gebhart/patrepeval huggingface dataset:
Global Analysis of Altered Gene Expressions during the Process of Esophageal Squamous Cell Carcinogenesis in the Rat: A Study Combined with a Laser Microdissection and a cDNA Microarray (2005)

The genetic alterations that occur during esophageal tumorigenesis have yet to be determined. We previously established a Wister rat carcinogenesis model of esophageal squamous cell carcinoma. To understand more about the molecular mechanisms during carcinogenesis, we produced esophageal neoplastic lesions by administering N-amyl-N-methylnitrosamine and 12-O-tetradecanoylphorbol-13-acetate to rats. We used laser microdissection to specifically isolate the cells from the normal epithelium, papilloma, dysplasia, and invasive carcinoma. Using a cDNA microarray representing 14,815 clones, we then analyzed the gene expression profiles for each esophageal lesion. The number of differentially expressed genes compared with the normal control dramatically increased in a step-by-step fashion from normal epithelium (1,151 +/- 119 genes) to papilloma (1,899 +/- 543 genes), dysplasia (1,991 +/- 193 genes), and invasive carcinoma (2,756 +/- 87 genes). A hierarchical clustering analysis showed that the three stages of normal epithelium, dysplasia (papilloma), and invasive carcinoma could be clearly classified, whereas the gene expression patterns of papilloma and dysplasia were indistinguishable. Using the Fisher criterion, we also identified 50 genes whose expression level had either significantly increased or decreased in a step-by-step manner from the normal epithelium to dysplasia and then finally to invasive carcinoma. Many of these genes were not previously known to be associated with esophageal carcinogenesis. The present findings in our rat model thus seem to provide us with a better understanding of the molecular alterations that occur during esophageal carcinogenesis and hopefully will also help lead to the development of novel diagnostic and therapeutic targets.
RASSF1A promoter methylation is frequently detected in both pre‐malignant and non‐malignant microdissected prostatic epithelial tissues (2007)

These observations suggest that methylation of the RASSF1A gene is present in both pre-malignant and benign epithelia and suggests quantitation is required for it to be an effective marker of early prostate cancer.
Suppression of Gene Expression by Targeted Disruption of Messenger RNA: Available Options and Current Strategies (2000)

At least three different approaches may be used for gene targeting including: A) gene knockout by homologous recombination; B) employment of synthetic oligonucleotides capable of hybridizing with DNA or RNA, and C) use of polyamides and other natural DNA-bonding molecules called lexitropsins. Targeting mRNA is attractive because mRNA is more accessible than the corresponding gene. Three basic strategies have emerged for this purpose, the most familiar being to introduce antisense nucleic acids into a cell in the hopes that they will form Watson-Crick base pairs with the targeted gene's mRNA. Duplexed mRNA cannot be translated, and almost certainly initiates processes which lead to its destruction. The antisense nucleic acid can take the form of RNA expressed from a vector which has been transfected into the cell, or take the form of a DNA or RNA oligonucleotide which can be introduced into cells through a variety of means. DNA and RNA oligonucleotides can be modified for stability as well as engineered to contain inherent cleaving activity. It has also been proven that because RNA and DNA are very similar chemical compounds, DNA molecules with enzymatic activity could also be developed. This assumption proved correct and led to the development of a "general-purpose" RNA-cleaving DNA enzyme. The attraction of DNAzymes over ribozymes is that they are very inexpensive to make and that because they are composed of DNA and not RNA, they are inherently more stable than ribozymes. Although mRNA targeting is impeccable in theory, many additional considerations must be taken into account in applying these strategies in living cells including mRNA site selection, drug delivery and intracellular localization of the antisense agent. Nevertheless, the ongoing revolution in cell and molecular biology, combined with advances in the emerging disciplines of genomics and informatics, has made the concept of nontoxic, cancer-specific therapies more viable then ever and continues to drive interest in this field.
Directed assembly of carbon nanotube electronic circuits (2000)

We report on a method for directed assembly of integrated carbon nanotube circuits using selective area chemical vapor deposition on prepatterned catalyst electrodes. The circuits consist of a multiwall carbon nanotube bridging a pair of electrodes, forming a metal/carbon nanotube/metal structure. Electron-beam lithography was used to define electrode sets separated by a desired distance on a SiO2/Si substrate. Following metal evaporation and lift-off, molecular jet chemical vapor deposition was used for selective growth of carbon nanotubes on the catalyst electrodes. The carbon nanotubes eventually form a bridge between nearby electrodes consisting of one, or in some cases more than one multiwall nanotubes. The room temperature resistance of the carbon nanotube circuits measured at the electrode leads is typically less than 100 kΩ. The carbon nanotube circuits were characterized by electronic transport measurements in the temperature range from room temperature to 2 K.
A 1.5GHz-modulation-range 10ms-modulation-period 180kHz<inf>rms</inf>-frequency-error 26MHz-reference mixed-mode FMCW synthesizer for mm-wave radar application (2011)

A frequency modulated continuous-wave (FMCW) radar using triangular modulation is one of the promising candidates for realizing a CMOS radar IC. Range and velocity resolutions of the FMCW radar are determined by the band width and period of triangular modulation (Pourvoyeur et al., 2008). A short-range measurement requires wide (several GHz) bandwidth, while a long-range measurement with high-velocity resolution requires moderate (hundreds of MHz) bandwidth and long (several ms) period. Furthermore, since frequency error in the FMCW signal deteriorates range and velocity accuracy, a highly linear frequency chirp signal is required. However FMCW radars reported so far exhibit a period up to 1.5ms because a long period degrades the chirp linearity in a conventional analog PLL. In this work, an analog/digital mixed-mode 82GHz FMCW synthesizer with 1.5GHz bandwidth, a period from 1ms to 10ms and less than 180kHz <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">rms</sub> frequency error is described. The achieved performance corresponds to range and velocity resolutions of 10cm and 1.4km/h, respectively.
A hole-filling strategy for reconstruction of smooth surfaces in range images (2004)

Creating models of real scenes is a complex task for which the use of traditional modelling techniques is inappropriate. For this task, laser rangefinders are frequently used to sample the scene from several viewpoints, with the resulting range images integrated into a final model. In practice, due to surface reflectance properties, occlusions and accessibility limitations, certain areas of the scenes are usually not sampled, leading to holes and introducing undesirable artifacts in the resulting models. We present an algorithm for filling holes on surfaces reconstructed from point clouds. The algorithm is based on moving least squares and can recover both geometry and shading information, providing a good alternative when the properties to be reconstructed are locally smooth. The reconstruction process is mostly automatic and the sampling rate in the reconstructed areas follows the given samples. We demonstrate the use of the algorithm on both real and synthetic data sets to obtain complete geometry and reasonable shading.
The Iron-Hydrogenase of Thermotoga maritima Utilizes Ferredoxin and NADH Synergistically: a New Perspective on Anaerobic Hydrogen Production (2009)

The hyperthermophilic and anaerobic bacterium Thermotoga maritima ferments a wide variety of carbohydrates, producing acetate, CO(2), and H(2). Glucose is degraded through a classical Embden-Meyerhof pathway, and both NADH and reduced ferredoxin are generated. The oxidation of these electron carriers must be coupled to H(2) production, but the mechanism by which this occurs is unknown. The trimeric [FeFe]-type hydrogenase that was previously purified from T. maritima does not use either reduced ferredoxin or NADH as a sole electron donor. This problem has now been resolved by the demonstration that this hydrogenase requires the presence of both electron carriers for catalysis of H(2) production. The enzyme oxidizes NADH and ferredoxin simultaneously in an approximately 1:1 ratio and in a synergistic fashion to produce H(2). It is proposed that the enzyme represents a new class of bifurcating [FeFe] hydrogenase in which the exergonic oxidation of ferredoxin (midpoint potential, -453 mV) is used to drive the unfavorable oxidation of NADH (E(0)' = -320 mV) to produce H(2) (E(0)' = -420 mV). From genome sequence analysis, it is now clear that there are two major types of [FeFe] hydrogenases: the trimeric bifurcating enzyme and the more well-studied monomeric ferredoxin-dependent [FeFe] hydrogenase. Almost one-third of the known H(2)-producing anaerobes appear to contain homologs of the trimeric bifurcating enzyme, although many of them also harbor one or more homologs of the simpler ferredoxin-dependent hydrogenase. The discovery of the bifurcating hydrogenase gives a new perspective on our understanding of the bioenergetics and mechanism of H(2) production and of anaerobic metabolism in general.
Senile Dementia of the Alzheimer Type Without Neocortical Neurofibrillary Tangles (1987)

Senile dementia of the Alzheimer type (SDAT) is typified pathologically by neuritic plaques (NP) and neurofibrillary tangles (NFT) in the neocortex and hippocampus. However, in a large series of cases (60) over age 74 a significant minority (30%) lacked neocortical tangles. In order to determine if these latter cases (Group B) otherwise differ from the majority which have both neocortical plaques and tangles (Group A), various clinical and neuropathological parameters were measured for both groups and the results compared. The following indices were examined: degree of dementia, rate of progression of dementia, age at death, brain weight, cerebral hemispheric weight, cortical cell counts from the frontal, temporal, and parietal lobes, the number of neocortical NP, the number of hippocampal NP and NFT, and the levels of neocortical choline acetyltransferase and somatostatin. The two groups showed no statistically significant differences in any of these categories except for increased numbers of neocortical NP in Group A in midfrontal and superior temporal regions. However, cases in Group A showed greater pathologic abnormality in nearly every parameter, albeit without attaining statistical significance. We conclude that SDAT with neocortical NFT is the same disease as SDAT without them, although the presence of such tangles is associated with a tendency towards greater severity.
Gauge invariance of the Dirac equation (1973)

The Dirac equation in its most usual form can be derived by the minimum action principle from the Lagrangian density where γ k ( k =1,2,3,4) are the Dirac 4 × 4 matrices satisfying relations; ψ( x ) is a column matrix with 4 complex elements being functions of x 1 , x 2 , x 3 , x 4 , coordinates of the pseudo-Euclidean space with metric g ik .(
GroupBuild: a fragment-based method for de novo drug design (1993)

A novel method for de novo drug design, GroupBuild, has been developed to suggest chemically reasonable structures which fill the active sites of enzymes. The proposed molecules provide good steric and electrostatic contact with the enzyme and exist in low-energy conformations. These structures are composed entirely of individual functional groups (also known as "building blocks" or "fragments") which the program chooses from a predefined library. User-selected enzyme seed atom(s) may be used to determine the area(s) in which structure generation begins. Alternatively, GroupBuild may begin with a predocked "inhibitor core" from which fragments are grown. For each new fragment generated by the program, several thousand candidates in a variety of locations and orientations are considered. Each of these candidates is scored based on a standard molecular mechanics potential function. The selected fragment and orientation are chosen from among the highest scoring cases. Tests of the method using HIV protease, FK506 binding protein, and human carbonic anhydrase demonstrate that structures similar to known potent inhibitors may be generated with GroupBuild.
Structural Characterization of the Lactoferrin Receptor from Neisseria meningitidis (1999)

The meningococcal lactoferrin receptor is composed of the integral outer membrane protein LbpA and the peripheral lipoprotein LbpB. Homooligomeric complexes of LbpA and heterooligomers consisting of LbpA and LbpB were identified. Furthermore, five cell surface-exposed loops of LbpA were identified, which partially confirms a previously proposed topology model.
Generation of stable cell clones expressing mixtures of human antibodies (2010)

Therapeutic monoclonal antibodies, a highly successful class of biological drugs, are conventionally manufactured in mammalian cell lines. A recent approach to increase the therapeutic effectiveness of monoclonal antibodies has been to combine two or more of them; however this increases the complexity of development and manufacture. To address this issue a method to efficiently express multiple monoclonal antibodies from a single cell has been developed and we describe here the generation of stable cell clones that express high levels of a human monoclonal antibody mixture. PER.C6 cells were transfected with a combination of plasmids containing genes encoding three different antibodies. Clones that express the three corresponding antibody specificities were identified, subcloned, and passaged in the absence of antibiotic selection pressure. At several time points, batch production runs were analyzed for stable growth and IgG production characteristics. The majority (11/12) of subclones analyzed expressed all three antibody specificities in constant ratios with total IgG productivity ranging between 15 and 20 pg/cell/day under suboptimal culture conditions after up to 67 population doublings. The growth and IgG production characteristics of the stable clones reported here resemble those of single monoclonal antibody cell lines from conventional clone generation programs. We conclude that the methodology described here is applicable to the generation of stable PER.C6(R) clones for industrial scale production of mixtures of antibodies.
Serum beta 2 microglobulin and C-reactive protein in the monitoring of lymphomas findings in a multicenter study and experience in selected patients (1980)

Serum beta 2 microglobulin (P2m) and C-Reactive protein (C
Optimal corneal ablation for eyes with arbitrary Hartmann–Shack aberrations (1998)

New technologies for accurately measuring corneal shape and full eye aberrations are now available. An algorithm that uses these technologies to predict the amount of ablation needed to produce a corneal surface that optimally focuses light is developed. It is found that knowledge of the aberrations is far more important than knowledge of corneal shape. Neglect of corneal shape information introduces an error of less than approximately 0.05 micron in the optimal ablation depth. Neglect of the aberrations is a different story. Small changes in the aberration structure, such as going from the optimal ablation to a spherical ablation, introduce ablation changes of greater than 10 microns. It is argued that there are many occasions when less ablation can lead to improved image quality.
ATV: display and manipulation of annotated phylogenetic trees (2001)

A Tree Viewer (ATV) is a Java tool for the display and manipulation of annotated phylogenetic trees. It can be utilized both as a standalone application and as an applet in a web browser.
Green fluorescent protein as a scaffold for intracellular presentation of peptides (1998)

Peptide aptamers provide probes for biological processes and adjuncts for development of novel pharmaceutical molecules. Such aptamers are analogous to compounds derived from combinatorial chemical libraries which have specific binding or inhibitory activities. Much as it is generally difficult to determine the composition of combinatorial chemical libraries in a quantitative manner, determining the quality and characteristics of peptide libraries displayed in vivo is problematical. To help address these issues we have adapted green fluorescent protein (GFP) as a scaffold for display of conformationally constrained peptides. The GFP-peptide libraries permit analysis of library diversity and expression levels in cells and allow enrichment of the libraries for sequences with predetermined characteristics, such as high expression of correctly folded protein, by selection for high fluorescence.
LILRA2 Activation Inhibits Dendritic Cell Differentiation and Antigen Presentation to T Cells (2007)

The differentiation of monocytes into dendritic cells (DC) is a key mechanism by which the innate immune system instructs the adaptive T cell response. In this study, we investigated whether leukocyte Ig-like receptor A2 (LILRA2) regulates DC differentiation by using leprosy as a model. LILRA2 protein expression was increased in the lesions of the progressive, lepromatous form vs the self-limited, tuberculoid form of leprosy. Double immunolabeling revealed LILRA2 expression on CD14+, CD68+ monocytes/macrophages. Activation of LILRA2 on peripheral blood monocytes impaired GM-CSF induced differentiation into immature DC, as evidenced by reduced expression of DC markers (MHC class II, CD1b, CD40, and CD206), but not macrophage markers (CD209 and CD14). Furthermore, LILRA2 activation abrogated Ag presentation to both CD1b- and MHC class II-restricted, Mycobacterium leprae-reactive T cells derived from leprosy patients, while cytokine profiles of LILRA2-activated monocytes demonstrated an increase in TNF-alpha, IL-6, IL-8, IL-12, and IL-10, but little effect on TGF-beta. Therefore, LILRA2 activation, by altering GM-CSF-induced monocyte differentiation into immature DC, provides a mechanism for down-regulating the ability of the innate immune system to activate the adaptive T cell response while promoting an inflammatory response.
Correction of field inhomogeneity effects on limited k-space MRSI data using anatomical constraints (2010)

Magnetic field inhomogeneity is a long-standing problem in magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI). Specifically, in MRSI, field inhomogeneity, if not corrected, can cause frequency shifts, line broadening, and lineshape distortions in the spectral peaks. This paper addresses the problem of correcting the field inhomogeneity effects on limited k-space MRSI data. A penalized maximum-likelihood method is proposed, which enables the use of anatomical constraints for improving the correction performance with only limited k-space data. Simulation results are shown to demonstrate the effectiveness of the proposed method.
Decision-Based Adversarial Attacks: Reliable Attacks Against Black-Box Machine Learning Models (2017)

Many machine learning algorithms are vulnerable to almost imperceptible perturbations of their inputs. So far it was unclear how much risk adversarial perturbations carry for the safety of real-world machine learning applications because most methods used to generate such perturbations rely either on detailed model information (gradient-based attacks) or on confidence scores such as class probabilities (score-based attacks), neither of which are available in most real-world scenarios. In many such cases one currently needs to retreat to transfer-based attacks which rely on cumbersome substitute models, need access to the training data and can be defended against. Here we emphasise the importance of attacks which solely rely on the final model decision. Such decision-based attacks are (1) applicable to real-world black-box models such as autonomous cars, (2) need less knowledge and are easier to apply than transfer-based attacks and (3) are more robust to simple defences than gradient- or score-based attacks. Previous attacks in this category were limited to simple models or simple datasets. Here we introduce the Boundary Attack, a decision-based attack that starts from a large adversarial perturbation and then seeks to reduce the perturbation while staying adversarial. The attack is conceptually simple, requires close to no hyperparameter tuning, does not rely on substitute models and is competitive with the best gradient-based attacks in standard computer vision tasks like ImageNet. We apply the attack on two black-box algorithms from Clarifai.com. The Boundary Attack in particular and the class of decision-based attacks in general open new avenues to study the robustness of machine learning models and raise new questions regarding the safety of deployed machine learning systems. An implementation of the attack is available as part of Foolbox at https://github.com/bethgelab/foolbox .
Exoenzyme S ADP-Ribosylates Rab5 Effector Sites To Uncouple Intracellular Trafficking (2013)

Pseudomonas aeruginosa exoenzyme S (ExoS) ADP-ribosylates multiple eukaryotic targets to promote cytopathology and bacterial colonization. ADP-ribosylation of the small GTPase Rab5 has previously been shown to block fluid-phase endocytosis and trafficking of plasma membrane receptors to the early endosomes as well as inhibit phagocytosis of the bacterium. In this study, ExoS is shown to be capable of ADP-ribosylating 6 candidate arginine residues that are located in the effector binding region or in the C terminus of Rab5. Two Rab5 derivatives were engineered, which contained Arg→Ala mutations at four Arg residues within the effector binding region (EF) or two Arg residues within the C-terminal tail (TL). Expression of Rab5(TL) does not affect the ability of ExoS to modify intracellular trafficking, while expression of Rab5(EF) rescued the ability of ExoS to inhibit intracellular trafficking. ADP-ribosylation of effector arginines likely uncouples Rab5 signaling to downstream effectors. This is a different mechanism for inhibition than observed for the ADP-ribosylation of Ras by ExoS, where ADP-ribosylated Ras loses the ability to bind guanine nucleotide exchange factor (GEF). Other experiments showed that expression of dominant negative Rab5(Ser34Asn) does not inhibit ExoS trafficking to the perinuclear region of intoxicated cells. This study provides insight into a mechanism for how ExoS ADP-ribosylation of Rab5 inhibits Rab5 function.
β-Catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis (2007)

Recent studies have demonstrated that the LIM homeodomain transcription factor Islet1 (Isl1) marks pluripotent cardiovascular progenitor cells and is required for proliferation, survival, and migration of recently defined second heart field progenitors. Factors that are upstream of Isl1 in cardiovascular progenitors have not yet been defined. Here we demonstrate that beta-catenin is required for Isl1 expression in cardiac progenitors, directly regulating the Isl1 promoter. Ablation of beta-catenin in Isl1-expressing progenitors disrupts multiple aspects of cardiogenesis, resulting in embryonic lethality at E13. beta-Catenin is also required upstream of a number of genes required for pharyngeal arch, outflow tract, and/or atrial septal morphogenesis, including Tbx2, Tbx3, Wnt11, Shh, and Pitx2. Our findings demonstrate that beta-catenin signaling regulates proliferation and survival of cardiac progenitors.