gebhart/patrepeval huggingface dataset:
The Alzheimer β-amyloid protein precursor/protease nexin-II is cleaved by secretase in a trans-Golgi secretory compartment in human neuroglioma cells (1993)

Alzheimer beta-amyloid protein precursor (beta APP) is expressed endogenously and abundantly by human neuroglioma (H4) cells. Its secretory processing has been shown to involve discrete proteolysis within the beta A4 region, thus preventing beta-amyloid formation, by an enzyme which has been referred to as 'beta APP secretase'. This cleavage results in secretion of a soluble N-terminal 135 kDa protein and retention of an integral membrane C-terminal fragment within the cell. The membrane-associated C-terminal fragment is sorted to lysosomes where it undergoes limited degradation. We show here that most newly synthesized beta APP is degraded via a non-lysosomal pathway before maturation in H4 cells, and most mature beta APP is processed predominantly by the so-called secretase. The rapid kinetics of appearance/disappearance of a cleaved 135 kDa protein within a microsomal fraction and the slow accumulation of this form in the extracellular medium indicated that secretase cleaves beta APP in an intracellular compartment. Low-temperature block (20 degrees C) was used to demonstrate that beta APP is cleaved within a late Golgi compartment after sulphation which occurs in the trans-Golgi network (TGN). This is consistent with (1) the immunolocalization of most of the beta APP within a Golgi compartment that reacts with wheat germ agglutinin, (2) the fact that less than 1.5% of the total mature full-length beta APP is present at the plasma membrane and (3) subcellular fractionation studies which showed that the mature full-length and intracellular cleaved beta APPs co-sediment with a membrane fraction that is slightly more dense than the plasma membrane. This study provides evidence that most of the beta APP secretase in H4 cells is intracellular, and confirms that the resulting C-terminal fragment is delivered to lysosomes immediately after cleavage. These results are discussed with regard to the possibility that mature full-length beta APP escapes secretase cleavage and is delivered directly from the TGN to the lysosome without passing through the plasma membrane. Either pathway will result in the generation of amyloidogenic fragments.
Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK (2003)

Allergic asthma patients manifest airway inflammation and some show increases in eosinophils, T(H)2 cells, and cytokines, increased mucous production in the lung, and elevated serum IgE. This T(H)2-type response suggests a prominent role for T(H)2 cells and their cytokines in the pathology of this disease. The Tec family nonreceptor tyrosine kinase inducible T cell kinase (ITK) has been shown to play a role in the differentiation and/or function of T(H)2-type cells, suggesting that ITK may represent a good target for the control of asthma. Using a murine model of allergic asthma, we show here that ITK is involved in the development of immunological symptoms seen in this model. We show that mice lacking ITK have drastically reduced lung inflammation, eosinophil infiltration, and mucous production following induction of allergic asthma. Notably, T cell influx into the lung was reduced in mice lacking ITK. T cells from ITK(-/-) mice also exhibited reduced proliferation and cytokine secretion, in particular IL-5 and IL-13, in response to challenge with the allergen OVA, despite elevated levels of total IgE and increased OVA-specific IgE responses. Our results suggest that the tyrosine kinase ITK preferentially regulates the secretion of the T(H)2 cytokines IL-5 and IL-13 and may be an attractive target for antiasthmatic drugs.
Battery-free, skin-interfaced microfluidic/electronic systems for simultaneous electrochemical, colorimetric, and volumetric analysis of sweat (2019)

Wearable sweat sensors rely either on electronics for electrochemical detection or on colorimetry for visual readout. Non-ideal form factors represent disadvantages of the former, while semiquantitative operation and narrow scope of measurable biomarkers characterize the latter. Here, we introduce a battery-free, wireless electronic sensing platform inspired by biofuel cells that integrates chronometric microfluidic platforms with embedded colorimetric assays. The resulting sensors combine advantages of electronic and microfluidic functionality in a platform that is significantly lighter, cheaper, and smaller than alternatives. A demonstration device simultaneously monitors sweat rate/loss, pH, lactate, glucose, and chloride. Systematic studies of the electronics, microfluidics, and integration schemes establish the key design considerations and performance attributes. Two-day human trials that compare concentrations of glucose and lactate in sweat and blood suggest a potential basis for noninvasive, semi-quantitative tracking of physiological status.
SEROTONERGIC MECHANISMS IN AMYOTROPHIC LATERAL SCLEROSIS (2006)

Serotonin (5-HT) has been intimately linked with global regulation of motor behavior, local control of motoneuron excitability, functional recovery of spinal motoneurons as well as neuronal maturation and aging. Selective degeneration of motoneurons is the pathological hallmark of amyotrophic lateral sclerosis (ALS). Motoneurons that are preferentially affected in ALS are also densely innervated by 5-HT neurons (e.g., trigeminal, facial, ambiguus, and hypoglossal brainstem nuclei as well as ventral horn and motor cortex). Conversely, motoneuron groups that appear more resistant to the process of neurodegeneration in ALS (e.g., oculomotor, trochlear, and abducens nuclei) as well as the cerebellum receive only sparse 5-HT input. The glutamate excitotoxicity theory maintains that in ALS degeneration of motoneurons is caused by excessive glutamate neurotransmission, which is neurotoxic. Because of its facilitatory effects on glutaminergic motoneuron excitation, 5-HT may be pivotal to the pathogenesis and therapy of ALS. 5-HT levels as well as the concentrations 5-hydroxyindole acetic acid (5-HIAA), the major metabolite of 5-HT, are reduced in postmortem spinal cord tissue of ALS patients indicating decreased 5-HT release. Furthermore, cerebrospinal fluid levels of tryptophan, a precursor of 5-HT, are decreased in patients with ALS and plasma concentrations of tryptophan are also decreased with the lowest levels found in the most severely affected patients. In ALS progressive degeneration of 5-HT neurons would result in a compensatory increase in glutamate excitation of motoneurons. Additionally, because 5-HT, acting through presynaptic 5-HT1B receptors, inhibits glutamatergic synaptic transmission, lowered 5-HT activity would lead to increased synaptic glutamate release. Furthermore, 5-HT is a precursor of melatonin, which inhibits glutamate release and glutamate-induced neurotoxicity. Thus, progressive degeneration of 5-HT neurons affecting motoneuron activity constitutes the prime mover of the disease and its progression and treatment of ALS needs to be focused primarily on boosting 5-HT functions (e.g., pharmacologically via its precursors, reuptake inhibitors, selective 5-HT1A receptor agonists/5-HT2 receptor antagonists, and electrically through transcranial administration of AC pulsed picotesla electromagnetic fields) to prevent excessive glutamate activity in the motoneurons. In fact, 5HT1A and 5HT2 receptor agonists have been shown to prevent glutamate-induced neurotoxicity in primary cortical cell cultures and the 5-HT precursor 5-hydroxytryptophan (5-HTP) improved locomotor function and survival of transgenic SOD1 G93A mice, an animal model of ALS.
Robotic telemanipulation for percutaneous renal access (1998)

Robotic telemanipulation for percutaneous renal access
Heparan Sulfate–like Glycosaminoglycan Is a Cellular Receptor forChlamydia pneumoniae (2001)

Chlamydia pneumoniae is an important human intracellular pathogen; however, the pathogenesis of C. pneumoniae infection is poorly understood, and the bacterial adherence mechanism to host cells is unknown. This study examined the role of glycosaminoglycans (GAGs) in the adhesion of C. pneumoniae to eukaryotic cells. Heparin and heparan sulfate were found to inhibit the attachment of C. pneumoniae to human epithelial cells. Reduction in infectivity resulted from the binding of heparin to the organism. Enzymatic removal of heparan sulfate moieties from the host cell surface led to a marked decrease in C. pneumoniae infectivity. Mutant CHO cell lines that were defective in heparan sulfate biosynthesis were less susceptible to C. pneumoniae infection than was the wild-type cell line. However, preincubation of the GAG-deficient CHO cells with exogenous heparin greatly increased infectivity.
Modeling nanoelectronic CNN cells: CMOS, SETs and QCAs (2000)

Summary form only given, as follows. We investigate the use of nanoelectronic structures in cellular neural network (CNN) architectures, for future high-density and low-power CMOS-nanodevice hybrid circuits. We present simulation results for Single Electron Tunneling (SET) transistors configured as a voltage-to-current transducer for CNN cells. We also present an example of quantum-dot cellular arrays which may be used to realize binary CNN algorithms. Nanoelectronics offers the promise of ultra-low power and ultra-high integration density. Several device structures have been proposed and realized experimentally, yet the main challenge remains the organization of these devices in new circuit architectures. Here, we investigate the use of nanodevices in CNN architectures. Specifically, we focus on nanostructures based on SET devices and Coulomb-coupled quantum-dot arrays, the so-called Quantum-Dot Cellular Automata (QCA). CNN-type architectures for nanostructures are motivated by the following considerations: on the one hand, locally-interconnected architectures appear to be natural for nanodevices where some of the connectivity may be provided by direct physical device-device interactions. On the other hand, CNN arrays with sizes on the order of 1000-by-1000 (which are desirable for applications such as image processing) will require the use of nanostructures since such integration densities are beyond what can be achieved by scaling conventional CMOS devices.
A Revisit of Sparse Coding Based Anomaly Detection in Stacked RNN Framework (2017)

Motivated by the capability of sparse coding based anomaly detection, we propose a Temporally-coherent Sparse Coding (TSC) where we enforce similar neighbouring frames be encoded with similar reconstruction coefficients. Then we map the TSC with a special type of stacked Recurrent Neural Network (sRNN). By taking advantage of sRNN in learning all parameters simultaneously, the nontrivial hyper-parameter selection to TSC can be avoided, meanwhile with a shallow sRNN, the reconstruction coefficients can be inferred within a forward pass, which reduces the computational cost for learning sparse coefficients. The contributions of this paper are two-fold: i) We propose a TSC, which can be mapped to a sRNN which facilitates the parameter optimization and accelerates the anomaly prediction. ii) We build a very large dataset which is even larger than the summation of all existing dataset for anomaly detection in terms of both the volume of data and the diversity of scenes. Extensive experiments on both a toy dataset and real datasets demonstrate that our TSC based and sRNN based method consistently outperform existing methods, which validates the effectiveness of our method.
Conditional mutants of RPC160, the gene encoding the largest subunit of RNA polymerase C in Saccharomyces cerevisiae. (1988)

A 18.4-kb fragment of the yeast genome containing the gene of the largest subunit of RNA polymerase C (RPC160) was cloned by hybridization to a previously isolated fragment of that gene. RPC160 maps on chromosome XV, tightly linked but not allelic to the essential gene TSM8740. Temperature sensitive (ts) mutant alleles were constructed by in vitro mutagenesis with NaHSO3 and substituted for the wild-type allele on the chromosome. Four of them were unambiguously identified as rpc160 mutants by failure to complement a fully defective mutation rpc160::URA3. The faithful transcription of a yeast tRNA gene by mutant cell-free extracts is strongly reduced as compared to wild-type. In vivo, the rpc160 mutations specifically affect the synthesis of tRNA in a temperature sensitive way, with comparatively little effect on the synthesis of 5S rRNA and no effect on 5.8S rRNA. An unlinked mutation (pcil-3) suppresses the temperature sensitive phenotype of the rpc160-41 mutation.
Spectroscopic imaging of self-organization in high power impulse magnetron sputtering plasmas (2013)

Excitation and ionization conditions in traveling ionization zones of high power impulse magnetron sputtering plasmas were investigated using fast camera imaging through interference filters. The images, taken in end-on and side-on views using light of selected gas and target atom and ion spectral lines, suggest that ionization zones are regions of enhanced densities of electrons, and excited atoms and ions. Excited atoms and ions of the target material (Al) are strongly concentrated near the target surface. Images from the highest excitation energies exhibit the most localized regions, suggesting localized Ohmic heating consistent with double layer formation.
Limited proteolysis in porous membrane reactors containing immobilized trypsin (2017)

Proteolysis is often a critical step in protein characterization via mass spectrometry. Compared to complete digestion, limited proteolysis gives larger peptides, and the dominant cleavage sites may identify highly accessible, flexible protein regions. This paper explores controlled proteolysis in porous nylon membranes containing immobilized trypsin. Passage of protein solutions through ∼100 μm thick membranes provides reaction residence times as short as milliseconds to limit digestion. Additionally, variation of the membrane pore size and the protease-immobilization method (electrostatic adsorption or covalent anchoring to adsorbed polymer in membrane pores) affords control over the proteolysis rate. When digesting the highly labile protein β-casein, large membrane pores (5.0 μm) and covalent enzyme anchoring to adsorbed polymer lead to particularly long tryptic peptides. With the more trypsin-resistant proteins cytochrome c and apomyoglobin, in-membrane proteolysis with short residence times, 1.2 μm membrane pores, and trypsin electrostatically immobilized to an adsorbed polyanion cleaves the proteins after lysine residues in flexible regions. For both cytochrome c and apomyoglobin, cleavages in an interhelix region yield two particularly large peptides that cover the entire protein sequence.
Dual contouring of hermite data (2002)

This paper describes a new method for contouring a signed grid whose edges are tagged by Hermite data (i.e; exact intersection points and normals). This method avoids the need to explicitly identify and process "features" as required in previous Hermite contouring methods. Using a new, numerically stable representation for quadratic error functions, we develop an octree-based method for simplifying contours produced by this method. We next extend our contouring method to these simpli£ed octrees. This new method imposes no constraints on the octree (such as being a restricted octree) and requires no "crack patching". We conclude with a simple test for preserving the topology of the contour during simplification.
Recent Advances in Ophthalmic Drug Delivery (2010)

Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert (-6 months), Retisert (-3 years) and Iluvien (-3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems.
Role of Ribosomal Protein L12 in Gonococcal Invasion of Hec1B Cells (2000)

Previous studies led to the development of a model of contact-induced enhanced gonococcal invasion of human reproductive cells that utilizes the lutropin receptor (LHr) as both the induction signal for conversion to this enhanced-gonococcal-invasion phenotype (Inv(+) GC) and as the specific Inv(+) GC uptake mechanism. This model proposes that gonococci express a surface feature that mimics human chorionic gonadotropin (hCG), the cognate ligand for LHr, and that this structure is responsible for the specific and productive interaction of GC with LHr. In this report, we identify a 13-kDa gonococcal protein with immunological similarities to hCG. The antiserum reactivity is specific since interaction with the 13-kDa gonococcal protein can be blocked by the addition of highly purified hCG. This gonococcal "hCG-like" protein, purified from two-dimensional gels and by immunoprecipitation, was determined by N-terminal sequencing to be the ribosomal protein L12. We present evidence that gonococcal L12 is membrane associated and surface exposed in gonococci, as shown by immunoblot analysis of soluble and insoluble gonococcal protein and antibody adsorption studies with fixed GC. Using highly purified recombinant gonococcal L12, we show that preincubation of Inv(-) GC with micromolar amounts of rL12 leads to a subsequent five- to eightfold increase in invasion of the human endometrial cell line, Hec1B. In addition, nanomolar concentrations of exogenous L12 inhibits gonococcal invasion to approximately 70% of the level in controls. Thus, we propose a novel cellular location for the gonococcal ribosomal protein L12 and concomitant function in LHr-mediated gonococcal invasion of human reproductive cells.
Simultaneous three-dimensional tracking of individual signals from multi-trap optical tweezers using fast and accurate photodiode detection (2014)

Multiple-beam optical traps facilitate advanced trapping geometries and exciting discoveries. However, the increased manipulation capabilities come at the price of more challenging position and force detection. Due to unrivaled bandwidth and resolution, photodiode based detection is preferred over camera based detection in most single/dual-beam optical traps assays. However, it has not been trivial to implement photodiode based detection for multiple-beam optical traps. Here, we present a simple and efficient method based on spatial filtering for parallel photodiode detection of multiple traps. The technique enables fast and accurate 3D force and distance detection of multiple objects simultaneously manipulated by multiple-beam optical tweezers.
Intracerebral Gene Transfer Using Viral Vectors (2000)

The recent development of recombinant viral vectors that are capable of transducing postmitotic cells may provide a powerful new tool for studying brain function, as well as ameliorative strategies in models of neurological disease. Some of these vectors have recently demonstrated direct expression of biologically relevant levels of protein expression (, ; ; ) for varying periods of time of up to 1 yr after direct intracerebral injection (, ; ; ). Moreover, vectors injected into the nervous system have been shown, not only to be capable of expressing de novo transgenes, but also to be able to regionally suppress gene expression by delivery of antisense oligonucleotides (), by expression of a dominant-negative protein, by local knock-out of genes in transgenic animals carrying a transgene surrounded by lox-P sites (), or by the production of molecules capable of inhibiting specific mRNAs, called ribozymes (). Thus, the use of viral vectors has great potential, not only for the study of gene therapy (GT), but also for the study of the molecular basis of certain brain functions.
Showdomycin as a Versatile Chemical Tool for the Detection of Pathogenesis-Associated Enzymes in Bacteria (2010)

Showdomycin is a potent nucleoside antibiotic that displays a high structural similarity to uridine and pseudouridine. No detailed target analysis of this very unusual electrophilic natural product has been carried out so far. To unravel its biological function, we synthesized a showdomycin probe that can be appended with a fluorophor or a biotin marker via click chemistry and identified diverse enzymes which were important for either the viability or virulence of pathogenic bacteria. Our results indicate that the antibiotic effect of showdomycin against Staphylococcus aureus may be due to the inhibition of various essential enzymes, especially MurA1 and MurA2, which are required for cell wall biosynthesis. Although real-time polymerase chain reaction revealed that the MurA2 gene was expressed equally in four S. aureus strains, our probe studies showed that MurA2 was activated in only one multiresistant S. aureus strain, and only this strain was resistant to elevated concentrations of the MurA inhibitor fosfomycin, suggesting its potential role as an antibiotic bypass mechanism in the case of MurA1 inhibition. Moreover, we utilized this tool to compare enzyme profiles of different pathogenic strains, which provided unique insights in regulatory differences as well as strain-specific signatures.
High-brightness InGaN/AlGaN double-heterostructure blue-green-light-emitting diodes (1994)

High-brightness InGaN/AlGaN double-heterostructure blue-green-light-emitting diodes with a luminous intensity of 2 cd were fabricated by increasing an indium mole fraction of the InGaN active layer up to 0.23. Both Zn and Si were codoped into the InGaN active layer to afford relatively stronger luminescence. The blue-green emission intensity of room-temperature photoluminescence became maximum when the electron carrier concentration of the InGaN active layer was around 1×1019 cm−3. Donor-acceptor pair recombination is a dominant emission mechanism of the InGaN active layer. The external quantum efficiency was as high as 2.4% at a forward current of 20 mA at room temperature. The peak wavelength and the full width at half-maximum of the electroluminescence were 500 and 80 nm, respectively.
View Through a Window May Influence Recovery from Surgery (1984)

Records on recovery after cholecystectomy of patients in a suburban Pennsylvania hospital between 1972 and 1981 were examined to determine whether assignment to a room with a window view of a natural setting might have restorative influences. Twenty-three surgical patients assigned to rooms with windows looking out on a natural scene had shorter postoperative hospital stays, received fewer negative evaluative comments in nurses' notes, and took fewer potent analgesics than 23 matched patients in similar rooms with windows facing a brick building wall.