gebhart/patrepeval huggingface dataset:
Motif Trap: a rapid method to clone motifs that can target proteins to defined subcellular localisations (1999)

We have developed a rapid procedure termed Motif Trap (MT) to identify protein motifs that are able to target proteins to a distinct subcellular localisation in eukaryotic cells. By expressing random DNA fragments fused to green fluorescent protein (GFP), individual cells with the GFP localisation of interest are readily isolated allowing for the expressed DNA fragments to be cloned by RT-PCR. These can then be used to identify the corresponding full-length cDNAs. Using MT, we have identified patterns of GFP localisation which correspond to every major organelle and compartment. We have shown that MT is useful to identify new sequences that determine subcellular localisation as well as known targeting motifs.
ANTIBODIES TO COMPLEMENT RECEPTOR 3 (CR3) CAN EFFECTIVELY ABROGATE EXPERIMENTAL COLITIS THROUGH DOWNREGULATION OF IL-12 SIGNALING (1998)

7 It has been shown that the intrarectal administration of the reagent TNBS leads to a dysregulated Th1 T cell (IFN-γ) response with increased IL-12 secretion in the lamina propria (LP), which mediates the onset of a transmural colitis resembling Crohn's disease. Treatment of TNBS colitis with antibodies to IL-12 results in a rapid resolution of mucosal inflammation through downregulation of this IL-12/IFN-γ pathway. These present studies explored whether antibodies directed against CR3 can effectively treat an IL-12-dependent model of inflammation. CR3 a member of the family of cell adhesion molecules and is expressed on cells such as leukocytes, natural killer cells and monocytes/macrophages. It serves as the receptor for ligands including complement fragments (C3b), and ICAM. Important functions of CR3 are cellular adhesion and transmigration however, recent reports indicate administration of antibodies to CR3 can lead to suppressed DTH responses indicating a possible role/effect on T cell function. Therefore, antibodies to CR3 were administered in vivo to mice with TNBS colitis. This resulted in significant weight gain, reversal of the diarrheal symptoms and rapid amelioration of mucosal inflammation. Furthermore, in-situ staining of colonic cryosections of mice with TNBS-colitis treated with anti-CR3 resulted in a significant decreased staining expression for IL-12 p70 heterodimer. In related studies, LP macrophages isolated from anti-CR3-treated mice produced 10 fold less IL-12 p70 when stimulated in vitro with LPS/IFN-γ. These results were corroborated by Northern blots of macrophages from such treated mice which revealed a greater than 90% decrease in p40 expression. We also determined via Western blot analysis that the mechanism by which CR3 antibodies suppress IL-12 is by the inhibition of IFN-γ-induced tyrosine phosphorylation which is vital for IL-12 synthesis. Interestingly, suppression of IL-12 from LP macrophages of untreated TNBS-colitic mice could be achieved by in vitro co-culture of macrophages with C3b. Finally, we found that LP CD4 T cells isolated from anti-CR3 treated animals also produced 80-fold less IFN-γ when stimulated in vitro, as compared to untreated TNBS group. Together, these studies suggest that IL-12 signaling crucial for the onset of Th1 mediated mucosal inflammation may be regulated by CR3/complement signaling. In addition, the targeting of this pathway may be an attractive therapeutic intervention in CD patients as genetic abnormalities have been found on chromosome 16 which has been linked to CR3.
Interactive cell injection simulation based on 3D biomechanical tensegrity model (2008)

To facilitate training of biological cell injection operations, we are developing an interactive virtual environment to simulate needle insertion into biological cells. A key challenge of deformable simulation is to satisfy the conflicting requirements of real-time interactivity and physical realism. This paper presents methodologies for dynamic modeling, visual/haptic display and model validation of cell injection. We first investigate the challenging issues in the modeling of the bio-mechanical properties of living cells. We propose a dynamic model to simulate cell deformation and puncture. The developed approach is based on the assumptions that the mechanical response of living cells is mainly determined by the cytoskeleton and that the cytoskeleton is organised as a tensegrity structure including microfilaments, microtubules and intermediate filaments. Equivalent microtubules struts are represented with a linear mass-tensor finite element model and equivalent microfilaments and intermediate filaments with viscoelastic Kelvin-Voigt elements. The virtual environment has been implemented with both graphic and haptic interfaces.
Predictors of Hospital Mortality for Patients with Severe Sepsis Treated with Drotrecogin alfa (activated) (2004)

Number of acquired organ-system derangements, vasopressin administration, and treatment with an inappropriate initial antimicrobial regimen are independently associated with an increased risk of hospital mortality among patients treated with drotrecogin alfa (activated) for severe sepsis. These findings suggest that other specific medical interventions may increase survival in this patient population.
The role of structured water in mediating general anesthetic action on α4β2 nAChR (2010)

Water is an essential component for many biological processes. Pauling proposed that water might play a critical role in general anesthesia by forming water clathrates around anesthetic molecules. To examine potential involvement of water in general anesthesia, we analyzed water within alpha4beta2 nAChR, a putative protein target hypersensitive to volatile anesthetics. Experimental structure-derived closed- and open-channel nAChR systems in a fully hydrated lipid bilayer were examined using all-atom molecular dynamics simulations. At the majority of binding sites in alpha4beta2 nAChR, halothane replaced the slow-exchanging water molecules and caused a regional water population decrease. Only two binding sites had an increased quantity of water in the presence of halothane, where water arrangements resemble clathrate-like structures. The small number of such clathrate-like water clusters suggests that the formation of water clathrates is unlikely to be a primary cause for anesthesia. Despite the decrease in water population at most of the halothane binding sites, the number of sites that can be occupied transiently by water is actually increased in the presence of halothane. Many of these water sites were located between two subunits or in regions containing agonist binding sites or critical structural elements for transducing agonist binding to channel gating. Changes in water sites in the presence of halothane affected water-mediated protein-protein interactions and the protein dynamics, which can have direct impact on protein function. Collectively, water contributes to the action of anesthetics in proteins by mediating interactions between protein subunits and altering protein dynamics, instead of forming water clathrates around anesthetics.
Interoperability Issues Between DMARC and Indirect Email Flows (2016)

DMARC introduces a mechanism for expressing domain-level policies and
preferences for message validation, disposition, and reporting. The
DMARC mechanism can encounter interoperability issues when messages
originate from third party sources, are modified in transit, or are
forwarded enroute to their final destination. Collectively these email
flows are referred to as indirect email flows. This document describes
interoperability issues between DMARC and indirect email flows.
Possible methods for addressing interoperability issues are presented.
Characterization of novel murine anti-CD20 monoclonal antibodies and their comparison to 2B8 and c2B8 (rituximab) (2007)

Rituximab is the first anti-cancer antibody approved by the FDA for the treatment of B-cell non-Hodgkin lymphoma (B-NHL), alone or in combination with chemotherapeutic drugs. Further, rituximab is now being examined in a variety of CD20+ neoplastic diseases as well as B-cell-induced autoimmune diseases. The clinical response to rituximab is significant, resulting not only in tumor regression but also prolongation of survival. However, a subset of patients does not initially respond to rituximab or develops resistance to its further treatment. Therefore, alternative therapies for these patients are strongly desired. Rituximab activity has been thought to be by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and apoptosis, and studies in model systems established the role of rituximab in cell signaling-induced perturbation of anti-apoptotic survival pathways, suggesting that the patients unresponsive to rituximab may be overcome with other CD20 antibodies with different activities. This study investigated eight novel murine antibodies directed against CD20 for their physical and biological properties in comparison with 2B8 and c2B8 (rituximab). These antibodies were derived by various antigenic and immunization procedures and selected for CD20 activity. Analysis of these antibodies revealed that they all bound to various B-cell lines and CD20-transfected CHO cells. Six of the eight antibodies shared similar variable-region amino acid sequences that were also shared by 2B8 while two monoclonal antibodies did not. Of them, 1K1791 has a distinct heavy chain and both 1K1791 and 1K1782 have distinct light chains. Not all of the antibodies inhibited cell growth and only two antibodies reacted with fixed GST-CD20 recombinant fusion protein. Noteworthy, 1K1791 was found to inhibit cell proliferation and also induced caspase-independent apoptosis in the absence of cross-linker. These findings identified new antibodies with properties and epitope specificities different from 2B8. The potential clinical application of such antibodies in the treatment of B-NHL and rituximab-resistant B-NHL is discussed.
In vitro elution characteristics of commercially and noncommercially prepared antibiotic PMMA beads. (1992)

The successful treatment of osteomyelitis with commercially prepared gentamicin-polymethylmethacrylate (PMMA) (Septopal) beads and surgical debridement has led to the use of this technique in the United States. However, commercially prepared gentamicin-PMMA beads are not currently available to orthopedic surgeons in the United States. Therefore, these surgeons commonly manufacture their own antibiotic-containing cement beads in the operating room at the time of surgery. There is little data that compare the antibiotic elution characteristics of such preparations to commercially prepared gentamicin-PMMA beads. This study compares the measured amount of antibiotic elution of either gentamicin or tobramycin from laboratory manufactured Zimmer, Simplex, or Palacos beads to commercially prepared gentamicin-PMMA (Septopal) beads. During a 30-day study period, commercially prepared gentamicin-PMMA beads eluted more total antibiotic and maintain higher concentrations than did antibiotic acrylic composites manufactured in the authors' laboratory.
Differential inhibition of T cell receptor signal transduction and early activation events by a selective inhibitor of protein-tyrosine kinase. (1990)

Engagement of the TCR (CD3-Ti) by Ag/MHC, CD3 mAb, or lectin mitogen stimulates the very early tyrosine phosphorylation of several cellular substrates including TCR-zeta. The T cell specific protein-tyrosine kinase (PTK), p56lck, has been implicated in the tyrosine phosphorylation of TCR-zeta. However, the significance of this event with regard to CD3-Ti signal transduction remains unclear. Herein, we have investigated the effect of the selective PTK inhibitor genistein (4',5,7-trihydroxyisoflavone) on cellular events associated with activation via CD3-Ti triggering. Genistein inhibited the T cell PTK, p56lck, in a dose-dependent fashion with an ID50 = 40 microM. Genistein also inhibited CD3 mAb or PHA-induced TCR-zeta chain phosphorylation in intact peripheral blood T cells. Genistein blocked the expression of IL-2 and IL-2R (CD25) in T cells stimulated with PHA/PMA or CD3 mAb/PMA, but did not inhibit the de novo expression of the CD69 early activation Ag, which is induced primarily by a PKC-dependent pathway. IL-2 and CD25 expression induced by calcium ionophore A23187 and PMA was largely refractory to inhibition by genistein, suggesting an effect of the drug on calcium-dependent pathways stimulated via CD3-Ti triggering. In this last regard, genistein partially inhibited the CD3 mAb-induced rise in [Ca2+]i but did not inhibit PHA- or CD3 mAb-induced phosphatidylinositol hydrolysis. Consequently, protein-tyrosine phosphorylation does not appear to be a prerequisite for CD3-Ti-mediated activation of phosphatidylinositol-specific phospholipase C activity and PIP2 hydrolysis. An alternative role for PTK in CD3-Ti signal transduction is suggested.
Creating New Types of Carbon-Based Membranes (2012)

Graphene oxide membranes can show unusually high water permeability, and diamond-like carbon membranes exhibited ultrafast permeation of organic solvents.
Electroanalytical and Bioelectroanalytical Systems Based on Metal and Semiconductor Nanoparticles (2004)

Abstract Metal, semiconductor and magnetic particles act as functional units for electroanalytical applications. Metal nanoparticles provide three important functions for electroanalysis. These include the roughening of the conductive sensing interface, the catalytic properties of the nanoparticles permiting their enlargement with metals and the amplified electrochemical detection of the metal deposits and the conductivity properties of nanoparticles at nanoscale dimensions that allow the electrical contact of redox‐centers in proteins with electrode surfaces. Also, metal and semiconductor nanoparticles provide versatile labels for amplified electroanalysis. Dissolution of the nanoparticle labels and the electrochemical collection of the dissolved ions on the electrode followed by the stripping‐off of the deposited metals represents a general electroanalytical procedure. These unique functions of nanoparticles were employed for developing electrochemical gas sensors, electrochemical sensors based on molecular‐ or polymer‐functionalized nanoparticle sensing interfaces, and for the construction of different biosensors including enzyme‐based electrodes, immunosensors and DNA sensors. Semiconductor nanoparticles enable the photoelectrochemical detection of analytes. Several studies have revealed the photocurrent generation by enzyme‐mediated processes and as a result of DNA hybridization. Magnetic particles act as functional components for the separation of biorecognition complexes and for the amplified electrochemical sensing of DNA or antigen/antibody complexes. Also, electrocatalytic and bioelectrocatalytic processes at electrode surfaces are switched by means of functionalized magnetic particles and in the presence of an external magnet.
Sympathetic Nerve Stimulation Versus Pancreatic Norepinephrine Infusion in the Dog: 1) Effects on Basal Release of Insulin and Glucagon* (1987)

We investigated whether pancreatic norepinephrine (NE) infusions could reproduce the inhibition of insulin secretion and the stimulation of glucagon secretion observed during sympathetic nerve stimulation in halothane-anesthetized dogs. Three minutes of stimulating the sympathetic nerves (8 Hz, 1 msec, 10 mA, n = 6) surrounding the pancreatic artery decreased both the blood flow in the superior pancreatic vein (SPV) (delta = -1.7 +/- 0.6 ml/min, P less than 0.05) and the basal pancreatic output of immunoreactive insulin (IRI) (delta = -79 +/- 5%, P less than 0.001). SPV levels of NE increased by 683 +/- 177 pg/ml (P less than 0.02). Infusion of NE into the superior pancreatic artery at the low dose of 12 ng/min (n = 6) reproduced this increase of SPV levels of NE (delta = +740 +/- 130 pg/ml; P less than 0.01) and caused a small reduction of SPV blood flow (delta = -1.0 +/- 0.4 ml/min, P less than 0.05), but did not change pancreatic IRI (delta = -26 +/- 16%, NS). The medium dose of NE (120 ng/min, n = 6) reproduced the nerve stimulation-induced decrease of SPV blood flow (delta = -1.5 +/- 0.2 ml/min; P less than 0.01) and increased the SPV NE levels by 6,306 +/- 1,839 pg/ml (P less than 0.02), yet did not decrease pancreatic IRI output (delta = +62 +/- 49%, NS). The high dose of NE (1,200 ng/min, n = 6) produced an extreme increment of SPV NE levels (delta = +180,000 +/- 44,000 pg/ml, P less than 0.001) and a much larger reduction of SPV blood flow (delta = -3.7 +/- 0.7 ml/min, P less than 0.01) than did nerve stimulation, yet still did not inhibit insulin output (delta = -13 +/- 46%, NS). Ten minutes of sympathetic nerve stimulation increased the pancreatic output of immunoreactive glucagon (IRG) by 1435 +/- 419 pg/min (P less than 0.02). Pancreatic IRG output increased as well during infusion of NE for 10 min at both 12 ng/min (by 575 +/- 205 pg/min, P less than 0.05) and 120 ng/min (by 718 +/- 231 pg/min, P less than 0.05). In marked contrast, during infusion of NE at 1200 ng/min, pancreatic IRG output decreased (by 400 +/- 190 pg/min, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
Renal hemodynamic effects of activation of specific renal sympathetic nerve fiber groups (1999)

To examine the effect of activation of a unique population of renal sympathetic nerve fibers on renal blood flow (RBF) dynamics, anesthetized rats were instrumented with a renal sympathetic nerve activity (RSNA) recording electrode and an electromagnetic flow probe on the ipsilateral renal artery. Peripheral thermal receptor stimulation (external heat) was used to activate a unique population of renal sympathetic nerve fibers and to increase total RSNA. Total RSNA was reflexly increased to the same degree with somatic receptor stimulation (tail compression). Arterial pressure and heart rate were increased by both stimuli. Total RSNA was increased to the same degree by both stimuli but external heat produced a greater renal vasoconstrictor response than tail compression. Whereas both stimuli increased spectral density power of RSNA at both cardiac and respiratory frequencies, modulation of RBF variability by fluctuations of RSNA was small at these frequencies, with values for the normalized transfer gain being approximately 0.1 at >0.5 Hz. During tail compression coherent oscillations of RSNA and RBF were found at 0.3-0.4 Hz with normalized transfer gain of 0.33 +/- 0.02. During external heat coherent oscillations of RSNA and RBF were found at both 0.2 and 0.3-0.4 Hz with normalized transfer gains of 0. 63 +/- 0.05 at 0.2 Hz and 0.53 +/- 0.04 to 0.36 +/- 0.02 at 0.3-0.4 Hz. Renal denervation eliminated the oscillations in RBF at both 0.2 and 0.3-0.4 Hz. These findings indicate that despite similar increases in total RSNA, external heat results in a greater renal vasoconstrictor response than tail compression due to the activation of a unique population of renal sympathetic nerve fibers with different frequency-response characteristics of the renal vasculature.
In Situ Analysis of the Evolution of the Primary Immune Response in MurineChlamydia trachomatisGenital Tract Infection (2000)

Adaptive immune responses contribute to the resolution of Chlamydia trachomatis genital tract infection and protect against reinfection, but our understanding of the mechanisms of those protective responses is incomplete. In this study, we analyzed by in situ immunohistochemistry the progression of the inflammatory and cytokine responses in the genital tracts of mice vaginally infected with C. trachomatis strain mouse pneumonitis. The cellular inflammatory response was characterized by an initial elevation in myeloid cells in the vagina (day 3) and uterine horns (day 7), followed by a marked rise in the number of T cells, predominantly CD4(+) cells. CD8(+) T cells and CD45R(+) B cells were also detected but were much less numerous. Perivascular clusters of CD4(+) T cells, which resembled clusters of T cells seen in delayed-type hypersensitivity responses, were evident by 2 weeks postinfection. Following the resolution of infection, few CD8(+) T cells and CD45R(+) B cells remained, whereas numerous CD4(+) T cells and perivascular clusters of CD4(+) T cells persisted in genital tract tissues. Interleukin-12 (IL-12)- and tumor necrosis factor alpha (TNF-alpha)-producing cells were observed in vaginal tissue by day 3 of infection and in uterine tissues by day 7. Cells producing IL-4 or IL-10 were absent from vaginal tissues at day 3 of infection but were present in uterine tissues by day 7 and were consistently more numerous than IL-12- and TNF-alpha-producing cells. Thus, the evolution of the local inflammatory response was characterized by the accumulation of CD4(+) T cells into perivascular clusters and the presence of cells secreting both Th1- and Th2-type cytokines. The persistence of CD4(+)-T-cell clusters long after infection had resolved (day 70) may provide for a readily mobilizable T-cell response by which previously infected animals can quickly respond to and control a secondary infectious challenge.
Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path (1973)

1. Potential changes evoked by stimulation of the perforant path have been recorded in the dentate area of the hippocampal formation in chronically prepared unanaesthetized rabbits.2. Components attributed to excitatory synaptic current flow and to action potentials in the granule cell population were distinguishable, with characteristics largely the same as in anaesthetized rabbits.3. Stimulation at 15/sec for several seconds usually led to the granule cells being more effectively activated by the individual stimuli of the train (;frequency potentiation'). Single stimuli then commonly produced multiple discharges in the granule cell population.4. After single periods of stimulation at 15/sec for 15-20 sec there was on 26% of the occasions (41% of those on which there was good frequency potentiation) a long-lasting potentiation of the responses to subsequent stimuli, lasting from 1 hr to 3 days.5. After a further 20% of the periods of repetitive stimulation there was a shorter lasting potentiation, and after 8% there was a short lasting depression.6. The potentiation, when present, was characterized by some or all of the following changes: increases in the amplitudes of the synaptic wave and population spike, reduction in the latency of the population spike, and reductions in the variability of the characteristics of the population spike.7. During the long-lasting potentiation there was an increase in the excitability of the post-synaptic cells and, on some but not all occasions, an increase in the extracellular current flow produced directly by synaptic action.