gebhart/patrepeval huggingface dataset:
Codon bias and plasticity in immunoglobulins (1997)

Immunoglobulin genes experience Darwinian evolution twice. In addition to the germline evolution all genes experience, immunoglobulins are subjected, upon exposure to antigen, to somatic hypermutation. This is accompanied by selection for high affinity to the eliciting antigen and frequently results in a significant increase in the specificity of the responding population. The hypermutation mechanism displays a strong sequence specificity. Thus arises the opportunity to manipulate codon bias in a site-specific manner so as to direct hypermutation to those parts of the gene that encode the antigen-binding portions of the molecule and away from those that encode the structurally conserved regions. This segregation of mutability would clearly be advantageous; it would enhance the generation of potentially useful variants while keeping mutational loss to acceptably low levels. But it is not clear that the advantage gained would be large enough to produce a measurable effect within the background stochasticity of the evolutionary process. I have performed a pair of statistical tests to determine whether site-specific codon bias in human immunoglobulin genes is correlated with the sequence specificity of the somatic mutation mechanism. The sequence specificity of the mutator was determined by analysis of a database of published immunoglobulin intron sequences that had experienced somatic mutation but not selection. The site-specific codon bias was determined by analysis of published sequences of human germline immunoglobulin V genes. Both tests strongly suggest that evolution has acted to enhance the plasticity of immunoglobulin genes under somatic hypermutation.
Conditioned Placebo Dose Reduction: A New Treatment in Attention-Deficit Hyperactivity Disorder? (2010)

Pairing placebos with stimulant medication elicits a placebo response that allows children with ADHD to be effectively treated on 50% of their optimal stimulant dose.
Atorvastatin Attenuates Bleomycin-Induced Pulmonary Fibrosis via Suppressing iNOS Expression and the CTGF (CCN2)/ERK Signaling Pathway (2013)

Pulmonary fibrosis is a progressive and fatal lung disorder with high mortality rate. To date, despite the fact that extensive research trials are ongoing, pulmonary fibrosis continues to have a poor response to available medical therapy. Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known for its broad pharmacological activities, remains a remedy against multiple diseases. The present study investigated the antifibrotic potential of atorvastatin against bleomycin-induced lung fibrosis and to further explore the possible underlying mechanisms. Our results showed that atorvastatin administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. Atorvastatin reduced malondialdehyde (MDA) level and lung indices. Atorvastatin also markedly decreased the expression of inducible nitric oxide synthase (iNOS) in lung tissues and, thus, prevented nitric oxide (NO) release in response to bleomycin challenge. Furthermore, atorvastatin exhibited target down-regulation of connective tissue growth factor (CTGF (CCN2)) and phosphorylation extracellular regulated protein kinases (p-ERK) expression. Taken together, atorvastatin significantly ameliorated bleomycin-induced pulmonary fibrosis in rats, via the inhibition of iNOS expression and the CTGF (CCN2)/ERK signaling pathway. The present study provides evidence that atorvastatin may be a potential therapeutic reagent for the treatment of lung fibrosis.
The role of the VQIVYK peptide in tau protein phosphorylation (2007)

Although it remains unclear whether they are related to one another, tau aggregation and phosphorylation are the main pathological hallmarks of the neuronal disorders known as tauopathies. The capacity to aggregate is impaired in a variant of the tau 3R isoform that lacks residues 306-311 (nomenclature for the largest CNS tau isoform) and hence, we have taken advantage of this feature to study how phosphorylation and aggregation may be related as well as the role of this six amino acid peptide (VQIVYK). Through these analyses, we found that the phosphorylation of the tau variant was higher than that of the complete tau protein and that not only the deletion of these residues, but also the interaction of these residues, in tau 3R, with thioflavin-S augmented tau phosphorylation by glycogen synthase kinase 3. In addition, the binding of the peptide containing the residues 306-311 to the whole tau protein provoked an increase in tau phosphorylation. This observation could be physiologically relevant as may suggest that tau-tau interactions, through those residues, facilitate tau phosphorylation. In summary, our data indicate that deletion of residues VQIVYK, in tau protein produces an increase in tau phosphorylation, without tau aggregation, because the VQIVYK peptide, that favors aggregation, is missing. On the other hand, when the whole tau protein interacts with thioflavin-S or the peptide VQIVYK, an increase in both aggregation and phosphorylation occurs.
First Observation of α‐Ca 2 [SiO 3 (OH)](OH)–Ca 6 [Si 2 O 7 ][SiO 4 ](OH) 2 Phase Transformation upon Thermal Treatment in Air (2007)

Thermal treatment transforms α‐Ca 2 [SiO 3 (OH)](OH) (α‐C 2 SH) into hydraulic Ca 2 SiO 4 polymorphs, which is a process of considerable interest to the cement chemistry community. The thermal behavior of differently synthesized samples of α‐C 2 SH in air at ambient pressure has been investigated in detail by high‐temperature powder X‐ray diffraction (XRD), synchrotron‐based infrared (IR) microspectroscopy of single crystals, trimethylsilylation method (TMSM), and thermal analysis. Powder XRD data on α‐C 2 SH samples heated to different temperatures between 300° and 500°C suggest coexistance of α‐C 2 SH and dellaite, Ca 6 [Si 2 O 7 ][SiO 4 ](OH) 2 . IR absorption bands typical for the initial α‐C 2 SH phase diminish over the course of thermal treatment, accompanied by the appearance of bands characteristic for dellaite. The partial polymerization of the isolated SiO 3 (OH) tetrahedra present in α‐C 2 SH to [Si 2 O 7 ] dimers, as expected for dellaite, was proven by the presence of an IR band at 1050 cm −1 and by TMSM. For the first time, dellaite, along with x ‐Ca 2 SiO 4 , was observed as an intermediate product of the dehydration of α‐C 2 SH. Until now, dellaite was believed to be only a high‐pressure phase. Dellaite coexists with x ‐Ca 2 SiO 4 up to 560°–620°C and decomposes to x ‐Ca 2 SiO 4 at higher temperatures. Upon further heating, the latter phase transforms into α′ l ‐Ca 2 SiO 4 , and finally gives β‐Ca 2 SiO 4 after cooling to room temperature. The thermal decomposition of α‐C 2 SH is a much more complicated process than reported previously. Different factors, such as the source of Ca and the presence of NaOH during synthesis, seem to control the mechanism of its dehydration. The presence of dellaite is shown to lower the temperature of formation of β‐Ca 2 SiO 4 .
Infliximab for Crohn's disease in clinical practice at the Mayo Clinic: the first 100 patients (2001)

This study provides additional evidence that infliximab is safe and beneficial in clinical practice for refractory Crohn's disease.
Enhancement of Resistant Starch (RS3) in Amylomaize, Barley, Field Pea and Lentil Starches (1998)

Native starches isolated from amylomaize. Glacier high amylose barley, field peas and lentils contained 3–5% (w/w) resistant starch (RS3). Retrograded gels that were prepared from these starches had higher RS3 (6–9%) contents. The effects of gel concentration (% starch), storage temperature and time on the RS3 content of the retrograded gels were investigated; the optimum RS3 content was determined in gels prepared at = 10% (w/v) starch concentration and stored under = 20°C for = 5 days. Annealing of the retrograded starch gels by heating and cooling cycles, further enhanced RS3 content to 9–19%; the effect of annealing temperature and number of heat-cool cycles on the RS3 content of the annealed gel were studied. The hydrolysis of retrograded starch gels by pulanase enzyme or acid (2.2 N HCl), prior to annealing, enhanced the RS3 formation during annealing; the enzyme or acid treatment increased RS3 content of the annealed gel to 15–24% or 17–24%, respectively. The potential molecular mechanism that is responsible for the RS3 increase is discussed.
Speech coding using waveform matching based on LPC residual phase equalization (2002)

A speech analysis-synthesis method based on linear predictive coding (LPC) residual phase equalization is presented for low-bit- rate natural sounding speech coding. In this method, the phase-equalized LPC residual signal is represented as the output of the quasi-periodic impulsive excitation to an all-zero filter, which captures harmonic deviation in the residual spectrum which has not been compensated for by LPC inverse filtering of the input speech signal. The impulsive excitation is specified by the instantaneous pitch excitation instant and amplitude. A procedure is presented to determine the excitation parameters and the all-zero filter using a waveform matching criterion. The coder performance is studied objectively and subjectively with a focus on the potential of the excitation model to produce high-quality speech. A speech coder designed for bit rates lower than 4.8 kb/s is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Efficient location tracking using sensor networks (2004)

We apply sensor networks to the problem of tracking moving objects. We describe a publish-and-subscribe tracking method, called scalable tracking using networked sensors (STUN), that scales well to large numbers of sensors and moving objects by using hierarchy. We also describe a method, called drain-and-balance (DAB), for building efficient tracking hierarchies, computed from expected characteristics of the objects movement patterns. DAB is shown to perform well by running it on 1D and 2D sensor network topologies, and comparing it to schemes, which do not utilize movement information.
Ginkgo for Memory Enhancement (2002)

The results of this 6-week study indicate that ginkgo did not facilitate performance on standard neuropsychological tests of learning, memory, attention, and concentration or naming and verbal fluency in elderly adults without cognitive impairment. The ginkgo group also did not differ from the control group in terms of self-reported memory function or global rating by spouses, friends, and relatives. These data suggest that when taken following the manufacturer's instructions, ginkgo provides no measurable benefit in memory or related cognitive function to adults with healthy cognitive function.
Tear Film Lipid Layer Formation: Implications for Contact Lens Wear (1996)

An overview of the relation between lipid layer formation and contact lens wear is provided, with particular emphasis on factors that influence the delivery and spreading of lipid on the tear film. The disruption of the lipid layer by a contact lens is discussed, as well as factors that may enhance the stability of the prelens tear film lipid layer.
Suppressor of cytokine signaling (SOCS)1 is a key determinant of differential macrophage activation and function (2011)

Macrophages become activated by their environment and develop polarized functions: classically activated (M1) macrophages eliminate pathogens but can cause tissue injury, whereas alternatively activated (M2) macrophages promote healing and repair. Mechanisms directing polarized activation, especially in vivo, are not understood completely, and here, we examined the role of SOCS proteins. M2 macrophages activated in vitro or elicited by implanting mice i.p. with the parasitic nematode Brugia malayi display a selective and IL-4-dependent up-regulation of SOCS1 but not SOCS3. Using siRNA-targeted knockdown in BMDM, we reveal that the enhanced SOCS1 is crucial for IL-4-induced M2 characteristics, including a high arginase I:iNOS activity ratio, suppression of T cell proliferation, attenuated responses to IFN-γ/LPS, and curtailed SOCS3 expression. Importantly, SOCS1 was essential in sustaining the enhanced PI3K activity that drives M2 activation, defining a new regulatory mechanism by which SOCS1 controls M2 polarization. By contrast, for M1 macrophages, SOCS1 was not only an important regulator of proinflammatory mediators (IL-6, IL-12, MHC class II, NO), but critically, for M1, we show that SOCS1 also restricted IL-10 secretion and arginase I activity, which otherwise would limit the efficiency of M1 macrophage proinflammatory responses. Together, our results uncover SOCS1, not only as a feedback inhibitor of inflammation but also as a critical molecular switch that tunes key signaling pathways to effectively program different sides of the macrophage balance.
Structural basis for platelet collagen responses by the immune-type receptor glycoprotein VI (2006)

Activation of circulating platelets by exposed vessel wall collagen is a primary step in the pathogenesis of heart attack and stroke, and drugs to block platelet activation have successfully reduced cardiovascular morbidity and mortality. In humans and mice, collagen activation of platelets is mediated by glycoprotein VI (GPVI), a receptor that is homologous to immune receptors but bears little sequence similarity to known matrix protein adhesion receptors. Here we present the crystal structure of the collagen-binding domain of human GPVI and characterize its interaction with a collagen-related peptide. Like related immune receptors, GPVI contains 2 immunoglobulin-like domains arranged in a perpendicular orientation. Significantly, GPVI forms a back-to-back dimer in the crystal, an arrangement that could explain data previously obtained from cell-surface GPVI inhibition studies. Docking algorithms identify 2 parallel grooves on the GPVI dimer surface as collagen-binding sites, and the orientation and spacing of these grooves precisely match the dimensions of an intact collagen fiber. These findings provide a structural basis for the ability of an immune-type receptor to generate signaling responses to collagen and for the development of GPVI inhibitors as new therapies for human cardiovascular disease.
Novel Midinfrared Plasmonic Properties of Bilayer Graphene (2014)

We study the midinfrared plasmonic response in Bernal-stacked bilayer graphene. Unlike its monolayer counterpart, bilayer graphene accommodates optically active phonon modes and a resonant interband transition at infrared frequencies. They strongly modify the plasmonic properties of bilayer graphene, leading to Fano-type resonances, giant plasmonic enhancement of infrared phonon absorption, a narrow window of optical transparency, and a new plasmonic mode at higher energy than that of the classical plasmon.
Immunocytochemical characteristics of human osteosarcoma cell line HS-Os-1: Possible implication in apoptotic resistance against irradiation (2004)

In our previous study, we examined reactive oxygen species (ROS) formation in T lymphocytes following 5 Gy irradiation. We found that ROS formation occurred immediately after irradiation, continued for several hours, and resulted in oxidative DNA damage. Therefore, the origin of the hyper-radiosensitivity of T lymphocytes seemed to be the high production of ROS in the mitochondrial DNA following irradiation. In the succeeding study, we examined radiation-induced ROS formation, oxidative DNA damage, early apoptotic changes, and mitochondrial membrane dysfunction in the human osteosarcoma cell line HS-Os-1. We found that ROS formation and oxidative DNA damage were actually scarcely seen after irradiation of up to 30 Gy in these cells, that mitochondrial membrane potential was preserved, and that apoptotic changes were not demonstrated despite the relatively high-dose irradiation of 30 Gy. In the present study, we examined the immunocytochemical characteristics of the apoptotic-resistance of the HS-Os-1 cell line against irradiation in order to clarify its possible implications regarding radiosensitivity. The results showed that these cells lack P53 and Bax protein expression, and strong peroxidase activity was confirmed in the nuclei of the cells. Moreover, SODII (manganese superoxide dismutase II) protein expression was gradually increased in spite of irradiation of up to 30 Gy. Therefore, it is concluded that HS-Os-1 cells are originally apoptotic-resistant and that the cells possess a strong ability to scavenge for free radicals. To convert these cells to a state of apoptotic-susceptibility, a powerful oxidant such as hydrogen peroxide might exert such an effect in terms of the production of hydroxyl radicals in lysosomes in the cells as shown in our previous studies. The origin of the radioresistance of the human osteosarcoma cell line HS-Os-1 is considered to to be low degree of ROS formation following irradiation, reflecting the strong scavenging ability of these cells for free radicals including hydroxyl radicals.
Correlation of color doppler flow in the prostate with tissue microvascularity (1998)

Increased CD flow in biopsies of benign tissue was correlated with a greater number of vessels/mm2, yet all biopsies of malignant tissue had more vessels/mm2 than those of benign tissue. Increased CD flow in biopsies of malignant tissue cannot be explained by standard microvasculature analysis but significantly guides biopsies to regions with a greater Gleason score.
Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2 (2004)

Neuropilin-1 (NRP-1) is a type 1 membrane protein that binds the axon guidance factors belonging to the class-3 semaforin family. In endothelial cells, NRP-1 serves as a co-receptor for vascular endothelial growth factor (VEGF) and regulates VEGF receptor 2 (VEGFR-2)-dependent angiogenesis. Although gene-targeting studies documenting embryonic lethality in NRP-1 null mice have demonstrated a critical role for NRP-1 in vascular development, the activities of NRP-1 in mature endothelial cells have been incompletely defined. Using RNA interference-mediated silencing of NRP-1 or VEGFR-2 in primary human endothelial cells, we confirm that NRP-1 modulates VEGFR-2 signaling-dependent mitogenic functions of VEGF. Importantly, we now show that NRP-1 regulates endothelial cell adhesion to extracellular matrix proteins independently of VEGFR-2. Based on its dual role as an enhancer of VEGF activity and a mediator of endothelial cell adhesiveness described here, NRP-1 emerges as a promising molecular target for the development of antiangiogenic drugs.
Rac and Phosphatidylinositol 3-Kinase Regulate the Protein Kinase B in FcεRI Signaling in RBL 2H3 Mast Cells (2001)

FcepsilonRI signaling in rat basophilic leukemia cells depends on phosphatidylinositol 3-kinase (PI3-kinase) and the small GTPase Rac. Here, we studied the functional relationship among PI3-kinase, its effector protein kinase B (PKB), and Rac using inhibitors of PI3-kinase and toxins inhibiting Rac. Wortmannin, an inhibitor of PI3-kinase, blocked FcepsilonRI-mediated tyrosine phosphorylation of phospholipase Cgamma, inositol phosphate formation, calcium mobilization, and secretion of hexosaminidase. Similarly, Clostridium difficile toxin B, which inactivates all Rho GTPases including Rho, Rac and Cdc42, and Clostridium sordellii lethal toxin, which inhibits Rac (possibly Cdc42) but not Rho, blocked these responses. Stimulation of the FcepsilonRI receptor induced a rapid increase in the GTP-bound form of Rac. Whereas toxin B inhibited the Rac activation, PI3-kinase inhibitors (wortmannin and LY294002) had no effect on activation of Rac. In line with this, wortmannin had no effect on tyrosine phosphorylation of the guanine nucleotide exchange factor Vav. Wortmannin, toxin B, and lethal toxin inhibited phosphorylation of PKB on Ser(473). Similarly, translocation of the pleckstrin homology domain of PKB tagged with the green fluorescent protein to the membrane, which was induced by activation of the FcepsilonRI receptor, was blocked by inhibitors of PI3-kinase and Rac inactivation. Our results indicate that in rat basophilic leukemia cells Rac and PI3-kinase regulate PKB and suggest that Rac is functionally located upstream and/or parallel of PI3-kinase/PKB in FcepsilonRI signaling.
Monoclonal Antibodies to Phosphatidylinositol Phosphate Neutralize Human Immunodeficiency Virus Type 1: Role of Phosphate-Binding Subsites (2006)

Both a murine monoclonal antibody to phosphatidylinositol phosphate (PIP) and a human monoclonal antibody (4E10) that is known to have broadly neutralizing capabilities against primary isolates of human immunodeficiency virus type 1 (HIV-1) bound to PIP, as determined by enzyme-linked immunosorbent assay. Each of the antibodies had antigen subsite binding specificities in aqueous medium for small phosphate-containing molecules and for inositol. The anti-PIP monoclonal antibody inhibited infection by two HIV-1 primary isolates in neutralization assays employing primary human peripheral blood mononuclear cells. The data suggest that PIP or related lipids having free phosphates could serve as targets for the neutralization of HIV-1.
Mutant p53 DNA clones from human colon carcinomas cooperate with ras in transforming primary rat cells: a comparison of the "hot spot" mutant phenotypes. (1990)

The majority of the p53 genes derived from human colorectal carcinomas contain point mutations. A significant number of these mutations occur in or around amino acids 143, 175, 273, or 281. Experiments presented here demonstrate for the first time that p53 DNA clones containing any one of these mutations cooperate with the activated ras oncogene to transform primary rat embryo cells in culture. These transformed cells produce elevated levels of the human p53 protein, which has extended half-lives (1.5-7 h), as compared to the wild-type human p53 protein (20-30 min). The p53 mutant with an alteration at residue 175 (p53-175H) binds tightly to the cellular heat shock protein, hsc70. In contrast, the p53 mutants possessing mutations at either residue 273 or 281 (p53-273H/281G) do not bind detectably to this heat shock protein and generally are less efficient at forming transformed foci in culture. The transformed cell lines are tumorigenic in nude mice. Thus, two classes of p53 mutant proteins can be distinguished: p53-175H, which cooperates with ras efficiently and binds to hsc70, and p53-273H/281G, which has a reduced efficiency of transformed foci formation and does not bind hsc70. This demonstrates that complex formation between mutant p53 and hsc70 is not required for p53-mediated transformation, but rather it facilitates this function, perhaps by ensuring sequestration of the endogenous wild-type p53 protein. The positive effect on cell proliferation by these mutant p53 proteins is consistent with a role for activated p53 mutants in the genesis of colorectal carcinomas.