gebhart/patrepeval huggingface dataset:
Noise From Voltage-Gated Ion Channels May Influence Neuronal Dynamics in the Entorhinal Cortex (1998)

Neurons of the superficial medial entorhinal cortex (MEC), which deliver neocortical input to the hippocampus, exhibit intrinsic, subthreshold oscillations with slow dynamics. These intrinsic oscillations, driven by a persistent Na+ current and a slow outward current, may help to generate the theta rhythm, a slow rhythm that plays an important role in spatial and declarative learning. Here we show that the number of persistent Na+ channels underlying subthreshold oscillations is relatively small (<10(4)) and use a physiologically based stochastic model to argue that the random behavior of these channels may contribute crucially to cellular-level responses. In acutely isolated MEC neurons under voltage clamp, the mean and variance of the persistent Na+ current were used to estimate the single channel conductance and voltage-dependent probability of opening. A hybrid stochastic-deterministic model was built by using voltage-clamp descriptions of the persistent and fast-inactivating Na+ conductances, along with the fast and slow K+ conductances. All voltage-dependent conductances were represented with nonlinear ordinary differential equations, with the exception of the persistent Na+ conductance, which was represented as a population of stochastic ion channels. The model predicts that the probabilistic nature of Na+ channels increases the cell's repertoire of qualitative behaviors; although deterministic models at a particular point in parameter space can generate either subthreshold oscillations or phase-locked spikes (but rarely both), models with an appropriate level of channel noise can replicate physiological behavior by generating both patterns of electrical activity for a single set of parameters. Channel noise may contribute to higher order interspike interval statistics seen in vitro with DC current stimulation. Models with channel noise show evidence of spike clustering seen in brain slice experiments, although the effect is apparently not as prominent as seen in experimental results. Channel noise may contribute to cellular responses in vivo as well; the stochastic system has enhanced sensitivity to small periodic stimuli in a form of stochastic resonance that is novel (in that the relevant noise source is intrinsic and voltage-dependent) and potentially physiologically relevant. Although based on a simple model that does not include all known membrane mechanisms of MEC stellate cells, these results nevertheless imply that the stochastic nature of small collections of molecules may have important effects at the cellular and network levels.
Vascular ultrasound for the pre-operative evaluation prior to arteriovenous fistula formation for haemodialysis: review of the evidence (2008)

The arteriovenous fistula (AVF) is the preferred access for haemodialysis [1]. However, AVF failure has become more common over the last three decades as more patients are older, and have diabetes or vascular disease. For radiocephalic AVF, a meta-analysis estimated modest primary (63%) and secondary (66%) patencies at 1 year [2]. AVF failures have been attributed to inadequate vessels used for surgery [3]. Pre-operative evaluation with ultrasound may select suitable vessels and reduce AVF failures [3]. We review the evidence for ultrasound evaluation for AVF formation. The following areas are addressed: • Ultrasound criteria for pre-operative evaluation • Pre-operative ultrasound findings and AVF outcomes • Comparison of pre-operative physical examination and ultrasound in terms of AVF outcomes.
Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence (2002)

Multiphoton microscopy relies on nonlinear light-matter interactions to provide contrast and optical sectioning capability for high-resolution imaging. Most multiphoton microscopy studies in biological systems have relied on two-photon excited fluorescence (TPEF) to produce images. With increasing applications of multiphoton microscopy to thick-tissue "intravital" imaging, second-harmonic generation (SHG) from structural proteins has emerged as a potentially important new contrast mechanism. However, SHG is typically detected in transmission mode, thus limiting TPEF/SHG coregistration and its practical utility for in vivo thick-tissue applications. In this study, we use a broad range of excitation wavelengths (730-880 nm) to demonstrate that TPEF/SHG coregistration can easily be achieved in unstained tissues by using a simple backscattering geometry. The combined TPEF/SHG technique was applied to imaging a three-dimensional organotypic tissue model (RAFT). The structural and molecular origin of the image-forming signal from the various tissue constituents was determined by simultaneous spectroscopic measurements and confirming immunofluorescence staining. Our results show that at shorter excitation wavelengths (<800 nm), the signal emitted from the extracellular matrix (ECM) is a combination of SHG and TPEF from collagen, whereas at longer excitation wavelengths the ECM signal is exclusively due to SHG. Endogenous cellular signals are consistent with TPEF spectra of cofactors NAD(P)H and FAD at all excitation wavelengths. The reflected SHG intensity follows a quadratic dependence on the excitation power, decays exponentially with depth, and exhibits a spectral dependence in accordance with previous theoretical studies. The use of SHG and TPEF in combination provides complementary information that allows noninvasive, spatially localized in vivo characterization of cell-ECM interactions in unstained thick tissues.
Soluble markers of allergic inflammation (1994)

Venge P. Soluble markers of allergic inflammation.
Transport of long-chain fatty acids by Escherichia coli: mapping and characterization of mutants in the fadL gene. (1978)

A new locus (fadL) that is required for the utilization of long-chain fatty acids has been mapped and partially characterized in an Escherichia coli mutant. The fadL locus has been mapped at 50 min on the chromosome. A mutant bearing a defect in this locus cannot utilize long-chain fatty acids as a sole carbon source. Derivatives of this mutant that can grow on decanoate (termed fadR) are capable of growth on medium-chain but not long-chain fatty acids. It is believed that the fadL mutants is defective in the transport of long-chain fatty acids into the cell for the following reasons: (i) fadR fadL strains can oxidize in vivo decanoate but not oleate; (ii) neither fadL nor fadR fadL strains can incorporate oleate into their membrane lipids; (iii) the activity of the acyl-CoA synthetase (EC 6.2.1.3) in fadR fadL strains is comparable to the acyl-CoA synthetase activity in fadR fadL+ strains; and (iv) in vitro extracts from fadR fadL+ strains. If the above hypothesis is correct, the uptake of long-chain fatty acids by E. coli requires at least two gene products.
Interferon, Cortisone, and Antivirals in the Treatment of Chronic Viral Hepatitis: A Review of 30 Years of Therapy (1997)

Over the last 30 years many approaches have been adopted to treat chronic hepatitis. We conducted a meta-analysis to assess the efficacy of various types of treatments. We selected 4 studies of cortisone in chronic hepatitis B; 21 trials of interferon treatment, 6 in chronic hepatitis B, 10 in chronic hepatitis C, and 5 in chronic hepatitis D; and 5 of combined cortisone and interferon treatment in chronic hepatitis B. The Mantel-Haenszel-Peto method was applied to extrapolated data. We completed the study by analyzing four studies of cortisone treatment of chronic hepatitis C, two of cortisone plus interferon alpha (IFN-alpha) for chronic hepatitis C, and antiviral therapy for hepatitis B, C, and D. Trials administering cortisone for chronic hepatitis B had an overall OR of 0.29 (CI 0.12-0.73). No virologic remissions were observed in patients with hepatitis C receiving prednisone, even if those with features of autoimmunity achieved a biohumoral sustained response. Overall ORs in the trials were were as follows: IFN for chronic hepatitis B, 0.27 (CI 0.17-0.46); IFN for chronic hepatitis C, 0.3 (CI 0.21-0.44); IFN for chronic hepatitis D, 0.16 (CI 0.06-0.47); and cortisone plus interferon for chronic hepatitis B, 0.25 (CI 0.15-0.41). Sustained response rates of chronic hepatitis C ranged from 15-24.2%. The only encouraging results were obtained by antivirals. To date the lack of a specific antiviral drug makes it uncertain as to the preferred agent for this disease.
Bacterial Volatiles Induce Systemic Resistance in Arabidopsis (2004)

Plant growth-promoting rhizobacteria, in association with plant roots, can trigger induced systemic resistance (ISR). Considering that low-molecular weight volatile hormone analogues such as methyl jasmonate and methyl salicylate can trigger defense responses in plants, we examined whether volatile organic compounds (VOCs) associated with rhizobacteria can initiate ISR. In Arabidopsis seedlings exposed to bacterial volatile blends from Bacillus subtilis GB03 and Bacillus amyloliquefaciens IN937a, disease severity by the bacterial pathogen Erwinia carotovora subsp. carotovora was significantly reduced compared with seedlings not exposed to bacterial volatiles before pathogen inoculation. Exposure to VOCs from rhizobacteria for as little as 4 d was sufficient to activate ISR in Arabidopsis seedlings. Chemical analysis of the bacterial volatile emissions revealed the release of a series of low-molecular weight hydrocarbons including the growth promoting VOC (2R,3R)-(-)-butanediol. Exogenous application of racemic mixture of (RR) and (SS) isomers of 2,3-butanediol was found to trigger ISR and transgenic lines of B. subtilis that emitted reduced levels of 2,3-butanediol and acetoin conferred reduced Arabidopsis protection to pathogen infection compared with seedlings exposed to VOCs from wild-type bacterial lines. Using transgenic and mutant lines of Arabidopsis, we provide evidence that the signaling pathway activated by volatiles from GB03 is dependent on ethylene, albeit independent of the salicylic acid or jasmonic acid signaling pathways. This study provides new insight into the role of bacteria VOCs as initiators of defense responses in plants.
Poly(γ-d-glutamic acid) protein conjugates induce IgG antibodies in mice to the capsule ofBacillus anthracis: A potential addition to the anthrax vaccine (2003)

Both the protective antigen (PA) and the poly(gamma-d-glutamic acid) capsule (gamma dPGA) are essential for the virulence of Bacillus anthracis. A critical level of vaccine-induced IgG anti-PA confers immunity to anthrax, but there is no information about the protective action of IgG anti-gamma dPGA. Because the number of spores presented by bioterrorists might be greater than encountered in nature, we sought to induce capsular antibodies to expand the immunity conferred by available anthrax vaccines. The nonimmunogenic gamma dPGA or corresponding synthetic peptides were bound to BSA, recombinant B. anthracis PA (rPA), or recombinant Pseudomonas aeruginosa exotoxin A (rEPA). To identify the optimal construct, conjugates of B. anthracis gamma dPGA, Bacillus pumilus gamma dLPGA, and peptides of varying lengths (5-, 10-, or 20-mers), of the d or l configuration with active groups at the N or C termini, were bound at 5-32 mol per protein. The conjugates were characterized by physico-chemical and immunological assays, including GLC-MS and matrix-assisted laser desorption ionization time-of-flight spectrometry, and immunogenicity in 5- to 6-week-old mice. IgG anti-gamma dPGA and antiprotein were measured by ELISA. The highest levels of IgG anti-gamma dPGA were elicited by decamers of gamma dPGA at 10 -20 mol per protein bound to the N- or C-terminal end. High IgG anti-gamma dPGA levels were elicited by two injections of 2.5 microg of gamma dPGA per mouse, whereas three injections were needed to achieve high levels of protein antibodies. rPA was the most effective carrier. Anti-gamma dPGA induced opsonophagocytic killing of B. anthracis tox-, cap+. gamma dPGA conjugates may enhance the protection conferred by PA alone. gamma dPGA-rPA conjugates induced both anti-PA and anti-gamma dPGA.
Acceptability of an oral contraceptive that reduces the frequency of menstruation: the tri-cycle pill regimen. (1977)

The frequency of menstruation was reduced to once every three months in 196 women by the continuous administration of the oral contraceptive pill, Minilyn, for 84 days (tri-cycle regimen). No pregnancies occurred. One hundred and sixty-one women (82%) welcomed the reduction in the number of periods with the associated freedom from menstrual and premenstrual symptoms, and many found the tri-cycle regimen easier to follow. Weight gain of more than 2 kg, irregular cycle control, especially in the first three months, breast tenderness, and headaches were the main side effects. Menstrual loss was unchanged or reduced in all but seven women. The doctors and nurses on the clinic staff were less enthusiastic about this regimen than the volunteers themselves.
Investigation of the Candidate Tumor Suppressor Gene prk in Prostate Cancer (2001)

Abstract : Prostate cancer is the most common malignancy among American men. Yet our understanding of the genetic events which occur during the course of the development of this disease has lagged behind that for other common tumors. Recent studies suggest that prostate cancer appears to be driven by the mutation of as yet unknown genes. The identification of such genes should be essential to the understanding of the biology and pathology of this disease. Allelotype analysis of prostate cancer has implicated several loci of candidate tumor suppressor genes (1-3). For example, loss of heterozygosity of polymorphic markers has been identified at 7q, 8p, 10, 16q and 18q (2,3). Of these, 8p is among the most frequently lost in prostate carcinoma (1-3). Detailed analyses have defined the region of allele loss in prostate and other cancers to 8p12-21 and 8p22-pter (1,4), suggesting that the presence of two or more tumor suppressor genes at this genomic locus.
Architectures for molecular electronic computers. I. Logic structures and an adder designed from molecular electronic diodes (2000)

Recently, there have been significant advances in the fabrication and demonstration of individual molecular electronic wires and diode switches. This paper reviews those developments and shows how demonstrated molecular devices might be combined to design molecular-scale electronic digital computer logic. The design for the demonstrated rectifying molecular diode switches is refined and made more compatible with the demonstrated wires through the introduction of intramolecular dopant groups chemically bonded to modified molecular wires. Quantum mechanical calculations are performed to characterize some of the electrical properties of the proposed molecular diode switches. Explicit structural designs are displayed for AND, OR, and XOR gates that are built from molecular wires and molecular diode switches. The diode-based molecular electronic logic gates are combined to produce a design for a molecular-scale electronic half adder and a molecular-scale electronic full adder. These designs correspond to conductive monomolecular circuit structures that would be one million times smaller in area than the corresponding micron-scale digital logic circuits fabricated on conventional solid-state semiconductor computer chips. It appears likely that these nanometer-scale molecular electronic logic circuits could be fabricated and tested in the foreseeable future. At the very least, such molecular circuit designs constitute an exploration of the ultimate limits of electronic computer circuit miniaturization.
Determination of Phenylalanine and Tyrosine by Liquid Chromatography/Mass Spectrometry (2003)

Phenylketonuria is a common metabolic disorder disease. Those affected appear normal at birth, but without treatment they develop severe psychomotor retardation. Throughout life, they must control their blood levels of phenylalanine (Phe) and consume a diet containing adequate amounts of Phe and tyrosine (Tyr). We have developed a liquid chromatographic/mass spectrometric (LC/MS) method for the quantitative evaluation of Phe and Tyr in food samples. This method takes advantage of the good separation of LC and the selective and reliable quantification provided by MS in the electrospray ionization mode. The LC/MS method is very suitable for the determination of selected amino acids in various matrixes. It is sensitive to levels as low as about 0.30 ppm for Tyr and 0.70 ppm for Phe and robust. Nearly 100 nondietary food samples were analyzed by the developed method.
Tissue engineering and cartilage (2008)

Human articular cartilage is an avascular structure, which, when injured, poses significant hurdles to repair strategies. Not only does the defect need to be repopulated with cells, but preferentially with hyaline-like cartilage.SUCCESSFUL TISSUE ENGINEERING RELIES ON FOUR SPECIFIC CRITERIA: cells, growth factors, scaffolds, and the mechanical environment. The cell population utilized may originate from cartilage itself (chondrocytes) or from growth factors that direct the development of mesenchymal stem cells toward a chondrogenic phenotype. These stem cells may originate from various mesenchymal tissues including bone marrow, synovium, adipose tissue, skeletal muscle, and periosteum. Another unique population of multipotent cells arises from Wharton's jelly in human umbilical cords. A number of growth factors have been associated with chondrogenic differentiation of stem cells and the maintenance of the chondrogenic phenotype by chondrocytes in vitro, including TGFbeta; BMP-2, 4 and 7; IGF-1; and GDF-5.Scaffolds chosen for effective tissue engineering with respect to cartilage repair can be protein based (collagen, fibrin, and gelatin), carbohydrate based (hyaluronan, agarose, alginate, PLLA/PGA, and chitosan), or formed by hydrogels. Mechanical compression, fluid-induced shear stress, and hydrostatic pressure are aspects of mechanical loading found in within the human knee joint, both during gait and at rest. Utilizing these factors may assist in stimulating the development of more robust cells for implantation.Effective tissue engineering has the potential to improve the quality of life of millions of patients and delay future medical costs related to joint arthroplasty and associated procedures.
Emerging Role of Lactobacilli in the Control and Maintenance of the Vaginal Bacterial Microflora (1990)

The vaginal microflora of healthy asymptomatic women consists of a wide variety (two to five isolates at any one time) of anaerobic and aerobic bacterial genera and species dominated by the facultative, microaerophilic, anaerobic genus Lactobacillus. That the vaginal flora forms part of a dynamically changing ecosystem is evident from the variable prevalence and population levels of each bacterial species detected with repetitive longitudinal sampling, with pregnancy, and with stage in the menstrual cycle. This review emphasizes the role that vaginal lactobacilli may play in control of the vaginal microflora and maintenance of the normal state. Lactobacilli possess many antagonistic properties and produce many metabolites that may be important in maintaining dominance in the vagina. Contradictory data from previous studies regarding the impact of factors such as contraception, catamenial products, and physiologic elements on the vaginal microflora are due in part to poor study design and differences in methodology. Well-designed and controlled investigations with large numbers of individuals in each group are needed, and the limitations of the methodology for such investigations must be considered. Studies of the normal flora, exploring the interaction of lactobacilli and other bacterial species, must be performed before the pathologic processes resulting in vaginitis or systemic sequelae are investigated.
Firefly luciferase gene: structure and expression in mammalian cells. (1987)

The nucleotide sequence of the luciferase gene from the firefly Photinus pyralis was determined from the analysis of cDNA and genomic clones. The gene contains six introns, all less than 60 bases in length. The 5' end of the luciferase mRNA was determined by both S1 nuclease analysis and primer extension. Although the luciferase cDNA clone lacked the six N-terminal codons of the open reading frame, we were able to reconstruct the equivalent of a full-length cDNA using the genomic clone as a source of the missing 5' sequence. The full-length, intronless luciferase gene was inserted into mammalian expression vectors and introduced into monkey (CV-1) cells in which enzymatically active firefly luciferase was transiently expressed. In addition, cell lines stably expressing firefly luciferase were isolated. Deleting a portion of the 5'-untranslated region of the luciferase gene removed an upstream initiation (AUG) codon and resulted in a twofold increase in the level of luciferase expression. The ability of the full-length luciferase gene to activate cryptic or enhancerless promoters was also greatly reduced or eliminated by this 5' deletion. Assaying the expression of luciferase provides a rapid and inexpensive method for monitoring promoter activity. Depending on the instrumentation employed to detect luciferase activity, we estimate this assay to be from 30- to 1,000-fold more sensitive than assaying chloramphenicol acetyltransferase expression.
Differential Effects of PAK1-activating Mutations Reveal Activity-dependent and -independent Effects on Cytoskeletal Regulation (1998)

PAKs are serine/threonine protein kinases that are activated by binding to Rac or Cdc42hs. Different forms of activated PAK1 have been reported to either promote membrane ruffling and focal adhesion assembly or cause focal adhesion disassembly and stress fiber dissolution. To understand the basis for these distinct morphological effects, we have examined the mechanism of mutational activation of PAK1, and characterized the effects of different active PAK1 proteins on cytoskeletal structure in vivo. We find that PAK1 contains an autoinhibitory domain that overlaps with its small G protein binding domain and that two separate activating mutations within this regulatory region each decrease autoinhibitory activity. Because only one of these mutations affects Cdc42hs binding activity, this indicates that activation of PAK1 by these mutations results from interference with the function of the autoinhibitory domain and not with small G protein binding activity. When we examined the morphological effects of these different forms of PAK1 in vivo, we found that PAK1 kinase activity was associated with disassembly of focal adhesions and actin stress fibers and that this may require interaction with potential SH3 domain-containing proteins. Lamellipodia formation and membrane ruffling caused by active PAK1 expression, however, was independent of PAK1 catalytic activity and likely requires interaction among multiple proteins binding to the PAK1 regulatory domain.
Novel tetracyclic spiropiperidines. II. Synthesis of 2‐aryl‐2,3‐dihydrospiro[benzofuran‐3,4′‐piperidines] (1981)

Abstract A series of 2‐aryl‐2,3‐dihydropsiro[benzofuran‐3,4′‐piperidines] has been synthesized as potential psychotropic agents via an efficient intramolecular fluorine displacement reaction. Treatment of a key intermediate, 4‐cyano‐4‐(2‐fluorophenyl)‐1‐methylpiperidine ( 2 ), with a large excess of phenylmagnesium bromide in refluxing tetrahydrofuran led to some 2‐arylspiro[3 H ‐indole‐3,4′‐piperidine] derivatives, 10 and 11 , whose structures are elucidated on the basis of chemical and spectral evidence.