gebhart/patrepeval huggingface dataset:
Blood-Cerebrospinal Fluid Barrier Dysfunction for High Molecular Weight Proteins in Alzheimer Disease and Major Depression (1997)

There is a diversity of opinions concerning the function of the blood-brain barrier and the blood-cerebrospinal fluid barrier (BCB) in Alzheimer disease and other neuropsychiatric disorders. In this paper we investigate and review the evidence for BCB dysfunction in Alzheimer disease and major depression. The hypothetical roles of immunologically mediated mechanisms in the central nervous system (CNS) are discussed. Special consideration is given to methodological factors influencing BCB function and analysis. Serum and cerebrospinal fluid (CSF) of 29 patients with major depression (MD) and 51 patients with "probable Alzheimer disease" (AD) were investigated. The AD patients were subdivided in two groups of 21 early-onset (EO) and 30 late-onset (LO) cases and assayed for concentrations of albumin and IgG. The results were compared with those for 11 age-matched healthy controls. The severity of dementia was assessed with the Mini-Mental State Examination (MMSE). AD and MD patients showed significantly lower serum albumin [AD: p < 0.05 (LO: p < 0.038); MD p < 0.01] and IgG (AD: p < 0.01; MD: p < 0.013) concentrations compared with controls. MD (p < 0.001) and LO-AD (p < 0.07) patients displayed significantly lower absolute serum albumin levels than did EO-AD patients. The CSF/serum ratio for albumin and IgG was used to evaluate BCB function. There were no significant group differences; however, subsets of MD (29%) and AD (16%) patients showed a higher frequency of a pathological albumin ratio than did control subjects. Furthermore, a subset of 24% of MD and18% of AD patients and none of the controls showed an elevated IgG ratio. Different mechanisms of alteration of IgG distribution are presented. The degree of cognitive impairment in AD did not correlate positively with protein and ratio parameters. The BCB is critical to the maintenance of homeostasis within nervous system tissue. We suggest that the altered function can result from immune-mediated events such as altered levels of circulating inflammatory mediators. Furthermore, we assume that in the AD and MD subgroups, the BCB dysfunction for high molecular weight proteins permits access of components of the immune system to the CNS, which may contribute to disease pathology.
Dendrimer-Based Postnatal Therapy for Neuroinflammation and Cerebral Palsy in a Rabbit Model (2012)

Cerebral palsy (CP) is a chronic childhood disorder with no effective cure. Neuroinflammation, caused by activated microglia and astrocytes, plays a key role in the pathogenesis of CP and disorders such as Alzheimer's disease and multiple sclerosis. Targeting neuroinflammation can be a potent therapeutic strategy. However, delivering drugs across the blood-brain barrier to the target cells for treating diffuse brain injury is a major challenge. We show that systemically administered polyamidoamine dendrimers localize in activated microglia and astrocytes in the brain of newborn rabbits with CP, but not healthy controls. We further demonstrate that dendrimer-based N-acetyl-l-cysteine (NAC) therapy for brain injury suppresses neuroinflammation and leads to a marked improvement in motor function in the CP kits. The well-known and safe clinical profile for NAC, when combined with dendrimer-based targeting, provides opportunities for clinical translation in the treatment of neuroinflammatory disorders in humans. The effectiveness of the dendrimer-NAC treatment, administered in the postnatal period for a prenatal insult, suggests a window of opportunity for treatment of CP in humans after birth.
Hazard Assessment of Chemical Air Contaminants Measured in Residences - eScholarship (2010)

Hazard Assessment of Chemical Air Contaminants Measured in Residences J.M. Logue, T.E. McKone, M. H. Sherman, B.C. Singer Environmental Energy Technologies Division June 2010 Funding was provided by the U.S. Dept. of Energy Building Technologies Program, Office of Energy Efficiency and Renewable Energy under DOE Contract No. DE-AC02-05CH11231; by the U.S. Dept. of Housing and Urban Development Office of Healthy Homes and Lead Hazard Control through Interagency Agreement I-PHI-01070, and by the California Energy Commission through Contract 500-08-06. LBNL Report Number xxxx
High- and Low-Affinity Epidermal Growth Factor Receptor-Ligand Interactions Activate Distinct Signaling Pathways (2011)

Signaling mediated by the Epidermal Growth Factor Receptor (EGFR) is crucial in normal development, and aberrant EGFR signaling has been implicated in a wide variety of cancers. Here we find that the high- and low-affinity interactions between EGFR and its ligands activate different signaling pathways. While high-affinity ligand binding is sufficient for activation of most canonical signaling pathways, low-affinity binding is required for the activation of the Signal transducers and activators of transcription (Stats) and Phospholipase C-gamma 1 (PLCγ1). As the Stat proteins are involved in many cellular responses including proliferation, migration and apoptosis, these results assign a function to low-affinity interactions that has been omitted from computational models of EGFR signaling. The existence of receptors with distinct signaling properties provides a way for EGFR to respond to different concentrations of the same ligand in qualitatively different ways.
Comprehensive Heterocyclic Chemistry II (1997)

CHEC III is organized in 15 Volumes and closely follows the organization used in the previous edition: Volumes 1 and 2: Cover respectively three- and four-membered heterocycles, together with all fused systems containing a three- or four-membered heterocyclic ring. Volume 3: Five-membered rings with one heteroatom together with their benzo- and other carbocyclic-fused derivatives. Volumes 4, 5 and 6: Cover five-membered rings with two heteroatoms, and three or more heteroatoms, respectively, each with their fused carbocyclic compounds. Volumes 7, 8 and 9: Dedicated to six-membered rings with one, two, and more than two heteroatoms, respectively, again with the corresponding fused carbocylic compounds. Volumes 10, 11 and 12: Cover systems containing at least two directly fused heterocyclic five- and/or six-membered rings: of these Volume 10 deals with bi-heterocyclic rings without a ring junction heteroatom, and Volume 11 deals with 5:5 and 5:6 fused rings systems with at least one ring junction nitrogen, while Volume 12 is devoted to all other systems of five and/or six-membered fused or spiro heterocyclic rings with ring junction heteroatoms. Volumes 13 and 14: Seven-membered and larger heterocyclic rings including all their fused derivatives (except those containing three- or four-membered heterocyclic rings which are included in Volume 1 and 2, respectively). Volume 15: Author, ring and subject indexes.
Quantum nondemolition measurement of small photon numbers by Rydberg-atom phase-sensitive detection (1990)

We describe a new quantum nondemolition method to monitor the number N of photons in a microwave cavity. We propose coupling the field to a quasiresonant beam of Rydberg atoms and measuring the resulting phase shift of the atom wave function by the Ramsey separated-oscillatory-fields technique. The detection of a sequence of atoms reduces the field into a Fock state. With realistic Rydberg atom-cavity systems, small-photon-number states down to N=0 could be prepared and continuously monitored.
Structurally Minimized μ‐Conotoxin Analogues as Sodium Channel Blockers: Implications for Designing Conopeptide‐Based Therapeutics (2008)

Disulfide bridges that stabilize the native conformation of conotoxins pose a challenge in the synthesis of smaller conotoxin analogues. Herein we describe the synthesis of a minimized analogue of the analgesic mu-conotoxin KIIIA that blocks two sodium channel subtypes, the neuronal Na(V)1.2 and skeletal muscle Na(V)1.4. Three disulfide-deficient analogues of KIIIA were initially synthesized in which the native disulfide bridge formed between either C1-C9, C2-C15, or C4-C16 was removed. Deletion of the first bridge only slightly affected the peptide's bioactivity. To further minimize this analogue, the N-terminal residue was removed and two nonessential serine residues were replaced by a single 5-amino-3-oxapentanoic acid residue. The resulting "polytide" analogue retained the ability to block sodium channels and to produce analgesia. Until now, the peptidomimetic approach applied to conotoxins has progressed only modestly at best; thus, the disulfide-deficient analogues containing backbone spacers provide an alternative advance toward the development of conopeptide-based therapeutics.
Vascular Compliance as a Measure of Biological Age (1999)

Because of the close relationship between aortic and carotid compliance and chronological age, deviation from the age-predicted norm (biological age) may prove to be a good predictor of cardiovascular pathology.
Emerging Role of ImmunoPET in Receptor Targeted Cancer Therapy (2010)

ImmunoPET is a non-invasive imaging technology based on tracking and quantification of radiolabeled monoclonal antibodies, antibody fragments and peptides in vivo. The knowledge of distribution and expression levels of a given receptor is a key for successful receptor targeted cancer therapy. ImmunoPET performed with probes with high affinity and specificity to a given receptor aspires to be a method for obtaining comprehensive information about current in vivo status of the targeted receptor. This review describes methods for radiolabeling of peptides, monoclonal antibodies, and antibody fragments for immunoPET and highlights the recently reported pre-clinical and clinical applications of immunoPET in receptor targeted therapy.
Amino acid sequence of heavy chain from Xenopus laevis IgM deduced from cDNA sequence: implications for evolution of immunoglobulin domains. (1988)

Present understanding of the evolution of immunoglobulins is derived almost entirely from studies of a few mammalian species. To obtain information about immunoglobulin genes in Xenopus laevis, a cDNA library was prepared in the expression vector lambda gt11 from mitogen-stimulated splenocytes of this species. Of approximately equal to 50,000 clones screened, 18 were found to express IgM epitopes. One of these, lambda XIg14, hybridized with RNA of RNA of approximately equal to 2 kilobases from splenocytes. The insert of this clone appears to encode a variable region and part of a mu constant region; that of another clone, lambda XIg8, appears to encode a variable region and a complete mu constant region. Both inserts contain sequence corresponding to the three gene segments (VH, DH, and JH) that encode heavy-chain variable regions. The heavy-chain constant region (CH) encoded by lambda XIg8 has the characteristic features of C mu, including a four-domain structure and a carboxyl-terminal tail. The amino acid sequences of two mu-chain peptides agree with the cDNA sequence. The identity in amino acid sequence between the corresponding Xenopus and mouse C mu domains ranges from 31 to 47%. The C mu domains vary in the extent to which their sequences resemble the sequences of other immunoglobulins, consistent with previous suggestions that the immunoglobulin domains have an independent evolutionary history.
MASS SPECTROMETRY OF PEPTIDES AND PROTEINS (1992)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Investigating Haze-Relevant Features in a Learning Framework for Image Dehazing (2014)

Haze is one of the major factors that degrade outdoor images. Removing haze from a single image is known to be severely ill-posed, and assumptions made in previous methods do not hold in many situations. In this paper, we systematically investigate different haze-relevant features in a learning framework to identify the best feature combination for image dehazing. We show that the dark-channel feature is the most informative one for this task, which confirms the observation of He et al. [8] from a learning perspective, while other haze-relevant features also contribute significantly in a complementary way. We also find that surprisingly, the synthetic hazy image patches we use for feature investigation serve well as training data for realworld images, which allows us to train specific models for specific applications. Experiment results demonstrate that the proposed algorithm outperforms state-of-the-art methods on both synthetic and real-world datasets.
Felbamate and tremor (1995)

To the Editor: I read with interest the article by Kerrick et al [1] concerning two cases of involuntary movement, one with choreoathetosis and the other with an acute dystonic reaction. …
Differential Effects of Tamoxifen and Analogs with Nonbasic Side Chains on Cell Proliferationin Vitro (1985)

Structural analogs of the nonsteroidal antiestrogen tamoxifen, in which the basic dimethylaminoethoxy side chain was either absent or replaced with a variety of nonbasic side chains, were examined for their ability to inhibit the proliferation of a hormonally responsive cell line, MCF 7 human breast cancer. The degree of inhibition was compared with relative binding affinities for the estrogen receptor (RE) and a microsomal antiestrogen binding site (AEBS). All modifications resulted in loss of detectable affinity for AEBS. Replacement of the basic side chain of tamoxifen with a series of nonbasic side chains reduced affinity for RE by 78-93% except in the case of 1-(4-(1,2-diphenylbut-1-enyl)phenyl)-2,3-butanediol (ICI 145-680) where affinity was unchanged. When the basic side chain of tamoxifen was replaced by a hydroxyl group, to form the estrogenic analog ICI 141389 (Metabolite E), affinity for RE was reduced by 39%. ICI 141389 was a very weak inhibitor of MCF 7 cell growth, showing no significant growth inhibition at concentrations less than 10 microM. Despite the fact that ICI 145680 and tamoxifen had identical affinities for RE, ICI 145680 was a significantly weaker growth inhibitor than tamoxifen over the concentration range studied, i.e. 0.1-20 microM. Differences in potency were greatest at concentrations greater than 7.5 microM where the effects were not reversed by estradiol and where cytotoxicity played a major role in the decrease in cell numbers induced by tamoxifen. Like tamoxifen, ICI 145680 demonstrated both estrogen-reversible (at concentrations between 0.5-7.5 microM) and estrogen-irreversible (10-20 microM) inhibition of MCF 7 cell proliferation which was associated with a concentration-dependent accumulation of cells in the G0/G1 phase of the cell cycle. In contrast to tamoxifen, however, ICI 145680 appeared not to possess cytotoxic activity. Whereas ICI 145680 was without effect on proliferation of the RE negative human breast cancer cell line, MDA-MB-330, at doses less than 20 microM, tamoxifen inhibited growth at concentrations greater than 5 microM, but with changes in cell cycle kinetic parameters that were markedly different from those seen in RE positive cells.(ABSTRACT TRUNCATED AT 400 WORDS)
A conserved leucine zipper-like motif accounts for strong tetramerization capabilities of SEPALLATA-like MADS-domain transcription factors (2018)

The development of angiosperm flowers is regulated by homeotic MIKC-type MADS-domain transcription factors that activate or repress target genes via the formation of DNA-bound, organ-specific tetrameric complexes. The protein-protein interaction (PPI) capabilities differ considerably between different MIKC-type proteins. In Arabidopsis thaliana the floral homeotic protein SEPALLATA3 (SEP3) acts as a hub that incorporates numerous other MADS-domain proteins into tetrameric complexes that would otherwise not form. However, the molecular mechanisms that underlie these promiscuous interactions remain largely unknown. In this study, we created a collection of amino acid substitution mutants of SEP3 to quantify the contribution of individual residues on protein tetramerization during DNA-binding, employing methods of molecular biophysics. We show that leucine residues at certain key positions form a leucine-zipper structure that is essential for tetramerization of SEP3, whereas the introduction of physicochemically very similar residues at respective sites impedes the formation of DNA-bound tetramers. Comprehensive molecular evolutionary analyses of MADS-domain proteins from a diverse set of flowering plants revealed exceedingly high conservation of the identified leucine residues within SEP3-subfamily proteins throughout angiosperm evolution. In contrast, MADS-domain proteins that are unable to tetramerize among themselves exhibit preferences for other amino acids at homologous sites. Our findings indicate that the subfamily-specific conservation of amino acid residues at just a few key positions accounts for subfamily-specific interaction capabilities of MADS-domain transcription factors and this has shaped the present-day structure of the PPI network controlling flower development.
Anti-C1q antibodies in systemic lupus erythematosus (2014)

Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.
Fast and Non-Toxic In Situ Hybridization without Blocking of Repetitive Sequences (2012)

Formamide is the preferred solvent to lower the melting point and annealing temperature of nucleic acid strands in in situ hybridization (ISH). A key benefit of formamide is better preservation of morphology due to a lower incubation temperature. However, in fluorescence in situ hybridization (FISH), against unique DNA targets in tissue sections, an overnight hybridization is required to obtain sufficient signal intensity. Here, we identified alternative solvents and developed a new hybridization buffer that reduces the required hybridization time to one hour (IQFISH method). Remarkably, denaturation and blocking against repetitive DNA sequences to prevent non-specific binding is not required. Furthermore, the new hybridization buffer is less hazardous than formamide containing buffers. The results demonstrate a significant increased hybridization rate at a lowered denaturation and hybridization temperature for both DNA and PNA (peptide nucleic acid) probes. We anticipate that these formamide substituting solvents will become the foundation for changes in the understanding and performance of denaturation and hybridization of nucleic acids. For example, the process time for tissue-based ISH for gene aberration tests in cancer diagnostics can be reduced from days to a few hours. Furthermore, the understanding of the interactions and duplex formation of nucleic acid strands may benefit from the properties of these solvents.
Long-term testing of an intracranial pressure monitoring device (2000)

The authors demonstrate a new implantable solid-state sensor that reliably measures ICP for months, with minimal drift. The clinical application of this sensor and its telemetry is for long-term monitoring of patients with head injury, mass lesions, and hydrocephalus.
Cell-Free Approach To Antibody-Drug Conjugates (2013)

RETURN TO ISSUENewsNEXTCell-Free Approach To Antibody-Drug ConjugatesCite this: Chem. Eng. News 2013, 91, 44, XXX-XXXPublication Date (Print):November 4, 2013Publication History Published online31 March 2014Published inissue 4 November 2013https://pubs.acs.org/doi/10.1021/cen-09144-bus3https://doi.org/10.1021/cen-09144-bus3newsACS PublicationsCopyright © 2013 Chemical & Engineering NewsArticle Views11Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Cancer therapy Get e-Alerts
Regulation of sorting and post-Golgi trafficking of rhodopsin by its C-terminal sequence QVS(A)PA (1998)

Several mutations that cause severe forms of the human disease autosomal dominant retinitis pigmentosa cluster in the C-terminal region of rhodopsin. Recent studies have implicated the C-terminal domain of rhodopsin in its trafficking on specialized post-Golgi membranes to the rod outer segment of the photoreceptor cell. Here we used synthetic peptides as competitive inhibitors of rhodopsin trafficking in the frog retinal cell-free system to delineate the potential regulatory sequence within the C terminus of rhodopsin and model the effects of severe retinitis pigmentosa alleles on rhodopsin sorting. The rhodopsin C-terminal sequence QVS(A)PA is highly conserved among different species. Peptides that correspond to the C terminus of bovine (amino acids 324-348) and frog (amino acids 330-354) rhodopsin inhibited post-Golgi trafficking by 50% and 60%, respectively, and arrested newly synthesized rhodopsin in the trans-Golgi network. Peptides corresponding to the cytoplasmic loops of rhodopsin and other control peptides had no effect. When three naturally occurring mutations: Q344ter (lacking the last five amino acids QVAPA), V345M, and P347S were introduced into the frog C-terminal peptide, the inhibitory activity of the peptides was no longer detectable. These observations suggest that the amino acids QVS(A)PA comprise a signal that is recognized by specific factors in the trans-Golgi network. A lack of recognition of this sequence, because of mutations in the last five amino acids causing autosomal dominant retinitis pigmentosa, most likely results in abnormal post-Golgi membrane formation and in an aberrant subcellular localization of rhodopsin.