gebhart/patrepeval huggingface dataset:
Anti-amyloid-beta to tau-based immunization: developments in immunotherapy for Alzheimer&#39;s disease (2013)

Immunotherapy might provide an effective treatment for Alzheimer disease (AD). A unique feature of AD immunotherapies is that an immune response against a self antigen needs to be elicited without causing adverse autoimmune reactions. Current research is focussed on two possible targets in this regard: One is the inhibition of accumulation and deposition of Amyloid beta 1-42 (Aβ42), which is one of the major peptides found in senile plaques and the second target is hyperphosphorylated tau, which forms neurofibrillary tangles inside the nerve cell and shows association with the progression of dementia. Mouse models have shown that immunotherapy targeting Aβ42 as well as tau with the respective anti-Aβ or anti-tau antibodies can provide significant improvements in these mice. While anti-Aβ immunotherapy (active and passive immunizations) is already in several stages of clinical trials, tau based immunizations have been analyzed only in mouse models. Recently, as a significant correlation of progression of dementia and levels of phoshorylated tau was found, high interest has again focussed on further development of tau based therapies. While Aβ immunotherapy might delay the onset of AD, immunotherapy targeting tau might provide benefits in later stages of this disease. And last but not least, targeting Aβ and tau simultaneously with immunotherapy might provide additional therapeutic effects as these two pathologies are likely synergistic; an approach which has not been tested yet. In this review, we will summarize animal models used to test possible therapies for AD, some of the facts about Aβ42 and tau biology, present on overview on halted, ongoing and upcoming clinical trials together with ongoing preclinical studies targeting tau or Aβ42.
A New Method for Microlens Fabrication by a Heating Encapsulated Air Process (2006)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> This letter reports a new method to fabricate thin microlens array on a silicon substrate by a heating encapsulated air process. We use silicon bulk micromachining, wafer-to-wafer bonding, and photoresist (PR) spin coating to achieve the air sealing process. Under a heating process, the PR filled in the micro-through-hole of cap wafer is compressed by the thermal expansion of the sealed air to form a thin microlens with out-of-plane sphere shape. By adjusting the heating temperature and the sealed air volume, the curvature and size of the lens are controllable. A typical microlens with a diameter of 1475 <formula formulatype="inline"><tex>$\mu$</tex></formula>m and sag height of 486 <formula formulatype="inline"><tex>$\mu$</tex> </formula>m was fabricated. The calculated radius of curvature and focal length are about 800 and 1200 <formula formulatype="inline"><tex>$\mu$</tex></formula>m, respectively. The fabrication provides an alternative way to manufacture thin microlens or microlens mold serve as master elements for replication. </para>
Relationship of morphological traits and grain yield in recombinant inbred wheat lines grown under drought conditions. (2010)

The paper deals with the status of the woodlands, notably Acacia woodlands, and juniper forests in Africa and Asia and the causes of destruction and or damage observed in recent times to some of these communities.
Physics for scientists and engineers with modern physics (2008)

Tipler's textbook sets the standard in introductory physics courses for clarity, accuracy, and precision.
Discrimination of Single-Nucleotide Polymorphisms in Human DNA Using Peptide Nucleic Acid Probes Detected by MALDI-TOF Mass Spectrometry (1997)

Human genomic and mitochondrial DNA contain large numbers of single-nucleotide polymorphisms (SNPs), many of which are linked to known diseases. Rapid and accurate genetic screening for important SNPs requires a general methodology which is easily implemented. We present here an approach to SNP discrimination based on high-specificity hybridization of peptide nucleic acid (PNA) probes to PCR-amplified DNA. The assay is directly applied to polymorphisms located within hypervariable region 1 of the human mitochondrial genome and type 1 suballeles of the human leukocyte antigen DQ alpha gene. Captured, single-stranded DNA molecules prepared by PCR amplification are hybridized with PNA probes in an allele-specific fashion. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) is then used for rapid, precise, and unambiguous detection and identification of the hybridized PNA probes. Since PNA oligomers bind strongly to complementary DNA under minimal salt conditions, the use of PNA probes is compatible with MALDI-TOFMS. The unparalleled ability of MALDI-TOFMS analysis in terms of molecular weight resolution and accuracy, in conjunction with the highly specific PNA hybridization afforded by this method, offers promise for development into a multiplexed, high-throughput screening technique.
Synergistic Effects of Alpha-Toxin and Perfringolysin O in Clostridium perfringens -Mediated Gas Gangrene (2001)

To examine the synergistic effects of alpha-toxin and perfringolysin O in clostridial myonecrosis, homologous recombination was used to construct an alpha-toxin deficient derivative of a perfringolysin O mutant of Clostridium perfringens. The subsequent strain was complemented with separate plasmids that carried the alpha-toxin structural gene (plc), the perfringolysin O gene (pfoA), or both toxin genes, and the resultant isogenic strains were examined in a mouse myonecrosis model. Synergistic effects were clearly observed in these experiments. Infection with the control strain, which did not produce either toxin, resulted in very minimal gross pathological changes, whereas the isogenic strain that was reconstituted for both toxins produced a pathology that was clearly more severe than when alpha-toxin alone was reconstituted. These changes were most apparent in the rapid spread of the disease, the gross pathology of the footpad and in the rate at which the mice had to be euthanatized for ethical reasons. Elimination of both alpha-toxin and perfringolysin O production removed most of the histopathological features typical of clostridial myonecrosis. These effects were restored when the mutant was complemented with the alpha-toxin structural gene, but reconstituting only perfringolysin O activity produced vastly different results, with regions of coagulative necrosis, apparently enhanced by vascular disruption, being observed. Reconstitution of both alpha-toxin and perfringolysin O activity produced histopathology most similar to that observed with the alpha-toxin reconstituted strain. The spreading of myonecrosis was very rapid in these tissues, and coagulative necrosis appeared to be restricted to the lumen of the blood vessels. The results of these virulence experiments clearly support the hypothesis that alpha-toxin and perfringolysin O have a synergistic effect in the pathology of gas gangrene.
Sideband spectroscopy and dispersion measurement in microcavities (2012)

The measurement of dispersion and its control have become important considerations in nonlinear devices based on microcavities. A sideband technique is applied here to accurately measure dispersion in a microcavity resulting from both geometrical and material contributions. Moreover, by combining the method with finite element simulations, we show that mapping of spectral lines to their corresponding transverse mode families is possible. The method is applicable for high-Q, micro-cavities having microwave rate free spectral range and has a relative precision of 5.5 × 10(-6) for a 2 mm disk cavity with FSR of 32.9382 GHz and Q of 150 milllion.
CELL BIOLOGY OFMYCOBACTERIUM TUBERCULOSISPHAGOSOME (2004)

Phagocytosis and phagolysosome biogenesis represent fundamental biological processes essential for proper tissue homeostasis, development, elimination of invading microorganisms, and antigen processing and presentation. Phagosome formation triggers a preprogrammed pathway of maturation into the phagolysosome, a process controlled by Ca2+ and the regulators of organellar trafficking centered around the small GTP-binding proteins Rabs and their downstream effectors, including lipid kinases, organellar tethering molecules, and membrane fusion apparatus. Mycobacterium tuberculosis is a potent human pathogen parasitizing macrophages. It interferes with the Rab-controlled membrane trafficking and arrests the maturing phagosome at a stage where no harm can be done to the pathogen while the delivery of nutrients and membrane to the vacuole harboring the microorganism continues. This process, referred to as the M. tuberculosis phagosome maturation arrest or inhibition of phagosome-lysosome fusion, is critical for M. tuberculosis persistence in human populations. It also provides a general model system for dissecting the phagolysosome biogenesis pathways. Here we review the fundamental trafficking processes targeted by M. tuberculosis and the mycobacterial products that interfere with phagosomal maturation.
Sphingolipid metabolism in the regulation of bioactive molecules (1999)

Conclusions In conclusion, the study of signaling and cell regulation through ceramide has now evolved to the biochemical level by focusing on specific enzymes of ceramide metabolism. A general hypothesis can be presented whereby individual enzymes of ceramide metabolism serve as input points in the regulation of ceramide levels (Scheme 1). For example, activation of SMases or ceramide synthase would elevate ceramide levels and activate ceramide‐induced responses. On the other hand, activation of enzymes of ceramide degradation or incorporation such as ceramidases or SM synthase decreases and attenuates ceramide levels. Also, as an important corollary, some of these enzymes may play an additional fundamental role in interconverting lipid signals. For example, SM synthase has the capacity of interconverting a ceramide signal into a DAG signal, whereas ceramidases can transform a ceramide signal into a sphingosine or sphingosine‐phosphate signal. This area of research promises great future insight into important areas of cell studies.
Expression of the Murine CD27 Ligand CD70 In Vitro and In Vivo (2003)

The interaction between TNFR family member CD27 and its ligand CD70 promotes lymphocyte expansion and effector cell formation. In humans, control of CD27 function is partly regulated by the restricted expression of CD70. We used newly developed mAbs to characterize murine (m) CD70 expression in vitro and in vivo. On resting lymphocytes and immature dendritic cells (DC), mCD70 is absent. In vitro, Ag receptor triggering induced mCD70 mRNA in T cells, but cell surface protein expression was very low. Activated B cells synthesized much higher levels of mCD70 mRNA than activated T cells and clearly expressed mCD70 at the cell surface. mCD70 cell surface expression could also be induced on the DC line D1 and on in vitro-generated murine DC upon maturation. In lymphoid organs of naive mice, virtually no mCD70-expressing cells were found, with exception of cells in the thymic medulla, which may be epithelial in origin. However, after intranasal infection with influenza virus, lung-infiltrating T cells and T and B cells in draining lymph nodes expressed mCD70 according to immunohistology. In such activated lymphocytes, mCD70 protein is largely retained intracellularly. Plasma membrane expression of mCD70 was only detectable by flow cytometry on a small proportion of lung-infiltrating T cells and peaked at the height of the primary response. Thus, expression of CD70 in the mouse is highly regulated at the transcriptional and posttranslational level. This most likely serves to limit excessive effector cell formation after antigenic stimulation.
Dynamic Cross‐Linking Is Retained in Duplex DNA after Multiple Exchange of Strands (2010)

Strands may come and go, but cross-linking is forever: Dynamic combinatorial chemistry can respond to changing environments, a characteristic that is now demonstrated with DNA cross-linking based on reversible alkylation of a quinone methide intermediate (see picture). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Myristoylation and Differential Palmitoylation of the HCK Protein-Tyrosine Kinases Govern Their Attachment to Membranes and Association with Caveolae (1995)

The human proto-oncogene HCK encodes two versions of a protein-tyrosine kinase, with molecular weights of 59,000 (p59hck) and 61,000 (p61hck). The two proteins arise from a single mRNA by alternative initiations of translation. In this study, we explored the functions of these proteins by determining their locations within cells and by characterizing lipid modifications required for the proteins to reach those locations. We found that p59hck is entirely associated with cellular membranes, including the organelles known as caveolae; in contrast, only a portion of p61hck is situated on membranes, and none is detectable in preparations of caveolae. These distinctions can be attributed to differential modification of the two HCK proteins with fatty acids. Both proteins are at least in part myristoylated, p59hck more so than p61hck. In addition, however, p59hck is palmitoylated on cysteine 3 in the protein. Palmitoylation of the protein requires prior myristoylation and, in turn, is required for targeting to caveolae. These findings are in accord with recent reports for other members of the SRC family of protein-tyrosine kinases. Taken together, the results suggest that HCK and several of its relatives may participate in the functions of caveolae, which apparently include the transduction of signals across the plasma membrane to the interior of the cell.
Coordinated Binding of Single-Stranded and Double-Stranded DNA by UvsX Recombinase (2013)

Homologous recombination is important for the error-free repair of DNA double-strand breaks and for replication fork restart. Recombinases of the RecA/Rad51 family perform the central catalytic role in this process. UvsX recombinase is the RecA/Rad51 ortholog of bacteriophage T4. UvsX and other recombinases form presynaptic filaments on ssDNA that are activated to search for homology in dsDNA and to perform DNA strand exchange. To effectively initiate recombination, UvsX must find and bind to ssDNA within an excess of dsDNA. Here we examine the binding of UvsX to ssDNA and dsDNA in the presence and absence of nucleotide cofactor, ATP. We also examine how the binding of one DNA substrate is affected by simultaneous binding of the other to determine how UvsX might selectively assemble on ssDNA. We show that the two DNA binding sites of UvsX are regulated by the nucleotide cofactor ATP and are coordinated with each other such that in the presence of ssDNA, dsDNA binding is significantly reduced and correlated with its homology to the ssDNA bound to the enzyme. UvsX has high affinity for dsDNA in the absence of ssDNA, which may allow for sequestration of the enzyme in an inactive form prior to ssDNA generation.
EFFECTS OF DECREASED FREE FATTY ACIDS ON FATIGUE DURING EXERCISE WITH CARBOHYDRATE FEEDINGS (1995)

Kohut, M. L; Davis, J. M. FACSM; Bailey, S. P.; Walsh, T. M.; Jackson, D. A. Author Information
RapidAIM: a culture- and metaproteomics-based Rapid Assay of Individual Microbiome responses to drugs (2020)

Current drug-microbiome interaction studies largely focus on relative microbiome composition and microbial drug metabolism. In contrast, our workflow enables multiple insights into microbiome absolute abundance and functional responses to drugs. The workflow is robust, reproducible, and quantitative and is scalable for personalized high-throughput drug screening applications.
Bovine osteogenic protein is composed of dimers of OP-1 and BMP-2A, two members of the transforming growth factor-beta superfamily. (1990)

A bone-inductive protein has been purified from bovine bone and designated as osteogenic protein (OP). The purified OP induces new bone at less than 5 ng with half-maximal bone differentiation activity at about 20 ng/25 mg of matrix implant in a subcutaneous bone induction assay. The purified osteogenic protein is composed of disulfide-linked dimers that migrate on sodium dodecyl sulfate gels as a diffuse band with an apparent molecular weight of 30,000. Upon reduction, the dimers yield two subunits that migrate with molecular weights of 18,000 and 16,000. Both subunits are glycosylated. After chemical or enzymatic deglycosylation, the dimers migrate as a diffuse 27-kDa band that upon reduction yields two polypeptides that migrate at 16 kDa and 14 kDa, respectively. The carbohydrate moiety does not appear to be essential for biological activity since the deglycosylated proteins are capable of inducing bone formation in vivo. Amino acid sequences of peptides generated by proteolytic digestion show that the subunits are distinct but related members of the transforming growth factor-beta super-family. The 18-kDa subunit is the protein product of the bovine equivalent of the human OP-1 gene and the 16-kDa subunit is the protein product of the bovine equivalent of the human BMP-2A gene.
Hydrogel Stamping of Arrays of Supported Lipid Bilayers with Various Lipid Compositions for the Screening of Drug–Membrane and Protein–Membrane Interactions (2005)

Fettflecken mit Funktion: Mit pikomolaren Lipidmengen erzeugten Agarosegel-Stempel 100 oder mehr Membrananordnungen (siehe Bild). Diese schnelle und direkte Methode zum Aufbau funktionaler Membrananordnungen mit verschiedenartigen Lipidzusammensetzungen bietet sich für Screenings an, z. B. bei Tests auf Wirkstoff-Lipidmembran-Wechselwirkungen. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2005/z502189_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Ezetimibe/Simvastatin 10/20 mg versus Rosuvastatin 10 mg in high-risk hypercholesterolemic patients stratified by prior statin treatment potency (2010)

Registered at ClinicalTrials.gov: NCT00479713.
Fine Tuning of Electrostatics around the Internucleotidic Phosphate through Incorporation of Modified 2′,4′-Carbocyclic-LNAs and -ENAs Leads to Significant Modulation of Antisense Properties (2008)

In the antisense (AS) and RNA interference (RNAi) technologies, the native single-stranded 2'-deoxyoligonucleotides (for AS) or double-stranded RNA (for RNAi) are chemically modified to bind to the target RNA in order to give improved downregulation of gene expression through inhibition of RNA translation. It is shown here how the fine adjustment of the electrostatic interaction by alteration of the substituents as well as their stereochemical environment around the internucleotidic phosphodiester moiety near the edge of the minor grove of the antisense oligonucleotides (AON)-RNA heteroduplex can lead to the modulation of the antisense properties. This was demonstrated through the synthesis of various modified carbocyclic-locked nucleic acids (LNAs) and -ethylene-bridged nucleic acids (ENAs) with hydroxyl and/or methyl substituents attached at the carbocyclic part and their integration into AONs by solid-phase DNA synthesis. The target affinity toward the complementary RNA and DNA, nuclease resistance, and RNase H elicitation by these modified AONs showed that both the nature of the modification (-OH versus -CH(3)) and their respective stereochemical orientations vis-a-vis vicinal phosphate play a very important role in modulating the AON properties. Whereas the affinity to the target RNA and the enzymatic stability of AONs were not favored by the hydrophobic and sterically bulky modifications in the center of the minor groove, their positioning at the edge of the minor groove near the phosphate linkage resulted in significantly improved nuclease resistance without loss of target affinity. On the other hand, hydrophilic modification, such as a hydroxyl group, close to the phosphate linkage made the internucleotidic phosphodiester especially nucleolytically unstable, and hence was not recommended. The substitutions on the carbocyclic moiety of the carba-LNA and -ENA did not affect significantly the choice of the cleavage sites of RNase H mediated RNA cleavage in the AON/RNA hybrid duplex, but the cleavage rate depended on the modification site in the AON sequence. If the original preferred cleavage site by RNase H was included in the 4-5nt stretch from the 3'-end of the modification site in the AON, decreased cleavage rate was observed. Upon screening of 52 modified AONs, containing 13 differently modified derivatives at C6' and C7' (or C8') of the carba-LNAs and -ENAs, two excellent modifications in the carba-LNA series were identified, which synergistically gave outstanding antisense properties such as the target RNA affinity, nuclease resistance, and RNase H activity and were deemed to be ideal candidates as potential antisense or siRNA therapeutic agents.
Soybean Protease Inhibitors in Foods (1989)

ABSTRACT The major types of soybean protease inhibitors are the Kunitz inhibitor (KSTI) and the Bowman‐Birk inhibitor (BBI). Enzymatic analysis and rocket Immunoelectrophoresis were used to specifically quantitate the amounts of KSTI and BBI in various soy foods. Many soy products such as soy flours, soy concentrates and soy isolates contained significant amounts of KSTI and BBI. Some soy foods contained small but still detectable levels of KSTI and BBI.
Targeting the Cell Cycle: A New Approach to Cancer Therapy (2005)

The cell cycle represents a series of tightly integrated events that allow the cell to grow and proliferate. Critical parts of the cell cycle machinery are the cyclin-dependent kinases (CDKs), which, when activated, provide a means for the cell to move from one phase of the cell cycle to the next. The CDKs are regulated positively by cyclins and regulated negatively by naturally occurring CDK inhibitors (CDKIs). Cancer represents a dysregulation of the cell cycle such that cells that overexpress cyclins or do not express the CDKIs continue to undergo unregulated cell growth. The cell cycle also serves to protect the cell from DNA damage. Thus, cell cycle arrest, in fact, represents a survival mechanism that provides the tumor cell the opportunity to repair its own damaged DNA. Thus, abrogation of cell cycle checkpoints, before DNA repair is complete, can activate the apoptotic cascade, leading to cell death. Now in clinical trials are a series of targeted agents that directly inhibit the CDKs, inhibit unrestricted cell growth, and induce growth arrest. Recent attention has also focused on these drugs as inhibitors of transcription. In addition, there are now agents that abrogate the cell cycle checkpoints at critical time points that make the tumor cell susceptible to apoptosis. An understanding of the cell cycle is critical to understanding how best to clinically develop these agents, both as single agents and in combination with chemotherapy.
BiCMOS silicon photonics platform for fabrication of high-bandwidth electronic-photonic integrated circuits (2016)

Photonic BiCMOS is a novel technology for fabricating electronic-photonic integrated circuits. Broadband silicon photonics devices such as germanium photodiodes and depletion type Mach-Zehnder modulators were monolithically integrated in a high performance SiGe BiCMOS baseline process. Integration aspects and examples of demonstrator circuits shall be reviewed.