gebhart/patrepeval huggingface dataset:
Accelerating Amyloid-β Fibrillization Reduces Oligomer Levels and Functional Deficits in Alzheimer Disease Mouse Models (2007)

Many proteins suspected of causing neurodegenerative diseases exist in diverse assembly states. For most, it is unclear whether shifts from one state to another would be helpful or harmful. We used mutagenesis to change the assembly state of Alzheimer disease (AD)-associated amyloid-beta (Abeta) peptides. In vitro, the "Arctic" mutation (AbetaE22G) accelerated Abeta fibrillization but decreased the abundance of nonfibrillar Abeta assemblies, compared with wild-type Abeta. In human amyloid precursor protein (hAPP) transgenic mice carrying mutations adjacent to Abeta that increase Abeta production, addition of the Arctic mutation markedly enhanced the formation of neuritic amyloid plaques but reduced the relative abundance of a specific nonfibrillar Abeta assembly (Abeta*56). Mice overexpressing Arctic mutant or wild-type Abeta had similar behavioral and neuronal deficits when they were matched for Abeta*56 levels but had vastly different plaque loads. Thus, Abeta*56 is a likelier determinant of functional deficits in hAPP mice than fibrillar Abeta deposits. Therapeutic interventions that reduce Abeta fibrils at the cost of augmenting nonfibrillar Abeta assemblies could be harmful.
Prognostic value of symptom burden for overall survival in patients receiving chemotherapy for advanced nonsmall cell lung cancer (2009)

An increased risk for shorter survival was indicated by moderate to severe coughing at baseline or by increased fatigue or shortness of breath during the first chemotherapy cycle in patients with advanced NSCLC. Although cross-validation is needed, these data suggest that an individual patient's symptom severity scores, quickly obtainable in the clinic, might contribute clinically useful information for treatment planning for that patient. Society.
InterPro, progress and status in 2005 (2004)

InterPro, an integrated documentation resource of protein families, domains and functional sites, was created to integrate the major protein signature databases. Currently, it includes PROSITE, Pfam, PRINTS, ProDom, SMART, TIGRFAMs, PIRSF and SUPERFAMILY. Signatures are manually integrated into InterPro entries that are curated to provide biological and functional information. Annotation is provided in an abstract, Gene Ontology mapping and links to specialized databases. New features of InterPro include extended protein match views, taxonomic range information and protein 3D structure data. One of the new match views is the InterPro Domain Architecture view, which shows the domain composition of protein matches. Two new entry types were introduced to better describe InterPro entries: these are active site and binding site. PIRSF and the structure-based SUPERFAMILY are the latest member databases to join InterPro, and CATH and PANTHER are soon to be integrated. InterPro release 8.0 contains 11 007 entries, representing 2573 domains, 8166 families, 201 repeats, 26 active sites, 21 binding sites and 20 post-translational modification sites. InterPro covers over 78% of all proteins in the Swiss-Prot and TrEMBL components of UniProt. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro).
New Lenses on Learning (1996)

Patricia Cross offers an important prescription for today's campuses: get everyone focused on student learning again.
Polymorphonuclear leukocytes mediate Staphylococcus aureus Panton-Valentine leukocidin-induced lung inflammation and injury (2010)

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is epidemic in the United States, even rivaling HIV/AIDS in its public health impact. The pandemic clone USA300, like other CA-MRSA strains, expresses Panton-Valentine leukocidin (PVL), a pore-forming toxin that targets polymorphonuclear leukocytes (PMNs). PVL is thought to play a key role in the pathogenesis of necrotizing pneumonia, but data from rodent infection models are inconclusive. Rodent PMNs are less susceptible than human PMNs to PVL-induced cytolysis, whereas rabbit PMNs, like those of humans, are highly susceptible to PVL-induced cytolysis. This difference in target cell susceptibility could affect results of experimental models. Therefore, we developed a rabbit model of necrotizing pneumonia to compare the virulence of a USA300 wild-type strain with that of isogenic PVL-deletion mutant and -complemented strains. PVL enhanced the capacity of USA300 to cause severe lung necrosis, pulmonary edema, alveolar hemorrhage, hemoptysis, and death, hallmark clinical features of fatal human necrotizing pneumonia. Purified PVL instilled directly into the lung caused lung inflammation and injury by recruiting and lysing PMNs, which damage the lung by releasing cytotoxic granule contents. These findings provide insights into the mechanism of PVL-induced lung injury and inflammation and demonstrate the utility of the rabbit for studying PVL-mediated pathogenesis.
Transposon Tagging of the Sulfur Gene of Tobacco Using Engineered Maize Ac/Ds Elements (1999)

The Sulfur gene of tobacco is nuclearly encoded. A Su allele at this locus acts as a dominant semilethal mutation and causes reduced accumulation of chlorophyll, resulting in a yellow color in the plant. An engineered transposon tagging system, based upon the maize element Ac/Ds, was used to mutate the gene. High frequency of transposon excision from the Su locus produced variegated sectors. Plants regenerated from the variegated sector exhibited a similar variegated phenotype. Genetic analyses showed that the variegation was always associated with the transposase construct and the transposon was linked to the Su locus. Sequences surrounding the transposon were isolated, and five revertant sectors possessed typical direct repeats following Ds excisions. These genetic and molecular data are consistent with the tagging of the Su allele by the transposon.
Matched Molecular Pairs as a Guide in the Optimization of Pharmaceutical Properties; a Study of Aqueous Solubility, Plasma Protein Binding and Oral Exposure (2006)

By identifying every pair of molecules that differ only by a particular, well-defined, structural transformation in a database of measured properties and computing the corresponding change in property, we obtain an overview of the effect that structural change has upon the property and set an expectation for what will happen when that transformation is applied elsewhere. The mean change indicates the expected magnitude of the change in the property and the number of cases in which the property increases give the probability that the structural transformation will cause the property to increase. Outliers indicate potential ways of avoiding the general trend. Comparing to changes in lipophilicity highlights structural transformations that have unusual effects, some of which can be explained by conformational changes. In this paper, we focus upon the effects on aqueous solubility, plasma protein binding and oral exposure of adding substituents to aromatic rings and methylating heteroatoms.
Methylthioadenosine phosphorylase cDNA transfection alters sensitivity to depletion of purine and methionine in A549 lung cancer cells. (1996)

Methylthioadenosine phosphorylase (MTAP), an enzyme involved in purine and methionine metabolism, is present in all normal tissues but is frequently deficient in a variety of cancers. It has been suggested that this metabolic difference between normal and cancer cells may be exploited to selectively treat MTAP-negative cancers by inhibiting de novo purine synthesis and by depleting L-methionine. However, these therapeutic strategies have only been tested in naturally occurring MTAP-positive and -negative cell lines, which might have additional genetic alterations that affect chemotherapeutic sensitivity. Therefore, it is of importance to examine the feasibility of enzyme-selective treatment using paired cell lines that have an identical genotype except for MTAP status. MTAP-negative A549 lung cancer cells were transfected with eukaryotic expression vectors encoding MTAP cDNA in sense and antisense orientations. The resultant stable transfectomas were treated with inhibitors of de novo purine synthesis such as methotrexate, 5,10-dideazatetrahydrofolate, and L-alanosine and by methionine depletion. The A549 cells transfected with an antisense construct (antisense transfectoma) expressed no MTAP protein and were more sensitive to both purine and methionine depletion than were cells expressing MTAP protein (sense transfectoma). Methylthioadenosine was able to completely rescue the sense transfectoma but not the antisense transfectoma from growth inhibition by depletion of purine and methionine. These results prove that MTAP deficiency contributes directly to the sensitivity of cancer cells to purine or methionine depletion. Inhibition of de novo purine synthesis, combined with methionine depletion in the presence of methylthioadenosine, is a highly selective treatment for MTAP-negative cancers.
Wireless LANs and mobile networking: standards and future directions (1996)

The emerging widespread use of wireless LAN systems together with the users' desire for such systems to interoperate has created a requirement for standards. Many standards bodies are currently defining standards for wireless systems that relate to different layers of the networking protocol stack. Of these, two influential physical and data link layer standards, IEEE 802.11 and the European HIPERLAN, are described. The article then considers the network layer by discussing extensions that are being made to the widely used Internet protocol (IP) to deal with mobility (wired or wireless). The final standards that are discussed relate to wireless link management. The article concludes by speculating on future directions for wireless LAN systems.
Fully Synthetic Carbohydrate-Based Vaccines in Biochemically Relapsed Prostate Cancer: Clinical Trial Results With α-N-Acetylgalactosamine-O-Serine/Threonine Conjugate Vaccine (2003)

A safe synthetic conjugate vaccine in a trimer formation was developed that can break immunologic tolerance by inducing specific humoral responses. It seemed to affect the biochemical progression of the disease as determined by a change in PSA log slope.
Tracking of Quantum Dot-labeled CFTR Shows Near Immobilization by C-Terminal PDZ Interactions (2006)

Mutations in cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel, cause cystic fibrosis. To investigate interactions of CFTR in living cells, we measured the diffusion of quantum dot-labeled CFTR molecules by single particle tracking. In multiple cell lines, including airway epithelia, CFTR diffused little in the plasma membrane, generally not moving beyond 100-200 nm. However, CFTR became mobile over micrometer distances after 1) truncations of the carboxy terminus, which contains a C-terminal PDZ (PSD95/Dlg/ZO-1) binding motif; 2) blocking PDZ binding by C-terminal green fluorescent protein fusion; 3) disrupting CFTR association with actin by expression of a mutant EBP50/NHERF1 lacking its ezrin binding domain; or 4) skeletal disruption by latrunculin. CFTR also became mobile when the cytoskeletal adaptor protein binding capacity was saturated by overexpressing CFTR or its C terminus. Our data demonstrate remarkable and previously unrecognized immobilization of CFTR in the plasma membrane and provide direct evidence that C-terminal coupling to the actin skeleton via EBP50/ezrin is responsible for its immobility.
Candida albicans Biofilm-Defective Mutants (2005)

Biofilm formation plays a key role in the life cycles and subsistence of many microorganisms. For the human fungal pathogen Candida albicans, biofilm development is arguably a virulence trait, because medical implants that serve as biofilm substrates are significant risk factors for infection. The development of C. albicans biofilms in vitro proceeds through an early phase, in which yeast cells populate a substrate, an intermediate phase, in which pseudohyphal and hyphal cell types are produced, and a maturation phase, in which continued cell growth is accompanied by accumulation of an extracellular matrix. Here we report the results of a screen for C. albicans biofilm-defective mutants, in which homozygous insertions in NUP85, MDS3, KEM1, and SUV3 were found to block biofilm development. Confocal microscopic examination suggests that nup85, suv3, and mds3 mutations cause early-phase arrest, whereas the kem1 mutation causes intermediate-phase arrest. All of the mutants are defective in hypha production in several media. Analysis of mixed-biofilm development indicates that all of the mutants are defective in the production of hyphae in the context of a biofilm. Because all of the mutants are defective in the retention of cells in the biofilm, we infer that hyphae provide an adherent scaffold that stabilizes the biofilm structure.
Cotton aerogels and cotton-cellulose aerogels from environmental waste for oil spillage cleanup (2017)

For the first time, successful fabrication of the cotton aerogels and cotton-cellulose aerogels is achieved using recycled fibers from environmental waste for oil absorption. The pure cotton and cotton-cellulose aerogels are obtained using a cost-effective mixing-blending method with polyamide-epichlorohydrin as strengthening additives. The obtained aerogels are silanized using methyltrimethoxysilane via a facile chemical vapor deposition to endow aerogels with hydrophobic surface. Effects of fiber concentrations and cotton-to-cellulose mass ratio on oil absorption performance in various solvents are also investigated. The cotton aerogel with an initial concentration of 0.25wt% presents the highest oil absorption capacity over 100gg−1. Besides, the cotton/cellulose aerogels also demonstrate good absorption capacity in different pollutant organics. The absorption kinetics of the aerogels with different cotton concentrations are also investigated using pseudo first-order model. Both equilibrium absorption and absorption kinetics demonstrate cotton/cellulose aerogels as promising materials for oil absorption and environmental pollution treatment. Keywords: Cotton fibers, Cellulose fibers, Aerogel, Oil absorption, Environmental waste
Organization of Diphtheria Toxin T Domain in Bilayers: A Site-Directed Spin Labeling Study (1996)

The diphtheria toxin transmembrane (T) domain was spin-labeled at consecutive residues in a helical segment, TH9. After binding of the T domain to membranes at low pH, the nitroxide side chains generated by spin labeling were measured with respect to their frequency of collision with polar and nonpolar reagents. The data showed that the helical structure of TH9 in solution is conserved, with one face exposed to water and the other to the hydrophobic interior of the bilayer. Measurement of the depth of the nitroxide side chains from the membrane surfaces revealed an incremental change of about 5 angstroms per turn, which is consistent with a transmembrane orientation of an alpha helix. These results indicate that the helix forms the lining of a transmembrane water-filled channel.
Proteolytic inactivation of alpha-1-proteinase inhibitor by a neutrophil metalloproteinase. (1988)

Human neutrophils triggered with phorbol myristate acetate or opsonized zymosan particles released a metalloproteinase (MP) capable of cleaving and inactivating alpha-1-proteinase inhibitor (alpha-1-PI). Sequence analysis of the amino acids in proteolyzed, native alpha-1-PI revealed a unique single cleavage site between Phe-352 and Leu-353. An analysis of the process regulating the enzyme's activity revealed that the neutrophil MP was released from cells in a latent form whose activation was tightly linked to the generation of hypochlorous acid. These results indicate that human neutrophils use chlorinated oxidants to activate a latent MP that is capable of proteolytically inactivating alpha-1-PI by cleaving the antiproteinase at a unique point in its inhibitory site region.
Improved MDS-based localization (2005)

It is often useful to know the geographic positions of nodes in a communications network, but adding GPS receivers or other sophisticated sensors to every node can be expensive. MDS-MAP is a recent localization method based on multidimensional scaling (MDS). It uses connectivity information - who is within communications range of whom - to derive the locations of the nodes in the network, and can take advantage of additional data, such as estimated distances between neighbors or known positions for certain anchor nodes, if they are available. However, MDS-MAP is an inherently centralized algorithm and is therefore of limited utility in many applications. In this paper, we present a new variant of the MDS-MAP method, which we call MDS-MAP(P) standing for MDS-MAP using patches of relative maps, that can be executed in a distributed fashion. Using extensive simulations, we show that the new algorithm not only preserves the good performance of the original method on relatively uniform layouts, but also performs much better than the original on irregularly-shaped networks. The main idea is to build a local map at each node of the immediate vicinity and then merge these maps together to form a global map. This approach works much better for topologies in which the shortest path distance between two nodes does not correspond well to their Euclidean distance. We also discuss an optional refinement step that improves solution quality even further at the expense of additional computation.
Total Variation-Based Image Deconvolution: a Majorization-Minimization Approach (2006)

The total variation regularizer is well suited to piecewise smooth images. If we add the fact that these regularizers are convex, we have, perhaps, the reason for the resurgence of interest on TV-based approaches to inverse problems. This paper proposes a new TV-based algorithm for image deconvolution, under the assumptions of linear observations and additive white Gaussian noise. To compute the TV estimate, we propose a majorization-minimization approach, which consists in replacing a difficult optimization problem by a sequence of simpler ones, by relying on convexity arguments. The resulting algorithm has O(N) computational complexity, for finite support convolutional kernels. In a comparison with state-of-the-art methods, the proposed algorithm either outperforms or equals them, with similar computational complexity
Transforming growth factor-beta 1 stimulates articular chondrocyte proteoglycan synthesis and induces osteophyte formation in the murine knee joint. (1994)

Our data indicate that TGF-beta 1 injection into a normal joint induces inflammation, synovial hyperplasia, osteophyte formation, and prolonged elevation of proteoglycan synthesis and content in articular cartilage.
AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements (2007)

Activation-induced cytidine deaminase (AID) is required for immunoglobulin (Ig) class switch recombination and somatic hypermutation, and has also been implicated in translocations between Ig switch regions and c-Myc in plasma cell tumors in mice. We asked if AID is required for accelerated tumor development in pristane-treated Bcl-xL transgenic BALB/c mice deficient in AID (pBxAicda-/-). pBxAicda-/- mice developed tumors with a lower frequency (24 vs. 62%) and a longer mean latency (108 vs. 36 d) than AID-sufficient mice. The tumors appeared in oil granuloma tissue and did not form ascites. By interphase fluorescence in situ hybridization, six out of nine pBxAicda-/- primary tumors had T(12;15) and one had T(6;15) chromosomal translocations. Two tumors were transplantable and established as stable cell lines. Molecular and cytogenetic analyses showed that one had an unusual unbalanced T(12;15) translocation, with IgH Cmu and Pvt-1 oriented head to tail at the breakpoint, resulting in an elevated expression of c-Myc. In contrast, the second was T(12;15) negative, but had an elevated N-Myc expression caused by a paracentric inversion of chromosome 12. Thus, novel mechanisms juxtapose Ig and Myc-family genes in AID-deficient plasma cell tumors.
Fully Automatic Facial Action Unit Detection and Temporal Analysis (2006)

In this work we report on the progress of building a system that enables fully automated fast and robust facial expression recognition from face video. We analyse subtle changes in facial expression by recognizing facial muscle action units (AUs) and analysing their temporal behavior. By detecting AUs from face video we enable the analysis of various facial communicative signals including facial expressions of emotion, attitude and mood. For an input video picturing a facial expression we detect per frame whether any of 15 different AUs is activated, whether that facial action is in the onset, apex, or offset phase, and what the total duration of the activation in question is. We base this process upon a set of spatio-temporal features calculated from tracking data for 20 facial fiducial points. To detect these 20 points of interest in the first frame of an input face video, we utilize a fully automatic, facial point localization method that uses individual feature GentleBoost templates built from Gabor wavelet features. Then, we exploit a particle filtering scheme that uses factorized likelihoods and a novel observation model that combines a rigid and a morphological model to track the facial points. The AUs displayed in the input video and their temporal segments are recognized finally by Support Vector Machines trained on a subset of most informative spatio-temporal features selected by AdaBoost. For Cohn-Kanade andMMI databases, the proposed system classifies 15 AUs occurring alone or in combination with other AUs with a mean agreement rate of 90.2% with human FACS coders.
Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick (2000)

The vertebrate eye develops from the neuroepithelium of the ventral forebrain by the evagination and formation of the optic vesicle. Classical embryological studies have shown that the surrounding extraocular tissues - the surface ectoderm and extraocular mesenchyme - are necessary for normal eye growth and differentiation. We have used explant cultures of chick optic vesicles to study the regulation of retinal pigmented epithelium (RPE) patterning and differentiation during early eye development. Our results show that extraocular mesenchyme is required for the induction and maintenance of expression of the RPE-specific genes Mitf and Wnt13 and the melanosomal matrix protein MMP115. In the absence of extraocular tissues, RPE development did not occur. Replacement of the extraocular mesenchyme with cranial mesenchyme, but not lateral plate mesoderm, could rescue expression of the RPE-marker Mitf. In addition to activating expression of RPE-specific genes, the extraocular mesenchyme inhibits the expression of the neural retina-specific transcription factor Chx10 and downregulates the eye-specific transcription factors Pax6 and Optx2. The TGF(&bgr;) family member activin can substitute for the extraocular mesenchyme by promoting expression of the RPE-specific genes and downregulating expression of the neural retina-specific markers. These data indicate that extraocular mesenchyme, and possibly an activin-like signal, pattern the domains of the optic vesicle into RPE and neural retina.