gebhart/patrepeval huggingface dataset:
Receptor-Based Antidote for Diphtheria (2002)

Although equine diphtheria antitoxin may be an effective therapy for human diphtheria, its use often induces serum sickness. We describe here a strategy for developing an alternative treatment based on the human diphtheria toxin (DT) receptor/heparin-binding epidermal growth factor-like growth factor (HB-EGF) precursor. Recombinant mature human HB-EGF acts as a soluble receptor analog, binding radioiodinated DT and preventing its binding to the cellular DT receptor/HB-EGF precursor. However, the possibility existed that radioiodinated DT-HB-EGF complexes associate with cells due to the binding of the heparin-binding domain of recombinant HB-EGF to cell surface heparan sulfate proteoglycans. This possibility was confirmed by performing DT binding studies in the presence of heparin. A recombinant truncated HB-EGF (residues 106 to 149), which lacks most of the heparin-binding domain, showed an essentially heparin-independent binding of radioiodinated DT to cells. Furthermore, it was a more effective inhibitor of DT binding than was recombinant mature HB-EGF. Since mature HB-EGF is a known ligand for the EGF receptor and is thus highly mitogenic (tumorigenic), we then changed amino acid residues in the EGF-like domain of the recombinant truncated HB-EGF and demonstrated that this DT receptor analog (I117A/L148A) displayed a low mitogenic effect. The truncated (I117A/L148A) HB-EGF protein retained high DT binding affinity, as confirmed by using surface plasmon resonance. Our results suggest that the truncated (I117A/L148A) HB-EGF protein could be an effective, safe antidote for human diphtheria.
Recombinant pheromone binding protein 1 from Mamestra brassicae (MbraPBP1) (1999)

Pheromone binding proteins (PBPs) are small proteins (17 kDa on average) present at high concentrations ( approximately 10 mM) in the sensillum lymph of Lepidoptera antennae, where they play a key role in the perception of pheromones. By expression in Escherichia coli, we have obtained large quantities (2-3 mg.L-1) of pure, soluble, Mamestra brassicae PBP1 (MbraPBP1). These quantities are compatible with the requirements of X-ray and NMR studies. The recombinant protein has been characterized by native-polyacrylamide gel electrophoresis, Western blotting, N-terminal sequencing, mass spectrometry, gel filtration, circular dichroism, and NMR. Moreover, the recombinant MbraPBP1 has been shown to be able to bind the specific pheromone and a structural analogue, Z11-16:TFMK (cis-11-hexadecenyl trifluoromethyl ketone), in displacement experiments. Our results on MbraPBP1 confirm and extend previous findings on PBPs. MbraPBP1 and two PBPs from different species have been found to exist as dimers under nondenaturing conditions. The CD and structural prediction data confirm a markedly helical structure for insect PBPs rather than the beta-barrel fold found in vertebrates odorant binding proteins. We have tentatively identified the location of the helices and the short beta-strands with respect to the binding site. Currently we have obtained small diffracting crystals of the recombinant MbraPBP1 and determined their space group and molecular content.
Code generation for multiple mappings (2002)

There has been a great amount of recent work toward unifying iteration reordering transformations. Many of these approaches represent transformations as affine mappings from the original iteration space to a new iteration space. These approaches show a great deal of promise, but they all rely on the ability to generate code that iterates over the points in these new iteration spaces in the appropriate order. This problem has been fairly well-studied in the case where all statements use the same mapping. We have developed an algorithm for the less well-studied case where each statement uses a potentially different mapping. Unlike many other approaches, our algorithm can also generate code from mappings corresponding to loop blocking. We address the important trade-off between reducing control overhead and duplicating code.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mass spectrometric analysis of tobacco-specific nitrosamine-DNA adducts in smokers and nonsmokers (1991)

A gas chromatography, negative ion chemical ionization mass spectrometry (GC-NICI-MS) based assay for tobacco-specific nitrosamine adducts of DNA is described. The assay is based on the observation that acid hydrolysis of DNA from animals treated with tobacco-specific nitrosamines releases 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB). HPB and the internal standard [4,4-D2]HPB are derivatized with pentafluorobenzoyl chloride and the resulting HPB-pentafluorobenzoate is purified by high-performance liquid chromatography prior to GC-NICI-MS analysis. DNA from human peripheral lung and tracheobronchial tissue, collected at autopsy, was analyzed for acid-released HPB. The mean HPB level (fmol/mg of DNA) for peripheral lung DNA was 11 +/- 16 (SD, n = 9) for smokers and 0.9 +/- 2.3 (n = 8) for nonsmokers. Mean adduct levels in tracheobronchus were 16 +/- 18 (n = 4) for smokers and 0.9 +/- 1.7 (n = 4) for nonsmokers. These are the first measurements of tobacco-specific nitrosamine-DNA adducts in humans. Further studies comparing the levels of DNA and globin adducts will provide a better understanding of the metabolic activation of tobacco-specific nitrosamines in humans and may provide a more accurate indication of an individual's risk of developing tobacco-related cancer.
Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn’s disease (2001)

We describe here the immunologic characterization of a new mouse strain, SAMP1/Yit, which spontaneously develops a chronic intestinal inflammation localized to the terminal ileum. The resulting ileitis bears a remarkable resemblance to human Crohn's disease. This strain of mice develops discontinuous, transmural inflammatory lesions in the terminal ileum with 100% penetrance by 30 weeks of age. The intestinal inflammation is characterized by massive infiltration of activated CD4+ and CD8alpha(+)TCRalphabeta(+) T cells into the lamina propria and is accompanied by a dramatic decrease in the intraepithelial lymphocyte CD8alpha(+)TCRgammadelta(+)/CD8alpha(+)TCRalphabeta(+) ratio. The results of adoptive transfer experiments strongly suggest that CD4+ T cells that produce a Th1-like profile of cytokines, e.g., IFN-gamma and TNF, mediate the intestinal inflammation found in SAMP1/Yit mice. In addition, pretreatment of adoptive transfer recipients with a neutralizing anti-TNF antibody prevents the development of intestinal inflammation, suggesting that TNF plays an important role in the pathogenesis of intestinal inflammation in this model. To our knowledge, these data provide the first direct evidence that Th1-producing T cells mediate intestinal inflammation in a spontaneous animal model of human Crohn's disease.
Multiresolution path planning for mobile robots (1986)

The problem of automatic collision-free path planning is central to mobile robot applications. An approach to automatic path planning based on a quadtree representation is presented. Hierarchical path-searching methods are introduced, which make use of this multiresolution representation, to speed up the path planning process considerably. The applicability of this approach to mobile robot path planning is discussed.
Classes of phosphoinositide 3-kinases at a glance (2014)

The phosphoinositide 3-kinase (PI3K) family is important to nearly all aspects of cell and tissue biology and central to human cancer, diabetes and aging. PI3Ks are spatially regulated and multifunctional, and together, act at nearly all membranes in the cell to regulate a wide range of signaling, membrane trafficking and metabolic processes. There is a broadening recognition of the importance of distinct roles for each of the three different PI3K classes (I, II and III), as well as for the different isoforms within each class. Ongoing issues include the need for a better understanding of the in vivo complexity of PI3K regulation and cellular functions. This Cell Science at a Glance article and the accompanying poster summarize the biochemical activities, cellular roles and functional requirements for the three classes of PI3Ks. In doing so, we aim to provide an overview of the parallels, the key differences and crucial interplays between the regulation and roles of the three PI3K classes.
Fabrication of bulk heterojunction plastic solar cells by screen printing (2001)

We demonstrate the use of screen printing in the fabrication of ultrasmooth organic-based solar cells. Organic films on the order of several tens of nanometers in thickness and 2.6 nm surface roughness were made. The first-generation screen-printed plastic solar cells demonstrated 4.3% in power conversion efficiency when using an aluminum electrode and 488 nm illumination.
Driving Oscillatory Activity in the Human Cortex Enhances Motor Performance (2012)

Voluntary movement is accompanied by changes in the degree to which neurons in the brain synchronize their activity within discrete frequency ranges. Two patterns of movement-related oscillatory activity stand out in human cortical motor areas. Activity in the beta frequency (15-30 Hz) band is prominent during tonic contractions but is attenuated prior to and during voluntary movement. Without such attenuation, movement may be slowed, leading to the suggestion that beta activity promotes postural and tonic contraction, possibly at a cost to the generation of new movements. In contrast, activity in the gamma (60-90 Hz) band increases during movement. The direction of change suggests that gamma activity might facilitate motor processing. In correspondence with this, increased frontal gamma activity is related with reduced reaction times. Yet the possibility remains that these functional correlations reflect an epiphenomenal rather than causal relationship. Here we provide strong evidence that oscillatory activities at the cortical level are mechanistically involved in determining motor behavior and can even improve performance. By driving cortical oscillations using noninvasive electrical stimulation, we show opposing effects at beta and gamma frequencies and interactions with motor task that reveal the potential quantitative importance of oscillations in motor behavior.
Bacterial Delivery of TALEN Proteins for Human Genome Editing (2014)

Transcription Activator-Like Effector Nucleases (TALENs) are a novel class of sequence-specific nucleases that have recently gained prominence for its ease of production and high efficiency in genome editing. A TALEN pair recognizes specific DNA sequences and introduce double-strand break in the target site, triggering non-homologous end joining and homologous recombination. Current methods of TALEN delivery involves introduction of foreign genetic materials, such as plasmid DNA or mRNA, through transfection. Here, we show an alternative way of TALEN delivery, bacterial type III secretion system (T3SS) mediated direct injection of the TALEN proteins into human cells. Bacterially injected TALEN was shown to efficiently target host cell nucleus where it persists for almost 12 hours. Using a pair of TALENs targeting venus gene, such injected nuclear TALENs were shown functional in introducing DNA mutation in the target site. Interestingly, S-phase cells seem to show greater sensitivity to the TALEN mediated target gene modification. Accordingly, efficiency of such genome editing can easily be manipulated by the infection dose, number of repeated infections as well as enrichment of S phase cells. This work further extends the utility of T3SS in the delivery of functional proteins into mammalian cells to alter their characters for biomedical applications.
Mutation of MouseCyp11a1Promoter Caused Tissue-Specific Reduction of Gene Expression and Blunted Stress Response without Affecting Reproduction (2008)

Steroids are synthesized mainly from the adrenal glands catalyzed by steroidogenic enzymes; the expression of these enzymes is controlled by transcription factor steroidogenic factor-1 (SF-1; NR5A1). To understand the physiological effect of genetic changes on steroid secretion, we used Cre-LoxP and gene targeting technology to mutate the binding sequence for SF-1 (SF-1 response element) on the promoter of the mouse Cyp11a1 gene, which encodes a critical enzyme for steroid biosynthesis. The resulting Cyp11a1 L/L mice expressed about 7-fold less cytochrome P450 side-chain cleavage enzyme (CYP11A1) in the adrenal and testis but expressed normal amounts of CYP11A1 in the placenta and ovary. This tissue-specific reduction of gene expression did not affect basal steroid secretion but attenuated the circadian rhythm of glucocorticoid secretion. These mice also failed to induce glucocorticoid secretion in response to stress, leading to retention of CD4+CD8+ double-positive thymocytes. Unlike complete Cyp11a1 disruption, which causes neonatal death, promoter mutation did not decrease life span and caused no defect in reproduction. Thus, CYP11A1 appears in normal mice to be expressed above the minimal required level, providing a large capacity for use in response to stress. Mutation of the SF-1 response element of Cyp11a1 results in reduced stress response due to decreased adrenal CYP11A1 expression and insufficient stress-induced glucocorticoids secretion.
Production of propylene oxide from propylene glycol (2007)

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.
New Strategies in HER2-Overexpressing Breast Cancer: Many Combinations of Targeted Drugs Available (2011)

The anti-HER2 drugs trastuzumab and lapatinib are increasingly changing the natural history of early and metastatic HER2-overexpressing breast cancer. Many other agents targeted against the HER2 signaling network are in clinical development, and these are or will soon be combined with the currently approved anti-HER2 therapies. We review herein recent data in support of the early use of combinations of agents targeted to the HER2 network as the most rational approach against this subtype of breast cancer. We propose that the optimal combination or combinations of anti-HER2 agents delivered early in the natural history of HER2+ breast cancer should close to eliminate acquired drug resistance, shorten the duration of therapy, and potentially dispense with the need of concurrent chemotherapy.
Unsupervised learning of narrative schemas and their participants (2009)

We describe an unsupervised system for learning narrative schemas, coherent sequences or sets of events (arrested(POLICE, SUSPECT), convicted(JUDGE, SUSPECT)) whose arguments are filled with participant semantic roles defined over words (Judge = {judge, jury, court}, Police = {police, agent, authorities}). Unlike most previous work in event structure or semantic role learning, our system does not use supervised techniques, hand-built knowledge, or predefined classes of events or roles. Our unsupervised learning algorithm uses coreferring arguments in chains of verbs to learn both rich narrative event structure and argument roles. By jointly addressing both tasks, we improve on previous results in narrative/frame learning and induce rich frame-specific semantic roles.
Synthesis and Conformation−Activity Relationships of the Peptide Isosteres of FK228 and Largazole (2009)

The peptide isosteres (10 and 11) of the naturally occurring and potent histone deacetylase (HDAC) inhibitors FK228 and largazole have been synthesized and evaluated side-by-side with FK228, largazole, and SAHA for inhibition of the class I HDACs 1, 2, 3, and 6.
Cloning and characterization of the brittle-2 gene of maize. (1990)

Acute pancreatitis is an unusual but recognized complication of percutaneous aspiration biopsy of the pancreas. As the pancreatic tail is located anterior to the left adrenal gland, percutaneous biopsy of a left adrenal mass via the anterior approach may result in needle passage through the tail of the pancreas with subsequent potential development of pancreatitis. To evaluate this risk, we retrospectively reviewed 48 CT-directed percutaneous aspiration biopsies of left adrenal masses done between 1984 and 1989 at two institutions. Positioning of the patient, the course of the needle, the number of needle passes, and the size of the needle were analyzed. Thirty-three (69%) of 48 biopsies of a left adrenal mass were performed by using the anterior approach. The pancreas was traversed by one or more needles in 32 of 33 cases. Biopsies were performed with 20- to 22-gauge needles, and the number of needle passes varied widely. The medical records of the 33 patients in whom the anterior approach was used also were reviewed for complications. Acute pancreatitis, which required 11-13 days of hospitalization, developed in two patients (6%). None of the other 31 patients suffered a complication. We conclude that the pancreatic tail is routinely traversed by the biopsy needle when biopsy of a left adrenal mass is done via the anterior approach and that severe acute pancreatitis can occur as a result.
Map-Enhanced UAV Image Sequence Registration and Synchronization of Multiple Image Sequences (2007)

Registering consecutive images from an airborne sensor into a mosaic is an essential tool for image analysts. Strictly local methods tend to accumulate errors, resulting in distortion. We propose here to use a reference image (such as a high resolution map image) to overcome this limitation. In our approach, we register a frame in an image sequence to the map using both frame-to-frame registration and frame-to-map registration iteratively. In frame-to-frame registration, a frame is registered to its previous frame. With its previous frame been registered to the map in the previous iteration, we can derive an estimated transformation from the frame to the map. In frame-to-map registration, we warp the frame to the map by this transformation to compensate for scale and rotation difference and then perform an area based matching using mutual information to find correspondences between this warped frame and the map. These correspondences together with the correspondences in previous frames could be regarded as correspondences between the partial local mosaic and the map. By registering the partial local mosaic to the map, we derive a transformation from the frame to the map. With this two-step registration, the errors between each consecutive frames are not accumulated. We then extend our approach to synchronize multiple image sequences by tracking moving objects in each image sequence, and aligning the frames based on the object's coordinates in the reference image.
Chemically Doped Double-Walled Carbon Nanotubes: Cylindrical Molecular Capacitors (2003)

A double-walled carbon nanotube is used to study the radial charge distribution on the positive inner electrode of a cylindrical molecular capacitor. The outer electrode is a shell of bromine anions. Resonant Raman scattering from phonons on each carbon shell reveals the radial charge distribution. A self-consistent tight-binding model confirms the observed molecular Faraday cage effect, i.e., most of the charge resides on the outer wall, even when this wall was originally semiconducting and the inner wall was metallic.
Incremental Feature Selection and l1 Regularization for Relaxed Maximum-Entropy Modeling. (2004)

We present an approach to bounded constraintrelaxation for entropy maximization that corresponds to using a double-exponential prior or `1 regularizer in likelihood maximization for log-linear models. We show that a combined incremental feature selection and regularization method can be established for maximum entropy modeling by a natural incorporation of the regularizer into gradientbased feature selection, following Perkins et al. (2003). This provides an efficient alternative to standard `1 regularization on the full feature set, and a mathematical justification for thresholding techniques used in likelihood-based feature selection. Also, we motivate an extension to n-best feature selection for linguistic features sets with moderate redundancy, and present experimental results showing its advantage over `0, 1-best `1, `2 regularization and over standard incremental feature selection for the task of maximum-entropy parsing.1
GeneDesign: Rapid, automated design of multikilobase synthetic genes (2006)

Modern molecular biology has brought many new tools to the geneticist as well as an exponentially expanding database of genomes and new genes for study. Of particular use in the analysis of these genes is the synthetic gene, a nucleotide sequence designed to the specifications of the investigator. Typically, synthetic genes encode the same product as the gene of interest, but the synthetic nucleotide sequence for that protein may contain modifications affecting expression or base composition. Other desirable changes typically involve the revision of restriction sites. Designing synthetic genes by hand is a time-consuming and error-prone process that may involve several computer programs. We have developed a tools environment that combines many modules to provide a platform for rapid synthetic gene design for multikilobase sequences. We have used GeneDesign to successfully design a synthetic Ty1 element and a large variety of other synthetic sequences. GeneDesign has been implemented as a publicly accessible Web-based resource and can be found at http://slam.bs.jhmi.edu/gd.
Channel Statistics-Based RF Pre-Processing with Antenna Selection (2006)

We introduce two novel joint radio-frequency (RF)-baseband designs for receivers in a MIMO system with N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> transmit antennas, N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> receive antennas, but only L < N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> RF chains at the receiver. The joint design introduces an RF pre-processing matrix that processes the signals from the different antennas, and is followed by selection (if necessary), down-conversion, and further processing in the baseband. The schemes are similar to conventional antenna selection in that they use fewer RF chains than antenna elements, but achieve superior performance by exploiting the spatial correlation of the received signals. The first of our proposed designs uses an L times N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> RF pre-processing matrix that outputs only L streams followed by baseband signal processing, and, thus, eliminates the need for a selection switch. The second one uses an N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> times N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> RF pre-processing matrix that outputs N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> streams and is followed by a switch that selects L streams for baseband signal processing. Both spatial diversity and spatial multiplexing systems are considered and the optimum pre-processing matrices are derived for all cases. To accommodate practical RF design constraints, which prefer a variable phase-shifter-based implementation, a sub-optimal phase approximation is also introduced. Performance better than conventional antenna selection and close to the full complexity receiver is observed in both single cluster and multi-cluster wireless channels. A beam-pattern-based geometric intuition is also developed to illustrate the effectiveness of the optimal solutions