gebhart/patrepeval huggingface dataset:
Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel) (2002)

Neuronal members of the degenerin/epithelial Na+ channel (DEG/ENaC) family of cation channels include the mammalian brain Na+ channel 1 (BNC1), acid-sensing ion channel (ASIC) and dorsal-root acid-sensing ion channel (DRASIC). Their response to acidic pH, their sequence similarity to nematode proteins involved in mechanotransduction and their modulation by neuropeptides suggest that they may function as receptors for a number of different stimuli. Using the yeast two-hybrid assay, we found that the PDZ domain-containing protein PICK1 (protein interacting with C kinase) interacts specifically with the C-termini of BNC1 and ASIC, but not DRASIC or the related αENaC or βENaC. In both the yeast two-hybrid system and mammalian cells, deletion of the BNC1 and ASIC C-termini abolished the interaction with PICK1. Likewise, mutating the PDZ domain in PICK1 abolished its interaction with BNC1 and ASIC. In addition, in a heterologous expression system PICK1 altered the distribution of BNC1 channels; this effect was dependent on the PDZ domain of PICK1 and the C-terminus of BNC1. We found crude synaptosomal fractions of brain to be enriched in ASIC, suggesting a possible synaptic localization. Moreover, in transfected hippocampal neurons ASIC co-localized with PICK1 in a punctate pattern at synapses. These data suggest that PICK1 binds ASIC and BNC1 via its PDZ domain. This interaction may be important for the localization and/or function of these channels in both the central and peripheral nervous systems.
Functional selectivity in phosphonate ester dealkylation with bromotrimethylsilane (1979)

Bromotrimethylsilane is highly selective for P–O silyldealkylation of mixed carboxylate–phosphonate alkyl esters and can be used to prepare trimethylsilyl amido-, alkynyl-, and iodoalkyl-phosphonates in good yield, thus making the corresponding phosphonic acids readily available via hydrolysis with neutral H2O.
Finding action tubes (2015)

We address the problem of action detection in videos. Driven by the latest progress in object detection from 2D images, we build action models using rich feature hierarchies derived from shape and kinematic cues. We incorporate appearance and motion in two ways. First, starting from image region proposals we select those that are motion salient and thus are more likely to contain the action. This leads to a significant reduction in the number of regions being processed and allows for faster computations. Second, we extract spatio-temporal feature representations to build strong classifiers using Convolutional Neural Networks. We link our predictions to produce detections consistent in time, which we call action tubes. We show that our approach outperforms other techniques in the task of action detection.
Influence of the Mature Portion of a Precursor Protein on the Mitochondrial Signal Sequence (1996)

Most mitochondrial proteins are synthesized with an N-terminal signal sequence that targets these proteins to various compartments within the mitochondria. Signal sequences have been shown to be functional by fusing them to a nonmitochondrial passenger protein and observing import. In many cases, a signal sequence has been fused to passenger proteins, such as dihydrofolate reductase, and import occurred. There are, though, several unexplained instances in which a signal sequence was attached to a passenger protein and import was not observed. In this study, the N-terminal 23 residues of the matrix enzyme rhodanese could import several passenger proteins but were unable to import the mature form of mitochondrial aldehyde dehydrogenase (mALDH). However, if these same 23 residues were fused to the middle portion of mALDH, import was recovered, suggesting that the rhodanese signal sequence and N terminus of mALDH were incompatible for import. Circular dichroism data indicated that a peptide corresponding to the region of fusion between rhodanese and mALDH had less structure than corresponding peptides from imported fusion proteins, suggesting that mALDH may alter the helix in the rhodanese signal sequence, thus preventing import.
ChemInform Abstract: ERGOT ALKALOIDS. 83. RADIOLABELED PEPTIDE ERGOT ALKALOIDS (1976)

Abstract Durch Verfütterung der verschieden markierten Tryptophane (I) hoher Aktivität, deren Darstellung beschrieben ist, an Kulturen von Claviceps paspali werden entsprechend markierte Paspalsäuren (II) [im 7 : 3‐Gemisch mit den isomeren Lysergsäuren (III)] gewonnen; durch basenkatalysierte Umlagerung sind auch aus (IIa)‐(IId) die radioaktiven Lysergsäuren (IIIa)‐(IIId) erhältlich.
Metal–Organic Framework Thin Films as Platforms for Atomic Layer Deposition of Cobalt Ions To Enable Electrocatalytic Water Oxidation (2015)

Thin films of the metal-organic framework (MOF) NU-1000 were grown on conducting glass substrates. The films uniformly cover the conducting glass substrates and are composed of free-standing sub-micrometer rods. Subsequently, atomic layer deposition (ALD) was utilized to deposit Co(2+) ions throughout the entire MOF film via self-limiting surface-mediated reaction chemistry. The Co ions bind at aqua and hydroxo sites lining the channels of NU-1000, resulting in three-dimensional arrays of separated Co ions in the MOF thin film. The Co-modified MOF thin films demonstrate promising electrocatalytic activity for water oxidation.
Nogo‐A antibody improves regeneration and locomotion of spinal cord–injured rats (2005)

Spinal cord trauma leads to loss of motor, sensory and autonomic functions below the lesion. Recovery is very restricted, due in part to neurite growth inhibitory myelin proteins, in particular Nogo-A. Two neutralizing antibodies against Nogo-A were used to study recovery and axonal regeneration after spinal cord lesions. Three months old Lewis rats were tested in sensory-motor tasks (open field locomotion, crossing of ladder rungs and narrow beams, the CatWalk(R) runway, reactions to heat and von Frey hairs). A T-shaped lesion was made at T8, and an intrathecal catheter delivered highly purified anti-Nogo-A monoclonal IgGs or unspecific IgGs for 2 weeks. A better outcome in motor behavior was obtained as early as two weeks after lesion in the animals receiving the Nogo-A antibodies. Withdrawal responses to heat and mechanical stimuli were not different between the groups. Histology showed enhanced regeneration of corticospinal axons in the anti-Nogo-A antibody groups. fMRI revealed significant cortical responses to stimulation of the hindpaw exclusively in anti-Nogo-A animals. These results demonstrate that neutralization of the neurite growth inhibitor Nogo-A by intrathecal antibodies leads to enhanced regeneration and reorganization of the injured CNS, resulting in improved recovery of compromised functions in the absence of dysfunctions.
Determination of a high‐precision NMR structure of the minicollagen cysteine rich domain from Hydra and characterization of its disulfide bond formation (2004)

A high-precision solution structure of the C-terminal minicollagen cysteine rich domain of Hydra has been determined using modern heteronuclear and weak alignment NMR techniques at natural isotope abundance. The domain consists of only 24 amino acids, six of which are prolines and six are cysteines bonded in disulfide bridges that constrain the structure into a new fold. The redox equilibrium of the structure has been characterized from a titration with glutathione. No local native structures are detectable in the reduced form. Thus, oxidation and folding are tightly coupled.
Towards Translation of Discrete Frequency Infrared Spectroscopic Imaging for Digital Histopathology of Clinical Biopsy Samples (2016)

Fourier transform infrared (FT-IR) spectroscopic imaging has been widely tested as a tool for stainless digital histology of biomedical specimens, including for the identification of infiltration and fibrosis in endomyocardial biopsy samples to assess transplant rejection. A major barrier in clinical translation has been the slow speed of imaging. To address this need, we tested and report here the viability of using high speed discrete frequency infrared (DFIR) imaging to obtain stain-free biochemical imaging in cardiovascular samples collected from patients. Images obtained by this method were classified with high accuracy by a Bayesian classification algorithm trained on FT-IR imaging data as well as on DFIR data. A single spectral feature correlated with instances of fibrosis, as identified by the pathologist, highlights the advantage of the DFIR imaging approach for rapid detection. The speed of digital pathologic recognition was at least 16 times faster than the fastest FT-IR imaging instrument. These results indicate that a fast, on-site identification of fibrosis using IR imaging has potential for real time assistance during surgeries. Further, the work describes development and applications of supervised classifiers on DFIR imaging data, comparing classifiers developed on FT-IR and DFIR imaging modalities and identifying specific spectral features for accurate identification of fibrosis. This addresses a topic of much debate on the use of training data and cross-modality validity of IR measurements. Together, the work is a step toward addressing a clinical diagnostic need at acquisition time scales that make IR imaging technology practical for medical use.
MicroRNAs in normal and malignant hematopoiesis (2008)

There is now strong evidence that miRNAs modulate not only hematopoietic differentiation and proliferation but also activity of hematopoietic cells, in particular those related to immune function. Extensive miRNA deregulation has been observed in leukemias and lymphomas and mechanistic studies support a role for miRNAs in the pathogenesis of these disorders.
Human insulin‐like growth‐factor‐binding protein (1989)

Two different insulin-like growth-factor (IGF)-binding proteins have been found in human blood, one of high molecular mass and dependent on growth hormone for synthesis, the other of low molecular mass and independent of growth hormone. The small IGF-binding protein is abundant in human amniotic fluid. Its amino acid sequence has now been determined by direct analysis of the protein and its proteolytic fragments. Also, by immunoscreening a partial cDNA clone was isolated from a human hepatoma cell line. The mature protein consists of 234 amino acids and is coded for by an mRNA of approximately 1700 nucleotides in length. The primary structure of the protein reveals 18 Cys residues in N-terminal and C-terminal clusters and an Arg-Gly-Asp peptide sequence, common to extracellular proteins binding to receptors of the integrin family. A protein-sequence polymorphism was detected at position Ile/Met-228, indicating possible allelic variation. The 3'-untranslated mRNA sequence has a high A + T content and shows five copies of an ATTTA sequence, which has been shown to be involved in the regulation of the stability of certain mRNAs coding for growth-regulating proteins.
The Vanilloid Receptor: A Molecular Gateway to the Pain Pathway (2001)

The detection of painful stimuli occurs primarily at the peripheral terminals of specialized sensory neurons called nociceptors. These small-diameter neurons transduce signals of a chemical, mechanical, or thermal nature into action potentials and transmit this information to the central nervous system, ultimately eliciting a perception of pain or discomfort. Little is known about the proteins that detect noxious stimuli, especially those of a physical nature. Here we review recent advances in the molecular characterization of the capsaicin (vanilloid) receptor, an excitatory ion channel expressed by nociceptors, which contributes to the detection and integration of pain-producing chemical and thermal stimuli. The analysis of vanilloid receptor gene knockout mice confirms the involvement of this channel in pain sensation, as well as in hypersensitivity to noxious stimuli following tissue injury. At the same time, these studies demonstrate the existence of redundant mechanisms for the sensation of heat-evoked pain.
Ring-Closing Metathesis of Olefinic Peptides:  Design, Synthesis, and Structural Characterization of Macrocyclic Helical Peptides (2001)

Heptapeptides containing residues with terminal olefin-derivatized side chains (3 and 4) have been treated with ruthenium alkylidene 1 and undergone facile ring-closing olefin metathesis (RCM) to give 21- and 23-membered macrocyclic peptides (5 and 6). The primary structures of peptides 3 and 4 were based upon a previously studied heptapeptide (2), which was shown to adopt a predominantly 3(10)-helical conformation in CDCl(3) solution and an alpha-helical conformation in the solid state. Circular dichroism, IR, and solution-phase (1)H NMR studies strongly suggested that acyclic precursors 3 and 4 and the fully saturated macrocyclic products 7 and 8 also adopted helical conformations in apolar organic solvents. Single-crystal X-ray diffraction of cyclic peptide 8 showed it to exist as a right-handed 3(10)-helix up to the fifth residue. Solution-phase NMR structures of both acyclic peptide 4 and cyclic peptide 8 in CD(2)Cl(2) indicated that the acyclic diene assumes a loosely 3(10)-helical conformation, which is considerably rigidified upon macrocyclization. The relative ease of introducing carbon-carbon bonds into peptide secondary structures by RCM and the predicted metabolic stability of these bonds renders olefin metathesis an exceptional methodology for the synthesis of rigidified peptide architectures.
Indoor Positioning and Navigation with Camera Phones (2009)

This low-cost indoor navigation system runs on off-the-shelf camera phones. More than 2,000 users at four different large-scale events have already used it. The system uses built-in cameras to determine user location in real time by detecting unobtrusive fiduciary markers. The required infrastructure is limited to paper markers and static digital maps, and common devices are used, facilitating quick deployment in new environments. The authors have studied the application quantitatively in a controlled environment and qualitatively during deployment at four large international events. According to test users, marker-based navigation is easier to use than conventional mobile digital maps. Moreover, the users' location awareness in navigation tasks improved. Experiences drawn from questionnaires, usage log data, and user interviews further highlight the benefits of this approach.
Multiplexed CRISPR/Cas9 genome editing increases the efficacy of homologous-dependent repair of donor sequences in mammalian cells (2015)

Efficient and robust genome editing tools and strategies allow for specific and exact genetic changes to be captured in model systems, thereby accelerating both forward and reverse genetics studies. The development of CRISPR/Cas9 as a facile designer nuclease toolset has allowed for defined genetic modifications to be efficiently made through homology-directed repair of targeted DNA double-stranded breaks (DSBs) using exogenous repair templates. However, traditional single DSB strategies are still relatively inefficient as the short gene conversion tracts of mammalian cell systems limit the extent of achievable gene alteration from the DSB site. In order to improve on the inefficiency, we devised a dual cut strategy, which relies on reconstituting entire deleted gene fragments to precisely modify extensive gene regions of interest. Using the CRISPR/Cas9 system, we were able to introduce targeted deletions and repair of the endogenous KRAS gene locus in cell culture. The use of two simultaneous DSBs can be employed for efficient application of homology-directed repair with a large dsDNA donor sequence, thereby improving the efficacy of deriving cells with a desired gene editing outcome. In conclusion, a multiplexed CRISPR/Cas9 editing strategy represents an efficient tool for the editing of complex, heterologous sequence tracts.
Measuring Fiber Orientation in Nonwovens Part III: Fourier Transform (1997)

This paper addresses the development of an image analysis technique using the Fourier transform of the image to evaluate orientation in a fibrous assembly. The algorithms are evaluated using simulated images presented in Part I of the series. The results are compared with those for the tracking method presented in Part II.
Risk Management Research Design Ideologies, Strategies, Methods and Techniques (2013)

The researcher interviewed 11 doctoral students and 12 International Disaster Conference attendees to understand how research guidelines could be improved to help these emerging scholars achieve more publications. Empirical studies were cited to substantiate the need for better research method guidance. A research design model was then created as a top-down typology based on a literature review and practitioner experience. The design model consisted of four components: research ideology, unit and level of analysis strategy, formal research method, and analysis techniques. The discussion illustrated how all researcher philosophies can be simplified into one of three ideologies: post-positivist, pragmatic or social-constructivist. Additionally, the author explained how the level and unit of analysis goals are developed into an analysis strategy with research questions or hypotheses. Inquire strategy was integrated with formal research method and ideology, to facilitate the selection of data collection sampling and analysis techniques. Numerous research methods thought leaders were cited to direct new scholars towards best practices. A unique feature of the model was its simplicity and application across all the generally accepted research philosophies, methods and techniques as well as disciplinary fields. Although the study was directed toward risk management practitioners, it applies to any field or industry.
High-acoustic-impedance tantalum oxide layers for insulating acoustic reflectors (2012)

This work describes the assessment of the acoustic properties of sputtered tantalum oxide films intended for use as high-impedance films of acoustic reflectors for solidly mounted resonators operating in the gigahertz frequency range. The films are grown by sputtering a metallic tantalum target under different oxygen and argon gas mixtures, total pressures, pulsed dc powers, and substrate biases. The structural properties of the films are assessed through infrared absorption spectroscopy and X-ray diffraction measurements. Their acoustic impedance is assessed by deriving the mass density from X-ray reflectometry measurements and the acoustic velocity from picosecond acoustic spectroscopy and the analysis of the frequency response of the test resonators.
ATS - Adaptive Teaching System: a WWW-based ITS (1998)

Adaptive Teaching System (ATS) is a WWW based tutoring system, which combines methods of knowledge representation, instructional planning and adaptive media generation to deliver individualized courseware over the WWW. ATS uses the CL-HTTP hypermedia server (Mallery, 1994) for generate this individualized courseware. The system is based on a domain model of the subject matter, a didactical model on how to teach a curriculum and learner modeling on different levels, e.g. preferences, interests, knowledge. Based on these three components individualized Web content (html, java, pictures) is generated and presented to the learners (M. Specht et al., 1997). Taking into account the interest and the knowledge of a learner, the system can adapt different aspects of the instructional process, e.g. adapting the curriculum by selection of content, adapting the presentation of contents by choosing appropriate media and combining them, adapting the teaching strategies for specific contents, annotating hyperlinks, recommending appropriate hyperlinks and contents. Some adaptive methods used in ATS have been empirically evaluated and showed improvements in efficiency and effectiveness of learning compared to classical static hypermedia learning environments.
High speed optical packet routing demonstration of a vertical coupler crosspoint space switch array (2000)

Summary form only given. Future all-optical networks require high-speed routing of packets. Current commercial optical space switches typically have switching times in the order of milliseconds, which is unsuitable for this kind of application. Other devices based on semiconductor optical amplifier (SOA) gates offer nanosecond switch times. These devices are essentially based on broadcast-block-combine architectures, which are chip-area hungry when integrated and difficult to upscale. They could also be power hungry because several gates have to be switched on to establish a route.
p38 Regulates Cyclooxygenase-2 in Human Mammary Epithelial Cells and Is Activated in Premalignant Tissue (2005)

Abstract The immediate-early gene, cyclooxygenase-2 (COX-2), is induced in a variety of inflammatory and neoplastic processes and is believed to play an important role in tumorigenesis. In this study, we identify an important upstream regulatory pathway of COX-2 expression in variant human mammary epithelial cells (vHMEC), which has been shown to exhibit phenotypes important for malignancy. We find that the stress-activated kinase, p38, is phosphorylated and activated in vHMEC compared with HMEC and is responsible for the expression of COX-2 in vHMEC as cells grow in culture. Furthermore in this capacity, p38 acts to stabilize the COX-2 transcript rather than activate COX-2 transcription. Inhibition of p38 kinase, using a chemical inhibitor, down-regulates COX-2 and decreases cell survival. Examination of archived tissue from women with ductal carcinoma in situ reveals epithelial cells that not only overexpress COX-2 but also have an abundance of activated phospho-p38 in the nucleus and cytoplasm, mirroring the expression observed in vitro. These epithelial cells are found within premalignant lesions as well as in fields of morphologically normal tissue that surround the lesions. In contrast, low phospho-p38 staining was observed in the majority of normal tissue obtained from reduction mammoplasty. These data help define the regulation of COX-2 expression in early carcinogenesis and provide alternative candidates for targeted prevention of COX-2-induced phenotypes and breast cancer.
Shark variable new antigen receptor biologics – a novel technology platform for therapeutic drug development (2014)

The inherent ability to specifically bind target and intervene in disease-related biological processes, while reducing off-site toxicity, makes mAbs an effective, potent and now proven class of therapeutics. There are, however, limitations to these 'magic bullets'. Their size and complexity can restrict their utility in certain diseases types and disease locations. In contrast, a number of so-called alternative scaffolds, derived from both immunoglobulin- and non-immunoglobulin-based sources have been developed with real potential to overcome many of the shortcomings documented for mAb treatments. Unlike competing approaches such as Darpins and Affibodies, we now know that shark VNAR domains (like camel VHH nanobody domains), are an integral part of the adaptive immune system of these animals and have evolved naturally (but from very different starting molecules) to exhibit high affinity and selectivity for target. In addition, and again influenced by the environment in which they have evolved naturally, their small size, simple architecture, high solubility and stability, deliver additional flexibility compared to classical antibodies (and many non-natural alternative scaffolds), thereby providing an attractive basis for particular clinical indications where these attributes may offer advantages.