gebhart/patrepeval huggingface dataset:
Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay (1991)

The kinetic properties and substrate specificity of two well-characterized peptidyl prolyl cis-trans isomerases (PPIases), cyclophilin and the FK-506 binding protein (FKBP), have been previously examined [Fischer, G., Bang, H., Berger, E., & Schellenberger, A. (1984) Biochim. Biophys. Acta 791, 87-97; Harrison, R.K., & Stein, R.L. (1990) Biochemistry 29, 1684-1689; Albers, M.W., Walsh, C.T., & Schreiber, S. L. (1990) J. Org. Chem. 55, 4984-4986]. The chymotrypsin-coupled enzymatic assay employed in these studies suffers from two serious shortcomings. Due to the low equilibrium population of the X-cis-Pro-Phe-pNA isomer (the PPIase substrate), in conjunction with the low solubility of p-nitroaniline generated by chymotrypsin hydrolysis, substrate concentrations in the saturating region are not experimentally attainable. Secondly, the uncatalyzed cis-trans isomerization obscures the interpretation of the initial velocity. As a result of these limitations, the steady-state kinetic parameters (Km,Kcat) have not been determined. Here we introduce an improved version of the spectrophotometric assay and report for the first time the Michaelis constants and turnover numbers for both PPIases with established substrates. The improvements in the experimental conditions originate in a medium-induced increase in the equilibrium population of the cis X-Pro conformer and in conducting the assay at 0 degrees C to suppress the uncatalyzed thermal isomerization. In addition, we present a rigorous mathematical model of the spectrophotometric progress curves that accounts for the contributions of the residual background rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Parametric Statistical Change Point Analysis (2000)

This work is an in-depth study of the change point problem from a general point of view and a further examination of change point analysis of the most commonly used statistical models Change point problems are encountered in such disciplines as economics, finance, medicine, psychology, signal processing, and geology, to mention only several The exposition is clear and systematic, with a great deal of introductory material included Different models are presented in each chapter, including gamma and exponential models, rarely examined thus far in the literature Other models covered in detail are the multivariate normal, univariate normal, regression, and discrete models Extensive examples throughout the text emphasize key concepts and different methodologies are used, namely the likelihood ratio criterion, and the Bayesian and information criterion approaches A comprehensive bibliography and two indices complete the study
Kinetic and Thermodynamic Studies of the Folding/Unfolding of a Tryptophan-Containing Mutant of Ribonuclease A (1996)

Tryptophan was substituted for Tyr92 to create a sensitive and unique optical probe in order to study the unfolding and refolding kinetics of disulfide-intact bovine pancreatic ribonuclease A by fluorescence-detected stopped-flow techniques. The stability of the Trp mutant was found to be similar to that of wild-type RNase A when denatured by heat or GdnHCl, and the mutant was found to have 85% of the activity of the wild-type protein. Single-jump unfolding experiments showed that the unfolding pathway of the Trp mutant contains a fast and a slow phase similar to those seen previously for the wild-type protein, indicating that the mutation did not alter the unfolding pathway significantly. The activation energy of the slow-unfolding phase suggested that proline isomerization is involved, with the Trp residue presumably reporting on changes in its local environment. Single-jump refolding experiments revealed the presence of GdnHCl-independent burst phase and a native-like intermediate, most likely IN, on the folding pathway. Single-jump refolding data at various final GdnHCl concentrations were fit to a kinetic folding model involving two pathways to the native state; one pathway involves the intermediate IN, and the other is a direct one to the native state. This model provides site-specific information, since Trp92 monitors the formation of local structure only in the neighborhood of that residue. Double-jump refolding experiments permitted the detection of a previously reported, hydrophobically collapsed intermediate, I phi. The refolding data support the hypothesis that the region around position 92 is a chain-folding initiation site in the folding pathway.
Impaired Endothelium-Dependent Vasodilation in Patients With Essential Hypertension (1995)

Patients with essential hypertension have impaired endothelium-dependent vasodilator responses to both acetylcholine and bradykinin. These findings indicate that the endothelial dysfunction in this condition is not related to a specific defect of a single intracellular signal-transduction pathway and suggest a more generalized abnormality of endothelial vasodilator function.
Intrinsic Antibacterial Activity of Nanoparticles Made of β-Cyclodextrins Potentiates Their Effect as Drug Nanocarriers against Tuberculosis (2019)

Multi-drug-resistant tuberculosis (TB) is a major public health problem, concerning about half a million cases each year. Patients hardly adhere to the current strict treatment consisting of more than 10 000 tablets over a 2-year period. There is a clear need for efficient and better formulated medications. We have previously shown that nanoparticles made of cross-linked poly-β-cyclodextrins (pβCD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, we report that in addition to being efficient drug carriers, pβCD nanoparticles are endowed with intrinsic antibacterial properties. Empty pβCD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. pβCD hamper colonization of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, pβCD provoke macrophage apoptosis, leading to depletion of infected cells, thus creating a lung microenvironment detrimental to Mtb persistence. Taken together, our results suggest that pβCD nanoparticles loaded or not with antibiotics have an antibacterial action on their own and could be used as a carrier in drug regimen formulations effective against TB.
Endoperoxide Synthesis by Photocatalytic Aerobic [2 + 2 + 2] Cycloadditions (2012)

Structurally novel endoperoxides can be sythesized by the photocatalytic cyclotrimerization of bis(styrene) substrates with molecular oxygen. The optimal catalyst for this process is Ru(bpz)(3)(2+), which is a markedly more efficient catalyst for these photooxygention reactions than conventional organic photosensitizers. The 1,2-dioxolane products are amenable to synthetic manipulation and can be easily processed to 1,4-diols and γ-hydroxyketones. An initial screen of the biological activity of these compounds reveals promising inhibition of cancer cell growth.
Charge Cluster-to-Alanine Scanning of UL128 for Fine Tuning of the Endothelial Cell Tropism of Human Cytomegalovirus (2008)

The viral genes UL128, UL130, and UL131A have been identified as major determinants of endothelial cell (EC) tropism of human cytomegalovirus (HCMV), with deletion of either gene causing a null phenotype. We hypothesized that a functional scanning of these genes by minor genetic modifications would allow for the generation of mutants with an intermediate phenotype. By combining charge cluster-to-alanine (CCTA) mutagenesis with markerless mutagenesis of a bacterial artificial chromosome-cloned endotheliotropic HCMV strain, we analyzed UL128 in order to identify functional sites and hence enable targeted modulation of the EC tropism of HCMV. A total of nine mutations in eight charge clusters were tested. Three of the CCTA mutations severely reduced EC tropism, three were irrelevant, two had a weak effect on cell tropism, and one mutation in the most C-terminal cluster caused an intermediate phenotype. All of the highly effective mutations were located in a core region (amino acids 72 to 106) which appears to be particularly crucial for EC tropism. The intermediate effect of mutations in the C-terminal cluster could be modulated by varying the number of amino acids replaced with alanine. This study provides a rational approach for targeted modulation of HCMV cell tropism, which may aid in the development of HCMV strains with a desired degree of attenuation.
Issues in routing for large and dynamic networks (1983)

The routing function is necessary in computer communication networks in order to create the appearance of complete connectivity in an environment of sparse physical links. The purpose of this dissertation is to examine ways of providing the routing function in large networks or networks which are characterized by frequent topological changes or both. The focus is on distributed routing algorithms because of their failsafe property.
Two new event driven distributed route table update algorithms, A and B, are introduced and proven correct. Algorithm A requires less buffer space to store route tables than other event driven algorithms. Algorithm B, a variation of algorithm A, allows each node to maintain a source tree, i.e. a tree rooted at the node and containing the shortest path to all possible destinations in the network. The source tree may be used to implement source routing, i.e. the whole path from source to destination is determined at the source. Transient route table looping is also studied for algorithms A, B, as well as other algorithms in the literature.
Hierarchical routing has been suggested in the literature as a means to reduce the size of the route tables when networks become very large. Reduction of the table size may also reduce the communication cost incurred during the update of the route tables. A possible effect of the shrinking of the route tables is that the resulting paths are not optimal. A classification of hierarchical routing schemes is introduced. The trade-off between between route table reduction and path length increase is studied in detail for two classes of schemes. Alternate policies for routing in the absence of necessary information are suggested and evaluated.
In order to implement hierarchical routing it is necessary to partition the network into clusters. The network partitioning problem is abstracted to a graph partitioning problem which is shown to be NP complete. A new heuristic procedure, V3.2, is developed which is compared to the agglomerative method, a procedure suggested in the literature. V3.2 is shown to perform considerably better computationally as well as in terms of desired properties of the partitions. The comparison is performed by simulation experiments. An algorithm is developed to randomly generate connected networks suitable to be used in the simulations.
Induction of MHC-class I restricted human suppressor T cells by peptide priming in vitro (1998)

The induction of regulatory T cells may offer an effective means for specific immunosuppression of autoimmune disease and allograft rejection. The existence of suppressor T cells has been previously documented, yet their mechanism of action remains poorly characterized. Our studies demonstrate that T suppressor (Ts) cell lines can be generated by in vitro immunization of human PBMCs, with synthetic peptides or soluble proteins coupled to beads. Such Ts cells express the CD8+CD28- phenotype and show the following characteristics: (a) antigen specificity and restriction by self MHC Class I molecules; (b) limited TCR V beta gene usage; (c) ability to inhibit antigen-specific, MHC Class II restricted, Th proliferative responses; and (d) capacity to downregulate and/or inhibit the upregulation by Th of CD40, CD80, and CD86 molecules on APCs. The inhibitory activity of Ts on Th proliferation requires the tripartite interaction between Th, Ts, and APCs and results from inefficient costimulation of Th.
A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E. (1992)

We have reported the identification of human gene MAGE-1, which directs the expression of an antigen recognized on a melanoma by autologous cytolytic T lymphocytes (CTL). We show here that CTL directed against this antigen, which was named MZ2-E, recognize a nonapeptide encoded by the third exon of gene MAGE-1. The CTL also recognize this peptide when it is presented by mouse cells transfected with an HLA-A1 gene, confirming the association of antigen MZ2-E with the HLA-A1 molecule. Other members of the MAGE gene family do not code for the same peptide, suggesting that only MAGE-1 produces the antigen recognized by the anti-MZ2-E CTL. Our results open the possibility of immunizing HLA-A1 patients whose tumor expresses MAGE-1 either with the antigenic peptide or with autologous antigen-presenting cells pulsed with the peptide.
Differentially Regulated Micro-RNAs and Actively Translated Messenger RNA Transcripts by Tumor Suppressor p53 in Colon Cancer (2006)

To the best of our knowledge, this is the first report demonstrating that wt-p53 and miRNAs interact in influencing gene expression and providing insights of how p53 regulates genes at multiple levels via unique mechanisms.
Combined Raman spectroscopy and optical coherence tomography device for tissue characterization (2008)

We report a dual-modal device capable of sequential acquisition of Raman spectroscopy (RS) and optical coherence tomography (OCT) along a common optical axis. The device enhances application of both RS and OCT by precisely guiding RS acquisition with OCT images while also compensating for the lack of molecular specificity in OCT with the biochemical specificity of RS. We characterize the system performance and demonstrate the capability to identify structurally ambiguous features within an OCT image with RS in a scattering phantom, guide acquisition of RS from a localized malignancy in ex vivo breast tissue, and perform in vivo tissue analysis of a scab.
Dysregulation of Angiopoietin 1 and 2 in Escherichia coli O157:H7 Infection and the Hemolytic-Uremic Syndrome (2013)

Escherichia coli O157:H7-associated hemolytic-uremic syndrome (HUS) is characterized by profound prothrombotic abnormalities. Endothelial dysfunction, manifested as dysregulation of angiopoietins 1 and 2 (Ang-1/2), could underlie HUS pathophysiology. We measured Ang-1/2 in 77 children with E. coli O157:H7 infection. Ang-1, Ang-2, and the Ang-2/Ang-1 ratio were significantly different in HUS vs the pre-HUS phase of illness or uncomplicated infection. Angiopoietin dysregulation preceded HUS and worsened as HUS developed. In vitro exposure of human microvascular endothelial cells to Shiga toxin recapitulated the in vivo observations. Angiopoietin regulation is profoundly affected before and during HUS, reflecting that subclinical endothelial dysfunction precedes overt microangiopathy.
Two Distinct Proteolytic Systems Responsible for Glucose-induced Degradation of Fructose-1,6-bisphosphatase and the Gal2p Transporter in the Yeast Saccharomyces cerevisiae Share the Same Protein Components of the Glucose Signaling Pathway (2002)

Addition of glucose to Saccharomyces cerevisiae inactivates the galactose transporter Gal2p and fructose-1,6-bisphosphatase (FBPase) by a mechanism called glucose- or catabolite-induced inactivation, which ultimately results in a degradation of both proteins. It is well established, however, that glucose induces internalization of Gal2p into the endocytotic pathway and its subsequent proteolysis in the vacuole, whereas FBPase is targeted to the 26 S proteasome for proteolysis under similar inactivation conditions. Here we report that two distinct proteolytic systems responsible for specific degradation of two conditionally short-lived protein targets, Gal2p and FBPase, utilize most (if not all) protein components of the same glucose sensing (signaling) pathway. Indeed, initiation of Gal2p and FBPase proteolysis appears to require rapid transport of those substrates of the Hxt transporters that are at least partially metabolized by hexokinase Hxk2p. Also, maltose transported via the maltose-specific transporter(s) generates an appropriate signal that culminates in the degradation of both proteins. In addition, Grr1p and Reg1p were found to play a role in transduction of the glucose signal for glucose-induced proteolysis of Gal2p and FBPase. Thus, one signaling pathway initiates two different proteolytic mechanisms of catabolite degradation, proteasomal proteolysis and endocytosis followed by lysosomal proteolysis.
Immunization with a Polyprotein Vaccine Consisting of the T-Cell Antigens Thiol-Specific Antioxidant,Leishmania majorStress-Inducible Protein 1, andLeishmaniaElongation Initiation Factor Protects against Leishmaniasis (2002)

Development of an effective vaccine against Leishmania infection is a priority of tropical disease research. We have recently demonstrated protection against Leishmania major in the murine and nonhuman primate models with individual or combinations of purified leishmanial recombinant antigens delivered as plasmid DNA constructs or formulated with recombinant interleukin-12 (IL-12) as adjuvant. In the present study, we immunized BALB/c mice with a recombinant polyprotein comprising a tandem fusion of the leishmanial antigens thiol-specific antioxidant, L. major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF) delivered with adjuvants suitable for human use. Aspects of the safety, immunogenicity, and vaccine efficacy of formulations with each individual component, as well as the polyprotein referred to as Leish-111f, were assessed by using the L. major challenge model with BALB/c mice. No adverse reactions were observed when three subcutaneous injections of the Leish-111f polyprotein formulated with either MPL-squalene (SE) or Ribi 529-SE were given to BALB/c mice. A predominant Th1 immune response characterized by in vitro lymphocyte proliferation, gamma interferon production, and immunoglobulin G2A antibodies was observed with little, if any, IL-4. Moreover, Leish-111f formulated with MPL-SE conferred immunity to leishmaniasis for at least 3 months. These data demonstrate success at designing and developing a prophylactic leishmaniasis vaccine that proved effective in a preclinical model using multiple leishmanial antigens produced as a single protein delivered with a powerful Th1 adjuvant suitable for human use.
Lymphotoxin amplification of tumor growth inhibition is specific for natural killer cells but not for macrophages (1983)

Lymphotoxin augments the susceptibility of tumorigenic guinea-pig cells to natural killer (NK) cell cytolysis in vitro but does not directly stimulate either NK cell or macrophage cytolytic action. The question whether lymphotoxin enhances the susceptibility of tumorigenic guinea-pig cells to cytolysis or other means of growth inhibition in vivo by syngeneic NK cells or macrophages was, therefore, examined using a modified tumor cell neutralization (Winn) assay. Mineral oil-, thioglycollate- or casein-induced peritoneal leukocytes, but not the macrophages isolated from the elicited leukocytes obtained from nonimmunized strain 2/N guinea-pigs, effected enhanced cytolysis of lymphotoxin-treated guinea-pig benzo (a)pyrene-induced 104CI tumor cells in vitro. Neither guinea-pig splenic NK cells nor oil-induced peritoneal macrophages alone inhibited the growth of 104CI cells as tumors in vivo when admixed with 104CI cells and injected into guinea-pigs. However, when the 104CI cells were treated with lymphotoxin before addition of effector cells, NK cells but not macrophages significantly reduced tumor growth in vivo. Therefore, the ability of lymphotoxin to increase the sensitivity of tumor cells to destruction mediated by natural leukocytes is specific for NK cells as compared to macrophages. This form of lymphokine amplification of natural leukocyte cytotoxicity may be one mechanism by which natural and acquired immunity serves or fails to prevent cancer and should be an important consideration in therapeutic approaches to eradicate or control tumor growth.
Performance of straight‐chain alkylbenzene sulfonates (LAS) in heavy‐duty detergents (1964)

Abstract The foamability (dishwashing and washing machine) and detergency of LAS in heavy‐duty detergents is directly compared with polypropylenɹ ABS (PPABS) at various mol wt, conen, water hardnesses and temp. In every case a peak in performance is obtained in the C 11 to C 17 side chain range. The peak is shifted to lower mol wt as water hardness is increased, especially at low detergent conen. LAS opt performance is generally equal to PPABS, except in dishwashing foam in soft water. The LAS peaks, however, are shifted to ca. one carbon lower mol wt than the PPABS. Therefore, best over‐all performance is obtained for LAS whose average mol wt corresponds to a 12.5 carbon side chain, whereas PPABS is best with an average 13.5 carbon side chain. Dishwashing foamability is markedly different for the different isomers contained in LAS. When the phenyl group it attached to the middle of the alkyl chain, surprisingly high results are obtained. This dishwashing difference is great enough to be noticeable when the isomer distribution changes in whole products made using different alkylation catalysts. Detergency and washing machine foam are not affected enough to see differences between whole alkylates. LAS solubility is greater than PPABS and is influenced by isomer distribution.
A new bottom-gated poly-Si thin-film transistor (1999)

We have proposed and fabricated the new bottom-gated poly-Si TFT with a partial amorphous-Si (a-Si) region by employing the selective laser annealing. The channel layer of the proposed TFTs is composed of poly-Si region in the center and a-Si region in the edge. The TEM image shows that the local a-Si region is successfully fabricated by the effective cut out of the incident laser light in the upper a-Si layer. Our experimental results show that the reverse leakage currents are decreased significantly in the new poly-Si TFT compared with conventional one. This reduction is due to the suppression of field emission currents by local a-Si region like that of a-Si TFTs while the ON currents are kept almost the same due to the considerable inducement of electron carriers in the short a-Si channel by the positive gate bias.
Surface micromachining for microelectromechanical systems (1998)

Surface micromachining is characterized by the fabrication of micromechanical structures from deposited thin films. Originally employed for integrated circuits, films composed of materials such as low-pressure chemical-vapor-deposition polycrystalline silicon, silicon nitride, and silicon dioxides can be sequentially deposited and selectively removed to build or "machine" three-dimensional structures whose functionality typically requires that they be freed from the planar substrate. Although the process to accomplish this fabrication dates from the 1960's, its rapid extension over the past few years and its application to batch fabrication of micromechanisms and of monolithic microelectromechanical systems (MEMS) make a thorough review of surface micromachining appropriate at this time. Four central issues of consequence to the MEMS technologist are: (i) the understanding and control of the material properties of microstructural films, such as polycrystalline silicon, (ii) the release of the microstructure, for example, by wet etching silicon dioxide sacrificial films, followed by its drying and surface passivation, (iii) the constraints defined by the combination of micromachining and integrated-circuit technologies when fabricating monolithic sensor devices, and (iv) the methods, materials, and practices used when packaging the completed device. Last, recent developments of hinged structures for postrelease assembly, high-aspect-ratio fabrication of molded parts from deposited thin films, and the advent of deep anisotropic silicon etching hold promise to extend markedly the capabilities of surface-micromachining technologies.