gebhart/patrepeval huggingface dataset:
Uranium Stabilization of C 28 : A Tetravalent Fullerene (1992)

Laser vaporization experiments with graphite in a supersonic cluster beam apparatus indicate that the smallest fullerene to form in substantial abundance is C(28). Although ab initio quantum chemical calculations predict that this cluster will favor a tetrahedral cage structure, it is electronically open shell. Further calculations reveal that C(28) in this structure should behave as a sort of hollow superatom with an effective valence of 4. This tetravalence should be exhibited toward chemical bonding both on the outside and on the inside of the cage. Thus, stable closed-shell derivatives of C(28) with large highest occupied molecular orbital-lowest unoccupied molecular orbital gaps should be attainable either by reacting at the four tetrahedral vertices on the outside of the C(28) cage to make, for example, C(28)H(4), or by trapping a tetravalent atom inside the cage to make endothedral fullerenes such as Ti@C(28). An example of this second, inside route to C(28) stabilization is reported here: the laser and carbon-arc production of U@C(28).
Evolutionary conservation in multiple faces of protein interaction (2009)

Protein interfaces are believed to be evolutionarily more conserved than the rest of the protein surface, but this has not been properly verified using a large protein structural set. Furthermore, recent systematic protein interaction analyses have proved that proteins interacting with many partners have multiple interfaces to connect protein interaction networks, which have never taken into account for conservation analysis of protein interface. Here, we studied the evolutionary conservation of protein interfaces using a large-scale dataset of 2646 protein interfaces with the classification of homodimeric/heterodimeric and obligatory/transient interactions, considering all their known multiple interfaces. We found that protein interfaces were indeed more conserved than noninterface surfaces, and the conservation level of protein interfaces increased when multiple interfaces were properly considered. These findings suggest that conservation analysis should be a good descriptor for protein interface identification and protein-protein interaction predictions. We applied this evolutionary feature to filter docking decoys and found that protein interface conservation worked remarkably well in selecting the near-native structures from the large number of generated docking complexes. Moreover, we discovered that a strong correlation exist between protein interface size and protein interface conservation, which could be a useful filter for the prediction of protein-protein interactions.
Prostaglandin E2 Activates HPK1 Kinase Activity via a PKA-dependent Pathway (2007)

Hematopoietic progenitor kinase 1 (HPK1) is a hematopoietic cell-restricted member of the Ste20 serine/threonine kinase super family. We recently reported that the immunosuppressive eicosanoid, prostaglandin E(2) (PGE(2)), is capable of activating HPK1 in T cells. In this report, we demonstrate that unlike the TCR-induced activation of HPK1 kinase activity, the induction of HPK1 catalytic activity by PGE(2) does not require the presence of phosphotyrosine-based signaling molecules such as Lck, ZAP-70, SLP-76, and Lat. Nor does the PGE(2)-induced HPK1 activation require the intermolecular interaction between its proline-rich regions and the SH3 domain-containing adaptor proteins, as required by the signaling from the TCR to HPK1. Instead, our study reveals that PGE(2) signal to HPK1 via a 3' -5 '-cyclic adenosine monophosphate-regulated, PKA-dependent pathway. Consistent with this observation, changing the serine 171 residue that forms the optimal PKA phosphorylation site within the "activation loop" of HPK1 to alanine completely prevents this mutant from responding to PGE(2)-generated stimulation signals. Moreover, the inability of HPK1 to respond to PGE(2) stimulation in PKA-deficient S49 cells further supports the importance of PKA in this signaling pathway. We speculate that this unique signaling pathway enables PGE(2) signals to engage a proven negative regulator of TCR signal transduction pathway and uses it to inhibit T cell activation.
Purification and characterization of factor VII 304-Gln: a variant molecule with reduced activity isolated from a clinically unaffected male (1991)

Factor VII (FVII) is the plasma serine protease zymogen which, on binding to its cellular receptor tissue factor (TF), initiates blood coagulation. A 47-year-old man with no clinical bleeding tendency was found to have undetectable plasma FVII activity when tested in a one- stage assay using rabbit brain TF, but 0.3 U/mL using recombinant human TF and 1.04 U/mL FVII antigen. Variant FVII purified from his plasma showed an identical migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis to wild-type zymogen. By enzyme kinetic analysis the Km of the variant using FX as a substrate was 12-fold higher than that of normal FVII. Also, the variant FVII was unable to compete with wild-type FVII for limited rabbit TF binding sites. A ligand blot procedure was used to directly demonstrate reduced binding of recombinant human TF to the variant FVII compared with normal FVII. Genetic analysis of leukocyte DNA showed a G to A mutation in the propositus' gene at codon 304 that results in the substitution of a glutamine for an arginine residue in the catalytic domain of the protease. We conclude that this region of the FVII molecule is important for its function.
Image-based face recognition under illumination and pose variations (2005)

We present an image-based method for face recognition across different illuminations and poses, where the term image-based means that no explicit prior three-dimensional models are needed. As face recognition under illumination and pose variations involves three factors, namely, identity, illumination, and pose, generalizations in all these three factors are desired. We present a recognition approach that is able to generalize in the identity and illumination dimensions and handle a given set of poses. Specifically, the proposed approach derives an identity signature that is illumination- and pose-invariant, where the identity is tackled by means of subspace encoding, the illumination is characterized with a Lambertian reflectance model, and the given set of poses is treated as a whole. Experimental results using the Pose, Illumination, and Expression (PIE) database demonstrate the effectiveness of the proposed approach.
Oxaliplatin may induce cytokine-release syndrome in colorectal cancer patients. (2003)

Our results clearly show that that idiosyncratic reaction observed in colorectal cancer patients after oxaliplatin infusion may be due to a massive release of cytokines such as TNF-alpha and IL-6. Symptom regression following steroid therapy administration went along with significant decrease of cytokines levels, confirming that TNF-alpha and IL-6 play a role in the pathogenesis of this reaction.
Design of RNAi Hairpins for Mutation-Specific Silencing of Ataxin-7 and Correction of a SCA7 Phenotype (2009)

Spinocerebellar ataxia type 7 is a polyglutamine disorder caused by an expanded CAG repeat mutation that results in neurodegeneration. Since no treatment exists for this chronic disease, novel therapies such post-transcriptional RNA interference-based gene silencing are under investigation, in particular those that might enable constitutive and tissue-specific silencing, such as expressed hairpins. Given that this method of silencing can be abolished by the presence of nucleotide mismatches against the target RNA, we sought to identify expressed RNA hairpins selective for silencing the mutant ataxin-7 transcript using a linked SNP. By targeting both short and full-length tagged ataxin-7 sequences, we show that mutation-specific selectivity can be obtained with single nucleotide mismatches to the wild-type RNA target incorporated 3' to the centre of the active strand of short hairpin RNAs. The activity of the most effective short hairpin RNA incorporating the nucleotide mismatch at position 16 was further studied in a heterozygous ataxin-7 disease model, demonstrating significantly reduced levels of toxic mutant ataxin-7 protein with decreased mutant protein aggregation and retention of normal wild-type protein in a non-aggregated diffuse cellular distribution. Allele-specific mutant ataxin7 silencing was also obtained with the use of primary microRNA mimics, the most highly effective construct also harbouring the single nucleotide mismatch at position 16, corroborating our earlier findings. Our data provide understanding of RNA interference guide strand anatomy optimised for the allele-specific silencing of a polyglutamine mutation linked SNP and give a basis for the use of allele-specific RNA interference as a viable therapeutic approach for spinocerebellar ataxia 7.
Kinetics and mechanism of the oxidation of human deoxyhemoglobin by nitrites. (1981)

The reactions of human hemoglobin with sodium nitrite and ethyl nitrite in deoxygenated media have been examined in kinetic detail. Nitrous acid has been identified from kinetic pH dependence studies as the principal oxidant of hemoglobin in reactions with sodium nitrite. Nitrosylhemoglobin is produced concurrently with methemoglobin as a result of reductive release of nitric oxide from nitrous acid. However, oxidation of hemoglobin by nitric oxide competes with association, and this process is proposed to arise from the action of the nitric oxide dimer on hemoglobin. Ethyl nitrite, which serves as a model for nitrous acid, reacts with hemoglobin at rates that are at least 10 times slower than those extrapolated for nitrous acid, and hydrolysis of the alkyl nitrite is not competitive with oxidation of hemoglobin. The composite experimental results are interpreted to describe alkyl nitrite, and, presumably, nitrous acid association with hemoglobin followed by rate-limiting electron transfer resulting in nitric oxide and alkoxide (or hydroxide) production. Proton transfer resulting in alcohol (or water) formation occurs subsequent to the rate-limiting step as do reactions of hemoglobin with nitric oxide.
Wavelet-vaguelette decompositions and homogeneous equations (1997)

.................................................................viii CHAPTER 1 INTRODUCTION ..............................................1 CHAPTER 2 PRELIMINARIES ..............................................5 2.1 Definitions and Notations ..............................................5 2.2 Theorems and Inequalities..............................................6 CHAPTER 3 WAVELETS AND BESOV SPACES ............................9 3.1 Biorthogonal Wavelets .................................................9 3.2 Besov Spaces .........................................................15 CHAPTER 4 EMBEDDING, INTERPOLATION, AND DUALITY BETWEEN BESOV SPACES .............................................................18 4.1 Embedding ...........................................................18 4.2 Interpolation..........................................................21 4.3 Duality ...............................................................23 CHAPTER 5 LINEAR HOMOGENEOUS EQUATION...
Association of ABCA1 with Syntaxin 13 and Flotillin-1 and Enhanced Phagocytosis in Tangier Cells (2004)

The ATP-binding cassette transporter A1 (ABCA1) facilitates the cellular release of cholesterol and choline-phospholipids to apolipoprotein A-I (apoA-I) and several studies indicate that vesicular transport is associated with ABCA1 function. Syntaxins play a major role in vesicular fusion and have also been demonstrated to interact with members of the ABC-transporter family. Therefore, we focused on the identification of syntaxins that directly interact with ABCA1. The expression of syntaxins and ABCA1 in cultured human monocytes during M-CSF differentiation and cholesterol loading was investigated and syntaxins 3, 6, and 13 were found induced in foam cells together with ABCA1. Immunoprecipitation experiments revealed a direct association of syntaxin 13 and full-length ABCA1, whereas syntaxin 3 and 6 failed to interact with ABCA1. The colocalization of ABCA1 and syntaxin 13 was also shown by immunofluorescence microscopy. Silencing of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein levels and hence to a significant decrease in apoA-I-dependent choline-phospholipid efflux. ABCA1 is localized in Lubrol WX-insoluble raft microdomains in macrophages and syntaxin 13 and flotillin-1 were also detected in these detergent resistant microdomains along with ABCA1. Syntaxin 13, flotillin-1, and ABCA1 were identified as phagosomal proteins, indicating the involvement of the phagosomal compartment in ABCA1-mediated lipid efflux. In addition, the uptake of latex phagobeads by fibroblasts with mutated ABCA1 was enhanced when compared with control cells and the recombinant expression of functional ABCA1 normalized the phagocytosis rate in Tangier fibroblasts. It is concluded that ABCA1 forms a complex with syntaxin 13 and flotillin-1, residing at the plasma membrane and in phagosomes that are partially located in raft microdomains.
TECHNIQUES OF HIGH-TEMPERATURE X-RAY DIFFRACTION USING METAL RIBBON FURNACES (1963)

The ribbon element x-ray diffractometer furnace is shown to have several advantages over more common resistance element designs. The most outstanding feature of the design is the maximum temperatures, which can be reached in various atmospheres. Physical properties of some of tlie elements used as heater materials are discussed with respect to heater performance. The techniques used in construction of the heaters are described. Problems involved in accurate measurement of temperature are discussed. Several calibration techniques that have been used successfully are described. The accuracy of temperature determinations is demonstrated by comparing measured thermal expansion values with data reported in the literature. The techniques of sample preparation are discussed in detail because of their importance in obtaining good data. Several examples are presented to point out the need of careful sample preparation and show the quality of data that can be obtained. (P.C.H.)
Tracking of time misalignments for OFOM systems in multipath fading channels (2003)

In this paper, new time offset tracking techniques for OFDM are proposed without devoting specific pilot symbols for synchronization. This can be attained since, in coherent OFDM, channel estimation is usually performed employing pilot symbol assisted modulation (PSAM), based on inserting known symbols in the time-frequency grid. We show how this two dimensional embedded signalling can also be used for tracking time-frequency offsets. A two-stage procedure is proposed, focusing this work on the time correction step. The ML estimator has been derived, but though optimal, may not be practical due to its complexity. Hence, a frequency-domain low-complex estimator has been proposed, based on only the samples at pilot positions. Also, the stability of the generated estimate can be improved by averaging over a few number of OFDM symbols. This estimator has been proven to be efficient against time dispersive channels.
Novel Evidence Suggesting Clostridium difficile Is Present in Human Gut Microbiota More Frequently than Previously Suspected (2004)

Prevalence rate of Clostridium difficile in healthy human adults is believed to be very low. Our RT-PCR system using glass powder, which can eliminate PCR inhibitors, detected C. difficile toxin B mRNA in 16 of 30 fecal samples (53.3%) from healthy human adults. In contrast, we failed to detect toxin B in the same fecal samples by PCR using DNA templates extracted with phenol-chloroform. Our results suggest that PCR inhibitors in feces carried through phenol-chloroform extraction procedure might suppress the sensitivity of PCR and that C. difficile is actually present in human gut microbiota more frequently than previously suspected.
Wound healing. (1985)

The majority of wounds encountered in the accident and emergency department are superficial in nature and a consequence of accidental trauma or the elective surgical incision of infected foci. The techniques of management of such cases have undergone few changes in recent years, and any advances of a practical or therapeutic nature have been comparatively modest. On the other hand, many major advances have occurred in our understanding of the factors involved in the basic pathophysiology of wound repair. This paper is a summary of our present concept of the process of repair in soft tissues.
Statins and Blockers of the Renin-Angiotensin System (1999)

In addition to their primary mode of action, statins and blockers of the renin-angiotensin system possess common additional properties that are under active investigation. The inhibition of cellular proliferation, the restoration of endothelial activity, the inhibition of platelet reactivity, and an antioxidant potential are only a few examples of shared effects that target the arterial wall. These and other properties may eventually become exploited for the improved treatment of cardiovascular diseases and of other diseases apparently unrelated to the cardiovascular field, including inflammation and cancer. This review analyzes the current knowledge on the pleiotropic properties of these classes of drugs. Direct comparison indicates that study of the associations among these drugs may eventually disclose additive or synergistic effects that, perhaps even at lower dosages, may provide improved vascular protection and a strong alliance against several atherogenic mechanisms.
Delivery is key: lessons learnt from developing splice‐switching antisense therapies (2017)

The use of splice-switching antisense therapy is highly promising, with a wealth of pre-clinical data and numerous clinical trials ongoing. Nevertheless, its potential to treat a variety of disorders has yet to be realized. The main obstacle impeding the clinical translation of this approach is the relatively poor delivery of antisense oligonucleotides to target tissues after systemic delivery. We are a group of researchers closely involved in the development of these therapies and would like to communicate our discussions concerning the validity of standard methodologies currently used in their pre-clinical development, the gaps in current knowledge and the pertinent challenges facing the field. We therefore make recommendations in order to focus future research efforts and facilitate a wider application of therapeutic antisense oligonucleotides.
Executioner Caspase-3, -6, and -7 Perform Distinct, Non-redundant Roles during the Demolition Phase of Apoptosis (2001)

Apoptosis is orchestrated by a family of cysteine proteases known as the caspases. Fourteen mammalian caspases have been identified, three of which (caspase-3, -6, and -7) are thought to coordinate the execution phase of apoptosis by cleaving multiple structural and repair proteins. However, the relative contributions that the "executioner" caspases make to the demolition of the cell remains speculative. Here we have used cell-free extracts immuno-depleted of either caspase-3, -6, or -7 to examine the caspase requirements for apoptosis-associated proteolysis of 14 caspase substrates as well as nuclear condensation, chromatin margination, and DNA fragmentation. We show that caspase-3 is the primary executioner caspase in this system, necessary for cytochrome c/dATP-inducible cleavage of fodrin, gelsolin, U1 small nuclear ribonucleoprotein, DNA fragmentation factor 45 (DFF45)/inhibitor of caspase-activated DNase (ICAD), receptor-interacting protein (RIP), X-linked inhibitor of apoptosis protein (X-IAP), signal transducer and activator of transcription-1 (STAT1), topoisomerase I, vimentin, Rb, and lamin B but not for cleavage of poly(ADP-ribose) polymerase (PARP) or lamin A. In addition, caspase-3 was also essential for apoptosis-associated chromatin margination, DNA fragmentation, and nuclear collapse in this system. Surprisingly, although caspase-6 and -7 are considered to be important downstream effector caspases, depletion of either caspase had minimal impact on any of the parameters investigated, calling into question their precise role during the execution phase of apoptosis.
Do prodrugs deliver? (2007)

This review examines the prodrug concept in the context of conventional prodrugs, which seek to increase systemic concentrations of a drug, and targeted prodrugs, which are designed to increase therapeutic ratio. In general, conventional prodrugs are designed to enhance oral absorption. With both types of prodrug, a pharmacokinetic/pharmacodynamic model must be created to understand the steps required and the barriers that need to be overcome to achieve success. This review highlights the role of polar surface area in identifying drugs that are suitable for oral absorption, and which have the required potency and retention at the intended site of pharmacology.
Solubilized nuclear "receptors" for thyroid hormones. Physical characteristics and binding properties, evidence for multiple forms. (1976)

Tissues regulated by thyroid hormones contain chromatin-localized "receptors" that may be involved in the actions of these hormones. In this report, we describe some properties of these receptors after their solubilization from rat liver nuclei and their separation from nucleic acids and basic proteins. The nuclear extract and partially purified preparations contain a dominant class of binding sites which have a high affinity for triiodothyronine (3,5,3'-triiodo-L-thyronine, Kd approximately 1 nM) and for the biologically potent isopropyl diiodothyronine (3,5-diiodo-3'-isopropyl-L-thyronine, Kd congruent to 1 nM) and also bind thyroxine (3,5,3',5'-tetraiodo-L-thyronine, Kd approximately 5 nM) and reverse triiodothyronine (3,3',5'-triiodo-L-thyronine, Kd approximately nM). This binding activity elutes on Sephadex G-100 in an included peak which has a Stokes radius of 35 A and sediments on glycerol gradients at 3.5 S. From these data a molecular weight ratio of 50,500 and a frictional ratio of 1.4 were calculated, suggesting that the receptor is somewhat asymmetrical. There was a sharp decline in triiodothyronine binding by this component above pH 8.7 (optimum around pH 7.6) where there is marked dissociation of the 4' phenolic hydroxyl of triiodothyronine (pKalpha approximately 8.5). A similar decrease in thyroxine (pKalpha approximately 6.7) binding with pH increases in this range was not observed. Thus, ionization of the phenolic hydroxyl may influence binding. The solubilized preparations can also contain a minor specific-binding component that can be identified by binding analyses, and by G-100 or quaternary aminoethyl Sephadex chromatography. this component has a much lower affinity for triiodothyronine and isopropyl diiodothyronine than for thyroxine as compared to the major component. It probably has a pH optima around 6.0 and demonstrates and apparent tendency to aggregate. The minor component was not always identified by direct Scatchard analysis and may be generated in part from the major component as it was more commonly observed after storage or purification of the nuclear extract. Thus, at least two thyroid hormone-binding components can be present in extracts of purified rat liver nuclei; the minor component may be an altered form or subunit of the major component. The relative binding activities of triiodothyronine, isopropyl diiodothyronine, and thyroxine by the major component, similar to those in intact nuclei, parallel the biological potencies of these compounds, and suggest that the dominant binding is by biologically relevant receptors. Since ionization of the phenolic hydroxyl may influence binding, the lower activity of thyroxine relative to triiodothyronine may in part be due to the fact that at physiological pH, the phenolic hydroxyl of thyroxine is more dissociated than is that of triiodothyronine. The finding that this receptor is somewhat asymmetrical provides an indication of the shape of an intrinsic chromatin protein implicated in specific gene regulation...