gebhart/patrepeval huggingface dataset:
Involvement of very late activation antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) in tumor necrosis factor alpha enhancement of experimental metastasis. (1994)

In this study, we examined the effect of tumor necrosis factor alpha (TNF-alpha) on pulmonary metastasis of murine melanoma B16-BL6 by focusing on the intercellular adhesion molecules involved in the metastatic process. TNF-alpha administration before B16-BL6 inoculation significantly enhanced the experimental pulmonary metastasis. The enhancement was seen when TNF-alpha was administered 4 h, but not 24 h, before B16-BL6 inoculation. Administration of 50-5000 units of TNF-alpha increased the number of metastatic lung colonies in a dose-dependent manner. Flow cytometric analysis demonstrated a high expression of very late activation antigen 4 (VLA-4) on the surface of B16-BL6 cells. Immunoperoxidase staining demonstrated that a ligand for VLA-4, vascular cell adhesion molecule 1, was expressed on lung vascular endothelium 4 h after administration of TNF-alpha. Pretreatment of B16-BL6 cells with an anti-VLA-4 monoclonal antibody abolished the TNF-alpha-enhanced pulmonary lung colonies. Administration of an anti-vascular cell adhesion molecule 1 monoclonal antibody also abolished the enhancement. These results indicate that the interaction between VLA-4 on tumor cells and vascular cell adhesion molecule 1 on activated endothelial cells is critically involved in TNF-alpha enhancement of metastasis.
Urate-oxidase for the treatment of tophaceous gout in heart transplant recipients. A report of three cases. (1995)

Gout in heart transplant recipients is common and poses a significant therapeutic challenge. Concomitant administration of azathioprine and allopurinol therapy carries a high risk of leukopenia. Uricosuric agents can cause renal lithiasis and/or acute renal failure in patients with renal failure and/or high urinary levels of uric acid. We report our experience with urate-oxidase in three heart transplant recipients with severe polyarticular and tophaceous gout, a history of leukopenia under allopurinol and unresponsiveness or contraindications to uricosuric agents. Urate-oxidase was given parenterally in a dosage of 1000 units per day, seven days a month. The injections were done intramuscularly in one patient and intravenously in the other two, who were under anticoagulant therapy. Patients 1 and 2 received 12 and 6 courses, respectively. The third patient had had four courses and was still under treatment at the time of this writing. Shrinking of the tophi and improved mobility of the fingers were seen in all three patients after the second course. No adverse effects were recorded. Our experience suggests that urate-oxidase therapy may decrease the urate burden in patients with severe tophaceous gout. Urate-oxidase therapy should be viewed as a phase in the treatment of gout, which must be followed by administration of another agent.
Molecular Insights into Mammalian End-binding Protein Heterodimerization (2009)

Microtubule plus-end tracking proteins (+TIPs) are involved in many microtubule-based processes. End binding (EB) proteins constitute a highly conserved family of +TIPs. They play a pivotal role in regulating microtubule dynamics and in the recruitment of diverse +TIPs to growing microtubule plus ends. Here we used a combination of methods to investigate the dimerization properties of the three human EB proteins EB1, EB2, and EB3. Based on Förster resonance energy transfer, we demonstrate that the C-terminal dimerization domains of EBs (EBc) can readily exchange their chains in solution. We further document that EB1c and EB3c preferentially form heterodimers, whereas EB2c does not participate significantly in the formation of heterotypic complexes. Measurements of the reaction thermodynamics and kinetics, homology modeling, and mutagenesis provide details of the molecular determinants of homo- versus heterodimer formation of EBc domains. Fluorescence spectroscopy and nuclear magnetic resonance studies in the presence of the cytoskeleton-associated protein-glycine-rich domains of either CLIP-170 or p150(glued) or of a fragment derived from the adenomatous polyposis coli tumor suppressor protein show that chain exchange of EBc domains can be controlled by binding partners. Extension of these studies of the EBc domains to full-length EBs demonstrate that heterodimer formation between EB1 and EB3, but not between EB2 and the other two EBs, occurs both in vitro and in cells as revealed by live cell imaging. Together, our data provide molecular insights for rationalizing the dominant negative control by C-terminal EB domains and form a basis for understanding the functional role of heterotypic chain exchange by EBs in cells.
In vivohigh-resolution 3D photoacoustic imaging of superficial vascular anatomy (2009)

The application of a photoacoustic imaging instrument based upon a Fabry-Perot polymer film ultrasound sensor to imaging the superficial vasculature is described. This approach provides a backward mode-sensing configuration that has the potential to overcome the limitations of current piezoelectric based detection systems used in superficial photoacoustic imaging. The system has been evaluated by obtaining non-invasive images of the vasculature in human and mouse skin as well as mouse models of human colorectal tumours. These studies showed that the system can provide high-resolution 3D images of vascular structures to depths of up to 5 mm. It is considered that this type of instrument may find a role in the clinical assessment of conditions characterized by changes in the vasculature such as skin tumours and superficial soft tissue damage due to burns, wounds or ulceration. It may also find application in the characterization of small animal cancer models where it is important to follow the tumour vasculature over time in order to study its development and/or response to therapy.
Integrating free-space optical communication links with existing WiFi (WiFO) network (2016)

Recently, free-space optical (FSO) systems have generated great interest due to their large bandwidth potential and a line-of-sight physical layer of protection. In this paper, we propose WiFO, a novel hybrid system, FSO downlink and WiFi uplink, which will integrate currently available WiFi infrastructure with inexpensive infrared light emitting diodes. This system takes full advantage of the mobility inherent in WiFi networks while increasing the downlink bandwidth available to each end user. We report the results of our preliminary investigation that show the capabilities of our prototype design in terms of bandwidth, bit error rates, delays and transmission distances.
Obstructive Sleep Apnea: Electrical Stimulation Treatment (2006)

Abstract Obstructive sleep apnea (OSA) is an intermittent occlusion of the upper airways resulting in frequent arousals during sleep. It is a prevalent problem among middle‐aged overweight males. Neuromuscular and anatomical factors play a major role predisposing the upper‐airways for obstructions. The limited success of current therapies and the strong correlation of the obstructions with the upper‐airway muscle mechanics has inspired researchers to apply the experience gained in the field of functional electrical stimulation to this common sleep disorder. A number of upper airway muscles have been tested in animal models and human subjects for their potential to remove or prevent the obstructions. Electrical activation of the extrinsic muscles of the tongue through the stimulation of the XIIth cranial (hypoglossal) nerve stands out as the most promising approach today. In this article, we review these recent attempts to treat OSA by electrical activation of the upper‐airway muscles.
Adoptive transfer of helminth antigen‐pulsed dendritic cells protects against the development of experimental colitis in mice (2015)

Infection with helminth parasites and treatment with worm extracts can suppress inflammatory disease, including colitis. Postulating that dendritic cells (DCs) participated in the suppression of inflammation and seeking to move beyond the use of helminths per se, we tested the ability of Hymenolepis diminuta antigen-pulsed DCs to suppress colitis as a novel cell-based immunotherapy. Bone marrow derived DCs pulsed with H. diminuta antigen (HD-DCs), or PBS-, BSA-, or LPS-DCs as controls, were transferred into wild-type (WT), interleukin-10 (IL-10) knock-out (KO), and RAG-1 KO mice, and the impact on dinitrobenzene sulphonic acid (DNBS)-induced colitis and splenic cytokine production assessed 72 h later. Mice receiving HD-DCs were significantly protected from DNBS-induced colitis and of the experimental groups only these mice displayed increased Th2 cytokines and IL-10 production. Adoptive transfer of HD-DCs protected neither RAG-1 nor IL-10 KO mice from DNBS-colitis. Furthermore, the transfer of CD4(+) splenocytes from recipients of HD-DCs protected naïve mice against DNBS-colitis, in an IL-10 dependent manner. Thus, HD-DCs are a novel anti-colitic immunotherapy that can educate anti-colitic CD4(+) T cells: mechanistically, the anti-colitic effect of HD-DCs requires that the host has an adaptive immune response and the ability to mobilize IL-10.
Metabolic similarities between fertilization and phagocytosis. Conservation of a peroxidatic mechanism. (1979)

At the time of fertilization, sea urchin eggs release a peroxidase which, together with H2O2 generated by a respiratory burst, is responsible for hardening of the fertilization membrane. We demonstrate here that the ovoperoxidase of unfertilized eggs is located in cortical granules and, after fertilization, is concentrated in the fertilization membrane. Fertilization of sea urchin eggs or their parthenogenetic activation with the ionophor A23187 also results in (a) the conversion of iodide to a trichloroacetic acid-precipitable form (iodination), (b) the deiodination of eggs exogenously labeled with myeloperoxidase and H2O2, (c) the degradation of thyroxine as measured by the recovery of the released radioiodine at the origin and in the inorganic iodide spot on paper chromatography, and (d) the conversion of estradiol to an alcohol-precipitable form (estrogen binding). The iodination reaction and the binding of estradio occurs predominantly in the fertilization membrane where the ovoperoxidase is concentrated. From the estimation of the kinetics of incorporation of iodine, we determine that the peroxidative system is active for 30 min after fertilization, long after hardening of the fertilization membrane is complete. Most of the bound iodine is lost during the hatching process. Iodination of albumin is catalyzed by the material released from the egg during fertilization, when combined with H2O2 and iodide. Iodination, thyroxine degradation, and estradiol binding are inhibited by azide, cyanide, aminotriazole, methimazole, ascorbic acid and ergothioneine, all of which can inhibit peroxidase-catalyzed reactions. These responses of the sea urchin egg to fertilization are strikingly similar to the changes induced in polymorphonuclear leukocytes by phagocytosis and, in both instances, a peroxidative mechanism may be involved.
Inventing the Lisa user interface (1997)

article Free Access Share on Inventing the Lisa user interface Authors: Roderick Perkins Interval Research Corp., Palo Alto, CA Interval Research Corp., Palo Alto, CAView Profile , Dan Smith Keller PowerAgent, Inc., Cupertino, CA PowerAgent, Inc., Cupertino, CAView Profile , Frank Ludolph Sun Microsystems, Inc., Mountain View, CA Sun Microsystems, Inc., Mountain View, CAView Profile Authors Info & Claims InteractionsVolume 4Issue 1Jan./Feb. 1997 pp 40–53https://doi.org/10.1145/242388.242405Published:01 January 1997Publication History 12citation1,233DownloadsMetricsTotal Citations12Total Downloads1,233Last 12 Months53Last 6 weeks19 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
The effects of geometry on skin penetration and failure of polymer microneedles (2012)

Microneedles are small-scale devices that may be used for drug delivery and biosensing. In this study, the forces required for mechanical failure, the modes of mechanical failure, as well as the mechanisms for microneedle penetration into porcine skin were examined. Microneedles produced from the acrylate-based polymer e-Shell 200 using an indirect rapid prototyping approach involving two-photon polymerization and poly(dimethylsiloxane) micromolding were found to possess sufficient strength for penetration of porcine skin. The failure forces were an order of magnitude greater than the forces necessary for full insertion into the skin. Bending was the most common form of failure; an increasing aspect ratio and a decreasing tip diameter were associated with lower failure forces. Video captured during skin penetration revealed that microneedle penetration into the skin occurred by means of a series of insertions and not by means of a single insertion event. Images obtained during and after skin penetration confirmed microneedle penetration of skin as well as transdermal delivery of lucifer yellow dye. These findings shed insight into the mechanisms of microneedle penetration and failure, facilitating design improvements for polymer microneedles.
In vivo results of hydrogel composite pericardial substitutes. (1992)

In this study, two improved pericardial patches were developed and evaluated for their efficacy as pericardial substitutes. The patches are composites consisting of a hydrogel (PHEMA) that coats an underlying mesh (either ETFE or PET). Studies were conducted using subcutaneous implants in rats and pericardial patch implants in greyhound dogs. Adhesions between the substitute and pericardium and the epicardium were minimal. The ETFE composite patch caused an unacceptable epicardial reaction. The PET patch results were encouraging; the epicardium was largely unaffected by the patch.
SUMF1 enhances sulfatase activitiesin vivoin five sulfatase deficiencies (2007)

Sulfatases are enzymes that hydrolyse a diverse range of sulfate esters. Deficiency of lysosomal sulfatases leads to human diseases characterized by the accumulation of either GAGs (glycosaminoglycans) or sulfolipids. The catalytic activity of sulfatases resides in a unique formylglycine residue in their active site generated by the post-translational modification of a highly conserved cysteine residue. This modification is performed by SUMF1 (sulfatase-modifying factor 1), which is an essential factor for sulfatase activities. Mutations in the SUMF1 gene cause MSD (multiple sulfatase deficiency), an autosomal recessive disease in which the activities of all sulfatases are profoundly reduced. In previous studies, we have shown that SUMF1 has an enhancing effect on sulfatase activity when co-expressed with sulfatase genes in COS-7 cells. In the present study, we demonstrate that SUMF1 displays an enhancing effect on sulfatases activity when co-delivered with a sulfatase cDNA via AAV (adeno-associated virus) and LV (lentivirus) vectors in cells from individuals affected by five different diseases owing to sulfatase deficiencies or from murine models of the same diseases [i.e. MLD (metachromatic leukodystrophy), CDPX (X-linked dominant chondrodysplasia punctata) and MPS (mucopolysaccharidosis) II, IIIA and VI]. The SUMF1-enhancing effect on sulfatase activity resulted in an improved clearance of the intracellular GAG or sulfolipid accumulation. Moreover, we demonstrate that the SUMF1-enhancing effect is also present in vivo after AAV-mediated delivery of the sulfamidase gene to the muscle of MPSIIIA mice, resulting in a more efficient rescue of the phenotype. These results indicate that co-delivery of SUMF1 may enhance the efficacy of gene therapy in several sulfatase deficiencies.
Effects of Multisite Biventricular Pacing in Patients with Heart Failure and Intraventricular Conduction Delay (2001)

Although it is technically complex, atriobiventricular pacing significantly improves exercise tolerance and quality of life in patients with chronic heart failure and intraventricular conduction delay.
Three-dimensional combined photoacoustic and optical coherence microscopy for in vivo microcirculation studies (2009)

Photoacoustic microscopy is predominantly sensitive to optical absorption, while optical coherence tomography relies on optical backscattering. Integrating their complementary contrasts can provide comprehensive information about biological tissue. We have developed a dual-modality microscope that combines the two for studying microcirculation. Three-dimensional imaging of microvasculature and its local environment has been demonstrated at micrometer-order resolution using endogenous contrast in vivo.
Influence of the beam spot size on ablation rates in pulsed-laser processing (1987)

Ablation rates in pulsed-laser processing depend heavily on the laser beam spot size. This has been observed for the first time for a number of different materials. Detailed investigations on this effect, performed by means of XeCl excimer-laser radiation and the example of LiNbO3, are reported in this letter. With this material, the ablation rate at constant fluence saturates at laser beam spot sizes of 2w≳80 μm and increases by about a factor of 3 when 2w is decreased to 24 μm. The effect is interpreted as being due to changes in the material transport which depend on the size of the region being processed.
Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells (2012)

We have used unbiased RNAi based approaches to identify and characterize the function of CASP8AP2/FLASH, a protein not previously reported as required for cell survival. This study further defines the role CASP8AP2/FLASH plays in the regulating expression of the replication-dependent histones and shows that its LOF results in broad and reproducible effects on the transcriptome of colorectal cancer cells including the induction of expression of the recently described tumor suppressor gene NEFH.
Vemurafenibfor the treatment of melanoma (2012)

Vemurafenib is an oral agent licensed for patients with BRAF V600E mutation-positive inoperable and metastatic melanoma. The most common adverse effects observed in Phase III clinical trials were dermatological events, arthralgia and fatigue. Specific dermatological toxicities included development of cutaneous squamous cell cancers and keratoacanthomas. Prolongation of the QT interval was also reported. Regular dermatological assessments and electrocardiograms are recommended. Ongoing trials are examining vemurafenib in both the adjuvant setting and metastatic setting in combination with ipilimumab and MEK inhibitors (mitogen-activated protein kinase/extracellular signal-regulated kinase). Understanding and overcoming mechanisms of resistance to BRAF inhibitors is the focus of ongoing research.
Overcoming the Inhibitors of Myelin with a Novel Neurotrophin Strategy (2004)

Myelin inhibitors activate a p75(NTR)-dependent signaling cascade in neurons that not only inhibits axonal growth but also prevents neurotrophins (NT) from stimulating growth. Most intriguingly, in addition to Trk receptors, neurotrophins also bind to p75(NTR). We have designed a "mini-neurotrophin" called B(AG) to activate TrkB in the absence of p75(NTR) binding. We find that B(AG) is as effective as the natural TrkB ligands (brain-derived neurotrophic factor (BDNF) and NT-4) at promoting neurite outgrowth from cerebellar neurons. Furthermore, the neurite outgrowth responses stimulated by BDNF and B(AG) are inhibited by a common set of reagents, including the Trk receptor inhibitor K252a, as well as protein kinase A and phosphoinositide 3-kinase inhibitors. However, in contrast to BDNF, B(AG) promotes growth in the presence of a myelin inhibitor or when antibodies directly activate the p75(NTR) inhibitory pathway. On the basis of this observation, we postulated that the binding of BDNF to the p75(NTR) might compromise the ability of BDNF to stimulate neurite outgrowth in an inhibitory environment. To test this, we used NGF, and an NGF-derived peptide, to compete for the BDNF/p75(NTR) interaction; remarkably, in the presence of either agent, BDNF acquired the ability to promote neurite outgrowth in the presence of a myelin inhibitor. The data suggest that in an inhibitory environment, the BDNF/p75(NTR) interaction compromises regeneration. Agents that activate Trk receptors in the absence of p75(NTR) binding, or agents that inhibit neurotrophin/p75(NTR) binding, might therefore be better therapeutic candidates than neurotrophins.
Intra prediction method based on the linear relationship between the channels for YUV 4&#x2236;2&#x2236;0 intra coding (2009)

In general, the transformation from RGB to YUV color space reduces the correlation between the channels. But some sources in the YUV space still have strong inter-channel correlation, which can be modeled as a linear function. Based on this linear model, we propose a new intra chrominance prediction method for color image compression in YUV 4∶2∶0 color space. A block of chrominance pixels to be encoded is predicted from the reconstructed luminance signal using the proposed prediction scheme and the residual is encoded based on the H.264/AVC. Also, an implicit prediction method that can obviate the transmission of side information is proposed. The experimental results show that there are about 0.35∼1.0dB gains for the luminance (Y) channel, and 0.5∼3.0dB gains for the chrominance (Cb or Cr) channels at the medium to high bit-rates. The proposed method also shows some gains at the low bit-rates.
FRACTURE TOUGHNESS OF SILICA AEROGELS (1989)

Silica aerogels of desired shape have been elaborated to perform critical stress intensity factors evaluations as a function of the density. The fracture toughness of aerogels is measured usin SENB technique in three-point bending. KIC varies in the range 0.8 to 4.8 KPa.m1/2. For aerogels whose bulk density ranges between 0.1 and 0.35 g/cm3 the analysis of the obtained results suggests that KIC varies as ρ1.6±0.2. The fracture energy variation and the critical size flaw derived from toughness, strength and Young's modulus are also presented and discussed.
Thrombopoietin expands hematopoietic stem cells after transplantation (2002)

Multiple lines of evidence indicate that thrombopoietin (TPO) contributes to the development of hematopoietic stem cells (HSC), supporting their survival and proliferation in vitro. To determine whether TPO supports the impressive expansion of HSC observed following transplantation, we transplanted normal marrow cells into lethally irradiated Tpo(-/-) and Tpo(+/+) mice and quantified HSC self-renewal and expansion and hematopoietic progenitor cell homing. Although essentially identical numbers of marrow-associated colony forming unit-culture (a surrogate measure of stem cell homing) were observed in each type of recipient 24 hours following transplantation, we found that a minimum of fourfold greater numbers of marrow cells were required to radioprotect Tpo-null mice than to radioprotect controls. To assess whether long-term repopulating (LTR) HSCs self-renew and expand in Tpo(-/-) recipients or controls, we performed limiting-dilution secondary transplants using donor cells from the Tpo(-/-) or Tpo(+/+) recipients 5-7.5 weeks following primary transplantation. We found that LTR HSCs expand to levels 10-20 times greater within this time period in normal recipients than in Tpo-null mice and that physiologically relevant amounts of TPO administered to the Tpo(-/-) recipients could substantially correct this defect. Our results establish that TPO greatly promotes the self-renewal and expansion of HSCs in vivo following marrow transplantation.