gebhart/patrepeval huggingface dataset:
Cytokine‐modified <i>Mycobacterium smegmatis</i> as a novel anticancer immunotherapy (2004)

Intravesical administration of live M. bovis BCG organisms for carcinoma in situ of the urinary bladder is the most successful immunotherapy for solid malignancy. Nevertheless BCG-therapy is associated with significant toxicity and is ineffective in 30-40% of cases. Recently it has been proposed that cytokine-modified mycobacteria may give greater efficacy. As any immunotherapy involving administration of live BCG organisms (wild-type or recombinant) is likely to have associated toxicity (notably in the immunocompromised), we examined the anti-tumour potential of the closely related nonpathogenic organism, Mycobacterium smegmatis, and a TNFalpha gene-modified recombinant M. smegmatis. When wild-type M. smegmatis were delivered to immunocompetent C57Bl/6 mice bearing the transplantable MB49 bladder tumour, efficacy comparable to live BCG was observed with 10-20% long-term survival. However, this effect was lost in both Nude and Beige mice, lacking functional T and NK cells, respectively. Recombinant M. smegmatis secreting TNFalpha, however, gave a 70% durable tumour-free survival. Lymphocytes from draining lymph-nodes and spleens of these mice exhibited pronounced IFNgamma production to mycobacterial-antigen and tumour-lysate, indicating a bias towards cell-mediated immunity. This was further supported by histopathological examination of the tumour site, which revealed significantly increased numbers of CD3+ lymphocytes in animals receiving the recombinant vaccine, but not in those receiving wild-type bacteria. Importantly, tumour rejection following M. smegmatis/TNFalpha was independent of T lymphocytes, as athymic Nude mice efficiently eradicated MB49 tumours. In contrast, the therapeutic efficacy of M. smegmatis/TNFalpha was reduced in animals deficient in NK cytolytic function, suggesting a role for NK-cells in initial tumour destruction. Furthermore the absence of NK-function in Beige mice did not prevent the establishment of tumour-protective memory. No toxicity was observed with wild-type or recombinant M. smegmatis in immunocompetent, T-deficient or NK-deficient models. We demonstrate for the first time that recombinant mycobacteria expressing mammalian cytokines have markedly increased anti-tumour properties. The lack of toxicity suggests that M. smegmatis is a "safe" vehicle for use in immunocompromised patients.
Local delivery of beta interferon using an adeno-associated virus type 5 effectively inhibits adjuvant arthritis in rats (2007)

Beta interferon (IFN-beta) is a cytokine with potent immunomodulatory properties and has been described as a promising therapeutic molecule for the treatment of rheumatoid arthritis (RA). IFN-beta was previously overexpressed intra-articularly using an adenoviral vector in rats with adjuvant arthritis (AA) as a model of RA. This effect was powerful, albeit transient due to the vector chosen. Therefore, in the context of pre-clinical development, a delivery vector optimized for intra-articular gene transfer, recombinant adeno-associated virus type 5 (rAAV5), was selected. To exert an optimal effect, protein production should parallel the course of the disease. For this reason, the gene for IFN-beta was placed under the control of an inflammation-responsive [nuclear factor (NF)-kappaB] promoter. After intra-articular injection of the rAAV5 constructs in rats with AA, local transcription of the transgene and production of the IFN-beta protein was found, leading to a pronounced and sustained effect on paw swelling when the expression was under the control of the NF-kappaB-responsive promoter. Additionally, a significant beneficial effect was observed on proteoglycan depletion and erosions. Thus, intra-articular overexpression of IFN-beta using a rAAV5 vector exhibits potential as an innovative therapy for the treatment of RA.
Substructures in deformed Fe-15 Ni-0.8 C austenite (1984)

In a recent study, the mechanical behavior of an Fe-15 Ni-0.8 C austenite was determined at various strain rates and temperatures. An important finding of this study was the formation of intense shear bands during deformation at temperatures much greater than which bore no resemblance to the common morphologies of martensites. There is much disagreement in the literature regarding the mechanism of band formation and the associated substructure. These bands have been reported to be fine BCC martensite particles or laths delineating slip bands or thin twins in the austenite matrix. The purpose of the present work was to determine by transmission electron microscopy and diffraction the substructure of the fine bands and to attempt to clarify the various interpretations. For comparison, the substructure produced at a lower deformation temperature was also evaluated where the martensite was known to have the normal strain-induced morphology.
Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma (2022)

NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit-risk ratio of NBTXR3 plus RT.
Improving area efficiency of FIR filters implemented using distributed arithmetic (2002)

In this paper we present techniques for improving area efficiency of FIR filters implemented using the distributed arithmetic (DA) approach. These techniques exploit the flexibility in partitioning the filter coefficients for a two lookup-table (LUT) based DA implementation. The first technique is targeted at a ROM based implementation of LUTs and aims at minimizing number of columns/outputs of the ROMs. The second technique is targeted at a hardwired implementation of LUTs. We have developed an estimation technique for relative area comparisons of hardwired LUTs having the same number of inputs and outputs. We present a heuristic approach, based on this estimation technique, to optimally partition coefficients so as to achieve area-efficient hardwired implementation of LUTs. We present results to show these techniques can result in 10% to 15% area reduction for ROM based implementations and 20% to 25% area reduction for hardwired implementations.
Observation of Nonlinear Standing Waves Excited by Plasma-Series-Resonance-Enhanced Harmonics in Capacitive Discharges (2019)

We report the first experimental observation of nonlinear standing waves excited by plasma-series-resonance-enhanced harmonics in low pressure, very high frequency, parallel plate, capacitively coupled plasmas. Spatial structures of the harmonics of the magnetic field, measured by a magnetic probe, are in very good agreement with simulations based on a nonlinear electromagnetics model. At relatively low pressure, the nonlinear sheath motion generates high-order harmonics that can be strongly enhanced near the series resonance frequencies. Satisfying certain conditions, such nonlinear harmonics induce radial standing waves, with voltage and current maxima on axis, resulting in center-high plasma density. Excitation of higher harmonics is suppressed at higher pressures.
Octreotide use and safety in infants with hyperinsulinism (2016)

This study highlights potential risks in administering octreotide off-label. This study, like several other published studies, has highlighted NEC in a full-term infant treated with octreotide. It is important to study the efficacy and the safety of octreotide for hyperinsulinism. In the interim, it might be prudent to prescribe octreotide in CHI neonates only in the absence of other risk factors for NEC. Copyright © 2016 John Wiley & Sons, Ltd.
0284 Differential gene expression in cattle challenged with single pathogens of the bovine respiratory disease complex (2016)

Bovine respiratory disease complex (BRDC) is an important infectious cause of mortality and morbidity in cattle. BRDC develops when stressed cattle are infected with one of several viruses followed by one or more bacterial pathogens. To evaluate the host response to each of these pathogens, we measured global transcript abundance using RNA sequence analysis, comparing infected steers with normal controls after single pathogen infections. At maximum clinical signs, steers were euthanized for necropsy and collection of lung, bronchial, nasopharyngeal, and retropharyngeal lymph nodes, and pharyngeal tonsils for RNA sequencing. Viral agents used for the challenge were: bovine respiratory syncytial virus (BRSV), infectious bovine rhinotracheitis (IBR), and bovine viral diarrhea virus (BVDV). Bacteria used to challenge included: Mannheimnia hemolytica, Pasteurella multocida, and Mycoplasma bovis. Differential expression of genes coding for non-specific defense innate immunity and the acute phase response was found among all pathogen infections. These included pattern recognition receptors, mucins, and host defense peptides; more specific immune response genes were differentially expressed in individual pathogen infections. Adaptive immune system pathways for both T and B cells were activated in BRSV infection. In general viral infections elicited a greater number of differentially expressed genes than bacterial pathogens. Tissues were compared and found to contain both differentially expressed genes shared among all tissues examined and specific to tissue type. Overall data obtained will have important implications for design of better therapeutic modalities; and will help further elucidate the complex pathogenesis of BRDC.
Compositional Variations in Sedimentary Deposits in Gale Crater as Observed by ChemCam Passive and Active Spectra (2022)

During the first 2934 sols of the Curiosity rover’s mission 33,468 passive visible/near-infrared reflectance spectra were taken of the surface by the mast-mounted ChemCam instrument on a range of target types. ChemCam spectra of bedrock targets from the Murray and Carolyn Shoemaker formations on Mt. Sharp were investigated using principal component analysis (PCA) and various spectral parameters including the band depth at 535 nm and the slope between 840 nm and 750 nm. Four endmember spectra were identified. Passive spectra were compared to Laser Induced Breakdown Spectroscopy (LIBS) data to search for correlations between spectral properties and elemental abundances. The correlation coefficient between FeOT reported by LIBS and BD535 from passive spectra was used to search for regions where iron may have been added to the bedrock through oxidation of ferrous-bearing fluids, but no correlations were found. Rocks in the Blunts Point-Sutton Island transition that have unique spectral properties compared to surrounding rocks, that is flat near-infrared (NIR) slopes and weak 535 nm absorptions, are associated with higher Mn and Mg in the LIBS spectra of bedrock. Additionally, calcium-sulfate cements, previously identified by Ca and S enrichments in the LIBS spectra of bedrock, were also shown to be associated with spectral trends seen in Blunts Point. A shift towards steeper near-infrared slope is seen in the Hutton interval, indicative of changing depositional conditions or increased diagenesis.
Sol-gel entrapped visible light photocatalysts for selective conversions (2014)

A new photoactive, low-cost nanomaterial to harvest solar energy and use it a selective reactant is now available. Sol–gel encapsulation of flower-like Bi<sub>2</sub>WO<sub>6</sub>into transparent silica glass affords a catalyst far more active, but still highly selective, compared to the non-entrapped species.
Assessment of bone dysplasia by micro‐CT and glycosaminoglycan levels in mouse models for mucopolysaccharidosis type I, IIIA, IVA, and VII (2012)

Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases caused by mutations in lysosomal enzymes involved in degradation of glycosaminoglycans (GAGs). Patients with MPS grow poorly and become physically disabled due to systemic bone disease. While many of the major skeletal effects in mouse models for MPS have been described, no detailed analysis that compares GAGs levels and characteristics of bone by micro-CT has been done. The aims of this study were to assess severity of bone dysplasia among four MPS mouse models (MPS I, IIIA, IVA and VII), to determine the relationship between severity of bone dysplasia and serum keratan sulfate (KS) and heparan sulfate (HS) levels in those models, and to explore the mechanism of KS elevation in MPS I, IIIA, and VII mouse models. Clinically, MPS VII mice had the most severe bone pathology; however, MPS I and IVA mice also showed skeletal pathology. MPS I and VII mice showed severe bone dysplasia, higher bone mineral density, narrowed spinal canal, and shorter sclerotic bones by micro-CT and radiographs. Serum KS and HS levels were elevated in MPS I, IIIA, and VII mice. Severity of skeletal disease displayed by micro-CT, radiographs and histopathology correlated with the level of KS elevation. We showed that elevated HS levels in MPS mouse models could inhibit N-acetylgalactosamine-6-sulfate sulfatase enzyme. These studies suggest that KS could be released from chondrocytes affected by accumulation of other GAGs and that KS could be useful as a biomarker for severity of bone dysplasia in MPS disorders.
Evaluation of Cell-Based and Surrogate SARS-CoV-2 Neutralization Assays (2021)

Determinants of protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require the development of well-standardized, reproducible antibody assays. This need has led to the emergence of a variety of neutralization assays. Head-to-head evaluation of different SARS-CoV-2 neutralization platforms could facilitate comparisons across studies and laboratories. Five neutralization assays were compared using 40 plasma samples from convalescent individuals with mild to moderate coronavirus disease 2019 (COVID-19): four cell-based systems using either live recombinant SARS-CoV-2 or pseudotyped viral particles created with lentivirus (LV) or vesicular stomatitis virus (VSV) packaging and one surrogate enzyme-linked immunosorbent assay (ELISA)-based test that measures inhibition of the spike protein receptor binding domain (RBD) binding its receptor human angiotensin converting enzyme 2 (hACE2). Vero cells, Vero E6 cells, HEK293T cells expressing hACE2, and TZM-bl cells expressing hACE2 and transmembrane serine protease 2 were tested. All cell-based assays showed 50% neutralizing dilution (ND<sub>50</sub>) geometric mean titers (GMTs) that were highly correlated (Pearson <i>r </i>= 0.81 to 0.89) and ranged within 3.4-fold. The live virus assay and LV pseudovirus assays with HEK293T/hACE2 cells showed very similar mean titers, 141 and 178, respectively. ND<sub>50</sub> titers positively correlated with plasma IgG targeting SARS-CoV-2 spike protein and RBD (<i>r </i>= 0.63 to 0.89), but moderately correlated with nucleoprotein IgG (<i>r </i>= 0.46 to 0.73). ND<sub>80</sub> GMTs mirrored ND<sub>50</sub> data and showed similar correlation between assays and with IgG concentrations. The VSV pseudovirus assay and LV pseudovirus assay with HEK293T/hACE2 cells in low- and high-throughput versions were calibrated against the WHO SARS-CoV-2 IgG standard. High concordance between the outcomes of cell-based assays with live and pseudotyped virions enables valid cross-study comparison using these platforms.
Femtosecond direct written waveguides in Bismuth Germanate (2011)

We have identified a waveguide writing regime that allows us to fabricate low loss (-1dB/cm) multimode waveguides in BGO without damaging the surrounding material or by creating a stress field. Fig. 1 (a) shows the micrograph of the cross section of a written waveguide, no damage is visible, the core is elliptical and supports multimode guiding at a wavelength of 1.5 μm.
Minimizing Dilutional Coagulopathy in Exsanguinating Hemorrhage: A Computer Simulation (2003)

Existing protocols underestimate the dilution of clotting factors in severely bleeding patients. The model presents an innovative approach to optimizing component replacement in exsanguinating hemorrhage.
P510 Dose escalation of subcutaneous vedolizumab in patients with ulcerative colitis: A post hoc analysis of the VISIBLE trial data (2020)

Abstract Background Vedolizumab (VDZ), a gut-selective, α 4β7 integrin monoclonal antibody, is approved for intravenous (IV) administration to patients with moderate-severe ulcerative colitis (UC). Subcutaneous (SC) VDZ was evaluated for maintenance therapy for UC in VISIBLE 1, a double-blind, placebo-controlled, Phase 3 study, and its open-label extension (OLE). We evaluated the efficacy of increasing dose frequency of VDZ SC from every-2-weeks (Q2W) to weekly administration (QW) after treatment failure (disease worsening or need for rescue medication). Methods In VISIBLE 1 (NCT02611830; EudraCT 2015-000480-14), a Q2W dosing regimen was used for patients with UC who achieved clinical response at week 6 (after open-label IV VDZ inductions at weeks 0 and 2) and were randomised to maintenance treatment with VDZ SC. Patients who did not respond at week 6 but responded by week 14 rolled over to the VISIBLE OLE (NCT02620046; EudraCT: 2015-000482-31) and received Q2W VDZ SC dosing. In VISIBLE 1 and the OLE, 2 groups of patients experienced dose escalation: (1) patients who entered the VISIBLE OLE study on a Q2W VDZ dosing regimen but experienced disease worsening and were escalated to QW dosing (OLE Q2W/QW); and (2) patients who experienced treatment failure during Q2W VDZ treatment in VISIBLE 1, rolled over to OLE, and were escalated to a QW dosing regimen (VISIBLE 1 treatment failure). Efficacy was evaluated by clinical remission and response rates after dose escalation using partial Mayo scores at the visits in the Visible OLE study. In this interim analysis, not all patients continuing in the trial had not completed all study visits. Only patients who had completed a given visit (evaluable patients) were included in the analyses for that visit. Results Of the 54 patients who received dose escalation 52% were male. Mean age was 39 years, mean UC duration was 7.4 years; 76% had severe disease activity (Mayo 9–12) at baseline, and 43% had prior anti-TNF therapy failure (Table 1). Of the patients with dose escalation, 27.1% (13/48 evaluable patients) recaptured clinical remission 16 weeks after dose escalation and 10.8% (4/37 evaluable patients) were in clinical remission after 48 weeks (Table 2). A similar trend was observed for clinical response rates in this patient population. Conclusion Increasing the frequency of VDZ SC dosing to QW recaptured lost response to treatment for some patients. These are interim results of the OLE study; further follow-up during the ongoing OLE will provide more insight into the long-term efficacy and safety of dose escalation with VDZ SC.
Factors controlling <i>T</i><sub>2</sub> mapping from partially spoiled SSFP sequence: Optimization for skeletal muscle characterization (2011)

A fast and robust methodology for in vivo T(2) mapping is presented. The approach is based on the partially spoiled steady state free precession technique recently proposed by Bieri et al. (Magn Reson Med 2011). The accuracy of this method was demonstrated in simulations and phantom experiments. Variations in skeletal muscle T(2) relaxation time have been correlated with cell damage and inflammatory response. Nonetheless, the lack of easily implementable, fast, accurate and reproducible methods has hampered the adoption of T(2) measurement as a noninvasive tool for skeletal muscle characterization. The applicability of the partially spoiled steady state free precession method for tissue characterization in muscle disease is illustrated in this work by several examples. Quantitative MRI, in particular T(2) mapping based on partially spoiled steady state free precession acquisitions, might provide objective markers of muscle damage and degenerative changes, and an alternative to serial muscle biopsies.
Visual Acuity, Crowding, and Stereo-Vision Are Linked in Children with and without Amblyopia (2012)

Our results demonstrate an association between IODs in acuity and crowding and, furthermore, between these IODs and the presence of stereo-vision. We suggest that the deficits derived from strabismus and anisometropia lay along a continuum with abilities observed during normal development.
An Ad/MVA vectored Theileria parva antigen induces schizont-specific CD8+ central memory T cells and confers partial protection against a lethal challenge (2018)

The parasite <i>Theileria parva</i> is the causative agent of East Coast fever (ECF), one of the most serious cattle diseases in sub-Saharan Africa, and directly impacts smallholder farmers' livelihoods. There is an efficient live-parasite vaccine, but issues with transmission of vaccine strains, need of a cold chain, and antibiotics limit its utilization. This has fostered research towards subunit vaccination. Cytotoxic T lymphocytes (CTL) are crucial in combating the infection by lysing <i>T. parva</i>-infected cells. Tp1 is an immunodominant CTL antigen, which induces Tp1-specific responses in 70-80% of cattle of the A18 or A18v haplotype during vaccination with the live vaccine. In this study, human adenovirus serotype 5 (HAd5) and modified vaccinia Ankara (MVA) were assessed for their ability to induce Tp1-specific immunity. Both viral vectors expressing the Tp1 antigen were inoculated in cattle by a heterologous prime-boost vaccination regimen. All 15 animals responded to Tp1 as determined by ELISpot. Of these, 14 reacted to the known Tp1 epitope, assayed by ELISpot and tetramer analyses, with CTL peaking 1-week post-MVA boost. Eleven animals developed CTL with specific cytotoxic activity towards peripheral blood mononuclear cells (PBMC) pulsed with the Tp1 epitope. Moreover, 36% of the animals with a Tp1 epitope-specific response survived a lethal challenge with <i>T. parva</i> 5 weeks post-MVA boost. Reduction of the parasitemia correlated with increased percentages of central memory lymphocytes in the Tp1 epitope-specific CD8<sup>+</sup> populations. These results indicate that Tp1 is a promising antigen to include in a subunit vaccine and central memory cells are crucial for clearing the parasite.
Supplementary Figure Legends from TIG1 Promotes the Development and Progression of Inflammatory Breast Cancer through Activation of Axl Kinase (2023)

&lt;p&gt;PDF file, 80K.&lt;/p&gt;
Optimal and Suboptimal Routing Based on Partial CSI in Random Ad-Hoc Networks (2018)

In this paper, we consider routing in random wireless-ad hoc-networks, where each node is equipped with a single antenna. Our analysis uses a proper model of the physical layer together with an abstraction of higher communication layers. We assume that the nodes are distributed according to a Poisson-point-process and consider routing schemes that select the next relay based on the geographical locations, the channel gains of its neighbor nodes and the statistical characterization of all other nodes. While many routing problems are formulated as optimization problems, the optimal distributed solution is rarely accessible. In this paper, we present the exact optimal solution for the scenario analyzed. The optimal routing is given as a maximization of a routing metric, which depends solely on the known partial channel state information and includes an expectation with respect to the interference statistics. The optimal routing scheme is important because it gives an upper bound on the performance of any other routing scheme. We also present sub-optimal routing schemes that only use part of the available knowledge and require much lower computational complexity. Numerical results demonstrate that the performance of the low complexity schemes is close to optimal and outperforms other tested routing schemes.