gebhart/patrepeval huggingface dataset:
9. Biology of rAAV8 in Mouse Liver Following Vector Administration at Birth (2006)

rAAV8 vectors transduce various tissues with extremely high efficiency in neonates and infants. Many applications of rAAV8 vector injection into prenatal or neonatal mice have been proposed to treat various disorders. Intraperitoneal or intravascular injection of rAAV8 vector into neonatal mice results in widespread efficient transduction in heart and skeletal muscles, which can stably persist even at adult ages. In contrast, the liver is transduced efficiently with rAAV8 only in the neonatal period, and liver transduction substantially declines thereafter. Despite the limited efficacy in neonatal liver transduction, it is important to understand the biology of rAAV8 vectors in the liver following neonatal administration because 1) the neonatal liver is an ideal target organ for gene transfer in many instances; and 2) substantial vector genome dissemination to the liver is likely to occur in non-hepatic gene transfer. In order to substantially understand the biology of rAAV8 injected into neonates, we non-injected or injected intraperitoneally C57BL/6 and 44Bri mice with AAV8-EF1α-nlslacZ vector at birth, and followed up total 69 animals. 44Bri is an HBV transgenic strain that develops chronic liver injury at ∼3 months of age, causing continuous liver regeneration. At the age of 110–179 days, the mice received AAV9-LSP (liver-specific promoter)-hFIX vector via the tail vein. 17 days post rAAV9 injection, half of the mice underwent 2/3 partial hepatectomy (PHx), and all the mice were sacrificed 6 weeks after PHx. The rAAV9 vector served as an internal control for PHx in rAAV8-injected animals. Xgal staining of the liver sections revealed sparsely scattered single blue hepatocytes and occasional clusters comprising 2–20 blue hepatocytes. Non-parenchymal blue cell foci were also found in many liver sections analyzed. Several relatively large blue hepatocyte clusters comprising of supposedly 10e2∼10e4 hepatocytes were found in one wild type and two 44Bri mice after PHx, suggesting that rAAV8-transduced cells in these foci might have had growth advantage over surrounding non-transduced hepatocytes. hFIX expression from the rAAV9 and rAAV9 genome copy numbers in the liver substantially dropped (over 90%) by PHx, while rAAV8 vector copy number drops were significantly smaller than those of rAAV9 vector (27-92% vector copy number drops for wild type and 73% drop-869% increase for 44Bri mice). This indicates that, although a significant portion of rAAV8 vector genomes were extrachromosomal, vector genomes were apparently integrated into chromosomes, with frequency of at most 2.7 vector genome copy/cell in our study. Thus, rAAV8 injected at birth integrates into chromosomes in the liver, stably transducing both parenchymal and non-parenchymal hepatic cells sparsely. In parallel to this experiment, we are following up 69 non-injected and 117 rAAV8-injected (at birth) wild type and 44Bri male mice over 400 days to investigate procarcinogenic potential of rAAV8 in mice. A preliminary result in this study will be also presented.
Fast algorithm for respiratory motion correction in free-breathing contrast-enhanced ultrasound imaging (2011)

Respiratory motion affects the accurate quantification of the hepatic fusion, which does not benefit the early detection and treatment of hepatic cancers. A new strategy based on template matching is proposed to correct respiratory motion in the free-breathing time-series contrast-enhanced ultrasound (CEUS) images. Ultrasound machines generally have a dual-display feature of contrast and tissue windows under contrast-enhanced mode. The tissue window is used to track the targeted tumor in the contrast window. Therefore, the registration of contrast images is first achieved by the registration of the corresponding tissue images due to the low variation of grey level in the tissue image. Then, a simple double-selection method is proposed to select the similar images from a large number of successive matched images via the global and local threshold setting. Finally, the motion-corrected contrast images can be acquired by using the position mapping. This strategy was tested on 4 free-breathing CEUS image sequences using the sum of absolute differences metric. Results showed that the time-intensity curves could be extracted more accurately with this strategy. Moreover, the quality of curve fitting and the corresponding parametric imaging computed on the motion-corrected sequences was improved significantly. In conclusion, the image-based strategy can quickly correct the respiratory motion in CEUS image sequences, which is potentially suitable for the local quantification of hepatic perfusion studies.
The Immunomodulatory Activity of Meningococcal Lipoprotein Ag473 Depends on the Conformation Made up of the Lipid and Protein Moieties (2012)

We have previously demonstrated that the meningococcal antigen Ag473 in the presence of Freund's adjuvant can elicit protective immune responses in mouse challenge model. In this study, we evaluated the structural requirement for the immunological activity and the possible signaling pathway of recombinant Ag473 antigen produced in E. coli. We found that lipidated Ag473 (L-Ag473) possesses an intrinsic adjuvant activity that could be attributed to its ability to activate dendritic cells and promote their maturation. In addition, we found that L-Ag473 can activate human monocytes and promote maturation of human monocyte-derived dendritic cells. These results provide an indirect support that L-Ag473 may also be immunogenic in human. Interestingly, the observed activity is dependent on the overall conformation of L-Ag473 because heating and proteinase K treatment can diminish and abolish the activity. Furthermore, our data suggest a species-differential TLR recognition of L-Ag473. Overall, these data suggest a new paradigm for the ligand-TLR interaction in addition to demonstrating the self-adjuvanting activity of the vaccine candidate L-Ag473.
EMG-controlled functional electrical stimulation of the paretic hand. (1979)

A new apparatus is described which delivers a functional electric stimulation, controlled by the peak EMG output signal as recorded from the forearm muscles. Twelve paretic hands were stimulated with this apparatus. The EMG output, the stimulus strength, the stimulus frequency, and the corresponding improvement of the wrist extension force were measured. Different arrangements of electrodes and various relay adjustments were tested. The investigations showed that even severely paretic muscles were capable of delivering an efficient EMG output, and the resulting improvement of wrist extension force was statistically significant. The necessary stimulus intensity showed no relationship to the degree of paresis, but a certain relationship to the recovery tendency of the hand was evident. Acceptance of the apparatus among the patients was satisfactory; only a few complained of pain during stimulation.
Oxidative Stress and Diabetic Complications (2010)

Oxidative stress plays a pivotal role in the development of diabetes complications, both microvascular and cardiovascular. The metabolic abnormalities of diabetes cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. This increased superoxide production causes the activation of 5 major pathways involved in the pathogenesis of complications: polyol pathway flux, increased formation of AGEs (advanced glycation end products), increased expression of the receptor for AGEs and its activating ligands, activation of protein kinase C isoforms, and overactivity of the hexosamine pathway. It also directly inactivates 2 critical antiatherosclerotic enzymes, endothelial nitric oxide synthase and prostacyclin synthase. Through these pathways, increased intracellular reactive oxygen species (ROS) cause defective angiogenesis in response to ischemia, activate a number of proinflammatory pathways, and cause long-lasting epigenetic changes that drive persistent expression of proinflammatory genes after glycemia is normalized ("hyperglycemic memory"). Atherosclerosis and cardiomyopathy in type 2 diabetes are caused in part by pathway-selective insulin resistance, which increases mitochondrial ROS production from free fatty acids and by inactivation of antiatherosclerosis enzymes by ROS. Overexpression of superoxide dismutase in transgenic diabetic mice prevents diabetic retinopathy, nephropathy, and cardiomyopathy. The aim of this review is to highlight advances in understanding the role of metabolite-generated ROS in the development of diabetic complications.
Address Layer (2016)

Abstract This chapter discusses the fourth of six layers in The Stack, the Address layer. For any entity to participate in the wider Stack architecture it has to be known to it. It must be enumerated and enunciated by an address. The chapter examines very-large scale universal internet addressing systems (such as IPv6) that would allow for an abyssal volume of individual addressees. Some programs for ubiquitous computing and an ‘internet of things’ suggest scenarios that draw almost any, into a landscape of addressable objects. However, for “Deep Address,” the computational landscape can absorb any conceivable object, event or relation, regardless of scale or temporality into a vast, if also fragile, communicative field. Ultimately the scope and complexity of than landscape may exceed the limits of human control or literacy. The chapter also discusses the ramifications of the superimposition of multiple, internally-complete and self-sufficient addressing schemes onto the same territory, and how this complicates platform interoperability but also may allow for important variation and resiliency.
Critical observations on neuroblastoma treatment with 131‐I‐metaiodobenzylguanidine at diagnosis (1993)

Results of treatment with 131-I-Metaiodobenzylguanidine (131-I-MIBG) in patients with resistant neuroblastoma appear encouraging if one considers that most of the patients had far advanced, intensively pre-treated disease. To further explore the potential role of this new drug in untreated patients, we treated 3 children with stage III neuroblastoma. All three of our cases received 131-I-MIBG at relatively low dose with the complete disappearance of the tumor mass in case 1, whereas in cases 2 and 3 CT scan showed a significant reduction of the tumor mass and, interestingly enough, no evidence of 131-I-MIBG uptake of a tracer dose in the remaining tumor. Particularly, in case 2, the persistence and subsequent progression of part of the tumor mass without 131-I-MIBG uptake after a therapeutic dose of 131-I-MIBG, which apparently destroyed the 131-I-MIBG-positive cell population, clearly suggest heterogeneity at diagnosis, with a dual neuroblastoma cell population, one with 131-I-MIBG uptake and the other without. Besides the biological implications of the 131-I-MIBG uptake heterogeneity in neuroblastoma at diagnosis, our findings suggest that in stage III neuroblastoma patients even a relatively small dose of 131-I-MIBG administered at diagnosis is sufficient to destroy either the primary tumor completely (case 1) or the part of the tumor (case 2 and 3) which shows 131-I-MIBG uptake, without any significant hematologic toxicity. Furthermore, a single course of 131-I-MIBG at the dosage employed does not appear to jeopardize the subsequent use of chemotherapy. In conclusion, if our data are confirmed by further investigation, 131-I-MIBG may be included as a front line drug shortly followed by chemotherapy in future treatment strategies of advanced neuroblastoma without or with minimal bone marrow infiltration.
Observation of Crystallographic Morphology of Diamond-Shaped &beta; Phase in Stainless Steel Using a Non-aqueous Electrolyte-Potentiostatic Etching Method (1981)

Crystallographic morphology of the diamond-shaped β phase in stainless steel (25%Ni-19%Cr-5%Al) has been studied using the non-aqcuous electrolyte-potentiostatic etching method (the SPEED method).The results are summarized as follows;(1) The diamond-shaped β phase crystals which existed in the same δ-ferrite phase were found to be identical in morphology. The β phase crystal grows to eight 〈111〉 directions. The three typical shapes of the β phase crystal were newly observed from low indexes by SEM.(2) The three shapes of the β phase were observed by the rotation of the β phase crystal.(3) The β phase crystals are grown by agglomeration.(4) The composition of the β phase was found to be (Ni, Fe, Cr)Al by EDX analysis of the residues collected on a silver membrane filter after the non-aqueous electrolyte-potentiostatic isolation.
Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 Phosphorylation (2023)

(Cell Reports 32, 108151; September 15, 2020) This article, which was originally published with the September 15, 2020 issue of Cell Reports, contains incorrect immunohistochemical images in Figure 1D. The corrected version of this figure appears below. This correction to Figure 1D has not changed the original conclusions of the article. The authors sincerely regret the error and any confusion that it may have caused. Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 PhosphorylationChen et al.Cell ReportsSeptember 15, 2020In BriefChen et al. show that the rate of onset and maximal cellular Akt1 activity induced by mitogens was augmented by cyclin D1. Cyclin D1 bound and phosphorylated Akt1 at Ser473. These studies identify a novel extranuclear function of cyclin D1 to enhance proliferative functions via augmenting Akt1 phosphorylation at Ser473. Full-Text PDF Open Access
Mechanics of microtubule organizing center clustering and spindle positioning in budding yeast Cryptococcus neoformans (2021)

The dynamic process of mitotic spindle assembly depends on multitudes of inter-dependent interactions involving kinetochores (KTs), microtubules (MTs), spindle pole bodies (SPBs), and molecular motors. Before forming the mitotic spindle, multiple visible microtubule organizing centers (MTOCs) coalesce into a single focus to serve as an SPB in the pathogenic budding yeast, Cryptococcus neoformans. To explain this unusual phenomenon in the fungal kingdom, we propose a "search and capture" model, in which cytoplasmic MTs (cMTs) nucleated by MTOCs grow and capture each other to promote MTOC clustering. Our quantitative modeling identifies multiple redundant mechanisms mediated by a combination of cMT-cell cortex interactions and inter-cMT coupling to facilitate MTOC clustering within the physiological time limit as determined by time-lapse live-cell microscopy. Besides, we screen various possible mechanisms by computational modeling and propose optimal conditions that favor proper spindle positioning-a critical determinant for timely chromosome segregation. These analyses also reveal that a combined effect of MT buckling, dynein pull, and cortical push maintains spatiotemporal spindle localization.
Modelling effects of recent suction history on small-strain stiffness of unsaturated soil (2018)

Recent suction history has been found to affect shear modulus of unsaturated soil at small strains (i.e., from 0.001% to 1%). In this study, a bubble model for unsaturated soil is developed within the framework of kinematic hardening and bounding surface plasticity. An elliptical elastic bubble is defined inside a modified Cam-clay bounding surface. Being a key feature of the proposed model, the size of the elastic bubble is modelled as a function of suction, degree of saturation, and plastic volumetric strain. Translation of the elastic bubble is governed by suction, degree of saturation, and stress increments. Moreover, hardening modulus depends on not only stress and void ratio, but also suction, degree of saturation, and relative position of the elastic bubble and the bounding surface. The proposed model is evaluated using suction-controlled constant-p shear tests on completely decomposed tuff (silt). It is evident that the new model is capable of capturing well the effects of recent suction history on nonlinear stress–strain relation and shear modulus degradation at small strains.
Synesthesia audio-visual interactive-sound and music visualization in virtual reality with orbital observation and navigation (2016)

Music visualization is particularly suited to enjoying music and for new modes of interaction and embodiment in virtual reality. Here I demonstrate several real-time virtual reality sound and music visualization techniques and applications using both music from electronic music producer James Le Roux, and sound from a user's microphone. Additionally, the adoption of an `orbital mode' interaction technique allows unprecedented hands-free user observation and navigation control. Users are able to pause the sound, halting the visualization data so that it can be viewed in freeze-frame from any angle.
Associations between insulin resistance and thrombotic risk factors in high‐risk South Asian subjects (2003)

Abstract Aims There is recognized association of thrombotic factors to insulin resistance in White Europeans. South Asians are more insulin resistant compared with white Europeans and express increased metabolic features of insulin resistance. The aim of the study was to determine whether there was any relationship between insulin resistance and thrombotic risk factors in healthy South Asian subjects. Methods Healthy South Asians ( n = 185) clinically free from ischaemic heart disease, ischaemic stroke or peripheral vascular disease were randomly recruited. Partial correlations of homeostasis model assessment (HOMA) (surrogate of insulin resistance) were analysed with two fibrinolytic and five coagulation factors. Results Age and gender‐adjusted HOMA was significantly correlated to plasminogen activator inhibitor‐1 (0.51, P = 0.0001), tissue plasminogen activator antigen ( r = 0.40, P = 0.0001), fibrinogen ( r = 0.28, P = 0.0001), von Willebrand factor ( r = 0.17, P = 0.03), factor XIIa ( r = 0.22, P = 0.006) factor VII antigen ( r = 0.19, P = 0.02) and factor XIII B subunit ( r = 0.30, P = 0.001). Conclusions Insulin resistance significantly clusters with fibrinolytic and coagulation factors in South Asians, which may contribute to high prevalence of vascular disease in this population.
Sol–gel derived carrier for the controlled release of proteins (1999)

Sol-gel derived porous silica carriers for the controlled release of proteins were synthesized using a room temperature process. The materials are intended to serve as both substrates for bone growth as well as to allow incorporated proteins such as growth factors to diffuse out and stimulate cell function and tissue healing. The data document that the in vitro release of trypsin inhibitor, a model protein of size similar to growth factors with documented effect in bone, was dose and time dependent during immersion up to nine weeks. The release pattern included an initially slow release, with further release occurring at a rate which is proportionate to the square root of time, an indicative of a diffusion-driven process.
Functional Imaging of Numerical Processing in Adults and 4-y-Old Children (2006)

Adult humans, infants, pre-school children, and non-human animals appear to share a system of approximate numerical processing for non-symbolic stimuli such as arrays of dots or sequences of tones. Behavioral studies of adult humans implicate a link between these non-symbolic numerical abilities and symbolic numerical processing (e.g., similar distance effects in accuracy and reaction-time for arrays of dots and Arabic numerals). However, neuroimaging studies have remained inconclusive on the neural basis of this link. The intraparietal sulcus (IPS) is known to respond selectively to symbolic numerical stimuli such as Arabic numerals. Recent studies, however, have arrived at conflicting conclusions regarding the role of the IPS in processing non-symbolic, numerosity arrays in adulthood, and very little is known about the brain basis of numerical processing early in development. Addressing the question of whether there is an early-developing neural basis for abstract numerical processing is essential for understanding the cognitive origins of our uniquely human capacity for math and science. Using functional magnetic resonance imaging (fMRI) at 4-Tesla and an event-related fMRI adaptation paradigm, we found that adults showed a greater IPS response to visual arrays that deviated from standard stimuli in their number of elements, than to stimuli that deviated in local element shape. These results support previous claims that there is a neurophysiological link between non-symbolic and symbolic numerical processing in adulthood. In parallel, we tested 4-y-old children with the same fMRI adaptation paradigm as adults to determine whether the neural locus of non-symbolic numerical activity in adults shows continuity in function over development. We found that the IPS responded to numerical deviants similarly in 4-y-old children and adults. To our knowledge, this is the first evidence that the neural locus of adult numerical cognition takes form early in development, prior to sophisticated symbolic numerical experience. More broadly, this is also, to our knowledge, the first cognitive fMRI study to test healthy children as young as 4 y, providing new insights into the neurophysiology of human cognitive development.
Highlights from the First Annual Spinal Navigation, Emerging Technologies and Systems Integration Meeting (2018)

This paper provides a detailed report of the "First Annual Spinal Navigation, Emerging Technologies and Systems Integration" meeting held December 3, 2016 at the Seattle Science Foundation.
Endothelin-1 induces lipolysis in 3T3-L1 adipocytes (2005)

Endothelin-1 (ET-1) affects glucose uptake in adipocytes and may play an important role in adipose physiology. One of the principal functions of adipose tissue is the provision of energy substrate through lipolysis. In the present study, we investigated the effects of ET-1 on lipolysis in 3T3-L1 adipocytes. When glycerol release in the culture medium was measured as an index of lipolysis, the results showed that ET-1 caused a significant increase that was time and dose dependent. With a concentration of 10 nM ET-1, stimulation of glycerol release plateaued after 4 h of exposure. This effect was inhibited by the ETA receptor antagonist BQ-610 (10 microM) but not by the ETB receptor antagonist BQ-788 (10 microM). To further explore the underlying mechanisms of ET-1 action, we examined the involvement of the cAMP-dependent protein kinase A-mediated, phospholipase A2 (PLA2)-mediated, protein kinase C (PKC)-mediated, phosphatidylinositol 3 (PI 3)-kinase-mediated, and the mitogen-activated protein kinase (MAPK)-mediated pathways. Inhibition of adenylyl cyclase activation by SQ-22536 (100 microM) did not block ET-1-induced lipolysis. Pretreatment of adipocytes with the PLA2 inhibitor dexamethasone (100 nM), the PKC inhibitor H-7 (6 microM), or the PI 3-kinase inhibitor wortmannin (100 nM) also had no effect. ET-1-induced lipolysis was blocked by inhibition of extracellular signal-regulated kinase (ERK) activation using PD-98059 (75 microM), whereas a p38 MAPK inhibitor (SB-203580; 20 microM) had no effect. Results of Western blot further demonstrated that ET-1 induced ERK phosphorylation. These data show that ET-1 induces lipolysis in 3T3-L1 adipocytes via a pathway that is different from the conventional cAMP-dependent pathway used by isoproterenol and that involves ERK activation.