gebhart/patrepeval huggingface dataset:
Identification of the YopE and YopH domains required for secretion and internalization into the cytosol of macrophages, using the cyaA gene fusion approach. (1995)

Pathogenic yersiniae secrete a set of antihost proteins, called Yops, by a type III secretion mechanism. Upon infection of cultured epithelial cells, extracellular Yersinia pseudotuberculosis and Yersinia enterocolitica translocate cytotoxin YopE across the host cell plasma membrane. Several lines of evidence suggest that tyrosine phosphatase YopH follows the same pathway. We analyzed internalization of YopE and YopH into murine PU5-1.8 macrophages by using recombinant Y. enterocolitica producing truncated YopE and YopH proteins fused to a calmodulin-dependent adenylate cyclase. The YopE-cyclase and YopH-cyclase hybrids were readily secreted by Y. enterocolitica. The N-terminal domain required for secretion was not longer than 15 residues of YopE and 17 residues of YopH. Internalization into eukaryotic cells, revealed by cAMP production, only required the N-terminal 50 amino acid residues of YopE and the N-terminal 71 amino acid residues of YopH. YopE and YopH are thus modular proteins composed of a secretion domain, a translocation domain, and an effector domain. Translocation of YopE and YopH across host cell's membranes was also dependent on the secretion of YopB and YopD by the same bacterium. The cyclase fusion approach could be readily extended to study the fate of other proteins secreted by invasive bacterial pathogens.
Nitric Oxide Chemisorption in a Postsynthetically Modified Metal−Organic Framework (2009)

Postsynthetic metal-organic framework (MOF) derivatization introduces accessible secondary amine functionalities that react with nitric oxide (NO) to form N-diazenium diolates. This is in contrast to the parent MOF that binds NO essentially irreversibly at open metal coordination sites.
Digital pressure-switch array with aligned silicon fusion bonding (1991)

The design, fabrication and testing of a micromechanical pressure-switch array is described. This two-terminal device array is formed using aligned fusion bonding of two prefabricated silicon wafers. A pattern-etched thermally grown silicon dioxide is used to determine the size of pressure membranes with the desired switch gap set by the oxide thickness. The silicon membranes are formed by controlled thinning of one of the bonded silicon wafers. Pressure-switch points of 1/4, 1/2, 3/4, and 1 atm are designed as the threshold levels in this work. The switches operate on the principle of closing electrical contacts by deflecting diaphragms in the array to a point of contact with the bottom wafer. It is found that the switches close at the desired pressure threshold with negligible hysteresis for both directions of pressure change. The array produces a digital output describing the pressure level being monitored. Experimental accuracy to within 4% of calculated pressure-switch points have been achieved.
Ghost imaging through turbulent atmosphere (2009)

Ghost imaging through turbulent atmospheres are theoretically studied. Based on the extended Huygens-Fresnel integral, we obtain an analytical imaging formula. The ghost image can be viewed as the convolution of the original object and a point-spread function (PSF). The imaging quality is determined by the size of the PSF. Increasing the turbulence strength and propagation distance, or decreasing the source size, will increase the size of the PSF, and lead to the degradation of the imaging quality.
Paroxysmal nocturnal hemoglobinuria and the glycosylphosphatidylinositol-linkted proteins (2000)

Paroxysmal Nocturnal Hemoglobinuria (PNH) has been recognized for over a century. This mysterious disease is now understood at the level of the gene and the protein. The pathophysiology is related to a class of cell surface proteins with distinctive biochemical and physical characteristics. Recently, it has been acknowledged that PNH is not rare, and once sensitive assays - based on the chemistry of the proteins - can be applied to many patients. Written by international experts in the field, this book includes a number of distinctive characteristics, such as the clinical features of PNH, the mechanism of hemolysis, the biochemistry of glycosylphosphoinositol anchors, and the chemistry and biophysics of GPI-anchored proteins. This unique and timely volume will have a wide audience, including hematologists and oncologists with a clinical interest in this disease, as well as basic biochemists, immunologists, and cell biologists studying this class of proteins. It outlines the chemical features of PNH; explains the mechanism of hemolysis; includes work on the biochemistry of glycophosphoinositol anchors; and contains descriptions of the chemistry and biophysics of GPI-anchored proteins.
Amplification and overexpression of HER-2/neu in carcinomas of the salivary gland: correlation with poor prognosis. (1994)

There are few reliable prognostic markers of biological aggressiveness for head and neck carcinomas in general. For salivary gland carcinomas, anatomic location, tumor size, histological grade, and extent of disease involvement are considered to be clinically important risk factors for recurrent disease. Molecular genetic alterations in salivary gland carcinomas have not been characterized, and tumor cell proteins have not been shown to be prognostically significant. Here a cohort of mucoepidermoid carcinomas of the major (parotid and submandibular) salivary glands are analyzed for a molecular genetic alteration, HER-2/neu gene amplification, and gene amplification and expression results are compared with long-term clinical follow-up information. Archival tissues resected from 58 patients with mucoepidermoid carcinoma of salivary glands were evaluated for HER-2/neu gene amplification by fluorescence in situ hybridization and for gene expression by immunohistochemistry in a blinded fashion. Clinical follow-up information was compared with the results of these analyses to determine whether there were significant associations. Overexpression, identified as membrane immunostaining by immunohistochemistry, was observed in 22 of 58 (38%) mucoepidermoid carcinomas. Gene amplification, characterized by fluorescence in situ hybridization, was observed in 12 (21%) cases. Eleven of the 12 cases with gene amplification were also immunostained for HER-2/neu. Both gene amplification (P = 0.0001, P < 0.0001) and immunostaining (P < 0.0001, P < 0.0001) were correlated with shorter disease-free interval and poorer overall patient survival, respectively. Multivariate analysis showed that HER-2/neu immunostaining and amplification were markers of poor prognosis independent of histopathological grade, tumor size, and involvement of regional lymph nodes. HER-2/neu is amplified and/or overexpressed in approximately one-third of mucoepidermoid carcinomas of salivary glands. Amplification and/or overexpression appears to be an independent marker of poor prognosis in mucoepidermoid carcinomas of the salivary glands as it is in carcinomas of the breast, ovary, and endometrium.
Semiconductor space switches based on multimode interference couplers (2002)

It is shown theoretically that selective perturbation by electrorefractive effect of the even-order modes in III-V semiconductor multimode interference couplers gives rise to high-performance optical switching. The calculated performance of the proposed switch is 3.4 GHz/Vmm, compared to 0.85 GHz/Vmm for an equivalent Mach-Zehnder interferometer (MZI) switch. The effects of electroabsorption and dimension variations are analyzed to demonstrate the feasibility of the proposed device.
Epidermal Growth Factor Activates Hyaluronan Synthase 2 in Epidermal Keratinocytes and Increases Pericellular and Intracellular Hyaluronan (2001)

Hyaluronan is an abundant and rapidly turned over matrix molecule between the vital cell layers of the epidermis. In this study, epidermal growth factor (EGF) induced a coat of hyaluronan and a 3-5-fold increase in its rate of synthesis in a rat epidermal keratinocyte cell line that has retained its ability for differentiation. EGF also increased hyaluronan in perinuclear vesicles, suggesting concurrent enhancement in its endocytosis. Cell-associated hyaluronan was most abundant in elongated cells that were stimulated to migrate by EGF, as determined in vitro in a wound healing assay. Large fluctuations in the pool size of UDP-N-acetylglucosamine, the metabolic precursor of hyaluronan, correlated with medium glucose concentrations but not with EGF. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed no increase in hyaluronan synthases 1 and 3 (Has1 and Has3), whereas Has2 mRNA increased 2-3-fold in less than 2 h following the introduction of EGF, as estimated by quantitative RT-PCR with a truncated Has2 mRNA internal standard. The average level of Has2 mRNA increased from approximately 6 copies/cell in cultures before change of fresh medium, up to approximately 54 copies/cell after 6 h in EGF-containing medium. A control medium with 10% serum caused a maximum level of approximately 21 copies/cell at 6 h. The change in the Has2 mRNA levels and the stimulation of hyaluronan synthesis followed a similar temporal pattern, reaching a maximum level at 6 h and declining toward 24 h, a finding in line with a predominantly Has2-dependent hyaluronan synthesis and its transcriptional regulation.
The insulin-like growth factor I receptor protects tumor cells from apoptosis in vivo. (1995)

The role of the insulin-like growth factor I receptor (IGF-IR) in programmed cell death has been investigated in vivo in a biodiffusion chamber, where the extent of cell death could be determined quantitatively. We found that a decrease in the number of IGF-IRs causes massive apoptosis in vivo in several transplantable tumors, either from humans or rodents. Conversely, an overexpressed IGF-IR protects cells from apoptosis in vivo. We also show that the same conditions that in vitro cause only partial growth arrest with a minimum of cell death, induce in vivo almost complete cell death. We conclude that the IGF-IR activated by its ligands plays a very important protective role in programmed cell death, and that its protective action is even more striking in vivo than in vitro.
Minimal models for text production and Zipf's law (2006)

Mathematical models used to explain the power-law distribution of word frequencies observed in natural languages - Zipf's law - generally assume that symbols and words occur independently, i.e., they do not interact. Here we show that when interaction is taken into account by allowing the words to compete amongst themselves for space in the memory of the users, the resulting word frequency distribution is best described by an exponential, rather than by a power-law. The implications of the failure to derive Zipf's law under more realistic assumptions are discussed.
Adjuvant Immunotherapy with BCG in Treatment of Regional-Lymph-Node Metastases from Malignant Melanoma (1976)

Despite current surgical therapy, about 80 per cent of patients with malignant melanoma metastatic to lymph nodes succumb to systemic metastatic disease. To determine if postoperative adjuvant immunization with BCG was an effective systemic treatment in these patients with microscopic subclinical metastatic disease, the clinical course of 42 patients treated by operation alone was compared with that of 84 treated by operation and BCG. At two years, the incidence of metastasis in BCG-treated patients was half that of the control group. BCG was more effective in patients with a smaller tumor burden at the time of initial surgical treatment. In patients receiving BCG adjuvant therapy, 90 per cent with microscopic disease in one lymph node appeared free of disease as compared to 40 per cent with macroscopic disease in multiple nodes. In patients with recurrences, an immunotherapeutic effect was demonstrated by a delay of six months in the time to recurrence. Thus, BCG immunotherapy appears to have an inhibiting effect on the "micrometastases" of malignant melanoma.
Comparative analysis of human NK cell activation induced by NKG2D and natural cytotoxicity receptors (2004)

NKG2D and natural cytotoxicity receptors (NCR) are essential recognition structures that mediate NK cell activation. NKG2D and NCR signaling is achieved through membrane association with signaling adaptors. The adaptors that associate with NCR--such as CD3 zeta, FcR gamma and KARAP/DAP12--bear intracytoplasmic immunoreceptor tyrosine-based activation motifs that activate Syk protein tyrosine kinases. Human NKG2D associates with the DAP10 transmembrane adaptor, which bears a YxxM motif and activates the phosphatidylinositol 3-kinase pathway. In the mouse, a short NKG2D-S isoform, generated by Nkg2d alternative splicing, can associate with either DAP10 or KARAP/DAP12. Here, we report that neither short human NKG2D alternative transcripts nor NKG2D association with KARAP/DAP12 was detected in activated human NK cells. Despite these results, NK cell triggering by both recombinant soluble NKG2D ligands (MICA and ULBP-1) and anti-NCR cross-linking antibodies induced similar CD25 expression, NK cell proliferation and cytokine production. In contrast, NKG2D triggering by anti-NKG2D antibodies did not lead to any detectable activation signals. These data thus show that target recognition via NKG2D or NCR triggers all aspects of NK activation, and pave the way for further dissection of the signaling pathways induced by NK cell recognition of ULBP-1 and MICA.
Towards Automating Social Engineering Using Social Networking Sites (2009)

A growing number of people use social networking sites to foster social relationships among each other. While the advantages of the provided services are obvious, drawbacks on a users' privacy and arising implications are often neglected. In this paper we introduce a novel attack called automated social engineering which illustrates how social networking sites can be used for social engineering. Our approach takes classical social engineering one step further by automating tasks which formerly were very time-intensive. In order to evaluate our proposed attack cycle and our prototypical implementation (ASE bot), we conducted two experiments. Within the first experiment we examine the information gathering capabilities of our bot. The second evaluation of our prototype performs a turing test. The promising results of the evaluation highlight the possibility to efficiently and effectively perform social engineering attacks by applying automated social engineering bots.
Synthesis and degradation of cytochrome oxidase subunit mRNAs in neurons: Differential bigenomic regulation by neuronal activity (2000)

Cytochrome oxidase (CO) plays a key role in oxidative capacity of neurons and serves as a sensitive indicator of neuronal activity. The mechanism(s) involved in the regulation of this bigenomic-encoded mitochondrial enzyme is still not clearly understood. Previous studies have shown changes in the level of its subunit mRNAs encoded by the nuclear or mitochondrial genome in response to changing neuronal activity. Our goals in the present study were to determine whether such changes were due to RNA synthesis rate or stability or both. The level of CO activity of neurons in primary cultures assayed histochemically was increased after depolarizing KCl treatment. The steady-state levels of CO subunit II (CO II; mitochondrial-encoded) and IV (CO IV; nuclear-encoded) mRNAs were up-regulated in response to 5 hr of 20 mM KCl treatment. By using gene-specific probes, the relative rates of synthesis of CO II and IV mRNA were elevated significantly after KCl treatment (P < 0.05). The degradation of CO II and IV mRNAs was monitored by (3)H-uridine pulse-chase labeling, which revealed half-lives of 84 min for CO II mRNA and 50 min for CO IV mRNA. Under KCl treatment, the half-life of CO IV was increased to 102 min, but there was no statistically significant change in the half-life of CO II mRNA. These results indicate that mitochondrial subunit CO II mRNA is regulated mainly at the transcriptional level, whereas the nuclear subunit CO IV mRNA is regulated at both the synthetic and the degradative levels. Both subunits, however, are tightly governed by neuronal activity.
Interleukin-4 induces programmed cell death (apoptosis) in cases of high-risk acute lymphoblastic leukemia (1994)

We investigated the effects of interleukin-4 (IL-4) on the survival of leukemic and normal B-cell progenitors cultured on bone marrow stroma. IL-4 (at 100 U/mL) was cytotoxic in 16 of 21 cases of B-lineage acute lymphoblastic leukemia, causing reductions in CD19+ cell numbers that ranged from 50% to greater than 99% (median 83.5%) of those in parallel cultures not exposed to the cytokine. All nine cases with the t(9;22)(q34;q11) or the t(4;11)(q21;q23), chromosomal features that are often associated with multidrug resistance and a fatal outcome, were susceptible to IL-4 toxicity. IL-4 cytotoxicity resulted from induction of programmed cell death (apoptosis); there was no evidence of cell killing mediated by T, natural killer, or stromal cells. IL-4 cytotoxicity extended to a proportion of normal B-cell progenitors. After 7 days of culture with IL-4 at 100 U/mL, fewer CD19+, CD34+ normal lymphoblasts (the most immature subset) survived: in five experiments the mean (+/- SEM) reduction in cell recoveries caused by IL-4 was 60.0% +/- 6.0%. By contrast, reductions in recovery of more differentiated bone marrow B cells (CD19+, CD34-, surface Ig+) were low (6.6% +/- 2.2%; P < .001 by t-test). Our findings indicate that IL-4 is cytotoxic for human B-cell precursors and support clinical testing of IL-4 in cases of high-risk lymphoblastic leukemia resistant to conventional therapy.
Arthroscopic autologous chondrocyte implantation for the treatment of a chondral defect in the tibial plateau of the knee (2004)

The matrix-induced autologous chondrocyte implantation (MACI; Verigen, Leverküsen, Germany) is a tissue engineering technique for the treatment of deep chondral lesions. Cultured chondrocytes are seeded on a collagen membrane that can be implanted into the defect using exclusively fibrin glue. These features imply some surgical advantages with respect to the traditional ACI technique, such as the possibility of performing the procedure in articular sites, in which putting stitches for the periosteal patch is impossible. We report on the arthroscopic MACI technique for the treatment of a chondral defect of the knee. A 25-year-old man suffered persistent pain at the left knee after a violent direct trauma. Magnetic resonance imaging (MRI) and arthroscopic examination at the time of cartilage biopsy revealed a 2-cm2 chondral lesion in the posterior portion of the lateral tibial plateau. The implantation procedure was performed through traditional arthroscopic portals, and the seeded membrane was fixed with fibrin glue, excluding water flow temporarily. Implant stability was verified intraoperatively, and filling of the defect was shown 12 months after surgery by MRI, which showed a hyaline-like cartilage signal. In this specific case, the arthroscopic approach allowed to achieve an optimal view of the lesion, without sacrificing any tendinous or ligamentous structure of the knee.
Novel Properties of Tyrosine-mutant AAV2 Vectors in the Mouse Retina (2010)

Vectors based on adeno-associated virus serotype 2 (AAV2) have been used extensively in many gene-delivery applications, including several successful clinical trials for one type of Leber congenital amaurosis in the retina. Many studies have focused on improving AAV2 transduction efficiency and cellular specificity by genetically engineering its capsid. We have previously shown that vectors-containing single-point mutations of capsid surface tyrosines in serotypes AAV2, AAV8, and AAV9 displayed significantly increased transduction efficiency in the retina compared with their wild-type counterparts. In the present study, we evaluated the transduction characteristics of AAV2 vectors containing combinations of multiple tyrosine to phenylalanine mutations in seven highly conserved surface-exposed capsid tyrosine residues following subretinal or intravitreal delivery in adult mice. The multiply mutated vectors exhibited different in vivo transduction properties, with some having a unique ability of transgene expression in all retinal layers. Such novel vectors may be useful in developing valuable new therapeutic strategies for the treatment of many genetic diseases.
Evaluating the Strength of Salt Bridges: A Comparison of Current Biomolecular Force Fields (2014)

Recent advances in computer hardware and software have made rigorous evaluation of current biomolecular force fields using microsecond-scale simulations possible. Force fields differ in their treatment of electrostatic interactions, including the formation of salt bridges in proteins. Here we conducted an extensive evaluation of salt bridge interactions in the latest AMBER, CHARMM, and OPLS force fields, using microsecond-scale molecular dynamics simulations of amino acid analogues in explicit solvent. We focused on salt bridges between three different pairs of oppositely charged amino acids: Arg/Asp, Lys/Asp, and His(+)/Asp. Our results reveal considerable variability in the predicted KA values of the salt bridges for these force fields, as well as differences from experimental data: almost all of the force fields overestimate the strengths of the salt bridges. When amino acids are represented by side-chain analogues, the AMBER ff03 force field overestimates the KA values the least, while for complete amino acids, the AMBER ff13α force field yields the lowest KA value, most likely caused by an altered balance of side-chain/side-chain and side-chain/backbone contacts. These findings confirm the notion that the implicit incorporation of solvent polarization improves the accuracy of modeling salt bridge interactions.
Dexmedetomidine vs midazolam for premedication of pediatric patients undergoing anesthesia (2012)

Intranasal dexmedetomidine and midazolam are equally effective in decreasing anxiety upon separation from parents; however, midazolam is superior in providing satisfactory conditions during mask induction.
Bronchoalveolar Lavage Cellularity: The Distribution in Normal Volunteers (1992)

Bronchoalveolar lavage (BAL) is used to obtain inflammatory cells from the lung. For clinical research, parametric statistics are frequently used to compare cells present in BAL of patients with lung disease with cells present in BAL of normal subjects. To determine if these populations can be compared in this manner we performed BAL on 111 never-smoking, normal volunteers and determined: (1) the mean, median, standard deviation, and range of the cells in BAL; (2) whether the data are normally distributed and satisfy the criteria for use of parametric statistical analysis. The BAL cellularity was expressed as a percentage of total cells, cells per milliliter return, and total cells per lavage. Regardless of the means of expression, no measure of BAL cellularity (total cells, macrophages, lymphocytes, neutrophils, or eosinophils) conformed to the normal (bell-shaped) distribution when tested for goodness of fit with the G statistic (all p < 0.001). The lack of fit to the normal distribution was not substantially altered by either the method of expressing the data (i.e., cells per milliliter, total cells, or percent of cells) or log transformation of the data. The poor fit in all cases resulted from clumping of the data about the mean and large tails. The percent of cells were, therefore, tested for goodness of fit to the Poisson distribution, a distribution of discrete variables. The neutrophil and eosinophil percentages resulted in an excellent fit to the Poisson distribution, but macrophage and lymphocyte percentages did not.(ABSTRACT TRUNCATED AT 250 WORDS)