gebhart/patrepeval huggingface dataset:
Glycoengineering of Therapeutic Antibodies (2012)

Antibody dependent cellular cytotoxicity (ADCC) is the process of lysis of (tumor) target cells by immune effector cells. It requires the simultaneous binding of an antibody to a cell surface receptor on the target cell and via the Fc region of the antibody to the FcgRIIIa receptor on immune effector cells such as NK cells or macrophages/monocytes. Binding of the antibody to target and immune effector cells results in the cross-linking of FcgRIIIa with subsequent activation of FcgRIIIa signaling and release of proteins mediating the killing of the target cells such as perforin and of proteases such as granzymes. ADCC has been established as an important mode of action of therapeutic antibodies such as rituximab/MabThera (targeting CD20), cetuximab/Erbitux (targeting EGFR) and trastuzumab/Herceptin (targeting HER2) which are approved for the treatment of various cancers. Translational research on rituximab and cetuximab has established that the response to therapeutic antibodies in patients can be influenced by the FcgRIIIa-158V/F polymorphism. This polymorphism results in the expression of a high affinity FcgRIIIa receptor (158 V) and a low affinity FcgRIIIa receptor (158F) on immune effector cells and impacts the capability of antibodies to mediate ADCC [1], [2], [3], [4], [5], [6], [7]. We have recently developed a so-called GlycoMab technology that enhances the affinity of therapeutic antibodies for both the high and low affinity FcgRIIIa receptors through the introduction of a bisecting N-acetyl-glucosamine residue in the carbohydrate chain of the Fc region of the antibodies. The introduction of this bisecting N-acetyl-glucosamine moiety in the carbohydrate chain results in a steric interference with core fucosylation of the carbohydrate. This process and other approaches resulting in the afucosylation of therapeutic antibodies are known as "antibody glycoengineering". We and others have demonstrated that glycoengineering and lack of the core fucose residue results in an up to 50-fold enhanced affinity of human IgG1 antibodies for the human FcgRIIIa receptors, and this subsequently results in an up to 100-fold enhanced ADCC induction (potency). Recently, we have demonstrated the structural basis of the enhanced affinity of afucosylated Fc regions for FcgRIIIa by X-ray crystallography. These studies provide a structural explanation for the high affinity and FcgRIIIa specificity of glycoengineering as opposed to other technologies used for Fc-engineering such as the introduction of mutations in the Fc region that also affect binding to other FcgRs [8], [9], [10], [11], [12], [13], [14], [15].
Evaluating Protection Against Infectious Bronchitis Virus by Clinical Signs, Ciliostasis, Challenge Virus Detection, and Histopathology (2015)

In this study, we examined the association among clinical signs, ciliostasis, virus detection, and histopathology for evaluating protection of vaccinated chickens against homologous and heterologous infectious bronchitis virus (IBV) challenge. At 5 days following challenge with IBV, we found a good correlation among clinical signs, ciliostasis in the trachea, challenge virus detection, and microscopic lesions in the trachea, with all four criteria being negative in fully protected birds and positive in fully susceptible birds. In partially protected birds we observed clinical signs and detected challenge virus; however, the ciliated epithelium was intact. In a second experiment, we challenged fully protected, partially protected, and fully susceptible birds with IBV, and then at 5 days postchallenge we gave the birds an opportunistic bacterium intranasally. Twenty Bordetella avium colonies were recovered from one of five fully protected birds, and only five colonies were isolated from two of five partially protected birds without ciliostasis, whereas in birds with ciliostasis, numerous colonies were isolated. Obviously, decreasing IBV infection and replication in the upper respiratory tract will decrease transmission and mutations, leading to variant viruses, and herein we demonstrate that protection of the cilia will decrease secondary bacterial infections, which have been shown to lead to condemnations and increased mortality. Thus, it appears that examining both criteria would be important when evaluating IBV vaccine efficacy.
SCN2A encephalopathy (2015)

Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome. Sodium channel blockers, particularly phenytoin, may improve seizure control.
Bacterial DNA and CpG–Containing Oligodeoxynucleotides Activate Cutaneous Dendritic Cells and Induce IL–12 Production: Implications for the Augmentation of Th1 Responses (1999)

Bacterial DNA and CpG ODN stimulate DC in vitro and in vivo and may preferentially elicit Th1-predominant immune responses because they can activate and mobilize DC, inducing them to produce IL-12.
How to Optimize In Vivo Gene Transfer to Cardiac Myocytes: Mechanical or Pharmacological Procedures? (2001)

An efficient gene delivery system is a prerequisite for myocardial gene therapy. Among the various procedures studied so far, catheter-based percutaneous gene delivery to the myocardium through the coronary vessels seems the most relevant to routine clinical practice; however, the optimal conditions remain to be determined. We selectively infused adenoviral vectors encoding luciferase (1 x 10(9) PFU) or beta-galactosidase (1 x 10(10) PFU) into coronary arteries of adult rabbits in various experimental conditions. Coronary artery occlusion for 30 sec, during and after adenovirus delivery, was required to observe luciferase activity in the target area of the circumflex artery (4.0 +/- 1.0 x 10(5) vs. 1.1 +/- 0.2 x 10(4) RLU/mg with and without coronary occlusion, respectively, p < 0.01, and 1.0 +/- 0.1 x 10(3) RLU/mg using nonselective infusion). When adenoviruses were delivered using high-pressure infusion (82 +/- 12 vs. 415 +/- 25 mmHg before and during infusion, respectively, p < 0.01), luciferase activity increased to 8.5 +/- 2.5 x 10(5) RLU/mg (p < 0.05 vs coronary occlusion alone). Coronary venous sinus occlusion with saline buffer retroinfusion starting before and during anterograde adenovirus delivery resulted in a further 4.7-fold increase in luciferase activity (4.4 +/- 0.8 x 10(6) RLU/mg, p < 0.01) with 5-25% blue-stained myocytes in the target area, compared with 0-5% with the other procedures. Histamine or VEGF-A(165) pretreatment, used to increase vascular permeability, slightly increased gene transfer efficiency (8.5 +/- 2.0 x 10(5) and 9.0 +/- 2.5 x 10(5) RLU/mg respectively, p < 0.05 vs. coronary occlusion alone). We conclude that catheter-mediated adenoviral gene transfer to cardiac myocytes through coronary vessels can be a very efficient procedure for myocardial gene therapy, particularly when the vector residence time and perfusion pressure in the vessels are increased.
Deoxyribonucleic acid-polylysine complexes. Structure and nucleotide specificity (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDeoxyribonucleic acid-polylysine complexes. Structure and nucleotide specificityJewel T. Shapiro, Marc Leng, and Gary FelsenfeldCite this: Biochemistry 1969, 8, 8, 3219–3232Publication Date (Print):August 1, 1969Publication History Published online1 May 2002Published inissue 1 August 1969https://pubs.acs.org/doi/10.1021/bi00836a014https://doi.org/10.1021/bi00836a014research-articleACS PublicationsRequest reuse permissionsArticle Views379Altmetric-Citations176LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Triple-Negative Breast Cancer: Risk Factors to Potential Targets (2008)

Triple-negative breast cancer has recently been recognized as an important subgroup of breast cancer with a distinct outcome and therapeutic approach when compared with other subgroups of breast cancer. Triple-negative breast cancer comprises primarily, but not exclusively, a molecularly distinct subtype of breast cancer, the basal-like subtype. We do not yet have an assay to identify basal-like breast cancer in clinical samples, so triple-negative breast cancer has become a commonly used proxy for this subtype. The molecular biology and pathophysiology of triple-negative breast cancer are not completely understood, but understanding is improving rapidly with the advent of sophisticated molecular biology platforms. Moreover, the established risk factors of breast cancer as a whole may not apply to this unique subgroup of patients. Finally, because triple-negative breast cancer is defined by the absence of a target, there are currently limitations to using a tailored therapeutic approach, leaving conventional cytotoxic therapies as the mainstay. Active preclinical and clinical research programs focus on defining the clinical behavior, delineating the risk factors, and more completely understanding the molecular biology of triple-negative breast cancer to improve prevention, optimize conventional agents, and unveil novel therapeutic targets. This CCR focus article will review the current state of the art on triple-negative breast cancer.
Analysis of the fine B cell specificity during the chronic/relapsing course of a multiple sclerosis-like disease in Lewis rats injected with the encephalitogenic myelin oligodendrocyte glycoprotein peptide 35-55 (1996)

We have recently shown that a single injection of myelin oligodendrocyte glycoprotein (MOG), or the MOG35-55 peptide, produces a relapsing-remitting neurologic disease with extensive plaque-like demyelination. Given the features that this new autoimmune demyelinating model has in common with the clinicopathologic manifestations of multiple sclerosis, we have examined the Ab reactivity to native MOG and MOG35-55 peptide during the course of the disease in Lewis rats. Following immunization with MOG35-55, varied clinical symptoms were observed; these included hind and foreleg paralysis and various degrees of balance impairment. Disease progression also varied: 3 out of 21 animals had a single mild disease episode; 4 out of 21 had a mild relapsing-remitting disease; and 14 out of 21 had severe relapsing-remitting disease. Ab reactivity to MOG35-55 and native MOG was first detected in all rats 4 wk postimmunization and persisted throughout the 12 wk of observation. The Ab response was highly restricted with no reactivity to other peptides encompassing different extracellular segments of MOG. Fine epitope mapping showed that Ab from serum and cerebrospinal fluid of injected rats reacted strongly to MOG37-46 and to a lesser extent to MOG43-50. Although significant levels of anti-MOG Abs appeared necessary for the development of demyelinating lesions, their presence in blood and cerebrospinal fluid alone was not sufficient to produce severe clinical symptoms. These results demonstrate that the MOG35-55 peptide is highly encephalitogenic and can induce strong T and B cell responses. It is probably the complex interaction between these T and B cells that determines the severity of disease in individual rats.
Impairment of CD8+ T Suppressor Cell Function in Patients with Active Systemic Lupus Erythematosus (2001)

Alteration of T cell suppression function has been recognized in patients with systemic lupus erythematosus (SLE). Recently, CD8(+) T suppressor lymphocytes (CD8(+) Ts) have been generated in vitro by incubating purified CD8(+) T cells with IL-2 and GM-CSF. Using this method, we generated CD8(+) Ts from patients affected by SLE. No major differences were found in the CD8(+) Ts phenotype between SLE patients and healthy subjects. CD8(+) Ts from SLE patients with active disease did not inhibit the anti-CD3 mAb-induced proliferation of autologous PBMC, whereas CD8(+) Ts from SLE patients in remission exerted an inhibitory activity comparable to normal subjects. The inhibitory effect of CD8(+) Ts cells was neither mediated by cytotoxic activity nor by apoptosis induction. Two cytokines, IFN-gamma and IL-6, were found to be responsible for the function of CD8(+) TS: In fact, counteraction of CD8(+) Ts suppression activity was obtained by blocking IFN-gamma with a specific Ab or by inhibiting CD8(+) Ts-mediated IL-6 secretion by an antisense oligonucleotide. Interestingly, CD8(+) Ts from SLE patients showed a peculiar cytokine pattern characterized by an impaired secretion of IL-6 and an increased secretion of IL-12. Thus, it appears that an altered balance between inhibitory (IL-6) and stimulatory (IL-12) cytokines might be responsible for the functional impairment of CD8(+) Ts in SLE patients.
Regioselective epoxidations of dienes with manganese(III) porphyrin catalysts (1987)

A series of sterically hindered manganese porphyrins are shown to be shape-selective catalysts for the epoxidation of a variety of dienes; product ration differences for conjugated vs. non-conjugated dienes indicate the existence of at least two competing epoxidation pathways.
Successful Correction of the Human Cooley's Anemia β‐Thalassemia Major Phenotype Using a Lentiviral Vector Flanked by the Chicken Hypersensitive Site 4 Chromatin Insulator (2005)

beta-Thalassemias are the most common single-gene disorders and are potentially amenable to gene therapy. While retroviral vectors carrying the human beta-globin cassette were notoriously unstable and expressed poorly, considerable progress has now been made using lentiviral vectors (LVs), which stably transmit the beta-globin expression cassette. Mouse studies using LVs have shown correction of the beta-thalassemia-intermedia phenotype and a partial, variable correction of the mouse beta-thalassemia major phenotype, despite the use of beta-globin-hypersensitive sites that are known to result in position-independent effects. Our group used the alpha-globin-hypersensitive site in self-inactivating (SIN) LVs with long-term expression in secondary mice that resisted methylation-associated proviral silencing. However, these vectors also suffered from chromatin position effects. We therefore flanked a SIN-lentiviral vector carrying the human beta-globin expression cassette with a chromatin insulator and studied expression in bone marrow from four patients with transfusion-dependent human thalassemia major. We demonstrated normal levels of human beta-globin expression in erythroid cells produced in in vitro cultures for unilineage erythroid differentiation. There was restoration of effective erythropoiesis and reversal of the abnormally elevated apoptosis that characterizes beta-thalassemia. The gene-corrected human beta-thalassemia progenitor cells were transplanted into immune-deficient mice, where they underwent normal erythroid differentiation, expressed normal levels of human beta-globin, and displayed normal effective erythropoiesis 3-4 months after xenotransplantation. Variability of beta-globin expression in erythroid colonies derived in vitro or from xenograft bone marrow was similar to that seen in normal control subjects. Results show genetic correction of primitive human progenitor cells and normalization of the human thalassemia major phenotype.
Glycosylation by Chinese hamster ovary cells in dolichol phosphate‐supplemented cultures (2002)

N-linked glycosylation often imparts important properties to protein therapeutics. An essential step in this intracellular process is the transfer of oligosaccharide from dolichol monophosphate (Dol-P) to a potential glycosylation site. Variability in the success rate of this reaction affects the extent of protein glycosylation. The critical role of Dol-P suggests that its availability may influence the extent of glycosylation by limiting the pool of lipid-linked oligosaccharides (LLOs), the glycosyl donor. To test this hypothesis, the impact of Dol-P supplementation on protein glycosylation in Chinese hamster ovary (CHO) cells was investigated. Although exogenous Dol-P was incorporated by CHO cells and processed into LLOs in a dose-dependent manner, Dol-P supplementation had no marked effects on LLO or overall cellular glycosylation levels. While concentrations of exogenous Dol-P exceeding 100 microg/ml were detrimental to CHO cell viability, maximum non-toxic supplemental doses of Dol-P had no significant impact on the glycosylation of recombinant interferon- gamma produced by batch cultures of CHO cells. These results show that glycosylation in CHO cells cannot be readily enhanced by Dol-P feeding under normal culture conditions.
Characterization of interferon gamma receptors on osteoclasts: Effect of interferon gamma on osteoclastic superoxide generation (2002)

Osteoclasts are the primary cells responsible for bone resorption. Osteoclast formation and bone resorption activities involve processes tightly controlled by a network of cytokines. The presence of interferon gamma (IFN-γ) receptors on osteoclasts is a necessary prerequisite for IFN-γ to directly affect osteoclastic activity. To date, the presence of the IFN-γ receptor on osteoclasts has not been established. This study provides evidence that osteoclasts express the IFN-γ receptor. Specific binding of IFN-γ to the osteoclastic receptor stimulates osteoclastic superoxide generation. The p91 and p47 components of the NADPH oxidase increase after IFN-γ stimulation and may account for the enhanced superoxide generation. Antisense experiments targeting p91 and p47 subunits abrogate the increased osteoclastic superoxide production stimulated by IFN-γ. Thus, superoxide generation by osteoclasts is stimulated by activation of a functional IFN-γ receptor on the osteoclast. J. Cell. Biochem. 84: 645–654, 2002. © 2001 Wiley-Liss, Inc.
A competitive receptor binding assay for platelet-activating factor (PAF): quantification of PAF in rat brain. (1992)

A radioreceptor assay (RRA) was developed using rabbit platelet membrane preparations to quantify platelet-activating factor (PAF) and lyso-PAF, the deacylated derivative of PAF, in a variety of tissues and biological fluids. We examined PAF and lyso-PAF levels in different rat brain areas with regard to the many proven and postulated actions of PAF in brain functions. Human saliva was selected to check the validity of this RRA. The samples were extracted with methanol/chloroform/water and purified by high-performance liquid chromatography on a 5-microns Nucleosil Si column (overall recovery: 78%). Sample extracts were acetylated before chromatography to assay lyso-PAF. PAF itself was assayed in non-aceylated samples. A competitive binding assay was performed using aliquots of platelet membrane preparation and tritiated PAF. The minimum detectable amount of PAF was 144 pg per tube and the receptor was highly specific for PAF. In human saliva, we confirm the presence of PAF and lyso-PAF within the range expected. Moreover there was a good correlation between the RRA and the aggregation assay (r = 0.976). A defined cocktail of protease inhibitors allowed storage of platelet membrane preparations for at least 3 months at -20 degrees C with no change in binding properties. In the brain we observed the prevalent presence of lyso-PAF and large variations in PAF and lyso-PAF concentrations between the different brain areas analyzed. PAF was undetectable in the hypothalamus but the lyso-PAF concentration was 2.5 micrograms/g wet tissue. The PAF concentration in the cortex varied from 0 to 16 ng/g wet tissue while that of lyso-PAF was 0.7 micrograms/g wet tissue. Moreover the amount of lyso-PAF varied between the different brain areas analyzed. The hippocampus contained the highest amount (7 micrograms/g wet tissue), and relatively high levels were found in the hypothalamus, medulla oblongata and corpus striatum. The cerebellum and cortex contained the lowest levels of lyso-PAF. These findings show that PAF is present in the central nervous system mainly in its inactive form, lyso-PAF, and suggest that its effects as a modulator of brain function may be dependent on deacetylation, rather than synthesis.
Lossless Video Coding Using Lattice Based Distributed Source Coding Techniques (2006)

Information theoretic proof exists to support that independent encoding of distributed sources with a joint decoder by exploiting the correlation among the sources can be as efficient as encoding them jointly. This paper successfully attempts to apply this concept for lossless video coding using lattices to divide the multidimensional integer pixel intensity hyperspace of a block of pixels into a finite number of cosets and encoding each block with its coset index. This radical departure from conventional predictive coding techniques not only offers very low computational complexity by avoiding expensive learning of predictor coefficients but also avoids any coding loss due to rounding of real-valued predictions. On standard test video sequences, this scheme achieved compression within as low as 4.6% of the latest scheme with optimal learning of predictor coefficients. The former, however, outperformed the latter as soon as it started updating the optimal predictor coefficients less frequently to reduce the computational complexity.
Serum autoantibody profiles of IgA, IgE and IgM in canine pemphigus foliaceus (2014)

Our findings suggest that sera from dogs with PF rarely contain IgA or IgE autoantibodies at levels detectable by indirect immunofluorescence, while IgM autoreactivity appears not to be a feature of this disease. Considering these findings, it appears that canine PF is aetiologically and immunologically similar to that of the classic human PF, in which the IgG autoantibody response is also the predominant type.
Evaluation of the Defense System in Chloroplasts to Photooxidative Stress Caused by Paraquat Using Transgenic Tobacco Plants Expressing Catalase from Escherichia coli (2000)

We evaluated the defense system in chloroplasts to photooxidative stress imposed by paraquat treatment under illumination in transgenic tobacco plants with increased tolerance to drought stress at a high light intensity produced by catalase from Escherichia coli targeted to chloroplasts [Shikanai et al. (1998) FEBS Lett. 428: 47]. At 24 h after the paraquat application, Chl was destroyed in the wild-type plants, but not in transgenic plants. Photosynthetic activities monitored by CO2 fixation and Chl fluorescence were much less affected by the paraquat treatment in transgenic lines. The activities of chloroplastic ascorbate peroxidase (APX) isoenzymes decreased in parallel with the depletion of ascorbate (AsA) in leaves in both lines. Paraquat treatment had no effect on the transcript level of chloroplastic APX isoenzymes, while it significantly lowered the level of their proteins. These data suggest that the depletion of AsA in chloroplasts under severe stress conditions inactivates and degrades chloroplastic APX isoenzymes.