gebhart/patrepeval huggingface dataset:
The Protective Effect of Quercetin against Oxidative Stress in the Human RPE In Vitro (2008)

The data demonstrate that quercetin is able to protect RPE cells from oxidative damage and cellular senescence in vitro in a dose-dependent manner. The authors suggest that this increase in antioxidative capacity is--among other mechanisms, such as the intracellular redox state--also mediated by inhibiting the upregulation of caveolin-1. Downregulation of caveolin-1 may be important for the retinal pigment epithelium to prevent apoptotic cell death in response to cellular stress, a condition implicated in the early pathogenesis of AMD. Therefore, the authors believe that the use of antioxidative dietary flavonoids such as quercetin is a promising approach in the prevention of early AMD.
Genetic Manipulation of Human Embryonic Stem Cells: A System to Study Early Human Development and Potential Therapeutic Applications (2005)

The successful derivation of human embryonic stem cell (hESC) lines by Thomson and colleagues [Thomson et al., 1998] provided a new area of investigation in both regenerative medicine and early human development. Fundamental study of the molecular and cellular mechanisms responsible for normal lineage development will rely on reproducible protocols to direct the differentiation of hESCs into specific lineages of interest and genetically manipulate both hESCs and their derivatives. Identifying standards for maintenance of hESCs, methods for controlled differentiation and genetic manipulation of hESCs and their derivatives will provide a foundation to explore their potential therapeutic use in cell and gene therapy. In the present review, our goal is to outline the latest advances in the field with particular focus on how hESCs and their derivatives can be genetically altered, how this may be useful in better understanding the cellular and molecular events of lineage differentiation, and how deregulation of these cellular processes may lead to abnormal development and disease.
Proinsulin maturation, misfolding, and proteotoxicity (2007)

As a tool to explore proinsulin (PI) trafficking, a human PI cDNA has been constructed with GFP fused within the C peptide. In regulated secretory cells containing appropriate prohormone convertases, the hProCpepGFP construct undergoes endoproteolytic processing to CpepGFP and native human insulin, which are specifically detected and cosecreted in parallel with endogenous insulin. Expression of C(A7)Y mutant PI results in autosomal dominant diabetes in Akita mice. We directly identify the misfolded PI in Akita islets and also show that C(A7)Y mutant PI, either in the context of the hProCpepGFP chimera or not, engages directly in protein complexes with nonmutant PI, impairing the trafficking and recovery of nonmutant PI. This trapping mechanism decreases insulin production in beta cells. Thereafter we observe a loss of beta cell viability. The data imply that PI misfolding leading to impaired endoplasmic reticulum exit of nonmutant PI may be a key early step in a chain reaction of beta cell dysfunction and demise leading to onset and progression of diabetes.
Genetic Reassortment of Avian, Swine, and Human Influenza A Viruses in American Pigs (1999)

In late summer through early winter of 1998, there were several outbreaks of respiratory disease in the swine herds of North Carolina, Texas, Minnesota, and Iowa. Four viral isolates from outbreaks in different states were analyzed genetically. Genotyping and phylogenetic analyses demonstrated that the four swine viruses had emerged through two different pathways. The North Carolina isolate is the product of genetic reassortment between H3N2 human and classic swine H1N1 influenza viruses, while the others arose from reassortment of human H3N2, classic swine H1N1, and avian viral genes. The hemagglutinin genes of the four isolates were all derived from the human H3N2 virus circulating in 1995. It remains to be determined if either of these recently emerged viruses will become established in the pigs in North America and whether they will become an economic burden.
Mechanisms of anti-NMDAR Antibody Mediated Damage to the Fetal Brain (2020)

Abstract Mothers with systemic lupus erythematosus (SLE) have an increased frequency of children with learning disorders and autism spectrum disorder (ASD) which associates with maternal anti-DNA antibodies, indicating that in utero exposure to autoantibodies may lead to neurodevelopmental alterations. A subset of anti-dsDNA antibodies present in 40% of SLE patients has been shown to cross-react with the N-methyl D-aspartate receptor (NMDAR) excitatory neuronal receptor. Immunizing mice with these antibodies (DNRAbs) causes morphological neurodevelopmental alterations and persistent behavioral and neurocognitive abnormalities in male offspring, as well as the death of a high proportion (~40%) of female fetuses due to their earlier expression of the GluN2A NMDAR subunit. The brains of the fetuses from DNRAb+ dams display increased neuronal apoptosis and thinned cortical plates, indicating alterations in neuronal migration. Male offspring of DNRAb+ dams exhibit delayed reflex acquisition, cognitive impairments in fear extinction and novel object recognition, and decreased overall cortical volume. These results parallel the substantially higher proportion of male children born to women with SLE, as well as the higher rate of developmental disorders in these children. Current studies are addressing the mechanisms of this antibody-mediated damage and whether these offspring exhibit characteristics of ASD.
High‐Temperature and Chemically Resistant Foams from Sustainable Nanostructured Protein (2021)

Abstract Covalently crosslinked protein networks produced from whey protein nanofibrils (PNFs) are demonstrated to be sustainable high‐performance foams that show chemical resistance and mechanical strength, stiffness, and toughness on harsh aging at 150 °C. The aged foams are able to retain their properties at 180 °C for as long as 24 h, far exceeding the properties of most classical petroleum‐based thermoplastics. The foams are further developed into soft foams by the addition of glycerol as a plasticizer. The improvement in the mechanical performance of the foams with aging, which is equivalent to an increase by one order of magnitude in modulus and yield strength, is confirmed to be associated with (iso)peptide crosslinks. The results open the way for using protein‐based foam materials in severe/corrosive environments such as filtration, thermal insulation, and fluid absorption. The protein foams produced are suggested as suitable alternatives to petroleum‐based porous polymers.
ChemInform Abstract: Spiroforskolin: Structure and Mode of Formation. (1993)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A phase II study of alemtuzumab, fludarabine, cyclophosphamide, and doxorubicin (Campath-FCD) in peripheral T-cell lymphomas (2010)

The clinical course of peripheral T-cell lymphoma (PTCL) is usually aggressive and the prognosis unfavorable. Therefore, there is a need for improvement of treatment options. Patients with newly diagnosed (n = 27) or refractory/relapsed (n = 11) PTCL received a combination of alemtuzumab, fludarabine, cyclophosphamide, and doxorubicin. The overall response rate (ORR) was 61%, with a complete response rate of 39%. In newly diagnosed patients the ORR was 63%, the median overall survival 25.9 months, and progression-free survival 11.8 months. In relapsed/refractory patients the median OS was 6.1 months. The most frequent grade 3/4 toxicities were leukopenia (95% of patients) and thrombocytopenia (58%). Cytomegalovirus (CMV) reactivation occurred in 12 patients, but only two had CMV disease. Treatment-related deaths occurred in six newly diagnosed patients and one with relapsed/refractory disease. In conclusion, Campath-FCD is active in PTCL but is associated with significant toxicity and is, therefore, not recommended for use or further study. Further studies are warranted to investigate other approaches to combining alemtuzumab with chemotherapy for the treatment of PTCL.
Distinct Disulfide Isomers of μ-Conotoxins KIIIA and KIIIB Block Voltage-Gated Sodium Channels (2012)

In the preparation of synthetic conotoxins containing multiple disulfide bonds, oxidative folding can produce numerous permutations of disulfide bond connectivities. Establishing the native disulfide connectivities thus presents a significant challenge when the venom-derived peptide is not available, as is increasingly the case when conotoxins are identified from cDNA sequences. Here, we investigate the disulfide connectivity of μ-conotoxin KIIIA, which was predicted originally to have a [C1-C9,C2-C15,C4-C16] disulfide pattern based on homology with closely related μ-conotoxins. The two major isomers of synthetic μ-KIIIA formed during oxidative folding were purified and their disulfide connectivities mapped by direct mass spectrometric collision-induced dissociation fragmentation of the disulfide-bonded polypeptides. Our results show that the major oxidative folding product adopts a [C1-C15,C2-C9,C4-C16] disulfide connectivity, while the minor product adopts a [C1-C16,C2-C9,C4-C15] connectivity. Both of these peptides were potent blockers of Na(V)1.2 (K(d) values of 5 and 230 nM, respectively). The solution structure for μ-KIIIA based on nuclear magnetic resonance data was recalculated with the [C1-C15,C2-C9,C4-C16] disulfide pattern; its structure was very similar to the μ-KIIIA structure calculated with the incorrect [C1-C9,C2-C15,C4-C16] disulfide pattern, with an α-helix spanning residues 7-12. In addition, the major folding isomers of μ-KIIIB, an N-terminally extended isoform of μ-KIIIA identified from its cDNA sequence, were isolated. These folding products had the same disulfide connectivities as μ-KIIIA, and both blocked Na(V)1.2 (K(d) values of 470 and 26 nM, respectively). Our results establish that the preferred disulfide pattern of synthetic μ-KIIIA and μ-KIIIB folded in vitro is 1-5/2-4/3-6 but that other disulfide isomers are also potent sodium channel blockers. These findings raise questions about the disulfide pattern(s) of μ-KIIIA in the venom of Conus kinoshitai; indeed, the presence of multiple disulfide isomers in the venom could provide a means of further expanding the snail's repertoire of active peptides.
Optimal surgical care for adolescent idiopathic scoliosis: an international consensus (2014)

International consensus was found on many aspects of what does and does not constitute optimal operative care for adolescents with AIS. In the absence of current high-level evidence, at present, these expert opinion findings will aid health care providers worldwide define appropriate care in their regions. Areas with no consensus provide excellent insight and priorities for future research.
Neural Taylor Approximations: Convergence and Exploration in Rectifier\n Networks (2016)

Modern convolutional networks, incorporating rectifiers and max-pooling, are\nneither smooth nor convex; standard guarantees therefore do not apply.\nNevertheless, methods from convex optimization such as gradient descent and\nAdam are widely used as building blocks for deep learning algorithms. This\npaper provides the first convergence guarantee applicable to modern convnets,\nwhich furthermore matches a lower bound for convex nonsmooth functions. The key\ntechnical tool is the neural Taylor approximation -- a straightforward\napplication of Taylor expansions to neural networks -- and the associated\nTaylor loss. Experiments on a range of optimizers, layers, and tasks provide\nevidence that the analysis accurately captures the dynamics of neural\noptimization. The second half of the paper applies the Taylor approximation to\nisolate the main difficulty in training rectifier nets -- that gradients are\nshattered -- and investigates the hypothesis that, by exploring the space of\nactivation configurations more thoroughly, adaptive optimizers such as RMSProp\nand Adam are able to converge to better solutions.\n
On-Chip Identification and Interaction Analysis of Gel-Resolved Proteins Using a Diamond-like Carbon-Coated Plate (2007)

We developed a novel protein chip made of a diamond-like, carbon-coated stainless steel plate (DLC plate), the surface of which is chemically modified with N-hydroxysuccinimide ester. To produce a high-density protein chip using the DLC plate, proteins separated by SDS gel electrophoresis or two-dimensional electrophoresis were electroblotted onto the DLC plate and immobilized covalently. A high blotting efficiency (25-70%) for transferring proteins from the gels onto the DLC plates was achieved by improvement of the electrophoresis device and electroblotting techniques. With the use of the DLC plate, we developed novel techniques to identify proteins immobilized on the chip and to detect protein-protein interactions on the chip by mass spectrometric analysis. We also developed a technique to identify post-translationally modified proteins, such as glycoproteins, on the protein chip.
Polymeric micelle mediated follicular delivery of spironolactone: Targeting the mineralocorticoid receptor to prevent glucocorticoid-induced activation and delayed cutaneous wound healing (2021)

Impaired wound healing in patients receiving glucocorticoid therapy is a serious clinical concern: mineralocorticoid receptor (MR) antagonists can counter glucocorticoid-induced off-target activation of MR receptors. The aim of this study was to investigate the cutaneous delivery of the potent MR antagonist, spironolactone (SPL), from polymeric micelle nanocarriers, prepared using a biodegradable copolymer, methoxy-poly(ethylene glycol)-di-hexyl-substituted-poly(lactic acid). Immunofluorescent labelling of the MR showed that it was principally located in the pilosebaceous unit (PSU), justifying the study rationale since polymeric micelles accumulate preferentially in appendageal structures. Cutaneous biodistribution studies under infinite and finite dose conditions, demonstrated delivery of pharmacologically relevant amounts of SPL to the epidermis and upper dermis. Preferential PSU targeting was confirmed by comparing amounts of SPL in PSU-containing and PSU-free skin biopsies: SPL nanomicelles showed 5-fold higher delivery of SPL in the PSU-containing biopsies, 0.54 ± 0.18 ng/mm<sup>2</sup>vs. 0.10 ± 0.03 ng/mm<sup>2</sup>, after application of a hydrogel in finite conditions. Canrenone, an active metabolite of SPL, was also quantified in skin samples. In addition to being used for the treatment of delayed cutaneous wound healing by site-specific antagonism of the MR, the formulation might also be used to treat pilosebaceous androgen-related skin diseases, e.g. acne vulgaris, since SPL is a potent androgen receptor antagonist.
Electron-Based Dissociation Is Needed for O-Glycopeptides Derived from OpeRATOR Proteolysis (2020)

The recently described O-glycoprotease OpeRATOR presents exciting opportunities for O-glycoproteomics. This bacterial enzyme purified from Akkermansia (Sp). muciniphila cleaves N-terminally to serine and threonine residues that are modified with (preferably asialylated) O-glycans. This provides orthogonal cleavage relative to canonical proteases (e.g., trypsin) for improved O-glycopeptide characterization with tandem mass spectrometry (MS/MS). O-glycopeptides with a modified N-terminal residue, such as those generated by OpeRATOR, present several potential benefits, perhaps the most notable being de facto O-glycosite localization without the need of glycan-retaining fragments in MS/MS spectra. Indeed, O-glycopeptides modified exclusively at the N-terminus would enable O-glycoproteomic methods to rely solely on collision-based fragmentation rather than electron-driven dissociation because glycan-retaining peptide fragments would not be required for localization. The caveat is that modified peptides would need to reliably contain only a single O-glycosite. Here we use methods that combine collision- and electron-based fragmentation to characterize the number of O-glycosites that are present in O-glycopeptides derived from OpeRATOR digestion of four known O-glycoproteins. Our data show that over 50% of O-glycopeptides generated from combined digestion using OpeRATOR and trypsin contain multiple O-glycosites, indicating that collision-based fragmentation alone is not sufficient. Electron-based dissociation methods are necessary to capture the O-glycopeptide diversity present in OpeRATOR digestions.
Monitoring therapy response with fluorescence imaging (2010)

We quantified fluorescence photobleaching kinetics of our novel bifunctional agent (HPPH-CD) during PDT with fluorescence imaging. Our results show that HPPH-CD exhibit preferential uptake in tumors compared to surrounding normal tissue and longer wavelength emitting CD allowed monitoring photobleaching in deep tumors.
Miniaturized Linear Wire Ion Trap Mass Analyzer (2016)

We report a linear ion trap (LIT) in which the electric field is formed by fine wires held under tension and accurately positioned using holes drilled in two end plates made of plastic. The coordinates of the hole positions were optimized in simulation. The stability diagram and mass spectra using boundary ejection were compared between simulation and experiment and good agreement was found. The mass spectra from experiments show peak widths (fwhm) in units of mass-to-charge of around 0.38 Th using a scan rate of 3830 Th/s. The limits of detection are 137 ppbv and 401 ppbv for benzene and toluene, respectively. Different sizes of the wire ion trap can be easily fabricated by drilling holes in scaled positions. Other distinguishing features, such as high ion and photon transmission, low capacitance, high tolerance to mechanical and assembly error, and low weight, are discussed.
An inactivated mycoplasma pneumoniae vaccine. (1965)

An experimental vaccine was prepared withMycoplasma pneumonia, the agent of primary atypical pneumonia. Its injection elicited antibody in rabbits and monkeys and induced resistance to multiplication of myoplasma in lungs of vaccinated hamsters. The vaccine was well tolerated in preliminary studies with 36 human subjects, and encouraging evidence of antigenicity was obtained when 25 of 30 developed significant rises in mycoplasma growth-inhibiting antibody titers. The response was best (17 of 19) in men in whom prevaccination antibody was absent or low. The vaccine was prepared with a new culture medium in which chloroform extract of egg yolk and a chemically defined salt-amino acid-vitamin solution was substituted for the allergenic horse serum and beef infusion components of standard medium.
Supplementary Data from Stress-Mediated Reprogramming of Prostate Cancer One-Carbon Cycle Drives Disease Progression (2023)

&lt;p&gt;Supplementary Tables&lt;/p&gt;
Supplementary Figure 4 from RapidCaP, a Novel GEM Model for Metastatic Prostate Cancer Analysis and Therapy, Reveals Myc as a Driver of <i>Pten</i>-Mutant Metastasis (2023)

&lt;p&gt;PDF file 199K, Analysis of metastatic prostate cancer in lung reveals the Akt-Myc switch&lt;/p&gt;
Inhalation treatment of cystic fibrosis with lumacaftor and ivacaftor co-delivered by nanostructured lipid carriers (2019)

Cystic fibrosis (CF), a most deadly genetic disorder, is caused by mutations of CF transmembrane receptor (CFTR) - a chloride channel present at the surface of epithelial cells. In general, two steps have to be involved in treatment of the disease: correction of cellular defects and potentiation to further increase channel opening. Consequently, a combinatorial simultaneous treatment with two drugs with different mechanisms of action, lumacaftor and ivacaftor, has been recently proposed. While lumacaftor is used to correct p.Phe508del mutation (the loss of phenylalanine at position 508) and increase the amount of cell surface-localized CFTR protein, ivacaftor serves as a CFTR potentiator that increases the open probability of CFTR channels. Since the main organ that is affected by cystic fibrosis is the lung, the delivery of drugs directly to the lungs by inhalation has a potential to enhance the efficacy of the treatment of CF and limit adverse side effects upon healthy tissues and organs. Based on our extensive experience in inhalation delivering of drugs by different nanocarriers, we selected nanostructured lipid carriers (NLC) for the delivery both drugs directly to the lungs by inhalation and tested NLC loaded with drugs in vitro (normal and CF human bronchial epithelial cells) and in vivo (homozygote/homozygote bi-transgenic mice with CF). The results show that the designed NLCs demonstrated a high drug loading efficiency and were internalized in the cytoplasm of CF cells. It was found that NLC-loaded drugs were able to restore the expression and function of CFTR protein. As a result, the combination of lumacaftor and ivacaftor delivered by lipid nanoparticles directly into the lungs was highly effective in treating lung manifestations of cystic fibrosis.
MP34-11 RESECTOSCOPE WORKING ELEMENT WITH ROTATING HANDLE FOR A MORE ERGONOMIC SURGERY (2016)

referred to both 2 D and 3 D systems. The same results were obtained for the neuro-sensitive tests. At the optometric evaluation a significant alteration of pre vs post random dot test was found only in the contest of 3 D procedures (32.5+/-4.6 vs 45.0+/-7.5; p<0.05). After qualitative analysis a significant alteration was documented after 3D vs 2 D procedures for fixation disparity (75% vs 37.5%; p<0.05) and phoria-T test (37,5% vs 12.5%; p<0.05).
Channel Formation by LktA of Mannheimia (Pasteurella) haemolytica in Lipid Bilayer Membranes and Comparison of Channel Properties with Other RTX-Cytolysins (2019)

Cytolysin LktA is one of the major pathogenicity factors of <i>Mannheimia haemolytica</i> (formerly <i>Pasteurella haemolytica</i>) that is the cause of pasteurellosis, also known as shipping fever pneumonia, causing substantial loss of sheep and cattle during transport. LktA belongs to the family of RTX-toxins (Repeats in ToXins) that are produced as pathogenicity factors by a variety of Gram-negative bacteria. Sublytic concentrations of LktA cause inflammatory responses of ovine leukocytes. Higher concentrations result in formation of transmembrane channels in target cells that may cause cell lysis and apoptosis. In this study we investigated channel formation by LktA in artificial lipid bilayer membranes made of different lipids. LktA purified from culture supernatants by polyethylene glycol 4000 precipitation and lyophilization had to be activated to frequently form channels by solution in 6 M urea. The LktA channels had a single-channel conductance of about 60 pS in 0.1 M KCl, which is about one tenth of the conductance of most RTX-toxins with the exception of adenylate cyclase toxin of <i>Bordetella pertussis</i>. The LktA channels are highly cation-selective caused by negative net charges. The theoretical treatment of the conductance of LktA as a function of the bulk aqueous concentration allowed a rough estimate of the channel diameter, which is around 1.5 nm. The size of the LktA channel is discussed with respect to channels formed by other RTX-toxins. We present here the first investigation of LktA in a reconstituted system.