gebhart/patrepeval huggingface dataset:
Bio‐Inspired, Smart, Multiscale Interfacial Materials (2008)

Abstract In this review a strategy for the design of bioinspired, smart, multiscale interfacial (BSMI) materials is presented and put into context with recent progress in the field of BSMI materials spanning natural to artificial to reversibly stimuli‐sensitive interfaces. BSMI materials that respond to single/dual/multiple external stimuli, e.g., light, pH, electrical fields, and so on, can switch reversibly between two entirely opposite properties. This article utilizes hydrophobicity and hydrophilicity as an example to demonstrate the feasibility of the design strategy, which may also be extended to other properties, for example, conductor/insulator, p‐type/n‐type semiconductor, or ferromagnetism/anti‐ferromagnetism, for the design of other BSMI materials in the future.
Chlorobiphenyl-desleucyl-vancomycin inhibits the transglycosylation process required for peptidoglycan synthesis in bacteria in the absence of dipeptide binding (2000)

Novel glycopeptide analogs are known that have activity on vancomycin resistant enterococci despite the fact that the primary site for drug interaction, d-ala-d-ala, is replaced with d-ala-d-lactate. The mechanism of action of these compounds may involve dimerization and/or membrane binding, thus enhancing interaction with d-ala-d-lactate, or a direct interaction with the transglycosylase enzymes involved in peptidoglycan polymerization. We evaluated the ability of vancomycin (V), desleucyl-vancomycin (desleucyl-V), chlorobiphenyl-vancomycin (CBP-V), and chlorobiphenyl-desleucyl-vancomycin (CBP-desleucyl-V) to inhibit (a) peptidoglycan synthesis in vitro using UDP-muramyl-pentapeptide and UDP-muramyl-tetrapeptide substrates and (b) growth and peptidoglycan synthesis in vancomycin resistant enterococci. Compared to V or CBP-V, CBP-desleucyl-V retained equivalent potency in these assays, whereas desleucyl-V was inactive. In addition, CBP-desleucyl-V caused accumulation of N-acetylglucosamine-β-1,4-MurNAc-pentapeptide-pyrophosphoryl-undecaprenol (lipid II). These data show that CBP-desleucyl-V inhibits peptidoglycan synthesis at the transglycosylation stage in the absence of binding to dipeptide.
Hereditary cystatin C amyloid angiopathy: monitoring the presence of the Leu-68→Gln cystatin C variant in cerebrospinal fluids and monocyte cultures by MS (1998)

Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant condition in which the patients suffer at an early age from repeated cerebral haemorrhages. The development of HCCAA is directly linked to a Leu-68-->Gln (L68Q) mutation in the cystatin C protein sequence. The concentration of cystatin C in cerebrospinal fluid (CSF) of HCCAA patients is markedly diminished and cultivated monocytes from affected individuals accumulate cystatin C. The goal of this work was to characterize cystatin C isolated from CSF and monocyte cultures originating from healthy persons and HCCAA patients with respect to the L68Q mutation. Cystatin C was isolated by carboxymethylpapain affinity chromatography. Proteins from CSF and monocyte cultures that bound specifically to the carboxymethylated papain column were resolved by reverse-phase HPLC chromatography and tryptic peptides were subsequently analysed by matrix-assisted laser desorption ionization MS. No evidence for mutated cystatin C protein was found in CSF samples from healthy subjects or HCCAA patients, but approx. 60% of the protein was found to be hydroxylated on Pro-3. No evidence was found for secretion of mutated cystatin C from HCCAA monocytes. However, we obtained evidence for the presence of mutated cystatin C in HCCAA monocytes. These results support the conclusion that the mutated cystatin C is retained in association with the monocytes and not secreted. An increased intracellular concentration would presumably promote the aggregation and denaturation of the mutated cystatin C, leading to the formation of amyloid fibrils and cell death.
Onset of NIDDM occurs at Least 4–7 yr Before Clinical Diagnosis (1992)

These findings suggest that undiagnosed NIDDM is not a benign condition. Clinically significant morbidity is present at diagnosis and for years before diagnosis. During this preclinical period, treatment is not being offered for diabetes or its specific complications, despite the fact that reduction in hyperglycemia, hypertension, and cardiovascular risk factors is believed to benefit patients. Imprecise dating of diabetes onset also obscures investigations of the etiology of NIDDM and studies of the nature and importance of risk factors for diabetes complications.
Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory (2012)

One component of memory in the antibody system is long-lived memory B cells selected for the expression of somatically mutated, high-affinity antibodies in the T cell-dependent germinal center (GC) reaction. A puzzling observation has been that the memory B cell compartment also contains cells expressing unmutated, low-affinity antibodies. Using conditional Bcl6 ablation, we demonstrate that these cells are generated through proliferative expansion early after immunization in a T cell-dependent but GC-independent manner. They soon become resting and long-lived and display a novel distinct gene expression signature which distinguishes memory B cells from other classes of B cells. GC-independent memory B cells are later joined by somatically mutated GC descendants at roughly equal proportions and these two types of memory cells efficiently generate adoptive secondary antibody responses. Deletion of T follicular helper (Tfh) cells significantly reduces the generation of mutated, but not unmutated, memory cells early on in the response. Thus, B cell memory is generated along two fundamentally distinct cellular differentiation pathways. One pathway is dedicated to the generation of high-affinity somatic antibody mutants, whereas the other preserves germ line antibody specificities and may prepare the organism for rapid responses to antigenic variants of the invading pathogen.
Cancer DNA in the Circulation (2017)

This JAMA Insights article explains cell-free circulating tumor DNA and its utility in noninvasive cancer detection and characterization, prediction of treatment response, monitoring of disease relapse, and identification of mechanisms of resistance to targeted therapies.
Roy Campbell, John Davidson, and"The Flaming Terrapin" (1993)

A partir du reseau d'influences litteraires constitue par l'integration shawienne de la doctine du surhomme a l'evolutionnisme creatif et par le rapprochement davidsonien entre vitalisme heroique et materialisme, l'auteur met en evidence la revision nitzcheenne de l'imperialisme et de l'aristocratisme anglais dans The Flaming Terrapin de R. Campbell
EPIGENETICS AND HUMAN DISEASE (2004)

Epigenetics is comprised of the stable and heritable (or potentially heritable) changes in gene expression that do not entail a change in DNA sequence. The role of epigenetics in the etiology of human disease is increasingly recognized with the most obvious evidence found for genes subject to genomic imprinting. Mutations and epimutations in imprinted genes can give rise to genetic and epigenetic phenotypes, respectively; uniparental disomy and imprinting defects represent epigenetic disease phenotypes. There are also genetic disorders that affect chromatin structure and remodeling. These disorders can affect chromatin in trans or in cis, as well as expression of both imprinted and nonimprinted genes. Data from Angelman and Beckwith-Wiedemann syndromes and other disorders indicate that a monogenic or oligogenic phenotype can be caused by a mixed epigenetic and genetic and mixed de novo and inherited (MEGDI) model. The MEGDI model may apply to some complex disease traits and could explain negative results in genome-wide genetic scans.
Detection of homologous proteins by an intermediate sequence search (2003)

We developed a variant of the intermediate sequence search method (ISS(new)) for detection and alignment of weakly similar pairs of protein sequences. ISS(new) relates two query sequences by an intermediate sequence that is potentially homologous to both queries. The improvement was achieved by a more robust overlap score for a match between the queries through an intermediate. The approach was benchmarked on a data set of 2369 sequences of known structure with insignificant sequence similarity to each other (BLAST E-value larger than 0.001); 2050 of these sequences had a related structure in the set. ISS(new) performed significantly better than both PSI-BLAST and a previously described intermediate sequence search method. PSI-BLAST could not detect correct homologs for 1619 of the 2369 sequences. In contrast, ISS(new) assigned a correct homolog as the top hit for 121 of these 1619 sequences, while incorrectly assigning homologs for only nine targets; it did not assign homologs for the remainder of the sequences. By estimate, ISS(new) may be able to assign the folds of domains in approximately 29,000 of the approximately 500,000 sequences unassigned by PSI-BLAST, with 90% specificity (1 - false positives fraction). In addition, we show that the 15 alignments with the most significant BLAST E-values include the nearly best alignments constructed by ISS(new).
Electric Transport and Oxygen Permeation Properties of Lanthanum Cobaltite Membranes Synthesized by Different Methods (2000)

Dense perovskite-structured membranes with desired composition of La0.8Sr0.2Co0.6Fe0.4O3-δ (LSCF) were prepared from powders produced by four different methods. LSCF powders prepared by citrate, solid-state, and spray−pyrolysis methods had compositions close to the desired stoichiometry with a slight difference in cobalt concentration, whereas coprecipitated powders had a large strontium deficiency. The membrane composition was a determining factor that affected the electronic conductivity and therefore oxygen permeability. The membrane with a large strontium deficiency had much lower electronic conductivity and oxygen permeability (ionic conductivity) than the other three membranes with compositions close to the desired stoichiometry. The electronic conductivity of membranes prepared from citrate, solid-state, and spray−pyrolysis methods increases with the cobalt concentration of the membrane. For the three membranes with similar composition, the activation energy of oxygen flux decreases with increasing grain size. Oxygen pressure dependency of oxygen vacancy concentration is also influenced by the membrane microstructure and composition. LSCF membranes with same composition and similar microstructure should have similar electric and oxygen transport properties.
Photostick: a method for selective isolation of target cells from culture (2015)

Sorting of target cells from a heterogeneous pool is technically difficult when the selection criterion is complex, e.g. a dynamic response, a morphological feature, or a combination of multiple parameters. At present, mammalian cell selections are typically performed either via static fluorescence (e.g. fluorescence activated cell sorter), via survival (e.g. antibiotic resistance), or via serial operations (flow cytometry, laser capture microdissection). Here we present a simple protocol for selecting cells based on any static or dynamic property that can be identified by video microscopy and image processing. The "photostick" technique uses a cell-impermeant photochemical crosslinker and digital micromirror array-based patterned illumination to immobilize selected cells on the culture dish. Other cells are washed away with mild protease treatment. The crosslinker also labels the selected cells with a fluorescent dye and a biotin for later identification. The photostick protocol preserves cell viability, permits genetic profiling of selected cells, and can be performed with complex functional selection criteria such as neuronal firing patterns.
Expression and Functional Significance of Tumor Necrosis Factor Receptors in Human Myocardium (1995)

Results of the present study show that the adult human heart expresses both mRNA and receptor proteins for TNFR1 and TNFR2; moreover, the negative inotropic effects of TNF-alpha in adult cardiac myocytes appear to be initiated by activation of TNFR1.
Original Chemical Series of Pyrimidine Biosynthesis Inhibitors That Boost the Antiviral Interferon Response (2017)

<i>De novo</i> pyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1<i>H</i>-indol-3-yl)-2,3-dihydro-4<i>H</i>-furo[3,2-<i>c</i>]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit broad-spectrum antiviral activity and immunostimulatory properties, in line with recent reports linking <i>de novo</i> pyrimidine biosynthesis with innate defense mechanisms against viruses. Most importantly, we establish that pyrimidine deprivation can amplify the production of both type I and type III interferons by cells stimulated with retinoic acid-inducible gene 1 (RIG-I) ligands. Altogether, our results further expand the current panel of pyrimidine biosynthesis inhibitors and illustrate how the production of antiviral interferons is tightly coupled to this metabolic pathway. Functional and structural similarities between this new chemical series and dicoumarol, which was reported before to inhibit pyrimidine biosynthesis at the dihydroorotate dehydrogenase (DHODH) step, are discussed.
Nuclear and nucleolar targeting sequences of c-erb-A, c-myb, N-myc, p53, HSP70, and HIV tat proteins (1989)

Protein import into the cell nucleus requires specific binding of nuclear proteins to the nuclear pore complex. Based on amino acid sequence "motifs" of known nuclear targeting signals, we identified peptides within a number of nuclear proteins with likely nuclear targeting potential and tested their function by transfecting into cells fusion genes that produce the cytoplasmic "reporter" protein, pyruvate kinase (PK), joined to the test sequence. Sequences within c-myb (PLLKKIKQ), N-myc (PPQKKIKS), p53 (PQPKKKP), and c-erb-A (SKRVAKRKL) oncoproteins that direct PK hybrids into the nucleus were identified. A peptide (GRKKRRQRRRAP) of the human immunodeficiency virus (HIV) tat protein (Tat), which contains two short basic regions, targets fusion proteins to the nucleolus. The COOH-terminal basic Tat region (QRRRAP) does not target PK hybrid proteins into the nucleus, but mutation of two basic amino acids in this region decreases but does not abolish nucleolar accumulation mediated by the entire Tat nucleolar targeting sequence. Moreover, the c-Myc nuclear targeting sequence fused to the COOH-terminal basic Tat region (PAAKRVKLDQRRRAP) effectively localizes PK hybrids to the nucleus and nucleolus. A similar sequence (FKRKHKKDISQNKRAVRR) in the human heat-shock protein HSP70 also localizes PK to the nucleus and nucleolus.
Biochemical basis of the constitutive repressor cleavage activity of recA730 protein. A comparison to recA441 and recA803 proteins. (1992)

The recA730 mutation results in constitutive SOS and prophage induction. We examined biochemical properties of recA730 protein in an effort to explain the constitutive activity observed in recA730 strains. We find that recA730 protein is more proficient than the wild-type recA protein in the competition with single-stranded DNA binding protein (SSB protein) for single-stranded DNA (ssDNA) binding sites. Because an increased aptitude in the competition with SSB protein has been previously reported for recA441 protein and recA803 protein, we directly compared their in vitro activities with those of recA730 protein. At low magnesium ion concentration, both ATP hydrolysis and lexA protein cleavage experiments demonstrate that these recA proteins displace SSB protein from ssDNA in a manner consistent with their in vivo repressor cleavage activity, i.e. recA730 protein > recA441 protein > recA803 protein > recAwt protein. Additionally, a correlation exists between the proficiency of the recA proteins in SSB protein displacement and their rate of association with ssDNA. We propose that an increased rate of association with ssDNA allows recA730 protein to displace SSB protein from the ssDNA that occurs naturally in Escherichia coli and thereby to become activated for the repressor cleavage that leads to SOS induction. RecA441 protein is similarly activated for repressor cleavage; however, in this case, significant SSB protein displacement occurs only at elevated temperature. At physiological magnesium ion concentration, we argue that recA803 protein and wild-type recA protein do not displace sufficient SSB protein from ssDNA to constitutively induce the SOS response.
Combining two repurposed drugs as a promising approach for Alzheimer's disease therapy (2015)

Alzheimer disease (AD) represents a major medical problem where mono-therapeutic interventions demonstrated only a limited efficacy so far. We explored the possibility of developing a combinational therapy that might prevent the degradation of neuronal and endothelial structures in this disease. We argued that the distorted balance between excitatory (glutamate) and inhibitory (GABA/glycine) systems constitutes a therapeutic target for such intervention. We found that a combination of two approved drugs - acamprosate and baclofen - synergistically protected neurons and endothelial structures in vitro against amyloid-beta (Aβ) oligomers. The neuroprotective effects of these drugs were mediated by modulation of targets in GABA/glycinergic and glutamatergic pathways. In vivo, the combination alleviated cognitive deficits in the acute Aβ25-35 peptide injection model and in the mouse mutant APP transgenic model. Several patterns altered in AD were also synergistically normalised. Our results open up the possibility for a promising therapeutic approach for AD by combining repurposed drugs.
ATP, an extracellular signaling molecule in red blood cells: A messenger for malaria? (2014)

Adenosine 5' triphosphate (ATP), discovered in 1929 by Karl Lohmannest, is described as an essential energy source for cells. In the biochemistry of all living organisms, ATP hydrolysis provides the energy required for the chemical reactions of metabolism. It is the precursor of a number of essential enzyme cofactors, such as nicotinamide adenine dinucleotide (NAD + ) and coenzyme A [NAD + , flavin adenine dinucleotide (FAD), and is ATP coenzyme A are all formed from ATP] and is the source of the phosphoryl group in most kinase-mediated phosphorylation reactions. Another essential, but less known function is that ATP plays a very important role as an extracellular signaling molecule, allowing cells and tissues to communicate. ATP is converted into cAMP, a major second messenger involved in many cellular processes, by adenylyl cyclase, a membrane-associated enzyme. In this review, we describe the role of ATP as a beneficial extracellular molecule released by healthy red blood cells (RBCs) in response to hypoxia to mediate a vasodilator signal, by oxidatively stressed RBCs, and by Plasmodium falciparum-infected RBCs (iRBCs), and its similarity with released ATP that by the combined action of the ectonucleotidases CD39 and CD73 is converted to adenosine that mediates sickling in sickle cell disease (SCD).
Stimulation of tyrosine phosphorylation and accumulation of GTP-bound p21ras upon antibody-mediated alpha 2 beta 1 integrin activation in T-lymphoblastic cells. (1993)

Integrins are a family of heterodimeric integral plasma membrane proteins that behave as receptors for components of the extracellular matrix and also mediate cell to cell adhesion. Occupation of integrins can result in the transduction of intracellular signals, leading to cytoskeletal reorganization, tyrosine phosphorylation, and induction of gene expression. We report here that the ligation of alpha 2 beta 1 integrin by collagen-adhesion stimulatory anti-alpha 2 and anti-beta 1 antibodies resulted in the accumulation of p21ras in the active GTP-bound state in Jurkat T-lymphoblastoid cells. The activation was accompanied by the tyrosine phosphorylation of proteins of 47-52 kDa. This stimulation of tyrosine phosphorylation and p21ras activation was specific for the activating antibodies and occurred within 2 min of the addition of these antibodies. Although treatment of the cells with the protein kinase C activator, phorbol 12-myristate 13-acetate also resulted in an induction of both cell attachment to collagen and of p21ras activation, tyrosine phosphorylation was not observed. These results demonstrate that alpha 2 beta 1 integrin activation can result in the specific stimulation of tyrosine phosphorylation of 47-52-kDa proteins, as well as activation of a signaling pathway involving p21ras.
Use of phlebotomy treatment in Atlantic bottlenose dolphins with iron overload (2009)

Although the cause of the iron overload and high serum aminotransferase activities remained unknown, phlebotomy treatment successfully resolved the clinicopathologic abnormalities, supporting a role of iron overload in the hepatopathy of the 3 dolphins.
Multilayered Films Fabricated from Combinations of Degradable Polyamines:  Tunable Erosion and Release of Anionic Polyelectrolytes (2006)

This investigation sought to develop methods that permit broad and tunable control over the erosion of multilayered polyelectrolyte assemblies and the release of anionic polymers in physiologically relevant media. We report the fabrication and characterization of multilayered films ~60 nm thick using sodium poly(styrene sulfonate) (SPS) and different combinations of three different hydrolytically degradable polyamines (1-3). We investigated two different approaches to film fabrication: 1) fabrication using solutions comprised of defined mixtures of two different polyamines, and 2) fabrication of films composed of different numbers of layers of two different polyamines. In general, films fabricated using polyamine solutions composed of defined mixtures of two different polyamines had erosion and release profiles that were dictated almost entirely by the most hydrophobic polyamine used to fabricate the films. In contrast, the fabrication of films having different numbers of layers of different polyamines permitted broad and tunable control over film erosion and the release of SPS. For example, films having the architecture (1/SPS)(n)(2/SPS)(m) released SPS with profiles that were intermediate to those of films fabricated exclusively from polymer 1 or polymer 2. Further, we demonstrated that it is possible to exert systematic control over the release of SPS by varying the relative numbers of layers of (1/SPS) or (2/SPS) incorporated into the films. The approaches reported here provide tunable control over the rate of the release of anionic polymers from surfaces coated with ultrathin multilayered films. This work could, with further development, contribute to the design of ultrathin films that permit tunable control over the release and delivery of therapeutically relevant macromolecules, such as proteins or DNA, from surfaces.