gebhart/patrepeval huggingface dataset:
2-Keto-4-hydroxyglutarate aldolase: purification and characterization of the homogeneous enzyme from bovine kidney. (1992)

2-Keto-4-hydroxyglutarate aldolase, which catalyzes the reversible cleavage of 2-keto-4-hydroxyglutarate, yielding pyruvate plus glyoxylate, has been purified from extracts of bovine kidney to apparent homogeneity as judged by polyacrylamide gel electrophoresis, gel filtration chromatography, sucrose density gradient centrifugation, and meniscus depletion sedimentation equilibrium experiments. The enzyme from this source has a native and a subunit mass of 144 and 36 kDa, respectively; the pH-activity optimum is 8.8. Rather than being stimulated, aldolase activity is inhibited to varying degrees by added divalent metal ions, whereas a number of metal ion-chelating agents have no effect. An absolute requirement for added thiol compounds could not be shown, but 2-mercaptoethanol enhances activity 2-fold, and added Hg2+ as well as p-mercuribenzoate or dithiodipyridine markedly inhibit catalysis. Incubation of the enzyme with either pyruvate or glyoxylate in the presence of NaBH4 causes extensive loss of aldolase activity concomitant with stable binding of approximately 1.0-1.5 mol of 14C-labeled substrate/mol of enzyme. The circular dichroism spectrum for native aldolase is characteristic of an alpha-helix; incubation of the enzyme with glyoxylate has no effect on this spectrum, but it is considerably altered by pyruvate. Bovine kidney aldolase shows no stereospecificity in catalyzing the aldol cleavage of the two optical isomers of 2-keto-4-hydroxyglutarate, and although it also catalyzes the beta-decarboxylation of oxalacetate, its decarboxylase/aldolase activity ratio is lower than that seen with the pure enzyme from either bovine liver or Escherichia coli.
Acoustic Modeling Using Deep Belief Networks (2011)

Gaussian mixture models are currently the dominant technique for modeling the emission distribution of hidden Markov models for speech recognition. We show that better phone recognition on the TIMIT dataset can be achieved by replacing Gaussian mixture models by deep neural networks that contain many layers of features and a very large number of parameters. These networks are first pre-trained as a multi-layer generative model of a window of spectral feature vectors without making use of any discriminative information. Once the generative pre-training has designed the features, we perform discriminative fine-tuning using backpropagation to adjust the features slightly to make them better at predicting a probability distribution over the states of monophone hidden Markov models.
Ex vivo hemostatic and immuno‐inflammatory profiles of freeze‐dried plasma (2021)

TFDP is equivalent to frozen plasma with respect to global hemostatic and immuno-inflammatory mediator profiles. Further investigations of TFDP in trauma-induced coagulopathy models and bleeding patients are warranted.
Min-max fair coordinated beamforming via large systems analysis (2011)

This paper considers base station (BS) cooperation in the form of coordinated beamforming, focusing on min-max fairness in the power usage subject to target SINR constraints. We show that the optimal beamforming strategies have an interesting nested zero-forcing structure. We then consider the asymptotic regime where the number of antennas at each BS and the number of users in each cell both grow large with their ratio tending to a finite constant. The limiting optimal beamformer structure is characterized in terms of the solution of a convex optimization problem. The dimensionality of this optimization problem is constant, as opposed to the problem of solving for the exactly optimal beamformer, and only knowledge of statistics is required to solve it. These asymptotic results provide insights into the average performance, as well as simple but efficient strategies for the finite system case. In particular, the optimal beamforming strategy from the large systems analysis only requires the base stations to have local instantaneous channel state information; the remaining parameters of the beamformer can be calculated using channel statistics which can easily be shared amongst the base stations.
Gold(iii) porphyrins as a new class of anticancer drugs: cytotoxicity, DNA binding and induction of apoptosis in human cervix epitheloid cancer cellsElectronic supplementary information (ESI) available: Further experimental and crystallographic details. See http://www.rsc.org/suppdata/cc/b3/b303294a/ (2003)

A series of gold(III) tetraarylporphyrins are stable in the presence of glutathione and exert much higher potency than cisplatin in killing human cancer cells, including the drug-resistant variants; the gold-induced cytotoxicity occurs through an apoptotic pathway according to laser confocal microscopy and flow cytometric studies.
Stereocontrol in Cyclophane Synthesis:  A Photochemical Method To Overlap Aromatic Rings (2000)

To overlap aromatic rings in cyclophanes, the inter- and intramolecular [2 + 2] photocycloaddition of vinylarenes has been developed. It gives cyclophanes, naphthalenophanes, phenanthrenophanes, thiophenophanes, and carbazolophanes in reasonable to excellent yields. The structures and properties of cyclophanes obtained are reviewed; especially the excimer emission of phenanthrenophanes, naphthalenophanes, and carbazolophanes stressed that many intriguing cyclophanes can be obtained through the fine molecular design of precursors.
Local Web advertisement through dynamic active proxy (2002)

Due to global access of the Web, Internet advertisements are often constrained to generic ones-those without local relevancy from a Web surfer's viewpoint. This seriously limits the potential and market size of Internet advertising. To make up for this, we propose an active proxy centric framework as an effective means to support local Web advertising. The basic idea is to insert a local advertisement dynamically into a Web page when it is retrieved through an active proxy server that is collaborating with the content server. Since a proxy server has a much better understanding of Web surfers than Web content servers, an advertisement uploaded by the proxy will be much more relevant and interesting. This model is very important to Internet advertising. It provides a win-win situation to the three parties involved in Web surfing: (i) a content provider increases his revenue without any extra effort to find and maintain a "remote" advertisement in Web site content, (ii) a proxy service provider (likely to be the Internet service access provider, IASP) has a new source of revenue by selling advertisement on Web pages that pass through them, and (iii) Web surfers are able to receive relevant, local advertisements.
Protein Replacement Therapy and Gene Transfer in Canine Models of Hemophilia A, Hemophilia B, von Willebrand Disease, and Factor VII Deficiency (2009)

Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders.
Use of diode laser energy (808 nm) for selective photothermolysis of contaminated wounds (1995)

The objective of this study was to compare the antibacterial effects of selective laser treatments on contaminated wounds. Comparisons were made using the diode (808 nm) laser with and without an accompanying chromophore, Nd:YAG (1064 nm), and KTP (532 nm) lasers. A known quantity (mean concentration of 7.9 +/- 1.9 CFU/ml X 10<SUP>8</SUP>) of bacterial organisms (Staphylococcus intermedius) was inoculated into skin incisions aseptically made on the backs of experimental rabbits. The bacteria were allowed to adhere/colonize for one hour, and each site was then treated with various laser modalities. Tissue samples were taken at one and forty-eight hours after treatment. The number of viable bacteria was then quantitated (CFU/ml) by a spot-plate counting technique. Initial results illustrated the fact that selective photothermolysis of superficial cellular layers of targeted tissue occurred with an accompanying decrease of bacterial numbers that virtually created a `clean' (organisms numbers less than 10<SUP>5</SUP> per gram of tissue) wound. This effect was especially noticeable using the diode laser (808 nm) and an accompanying chromophore, indocyanine green.
Addition of an Endoplasmic Reticulum Retention/Retrieval Signal Does Not Block Maturation of Enzymatically Active Peptidylglycine α-Amidating Monooxygenase (1995)

Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the COOH-terminal alpha-amidation of neural and endocrine peptides via a two-step reaction carried out in sequence by the monooxygenase and lyase domains contained in this bifunctional protein. Peptide alpha-amidation is thought to take place primarily in the secretory granules in which mature bioactive peptides are stored, and it is not known where in the secretory compartment newly synthesized PAM protein becomes enzymatically active. To address this question, PAM-3, a soluble bifunctional protein, was modified by addition of the KDEL endoplasmic reticulum (ER) retention/retrieval signal to its COOH terminus. PAM-3-KDEL protein stably expressed in hEK-293 cells or in AtT-20 cells was efficiently retained in the ER based on immunocytochemistry, pulse-chase experiments, and maintained endoglycosidase H sensitivity. The effect of the KDEL sequence was specific since PAM-3 with an inactive ER retention/retrieval signal (PAM-3-KDEV) moved through the secretory pathway like wild type PAM-3. In AtT-20 cells, PAM-3-KDEL was not subjected to the COOH-terminal endoproteolytic cleavage that generates a 75-kDa PAM protein from PAM-3 and PAM-3-KDEV. PAM-3-KDEL protein exhibited both monooxygenase and lyase activities with specific activities similar to those of the wild type PAM-3 and PAM-3-KDEV proteins. Thus, although PAM catalyzes a reaction that occurs primarily in the secretory granules, newly synthesized PAM protein becomes enzymatically competent in the ER.
Photovoltaic Measurements in Single-Nanowire Silicon Solar Cells (2008)

Single-nanowire solar cells were created by forming rectifying junctions in electrically contacted vapor-liquid-solid-grown Si nanowires. The nanowires had diameters in the range of 200 nm to 1.5 microm. Dark and light current-voltage measurements were made under simulated Air Mass 1.5 global illumination. Photovoltaic spectral response measurements were also performed. Scanning photocurrent microscopy indicated that the Si nanowire devices had minority carrier diffusion lengths of approximately 2 microm. Assuming bulk-dominated recombination, this value corresponds to a minimum carrier lifetime of approximately 15 ns, or assuming surface-dominated recombination, to a maximum surface recombination velocity of approximately 1350 cm s(-1). The methods described herein comprise a valuable platform for measuring the properties of semiconductor nanowires, and are expected to be instrumental when designing an efficient macroscopic solar cell based on arrays of such nanostructures.
A linear dilution microfluidic device for cytotoxicity assays (2006)

A two-layer polymer microfluidic device is presented which creates nine linear dilutions from two input fluid streams mixed in varying volumetric proportions. The linearity of the nine dilutions is conserved when the flow rate is held constant at 1.0 microl min(-1) (R(2) = 0.9995) and when it is varied from 0.5-16 microl min(-1) (R(2) = 0.9998). An analytical expression is presented for designing microfluidic devices with arbitrary numbers of linear dilutions. To demonstrate the efficacy of this device, primary human epidermal keratinocytes (HEK) were stained with nine dilutions of calcein, resulting in a linear spread of fluorescent intensities (R(2) = 0.94). The operating principles of the device can be scaled up to incorporate any number of linear dilutions. This scalability, coupled with an intrinsic ability to create linear dilutions under a variety of operating conditions, makes the device applicable to high throughput screening applications such as combinatorial chemistry or cytotoxicity assays.
A targeted IL-15 fusion protein with potent anti-tumor activity (2015)

IL-15 has been actively investigated for its potential in tumor immunotherapy. To enhance the anti-tumor activity of IL-15, the novel PFC-1 construct was designed, which comprises the following 3 parts: (1) IL-15Rα fused with IL-15 to enhance IL-15 activity, (2) an Fc fragment to increase protein half-life, and (3) an integrin-targeting RGD peptide to enhance tumor targeting. PFC-1 showed tumor cell targeting without compromising IL-15 activity. PFC-1 also had potent anti-tumor activities in xenograft models, suggesting the potential application of this multi-functional fusion protein in tumor therapy.
Heparan sulfate is essential to amphiregulin-induced mitogenic signaling by the epidermal growth factor receptor. (1994)

Human amphiregulin (AR) is a heparin-binding growth factor which functions by binding to and activating the epidermal growth factor (EGF) receptor tyrosine kinase. AR contains an EGF-like domain (residues 44-84) and a Lys/Arg-rich NH2-terminal extension (residues 1-43). Synthetic peptides corresponding to residues 8-26, 26-44, and 68-84 of AR were tested for their ability to compete for the binding of AR to immobilized heparin. AR8-26 and AR68-84 had no significant effect on the binding of AR to heparin, whereas AR26-44 bound to heparin and blocked the binding of AR to heparin. Both soluble heparin and heparan sulfate inhibited AR-induced mitogenesis in MCF-10A human mammary epithelial cells with an IC50 of 5 and 2 micrograms/ml, respectively, whereas soluble chondroitin sulfate had only a slight inhibitory effect. When MCF-10A cells were grown in the presence of chlorate, an inhibitor of sulfation, or exposed to the glycosaminoglycan-degrading enzymes heparitinase or heparinase, the ability of AR to evoke mitogenesis in these cells was lost. Chlorate, heparitinase, or heparinase treatment inhibited AR-induced autophosphorylation of tyrosine residues in the EGF receptor. None of these treatments had any significant effect on EGF-triggered mitogenic signaling by the EGF receptor. These results indicate that extracellular heparan sulfate glycosaminoglycan is essential to AR-induced mitogenic signaling by the EGF receptor tyrosine kinase.
Function, structure and therapeutic potential of complement C5a receptors (2007)

Complement fragment (C)5a is a 74 residue pro-inflammatory polypeptide produced during activation of the complement cascade of serum proteins in response to foreign surfaces such as microorganisms and tissue damaged by physical or chemical injury. C5a binds to at least two seven-transmembrane domain receptors, C5aR (C5R1, CD88) and C5L2 (gpr77), expressed ubiquitously on a wide variety of cells but particularly on the surface of immune cells like macrophages, neutrophils and T cells. C5aR is a classical G protein-coupled receptor that signals through G alpha i and G alpha 16, whereas C5L2 does not appear to couple to G proteins and has no known signalling activity. Although C5a was first described as an anaphylatoxin and later as a leukocyte chemoattractant, the widespread expression of C5aR suggested more general functionality. Our understanding of the physiology of C5a has improved significantly in recent years through exploitation of receptor knockout and knocking mice, C5 and C5a antibodies, soluble recombinant C5a and C5a analogues and newly developed receptor antagonists. C5a is now also implicated in non-immunological functions associated with developmental biology, CNS development and neurodegeneration, tissue regeneration, and haematopoiesis. Combined receptor mutagenesis, molecular modelling, structure-activity relationship studies and species dependence for ligand potency on C5aR have been helpful for identifying ligand binding sites on the receptor and for defining mechanisms of receptor activation and inactivation. This review will highlight major developments in C5a receptor research that support C5aR as an important therapeutic target. The intriguing possibilities raised by the existence of a non-signalling C5a receptor are also discussed.
The Effect of Three Practice Conditions on the Consistency of Chronic Dysarthric Speech (2004)

This study investigated whether it is possible for people with chronic dysarthria to adjust their articulation in three practice conditions. A speaker dependent, speech recognition system was used to compare participants' practice attempts with a model of a word made from previous recordings to give a recognition score. This score was used to indicate changes in production of practice words with different conditions. The three conditions were reading of written target words, visual feedback, and an auditory model followed by visual feedback. For eight participants with dysarthria, the ability to alter speech production was shown, together with a differential effect of the three conditions. Copying an auditory target gave significantly better recognition scores than just repeating the word. Visual feedback was no more effective than repetition alone. For four control participants, visual feedback did produce significantly better recognition scores than just repetition of written words, and the presence of an auditory model was Significantly more effective than visual feedback. Possible reasons for differences between conditions are discussed.
Tiermodelle in der Retinitis-pigmentosa-Forschung (1997)

Retinitis pigmentosa (RP) is the general term given to a group of genetically determined, degenerative retinal diseases which afflict some 1.5 million humans worldwide. Molecular genetic studies in recent years have shown that RP cannot be explained by a single genetic defect but rather that the hereditary aberration responsible for triggering the onset of the disease is localized in different genes and at different sites within these genes. A fuller understanding of these processes is possible only if the pathogenesis of the diseases can be followed as they develop. Animal models are an indispensable requirement for this. Only in the animal model is it possible to observe progressive degenerations in "time-lapse photography" as it were and to examine the biochemical, functional and morphological changes which appear at specific times in the retina. This article gives an overview of the animal models presently used in RP research, with a short description of genetic backgrounds and the progression of the disease in individual animals. In addition, a look at the future is provided of new molecular techniques which make it possible to create specific animal models with gene mutations identical to those appearing in human RP. Since hereditary human retinal degenerations can be brought about by numerous different genetic defects, comparative studies using animals with clearly defined genetic defects are essential. Only in this way is it possible to arrive at conclusions concerning this specialized syndrome and to clarify the mechanisms which are common to all retinal degenerations.
Large scale purification of the nuclear thyroid hormone receptor from rat liver and sequence-specific binding of the receptor to DNA. (1988)

Methodology is reported for extracting thyroid hormone receptors from rat liver nuclei and for purifying these such that certain receptor properties can be examined. The extraction technique resulted in 1700 pmol of receptor/2 kg of liver and bypasses centrifugation in dense sucrose. The receptor was then purified by sequential heparin-Sepharose, DEAE-Sepharose, and phospho-Ultrogel chromatography and size exclusion and hydrophobic interaction high performance liquid chromatography. These steps yielded 23-35 micrograms of receptor at 0.7-1.5% purity from two 2-kg liver preparations. The cross-linkers disuccinimidyl suberate and N-succinimidyl-6-(4-azido-2-nitrophenylamino)hexanoate were employed to covalently attach 125I-labeled 3,5,3'-triiodo-L-thyronine (T3) to the purified receptor. Autoradiography after denaturing polyacrylamide gel electrophoresis revealed major 49,000 Mr and minor 58,000 Mr specific T3-binding proteins. The purified receptors exhibited high affinity (Kd = 100 pM) single site T3-binding activity. Because of the high affinity and specificity of [125I]T3 for the receptor, it was possible to uniquely identify the receptor containing DNA-protein complexes in a gel retardation assay and thus directly demonstrate for the first time that the receptor can specifically recognize sequences in the 5'-flanking DNA of the rat growth hormone gene. [125I]T3-labeled receptor migrated at the same position as the major gel-retarded 32P-labeled DNA band. Specific DNA competed for the binding much more strongly than nonspecific DNA. Thus, the purification procedure results in relatively large quantities of receptor at a purity sufficient for detecting and studying a number of its properties including specific DNA binding activity.
Host range ofCanine minute virusin cell culture (2012)

Canine minute virus (CnMV) is a member of the Bocavirus genus, together with Bovine parvovirus (BPV), which emerged as a new pathogen of dogs in 1967. The genus Bocavirus gained more recognition after the recent identification of Human bocavirus in pooled specimens from the respiratory tract of children. The cell culture host range of CnMV appears to be restricted to the Walter Reed canine cell (WRCC) line, although there is a report that indicates susceptibility of the Madin-Darby canine kidney (MDCK) cell line. In order to study the susceptibility of different cell lines to CnMV, the replication in cell cultures of canine, bovine, and human origin and the interaction of the virus with freshly isolated canine peripheral blood mononuclear cells were evaluated. The in vitro host range was unexpectedly wide. As shown by indirect fluorescent antibody and polymerase chain reaction assays, CnMV replicates efficiently in the A72 and MDCK canine cell lines. Bovine and human cell lines support the replication of CnMV less efficiently. In contrast, canine mononuclear blood cells are permissive to replication of CnMV in vitro. The present study revealed the ability of CnMV to replicate in continuous cell lines of different origin and, partially, in canine mononuclear cells.