gebhart/patrepeval huggingface dataset:
Induction of acetylcholine receptor clustering by native polystyrene beads Implication of an endogenous muscle-derived signalling system (1992)

Aneural muscle cells in culture often form acetylcholine receptor (AChR) clusters, termed hot spots, which are similar to those found at the postsynaptic membrane both in structure and in molecular composition. Although hot spots form on both dorsal and ventral surfaces of the cell, the ventral ones are better characterized because of their association with sites of cell-substratum contact. To understand the stimuli and mechanisms involved in ventral hot spot formation, native, uncoated polystyrene beads were applied to cultured Xenopus myotomal muscle cells to create local membrane-substratum contacts. These beads were able to induce a postsynaptic-type development as evidenced by the clustering of AChRs and the development of a set of ultrastructural specializations, including membrane infoldings and a basement membrane. Whereas these native beads were effective in inducing clustering, beads coated with bovine serum albumin or treated with serum-containing medium were ineffective. Native beads were also capable of inducing clusters in serum-free medium, indicating that their effect was mediated by endogenous molecules that were locally presented by the beads, rather than by bead adsorption of components in the medium. Heparan sulfate proteoglycan (HSPG) is a major component of the muscle extracellular matrix and our previous study has shown that basic fibroblast growth factor (bFGF), a member of the heparin-binding growth factor (HBGF) family, and its receptor are present in Xenopus myotomal muscle during the period of synaptogenesis. Therefore, we tested the involvement of HBGF in bead induction. The results of this study show the following: (1) preincubation of cultures in heparin, which solubilizes matrix-bound HBGFs, suppressed the bead-induced AChR clustering. (2) Suramin, which interferes with the interaction between several growth factors and their receptors, also inhibited bead-induced clustering. (3) Tyrphostin, which blocks tyrosine kinase activity associated with a number of growth factor receptors, was also inhibitory to the bead effect. (4) The percentage of bead-induced AChR clusters was significantly enhanced by pretreating the cultures with bFGF prior to bead application. This exogenously applied bFGF could be largely removed by treatment of cultures with heparin, suggesting its association with HSPG at the cell surface. (5) An anti-bFGF neutralizing antiserum significantly reduced the efficacy of the bead stimulation. These data suggest that uncoated beads, which adhere to the cell surface and can mimic the cell-substratum interaction, effect a local presentation of HBGFs, such as bFGF, residing with the HSPG to their membrane receptors, thereby locally activating receptor-associated tyrosine kinases.(ABSTRACT TRUNCATED AT 400 WORDS)
Cell-Type-Specific Activation of PAK2 by Transforming Growth Factor β Independent of Smad2 and Smad3 (2003)

Transforming growth factor beta (TGF-beta) causes growth arrest in epithelial cells and proliferation and morphological transformation in fibroblasts. Despite the ability of TGF-beta to induce various cellular phenotypes, few discernible differences in TGF-beta signaling between cell types have been reported, with the only well-characterized pathway (the Smad cascade) seemingly under identical control. We determined that TGF-beta receptor signaling activates the STE20 homolog PAK2 in mammalian cells. PAK2 activation occurs in fibroblast but not epithelial cell cultures and is independent of Smad2 and/or Smad3. Furthermore, we show that TGF-beta-stimulated PAK2 activity is regulated by Rac1 and Cdc42 and dominant negative PAK2 or morpholino antisense oligonucleotides to PAK2 prevent the morphological alteration observed following TGF-beta addition. Thus, PAK2 represents a novel Smad-independent pathway that differentiates TGF-beta signaling in fibroblast (growth-stimulated) and epithelial cell (growth-inhibited) cultures.
Distributed sequences and search process (2004)

An analytical approach to a search process for a set of M fixed sequences in random data covers the problems of a search for the sequences with errors, as well as of a search for the distributed sequences. It is of greater practical interest than the formerly analysed case of search for a single sequence. This paper derives statistical parameters (probability distribution function, expected value, variance) of this process, introducing a new term "cross-bifix". The derived formulae are applied to the case of search for distributed sequences with errors.
Ontology-Based Approach for Managing Personal Health and Wellness Information (2007)

This paper describes a new approach for collecting and sharing personal health and wellness information. The approach is based on a Personal Health Record (PHR) including both clinical and non-clinical data. The PHR is located on a network server referred as Common Server. The overall service architecture for providing anonymous and private access to the PHR is described. Semantic interoperability is based on an ontology collection and usage of OID (Object Identifier) codes. The formal (upper) ontology combines a set of domain ontologies representing different aspects of personal health and wellness. The ontology collection emphasizes wellness aspects while clinical data is modelled by using OID references to existing vocabularies. Modular ontology approach enables distributed management and expansion of the data model.
Active mode-locking characteristics of InGaAsP-single mode fiber composite cavity lasers (1986)

Composite-cavity semiconductor lasers using integral single-mode fiber resonators are capable of producing short-duration mode-locked optical pulses at very high repetition rates. This paper summarizes recent experiments using a composite-cavity structure with an efficient single-mode fiber output port. The dependence of pulse-width on the electrical drive waveform and the repetition rate is investigated, and limitations on the pulsewidth are discussed.
Proxemic peddler (2012)

Effective street peddlers monitor passersby, where they tune their message to capture and keep the passerby's attention over the entire duration of the sales pitch. Similarly, advertising displays in today's public environments can be more effective if they were able to tune their content in response to how passersby were attending them vs. just showing fixed content in a loop. Previously, others have prototyped displays that monitor and react to the presence or absence of a person within a few proxemic (spatial) zones surrounding the screen, where these zones are used as an estimate of attention. However, the coarseness and discrete nature of these zones mean that they cannot respond to subtle changes in the user's attention towards the display. In this paper, we contribute an extension to existing proxemic models. Our Peddler Framework captures (1) fine-grained continuous proxemic measures by (2) monitoring the passerby's distance and orientation with respect to the display at all times. We use this information to infer (3) the passerby's interest or digression of attention at any given time, and (4) their attentional state with respect to their short-term interaction history over time. Depending on this attentional state, we tune content to lead the passerby into a more attentive stage, ultimately resulting in a purchase. We also contribute a prototype of a public advertising display -- called Proxemic Peddler -- that demonstrates these extensions as applied to content from the Amazon.com website.
Growth of continuous bonelike mineral within porous poly(lactide-co-glycolide) scaffoldsin vitro (2000)

Strategies to engineer bone have focused on the use of natural or synthetic degradable materials as scaffolds for cell transplantation or as substrates to guide bone regeneration. The basic requirements of the scaffold material are biocompatibility, degradability, mechanical integrity, and osteoconductivity. A major design problem is satisfying each of these requirements with a single scaffold material. This study addresses this problem by describing an approach to combine the biocompatibility and degradability of a polymer scaffold with the osteoconductivity and mechanical reinforcement of a bonelike mineral film. We report the nucleation and growth of a continuous carbonated apatite mineral on the interior pore surfaces of a porous, degradable polymer scaffold via a one step, room temperature incubation process. A 3-dimensional, porous scaffold of the copolymer 85:15 poly(lactide-co-glycolide) was fabricated by a solvent casting, particulate leaching process. Fourier transform IR spectroscopy and scanning electron microscopy (SEM) analysis after different incubation times in a simulated body fluid (SBF) demonstrate the growth of a continuous bonelike apatite layer within the pores of the polymer scaffold. Quantification of phosphate on the scaffold displays the growth and development of the mineral film over time with an incorporation of 0.43 mg of phosphate (equivalent to 0.76 mg of hydroxyapatite) per scaffold after 14 days in SBF. The compressive moduli of polymer scaffolds increased fivefold with formation of a mineral film after a 16-day incubation time as compared to control scaffolds. In summary, this biomimetic treatment provides a simple, one step, room temperature method for surface functionalization and subsequent mineral nucleation and growth on biodegradable polymer scaffolds for tissue engineering.
Building dynamic strategic capabilities: a human capital perspective (2011)

Abstract Based upon the dynamic perspective of RBV, we incorporated SHRM and organizational change literature to examine the processes of developing a firm's dynamic strategic capabilities through strategic human capital leveraging coupled with human-capital-oriented restructuring to cope with rapidly changing environments. Findings from 154 firms show that a total mediation model identifies that strategic human capital leveraging not only catches the benefits of complementary human capital process (deployment and inimitability) fitted to a firm's strategic need but also needs the co-specialized human-capital-oriented restructuring to facilitate a firm's flexible capabilities. Maintaining dynamic strategic capabilities requires firms to leverage their human capital for not only achieving maximum productivity but also contributing to core competence so that they will become distinctive and constantly be reconfigured and adapted in the process of organizational restructuring in correspondence with the dynamic environment. Keywords: dynamic strategic capabilitieshuman-capital-oriented restructuringstrategic human capital leveraging
Recent Syntheses and Reactions of Cyclic Imidic Esters (1966)

Abstract Δ 2 ‐Oxazolines and 4H‐5,6‐dihydrooxazines are readily obtainable from carboxylic acids and 2‐ or 3‐amino alcohols by gas‐phase dehydration, and 4H‐dihydrooxazines can also be obtained by condensation of N‐(hydroxymethyl) carboxamides with olefins. These cyclic imidic esters undergo reactions in which the ring is cleaved; these reactions include a new type of polymerization. The behavior of alkyl groups in position 2 and the cyclodditions in the 2,3‐position also have been studied. Reactions in side chains on position 2 and addition experiments on the sulfur analogues of the cyclic imidic esters are also reported. A table shows the principal infrared bands of substituted Δ 2 ‐oxazolines.
In vivo antinociceptive activity of anti-rat mGluR1 and mGluR5 antibodies in rats (1998)

To examine the specific roles of group I metabotropic glutamate receptors (mGluRs) in nociceptive processing, we examined the effects of intrathecal (i.t.) treatment with antibodies raised against the C-terminals of mGluR1 and mGluR5 in various rat pain models. The effects of anti-mGluR1 IgG and anti-mGluR5 IgG were assessed in a model of persistent pain induced by intrathecal administration of the mGluR1/5 agonist DHPG, as well as in models of heat pain (plantar test), chemical pain (formalin test) and neuropathic pain. DHPG-induced spontaneous nociceptive behaviours (SNB) were significantly attenuated by i.t. treatment with either anti-mGluR1 IgG (30 microg) or anti-mGluR5 IgG (10 and 30 microg). Neither anti-mGluR1 IgG (30 microg) nor anti-mGluR5 IgG (30 microg) significantly increased response latencies to noxious heat in the plantar test, compared with anti-rat IgG (control IgG). Moreover, neither antibody (30 microg) significantly reduced formalin pain scores as compared to control IgG. However, i.t. treatment with anti-mGluR1 IgG (30 microg) or anti-mGluR5 IgG (30 microg) significantly reduced cold hypersensitivity exhibited 8 days after constriction injury of the sciatic nerve, supporting the contention that group I mGluRs play a role in the development of neuropathic pain. Because these antibodies were effective against neuropathic pain, and not acute heat or chemical noxious stimuli, these results suggest that mGluRs are involved in nociceptive processing in chronic pain states rather than signaling acute noxious stimuli, and that DHPG-induced pain may be mediated by similar mechanisms as neuropathic pain.
A modified mammalian tandem affinity purification procedure to prepare functional polycystin‐2 channel (2004)

The tandem affinity purification (TAP) procedure was initially developed as a tool for rapid purification of native protein complexes expressed at their natural levels in yeast cells. This purification procedure was also applied to study interactions between soluble proteins in mammalian cells. In order to apply this procedure to mammalian membrane proteins, we created a modified TAP tag expression vector and fused with the PKD2 gene, encoding a membrane cation channel protein, polycystin-2, mutated in 15% of autosomal dominant polycystic kidney disease. We generated epithelial Madin-Darby canine kidney cell line stably expressing TAP-tagged polycystin-2, improved the subsequent steps for membrane protein release and stability, and succeeded in purifying this protein. Using patch clamp electrophysiology, we detected specific polycystin-2 channel activities when the purified protein was reconstituted into a lipid bilayer system. Thus, this modified TAP procedure provides a powerful alternative to functionally characterize membrane proteins, such as ion channels, transporters and receptors, using cell-free system derived from mammalian cells.
Convergence between public switching and the Internet (1998)

The Internet has developed into a global data network that is highly accepted as a multimedia information platform which has the potential to develop into an alternative carrier network in the future. Telecom operators increasingly act as Internet service providers to maximize network utilization, to attract or retain customers, and to generate additional revenue. To leverage their installed base in the PSTN/ISDN the optimal strategy for telco ISPs is the integration of their point of presence into the central office packetizing and grooming of IP traffic in the local office relieves load on the PSTN/ISDN trunk network, resolves existing bottlenecks due to Internet traffic upstream of the CO, and creates new opportunities for revenue-generating features for both telephony and Internet subscribers. This article shows that current telecommunication network elements can be upgraded with innovate cutting-edge technology to build a solid basis for a seamless multimedia network of tomorrow, thereby enabling telecom operators' and service providers' tremendous investment in existing network infrastructure to be fully utilized. An integrated Internet services platform is presented which turns the CO switch into an optimized link between the PSTN/ISDN and the Internet. Technically, it is proposed that the central office be expanded with an integrated Internet PoP (IPOP) configured from the following IP components: an internal high-speed data backbone (ATM or Ethernet); modem pools to terminate dial-in calls from analog modems using the PPP protocol; protocol handlers for UDP, TCP, IP, and lower-layer data protocols (X.25, frame relay, SMDS, etc.); access to data networks; IP router, RADIUS server, and name server database; a contents server (optionally), enabling telco ISPs to become content providers. This effectively turns the CO into an Internet access point that integrates smoothly into the existing telco OA&M/TMN. The IP functions integrated in the IPOP can interwork closely with PSTN/ISDN call processing.
Genome Mining Demonstrates the Widespread Occurrence of Gene Clusters Encoding Bacteriocins in Cyanobacteria (2011)

Cyanobacteria are a rich source of natural products with interesting biological activities. Many of these are peptides and the end products of a non-ribosomal pathway. However, several cyanobacterial peptide classes were recently shown to be produced through the proteolytic cleavage and post-translational modification of short precursor peptides. A new class of bacteriocins produced through the proteolytic cleavage and heterocyclization of precursor proteins was recently identified from marine cyanobacteria. Here we show the widespread occurrence of bacteriocin gene clusters in cyanobacteria through comparative analysis of 58 cyanobacterial genomes. A total of 145 bacteriocin gene clusters were discovered through genome mining. These clusters encoded 290 putative bacteriocin precursors. They ranged in length from 28 to 164 amino acids with very little sequence conservation of the core peptide. The gene clusters could be classified into seven groups according to their gene organization and domain composition. This classification is supported by phylogenetic analysis, which further indicated independent evolutionary trajectories of gene clusters in different groups. Our data suggests that cyanobacteria are a prolific source of low-molecular weight post-translationally modified peptides.
The natural human IgG anti-F(ab')2 antibody recognizes a conformational IgG1 hinge epitope. (1995)

Natural IgG anti-F(ab')2 Abs are part of the physiologic immune repertoire and have important immunoregulatory functions. Although previous work suggested that some of these Abs recognize epitopes located in the constant region of the F(ab')2 molecule, an exact epitope mapping has not been performed. We found that the anti-F(ab')2 Ab binds strongly to F(ab')2 but only weakly to Fab fragments. Fab fragments are lacking the core and lower hinge region. In our experiments, we show that the IgG anti-F(ab')2 Ab binds strongly to a synthetic double chain peptide (225-237/225'-237') comprising the core and lower hinge region of the human IgG1 molecule. In contrast, it binds only weakly to the same peptide in monomeric form (225-237) or to a short double chain hinge peptide (225-232/225'-232'). The double chain peptides comprise a cyclic region between the two cystine bridges and an exocyclic region. Previous nuclear magnetic resonance analyses showed that the cyclic portion of the short double chain hinge peptide adopts the same conformation as that found in the intact IgG1 molecule. The dichroic properties of the short and long double chain hinge peptides indicate that they have identical conformations in their cyclic regions, but have different conformations in their exocyclic regions. The conformational differences in the exocyclic regions explain the binding of the Ab to the long double chain hinge peptide and the lack of binding to the short one. The circular dichroism spectrum of the monomeric hinge peptide, which is not recognized by the Ab, is consistent with the absence of an ordered peptide structure. These findings lead us to conclude that the IgG anti-F(ab')2 Ab recognizes a conformational IgG1 hinge epitope.
MITTS: Memory Inter-arrival Time Traffic Shaping (2016)

Memory bandwidth severely limits the scalability and performance of multicore and manycore systems. Application performance can be very sensitive to both the delivered memory bandwidth and latency. In multicore systems, a memory channel is usually shared by multiple cores. Having the ability to precisely provision, schedule, and isolate memory bandwidth and latency on a per-core basis is particularly important when different memory guarantees are needed on a per-customer, per-application, or per-core basis. Infrastructure as a Service (IaaS) Cloud systems, and even general purpose multicores optimized for application throughput or fairness all benefit from the ability to control and schedule memory access on a fine-grain basis. In this paper, we propose MITTS (Memory Inter-arrival Time Traffic Shaping), a simple, distributed hardware mechanism which limits memory traffic at the source (Core or LLC). MITTS shapes memory traffic based on memory request inter-arrival time, enabling fine-grain bandwidth allocation. In an IaaS system, MITTS enables Cloud customers to express their memory distribution needs and pay commensurately. For instance, MITTS enables charging customers that have bursty memory traffic more than customers with uniform memory traffic for the same aggregate bandwidth. Beyond IaaS systems, MITTS can also be used to optimize for throughput or fairness in a general purpose multi-program workload. MITTS uses an online genetic algorithm to configure hardware bins, which can adapt for program phases and variable input sets. We have implemented MITTS in Verilog and have taped-out the design in a 25-core 32nm processor and find that MITTS requires less than 0.9% of core area. We evaluate across SPECint, PARSEC, Apache, and bhm Mail Server workloads, and find that MITTS achieves an average 1.18× performance gain compared to the best static bandwidth allocation, a 2.69× average performance/cost advantage in an IaaS setting, and up to 1.17x better throughput and 1.52× better fairness when compared to conventional memory bandwidth provisioning techniques.
Neoepitopes as Cancer Immunotherapy Targets: Key Challenges and Opportunities (2017)

Over the last half century, it has become well established that cancers can elicit a host immune response that can target them with high specificity. Only within the last decade, with the advances in high-throughput gene sequencing and bioinformatics approaches, are we now on the forefront of harnessing the host's immune system to treat cancer. Recently, some strides have been taken toward understanding effective tumor-specific MHC I restricted epitopes or neoepitopes. However, many fundamental questions still remain to be addressed before this therapy can live up to its full clinical potential. In this review, we discuss the major hurdles that lie ahead and the work being done to address them.