gebhart/patrepeval huggingface dataset:
Copper‐Catalyzed Regioselective Fluorination of Allylic Halides (2013)

Group activity: A novel copper-catalyzed fluorination of internal allylic bromides and chlorides has been developed by using Et3N⋅3 HF as the fluorine source. A functional group (FG) within the substrate is required to achieve the allylic fluorination, and a variety of secondary allylic fluoride compounds can be accessed in good yield with excellent regioselectivity.
Synthesizing Chest X-Ray Pathology for Training Deep Convolutional Neural Networks (2018)

Medical datasets are often highly imbalanced with over-representation of prevalent conditions and poor representation of rare medical conditions. Due to privacy concerns, it is challenging to aggregate large datasets between health care institutions. We propose synthesizing pathology in medical images as a means to overcome these challenges. We implement a deep convolutional generative adversarial network (DCGAN) to create synthesized chest X-rays based upon a modest sized labeled dataset. We used a combination of real and synthesized images to train deep convolutional neural networks (DCNNs) to detect pathology across five classes of chest X-rays. The comparative study of DCNNs trained with the combination of real and synthesized images showed that these networks can outperform similar networks trained solely with real images in pathology classification. This improved performance is largely attributable to the balancing of the dataset using DCGAN synthesized images, where classes that are lacking in example images are preferentially augmented.
Phage Displayed Peptide Libraries (1999)

Peptide libraries may be constructed by grafting, in vitro, random DNA sequences into a carrier gene and then introducing the degenerate hybrid coding sequence into an expression organism. This review will focus on phage display, which was the first expression organism for peptide library expression to be described and which still maintains predominance in this area because of its simplicity, minimal cost, ease of manipulation, power and robustness. Using phage as the host, a repertoire of random peptides can be expressed that may be searched by a variety of screening or selection procedures. By physically associating each element of the peptide library with its coding sequence, selection for a property of a specific peptide results in the enrichment of the corresponding gene thus facilitating its cloning and amplification. This review focuses on the construction and screening of peptide libraries displayed on filamentous phage capsid and only briefly discusses the display of proteins and protein domains.
Photoaffinity Labeling with UMP of Lysine 992 of Carbamyl Phosphate Synthetase from Escherichia coli Allows Identification of the Binding Site for the Pyrimidine Inhibitor (1996)

UMP is a highly specific reagent for photoaffinity labeling of the allosteric inhibitor site of carbamyl phosphate synthetase (CPS) from Escherichia coli and has been found to be photoincorporated in the COOH-terminal domain of the large subunit [Rubio et al. (1991) Biochemistry 30, 1068-1075]. In the present work we identify lysine 992 as the residue that is covalently attached to UMP. This identification is based on two lines of evidence. First, [14C]UMP is found to be incorporated between residues 939 and 1006, as shown by peptide mapping and by mass estimates of [14C]UMP-peptides generated by chemical and enzymatic cleavage of CPS. Secondly, we have purified two radioactive peptides derived exclusively from those enzyme molecules (approximately 5% of the total enzyme) that had incorporated [14C]-UMP. Edman analyses show the sequences of the labeled peptides (989)LVNXVHEGRPHIQD and (989)LVNXVHE to be overlapping. Since neither a phenylthiohydantoin (Pth) derivative (in cycle 4) nor any radioactivity is released from the membrane during sequencing, we can conclude that Lys992 and [14C]-UMP form a covalent adduct that remains bound to the membrane. Formation of this adduct agrees with all of the evidence and with the finding that UMP labeling prevents trypsin cleavage at Lys992. Lysine 992 is invariant in those CPSs that are inhibited by UMP, and is located 30 residues upstream of the site whose phosphorylation in hamster CAD reduces inhibition of CAD by UTP. Multiple sequence alignment of the residues surrounding Lys992 of the E. coli enzyme and the corresponding residues of the yeast and animal enzymes supports the existence of a uridine nucleotide binding fold in this region of the protein. We conclude that sequence changes in the binding fold provide a structural basis for the different regulatory properties found among CPSs I, II, and III.
Limitations of enzyme replacement therapy: Current and future (2006)

Orphan drug legislation passed in the USA in 1983 and in Europe in 1999 has encouraged biotechnology companies to develop treatments for diseases that the industry previously ignored because they affect only small numbers of people and promised only limited profitability. Incentives, exclusivity and the freedom to charge sufficient to cover development costs has led to a niche market, and patients with lysosomal storage disorders have been one of the main beneficiaries of these developments. The recombinant production of highly purified enzymes that are modified to improve tissue targeting has been a direct result of this legislation. The spectacular clinical and financial success of Cerezyme (and previously Ceredase, Genzyme) for the treatment of Gaucher disease has led to the development of enzyme replacement treatment(s) for Fabry disease and mucopolysaccharidoses types I and VI. A number of other enzyme replacement therapies are at an earlier stage in development and the next 12 months could see the launch of therapies for mucopolysaccharidosis type II and Pompe disease. Like all medical treatments, this approach has some limitations. Not all patients are suitable for treatment, some organs and tissues are corrected more readily than others, and there are problems with gauging efficacy in these highly variable disorders. Finally, the therapies are expensive, limiting access to patients from those countries that are able to afford expensive health care.
In Situ B Cell-Mediated Immune Responses and Tubulointerstitial Inflammation in Human Lupus Nephritis (2010)

The most prevalent severe manifestation of systemic lupus erythematosus is nephritis, which is characterized by immune complex deposition, inflammation, and scarring in glomeruli and the tubulointerstitium. Numerous studies indicated that glomerulonephritis results from a systemic break in B cell tolerance, resulting in the local deposition of immune complexes containing Abs reactive with ubiquitous self-Ags. However, the pathogenesis of systemic lupus erythematosus tubulointerstitial disease is not known. In this article, we demonstrate that in more than half of a cohort of 68 lupus nephritis biopsies, the tubulointerstitial infiltrate was organized into well-circumscribed T:B cell aggregates or germinal centers (GCs) containing follicular dendritic cells. Sampling of the in situ-expressed Ig repertoire revealed that both histological patterns were associated with intrarenal B cell clonal expansion and ongoing somatic hypermutation. However, in the GC histology, the proliferating cells were CD138(-)CD20(+) centroblasts, whereas they were CD138(+)CD20(low/-) plasmablasts in T:B aggregates. The presence of GCs or T:B aggregates was strongly associated with tubular basement membrane immune complexes. These data implicate tertiary lymphoid neogenesis in the pathogenesis of lupus tubulointerstitial inflammation.
Characterization of the Burkholderia mallei tonB Mutant and Its Potential as a Backbone Strain for Vaccine Development (2015)

Although further work is needed to prevent chronic infection by TMM001 while maintaining immunogenicity, our attenuated strain demonstrates great potential as a backbone strain for future vaccine development against both glanders and melioidosis.
Mitochondria-Division Inhibitor 1 Protects Against Amyloid-β induced Mitochondrial Fragmentation and Synaptic Damage in Alzheimer’s Disease (2017)

The purpose our study was to determine the protective effects of mitochondria division inhibitor 1 (Mdivi1) in Alzheimer's disease (AD). Mdivi1 is hypothesized to reduce excessive fragmentation of mitochondria and mitochondrial dysfunction in AD neurons. Very little is known about whether Mdivi1 can confer protective effects in AD. In the present study, we sought to determine the protective effects of Mdivi1 against amyloid-β (Aβ)- and mitochondrial fission protein, dynamin-related protein 1 (Drp1)-induced excessive fragmentation of mitochondria in AD progression. We also studied preventive (Mdivi1+Aβ42) and intervention (Aβ42+Mdivi1) effects against Aβ42 in N2a cells. Using real-time RT-PCR and immunoblotting analysis, we measured mRNA and protein levels of mitochondrial dynamics, mitochondrial biogenesis, and synaptic genes. We also assessed mitochondrial function by measuring H2O2, lipid peroxidation, cytochrome oxidase activity, and mitochondrial ATP. MTT assays were used to assess the cell viability. Aβ42 was found to impair mitochondrial dynamics, lower mitochondrial biogenesis, lower synaptic activity, and lower mitochondrial function. On the contrary, Mdivi1 enhanced mitochondrial fusion activity, lowered fission machinery, and increased biogenesis and synaptic proteins. Mitochondrial function and cell viability were elevated in Mdivi1-treated cells. Interestingly, Mdivi1 pre- and post-treated cells treated with Aβ showed reduced mitochondrial dysfunction, and maintained cell viability, mitochondrial dynamics, mitochondrial biogenesis, and synaptic activity. The protective effects of Mdivi1 were stronger in N2a+Aβ42 pre-treated with Mdivi1, than in N2a+Aβ42 cells than Mdivi1 post-treated cells, indicating that Mdivi1 works better in prevention than treatment in AD like neurons.
An acoustic boundary element method based on energy and intensity variables for prediction of high-frequency broadband sound fields (2001)

A boundary element method is formulated in terms of time-averaged energy and intensity variables. The approach is applicable to high modal density fields but is not restricted to the usual low-absorption, diffuse, and quasiuniform assumptions. A broadband acoustic energy/intensity source is the basic building block for the method. A directivity pattern for the source is derived to account for local spatial correlation effects and to model specular reflections approximately. A distribution of infinitesimal, uncorrelated, directional sources is used to model the boundaries of an enclosure. These sources are discretized in terms of boundary elements. A system of equations results from applying boundary conditions in terms of incident, reflected, and absorbed intensity. The unknown source power for each element is determined from this system of equations. A two-dimensional model problem is used to demonstrate and verify the method. Exact numerical solutions were also obtained for this model problem. The results show that spatially varying mean-square pressure levels are accurately predicted at very low computational cost.
Anonymous marker loci within 400 kb of HLA-A generate haplotypes in linkage disequilibrium with the hemochromatosis gene (HFE) (1994)

The hemochromatosis gene (HFE) maps to 6p21.3 and is less than 1 cM from the HLA class I genes; however, the precise physical location of the gene has remained elusive and controversial. The unambiguous identification of a crossover event within hemochromatosis families is very difficult; it is particularly hampered by the variability of the phenotypic expression as well as by the sex- and age-related penetrance of the disease. For these practical considerations, traditional linkage analysis could prove of limited value in further refining the extrapolated physical position of HFE. We therefore embarked upon a linkage-disequilibrium analysis of HFE and normal chromosomes from the Brittany population. In the present report, 66 hemochromatosis families yielding 151 hemochromatosis chromosomes and 182 normal chromosomes were RFLP-typed with a battery of probes, including two newly derived polymorphic markers from the 6.7 and HLA-F loci located 150 and 250 kb telomeric to HLA-A, respectively. The results suggest a strong peak of existing linkage disequilibrium focused within the i82-to-6.7 interval (approximately 250 kb). The zone of linkage disequilibrium is flanked by the i97 locus, positioned 30 kb proximal to i82, and the HLA-F gene, found 250 kb distal to HLA-A, markers of which display no significant association with HFE. These data support the possibility that HFE resides within the 400-kb expanse of DNA between i97 and HLA-F. Alternatively, the very tight association of HLA-A3 and allele 1 of the 6.7 locus, both of which are comprised by the major ancestral or founder HFE haplotype in Brittany, supports the possibility that the disease gene may reside immediately telomeric to the 6.7 locus within the linkage-disequilibrium zone. Additionally, hemochromatosis haplotypes possessing HLA-A11 and the low-frequency HLA-F polymorphism (allele 2) are supportive of a separate founder chromosome containing a second, independently arising mutant allele. Overall, the establishment of a likely "hemochromatosis critical region" centromeric boundary and the identification of a linkage-disequilibrium zone both significantly contribute to a reduction in the amount of DNA required to be searched for novel coding sequences constituting the HFE defect.
Lysophosphatidic acid stimulates mitogen-activated protein kinase activation via a G-protein-coupled pathway requiring p21ras and p74raf-1. (1993)

Activation of tyrosine kinase receptors causes mitogen-activated protein (MAP) kinase stimulation via a pathway involving p21ras, p74raf-1 (acting as a MAP kinase kinase kinase), and MAP kinase kinases; however, the pathway by which heterotrimeric G-protein-coupled receptors activate MAP kinases is undefined. Since there are several MAP kinase kinase kinases it has been suggested that p74raf-1 may only couple tyrosine kinase receptors to MAP kinase activation. We therefore investigated the requirement for p21ras and p74raf-1 in G-protein receptor-mediated MAP kinase activation. Lysophosphatidic acid stimulates MAP kinase via a pertussis toxin-sensitive pathway, which is blocked by dominant negative Ras. Lysophosphatidic acid-stimulated MAP kinase activation is potentiated by overexpression of p74raf-1 and blocked by expression of a dominant negative Raf protein comprising the N-terminal 259 amino acids. We conclude that lysophosphatidic acid activates MAP kinases by a G-protein-coupled pathway that requires both p21ras and p74raf-1.
Applications of FLC SLM dynamic holograms to WDM network components (1998)

This paper presents an overview of ferroelectric liquid crystal spatial light modulator (FLC SLM) dynamic digital holographic filtering technology and its application to WDM network components. Early work demonstrated a dynamically tunable filter and, in conjunction with an erbium-doped fibre amplifier (EDFA), a fibre laser[1]. The hologram design algorithm was subsequently expanded to yield a multiple variable amplitude passband filter, or spectral equaliser, for four[2] or six[3] WDM channels. Latest results for eight-channel equalisation are presented in this article, together with a demonstration of flattening the spectral shape of an individual passband. The paper concludes with a discussion of future work, including the redesign of filter parameters to meet ITU standards, and further improvements in computerised hologram design to achieve finer tuning resolution.
Repeated epitaxial growth and transfer of arrays of patterned, vertically aligned, crystalline Si wires from a single Si(111) substrate (2008)

Multiple arrays of Si wires were sequentially grown and transferred into a flexible polymer film from a single Si(111) wafer. After growth from a patterned, oxide-coated substrate, the wires were embedded in a polymer and then mechanically separated from the substrate, preserving the array structure in the film. The wire stubs that remained were selectively etched from the Si(111) surface to regenerate the patterned substrate. Then the growth catalyst was electrodeposited into the holes in the patterned oxide. Cycling through this set of steps allowed regrowth and polymer film transfer of several wire arrays from a single Si wafer.
Poly(ADP-ribosyl)ation accelerates DNA repair in a pathway dependent on Cockayne syndrome B protein (2003)

Activation of poly(ADP-ribose)polymerases 1 and 2 (PARP-1 and PARP-2) is one of the earliest responses of mammalian cells to DNA damage by numerous genotoxic agents. We have analysed the influence of PARP inhibition, either achieved by over-expression of the DNA binding domain of PARP-1 or by treatment with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone, on the repair of single-strand breaks (SSB), pyrimidine dimers and oxidative base modifications sensitive to Fpg protein (mostly 8-hydroxyguanine) in mammalian cells at very low, non-cytotoxic levels of DNA damage. The data show that the repair rates of all three types of DNA damage are significantly lower in PARP-inhibited cells. Importantly, the retardation of the repair of base modifications is not associated with accumulation of intermediates such as SSB or abasic sites. Moreover, the influence of the PARP inhibition is not observed in cells deficient in Cockayne syndrome B protein (Csb). The results indicate that PARP activation and Csb are both involved in a novel mechanism that accelerates the global repair of various types of DNA modifications.
Dilute Solution Routes to Various Controllable Morphologies of MCM-41 Silica with a Basic Medium (2001)

MCM-41 silica particles with several morphologies have been controllably synthesized with a basic medium. Nanospherical MCM-41 silica with an average size of 110 nm was produced through reaction of extremely low surfactant concentrations of CTAB with TEOS in the sodium hydroxide medium at 353 K, while a submicrometer-sized silica rod, 0.3−0.6 μm in diameter and 1 μm in length, and micrometer-sized oblate silica with nominal diameter around 1 μm were synthesized in aqueous ammonia, where the size and the morphology were controlled by varing the content of the solvent. A morphogenetic mechanism that is based on the deposition of self-assembled silicate surfactant rodlike micelles is proposed and explains well the controllability of the morphology.
CORRELATIONS BETWEEN THE CHEMICAL STRUCTURE AND THE PHARMACOLOGICAL ACTIONS OF THE STEROIDS1 (1942)

Journal Article CORRELATIONS BETWEEN THE CHEMICAL STRUCTURE AND THE PHARMACOLOGICAL ACTIONS OF THE STEROIDS Get access HANS SELYE HANS SELYE 1From the Department of Anatomy, McGill University MONTREAL, CANADA Search for other works by this author on: Oxford Academic Google Scholar Endocrinology, Volume 30, Issue 3, 1 March 1942, Pages 437–453, https://doi.org/10.1210/endo-30-3-437 Published: 01 March 1942 Article history Received: 28 October 1941 Published: 01 March 1942
In-betweeness: the (dis)connection between here and there. The case of Indian student-migrants in Australia (2013)

N-Acetylcysteine is a natural thiol-containing antioxidant, a precursor for cysteine and glutathione, and a potential detoxifying agent for heavy metal ions. However, previous accounts of the efficiency of N-acetylcysteine (H2NAC) in excretion of lead are few and contradicting. Here, we report results on the nature of lead(II) complexes formed with N-acetylcysteine in aqueous solution, which were obtained by combining information from several spectroscopic methods, including (207)Pb, (13)C, and (1)H NMR, Pb LIII-edge X-ray absorption, ultraviolet-visible (UV-vis) spectroscopy, and electro-spray ionization mass spectrometry (ESI-MS). Two series of solutions were used containing CPb(II) = 10 and 100 mM, respectively, varying the H2NAC/Pb(II) mole ratios from 2.1 to 10.0 at pH 9.1-9.4. The coordination environments obtained resemble those previously found for the Pb(II) glutathione system: at a ligand-to-lead mole ratio of 2.1, dimeric or oligomeric Pb(II) N-acetylcysteine complexes are formed, while a trithiolate [Pb(NAC)3](4-) complex dominates in solutions with H2NAC/Pb(II) mole ratios >3.0.
Morphology of nascent ultra-high molecular weight polyethylene reactor powder : chain-extended versus chain-folded crystals (1991)

Usually nascent ultra-high molecular weight polyethylene (UHMW-PE) reactor powders possess relatively high melting temperatures (138-143 o C), generally attributed to the presence of (more or less) chain-extended crystals. It is shown that the commonly accepted relationship between a high melting temperature and the presence of chain-extended crystals cannot be generalized in the case of UHMW-PE powders. It is concluded that the high melting temperatures could be related to a fast reorganization process during dynamic heating
Hypertonic shock inhibits growth factor receptor signaling, induces caspase-3 activation, and causes reversible fragmentation of the mitochondrial network (2004)

Hyperosmotic stress can be encountered by the kidney and the skin, as well as during treatment of acute brain damage. It can lead to cell cycle arrest or apoptosis. Exactly how mammalian cells detect hyperosmolarity and how the cell chooses between cell cycle arrest or death remains to be established. It has been proposed that hyperosmolarity is detected directly by growth factor receptor protein tyrosine kinases. To investigate this, we tested whether growth factors and osmotic stress cooperate in the activation of signaling pathways. Receptors responded normally to the presence of growth factors, and we observed normal levels of GTP-bound Ras under hyperosmotic conditions. In contrast, activation of Raf, Akt, ERK1, ERK2, and c-Jun NH 2 -terminal kinase was strongly reduced. These observations suggest that hyperosmotic conditions block signaling directly downstream of active Ras. It is thought that apoptotic cell death due to environmental stress is initiated by cytochrome c release from the mitochondria. Visualization of cytochrome c using immunofluorescence showed that hypertonic conditions result in a breakup of the mitochondrial network, which is reestablished within 1 h after hypertonic medium is replaced with isotonic medium. When we carried out live imaging, we observed that the mitochondrial membrane potential disappeared immediately after the onset of hyperosmotic shock. Our observations provide new insights into the hypertonic stress response pathway. In addition, they show that signaling downstream of Ras and mitochondrial dynamics can easily be manipulated by the exposure of cells to hyperosmotic conditions.