gebhart/patrepeval huggingface dataset:
RAGE-mediated signaling contributes to intraneuronal transport of amyloid-β and neuronal dysfunction (2009)

Intracellular amyloid-beta peptide (Abeta) has been implicated in neuronal death associated with Alzheimer's disease. Although Abeta is predominantly secreted into the extracellular space, mechanisms of Abeta transport at the level of the neuronal cell membrane remain to be fully elucidated. We demonstrate that receptor for advanced glycation end products (RAGE) contributes to transport of Abeta from the cell surface to the intracellular space. Mouse cortical neurons exposed to extracellular human Abeta subsequently showed detectable peptide intracellularly in the cytosol and mitochondria by confocal microscope and immunogold electron microscopy. Pretreatment of cultured neurons from wild-type mice with neutralizing antibody to RAGE, and neurons from RAGE knockout mice displayed decreased uptake of Abeta and protection from Abeta-mediated mitochondrial dysfunction. Abeta activated p38 MAPK, but not SAPK/JNK, and then stimulated intracellular uptake of Abeta-RAGE complex. Similar intraneuronal co-localization of Abeta and RAGE was observed in the hippocampus of transgenic mice overexpressing mutant amyloid precursor protein. These findings indicate that RAGE contributes to mechanisms involved in the translocation of Abeta from the extracellular to the intracellular space, thereby enhancing Abeta cytotoxicity.
Attenuation of Venezuelan equine encephalitis virus strain TC-83 is encoded by the 5'-noncoding region and the E2 envelope glycoprotein (1993)

The virulent Trinidad donkey (TRD) strain of Venezuelan equine encephalitis (VEE) virus and its live attenuated vaccine derivative, TC-83 virus, have different neurovirulence characteristics. A full-length cDNA clone of the TC-83 virus genome was constructed behind the bacteriophage T7 promoter in the polylinker of plasmid pUC18. To identify the genomic determinants of TC-83 virus attenuation, TRD virus-specific sequences were inserted into the TC-83 virus clone by in vitro mutagenesis or recombination. Antigenic analysis of recombinant viruses with VEE E2- and E1-specific monoclonal antibodies gave predicted antigenic reactivities. Mouse challenge experiments indicated that genetic markers responsible for the attenuated phenotype of TC-83 virus are composed of genome nucleotide position 3 in the 5'-noncoding region and the E2 envelope glycoprotein. TC-83 virus amino acid position E2-120 appeared to be the major structural determinant of attenuation. Insertion of the TRD virus-specific 5'-noncoding region, by itself, into the TC-83 virus full-length clone did not alter the attenuated phenotype of the virus. However, the TRD virus-specific 5'-noncoding region enhanced the virulence potential of downstream TRD virus amino acid sequences.
Novel NEMO/IκB Kinase and NF-κB Target Genes at the Pre-B to Immature B Cell Transition (2001)

The IkappaB kinase (IKK) signaling complex is responsible for activating NF-kappaB-dependent gene expression programs. Even though NF-kappaB-responsive genes are known to orchestrate stress-like responses, critical gaps in our knowledge remain about the global effects of NF-kappaB activation on cellular physiology. DNA microarrays were used to compare gene expression programs in a model system of 70Z/3 murine pre-B cells versus their IKK signaling-defective 1.3E2 variant with lipopolysaccharide (LPS), interleukin-1 (IL-1), or a combination of LPS + phorbol 12-myristate 13-acetate under brief (2 h) or long term (12 h) stimulation. 70Z/3-1.3E2 cells lack expression of NEMO/IKKgamma/IKKAP-1/FIP-3, an essential positive effector of the IKK complex. Some stimulated hits were known NF-kappaB target genes, but remarkably, the vast majority of the up-modulated genes and an unexpected class of repressed genes were all novel targets of this signaling pathway, encoding transcription factors, receptors, extracellular ligands, and intracellular signaling factors. Thirteen stimulated (B-ATF, Pim-2, MyD118, Pea-15/MAT1, CD82, CD40L, Wnt10a, Notch 1, R-ras, Rgs-16, PAC-1, ISG15, and CD36) and five repressed (CCR2, VpreB, lambda5, SLPI, and CMAP/Cystatin7) genes, respectively, were bona fide NF-kappaB targets by virtue of their response to a transdominant IkappaBalphaSR (super repressor). MyD118 and ISG15, although directly induced by LPS stimulation, were unaffected by IL-1, revealing the existence of direct NF-kappaB target genes, which are not co-induced by the LPS and IL-1 Toll-like receptors.
Effect of fiber crosslinking on collagen‐fiber reinforced collagen–chondroitin‐6‐sulfate materials for regenerating load‐bearing soft tissues (2012)

Porous collagen-glycosaminoglycan structures are bioactive and exhibit a pore architecture favorable for both cellular infiltration and attachment; however, their inferior mechanical properties limit use, particularly in load-bearing situations. Reinforcement with collagen fibers may be a feasible route for enhancing the mechanical characteristics of these materials, providing potential for composites used for the repair and regeneration of soft tissue such as tendon, ligaments, and cartilage. Therefore, this study investigates the reinforcement of collagen-chondroitin-6-sulfate (C6S) porous structures with bundles of extruded, reconstituted type I collagen fibers. Fiber bundles were produced through extrusion and then, where applicable, crosslinked using a solution of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide. Fibers were then submerged in the collagen-C6S matrix slurry before being lyophilized. A second 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide crosslinking process was then applied to the composite material before a secondary lyophilization cycle. Where bundles had been previously crosslinked, composites withstood a load of approximately 60 N before failure, the reinforcing fibers remained dense and a favorable matrix pore structure resulted, with good interaction between fiber and matrix. Fibers that had not been crosslinked before lyophilization showed significant internal porosity and a channel existed between them and the matrix. Mechanical properties were significantly reduced, but the additional porosity could prove favorable for cell migration and has potential for directing aligned tissue growth.
Discrimination of α<sub>1</sub>-Adrenoceptor Subtypes in Rat Aorta and Prostate (1998)

This study was designed to further discriminate alpha1-adrenoceptor subtypes in rat aorta and prostate using functional experiments. Responses induced by phenylephrine were equilibrated in both tissues. The pA2 values and slope factors of several alpha1-antagonists were assessed using concentration-response curves. The antagonists used were prazosin, WB-4101, 5-methylurapidil (5-MU), HV-723, and tamsulosin. In addition, the effects of chloroethylclonidine (CEC) and nifedipine on phenylephrine-induced contractions were investigated. A high pA2 value for prazosin was observed in both tissues (aorta 9.84, prostate 9.19) and the ranking of each drug's pA2 value is as follows: tamsulosin > prazosin > WB-4101 > HV-723 > 5-MU in the aorta, and tamsulosin > prazosin > 5-MU > WB-4101 = HV-723 in the prostate. A significant difference between the pA2 value of each drug except for tamsulosin in the aorta and in prostate was observed (p < 0.01). Inhibition of contraction by pretreatment with CEC was 83.9 +/- 2.42% in the aorta, and 6.17 +/- 0.94% in the prostate. On the other hand, inhibition of maximal response by pretreatment with nifedipine (1 micromol/l) was 35.1 +/- 2.2% in the aorta and 24.5 +/- 3.1% in the prostate. A good correlation between these pA2 values and pKi values for recombinant human alpha1b-adrenoceptor expressed in CHO cells (aorta) and alpha1a-subtypes of CEC pretreated rat hippocampus (prostate) were observed. In conclusion, these results suggest that: (1) the contraction of these two tissues is mediated by alpha1H-adrenoceptor with a high affinity for prazosin; (2) alpha1H-adrenoceptors correspond to alpha1b-(aorta) and alpha1a-subtypes (prostate), and (3) each alpha1-adrenoceptor subtype in the aorta and prostate may be alpha1b-(aorta) and alpha1a-subtypes (prostate), respectively.
Mitochondrial Fusion/Fission, Transport and Autophagy in Parkinson's Disease: When Mitochondria Get Nasty (2011)

Understanding the molecular basis of Parkinson's disease (PD) has proven to be a major challenge in the field of neurodegenerative diseases. Although several hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of PD, a growing body of evidence has highlighted the role of mitochondrial dysfunction and the disruption of the mechanisms of mitochondrial dynamics in PD and other parkinsonian disorders. In this paper, we comment on the recent advances in how changes in the mitochondrial function and mitochondrial dynamics (fusion/fission, transport, and clearance) contribute to neurodegeneration, specifically focusing on PD. We also evaluate the current controversies in those issues and discuss the role of fusion/fission dynamics in the mitochondrial lifecycle and maintenance. We propose that cellular demise and neurodegeneration in PD are due to the interplay between mitochondrial dysfunction, mitochondrial trafficking disruption, and impaired autophagic clearance.
System study of a dial-up text reading service for the blind (1972)

This paper describes a recent feasibility study of a system concept that could allow blind persons access on demand to the printed page. A portable, user-controlled scanner, based on the Optacon direct-translation reading aid, would collect image information from any printed text for presentation to a computer and optical character recognition unit, remotely connected via dial-up telephone lines. The OCR unit would recognize the letters of the text, the computer would assemble them into words and phrases, and intelligible speech would be returned to the user. The study indicated that such a system was feasible, or close to feasible, within the state of the art in the pertinent areas of development and that its cost might not be exorbitant in comparison with existing services for the blind.
Production-level facial performance capture using deep convolutional neural networks (2017)

We present a real-time deep learning framework for video-based facial performance capture---the dense 3D tracking of an actor's face given a monocular video. Our pipeline begins with accurately capturing a subject using a high-end production facial capture pipeline based on multi-view stereo tracking and artist-enhanced animations. With 5--10 minutes of captured footage, we train a convolutional neural network to produce high-quality output, including self-occluded regions, from a monocular video sequence of that subject. Since this 3D facial performance capture is fully automated, our system can drastically reduce the amount of labor involved in the development of modern narrative-driven video games or films involving realistic digital doubles of actors and potentially hours of animated dialogue per character. We compare our results with several state-of-the-art monocular real-time facial capture techniques and demonstrate compelling animation inference in challenging areas such as eyes and lips.
Nearest neighbor and generalized inverse distance interpolation for Fourier domain image reconstruction (2005)

Several well known imaging techniques operate by recording samples of the Fourier transform of the object function and then reconstructing the object function by means of the 2D inverse FFT. A central problem arises in interpolating from the inherent polar raster to a rectangular raster, so the inverse FFT can be properly applied. This paper considers the use of nearest neighbor and inverse distance interpolation when the angular recording interval is relatively small. The objective is to obtain a computationally simple reconstruction algorithm that achieves good resolution in the final image plane.
Minimally Invasive Protein Delivery with Rapidly Dissolving Polymer Microneedles (2008)

A new room-temperature, in situ polymerization process to produce microneedles (see figure), which can encapsulate functional biomolecules and dissolve within minutes, is presented. The dissolution rate and mechanical strength of these polymer microneedles can be tailored by changing monomer composition and microneedle geometry. Drug delivery using micrometer-scale needles that dissolve in the skin could eliminate the pain and dangers of hypodermic needle use.
A CHOP-regulated microRNA controls rhodopsin expression (2011)

Using genome-wide microribonucleic acid (microRNA [miRNA]) expression profiling, bioinformatics, and biochemical analyses, we identified miR-708, an endoplasmic reticulum (ER) stress-inducible miRNA whose expression is regulated by the transcription factor CCAAT enhancer-binding protein homologous protein (CHOP) in vertebrates. miR-708 is encoded within an intron of the CHOP-regulated gene Odz4, a member of the highly conserved teneurin family of developmental regulators. Odz4 and mir-708 expression is coregulated by CHOP, and the two transcripts are coexpressed in the brain and eyes of mice, suggesting common physiological functions in these tissues. We validated rhodopsin as a target of miR-708 through loss- and gain-of-function experiments. Together, our data implicate miR-708 in the homeostatic regulation of ER function in mammalian rod photoreceptors, whereby miR-708 may help prevent an excessive rhodopsin load from entering the ER. Hence, miR-708 may function analogously to other unfolded protein response controls that throttle protein influx into the ER to avoid ER stress through mechanisms, such as general translational attenuation by protein kinase RNA-like ER kinase or membrane-bound messenger RNA decay by inositol-requiring enzyme 1.
Comparative Toxicity of Stable Rare Earth Compounds (1964)

Stable rare earth chlorides, citrate, and EDTA salt complexes were injected into a total of 135 anesthetized dogs. All rare earths, except promethium, were included. Yttrium was also included in the series. An amount of 100 mg/kg doses was administered intravenously as 5% solutions, in 10 mg/kg increments at 10-min intervals. Observations were made on heart rate, blood pressure, and respiration. Blood samples were thken preanesthetically, and at 0, 10, 30, 60, 100, and 160 min for red blood cells, white blood cells, and differential counts, hemoglobin, hematocrit, sedimentation rate, prothrombin time, and coagulation time. No distinctive physiological response was found with any of the rare earths. Specific effects on blood constituents were an increase in prothrombin and coagulation times. The other constituents were not specifically affected by the rare earths. The chlorides were most toxic and the edentate complexes the least. Acute toxicity was of a low order; however, latent symptoms and pathology were found in single-injection preliminary studies. There also was a gradation of decreasing effects from the lower to the higher members of the atomic series. Gross and histopathological examinations were essentially negative. (auth)
User Profiling for Interest-focused Browsing History (2005)

Abstract. User profiling is an important part of the Semantic Web as it integrates the user into the concept of Web data with machine-readable semantics. In this paper, user profiling is presented as a way of providing the user with his/her interest-focused browsing history. We present a system that is incorporated into the Internet Explorer and maintains a dynamic user profile in a form of automatically constructed topic ontology. A subset of previously visited Web pages is associated with each topic in the ontology. By selecting a topic, the user can view the set of associated pages and choose to navigate to the page of his/her interest. Each topic can be seen as an interest of the user (hence the term interest-focused browsing history). The ontology is constructed by transforming the textual contents of the pages into sparse word-vectors and applying bisecting k-means clustering (i.e. a form of hierarchical clustering) on the set of sparse vectors. The most recently visited pages are used to identify the user’s current interest and map it to the ontology. The user can clearly see which topics, and their corresponding pages, are related (or are not related, for that matter) to his/her current interest. We see this as a useful way of organizing the user’s browsing history. To illustrate the functioning of the system, we demonstrate its behavior in one particular real-life scenario. 1
Reporter Expression Persists 1 Year After Adeno-Associated Virus-Mediated Gene Transfer to the Optic Nerve (1999)

We have previously shown that gene therapy with catalase suppressed experimental optic neuritis at 1 month after injection. Viral-mediated gene transfer may be a powerful technique for the treatment of optic neuropathies, particularly for recurrences of optic neuritis, if long-term expression of transduced protein can be demonstrated in the optic nerve.
Performance of an OFDM-TDMA mobile communication system (2002)

The multicarrier transmission technique (OFDM) is considered in combination with a TDMA/TDD multiple access scheme for a cellular mobile communication system. Performance analysis is presented for the uncoded and coded (TCM) case. It is shown that OFDM systems have a large potential concerning the flexible allocation of the total given bandwidth to different users. This flexibility can be exploited to adapt to the impairments of the radio channel, thus increasing the overall performance. Two methods, namely (1) a simple principle to leave out weak subcarriers, and (2) the individual modulation of each subcarrier (adaptive modulation) are studied (for the up-/downlink case in a frequency selective and time-variant radio channel), and results with respect to throughput and BER performance are discussed.
An evaluation of architectures incorporating wavelength division multiplexing for broad-band fiber access (1998)

Wavelength division multiplexing (WDM) offers the potential to transport very high bit rates in access systems serving residential and small business customers. We describe the options for WDM access systems, and evaluate them on the basis of an international standard that is emerging for passive optical networks (PONs) that use wavelength-independent power splitting. The greatest impediment to meeting the high-bandwidth potential of WDM for downstream (i.e., from the central office to the home) transmission is the need for a moderately priced multiple-wavelength light source, implementing WDM in the upstream (home to central office) direction presents greater hurdles than in the downstream. The technical aspects of overcoming these hurdles can all be met. The real challenge will be in finding technical solutions that can meet the very stringent cost requirements of access systems. Systems that use WDM in the downstream direction only, while using wavelength-independent power-combining in a PON configuration for upstream, may prove economical before full WDM systems. WDM may also prove valuable if upgrades are needed in the future for power-splitting PON's.
Therapeutic Antagonists and the Conformational Regulation of the &#946;2 Integrins (2004)

The beta2 integrins are validated therapeutic targets for inflammatory disorders. Two distinct mechanistic classes of small molecule inhibitors, termed alpha I allosteric and alpha/beta I-like allosteric antagonist, have recently been developed. The alpha I allosteric antagonists bind underneath the C-terminal helix of the I domain and stabilize the I domain in the inactive closed conformation. By contrast, the alpha/beta I-like allosteric antagonists bind to the beta2 I-like domain MIDAS and disrupt conformational signal transmission between the I and the I-like domain, leaving the I domain in a default inactive form. Furthermore, the two classes of the antagonists have opposite effects on integrin conformation; the alpha I allosteric antagonists stabilize the bent conformation, whereas the alpha/beta I-like allosteric antagonists induce the extended conformation with inactive I domain. The small molecule antagonists to the beta2 integrin highlight the importance of the structural linkages within and between integrin domains for transmission of the conformational signals and regulation of the overall conformation.
ATP Luminescence-Based Motility-Invasion Assay (2002)

Directional motility and invasion assays are largely based on the use of Boyden chambers or Transwell culture inserts in which porous membranes separate seeded cells from a chemotactic factor supplied in the medium outside the chamber. The major obstaclefor most currently available assays is that they lack a sensitive, easy, and reliable method of quantifying the nonmotile cell populations. Failure to accountfor all cells within the assay chamber prohibits the determination of percentages of migrated cells. Here we describe an ATP luminescence-based motility-invasion (ALMI) assay that circumvents this problem, enabling investigators to quantify directional cell migration or invasiveness easily. The ALMI assay is based on the detection of ATP in viable cells harvested from inert surfaces that do not generate background signals. We demonstrate how the ALMI assay can be used to assess the effects of various experimental conditions such as growth factor stimulation and ethanol exposure on cell migration. In addition, precoating the membranes with extracellular matrix molecules enabled the measurement of the cell invasion. In conclusion, the ALMI assay provides a reliable and flexible method to quantify cell motility and invasiveness using a luminescence microplate reader.
Locator/ID Separation Protocol (LISP) Map-Server Interface (2013)

This document describes the Mapping Service for the Locator/ID
Separation Protocol (LISP), implemented by two new types of LISP-
speaking devices -- the LISP Map-Resolver and LISP Map-Server -- that
provides a simplified front for one or more Endpoint ID to
Routing Locator mapping databases. By using this service interface
and communicating with Map-Resolvers and Map-Servers, LISP Ingress
Tunnel Routers and Egress Tunnel Routers are not dependent on the
details of mapping database systems, which facilitates experimentation
with different database designs. Since these devices implement the
edge of the LISP infrastructure, connect directly to LISP-capable
Internet end sites, and comprise the bulk of LISP-speaking devices,
reducing their implementation and operational complexity should also
reduce the overall cost and effort of deploying LISP. This document
defines an Experimental Protocol for the Internet community.
Glucagon and the Glucagon-like Peptides (1990)

Glucagon and the glucagon-like peptides are encoded within a larger precursor, proglucagon. The proglucagon gene is expressed in the pancreas, intestine, and brain, giving rise to a single proglucagon mRNA transcript that is identical in all tissues. Tissue-specific posttranslational processing of proglucagon accounts for the different molecular forms of the glucagon-related peptides present in each tissue. Glucagon-like peptide I has been demonstrated to have potent insulinotropic properties, but the biological importance of other glucagon-related peptides remains unclear. The recent advances that have increased our understanding of the biology of glucagon and the glucagon-like peptides are reviewed.