gebhart/patrepeval huggingface dataset:
Low-voltage backscattered electron imaging of non-coated biological samples in a low-vacuum environment using a variable-pressure scanning electron microscope with a YAG-detector (1998)

A variable-pressure scanning electron microscope (VP-SEM) equipped with a high-sensitive backscattered electron (BSE) detector of the YAG type was applied to studies of biological tissue samples. The rat kidney and trachea were fixed, dehydrated in ethanol, critical point-dried and examined in the VP-SEM under a specimen chamber pressure of 1 to 150 Pa. The high-resolution surface images of the non-coated specimens were obtained in a low-vacuum (1-20 Pa) environment at an accelerating voltage of 5 kV, while the images at 10-20 kV contained information beneath the surface of the specimens. The observation in the VP-SEM equipped with YAG detector in a low-vacuum (1-20 Pa) environment at low (3-5 kV) accelerating voltages is useful for the three-dimensional analysis of the surface morphology of biological non-coated samples.
C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector (2016)

Abstract The CRISPR-Cas adaptive immune system defends microbes against foreign genetic elements via DNA or RNA-DNA interference. We characterize the Class 2 type VI-A CRISPR-Caseffector C2c2 and demonstrate its RNA-guided RNase function. C2c2 from the bacterium Leptotrichia shahii provides interference against RNA phage. In vitro biochemical analysis show that C2c2 is guided by a single crRNA and can be programmed to cleave ssRNA targets carrying complementary protospacers. In bacteria, C2c2 can be programmed to knock down specific mRNAs. Cleavage is mediated by catalytic residues in the two conserved HEPN domains, mutations in which generate catalytically inactive RNA-binding proteins. These results broaden our understanding of CRISPR-Cas systems and suggest that C2c2 can be used to develop new RNA-targeting tools.
Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome (2015)

If replicated in future studies, serum NfL may represent a reliable and easily accessible biomarker of early axonal damage in CIS and MS.
A comparison of intense pulsed light, combination radiofrequency and intense pulsed light, and blue light in photodynamic therapy for acne vulgaris. (2007)

ALA-PDT with activation by IPL appears to provide greater, longer-lasting, and more consistent improvement than either RF-IPL or blue light activation in the treatment of moderate to severe acne vulgaris.
Cannabis Smoke Condensate I: The Effect of Different Preparation Methods on Tetrahydrocannabinol Levels (2008)

Cannabis sativa contains more than 400 known compounds, of which the terpene chemicals, called cannabinoids, are unique to this species. The cannabinoids, which occur as the corresponding acids in the plant material, are the major psychoactive components in this species. The compounds are decarboxylated from the inactive acidic form into the active form by means of smoking. Previous research has made use of the tobacco industry's standard method and adaptations thereof to produce a cannabis smoke condensate. In this study the method of smoke production, which includes the puff frequency, puff length, and puff volume, was tested and the concentration of the major cannabinoid, Delta(9)-tetrahydrocannabinol (THC), and the amount of by-products produced under the different conditions were quantified. This study aimed at combining the existing methodology and at providing quantitative results on the influence of the preparation method on the concentration of THC in the smoke. The results indicate that the method of smoke production influences the amount of THC produced (e.g., longer puff length yielding a higher amount of THC). The THC concentration in the smoke condensate varied between 22.17 mg/g of cannabis and 54.00 mg/g, while the amount of by-products produced varied between 25.57 mg/g and 107.40 mg/g.
The mast cell: a neuroimmunoendocrine master player. (1996)

This review of the literature on mast cells (MC) suggests that when activated they may play a central role in disease syndromes with a neural, immune and endocrine component exacerbated under stress. After a discussion of their biology, differential secretions and interaction with neurons, the effect of stress in causing MC degranulation is emphasized. The importance of MC in syndromes such as migraine, multiple sclerosis, interstitial cystitis and irritable bowel syndrome is assessed, along with possible therapeutic possibilities with compounds that inhibit MC activation.
Metabolic comparison between basophils and other leukocytes from human blood. (1986)

Basophilic granulocytes were purified from the blood of normal individuals by successive isopyknic centrifugation and elutriation centrifugation. Starting with the leukocyte-rich fraction of 500 ml of blood, we recovered 31 to 80% (mean 51%, n = 20) of the basophils in 45 to 87% purity (mean 69%, n = 23). The contaminating cells were mainly lymphocytes. The basophils were greater than 98% vital (exclusion of ethidium bromide and hydrolysis of fluorescein diacetate). The histamine content of the basophils was 1.1 to 2 pg/cell (mean 1.6 pg/cell, n = 22). With anti-IgE, 30 to 50% of the histamine was released; with phorbol myristic acetate (PMA) or the calcium ionophore A23187, 70 to 100% of the histamine was released. Serum-opsonized zymosan (STZ) did not induce histamine release. Reactions with monoclonal antibodies revealed that the basophils expressed the C3bi receptor (CR3) and the leukocyte function-associated antigen 1 (LFA1), but not the gp 150,95 antigen, the C3b receptor (CR1), or the low avidity Fc gamma receptor. Basophils carry class I but not class II HLA antigens. During incubation of the basophils with serum-opsonized Staphylococcus aureus or Escherichia coli, these bacteria were neither phagocytized nor killed. STZ, PMA, A23187, or anti-IgE did not initiate an "oxidative burst" in the basophils. This was tested with oxygen consumption, cytochrome c reduction, NBT reduction, chemiluminescence, and release of hydrogen peroxide. Moreover, we did not detect cytochrome b558, superoxide dismutase, catalase, or peroxidase in the basophils. Of the typical granule-associated enzymes lysozyme, Vitamin B12-binding protein, and beta-glucuronidase, only beta-glucuronidase was present in the basophils in detectable amounts. This enzyme was released, together with histamine, on incubation of the cells with PMA, A23187, or anti-IgE, but not with STZ. We conclude that basophils from normal human blood are not phagocytes and are probably not involved in the oxidative defense of the host against foreign antigens.
Notch1 and Jagged1 are expressed after CNS demyelination, but are not a major rate-determining factor during remyelination (2004)

The reasons for the eventual failure of repair mechanisms in multiple sclerosis are unknown. The presence of precursor and immature oligodendrocytes in some non-repairing lesions suggests a mechanism in which these cells either receive insufficient differentiation signals or are exposed to differentiation inhibitors. Jagged signalling via Notch receptors on oligodendrocyte precursor cells (OPCs) inhibits their differentiation during development and the finding that both notch and jagged are expressed in multiple sclerosis lesions has fostered the view that this signalling pathway may explain remyelination failure. In this study, we show that Notch1 is expressed on adult OPCs and that there are multiple cellular sources of its ligand Jagged1 in a rodent model of remyelination. However, despite their expression, the lesions undergo complete remyelination. To establish whether Notch-jagged signalling regulates the rate of remyelination we compared their expression profiles in young animals with those in older animals, where remyelination occurs more slowly, but could find no correlation between expression and remyelination rate. Finally we found that OPC-targeted Notch1 ablation in cuprizone-treated Plp-creER Notch1(lox/lox) transgenic mice yielded no significant differences in remyelination parameters between knock-out and control mice. Thus, in contrast to developmental myelination, adult expression of Notch1 and Jagged1 neither prevents nor plays a major rate-determining role in remyelination. More generally, the re-expression of developmentally expressed genes following injury in the adult does not per se imply similar function.
Longitudinal assessment of synovial, lymph node, and bone volumes in inflammatory arthritis in mice by in vivo magnetic resonance imaging and microfocal computed tomography (2007)

In vivo CE-MRI and micro-CT 3-D outcome measures are powerful tools that accurately demonstrate the progression of erosive inflammatory arthritis in mice. These methods can be used to identify mice with arthritis of similar severity before intervention studies are initiated, thus minimizing heterogeneity in outcome studies of chronic arthritis seen between genetically identical littermates.
CD40 molecules induce down-modulation and endocytosis of T cell surface T cell-B cell activating molecule/CD40-L. Potential role in regulating helper effector function. (1994)

The T-BAM/CD40-L molecule on CD4+ T cells interacts with B cell CD40 molecules to deliver contact-dependent signals that drive B cell activation and Ig secretion. Cell surface T-BAM/CD40-L expression is transient and may be closely regulated in order to limit the activation and clonal selection of noncognate B cells. We demonstrate that B cells, but not non-B cells, rapidly and specifically down-modulate surface T-BAM/CD40-L expression in a contact-dependent and temperature-sensitive manner that renders T cells unable to activate resting bystander B cells. Because the ability to down-modulate T-BAM/CD40-L correlated with CD40 expression, the role of CD40 molecules in down-modulating its ligand was directly assessed. Anti-CD40 mAb, but not control mAb, block B cell-induced T-BAM/CD40-L down-modulation. Furthermore, CD40+ nonlymphoid transfectants specifically down-modulate surface T-BAM/CD40-L expression. B cells induce T-BAM/CD40-L internalization into cytoplasmic compartments in a process that is inhibited by cytochalasin B. Pretreatment of activated T cells with lysosomotropic agents does not affect CD40-induced down-modulation of surface T-BAM/CD40-L but results in a marked accumulation of T-BAM/CD40-L in cytoplasmic vesicles. Together, these studies strongly suggest that CD40 induced T-BAM/CD40-L down-modulation occurs, in part, by receptor-mediated endocytosis followed by lysosomal degradation and may represent a mechanism to regulate CD4+ T cell helper effector functions.
Animal models of cutaneous lupus erythematosus and lupus erythematosus photosensitivity (1997)

Over the past decade, the most exciting and important finding in SLE-prone mice is the discovery of Fas/Fas ligand systems in the pathogenesis of autoimmune phenomena. A human model for murine lpr/gld disease has also been reported recently. Furthermore, as shown in Table 2, studies on Ig variable region genes, TCR genes and MHC class II genes have given us much information concerning human and murine SLE. With respect to cytokines, IL-2 deficiency and the key role of IL-6 have been found in SLE-prone mouse strains, and Th2 cytokine production has been demonstrated to play a more pathogenic role than Th1 cytokine production in human and murine SLE except for MRL/pr mice. TGF is also very intriguing because TGF-beta knockout mice show SLE-like autoantibodies and Sjögren syndrome-like lymphoproliferation. Apart from these basic scientific investigations, there are also many promising and practical therapeutic approaches. In particular, treatments with anti-CD4 antibody and murine CTLA4Ig which bound B7 and blocked binding of CD28 to B7 are outstanding. However, it remains obscure whether such new approaches are effective for the skin lesions of SLE-prone mice, although some immunosuppressive agents such as FK506, cyclosporin and Chinese herbal medicines have been evaluated to determine their selective effects on the skin lesions of MRL/lpr mice. Needless to say, mouse models are not identical, but similar, to human diseases. However, they are important in the search for the underlying pathogenesis of autoimmune diseases on the basis of careful evaluation of the similarities and differences between human diseases and these models. If such studies are steadily performed, then inbred or experimental models will become more promising tools for the investigation of cutaneous lupus erythematosus.
Long-Term, Low-Intensity Warfarin Therapy for the Prevention of Recurrent Venous Thromboembolism (2003)

Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism.
Development of a Sonically Powered Biodegradable Nanogenerator for Bone Regeneration (2019)

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.\nObjective: Here, we establish a biodegradable, piezoelectric Poly-L-Lactic Acid (PLLA) scaffold that uses external, non-invasive ultrasound to generate an electric charge that promotes stem cell osteogenesis.\nMethods: Demonstration of this system included (1) development of a piezoelectric PLLA mesh, (2) verification of its piezoelectric efficacy and degradation, (3) manufacturing of a PLLA scaffold, (4) in vitro testing of the system’s ability to enhance bone regeneration compared to a control, and (5) using assessments of cell proliferation and differentiation through protein, mineral, and gene assays.\nResults: Ultimately a 3000rpm electrospun PLLA nanofiber film that could output 40mV when stimulated with 40kHz 0.4W/cm2 ultrasound was assembled into a bone scaffold and seeded with adipose-derived stem cells (ADSCs). In vitro testing showed that relative to a control, in cells subjected to the experimental conditions alkaline phosphatase production increased 5-fold, mineral production increased 18-fold, osteocalcin gene 40-fold, and osterix gene 100-fold.\nConclusion: The production of surface-level charge from ultrasonic stimulation of PLLA and the use of that charge to promote osteogenic differentiation in ADSCs was successfully demonstrated. The fact that PLLA was successfully used in combination with externally applied ultrasound to produce electrical charge opens up new frontiers for the field of tissue regeneration. This advancement helps make tissue engineering a tool that can tackle problems of even greater magnitude.
Spatial Distribution of Fibrosis Governs Fibrillation Wave Dynamics in the Posterior Left Atrium During Heart Failure (2007)

Heart failure (HF) commonly results in atrial fibrillation (AF) and fibrosis, but how the distribution of fibrosis impacts AF dynamics has not been studied. HF was induced in sheep by ventricular tachypacing (220 bpm, 6 to 7 weeks). Optical mapping (Di-4-ANEPPS, 300 frames/sec) of the posterior left atrial (PLA) endocardium was performed during sustained AF (burst pacing) in Langendorff-perfused HF (n=7, 4 micromol/L acetylcholine; n=3, no acetylcholine) and control (n=6) hearts. PLA breakthroughs were the most frequent activation pattern in both groups (72.0+/-4.6 and 90.2+/-2.7%, HF and control, respectively). However, unlike control, HF breakthroughs preferentially occurred at the PLAs periphery near the pulmonary vein ostia, and their beat-to-beat variability was greater than control (1.93+/-0.14 versus 1.47+/-0.07 changes/[beats/sec], respectively, P<0.05). On histological analysis (picrosirius red), the area of diffuse fibrosis was larger in HF (23.4+/-0.4%) than control (14.1+/-0.6%; P<0.001, n=4). Also the number and size of fibrous patches were significantly larger and their location was more peripheral in HF than control. Computer simulations using 2-dimensional human atrial models with structural and ionic remodeling as in HF demonstrated that changes in AF activation frequency and dynamics were controlled by the interaction of electrical waves with clusters of fibrotic patches of various sizes and individual pulmonary vein ostia. During AF in failing hearts, heterogeneous spatial distribution of fibrosis at the PLA governs AF dynamics and fractionation.
IL-9 blockade attenuates inflammation in a murine model of methicillin-resistant &lt;italic&gt;Staphylococcus aureus&lt;/italic&gt; pneumonia (2019)

Methicillin-resistant Staphylococcus aureus (MRSA) is an important etiology of pneumonia. Interleukin (IL)-9 is a T helper 9 (Th9) cytokine and participates in the pathogenesis of infectious diseases. Here, we investigated the role of IL-9 by using an MRSA pneumonia animal model. The BALB/c mice underwent nasal inhalation with an ST239 MRSA strain to establish the mouse model of MRSA pneumonia, and a subset of mice were intravenously injected with IL-9 neutralizing antibody or immunoglobulin (Ig) G. At 3 and 8 days postinfection, the peripheral blood, bronchioalveolar lavage fluid (BALF), and lung tissues were collected. The frequencies of Th9 cells and the levels of cytokines in peripheral blood, BALF, and lung tissues were determined by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The colony counts of MRSA in BALF and lung tissue were detected. The lung pathological changes were examined using hematoxylin and eosin staining. Data from flow cytometry, qRT-PCR, and ELISA showed that MRSA-infected mice exhibited higher frequency of Th9 cells and higher IL-9 mRNA and protein levels in the peripheral blood, BALF, and lung tissues of mice. In contrast, the neutralization of IL-9 abrogated MRSA inoculation-induced Th9 cell generation and IL-9 production in BALF and lung tissues. Furthermore, bacterial counting and histological examination showed that the numbers of bacteria in BALF and lungs and the lung pathological scores induced by MRSA inoculation were attenuated by the neutralization of IL-9. Moreover, cell counting and ELISA results demonstrated that IL-9 neutralization diminished the MRSA inoculation-induced count of neutrophils and macrophages and levels of pro-inflammatory cytokines in BALF. Collectively, IL-9 neutralization attenuated inflammation of MRSA pneumonia by regulating Th9/IL-9 expression.
The &#x3C6;C31 Integrase System for Gene Therapy (2006)

The phiC31 integrase system represents a novel technology that opens up new possibilities for gene therapy. The phiC31 integrase can integrate introduced plasmid DNA into preferred locations in unmodified mammalian genomes, resulting in robust, long-term expression of the integrated transgene. This review describes the nature of the integration reaction and the genomic integration sites used by the enzyme in human cells. Preclinical applications of the system to gene therapy to date are summarized, including in vivo use in liver, muscle, eye, and joint and ex vivo use in skin keratinocytes, muscle precursor cells, and T cell lines. The safety of this phage integrase system for gene therapy is evaluated, and its strengths and limitations are compared to other gene therapy approaches. Ongoing and planned improvements to the phage integrase system are discussed. We conclude that gene therapy strategies using phiC31 integrase and its derivatives offer great promise for success in the near term.
HLA associations with multiple sclerosis in Sicily and Malta. (1987)

The islands of Sicily and Malta have very different prevalence rates for multiple sclerosis (MS): at least 44 per 100,000 in Sicily and only 4 per 100,000 in Malta. In Northern Europe, MS is associated with HLA-DR2/Dw2. The other components of the commonest DR2-containing haplotype of this region, HLA-A3-B7-DR2-Dw2, also tend to be present at higher frequency in MS patients. HLA Class I and II antigen frequencies and associations in controls and MS patients from Sicily and Malta were studied to discover whether they might account for the difference in MS prevalence. In Sicilian MS patients, DR2 is increased in frequency compared with controls and four out of five DR2-positive patients also type as Dw2. In the Maltese population, DR2 is present at high frequency but approximately half of the DR2 positive individuals do not type as Dw2 so that DR2 is probably most commonly present as part of Class II haplotypes other than those commonly associated with MS. Additional differences in HLA profile of the Sicilian and Maltese populations were found when HLA-A, -B, and B-DR antigen associations were examined. Therefore, some of the difference in MS prevalence might be explained by genetic factors.
Patient-Specific Modeling of Cardiovascular Mechanics (2009)

Advances in numerical methods and three-dimensional imaging techniques have enabled the quantification of cardiovascular mechanics in subject-specific anatomic and physiologic models. Patient-specific models are being used to guide cell culture and animal experiments and test hypotheses related to the role of biomechanical factors in vascular diseases. Furthermore, biomechanical models based on noninvasive medical imaging could provide invaluable data on the in vivo service environment where cardiovascular devices are employed and on the effect of the devices on physiologic function. Finally, patient-specific modeling has enabled an entirely new application of cardiovascular mechanics, namely predicting outcomes of alternate therapeutic interventions for individual patients. We review methods to create anatomic and physiologic models, obtain properties, assign boundary conditions, and solve the equations governing blood flow and vessel wall dynamics. Applications of patient-specific models of cardiovascular mechanics are presented, followed by a discussion of the challenges and opportunities that lie ahead.
T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells (2000)

These studies tested whether antigenic competition between T cells occurs. We generated CD8(+) T cell responses in H-2(b) mice against the dominant ovalbumin epitope SIINFEKL (ova8) and subdominant epitope KRVVFDKL, using either vaccinia virus expressing ovalbumin (VV-ova) or peptide-pulsed dendritic cells. CD8(+) T cell responses were visualized by major histocompatibility complex class I-peptide tetrameric molecules. Transfer of transgenic T cells with high affinity for ova8 (OT1 T cells) completely inhibited the response of host antigen-specific T cells to either antigen, demonstrating that T cells can directly compete with each other for response to antigen. OT1 cells also inhibited CD8(+) T cell responses to an unrelated peptide, SIYRYGGL, providing it was presented on the same dendritic cells as ova8. These inhibitions were not due to a more rapid clearance of virus or antigen-presenting cells (APCs) by the OT1 cells. Rather, the inhibition was caused by competition for antigen and antigen-bearing cells, since it could be overcome by the injection of large numbers of antigen-pulsed dendritic cells. These results imply that common properties of T cell responses, such as epitope dominance and secondary response affinity maturation, are the result of competitive interactions between antigen-bearing APC and T cell subsets.