gebhart/patrepeval huggingface dataset:
Isolation of peptide aptamers that inhibit intracellular processes (2000)

We have developed a method for isolation of random peptides that inhibit intracellular processes in bacteria. A library of random peptides expressed as fusions to Escherichia coli thioredoxin (aptamers) were expressed under the tight control of the arabinose-inducible P(BAD) promoter. A selection was applied to the library to isolate aptamers that interfered with the activity of thymidylate synthase (ThyA) in vivo. Expression of an aptamer isolated by this method resulted in a ThyA(-) phenotype that was suppressed by simultaneous overexpression of ThyA. Two-hybrid analysis showed that this aptamer is likely to interact with ThyA in vivo. The library also was screened for aptamers that inhibited growth of bacteria expressing them, and five such aptamers were characterized. Four aptamers were bacteriostatic when expressed, whereas one showed a bactericidal effect. Introduction of translational stop codons into various aptamers blocked their activity, suggesting that their biological effects were likely to be due to protein aptamer rather than RNA. Combinatorial aptamers provide a new genetic and biochemical tool for identifying targets for antibacterial drug development.
A superior synthesis of diaryl ethers by the use of ultrasound in the Ullmann reaction (1992)

The use of ultrasound in the reactions of phenols with bromoarenes, in the presence of potassium carbonate and copper(I) iodide but without added solvent, gives better yields of diaryl ethers(typically 70–90%), at lower temperature (140 °C) than is customary for traditional Ullmann reactions; the role of ultrasound is primarily to break up the particles of the inorganic solids.
Tomostatics: Turning-ray tomography + static corrections (1992)

Applications of tomographic velocities to static corrections have drawn much attention recently. In Computing field statics with the help of seismic tomography (Geophysical Prospecting 1987), W.N. de Amorin et al. showed that the waves refracted at the base of a low-velocity layer can be used successfully for computing and refining field static corrections. In Tomographic inversion for velocity plus statics (SEG Expanded Abstracts 1991), Livia Squires et al. pointed out that velocity variations and static shifts caused by near-surface effects and positional uncertainties can be solved simultaneously using constraint tomography.
Receptor-Mediated Peptide Transport through the Blood-Brain Barrier* (1986)

THERE are at least two incentives for investigating the mechanisms of transport of peptides through the brain capillary wall, i.e. the blood-brain barrier (BBB). First, it is important to understand how circulating peptides, such as insulin, insulin-like growth factors (IGFs), transferrin, angiotensinogen, PTH, or others affect the brain, and these effects must necessarily involve the interface between blood and brain. Second, the vast promise of peptides as neuropharmaceuticals has not been realized, and this is due, in large part, to the fact that virtually all of the potential peptide pharmaceuticals are water soluble and, thus, are substantially excluded from entry into brain by the BBB. However, a major purpose of this review is to emphasize that knowledge of the physiological mechanisms that mediate the transport of peptides through the BBB may lead to the development of new strategies for delivery of peptide pharmaceuticals to brain.
Antibody recognition of carbohydrate epitopes (2015)

Carbohydrate antigens are valuable as components of vaccines for bacterial infectious agents and human immunodeficiency virus (HIV), and for generating immunotherapeutics against cancer. The crystal structures of anti-carbohydrate antibodies in complex with antigen reveal the key features of antigen recognition and provide information that can guide the design of vaccines, particularly synthetic ones. This review summarizes structural features of anti-carbohydrate antibodies to over 20 antigens, based on six categories of glyco-antigen: (i) the glycan shield of HIV glycoproteins; (ii) tumor epitopes; (iii) glycolipids and blood group A antigen; (iv) internal epitopes of bacterial lipopolysaccharides; (v) terminal epitopes on polysaccharides and oligosaccharides, including a group of antibodies to Kdo-containing Chlamydia epitopes; and (vi) linear homopolysaccharides.
Preparation of Narrow Size Distribution Silica Particles Using Microemulsions (1997)

Monodisperse silica particles were prepared in microemulsion media using block copolymers and nonionic surfactants. The silica particles were obtained by hydrolysis and condensation of tetraethoxysilane, using NH3 as a catalyst, and they were characterized by optical and electron microscopy, nitrogen sorption, Fourier transform infrared spectroscopy and thin-layer chromatography. Particles, with average sizes from 0.1 to 1.5 μm and with specific surfaces lower than 100 m2/g could be obtained. The results showed that the size could be controlled by both the cosurfactant chain length and concentration. The higher the cosurfactant concentration and the shorter the chain length, the larger the particles. This has been attributed to the increase of interfacial flexibility with reduction of chain length. This causes an increase in the velocity of particle growth, then producing larger particles.
Stimulation of glycogen synthesis by insulin in human erythroleukemia cells requires the synthesis of glycosyl-phosphatidylinositol. (1994)

Although the insulin-dependent hydrolysis of glycosyl-phosphatidylinositol (GPI) may play an important role in insulin action, an absolute requirement for this glycolipid has not been demonstrated. Human K562 cells were mutated to produce a cell line (IA) incapable of the earliest step in PI glycosylation, the formation of PI-GlcNAc. Another cell line (IVD) was deficient in the deacetylation of PI-GlcNAc to form PI-GlcN and subsequent mannosylated species. Each line was transfected with wild-type human insulin receptors. Similar insulin-stimulated receptor autophosphorylation was observed in all three lines, along with a nearly identical increase in the association of phosphorylated insulin receptor substrate 1 with endogenous PI 3-kinase. Both normal and GPI-defective lines also displayed a similar 2- to 3-fold increase in phosphorylation of the Shc protein and its association with growth factor receptor-bound protein 2 in response to insulin. In contrast to these results, striking differences were noted in insulin-stimulated glycogen synthesis. In normal cells, glycogen synthesis was significantly increased by insulin, whereas no insulin stimulation was observed in GPI-deficient IA cells, and only a trace of stimulation was detected in IVD cells. These results indicate that tyrosine phosphorylation produced by insulin is not dependent on GPI synthesis, and this effect is not sufficient to elicit at least some of the metabolic effects of the hormone. In contrast, GPI synthesis is required for the stimulation of glycogen synthesis by insulin in these cells. These findings support the existence of divergent pathways in the action of insulin.
The effect of aglycosylation on the binding of mouse IgG to staphylococcal protein A (1983)

Aglycosylated IgG produced by hybridoma cells cultured in the presence of tunicamycin was compared with normal IgG for its ability to bind to staphylococcal protein A. No differences were found in binding or elution profiles. It is concluded that aglycosylation does not produce major structural alterations at the CH2-CH3 interface of the Fc region of IgG.
Identification and Functional Characterization of Distinct Critically Important Bone Morphogenetic Protein-specific Response Elements in the Id1 Promoter (2002)

Transforming growth factor-beta (TGF-beta) family members, which include bone morphogenetic proteins (BMPs) and TGF-betas, elicit their cellular effects by activating specific Smad proteins, which control the transcription of target genes. BMPs and TGF-betas have overlapping as well as specific effects on mesenchymal cell differentiation for which the mechanisms are incompletely understood. Here we report that Id1, a dominant negative inhibitor of basic helix-loop-helix proteins, is a direct target gene for BMP. BMP, but not TGF-beta, strongly activates the Id1 promoter in an Smad-dependent manner. We identified two BMP-responsive regions in the mouse Id1 promoter, which contain three distinct sequence elements; one region contains two Smad binding elements (SBEs), and the other region contains a GGCGCC palindromic sequence flanked by two CAGC and two CGCC motifs. Whereas SBEs and GGCGCC sequence are critically important, the CAGC and CGCC motifs are needed for efficient BMP-induced Id1 promoter activation. Smads are part of nuclear transcription factor complexes that specifically bind to SBEs and GGCGCC sequence in response to BMP but not TGF-beta. Multimerization of the all three distinct sequence motifs is needed to generate a highly sensitive and BMP/Smad-dependent specific enhancer. Our results provide important new insights into how the BMP/Smad pathway can specifically activate target genes.
Novel human monoclonal antibodies to insulin-like growth factor (IGF)-II that potently inhibit the IGF receptor type I signal transduction function (2006)

The insulin-like growth factor (IGF) system plays an important role in a variety of physiologic processes and in diseases such as cancer. Although the role of the IGF system in cancer has been recognized many years ago, components of the system have only recently been targeted and shown to affect cell transformation, proliferation, survival, motility, and migration in tissue cultures and in mouse models of cancer. We have been hypothesizing that targeting IGF-II in addition to blocking its interaction with the IGF receptor type I (IGF-IR) would also allow to block that portion of the signal transduction through the insulin receptor that is due to its interaction with IGF-II. Lowering its level may also not induce up-regulation of its production as for IGF-I. Finally, targeting a diffusable ligand as IGF-II may not require penetration of the antibody inside tumors but could shift the equilibrium to IGF-II complexed with antibody so the ligand concentration would decrease in the tumor environment without the need for the antibody to penetrate the tumor. Here, we describe the identification and characterization of three novel anti-IGF-II fully human monoclonal antibodies. They bound with high (subnanomolar) affinity to IGF-II, did not cross-react with IGF-I and insulin, and potently inhibited signal transduction mediated by the IGF-IR interaction with IGF-II. The most potent neutralizer, IgG1 m610, inhibited phosphorylation of the IGF-IR and the insulin receptor, as well as phosphorylation of the downstream kinases Akt and mitogen-activated protein kinase with an IC(50) of the order of 1 nmol/L at IGF-II concentration of 10 nmol/L. It also inhibited growth of the prostate cancer cell line DU145 and migration of the breast cancer line cells MCF-7. These results indicate an immunotherapeutic potential of IgG1 m610 likely in combination with other antibodies and anticancer drugs but only further experiments in mouse models of cancer and human clinical trials could evaluate this possibility.
Simulation optimization (2001)

In this tutorial introduction to simulation optimization, we present motivating and illustrative examples, summarize most of the major approaches, and briefly describe some software implementations. The focus is on issues and concepts, rather than mathematical rigor, so the format is Q & A rather than theorem-proof.
The Escherichia coli L-arabinose operon: binding sites of the regulatory proteins and a mechanism of positive and negative regulation. (1980)

The locations of DNA binding by the proteins involved with positive and negative regulation of transcription initiation of the L-arabinose operon in Escherichia coli have been determined by the DNase I protection method. Two cyclic AMP receptor protein sites were found, at positions -78 to -107 and -121 to -146, an araC protein--arabinose binding site was found at position -40 to -78, and an araC protein-fucose binding site was found at position -106 to -144. These locations, combined with in vivo data on induction of the two divergently oriented arabinose promoters, suggest the following regulatory mechanism: induction of the araBAD operon occurs when cyclic AMP receptor protein, araC protein, and RNA polymerase are all present and able to bind to DNA. Negative regulation is accomplished by the repressing form of araC protein binding to a site in the regulatory region such that it stimultaneously blocks access of cyclic AMP receptor protein to two sites on the DNA, one site of which serves each of the two promoters. Thus, from a single operator site, the negative regulator represses the two outwardly oriented ara promoters. This regulatory mechanism explains the known positive and negative regulatory properties of the ara promoters.
Circumsporozoite-Specific T Cell Responses in Children Vaccinated with RTS,S/AS01E and Protection against P falciparum Clinical Malaria (2011)

RTS,S/AS01(E) induces CS-specific Th1 T cell responses in young children living in a malaria endemic area. The combination of anti-CS antibody concentrations titers and CS-specific TNFα(+) CD4(+) T cells could account for the level of protection conferred by RTS,S/AS01(E). The correlation between CS-specific TNFα(+) CD4(+) T cells and protection needs confirmation in other datasets.
A minimal peach type II chlorophyll a/b-binding protein promoter retains tissue-specificity and light regulation in tomato (2007)

The minimal CAB19 promoter conferred GUS activity primarily in leaves and green fruit, as well as in response to light. GUS activity in the leaves of both Cab19 constructs averaged about 2/3 that observed with mas35S::GUS controls. Surprisingly, GUS activity in transgenic green fruit was considerably higher than leaves for all promoter constructs; however, in red, ripe fruit activities were much lower for the Cab19 promoter constructs than the mas35S::GUS. Although GUS activity was readily detectable in flowers and roots of mas35S::GUStransgenic plants, little activity was observed in plants carrying the Cab19 promoter constructs. In addition, the light-inducibility of the Cab19::GUS constructs indicated that all the requisite cis-elements for light responsiveness were contained on the Cab19 fragment. The minimal Cab19 promoter retains both tissue-specificity and light regulation and can be used to drive expression of foreign genes with minimal activity in mature, edible fruit.
Characterization of bacteriophage T4-coordinated leading- and lagging-strand synthesis on a minicircle substrate (2000)

The DNA replication complex of bacteriophage T4 has been assembled as a single unit on a minicircle substrate with a replication fork that permits an independent measurement of the amount of DNA synthesis on both the leading and lagging strands. The assembled replisome consists of the T4 polymerase [gene product 43 (gp43)], clamp protein (gp45), clamp loader (gp44/62), helicase (gp41), helicase accessory factor (gp59), primase (gp61), and single-stranded DNA binding protein (gp32). We demonstrate that on the minicircle the synthesis of the leading and lagging strands are coordinated and that the C-terminal domain of the gp32 protein regulates this coordination. We show that the reconstituted replisome encompasses two coupled holoenzyme complexes and present evidence that this coupling might include a gp43 homodimer interaction.
Effect of Cilazapril on the Proliferative Response After Vascular Damage (1993)

Cilazapril, a novel long-acting inhibitor of angiotensin-converting enzyme, markedly suppressed the proliferative response and neointima formation after balloon catheter-induced injury of the carotid artery in a rat model of angioplasty. The reduction in neointima was dose-dependent, required sustained high levels of enzyme inhibition, and was significantly greater in animals treated starting 6 days prior to the procedure than in animals starting treatment the day of catheterization. In experiments with vascular smooth-muscle cells (SMC) in culture, the addition of angiotensin II reduces increased mRNA levels for several growth factors and extracellular matrix proteins. Here we report that Ang II selectively induces mRNA for thrombospondin I, but not for thrombospondin II. Under selected conditions SMC can be induced to proliferate after exposure to Ang II, in vitro and in vivo. Using neutralizing anti transforming growth factor beta (TGF-beta) antibodies we found that Ang II stimulation of proliferation was threefold greater when the anti-TGF-beta was added to the cultures. We suggest (a) that an important effect of Ang II during the proliferative response is the induction of thrombospondin I, which is required for matrix interactions during the formation of neointima, and (b) that, among the complex array of growth factors potentially active in vivo, TGF-beta may be an important negative regulatory factor that limits the proliferative response and prevents restenosis in most cases of angioplasty.
Networking proteins in yeast (2001)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Interleukin-1 Mediates Pathological Effects of Microglia on Tau Phosphorylation and on Synaptophysin Synthesis in Cortical Neurons through a p38-MAPK Pathway (2003)

The presence of tangles of abnormally phosphorylated tau is a characteristic of Alzheimer's disease (AD), and the loss of synapses correlates with the degree of dementia. In addition, the overexpression of interleukin-1 (IL-1) has been implicated in tangle formation in AD. As a direct test of the requirement for IL-1 in tau phosphorylation and synaptophysin expression, IL-1 actions in neuron-microglia cocultures were manipulated. Activation of microglia with secreted beta-amyloid precursor protein or lipopolysaccharide elevated their expression of IL-1alpha, IL-1beta, and tumor necrosis factor alpha (TNFalpha) mRNA. When such activated microglia were placed in coculture with primary neocortical neurons, a significant increase in the phosphorylation of neuronal tau was accompanied by a decline in synaptophysin levels. Similar effects were evoked by treatment of neurons with recombinant IL-1beta. IL-1 receptor antagonist (IL-1ra) as well as anti-IL-1beta antibody attenuated the influence of activated microglia on neuronal tau and synaptophysin, but anti-TNFalpha antibody was ineffective. Some effects of microglial activation on neurons appear to be mediated by activation of p38 mitogen-activated protein kinase (p38-MAPK), because activated microglia stimulated p38-MAPK phosphorylation in neurons, and an inhibitor of p38-MAPK reversed the influence of IL-1beta on tau phosphorylation and synaptophysin levels. Our results, together with previous observations, suggest that activated microglia may contribute to neurofibrillary pathology in AD through their production of IL-1, activation of neuronal p38-MAPK, and resultant changes in neuronal cytoskeletal and synaptic elements.
Secure Isolation and Migration of Untrusted Legacy Applications (2004)

Sting applications often contain security holes that are not patched until after the system has already been compromised. Even when software updates are applied to address security issues, they often result in system services being unavailable for some time. To address these system security and availability issues, we have developed peas and pods. A pea provides a least privilege environment that can restrict processes to the minimal subset of system resources needed to run. This mechanism enables the creation of environments for privileged program execution that can help with intrusion prevention and containment. A pod provides a group of processes and associated users with a consistent, machine-independent virtualized environment. Pods are coupled with a novel checkpoint-restart mechanism which allows processes to be migrated across minor operating system kernel versions with different security patches. This mechanism allows system administrators the flexibility to patch their operating systems immediately without worrying over potential loss of data or needing to schedule system downtime. We have implemented peas and pods in Linux without requiring any application or operating system kernel changes. Our measurements on real world desktop and server applications demonstrate that peas and pods impose little overhead and enable secure isolation and migration of untrusted applications.
WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12 (2004)

The WHIM syndrome is a rare immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. Dominant heterozygous mutations of the gene encoding CXCR4, a G-protein-coupled receptor with a unique ligand, CXCL12, have been associated with this pathology. We studied patients belonging to 3 different pedigrees. Two siblings inherited a CXCR4 mutation encoding a novel C-terminally truncated receptor. Two unrelated patients were found to bear a wild-type CXCR4 open reading frame. Circulating lymphocytes and neutrophils from all patients displayed similar functional alterations of CXCR4-mediated responses featured by a marked enhancement of G-protein-dependent responses. This phenomenon relies on the refractoriness of CXCR4 to be both desensitized and internalized in response to CXCL12. Therefore, the aberrant dysfunction of the CXCR4-mediated signaling constitutes a common biologic trait of WHIM syndromes with different causative genetic anomalies. Responses to other chemokines, namely CCL4, CCL5, and CCL21, were preserved, suggesting that, in clinical forms associated with a wild-type CXCR4 open reading frame, the genetic anomaly might target an effector with some degree of selectivity for the CXCL12/CXCR4 axis. We propose that the sustained CXCR4 activity in patient cells accounts for the immune-hematologic clinical manifestations and the profusion of warts characteristic of the WHIM syndrome.
Apoptosis and Cell Senescence (2003)

This chapter contains sections titled: Introduction Apoptosis Cell Senescence Summary References
Robust entropy-based endpoint detection for speech recognition in noisy environments (1998)

This paper presents an entropy-based algorithm for accurate and robust endpoint detection for speech recognition under noisy environments. Instead of using the conventional energy-based features, the spectral entropy is developed to identify the speech segments accurately. Experimental results show that this algorithm outperforms the energy-based algorithms in both detection accuracy and recognition performance under noisy environments, with an average error rate reduction of more than 16%.