gebhart/patrepeval huggingface dataset:
Carbonic Anhydrase Inhibitors:  Synthesis of Membrane-Impermeant Low Molecular Weight Sulfonamides Possessing in Vivo Selectivity for the Membrane-Bound versus Cytosolic Isozymes (1999)

Aromatic/heterocyclic sulfonamides act as strong inhibitors of the zinc enzyme carbonic anhydrase (CA; EC 4.2.1.1), but the presently available compounds do not generally discriminate between the 14 isozymes isolated in higher vertebrates. Thus, clinically used drugs from this class of pharmacological agents show many undesired side effects due to unselective inhibition of all CA isozymes present in a tissue/organ. Here we propose a new approach for the selective in vivo inhibition of membrane-bound versus cytosolic CA isozymes with a new class of positively charged, membrane-impermeant sulfonamides. This approach is based on the attachment of trisubstituted-pyridinium-methylcarboxy moieties (obtained from 2,4, 6-trisubstituted-pyrylium salts and glycine) to the molecules of classical aromatic/heterocyclic sulfonamides possessing free amino, imino, hydrazino, or hydroxyl groups in their molecules. Efficient in vitro inhibition (in the nanomolar range) was observed with some of the new derivatives against three investigated CA isozymes: i.e., hCA I, hCA II (cytosolic forms), and bCA IV (membrane-bound isozyme) (h = human isozyme; b = bovine isozyme). Due to their salt-like character, the new type of inhibitors reported here, unlike the classical, clinically used compounds (such as acetazolamide, methazolamide, and ethoxzolamide), are unable to penetrate through biological membranes, as shown by ex vivo and in vivo perfusion experiments in rats. The level of bicarbonate excreted into the urine of the experimental animals perfused with solutions of the new and classical inhibitors undoubtedly proved that: (i) when using the new type of positively charged sulfonamides, only the membrane-bound enzyme (CA IV) was inhibited, whereas the cytosolic isozymes (CA I and II) were not affected; (ii) in the experiments in which the classical compounds (acetazolamide, benzolamide, etc.) were used, unselective inhibition of all CA isozymes (I, II, and IV) has been evidenced.
Crystal Structure of a Cross-reaction Complex between Fab F9.13.7 and Guinea Fowl Lysozyme (1995)

The crystal structure of the complex between the cross-reacting antigen Guinea fowl lysozyme and the Fab from monoclonal antibody F9.13.7, raised against hen egg lysozyme, has been determined by x-ray diffraction to 3-A resolution. The antibody interacts with exposed residues of an alpha-helix and surrounding loops adjacent to the lysozyme active site cleft. The epitope of lysozyme bound by antibody F9.13.7 overlaps almost completely with that bound by antibody HyHEL10; the same 12 residues of the antigen interact with the two antibodies. The antibodies, however, have different combining sites with no sequence homology at any of their complementarity-determining regions and show a dissimilar pattern of cross-reactivity with heterologous antigens. Side chain mobility of epitope residues contributes to confer steric and electrostatic complementarity to differently shaped combining sites, allowing functional mimicry to occur. The capacity of two antibodies that have different fine specificities to bind the same area of the antigen emphasizes the operational character of the definition of an antigenic determinant. This example demonstrates that degenerate binding of the same structural motif does not require the existence of sequence homology or other chemical similarities between the different binding sites.
Ovule Development: Identification of Stage-Specific and Tissue-Specific cDNAs (1996)

Jeanette A. Nadeau, Xian Sheng Zhang, Juan Li, Sharman D. O'Neill, Ovule Development: Identification of Stage-Specific and Tissue-Specific cDNAs, The Plant Cell, Vol. 8, No. 2 (Feb., 1996), pp. 213-239
Multiplexed Echo Planar Imaging for Sub-Second Whole Brain FMRI and Fast Diffusion Imaging (2010)

Echo planar imaging (EPI) is an MRI technique of particular value to neuroscience, with its use for virtually all functional MRI (fMRI) and diffusion imaging of fiber connections in the human brain. EPI generates a single 2D image in a fraction of a second; however, it requires 2-3 seconds to acquire multi-slice whole brain coverage for fMRI and even longer for diffusion imaging. Here we report on a large reduction in EPI whole brain scan time at 3 and 7 Tesla, without significantly sacrificing spatial resolution, and while gaining functional sensitivity. The multiplexed-EPI (M-EPI) pulse sequence combines two forms of multiplexing: temporal multiplexing (m) utilizing simultaneous echo refocused (SIR) EPI and spatial multiplexing (n) with multibanded RF pulses (MB) to achieve m×n images in an EPI echo train instead of the normal single image. This resulted in an unprecedented reduction in EPI scan time for whole brain fMRI performed at 3 Tesla, permitting TRs of 400 ms and 800 ms compared to a more conventional 2.5 sec TR, and 2-4 times reductions in scan time for HARDI imaging of neuronal fibertracks. The simultaneous SE refocusing of SIR imaging at 7 Tesla advantageously reduced SAR by using fewer RF refocusing pulses and by shifting fat signal out of the image plane so that fat suppression pulses were not required. In preliminary studies of resting state functional networks identified through independent component analysis, the 6-fold higher sampling rate increased the peak functional sensitivity by 60%. The novel M-EPI pulse sequence resulted in a significantly increased temporal resolution for whole brain fMRI, and as such, this new methodology can be used for studying non-stationarity in networks and generally for expanding and enriching the functional information.
Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degenerationin vivo (2005)

Neurofibrillary tangles composed of hyperphosphorylated, aggregated tau are a common pathological feature of tauopathies, including Alzheimer's disease. Abnormal phosphorylation of tau by kinases or phosphatases has been proposed as a pathogenic mechanism in tangle formation. To investigate whether kinase inhibition can reduce tauopathy and the degeneration associated with it in vivo, transgenic mice overexpressing mutant human tau were treated with the glycogen synthase kinase-3 (GSK-3) inhibitor lithium chloride. Treatment resulted in significant inhibition of GSK-3 activity. Lithium administration also resulted in significantly lower levels of phosphorylation at several epitopes of tau known to be hyperphosphorylated in Alzheimer's disease and significantly reduced levels of aggregated, insoluble tau. Administration of a second GSK-3 inhibitor also correlated with reduced insoluble tau levels, supporting the idea that lithium exerts its effect through GSK-3 inhibition. Levels of aggregated tau correlated strongly with degree of axonal degeneration, and lithium-chloride-treated mice showed less degeneration if administration was started during early stages of tangle development. These results support the idea that kinases are involved in tauopathy progression and that kinase inhibitors may be effective therapeutically.
Characterization of Neuronal Intermediate Filament Protein Expression in Cervical Spinal Motor Neurons in Sporadic Amyotrophic Lateral Sclerosis (ALS) (2000)

Because transgenic mice expressing an altered stoichiometry of neurofilament proteins develop a motor neuron degeneration associated with neurofilamentous aggregate formation similar to that found in amyotrophic lateral sclerosis (ALS), we studied the expression of intermediate filament proteins in sporadic ALS. Archival cervical spinal cord paraffin-embedded sections from 11 disease and 11 control cases were studied by either in situ hybridization using 35S-labeled riboprobes or immunohistochemically using specific antibodies for the individual neurofilament subunit proteins, alpha-internexin, nestin, peripherin, vimentin, beta-actin, or Talpha1-tubulin. Median NFL, alpha-internexin, and peripherin steady-state mRNA levels were significantly reduced in the lateral motor neuron cell column (p < 0.05) of ALS cases, while neither NFM nor NFH mRNA levels were altered. ALS cases demonstrated an elevation of beta-actin mRNA levels (p < 0.01) with no increase in Talpha1-tubulin mRNA levels. No motor neuronal expression of nestin or vimentin was observed. Ubiquitin-immunoreactive perikaryal aggregates were immunoreactive for NFH or beta-actin, but not for peripherin, alpha-internexin, vimentin, or nestin. In contrast, neuroaxonal spheroids were strongly immunoreactive for NFH and peripherin, but not for beta-actin, alpha-internexin, vimentin, or nestin. These findings suggest that the stoichiometry of cytoskeletal protein expression in ALS spinal motor neurons is significantly altered in a pattern conducive to the formation of neurofilamentous aggregates.
Process Modeling of CO2 Injection into Natural Gas Reservoirs for Carbon Sequestration and Enhanced Gas Recovery (2001)

Injection of CO2 into depleted natural gas reservoirs offers the potential to sequester carbon while simultaneously enhancing CH4 recovery. Enhanced CH4 recovery can partially offset the costs of CO2 injection. With the goal of analyzing the feasibility of carbon sequestration with enhanced gas recovery (CSEGR), we are investigating the physical processes associated with injecting CO2 into natural gas reservoirs. The properties of natural gas reservoirs and CO2 and CH4 appear to favor CSEGR. To simulate the processes of CSEGR, a module for the TOUGH2 reservoir simulator that includes water, brine, CO2, tracer, and CH4 in nonisothermal conditions has been developed. Simulations based on the Rio Vista Gas Field in the Central Valley of California are used to test the feasibility of CSEGR using CO2 separated from flue gas generated by the 680 MW Antioch gas-fired power plant. Model results show that CO2 injection allows additional CH4 to be produced during and after CO2 injection.
Noninvasive Remote-Controlled Release of Drug Molecules in Vitro Using Magnetic Actuation of Mechanized Nanoparticles (2010)

Mesoporous silica nanoparticles are useful nanomaterials that have demonstrated the ability to contain and release cargos with mediation by gatekeepers. Magnetic nanocrystals have the ability to exhibit hyperthermic effects when placed in an oscillating magnetic field. In a system combining these two materials and a thermally sensitive gatekeeper, a unique drug delivery system can be produced. A novel material that incorporates zinc-doped iron oxide nanocrystals within a mesoporous silica framework that has been surface-modified with pseudorotaxanes is described. Upon application of an AC magnetic field, the nanocrystals generate local internal heating, causing the molecular machines to disassemble and allowing the cargos (drugs) to be released. When breast cancer cells (MDA-MB-231) were treated with doxorubicin-loaded particles and exposed to an AC field, cell death occurred. This material promises to be a noninvasive, externally controlled drug delivery system with cancer-killing properties.
Limiting Amino Acid for Protein Synthesis with Mammary Cells in Tissue Culture (1976)

To identify the limiting amino acid in the minimal essential medium as published by Eagle (Science 130:432, 1959) for milk protein synthesis in rat mammary cells in tissue culture, two different experimental approaches were used. The first study involved the reduction of amino acids singly from the total amino acid complement of the medium for milk protein synthesis. The second study was to investigate the effect on milk protein synthesis of single amino acid addition to the basic complement of amino acids. Order of limiting amino acids was lysine (first) and possible methionine, valine, or arginine (second).
Development of a novel electrophoretic system for the isolation of human spermatozoa (2005)

Electrophoretic separation represents a highly effective, novel approach for the isolation of spermatozoa for assisted conception purposes.
Neurohumoral Features of Myocardial Stunning Due to Sudden Emotional Stress (2005)

Emotional stress can precipitate severe, reversible left ventricular dysfunction in patients without coronary disease. Exaggerated sympathetic stimulation is probably central to the cause of this syndrome.
The potential application of iron chelators for the treatment of neurodegenerative diseases (2011)

Many forms of neurodegenerative disease, for instance Alzheimer's disease, Parkinson's disease, Friedreich's ataxia, Hallervorden Spatz syndrome and macular degeneration, are associated with elevated levels of redox active metals in the brain and eye. A logical therapeutic approach therefore, is to remove the toxic levels of these metals, copper and iron in particular, by selective chelation. The increased number of iron-selective chelators now available for clinical use has enhanced interest in this type of therapy. This review summarises the recent developments in the design of chelators for treatment of neurodegenerative disease, identifies some of the essential properties for such molecules and suggests some future strategies.
Fully Homomorphic Encryption without Squashing Using Depth-3 Arithmetic Circuits (2011)

We describe a new approach for constructing fully homomorphic encryption (FHE) schemes. Previous FHE schemes all use the same blueprint from [Gentry 2009]: First construct a somewhat homomorphic encryption (SWHE) scheme, next "squash" the decryption circuit until it is simple enough to be handled within the homomorphic capacity of the SWHE scheme, and finally "bootstrap" to get a FHE scheme. In all existing schemes, the squashing technique induces an additional assumption: that the sparse subset sum problem (SSSP) is hard. Our new approach constructs FHE as a hybrid of a SWHE and a multiplicatively homomorphic encryption (MHE) scheme, such as Elgamal. Our construction eliminates the need for the squashing step, and thereby also removes the need to assume the SSSP is hard. We describe a few concrete instantiations of the new method, including a "simple" FHE scheme where we replace SSSP with Decision Diffle-Hellman, an optimization of the simple scheme that let us "compress" the FHE ciphertext into a single Elgamal ciphertext(J), and a scheme whose security can be (quantumly) reduced to the approximate ideal-SIVP. We stress that the new approach still relies on bootstrapping, but it shows how to bootstrap without having to "squash" the decryption circuit. The main technique is to express the decryption function of SWHE schemes as a depth-3 Q2 (Σ Π Σ) arithmetic circuit of a particular form. When evaluating this circuit homomorphically (as needed for bootstrapping), we temporarily switch to a MHE scheme, such as Elgamal, to handle the Π part. Due to the special form of the circuit, the switch to the MHE scheme can be done without having to evaluate anything homomorphically. We then translate the result back to the SWHE scheme by homomorphically evaluating the decryption function of the MHE scheme. Using our method, the SWHE scheme only needs to be capable of evaluating the MHE scheme's decryption function, not its own decryption function. We thereby avoid the circularity that necessitated squashing in the original blueprint.
A 0.2 V, 480 kb Subthreshold SRAM With 1 k Cells Per Bitline for Ultra-Low-Voltage Computing (2008)

A 2 muW, 100 kHz, 480 kb subthreshold SRAM operating at 0.2 V is demonstrated in a 130 nm CMOS process. A 10-T SRAM cell allows 1 k cells per bitline by eliminating the data-dependent bitline leakage. A virtual ground replica scheme is proposed for logic "0" level tracking and optimal sensing margin in read buffers. Utilizing the strong reverse short channel effect in the subthreshold region improves cell writability and row decoder performance due to the increased current drivability at a longer channel length. The sizing method leads to an equivalent write wordline voltage boost of 70 mV and a delay improvement of 28% in the row decoder compared to the conventional sizing scheme at 0.2 V. A bitline writeback scheme was used to eliminate the pseudo-write problem in unselected columns.
Echo-Doppler measurements of portal vein and hepatic artery in asymptomatic patients with hepatitis B virus and healthy adults. (2006)

Echo-Doppler measurements of portal vein and hepatic artery can detect significant hemodynamic changes in asymptomatic HBV carriers.
The computer expression recognition toolbox (CERT) (2011)

We present the Computer Expression Recognition Toolbox (CERT), a software tool for fully automatic real-time facial expression recognition, and officially release it for free academic use. CERT can automatically code the intensity of 19 different facial actions from the Facial Action Unit Coding System (FACS) and 6 different prototypical facial expressions. It also estimates the locations of 10 facial features as well as the 3-D orientation (yaw, pitch, roll) of the head. On a database of posed facial expressions, Extended Cohn-Kanade (CK+[1]), CERT achieves an average recognition performance (probability of correctness on a two-alternative forced choice (2AFC) task between one positive and one negative example) of 90.1% when analyzing facial actions. On a spontaneous facial expression dataset, CERT achieves an accuracy of nearly 80%. In a standard dual core laptop, CERT can process 320 × 240 video images in real time at approximately 10 frames per second.
Identification of a second human nm23 gene, nm23-H2. (1991)

Reduced RNA and/or protein levels corresponding to the murine nm23-1 and human nm23-H1 complementary DNA clones have been correlated with high tumor metastatic potential in several rodent model systems and human breast carcinomas. We report the identification of a second human nm23 gene, designated nm23-H2. The pNM23-H2S complementary DNA clone predicted a Mr 17,000 protein 88% identical to nm23-H1. nm23-H2 also shared a significant homology with nucleoside diphosphate kinases and a Drosophila developmental gene. Southern blots containing BglII-restricted genomic DNA, which exhibited an allelic restriction fragment length polymorphism for nm23-H1, contained nonallelic bands upon rehybridization to the nm23-H2 probe. Thus, nm23-H1 and nm23-H2 are distinct genes. Northern blot hybridization of nm23-H1- and nm23-H2-specific probes to breast tumors and cell lines indicated that nm23-H1 expression was reduced in high metastatic potential tumor cells to a greater extent than nm23-H2. The data indicate the existence of a family of independently regulated nm23 genes.
Trust Management in Distributed Systems (2007)

Distributed systems such as the Internet, peer-to-peer networks, and mobile ad hoc networks involve numerous entities, many of which haven't previously interacted. Trust management can help minimize risk and ensure the network activity of benign entities in distributed systems. This article presents different trust models. It also discusses trust management in P2P system
Insights into the mRNA Cleavage Mechanism by MazF, an mRNA Interferase (2004)

MazF is an Escherichia coli toxin that is highly conserved among the prokaryotes and plays an important role in growth regulation. When MazF is induced, protein synthesis is effectively inhibited. However, the mechanism of MazF action has been controversial. Here we unequivocally demonstrate that MazF is an endoribonuclease that specifically cleaves mRNAs at ACA sequences. We then demonstrate its enzymatic specificity using short RNA substrates. MazF cleaves RNA at the 5'-end of ACA sequences, yielding a 2',3'-cyclic phosphate at one side and a free 5'-OH group at the other. Using DNA-RNA chimeric substrates containing XACA, the 2'-OH group of residue X was found absolutely essential for MazF cleavage, whereas all the other residues may be deoxyriboses. Therefore, MazF exhibits exquisite site specificity and has utility as an RNA-restriction enzyme for RNA structural studies or as an mRNA interferase to regulate cell growth in prokaryotic and eukaryotic cells.
Identification of a CXCR4 antagonist, a T140 analog, as an anti‐rheumatoid arthritis agent (2004)

Several recent papers support the involvement of an interaction between stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor, chemokine receptor CXCR4, in memory T cell migration in the inflamed rheumatoid arthritis (RA) synovium. Analogs of the 14-mer peptide T140 were previously found to be specific CXCR4 antagonists that were characterized as not only HIV-entry inhibitors but also anti-cancer-metastatic agents. In this study, a T140 analog, 4F-benzoyl-TN14003, was proven to inhibit CXCL12-mediated migration of human Jurkat cells and mouse splenocyte in a dose-dependent manner in vitro (IC(50)=0.65 and 0.54 nM, respectively). Furthermore, slow release administration by subcutaneous injection (s.c.) of 4F-benzoyl-TN14003 using an Alzet osmotic pump significantly suppressed the delayed-type hypersensitivity response induced by sheep red blood cells in mice, and significantly ameliorated clinical severity in collagen-induced arthritis in mice. As such, T140 analogs might be attractive lead compounds for chemotherapy of RA.
Properties and functions of glutathione reductase in plants (1989)

The assay and in vitro characterization of glutathione reductase (EC 1.6.4.2) is discussed. In vivo the H 2 O 2 ‐scavenging system in chloroplasts is the best documented role of reduced glutathione and glutathione reductase in plants. Similarly, redaction of H 2 O 2 , outside of the chloroplasts, requires glutathione and glutathione reductase; but the pathway, in terms of intermediates, is controversial. The notion that biological stress frequently causes cellular oxidation has lead to the suggestion that glutathione and glutathione reductase may play a role in stress resistance or tolerance mechanisms. The changes in glutathione reductase levels in response to low temperature, oxidative stress and drought are discussed.
Tau aggregation and its interplay with amyloid-β (2014)

Neurofibrillary tangles and amyloid plaques constitute the hallmark brain lesions of Alzheimer's disease (AD) patients. Tangles are composed of fibrillar aggregates of the microtubule-associated protein tau, and plaques comprise fibrillar forms of a proteolytic cleavage product, amyloid-β (Aβ). Although plaques and tangles are the end-stage lesions in AD, small oligomers of Aβ and tau are now receiving increased attention as they are shown to correlate best with neurotoxicity. One key question of debate, however, is which of these pathologies appears first and hence is upstream in the pathocascade. Studies suggest that there is an intense crosstalk between the two molecules and, based on work in animal models, there is increasing evidence that Aβ, at least in part, exerts its toxicity via tau, with the Src kinase Fyn playing a crucial role in this process. In other experimental paradigms, Aβ and tau have been found to exert both separate and synergistic modes of toxicity. The challenge, however, is to integrate these different scenarios into a coherent picture. Furthermore, the ability of therapeutic interventions targeting just one of these molecules, to successfully neutralize the toxicity of the other, needs to be ascertained to improve current therapeutic strategies, such as immunotherapy, for the treatment of AD. Although this article is not intended to provide a comprehensive review of the currently pursued therapeutic strategies, we will discuss what has been achieved by immunotherapy and, in particular, how the inherent limitations of this approach can possibly be overcome by novel strategies that involve single-chain antibodies.