gebhart/patrepeval huggingface dataset:
Gas flow in ultra-tight shale strata (2012)

Abstract We study the gas flow processes in ultra-tight porous media in which the matrix pore network is composed of nanometre- to micrometre-size pores. We formulate a pressure-dependent permeability function, referred to as the apparent permeability function (APF), assuming that Knudsen diffusion and slip flow (the Klinkenberg effect) are the main contributors to the overall flow in porous media. The APF predicts that in nanometre-size pores, gas permeability values are as much as 10 times greater than results obtained by continuum hydrodynamics predictions, and with increasing pore size (i.e. of the order of the micrometre), gas permeability converges to continuum hydrodynamics values. In addition, the APF predicts that an increase in the fractal dimension of the pore surface leads to a decrease in Knudsen diffusion. Using the homogenization method, a rigorous analysis is performed to examine whether the APF is preserved throughout the process of upscaling from local scale to large scale. We use the well-known pulse-decay experiment to estimate the main parameter of the APF, which is Darcy permeability. Our newly derived late-transient analytical solution and the late-transient numerical solution consistently match the pressure decay data and yield approximately the same estimated value for Darcy permeability at the typical core-sample initial pressure range and pressure difference. Other parameters of the APF may be determined from independent laboratory experiments; however, a pulse-decay experiment can be used to estimate the unknown parameters of the APF if multiple tests are performed and/or the parameters are strictly constrained by upper and lower bounds.
The effects of sacral nerve stimulation on continence are temporarily maintained after turning the stimulator off (2013)

The effects of sacral nerve stimulation on faecal and urinary incontinence were maintained in about half of patients after switching the stimulator off, but in some symptoms returned after different periods of time. The data shed new light on possible effects of sacral nerve stimulation on brain neuroplasticity in the control of continence.
Effects of Renal Denervation on Sympathetic Activation, Blood Pressure, and Glucose Metabolism in Patients with Resistant Hypertension (2012)

Increased central sympathetic drive is a hallmark of several important clinical conditions including essential hypertension, heart failure, chronic kidney disease, and insulin resistance. Afferent signaling from the kidneys has been identified as an important contributor to elevated central sympathetic drive and increased sympathetic outflow to the kidney and other organs is crucially involved in cardiovascular control. While the resultant effects on renal hemodynamic parameters, sodium and water retention, and renin release are particularly relevant for both acute and long term regulation of blood pressure, increased sympathetic outflow to other vascular beds may facilitate further adverse consequences of sustained sympathetic activation such as insulin resistance, which is commonly associated with hypertension. Recent clinical studies using catheter-based radiofrequency ablation technology to achieve functional renal denervation in patients with resistant hypertension have identified the renal nerves as therapeutic target and have helped to further expose the sympathetic link between hypertension and insulin resistance. Initial data from two clinical trials and several smaller mechanistic clinical studies indicate that this novel approach may indeed provide a safe and effective treatment alternative for resistant hypertension and some of its adverse consequences.
Dendritic cell vaccines for cancer treatment. (2002)

The success of cancer immunotherapy depends on two major factors: adequate tumor-specific antigens and a vehicle capable of inducing a tumor-specific immune response by effective delivery of these antigens. Dendritic cells (DCs) are the most powerful antigen presenting cells, and because of their unique characteristics, these cells are actively used in cancer immunotherapy. In this review we describe recent data regarding different methods of loading these cells with tumor-associated antigens, including RNA or DNA transfer. We will discuss requirements for DC activation as pre-requisite for the success of cancer immunotherapy.
Synthesis and biological study of aminoglycoside derivatives to overcome bacterial resistance (2010)

Aminoglycosides are broad-spectrum antibiotics that target the A-site of bacterial 16S ribosomal RNA. Their use, however, is increasingly threatened by the rapid spread of resistance. One of the most common determinants of aminoglycoside resistance in bacteria is the expression of a class of enzymes known as aminoglycoside 6â²-N-acetyltransferases (AAC(6â²)s). These enzymes use acetylcoenzyme A (AcCoA) to acetylate most aminoglycosides at the 6â²-NH2, thus decreasing their affinity for RNA and leading to bacterial resistance. One strategy pursued by the Auclair research group to overcome aminoglycoside resistance is to develop AAC(6â²) inhibitors. Chapter 2 of this thesis describes enzymatic studies with the group's first generation of inhibitors, aminoglycoside-CoA bisubstrates and truncated analogs. The bisubstrates exhibited potent nanomolar competitive inhibition of the Enterococcus faecium isoform AAC(6â²)-Ii and proved to be useful mechanistic and structural probes. They did not however show activity in cells. Enzymatic studies with truncated bisubstrates allowed extensive SAR studies and led to the discovery of a second generation of inhibitors, one of which is capable of blocking aminoglycoside resistance in cells expressing AAC(6â²)-Ii. To improve the potency of this compound, a series of derivatives with various amide groups replacing the ester functionality were synthesized. It was hypothesized that this modification would increase potency and biological stability. To our surprise however these small changes had a negative impact on the interaction between the inhibitors and AAC(6â²)-Ii. Chapter 3 describes our second approach to counter aminoglycoside resistance, which involved the synthesis of new aminoglycosides designed to be active against resistant bacterial strains. A series of neamine N-6â²-acylated derivatives were designed to retain the hydrogen bonding ability of 6â²-N to RNA, yet disrupt binding to AAC(6â²)-Ii. Some of these compounds showed moderate but not clinically relevant activity in cells.Finally, the third approach elaborated in Chapter 4 is to design prodrugs with dual, resistance inhibition and antibacterial activities. The goal was to develop aminoglycoside N-6â² derivatives as prodrugs that were expected to be extended to bisubstrate analogs by the CoA biosynthetic enzymes in bacteria. The resulting bisubstrates were expected to not only block aminoglycoside resistance via AAC(6â²) inhibition, but to also kill bacteria by blocking the fatty acid biosynthetic pathway. A small series of aminoglycoside derivatives was thus synthesized. Unexpectedly none of them showed direct antibacterial activity. Preliminary biological studies however suggest that even in the absence of in vitro AAC(6â²) inhibition, these molecules can potentiate the activity of aminoglycosides against an aminoglycoside resistant strain. To our knowledge they are the first reported prodrugs able to block aminoglycoside resistance in cells.
Postoperative hepatitis status as a significant risk factor for recurrence in cirrhotic patients with small hepatocellular carcinoma (1996)

This study suggests that the hepatitis status of the remnant liver plays an important role in the recurrence rates and patterns of small HCC after hepatectomy.
The Maltodextrin System ofEscherichia coli: Metabolism and Transport (2005)

The maltose/maltodextrin regulon of Escherichia coli consists of 10 genes which encode a binding protein-dependent ABC transporter and four enzymes acting on maltodextrins. All mal genes are controlled by MalT, a transcriptional activator that is exclusively activated by maltotriose. By the action of amylomaltase, we prepared uniformly labeled [(14)C]maltodextrins from maltose up to maltoheptaose with identical specific radioactivities with respect to their glucosyl residues, which made it possible to quantitatively follow the rate of transport for each maltodextrin. Isogenic malQ mutants lacking maltodextrin phosphorylase (MalP) or maltodextrin glucosidase (MalZ) or both were constructed. The resulting in vivo pattern of maltodextrin metabolism was determined by analyzing accumulated [(14)C]maltodextrins. MalP(-) MalZ(+) strains degraded all dextrins to maltose, whereas MalP(+) MalZ(-) strains degraded them to maltotriose. The labeled dextrins were used to measure the rate of transport in the absence of cytoplasmic metabolism. Irrespective of the length of the dextrin, the rates of transport at a submicromolar concentration were similar for the maltodextrins when the rate was calculated per glucosyl residue, suggesting a novel mode for substrate translocation. Strains lacking MalQ and maltose transacetylase were tested for their ability to accumulate maltose. At 1.8 nM external maltose, the ratio of internal to external maltose concentration under equilibrium conditions reached 10(6) to 1 but declined at higher external maltose concentrations. The maximal internal level of maltose at increasing external maltose concentrations was around 100 mM. A strain lacking malQ, malP, and malZ as well as glycogen synthesis and in which maltodextrins are not chemically altered could be induced by external maltose as well as by all other maltodextrins, demonstrating the role of transport per se for induction.
Plasmid DNA containing multiple CpG motifs triggers a strong immune response to hepatitis B surface antigen when combined with incomplete Freund’s adjuvant but not aluminum hydroxide (2012)

Adjuvants are important components of recombinant protein vaccines which are often poorly immunogenic. For decades, the search for new vaccine adjuvants has been predominantly empirical. In addition, combinations of more than one adjuvant plus antigen have been systematically studied. Plasmid DNA containing additional oligodeoxynucleotides with unmethylated CpG motifs (CpG ODN) entrapped in liposomes has been used as an adjuvant for DNA vaccines and has shown powerful immunostimulatory functions. In our study, the combination of plasmid DNA containing 16 additional CpG ODNs (pv-16CpG) and aluminum hydroxide (AL) or incomplete Freund's adjuvant (IFA) was used as an adjuvant for a hepatitis B surface antigen (HBsAg) vaccine to immunize C57BL/6J mice. ELISA and ELISPOT assays were used to analyze the immunological effects of the novel vaccine. A significant enhancement of the anti-HBs titer and seroconversion was observed when the CpG plasmid was combined with IFA, but not with AL. In addition, anti-HBs antibody isotype analysis revealed that the combination of CpG plasmid and IFA induced a strong HBsAg-specific IgG2a response. Moreover, the ELISPOT assays suggested that pv-16CpG suspended in IFA evoked a strong T helper 1 (Th1) immune response and high IFN-γ production. These results demonstrate that pv-16CpG suspended in IFA is able to induce cellular and humoral immune responses to HBsAg, and confirm its potential as an adjuvant for use in protein vaccines.
Stereo- and Regiospecific Cu-Catalyzed Cross-Coupling Reaction of Vinyl Iodides and Thiols: A Very Mild and General Route for the Synthesis of Vinyl Sulfides (2008)

A mild and efficient method for the copper-catalyzed formation of vinylic carbon-sulfur bonds has been developed. The desired vinyl sulfides are obtained in good to excellent yields, with full retention of stereochemistry. This method is particularly noteworthy given its mild reaction conditions, simplicity, and generality, as well as low cost of the catalyst system.
Reduced Expression of Syndecan‐1 Affects Metastatic Potential and Clinical Outcome in Patients with Colorectal Cancer (2001)

Syndecan-1 is a transmembrane heparansulfate proteoglycan which regulates cell-to-cell or cell-to-extracellular matrix interactions and may influence malignant cell behavior. We investigated the alterations of syndecan-1 expressions in colorectal cancers and analyzed the relationship between histological and clinical characteristics. Syndecan-1 protein expression in colorectal cancer tissues was investigated with immunohistochemical staining of resected specimens. In situ hybridization was performed using syndecan-1 riboprobe to confirm the transcriptional signals. Syndecan-1 mRNA expression in cancer cell lines cultured with or without methylation inhibitor was also analyzed by quantitative PCR. Out of 105 specimens tested, less than 25% of tumor cells were stained with anti-syndecan-1 monoclonal antibody in 36 (34.3%). In situ hybridization showed a similar staining profile to that of immunohistochemistry. Syndecan-1 mRNA expression was increased by the methylation inhibitor 5-aza-2'-deoxycytidine, suggesting that the hypermethylation is involved in the suppression of syndecan-1 expression. Clinically, the incidence of metastasis to lymphnode or liver in patients with syndecan-1-negative tumors was significantly high. Among T1 colorectal cancers displaying a primary invasive phase, lymphnode metastasis, undifferentiated characters and 'budding' of cancer cells were more common in syndecan-1-negative tumors. The survival rate in patients with syndecan-1-negative tumors was decreased significantly in a stage-independent manner. These results suggest that the reduction of syndecan-1 expression in colorectal cancer cells, which is supposed to be regulated at the transcription level, is closely related to invasive character. The evaluation of syndecan-1 expression in colorectal cancer may allow prediction of patients' survival after surgery.
The NULL Encryption Algorithm and Its Use With IPsec (1998)

This memo defines the NULL encryption algorithm and its use with the IPsec Encapsulating Security Payload (ESP). NULL does nothing to alter plaintext data. In fact, NULL, by itself, does nothing. NULL provides the means for ESP to provide authentication and integrity without confidentiality.
Synthesis of lipid A and its analogues for investigation of the structural basis for their bioactivity (2005)

As a step to elucidate the structural requirements for the endotoxic and antagonistic activity of lipid A derivatives, we have focused, in the present study, on the effects of the acyl moieties and acidic groups at the 1- and 4′- positions. We synthesized a new analogue corresponding to Rubrivivax gelatinosus lipid A, which has a characteristic symmetrical distribution of acyl groups on the two glucosamine residues with shorter acyl groups (decanoyl groups [C 10 ] and lauryl groups [C 12 ]) than Escherichia coli lipid A. Carboxymethyl analogues in which one of the phosphates was replaced with a carboxymethyl group were also synthesized with different distribution of acyl groups. Biological tests revealed that the distribution of acyl groups strongly affected the bioactivity. The synthetic Ru. gelatinosus type lipid A showed potent antagonistic activity against LPS, whereas its 1- O-carboxymethyl analogue showed weak endotoxic activity. These results demonstrated that when the lipid A has shorter (C 10 , C 12 ) hexa-acyl groups, the bioactivity of lipid A is easily affected with small structural difference, such as the difference of acidic group or the distribution of acyl groups, and the bioactivity changes from endotoxic to agonistic or vice versa at this structural boundary for the bioactivity. We also designed, based on molecular mechanics calculations, and synthesized lipid A analogues possessing acidic amino acid residues in place of the non-reducing end phosphorylated glucosamine. Definite switching of the endotoxic or antagonistic activity was also observed depending on the difference of the acidic groups (phosphoric acid or carboxylic acid) in the lipid A analogues.
Cutting Edge: Rac GTPases Sensitize Activated T Cells to Die via Fas (2007)

In activated CD4(+) T cells, TCR restimulation triggers apoptosis that depends on interactions between the death receptor Fas and its ligand, FasL. This process, termed restimulation-induced cell death (RICD), is a mechanism of peripheral immune tolerance. TCR signaling sensitizes activated T cells to Fas-mediated apoptosis, but what pathways mediate this process are not known. In this study we identify the Rho GTPases Rac1 and Rac2 as essential components in restimulation-induced cell death. RNA interference-mediated knockdown of Rac GTPases greatly reduced Fas-dependent, TCR-induced apoptosis. The ability of Rac1 to sensitize T cells to Fas-induced apoptosis correlated with Rac-mediated cytoskeletal reorganization, dephosphorylation of the ERM (ezrin/radixin/moesin) family of cytoskeletal linker proteins, and the translocation of Fas to lipid raft microdomains. In primary activated CD4(+) T cells, Rac1 and Rac2 were independently required for maximal TCR-induced apoptosis. Activating Rac signaling may be a novel way to sensitize chronically stimulated lymphocytes to Fas-induced apoptosis, an important goal in the treatment of autoimmune diseases.
Heterogeneity in Serpin−Protease Complexes As Demonstrated by Differences in the Mechanism of Complex Breakdown (2001)

Serpins trap their target proteases in the form of an acyl-enzyme complex. The trap is kinetic, however, and thus serpin-protease complexes ultimately break down, releasing a cleaved inactive serpin and an active protease. The rates of this deacylation process vary greatly depending on the serpin-protease pair with half-lives ranging from minutes to months. The reasons for the diversity in breakdown rates are not clearly understood. In the current study, pH and solvent isotope effects were utilized to probe the mechanism of breakdown for an extremely stable complex and several unstable complexes. Two different patterns for the pH dependence of k(bkdn), the first-order rate constant of breakdown, were found. The stable complex, which breaks down at neutral pH with a half-life of approximately 2 weeks, exhibited a pH-k(bkdn) profile consistent with solvent-hydroxide ion mediated ester hydrolysis. There was no evidence for the participation of the catalytic machinery in the breakdown of this complex, suggesting extensive distortion of the active site. The unstable complexes, which break down with half-lives ranging from minutes to hours, exhibited a bell-shaped pH profile for k(bkdn), typical of the pH-rate profiles of free serine proteases. In the low to neutral pH range k(bkdn) increased with increasing pH in a manner characteristic of His57-mediated catalysis. In the alkaline pH range a decrease in k(bkdn) was observed, consistent with the titration of the Ile16-Asp194 salt bridge (chymotrypsinogen numbering). The alkaline pH dependence was not exhibited in pH-rate profiles of free or substrate-bound HNE, indicating that the salt bridge was significantly destabilized in the complexed protease. These results indicate that breakdown is catalytically mediated in the unstable complexes although, most likely, the protease is not in its native conformation and the catalytic machinery functions inefficiently. However, a mechanism in which breakdown is determined by the equilibrium between distorted and undistorted forms of the complexed protease cannot be completely dismissed. Overall, the results of this study suggest that the protease structure in unstable complexes is distorted to a lesser extent than in stable complexes.
Evaluation of Post-Weld Heat Treatments to Restore the Corrosion Resistance of Friction Stir Welded Aluminum Alloy 7075-T73 vs. 7075-T6 (2007)

Friction stir welding (FSW) is rapidly becoming accepted as a viable manufacturing process for aerospace applications. One potential area of concern, however, is the corrosion resistance of some FSW joints. While the corrosion resistance of friction stir welded 7075 aluminum has been investigated, and attempts made to enhance its corrosion resistance through different combinations of starting temper and post-weld artificial aging (PWAA) treatments, a clear approach for selecting pre-temper conditions and PWAA processing has not emerged. For this investigation, FSW butt-welds in sheets of 0.125-inch 7075-T73 and 7075-T6 were given a variety of PWAA treatments, some of which were developed previously by other authors. Thermal treatments were evaluated using optical microscopy, exfoliation, electrical conductivity, microhardness, tensile, and fatigue crack propagation testing. An important conclusion drawn from this work is that 7075-T73 can be friction stir welded and post-weld aged in a manner that produces superior exfoliation resistance and good mechanical properties without invalidating the bulk parent material temper specified in AMS 2770G.
Integrated-optic wavelength multiplexers on lithium niobate based on two-mode interference (1988)

The principle of the wavelength-dependent two-mode interference (TMI) in guided wave devices is utilized to build up integrated-optic dual-channel wavelength-division multi-/demultiplexers (WDM) for single-mode systems. The device characteristics are analyzed by analytical and numerical methods where special emphasis is given to the wavelength dependence of the channel spacing. These devices are fabricated by titanium indiffusion into X-cut and Y- and Z-propagating LiNbO/sub 3/, where the Z-propagating configuration is preferred for polarization independent operation. In the wavelength range between 1.3 and 1.6 mu m, insertion losses (fiber-waveguide-fiber) below 3 dB, channel spacings of 30-40 nm, and far-end crosstalk values of 26-40 dB are achieved. The measured low temperature sensitivity of the wavelength shift of 5.6*10/sup -2/ nm/ degrees C and the possibility of electrooptic tuning at a rate of 2.5 nm/V allow the realization of high performance devices at reduced fabrication tolerances.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Review article (1997)

Urantia: The Great Cult Mystery Martin Gardner Amherst: Prometheus Books, 1995 445 pp., 6 appendixes + name index, £22.00 (hb) ISBN 0–87975–955–0
Dissociation of Human Chorionic Gonadotrophin into its Free Subunits is Dependent on Naturally Occurring Molecular Structural Variation, Sample Matrix and Storage Conditions (1998)

Measurement of human chorionic gonadotrophin (hCG) is used in many areas of clinical medicine. Recent interest has focused on the stability of this molecule and its fragments during sample storage. In the body hCG is degraded and removed by specific metabolic processes which begin while the molecule is in the bloodstream. In particular, the receptor binding loop of the beta subunit is cut or 'nicked', initiating a catabolic cascade. Furthermore, the extent and nature of glycosylation is believed to have a significant influence on this process. In these studies we incubated seven glycoforms of hCG, each with different degrees of 'nicking', in phosphate-buffered saline, serum, defibrinated blood and urine from healthy non-pregnant women, under varying conditions. Degradation was expressed as the molar increase in free beta subunit. Under all conditions there was a steady dissociation of hCG over time, the process being more rapid at higher temperatures. 'Nicked' hCG dissociated more rapidly than did non-'nicked' hCG. Glycosylation reduced the rate of dissociation. Dissociation was most rapid in urine and buffer solutions, and slowest in serum and defibrinated blood.