gebhart/patrepeval huggingface dataset:
CTLA-4 tail fusion enhances CAR-T anti-tumor immunity (2023)

Chimeric antigen receptor (CAR) T cells are powerful therapeutics; however, their efficacy is often hindered by critical hurdles. Here, utilizing the endocytic feature of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) cytoplasmic tail (CT), we reprogram CAR function and substantially enhance CAR-T efficacy <i>in vivo</i> . CAR-T cells with monomeric, duplex, or triplex CTLA-4 CTs (CCTs) fused to the C-terminus of CAR exhibit a progressive increase in cytotoxicity under repeated stimulation, accompanied by reduced activation and production of pro-inflammatory cytokines. Further characterization reveals that CARs with increasing CCT fusion show a progressively lower surface expression, regulated by their constant endocytosis, recycling and degradation under steady state. The molecular dynamics of reengineered CAR with CCT fusion results in reduced CAR-mediated trogocytosis, loss of tumor antigen, and improved CAR-T survival. CARs with either monomeric (CAR-1CCT) or duplex CCTs (CAR-2CCT) have superior anti-tumor efficacy in a relapsed leukemia model. Single-cell RNA sequencing and flow cytometry analysis reveal that CAR-2CCT cells retain a stronger central memory phenotype and exhibit increased persistence. These findings illuminate a unique strategy for engineering therapeutic T cells and improving CAR-T function through synthetic CCT fusion, which is orthogonal to other cell engineering techniques.
<title>Web caching and prefetching: a data mining approach</title> (2001)

With the increase in popularity of the Internet, the latency experienced by an individual, while accessing the Web, is increasing. In this paper, we investigate one approach to reducing latency by increasing the hit rate for a web cache. To this effect, we developed a predictive model for pre- fetching and a modified Least Recently Used (LRU) method called AssocLRU. This paper investigates the application of a data mining technique, called Association rules to the web domain. The association rules, predict the URLs a user might reference next, and this knowledge is used in our web caching and pre-fetching model. We developed a trace driven cache simulator to compare the performance of our predictive model with the widely used replacement policy, namely, LRU. The traces we used in our experiments were the traces of Web proxy activity taken at Virginia Tech and EPA HTTP. Our results show that our predictive pre-fetching model using association rules achieves a better hit rate than both LRU and AssocLRU.
Stent-Graft Treatment of Pseudoaneurysms and Arteriovenous Fistulae in the Carotid Artery (2006)

The purpose of this study was to assess the safety and efficacy of stent-graft placement in the management of arteriovenous fistulae (AVF) and pseudoaneurysms (PAs) involving the carotid artery (CA). Twenty-two patients (16 men, 6 women) with a CA AVF ( n = 5) or PA ( n = 17) owing to a gunshot or stab wound, carotid endarterectomy, blunt trauma, a tumor, spontaneous dissection, or a central venous catheter were treated with percutaneous placement of stent grafts. The patients presented with tumor, bruit, headache, mouth and tracheostomy bleeding, transitory hemiparesis, seizure, or stroke. Diagnoses were made by using computed tomographic angiography (CTA) and digital subtraction angiography. Fourteen lesions were in the common CA; eight were in the internal CA. Homemade devices and stent grafts from a variety of manufacturers were employed. Follow-up evaluations included clinical, CTA, and Doppler ultrasound assessments. All patients had resolution of the PA or AVF. In one patient with a large petrous PA, acute occlusion of the CA developed after placement of three balloon-expandable stent grafts, but there were no neurologic complications because the circle of Willis was functional. During follow-up ranging from 2 months to 13 years, asymptomatic 90% stenosis owing to stent compression was observed on Doppler ultrasound and angiographic examinations in a patient with an autologous vein–covered stent graft in the internal CA. Three other patients died of causes unrelated to stent-graft placement. In all other patients, the stent graft remained patent. Our results indicate that stent grafting is an acceptable alternative to surgery in the treatment of AVF and PAs in the CA.
Altered gut microbial metabolites could mediate the effects of risk factors in Covid‐19 (2021)

Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is now pandemic. While most Covid-19 patients will experience mild symptoms, a small proportion will develop severe disease, which could be fatal. Clinically, Covid-19 patients manifest fever with dry cough, fatigue and dyspnoea, and in severe cases develop into acute respiratory distress syndrome (ARDS), sepsis and multi-organ failure. These severe patients are characterized by hyperinflammation with highly increased pro-inflammatory cytokines including IL-6, IL-17 and TNF-alpha as well as C-reactive protein, which are accompanied by decreased lymphocyte counts. Clinical evidence supports that gut microbiota dysregulation is common in Covid-19 and plays a key role in the pathogenesis of Covid-19. In this narrative review, we summarize the roles of intestinal dysbiosis in Covid-19 pathogenesis and posit that the associated mechanisms are being mediated by gut bacterial metabolites. Based on this premise, we propose possible clinical implications. Various risk factors could be causal for severe Covid-19, and these include advanced age, concomitant chronic disease, SARS-CoV-2 infection of enterocytes, use of antibiotics and psychological distress. Gut dysbiosis is associated with risk factors and severe Covid-19 due to decreased commensal microbial metabolites, which cause reduced anti-inflammatory mechanisms and chronic low-grade inflammation. The preconditioned immune dysregulation enables SARS-CoV-2 infection to progress to an uncontrolled hyperinflammatory response. Thus, a pre-existing gut microbiota that is diverse and abundant could be beneficial for the prevention of severe Covid-19, and supplementation with commensal microbial metabolites may facilitate and augment the treatment of severe Covid-19.
Statistical Federated Learning for Beyond 5G SLA-Constrained RAN Slicing (2021)

A key enabler for both scalability and sustainability in beyond 5G (B5G) network slicing consists on minimizing the exchange of raw monitoring data across different domains. This is achieved by bringing the analysis functions closer to the data collection points. To this end, we introduce in this paper <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">statistical federated learning</i> (SFL) provisioning models that can learn over a live network non independent identically distributed (non-IID) datasets in an offline fashion while respecting slice-level service level agreement (SLA) long-term statistical constraints. Specifically, we consider three resource SLA metrics, namely, <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">cumulative distribution function</i> (CDF), <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$Q$ </tex-math></inline-formula> - <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th percentile</i> and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">maximum/minimum bounds</i> . These metrics are dataset-dependent and non-convex non-differentiable and, to sidestep the inaccuracy of settling only for surrogates, we propose a novel formulation that jointly considers the statistical objective and constraints as well as their smooth approximation using the <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">proxy-Lagrangian</i> framework, which we solve via a non-zero sum two-player game strategy. Numerical results on various slice-level resources show that SFL enables SLA enforcement while significantly reducing the overhead compared to both state-of-the-art FedAvg and centralized constrained deep learning schemes. Finally, we provide an analysis for the lower bound of the so-called <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">reliable convergence probability</i> in the SFL setup.
Localization and characterization of members of a family of repetitive sequences in the goat βglobin locus (1985)

We have characterized a family of repetitive DNA elements in the beta-globin locus of the goat. These sequences are structurally analogous to the Alu families of repeats of other mammals. Repetitive elements are located both in the intervening sequences and in the intergenic regions of the goat beta-globin locus. Nucleotide sequence analysis of five repetitive elements located within the large intervening sequence of the beta-like globin genes, and four repeats located 5' to the major developmentally regulated beta-globin genes has resulted in the definition of a consensus sequence for this family of repeats.
Tendon‐derived stem/progenitor cell aging: defective self‐renewal and altered fate (2010)

Aging is a major risk factor for tendon injury and impaired tendon healing, but the basis for these relationships remains poorly understood. Here we show that rat tendon- derived stem ⁄ progenitor cells (TSPCs) differ in both self-renewal and differentiation capability with age. The frequency of TSPCs in tendon tissues of aged animals is markedly reduced based on colony formation assays. Proliferation rate is decreased, cell cycle progression is delayed and cell fate patterns are also altered in aged TSPCs. In particular, expression of tendon lineage marker genes is reduced while adipocytic differentiation increased. Cited2, a multi-stimuli responsive transactivator involved in cell growth and senescence, is also downregulated in aged TSPCs while CD44, a matrix assembling and organizing protein implicated in tendon healing, is upregulated, suggesting that these genes participate in the control of TSPC function.
Multi-aperture photography (2007)

The emergent field of computational photography is proving that, by coupling generalized imaging optics with software processing, the quality and flexibility of imaging systems can be increased. In this paper, we capture and manipulate multiple images of a scene taken with different aperture settings (f-numbers). We design and implement a prototype optical system and associated algorithms to capture four images of the scene in a single exposure, each taken with a different aperture setting. Our system can be used with commercially available DSLR cameras and photographic lenses without modification to either. We leverage the fact that defocus blur is a function of scene depth and f/# to estimate a depth map. We demonstrate several applications of our multi-aperture camera, such as post-exposure editing of the depth of field, including extrapolation beyond the physical limits of the lens, synthetic refocusing, and depth-guided deconvolution.
Investigation of the effect of taurine supplementation on muscle taurine content in the mdx mouse model of Duchenne muscular dystrophy using chemically specific synchrotron imaging (2020)

Duchenne muscular dystrophy (DMD) is a lethal genetic muscle wasting disorder, which currently has no cure. Supplementation with the drug taurine has been shown to offer therapeutic benefit in the mdx model for DMD, however the mechanism by which taurine protects dystrophic muscle is not fully understood. Mdx muscle is deficient in taurine, however it is not known if this deficiency occurs in the extracellular space, in other cells present in the tissue (such as immune cells) or in the myofibre itself. Likewise, the tissue location of taurine enrichment in taurine treated mdx muscle is not known. In this study we applied X-ray absorption near edge spectroscopy (XANES) at the sulfur K-edge in an imaging format to determine taurine distribution in muscle tissue. XANES is the only technique currently capable of imaging taurine directly in muscle tissue, at a spatial resolution approaching myocyte cell size (20-50 μm). Using a multi-modal approach of XANES imaging and histology on the same tissue sections, we show that in mdx muscle, it is the myofibres that are deficient in taurine, and taurine supplementation ameliorates this deficiency. Increasing the taurine content of mdx myofibres was associated with a decrease in myofibre damage (as shown by the percentage of intact myofibres) and inflammation. These data will help drive future studies to better elucidate the molecular mechanisms through which taurine protects dystrophic muscle; they also support the continued investigation of taurine as a therapeutic intervention for DMD.
The transcription factor Bcl11b is specifically expressed in group 2 innate lymphoid cells and is essential for their development (2015)

Group 2 innate lymphoid cells (ILCs), or ILC2s, are a subset of recently identified ILCs, which play important roles in innate immunity by producing type 2 effector cytokines. Several transcription factors have been found to have critical functions in the development of both ILC2s and T cells. We report here that Bcl11b, a transcription factor essential in T cell lineage commitment and maintenance, is specifically expressed in progenitors committed to the ILC2 lineage and is required for ILC2 development. The Bcl11b gene is expressed in ∼28% of ILC progenitors (ILCPs; common helper innate lymphoid progenitors or ILCPs expressing either ID2 or promyelocytic leukemia zinc finger, respectively). Both in vitro and in vivo, these Bcl11b-expressing early ILCPs generate only ILC2s. Inactivation of Bcl11b causes a complete loss of ILC2 development from hematopoietic progenitors, which is confirmed upon immune challenge with either papain administration or influenza virus infection.
Principle of Photoconductive Ferroelectric Memory and Preliminary Experiments (2000)

A novel concept called photoconductive ferroelectric memory (PFM) is proposed as a means to fabricate ferroelectric random access memories (FeRAMs). The memory device is based on the new operating principle that skillfully integrates the photoconductive effect of the semiconductor with the spontaneous polarization reversal and the pyroelectric effect of ferroelectrics. The entire multilayer structure of the device consists of indium-tin oxide (ITO)/a-Si:H/lead zirconate titanate (PZT)/bottom electrode. The operating principle of the PFM device is designed and theoretically calculated, and the device is then prepared by RF magnetron sputtering. The photoconductive effect of amorphous silicon due to the focused laser light is used for address. The remanent polarization directions of the PZT layer are used for “1” or “0” of memory. The pyroelectric current directions are used for readout. The write-read operation of PFM is proven by observing the hysteresis loop in a single cell and different pyroelectric current direction readouts by light beam illumination.
Mechanisms of lipopolysaccharide-induced neutrophil retention. Relative contributions of adhesive and cellular mechanical properties (1992)

Intravascular LPS rapidly induces neutrophil sequestration in pulmonary capillaries by mechanisms that, although currently unknown, must take into account the size difference between the neutrophil and capillary diameter. To determine whether LPS alters neutrophil stiffness, and hence the ability of neutrophils to traverse capillaries, neutrophil passage through pulmonary capillaries was modeled by passage through filters with 6.5-microns pores. LPS increased retention in the pores in a concentration-dependent fashion that required the presence of heat-inactivated platelet-poor plasma, and was evident as early as 10 min after stimulation. The effect of LPS on the structural properties of the neutrophil was then studied. LPS induced f-actin reorganization in neutrophils in the presence of plasma. Disruption of actin organization and assembly with cytochalasin D completely inhibited early LPS-induced retention and attenuated retention at later timepoints, indicating that LPS-stimulated retention depends on filament organization. LPS-induced actin assembly and retention were abrogated by an antibody directed against CD14, a putative LPS receptor. CD18-dependent adherence of neutrophils contributed significantly to retention only at later timepoints with no significant contribution to retention at 20 min as determined by inhibition of adherence with the mAb 60.3. Morphometric assessment of neutrophil accumulation in the lungs of rabbits given 1 microgram LPS showed a marked increase in apparent neutrophil number, which was unaltered by antibodies to CD18, suggesting that mechanisms other than adhesion may account for accumulation in vivo. Direct measurements showed that neutrophil stiffness increased with exposure to LPS in a fashion similar to LPS-induced retention and actin organization. Pretreatment of neutrophils with cytochalasin D attenuated the increased stiffness. These data suggest that reorganization of filamentous-actin induced by LPS leads to cell stiffening and retention in capillary-sized pores. Although the organization of f-actin continues to be important in retention at later time points, adherence of cells also contributes significantly to cell retention. The changes in mechanical properties of the neutrophil may be important in the sequestration of neutrophils in pulmonary capillaries noted in endotoxemia.
Progressive sclerosing cholangitis after shock: a long-term follow-up study (2007)

Introduction: In 2003 we have described a new form of sclerosing cholangitis (Gut 52, 2003: 688–93). We now present a long-term follow-up study of 25 patients with progressive sclerosing cholangitis treated between 1994 and 2006.
Analyse zeitkontinuierlicher LTI-Systeme mit der Laplace-Transformation (1997)

Die in Kapitel 4 eingeführte Laplace-Transformation dient nicht nur zur Charakterisierung von Signalen, sondern sie erlaubt vor allem auch die elegante Beschreibung der Eigenschaften von LTI-Systemen. In der System- und Netzwerktheorie ist sie zur Standardmethode für die Berechnung der Systemreaktion geworden. Insbesondere können vorgegebene Anfangswerte des Ausgangssignals und Anfangszustände von Systemen berücksichtigt werden.
Two interferometer-type direction-finding systems (1959)

http://deepblue.lib.umich.edu/bitstream/2027.42/7700/5/bad2207.0001.001.pdf
Identification of a Novel Receptor Kinase That Phosphorylates a Phospholipase C-linked Muscarinic Receptor (1996)

Phosphorylation of G-protein-linked receptors is thought to play a central role in receptor regulation and desensitization. Unlike the case of the extensively studied beta-adrenergic receptor/adenylate cyclase pathway, in which receptor-specific phosphorylation is known to be mediated by beta-adrenergic receptor kinase ( beta-ARK), the kinases responsible for phosphorylation of phospholipase C-linked receptors have yet to be identified, although a role for beta-ARK has been implicated. This study describes the purification of a novel 40-kDa receptor kinase from porcine cerebellum that is able to phosphorylate the phospholipase C-linked m3-muscarinic receptor in an agonist-dependent manner. The assay for kinase activity was based on the ability of the kinase to phosphorylate a bacterial fusion protein, Ex-m3, containing amino acids Ser345-Leu463 of the third intracellular loop of the m3-muscarinic receptor. Purification of the muscarinic receptor kinase from a high speed supernatant fraction of porcine cerebellum was achieved using the following steps: (i) 30-60% ammonium sulfate cut and successive chromatography on (ii) butyl-Sepharose (iii) Resource Q, (iv) Resource S, and (v) heparin-Sepharose. The purified protein kinase represented an approximately 18,600-fold purification and was a single polypeptide with a molecular weight of approximately 40 kDa. Based on the chromatographic mobility, molecular weight, and kinase inhibitor studies, the kinase, designated MRK, was shown to be distinct from previously characterized second messenger regulated protein kinases, beta-ARK, and other members of the G-protein-linked receptor kinase family. It therefore represents a new class of receptor kinase.
Variation in the Luminescence Lifetimes of Eucl3·nH2O(N=0,L,2,3,6) (1999)

Abstract Eu3+ ion emission spectra and luminescence lifetimes were investigated for EuCl3 -nH2O (n=0,1,2,3,6). Each compound exhibited a characteristic set of emission bands and a specific luminescence lifetime. The number of water molecules and chloride ions coordinated to the Eu3+ ion in these materials was estimated from the observed lifetimes, spectroscopic implications, and expected lanthanide coordination numbers. Approximation of the observed luminescence decay constant for each material was possible through the use of arithmetic terms associated with both the complexed water molecules and the complexed chloride ions which make up the inner-coordination sphere of the Eu3+ ion.
F11 Progredient deterioration of hepatic mitochondrial function in Huntington's disease: measured by using the 13C-methionin breath test (2012)

<h3>Background</h3> Mitochondrial dysfunction is discussed as a key factor in pathogenesis of Huntington9s Disease. 13C-methionine breath test has been established for non-invasive and easy to perform quantification of hepatic mitochondrial function. <h3>Aim</h3> Aim of this pilot study was to investigate if there is evidence for subclinic hepatic mitochondrial dysfunction in manifest and/or premanifest Huntington9s Disease mutation carriers using the 13C-methionine breath test. <h3>Methods</h3> 13C-methionine breath test was performed within a group of 21 early manifest Huntington9s Disease patients without medication, 30 premanifest mutation carriers as well as 36 healthy controls. All HD participants were scored according to the Unified Huntington9s Disease Rating Scale, premanifest mutation carriers were stratified into the two groups preHD-A (further from predicted onset) and preHD-B (nearer) based on a calculation of the probability of estimated disease onset within 5 years. 13C-methionine breath test was performed after an overnight fasting, breath samples were analysed by non-dispersive isotope-selective infrared spectroscopy and results expressed as percentage dose recovered after 90 min of testing time. In 25 preHD participants a longtudinal follow-up investigation after 14.5 month was possible. Statistical analysis comprised ANCOVA and post hoc t-tests. <h3>Results</h3> Manifest Huntington9s Disease patients and mutation carriers from our PreHD-B group revealed a significant lower amount of exhaled 13CO2 compared to healthy controls (p&lt;0.001; p=0.017 respectively). In a stepwise linear regression model breath test results correlate significant to functional and cognitive scores of the Unified Huntington9s Disease Rating Scale in manifest and also in premanifest Huntington9s Disease. For all mutation carriers together there was a weak, but significant correlation of breath test results to ratio caudate volume/total intracranial volume. PreHD-B (nearer) mutation cariers showed a significant lower amount of exhaled 13CO2 after 14.5 month. <h3>Conclusions</h3> This study clearly demonstrates for the first time in vivo a subclinical, progredient hepatic involvement in manifest and premanifest Huntington9s Disease.