gebhart/patrepeval huggingface dataset:
Stimulus Dependency and Mechanisms of Surround Modulation in Cortical Area MT (2008)

The perceptual interpretation of a given visual feature depends on the surrounding context. To explore the neural mechanisms underlying such contextual interactions in the motion domain, we studied responses of neurons in the middle temporal area (MT) of macaque monkeys while presenting a variety of center-surround stimuli that stimulated both the classical receptive visual field (CRF) and the receptive field surround. In human psychophysical experiments, the perceptual impact of the surround stimulus on the center stimulus varied from motion capture ("integration") to motion contrast ("segmentation"). In our neurophysiological experiments, the directional tuning of surround modulation with these stimuli ranged from antagonistic (consistent with motion contrast) to integrative (consistent with motion capture) and agreed qualitatively with perception under some but not all conditions. Most strikingly, for a stimulus that elicited perceptual motion contrast, surround modulation was integrative if the CRF stimulus was ambiguous due to the aperture problem. In addition, we found that surround modulation was linked to response magnitude: stimuli eliciting the largest responses yielded the strongest antagonism and those eliciting the smallest responses yielded the strongest integration. We developed a neural network model that accounts for this finding as well as a previous finding that surround suppression in area MT is contrast-dependent. Our findings suggest that changes in MT surround modulation result from shifts in the balance between directionally tuned excitation and inhibition mediated by changes in input strength. We speculate that input strength is, in turn, linked with the ambiguity of the motion present within the CRF.
Functional and molecular characterisation of EO771.LMB tumours, a new C57BL/6-mouse-derived model of spontaneously metastatic mammary cancer (2015)

The translation of basic research into improved therapies for breast cancer patients requires relevant preclinical models that incorporate spontaneous metastasis. We have completed a functional and molecular characterisation of a new isogenic C57BL/6 mouse model of breast cancer metastasis, comparing and contrasting it with the established BALB/c 4T1 model. Metastatic EO771.LMB tumours were derived from poorly metastatic parental EO771 mammary tumours. Functional differences were evaluated using both in vitro assays and spontaneous metastasis assays in mice. Results were compared to non-metastatic 67NR and metastatic 4T1.2 tumours of the 4T1 model. Protein and transcript levels of markers of human breast cancer molecular subtypes were measured in the four tumour lines, as well as p53 (Tp53) tumour-suppressor gene status and responses to tamoxifen in vivo and in vitro. Array-based expression profiling of whole tumours identified genes and pathways that were deregulated in metastatic tumours. EO771.LMB cells metastasised spontaneously to lung in C57BL/6 mice and displayed increased invasive capacity compared with parental EO771. By immunohistochemical assessment, EO771 and EO771.LMB were basal-like, as was the 4T1.2 tumour, whereas 67NR had a luminal phenotype. Primary tumours from all lines were negative for progesterone receptor, Erb-b2/Neu and cytokeratin 5/6, but positive for epidermal growth factor receptor (EGFR). Only 67NR displayed nuclear estrogen receptor alpha (ERα) positivity. EO771 and EO771.LMB expressed mutant p53, whereas 67NR and 4T1.2 were p53-null. Integrated molecular analysis of both the EO771/EO771.LMB and 67NR/4T1.2 pairs indicated that upregulation of matrix metalloproteinase-3 (MMP-3), parathyroid hormone-like hormone (Pthlh) and S100 calcium binding protein A8 (S100a8) and downregulation of the thrombospondin receptor (Cd36) might be causally involved in metastatic dissemination of breast cancer.
Cloning and characterization of the mouse neu promoter. (1992)

We have isolated a genomic clone containing the mouse neu gene. The 5' end of the mouse neu gene was localized by Southern analysis, subcloned and characterized. DNA sequence analysis revealed that the promoter region is 67% G+C-rich and lacks a TATA box, although a CAAT box is present. By sequence comparison, we identified several consensus recognition sequences for general transcription factors such as Sp1, E4TF1, AP2, OTF-1 and GCF, as well as recognition sequences for RVF, E1A and GTG, which have recently been identified in the rat neu promoter. Functional promoter activity was demonstrated by the ability of the promoter to drive transcription of the bacterial chloramphenicol acetyltransferase gene. Using a series of 5'-end deletion mutants, we have identified multiple positive and negative cis-acting elements that regulate mouse neu gene transcription.
A plate reader-compatible microchannel array for cell biology assays (2007)

The use of microfluidic devices for studying cell biology holds considerable promise when compared to canonical culture systems. However, the lack of compatibility with existing infrastructure hinders the application of microfluidic devices in the life sciences. Here, we present a microchannel cell culture platform having both operational (compatible with plate readers and pipetting) and performance (lower detection limits, controlled microenvironment) advantages. We demonstrated rapid growth assays and immunocytochemistry on mammary epithelial cells (both a cell line and primary cells) in the microchannel arrays. The utilization of ubiquitous pipetting methods and plate reader endpoints lowers the barriers to use. The simplicity and flexibility of the platform, combined with the throughput of automated detection systems, will facilitate the adoption of microfluidic culture systems in biological laboratories.
Fabrication of low loss and high speed silicon optical modulator using doping compensation method (2011)

Compared with an optical modulator based on lithium niobate, the total loss of the current high speed silicon modulator is still too high for commercial use. Reduction of the total loss always comes along with the degradation of the other two characteristics including modulation efficiency or switching speed. In this paper, we reduce the phase shifter loss through optimizing the doping level out of the depletion region while keeping the modulation efficiency and switching speed at a high level. Compensated doping method is utilized to optimize the doping level on the cross section of the phase shift. With doping compensation, the Loss·Efficiency figure-of-merit (FOM) of 4 mm phase shifter is reduced from 25.8 dB·V to 19.4 dB·V while still keeping the small signal 3 dB-bandwidth at about 10 GHz. After doping profile optimizing, the measured bandwidth of the phase shifter with doping compensation can even reaches 17 GHz with a Loss·Efficiency FOM of about 25.4 dB·V.
Influence of adenovirus and MVA vaccines on the breadth and hierarchy of T cell responses (2016)

Viral-vectored vaccines are in clinical development for several infectious diseases where T-cell responses can mediate protection, and responses to sub-dominant epitopes is needed. Little is known about the influence of MVA or adenoviral vectors on the hierarchy of the dominant and sub-dominant T-cell epitopes. We investigated this aspect in mice using a malaria immunogen. Our results demonstrate that the T-cell hierarchy is influenced by the timing of analysis, rather than by the vector after a single immunization, with hierarchy changing over time. Repeated homologous immunization reduced the breadth of responses, while heterologous prime-boost induced the strongest response to the dominant epitope, albeit with only modest response to the sub-dominant epitopes.
Cutting Edge: Selective Requirement for the Wiskott-Aldrich Syndrome Protein in Cytokine, but Not Chemokine, Secretion by CD4+ T Cells (2004)

The mechanism of cytokine secretion is not well understood, but cytokines appear to be synthesized and released in a polarized fashion toward an Ag-specific target cell. In this study, we demonstrate that the Wiskott-Aldrich syndrome protein (WASp) is an essential component of the cytokine secretory pathway in CD4(+) T cells. Murine WASp-deficient CD4(+) T cells fail to polarize cytokines toward a target and show an unexpected and striking block in cytokine secretion. In contrast, chemokine secretion and trafficking of plasma membrane proteins, transported via the constitutive secretory pathway, are unaffected by the lack of WASp. These results suggest that CD4(+) T cell cytokines require a specialized, WASp-dependent pathway for cellular traffic and/or vesicle release that is distinct from that required for chemokine release. We propose that the use of different secretory pathways for cytokines and chemokines enables CD4(+) T cell activity to be further fine-tuned to serve specialized effector functions.
Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease (2001)

Spinal cord injury results in a massive loss of neurons, and thus of function. We recently reported that passive transfer of autoimmune T cells directed against myelin-associated antigens provides acutely damaged spinal cords with effective neuroprotection. The therapeutic time window for the passive transfer of T cells was found to be at least 1 week. Here we show that posttraumatic T cell-based active vaccination is also neuroprotective. Immunization with myelin-associated antigens such as myelin basic protein (MBP) significantly promoted recovery after spinal cord contusion injury in the rat model. To reduce the risk of autoimmune disease while retaining the benefit of the immunization, we vaccinated the rats immediately after severe incomplete spinal cord injury with MBP-derived altered peptide ligands. Immunization with these peptides resulted in significant protection from neuronal loss and thus in a reduced extent of paralysis, assessed by an open-field behavioral test. Retrograde labeling of the rubrospinal tracts and magnetic resonance imaging supported the behavioral results. Further optimization of nonpathogenic myelin-derived peptides can be expected to lead the way to the development of an effective therapeutic vaccination protocol as a strategy for the prevention of total paralysis after incomplete spinal cord injury.
gp96-Peptide Vaccination of Mice against Intracellular Bacteria (2001)

This work demonstrates that gp96 preparations isolated from cells infected with intracellular bacteria induce cytotoxic T-lymphocyte responses and confer protection. Our findings extend previous reports on the immunogenicity of gp96-associated peptides to antigens derived from intracellular bacteria. Immunization with gp96 may therefore represent a promising vaccination strategy against bacterial pathogens.
Real-time surveillance video display with salience (2005)

In this paper, we aim at providing a means for efficient display of surveillance video. In video surveillance, usually, there are certain regions of interest (ROIs), such as entrance or exit, and moving objects or persons, which should be paid more attention. By tracking and locally zooming the ROI, the proposed method adds salience on it to help surveillant to locate such important region effectively. Here, salience means highlighting special region locally. Given an input video signal, the ROI is detected first. The original video frame is mapped as a texture on a deformed mesh to produce the zoom effect. The position and shape of the ROI determine the mesh deformation. By experiment, we show that the proposed method is effective and efficient.
Catalytic Asymmetric Boration of Acyclic α,β‐Unsaturated Esters and Nitriles (2007)

Die asymmetrische β-Borierung acyclischer α,β-ungesättigter Carbonylverbindungen führt glatt zu enantiomerenangereicherten funktionalisierten Organoborverbindungen. Verschiedenste acyclische ungesättigte Ester und Nitrile reagierten bei Raumtemperatur hoch enantioselektiv und mit guten Ausbeuten in Gegenwart eines Kupferkatalysators und planar-chiraler Diphosphanliganden.
The Amsterdam Hypermedia Model: Extending Hypertext to Support Real Multimedia (1993)

We present a model of hypermedia that allows the combination of ‘hyper-structured’ information with dynamic multimedia information. The model is derived by extending the Dexter hypertext reference model and the CMIF multimedia model. The Amsterdam hypermedia model allows the following, in addition to the model provided by Dexter: * the composition of multiple dynamic media, in order to specify a collection of time-based media making up a complete multimedia presentation;* the definition of channels for specifying default presentation information, allowing the specification of the presentation characteristics of nodes at a more general level than that for an individual node;* the composition of existing presentations into larger presentations, taking into account possible clashes of resource usage;* the inclusion of temporal relations while maintaining the separation of structure and presentation information, where time-based relationships are treated as presentation information;* the definition of context for the source and destination anchors of a link in order to specify the parts of a presentation affected on following the link.The Amsterdam hypermedia model enables the description of structured multimedia documents, incorporating time at a fundamental level, and extending the hypertext notion of links to time-based media and compositions of different media.The paper is organised as follows. The Dexter hypertext model and the CMIF multimedia model are summarised, and their limitations for use as a more general hypermedia model are discussed. The extensions included in the Amsterdam hypermedia model are described and a summary of the resulting model is given.
Adaptive reorder buffers for SMT processors (2006)

In SMT processors, the complex interplay between private and shared datapath resources needs to be considered in order to realize the full performance potential. In this paper, we show that blindly increasing the size of the per-thread reorder buffers to provide a larger number of in-flight instructions does not result in the expected performance gains but, quite in contrast, degrades the instruction throughput for virtually all multithreaded workloads. The reason for this performance loss is the excessive pressure on the shared datapath resources, especially the instruction scheduling logic. We propose intelligent mechanisms for dynamically adapting the number of reorder buffer entries allocated to each thread in an effort to avoid such allocations if they detrimentally impact the scheduler. We achieve this goal through categorizing the program execution into issue-bound and commit-bound phases and only performing the buffer allocations to the threads operating in commit-bound phases. Our adaptive technique achieves improvements of 21% in instruction throughput and 10% in the fairness metric compared to the best performing baseline configuration with static ROBs.
Characterization of product-related low molecular weight impurities in therapeutic monoclonal antibodies using hydrophilic interaction chromatography coupled with mass spectrometry (2018)

Traditional SDS-PAGE method and its modern equivalent CE-SDS method are both widely applied to assess the purity of therapeutic monoclonal antibody (mAb) drug products. However, structural identification of low molecular weight (LMW) impurities using those methods has been challenging and largely based on empirical knowledges. In this paper, we present that hydrophilic interaction chromatography (HILIC) coupled with mass spectrometry analysis is a novel and orthogonal method to characterize such LMW impurities present within a purified mAb drug product sample. We show here that after removal of N-linked glycans, the HILIC method separates mAb-related LMW impurities with a size-based elution order. The subsequent mass measurement from a high-resolution accurate mass spectrometer provides direct and unambiguous identification of a variety of low-abundance LMW impurities within a single LC-MS analysis. Free light chain, half antibody, H2L species (antibody possessing a single light chain) and protein backbone-truncated species can all be confidently identified and elucidated in great detail, including the truncation sites and associated post-translational modifications. It is worth noting that this study provides the first example where the H2L species can be directly detected in a mAb drug product sample by intact mass analysis without prior enrichment.
Energy separation in signal modulations with application to speech analysis (1993)

An efficient solution to the fundamental problem of estimating the time-varying amplitude envelope and instantaneous frequency of a real-valued signal that has both an AM and FM structure is provided. Nonlinear combinations of instantaneous signal outputs from the energy operator are used to separate its output energy product into its AM and FM components. The theoretical analysis is done first for continuous-time signals. Then several efficient algorithms are developed and compared for estimating the amplitude envelope and instantaneous frequency of discrete-time AM-FM signals. These energy separation algorithms are used to search for modulations in speech resonances, which are modeled using AM-FM signals to account for time-varying amplitude envelopes and instantaneous frequencies. The experimental results provide evidence that bandpass-filtered speech signals around speech formants contain amplitude and frequency modulations within a pitch period.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Specific inhibition of bcr-abl gene expression by small interfering RNA (2003)

Small interfering RNAs (siRNAs) were designed to target the bcr-abl oncogene, which causes chronic myeloid leukemia (CML) and bcr-abl-positive acute lymphoblastic leukemia (ALL). Chemically synthesized anti-bcr-abl siRNAs were selected using reporter gene constructs and were found to reduce bcr-abl mRNA up to 87% in bcr-abl-positive cell lines and in primary cells from CML patients. This mRNA reduction was specific for bcr-abl because c-abl and c-bcr mRNA levels remained unaffected. Furthermore, protein expression of BCR-ABL and of laminA/C was reduced by specific siRNAs up to 80% in bcr-abl-positive and normal CD34(+) cells, respectively. Finally, anti-bcr-abl siRNA inhibited BCR-ABL-dependent, but not cytokine-dependent, proliferation in a bcr-abl-positive cell line. These data demonstrate that siRNA can specifically and efficiently interfere with the expression of an oncogenic fusion gene in hematopoietic cells.
Passive chloride permeability charge coupled to H(+)-ATPase of avian osteoclast ruffled membrane (1991)

We prepared proton-transporting membrane vesicles from the avian osteoclast's ruffled membrane, a specialized region of the cell surface that acidifies the bone resorption space. We demonstrated a unique conductive Cl- permeability that is charge coupled to the vesicle H(+)-ATPase and is required for acidification. Ion replacement indicated an anion selectivity of Br- approximately Cl- greater than SO4(2-) greater than NO3- approximately SCN- in supporting acidification. The anion channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (10 microM) was a competitive inhibitor of acidification and raised the Michaelis constant for ATP of the proton pump approximately 11-fold in 120 mM KCl. Inhibition was reversed by valinomycin, which provides an alternate path for charge neutralization. The Cl- dependence of acidification was nonlinear and yielded a Hill coefficient of 3-4, showing that it is distinct from a linear Cl- dependence reported for acidification of renal cortical endosomes. The K+ ionophore valinomycin augmented H+ transport in K2SO4, and not in KCl. Dependence of Cl- transport on membrane potential was confirmed by direct measurement of 36Cl- transport. We uncoupled charge transport from proton transport with a large excess of ammonia, which had no effect on 36Cl- accumulation in vesicles, and by measuring 36Cl- accumulation in response to a membrane diffusion potential, produced with a [K+] gradient and valinomycin in the absence of ATP. These experiments demonstrate that the electrogenic proton pump of the osteoclast ruffled membrane is charge coupled to a passive Cl- permeability in the same membrane.
From engineering crystals to engineering molecules: emergent consequences of controlling reactivity in the solid state using linear templates (2002)

Molecules that function as linear templates provide a means to organize two molecules, using the principles of molecular recognition and self-assembly, for a bimolecular reaction. The design and application of linear templates in order to direct reactivity in organic solids, particularly [2 + 2] photoreactivity, is outlined. The linear templates provide control of solid-state reactivity such that it is possible, in a similar way to the liquid phase, to conduct molecular synthesis by design.
Characterization of a Ca2+/Calmodulin-dependent Protein Kinase Cascade (1995)

Recent studies have demonstrated that Ca2+/calmodulin-dependent protein kinase IV (CaM-kinase IV) can mediate Ca(2+)-dependent regulation of gene expression through the phosphorylation of transcriptional activating proteins. We have previously identified and purified a 68-kDa rat brain CaM-kinase kinase that phosphorylates and increases total and Ca(2+)-independent activities of CaM-kinase IV (Tokumitsu, H., Brickey, D. A., Gold, J., Hidaka, H., Sikela, J., and Soderling, T. R. (1994) J. Biol. Chem. 269, 28640-28647). Using a partial amino acid sequence of the purified brain kinase, a CaM-kinase kinase cDNA was cloned from a rat brain cDNA library. Northern blot analysis showed that CaM-kinase kinase mRNA (3.4 kilobases) was expressed in rat brain, thymus, and spleen. Sequence analyses revealed that the cDNA encoded a 505-amino acid protein, which contained consensus protein kinase motifs and was 30-40% homologous with members of the CaM-kinase family. Expression of the cDNA in COS-7 cells yielded an apparent 68-kDa CaM-binding protein, which catalyzed in vitro activation in the presence of Mg2+/ATP and Ca2+/ CaM of CaM-kinases I and IV but not of CaM-kinase II. Co-expression of CaM-kinase kinase with CaM-kinase IV gave a 14-fold enhancement of cAMP-response element-binding protein-dependent gene expression compared with CaM-kinase IV alone. These results are consistent with the hypothesis that CaM-kinases I and IV are regulated through a unique signal transduction cascade involving CaM-kinase kinase.
Bradycardia and asystole induced by partial seizures (1997)

Bradyarrhythmias associated with partial seizures are uncommon, with most reported patients having temporal lobe seizure foci on scalp EEG recordings. We report a patient with bradycardia and sinus arrest during a complex partial seizure documented during bilateral subdural EEG and EEG and simultaneous video and EEG recordings. The seizure began in the left temporal lobe and spread to the right temporal region, with bradycardia occurring 55 seconds after ictal onset and asystole after 60 seconds.