gebhart/patrepeval huggingface dataset:
The long-awaited magic bullets: therapeutic human monoclonal antibodies from transgenic mice (1998)

The ability to produce a diverse repertoire of fully human monoclonal antibodies (mAbs) may have significant applications to human therapy. This update describes the creation of a novel tool for the production of therapeutic human mAbs: a mouse strain engineered to produce a large range of human antibodies in the absence of mouse antibodies. This strain, XenoMouse, has been generated by the introduction of large segments of human immunoglobulin loci, containing the majority of the human antibody gene repertoire, into mice deficient in mouse antibody production. The mice produce a diverse array of authentic fully human IgGkappa antibodies. Upon immunisation with multiple human antigens the mice generate large panels of high affinity, antigen-specific fully human mAbs with therapeutic activities. XenoMouse-derived hybridomas were shown to be stable, producing significant levels of human mAbs. XenoMouse technology represents an efficient and reliable tool for the production of therapeutic human mAbs, which can accelerate the evaluation and validation of antibody therapy in human disease.
Concordant loss of melanoma differentiation antigens in synchronous and asynchronous melanoma metastases: implications for immunotherapy (2006)

Because of its known heterogeneity, the analysis of antigen expression is crucial prior to the initiation of antigen-specific immunotherapy for melanoma. The melanoma differentiation antigens gp100, MART-1 and tyrosinase are involved in a common pathway of melanin synthesis. Peptides derived from these melanoma differentiation antigens are used in the immunotherapy of melanoma and antibodies recognizing these antigens are commonly applied to detect melanocytic lesions. One hundred and ninety-one paraffin-embedded melanoma metastases from 28 patients with 2-19 lesions (mean, 6.8) developing synchronously (n = 67) or asynchronously (n = 124) were analysed by immunohistochemistry for the expression of the melanoma differentiation antigens, as well as cancer/testis antigens of the melanoma antigen-A (MAGE-A) family (monoclonal antibodies 77B and 57B), anti-S100 and SM5-1. The overall reactivities were 81.6% (gp100), 79.5% (MART-1), 59.6% (tyrosinase), 59.1% (77B), 60.7% (57B), 93.2% (S100) and 91.6% (SM5-1). Twenty-seven lesions (14.1%) were positive for all tumour-associated antigens, 75 lesions (39.2%) were negative for one antigen and 87 lesions (45.5%) were negative for several tumour-associated antigens. Co-ordinated loss was found for lesions negative for gp100 and MART-1 (9.4%, P < 0.0005), gp100 and tyrosinase (11.0%, P = 0.009), MART-1 and tyrosinase (15.2%, P < 0.0005) and gp100, MART-1 and tyrosinase (8.9%, P < 0.0005), which is up to six times higher than the expected calculated loss. This co-ordinated loss of melanoma differentiation antigens in melanoma did not include cancer testis antigens and S100 or SM5-1. On average, the melanoma differentiation antigens stained 50-65% of cells within a lesion, and 10-39% of synchronous clusters were heterogeneous for melanoma differentiation antigen expression. In conclusion, broader polypeptide vaccines should be used for melanoma immunotherapy.
Interleukin-6: A multifunctional targetable cytokine in human prostate cancer (2011)

Several cytokines are involved in regulation of cellular events in prostate cancer. Interleukin-6 (IL-6) was frequently investigated in prostate cancer models because of its increased expression in cancer tissue at early stages of the disease. In patients with metastatic prostate cancer, it is well-known that IL-6 levels increase in serum. High levels of IL-6 were measured in the supernatants of cells which do not respond to androgenic stimulation. IL-6 expression in prostate cancer increases due to enhanced expression of transforming growth factor-beta, and members of the activating protein-1 complex, and loss of the retinoblastoma tumour suppressor. IL-6 activation of androgen receptor (AR) may contribute to progression of a subgroup of prostate cancers. Results obtained with two prostate cancer cell lines, LNCaP and MDA PCa 2b, indicate that IL-6 activation of AR may cause either stimulatory or inhibitory responses on proliferation. Interestingly, prolonged treatment with IL-6 led to establishment of an IL-6 autocrine loop, suppressed signal transducer and activator of transcription (STAT)3 activation, and increased mitogen-activated protein kinase phosphorylation. In several cell lines IL-6 acts as a survival molecule through activation of the signalling pathway of phosphotidylinositol 3-kinase. Expression of suppressors of cytokine signalling (SOCS) has been studied in prostate cancer. SOCS-3 prevents phosphorylation of STAT3 and is an important anti-apoptotic factor in AR-negative prostate cancer cells. Experimental therapy against IL-6 in prostate cancer is based on the use of the monoclonal antibody siltuximab which may be used for personalised therapy coming in the future.
Variable Rate Image Compression with Recurrent Neural Networks (2015)

A large fraction of Internet traffic is now driven by requests from mobile devices with relatively small screens and often stringent bandwidth requirements. Due to these factors, it has become the norm for modern graphics-heavy websites to transmit low-resolution, low-bytecount image previews (thumbnails) as part of the initial page load process to improve apparent page responsiveness. Increasing thumbnail compression beyond the capabilities of existing codecs is therefore a current research focus, as any byte savings will significantly enhance the experience of mobile device users. Toward this end, we propose a general framework for variable-rate image compression and a novel architecture based on convolutional and deconvolutional LSTM recurrent networks. Our models address the main issues that have prevented autoencoder neural networks from competing with existing image compression algorithms: (1) our networks only need to be trained once (not per-image), regardless of input image dimensions and the desired compression rate; (2) our networks are progressive, meaning that the more bits are sent, the more accurate the image reconstruction; and (3) the proposed architecture is at least as efficient as a standard purpose-trained autoencoder for a given number of bits. On a large-scale benchmark of 32$\times$32 thumbnails, our LSTM-based approaches provide better visual quality than (headerless) JPEG, JPEG2000 and WebP, with a storage size that is reduced by 10% or more.
Synthesis of Conformationally Defined Glutamic Acid Analogues from Readily Available Diels-Alder Adducts. (1995)

New amino acids, (±)-t-3, t-4-bis(carboxymethyl)-r-2-pyrrolidinecarboxylic acid (1d) and (±)-t-3a, t-6a-perhydro-r-1, t-4, t-6-cyclopenta[c]pyrroletricarboxylic acid (2), which possess relatively similar configurations to kainic acid, were synthesized from readily available Diels-Alder adducts.
Climate change and the adequacy of food and timber in the 21st century (2007)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Common Variants in Cardiac Ion Channel Genes Are Associated With Sudden Cardiac Death (2010)

In this combined analysis of 6 prospective cohort studies, 2 common intronic variants in KCNQ1 and SCN5A were associated with sudden cardiac death in individuals of European ancestry. Further study in other populations and investigation into the functional abnormalities associated with noncoding variation in these genes may lead to important insights into predisposition to lethal arrhythmias.
Extracardiac Progenitor Cells Repopulate Most Major Cell Types in the Transplanted Human Heart (2005)

Extracardiac progenitor cells are capable of repopulating most major cell types in the heart, but they do so with varying frequency. The signals for endothelial progenitor recruitment occur early and could relate to injury during allograft harvest or transplantation. The high degree of endothelial chimerism may have immune implications such as for myocardial rejection or graft vasculopathy.
Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons (2005)

Erythromelalgia is an autosomal dominant disorder characterized by burning pain in response to warm stimuli or moderate exercise. We describe a novel mutation in a family with erythromelalgia in SCN9A, the gene that encodes the Na(v)1.7 sodium channel. Na(v)1.7 produces threshold currents and is selectively expressed within sensory neurons including nociceptors. We demonstrate that this mutation, which produces a hyperpolarizing shift in activation and a depolarizing shift in steady-state inactivation, lowers thresholds for single action potentials and high frequency firing in dorsal root ganglion neurons. Erythromelalgia is the first inherited pain disorder in which it is possible to link a mutation with an abnormality in ion channel function and with altered firing of pain signalling neurons.
Towards biodegradable wireless implants (2012)

A new generation of partially or even fully biodegradable implants is emerging. The idea of using temporary devices is to avoid a second surgery to remove the implant after its period of use, thereby improving considerably the patient's comfort and safety. This paper provides a state-of-the-art overview and an experimental section that describes the key technological challenges for making biodegradable devices. The general considerations for the design and synthesis of biodegradable components are illustrated with radiofrequency-driven resistor-inductor-capacitor (RLC) resonators made of biodegradable metals (Mg, Mg alloy, Fe, Fe alloys) and biodegradable conductive polymer composites (polycaprolactone-polypyrrole, polylactide-polypyrrole). Two concepts for partially/fully biodegradable wireless implants are discussed, the ultimate goal being to obtain a fully biodegradable sensor for in vivo sensing.
Robust system design with built-in soft-error resilience (2005)

Transient errors caused by terrestrial radiation pose a major barrier to robust system design. A system's susceptibility to such errors increases in advanced technologies, making the incorporation of effective protection mechanisms into chip designs essential. A new design paradigm reuses design-for-testability and debug resources to eliminate such errors.
Cost of post-operative intravenous iron therapy in total lower limb arthroplasty: a retrospective, matched cohort study. (2014)

In patients presenting with or without pre-operative anaemia, post-operative intravenous iron after total lower limb arthroplasty seems to be safe and is associated with reduced transfusion rates, without incremental costs. For anaemic patients, its efficacy could be increased by associating some other blood-saving method.
Nudging hair shedding by antidandruff shampoos. A comparison of 1% ketoconazole, 1% piroctone olamine and 1% zinc pyrithione formulations (2002)

Hair shedding and hair thinning have been reported to be affected by dandruff and seborrhoeic dermatitis. The present study was conducted in 150 men presenting with telogen effluvium related to androgenic alopecia associated with dandruff. They were randomly allocated to three groups receiving each one of the three shampoos in the market containing either 1% ketoconazole (KTZ), 1% piroctone olamine (PTO) or 1% zinc pyrithione (ZPT). Shampoos had to be used 2-3 times a week for 6 months. Hair shedding during shampoo was evaluated semiquantitatively. Hair density on the vertex was evaluated on photographs using a Dermaphot. Trichograms were used for determining the anagen hair percentage and the mean proximal hair shaft diameter using computerized image analysis. The sebum excretion rate (SER, mug cm(-2) h(-1)) was also measured using a Sebumeter. The three treatments cleared pruritus and dandruff rapidly. At end point, hair density was unchanged, although hair shedding was decreased (KTZ: -17.3%, PTO: -16.5%, ZPT: -10.1%) and the anagen hair percentage was increased (KTZ: 4.9%, PTO: 7.9%, ZPT: 6.8%). The effect on the mean hair shaft diameter was contrasted between the three groups of volunteers (KTZ: 5.4%, PTO: 7.7%, ZPT: -2.2%). In conclusion, telogen effluvium was controlled by KTZ, PTO and ZPT shampoos at 1% concentration. In addition, KTZ and PTO increased the mean hair shaft thickness while discretely decreasing the sebum output at the skin surface.
CD4+T Cells Induced by a DNA Vaccine: Immunological Consequences of Epitope-Specific Lysosomal Targeting (2001)

Our previous studies have shown that targeting DNA vaccine-encoded major histocompatibility complex class I epitopes to the proteasome enhanced CD8(+) T-cell induction and protection against lymphocytic choriomeningitis virus (LCMV) challenge. Here, we expand these studies to evaluate CD4(+) T-cell responses induced by DNA immunization and describe a system for targeting proteins and minigenes to lysosomes. Full-length proteins can be targeted to the lysosomal compartment by covalent attachment to the 20-amino-acid C-terminal tail of lysosomal integral membrane protein-II (LIMP-II). Using minigenes encoding defined T-helper epitopes from lymphocytic choriomeningitis virus, we show that the CD4(+) T-cell response induced by the NP(309-328) epitope of LCMV was greatly enhanced by addition of the LIMP-II tail. However, the immunological consequence of lysosomal targeting is not invariably positive; the CD4(+) T-cell response induced by the GP(61-80) epitope was almost abolished when attached to the LIMP-II tail. We identify the mechanism which underlies this marked difference in outcome. The GP(61-80) epitope is highly susceptible to cleavage by cathepsin D, an aspartic endopeptidase found almost exclusively in lysosomes. We show, using mass spectrometry, that the GP(61-80) peptide is cleaved between residues F(74) and K(75) and that this destroys its ability to stimulate virus-specific CD4(+) T cells. Thus, the immunological result of lysosomal targeting varies, depending upon the primary sequence of the encoded antigen. We analyze the effects of CD4(+) T-cell priming on the virus-specific antibody and CD8(+) T-cell responses which are mounted after virus infection and show that neither response appears to be accelerated or enhanced. Finally, we evaluate the protective benefits of CD4(+) T-cell vaccination in the LCMV model system; in contrast to DNA vaccine-induced CD8(+) T cells, which can confer solid protection against LCMV challenge, DNA vaccine-mediated priming of CD4(+) T cells does not appear to enhance the vaccinee's ability to combat viral challenge.
Clinical utility of flow cytometry in the chronic lymphoid leukemias. (1998)

The chronic lymphoid leukemias comprise a number of biologically distinct neoplasms of mature lymphocytes. The availability of specific therapies for certain of these tumors makes accurate diagnosis imperative. In most cases, detailed immunophenotypic analysis of the chronic lymphoid leukemias permits specific classification and initiation of the most appropriate therapy. For example, the characteristic immunophenotype of B-cell chronic lymphocytic leukemia (CLL): CD5+, CD23+, FMC7-, CD20 dim+, clonal surface immunoglobulin (sIg) dim+, distinguishes it from another CD5+ B-cell lymphoproliferative disorder, mantle cell lymphoma, which typically displays the composite phenotype: CD5+, CD23-, FMC7+, CD20 bright+, clonal sIg bright+. Likewise, hairy cell leukemia has a characteristic immunophenotype: CD5-, CD11c bright+, CD25+, CD103+, which distinguishes it from other CD5- B-cell lymphoproliferative disorders, including the morphologically similar splenic lymphoma with circulating villous lymphocytes. Immunophenotypic analysis by flow cytometry may also identify clinically relevant subsets of patients within a diagnostic category of leukemia. Thus, in patients with CLL, deviation from the typical immunophenotype is associated with trisomy 12 and mixed-cell morphology. In summary, careful immunophenotyping by flow cytometry facilitates accurate diagnosis in the chronic lymphoid leukemias, and in some settings, may also offer additional therapeutically relevant information.
Diffusion maps for edge-aware image editing (2010)

Edge-aware operations, such as edge-preserving smoothing and edge-aware interpolation, require assessing the degree of similarity between pairs of pixels, typically defined as a simple monotonic function of the Euclidean distance between pixel values in some feature space. In this work we introduce the idea of replacing these Euclidean distances with diffusion distances, which better account for the global distribution of pixels in their feature space. These distances are approximated using diffusion maps: a set of the dominant eigenvectors of a large affinity matrix, which may be computed efficiently by sampling a small number of matrix columns (the Nystrom method). We demonstrate the benefits of using diffusion distances in a variety of image editing contexts, and explore the use of diffusion maps as a tool for facilitating the creation of complex selection masks. Finally, we present a new analysis that establishes a connection between the spatial interaction range between two pixels, and the number of samples necessary for accurate Nystrom approximations.
Single mRNAs visualized by ultrastructural in situ hybridization are principally localized at actin filament intersections in fibroblasts. (1994)

Considerable evidence indicates that mRNA associates with structural filaments in the cell (cytoskeleton). This relationship would be an important mechanism to effect mRNA sorting since specific mRNAs could be sequestered at sites within the cell. In addition, it can provide a mechanism for spatial regulation of mRNA expression. However, the precise structural interactions between mRNA and the cytoskeleton have yet to be defined. An objective of this work was to visualize "individual" poly(A) mRNA molecules in situ by electron microscopy to identify their relationship to individual filaments. Poly(A) RNA and filaments were identified simultaneously using antibodies to detect hybridized probe and filaments or actin-binding proteins. In human fibroblasts, most of the poly(A) mRNA (72%) was localized within 5 nm of orthogonal networks of F-actin filaments. Poly(A) mRNA also colocalized with vimentin filaments (29%) and microtubules (< 10%). The sites of mRNA localization were predominantly at filament intersections. The majority of poly(A) mRNA and polysomes colocalized with the actin crosslinking proteins, filamin, and alpha-actinin, and the elongation factor, EF-1 alpha (actin-binding protein; ABP-50). Evidence that intersections contained single mRNA molecules was provided by using a labeled oligo dT probe to prime the synthesis of cDNA in situ using reverse transcriptase. Both the poly(A) and cis sequences of the same mRNA molecule could then be visualized independently. We propose that the cytoskeletal intersection is a mRNA receptor and serves as a "microdomain" where mRNA is attached and functionally expressed.
[A pathological report of three COVID-19 cases by minimal invasive autopsies]. (2020)

<b>Objective:</b> To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19). <b>Methods:</b> Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV. <b>Results:</b> Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. <b>Conclusions:</b> The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.
Down‐regulatory effect of usnic acid on nuclear factor‐κB‐dependent tumor necrosis factor‐α and inducible nitric oxide synthase expression in lipopolysaccharide‐stimulated macrophages RAW 264.7 (2008)

The purpose of this study was to investigate the molecular mechanisms that are responsible for the antiinflammatory effect of usnic acid (UA). UA is one of the most common and abundant lichen metabolites. The present study examined the effects of UA on the tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and the underlying molecular mechanisms. UA decreased the TNF-alpha level in LPS-stimulated RAW264.7 macrophages in dose-dependent manner, the IC(50) value was 12.8 microM. RT-PCR analysis indicated that it inhibited TNF-alpha mRNA expression. Furthermore, it inhibited NO production in LPS-activated RAW264.7 macrophages, the IC(50) value was 4.7 microM. Western blot analysis showed that UA attenuated LPS-induced synthesis of iNOS protein and nuclear translocation of NF-kappaB p65 in the macrophages, in parallel. UA also inhibited LPS-mediated I-kappaBalpha degradation. Taken together, this suggests that UA has an antiinflammatory effect by inhibiting TNF-alpha and iNOS expression, possibly through suppression of nuclear translocation of NF-kappaB p65 and I-kappaBalpha degradation.