased fibroblast proliferation, given the narrow margin between activation of DNA synthesis and cytotoxicity we have found in our experimental model.