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PubMed1981

Community noise levels in Patras, Greece.

In the city of Patras (Greece), noise measurements were made for the purposes of determining the present noise-pollution levels and the reaction of the people to them. For the latter purpose, a social survey was conducted with the use of a relevant questionnaire which was applied to 500 citizens. Its results show that noise pollution is ranked second in order after air pollution, and that traffic was the principal noise pollutant. The mean noise levels, in 25 monitoring stations throughout the city, were found to be high and definitely unacceptable. For three representative locations, corresponding to high, medium, and low traffic volume, the various statistical noise descriptors, such as Leq, LNP Ldn and others, were used, together with the other measurements, to estimate the noise environment of the entire city. The high degree of annoyance of the people is justified by the high values of Leq, LNP, Ldn, and TNI that were found.

Behavior↗
PubMed1991

Properties of high-threshold mechanoreceptors in the oral mucosa. I. Responses to dynamic and static pressure.

1. Mechanical response properties of high-threshold mechanoreceptors (HTMs) of the goat oral mucosa were determined by single-unit recording from the palatine and alveolar nerves and from the trigeminal ganglion. The following observations were made. 2. HTMs of the oral mucosa could be separated into two subgroups on the basis of their threshold to mechanical stimulation. Intense pressure receptors (IPRs) comprised a group of A-delta afferents with thresholds of 2-16 g. Mechanonociceptors (MNs) comprised a group of relatively slowly conducting afferents (A-delta and C-fibers) with a higher threshold range (16-300 g). 3. In most instances, MNs lacked pressure-transducing capacity. Tests of reactivity to dynamically or statically applied stimuli revealed that significant functions were rarely fit between MN activity and pressure (4/20 cases). 4. IPRs differed from MNs by their pressure-transducing properties. The afferent response interval was in inverse proportion to the applied pressure. Significant pressure interval functions were fit in 16/20 cases. The relationship between pressure and response interval was best described by power functions. 5. Tests of reactivity to dynamically or statically applied stimuli revealed that IPRs preferred static pressure. Tighter fits and steeper slopes were observed in power functions fit to data generated by statically applied stimuli (mean fitted function, dynamic test: LnISI = -0.97 LnP + 3.4; mean fitted function, static test: LnISI = -1.6 LnP + 4.71). 6. Pressures-frequency thresholds (PFTs), asymptotes (PFAs), and mean response intervals (MRIs) were determined for IPRs from the static test series. The first two values are the pressures that produce the lower and upper limits of response frequency of mucosal HTMs (mean PFT, 1.48 N/mm2; mean PFA, 3.34 N/mm2). The MRI (28 ms) is simply computed from the function. When PFTs and PFAs are combined with activation threshold and power functions, they provide a relatively complete description of the range and form of reactivity of the IPR of the oral mucosa.

Animals↗
PubMed1981

Myocardial release of citrate and lactate during atrial pacing-induced angina pectoris.

Arterio-coronary sinus (A-Cs) differences of plasma citrate, glucose, free fatty acids and blood lactate were measured in 19 patients with coronary artery disease (CAD) and in eight control subjects exposed to atrial pacing. Among patients with CAD 11 showed a myocardial release of lactate during pacing (lactate producers, LP) while myocardial lactate extraction was unchanged in the remaining eight patients (lactate non-producers, LNP). In patients with CAD, (A-Cs) plasma citrate differences became increasingly negative during recovery from pacing, values at rest and at 3-5 min of recovery were: -5 +/- 2 mumol/l (mean +/- SD) vs. -12 +/- 5 mumol/l in LP (P less than 0.001) and -6 +/- 3 mumol/l vs. -8 +/- 4 mumol/l in LNP (P less than 0.01). In controls, (A-Cs) citrate difference varied inversely, from -8 +/- 4 mumol/l at rest to -2 +/- 4 mumol/l at 3-5 min of recovery (P less than 0.001). An increasingly negative (A-Cs) plasma citrate difference during recovery from pacing-induced angina pectoris is suggested to reflect a wash-out of accumulated citrate from ischaemic heart cells; and is proposed as a more sensitive marker of ischaemia in man than a myocardial release of lactate.

Adult↗
PubMed1979

[The diagnostic value of various stiffness indices in the evaluation of the diastolic properties of the left ventricle].

The results are presented of simulated calculations obtained with the aid of a continuum model of the left ventricle in a passive state on the basis of a nonlinear elasticity theory. Various empirical indexes of left ventricular rigidity are calculated from modelled diastolic pressure/volume curves, and are compared with myocardial elasticity indicators. With respect to sensitivity and specificity, as the best there were found the volume-standardized Diamond index (d[lnP]/dV)V0 and the Laird index d(lnP)/d/lnV). The indexes are calculated from two parts of enddiastolic pressure/volume values. An analysis of clinically measured values confirmed the model predictions.

Blood Pressure↗
PubMedDate not supplied

[Central circulation in the healthy human being during 7 days of head-down tilt and decompression of different body areas].

The effect of 7-day head-down tilt (-15 degrees) and decompression of various body parts (lower body-LBNP, upper body in the area of the hydrostatically indifferent point-UBNP, and local negative pressure applied to both calves-LNP) on central circulation was investigated on eight healthy test subjects who, for 10 days, had catheters (Swan-Ganz) implanted into the pulmonary and radial arteries. It was shown that, when calculated by square centimeter of the decompression area, the effect of UBNP on central venous pressure (CVP) and pulmonary artery pressure (PAP) was 3-4 times greater than that of LBNP or LNP. This indicates a high sensitivity of this body part to the exposure. During the 7-day study, CVP and PAP showed the most distinct changes. By the 7th hour of the head-down tilt study, CVP remained unchanged and systolic PAP increased by 5.5 mm Hg (27%) (p less than 0.05). This was paralleled by a decrease of plasma aldosterone and renin. By the 2nd day of the study, CVP and PAP were close to the pretest level; on the 3rd day, they began to decline and remained about 3 mm Hg lower than the pretest values to the end of the study (p less than 0.05). During this same period, the contractility of the right heart (the mean rate of right ventricular pressure increment) decreased by 34% (p less than 0.05) and its work by 27% (p less than 0.05). By the 24th hour after the study (the recovery period), CVP and PAP were close to the pretest values, whereas heart rate, cardiac index and oxygen tension in the mixed venous blood were significantly higher than the pretest values (p less than 0.05). The factors responsible for these changes and the potential application of the catheterization technique in biomedical investigations during real space flight are discussed.

Adult↗
PubMed1983

Central circulation of a normal man during 7-day head-down tilt and decompression of various body parts.

The effect of 7-d head-down tilt (-15 degrees) and decompression of various body parts (lower body--LBNP, upper body in the area of the hydrostatically indifferent point--UBNP, and local negative pressure applied to both calves--LNP) on central circulation was investigated on eight healthy test subjects who, for 10 d, had catheters (Swan-Ganz) implanted into the pulmonary and radial arteries. It was shown that, when calculated by square centimeter of the decompression area, the effect of UBNP on central venous pressure (CVP) and pulmonary artery pressure (PAP) was 3-4 times greater than that of LBNP or LNP. This indicates a high sensitivity of this body part to the exposure. During the 7-d study, CVP and PAP showed the most distinct changes. By the 7th hour of the head-down tilt study, CVP remained unchanged and systolic PAP increased by 5.5 mm Hg (27%) (p less than 0.05). This was paralleled by a decrease of plasma aldosterone and renin. By the 2nd day of the study, CVP and PAP were close to the pretest level; on the 3rd day, they began to decline and remained about 3 mm Hg lower than the pretest values to the end of the study (p less than 0.05). During this same period, the contractility of the right heart (the mean rate of right ventricular pressure increment) decreased by 34% (p less than 0.05) and its work by 27% (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

Visual evoked potential evidence for parallel processing of depth- and form-related information in human visual cortex.

This paper describes the first of two complementary studies designed to identify and to investigate the properties and likely functional significance of independently generated components of scalp-recorded responses evoked by stationary patterns. These experiments compared the influence of various stimulus parameters, including site of stimulation, pattern form, nature of background field and several binocular and monocular depth cues on a single subject's visual evoked potentials. The results revealed the presence, inter alia, of two topographically distinct components with the following properties. The earlier component (C2), whose polarity depends on the stimulus location in the visual field, is: contour-specific; best evoked by discrete pattern elements, but not gratings, in the central few degrees of the visual field; insensitive to any depth cues. By contrast, the later (consistently) negative potential (LNP) is not dependent on the form of the stimulus and is larger for paracentrally (beyond 1.5 degrees) than centrally located stimuli. It is also selectively enhanced by both monocular and binocular depth-cue stimuli, including the simulated forward movement of a pattern relative to a steady textured background; a stimulus which evokes no C2. The respective response properties of these scalp potentials suggest that there is parallel processing of depth- and contour-related features of stationary stimuli in anatomically separate regions of the human visual cortex.

Cues↗
PubMed2006

Opposite to alpha2-adrenergic agonists, an imidazoline I1 selective compound does not influence reflex bradycardia in rabbits.

This work aimed to study the respective effects of central alpha2-adrenergic receptors (alpha2-ARS) and I1 imidazoline receptors (I1Rs) in the facilitatory effects of imidazoline-like drugs on the reflex bradycardia (RB). Experiments were performed in anaesthetized rabbits. The reflex bradycardic response was induced by phenylephrine injected i.v. LNP 509, rilmenidine and dexmedetomidine were administered intracisternally (i.c.). LNP509 (1 mg/kg, i.c.), a ligand highly selective for I1Rs, induced hypotension (54+/-3 vs. 93+/-2 mm Hg) and bradycardia (260+/-13 vs. 322+/-13 beats/min) (p<0.05, n=5) but did not affect RB. Rilmenidine (1 microg/kg, i.c.), a hybrid ligand which binds to both I1 and alpha2-ARS, also decreased arterial pressure (61+/-2 vs. 101+/-2 mm Hg) and heart rate (260+/-4 vs. 308+/-8) (p<0.01, n=5); it potentiated the RB (maximum R-R interval: 284+/-17 vs. 196+/-6 ms) (p<0.05, n=5). Dexmedetomidine (1 microg/kg, i.c.), a ligand selective for alpha2-ARs, reduced blood pressure (53+/-3 vs. 104+/-2 mm Hg) and heart rate (246+/-4 vs. 312+/-8 beats/min) (p<0.05, n=5) and potentiated the RB (maximum R-R interval: 518+/-38 vs. 194+/-4 ms) (p<0.05, n=5). The potentiation of RB was much greater than that observed with rilmenidine and was significantly prevented by L-NNA injected centrally. This study shows that: (i) an exclusive action on I1Rs which decreases arterial pressure, does not potentiate the RB ii) activation of alpha2-ARs potentiates the RB (iii) the R-R prolongation caused by alpha2-ARs stimulation is prevented by central NOS inhibition.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2006

Information coding capacity of cerebellar parallel fibers.

Understanding synaptic connectivity is a prerequisite to gaining insight on how the central nervous system processes information. Cerebellar parallel fibers make an impressive number of synapses with the Purkinje cells. These synapses are the major structural elements of a large information processing system. The objective of the present report is to describe a method to estimate the coding capacity of this information processing system. We propose to derive the coding capacity from the linear distribution pattern of synaptic varicosities along parallel fibers in a manner consistent with Shannon's information theory formalism. The coding capacity of an average parallel fiber synapse is S=-kappaSigmaP(l(i))lnP(l(i)), where kappa=1/ln2, P(l(i)) is the probability of observing a particular inter-varicosital distance l(i), and ln is the natural logarithm to the base e. In the cerebellar parallel fibers of the mouse, and in a number of other unmyelinated axonal systems, the distribution pattern of P(l(i)) as a function of l(i) is exponential-like. According to information theory, the exponential-like distribution pattern suggests that information transmission in these axonal synaptic systems is operating at near-optimal coding capacity. This optimization in information coding may be the result of a stochastic-like process regulating the formation or elimination of parallel fiber synapses during development and maturation. In the adult nervous system, neuroplasticity-mediated synaptic remodeling may also regulate the coding capacity of axonal synapses via a similar stochastic-like process. The conceptual framework herein may be applicable to other axonal systems in the nervous system.

Animals↗
PubMed1994

A monoclonal antibody epitope on keratin 8 identified using a phage peptide library.

A bacteriophage random hexapeptide library was used to define the epitope of a monoclonal anti-keratin antibody. Phage selected by the keratin 8-specific antibody LE41 displayed highly related sequences on their pIII coat protein. The consensus sequence S(X)LNP allowed the precise localization of an LE41 epitope (SLLSP) within the head domain (H1 subdomain) of human keratin 8, known to be important for correct filament polymerisation. By sequencing the immunizing antigen, keratin 8 from Potorous tridactylis, it was shown that the natural epitope of LE41 is the pentapeptide SLLNP, which confirmed predictions from the phage library results. An SLL(X)P motif is found in the H1 region of all type II keratins (keratins 1 to 8) in different species, but mutational analysis revealed that LE41 can only bind to keratin 8 when Asn (N) or Ser (S) is found in the (X) position. Thus the monoclonal antibody LE41 retains its specificity for keratin 8, dependent on a single amino acid residue, even though it recognizes an epitope within the highly conserved H1 subdomain of the head region. Six other monoclonal antibodies tested on the phage library failed to select motifs.

Amino Acid Sequence↗
PubMed2002

Compactibility of mixtures of calcium carbonate and microcrystalline cellulose.

A patented coprocessed mixture of microcrystalline cellulose (MC) and calcium carbonate (CC) is claimed to perform, as a pharmaceutical excipient, equal or better than pure MC. To investigate it, the tensile strength (T) of tablets made of mixtures of MC type 102, CC, magnesium stearate (MS) and polyvinylpyrrolidone (PVP) and formed under a compaction pressure (P(c)) ranging up to 618 MPa has been determined. The compactibility of the mixtures was defined through regression parameters obtained with ln(-ln(1-T/T(max)))=slope x lnP(c) + intercept. MC/CC mixtures, P(c)=618 MPa, show a small decrease in tablet tensile strength with CC proportions up to about 20%, falling considerably thereafter. Lower compaction pressures, P(c)< or =332 MPa, show a continuous decrease in tensile strength as the CC proportion increases. A MC drastic fall in tablet tensile strength due to 2%-MS, P(c)=487 MPa, was recovered to 35% of its original value admixing about 25% CC. This maximal value of recovery showed a shift to lower proportions of CC, up to 10%, as compaction pressure decreased. This was attributed to lower CC-particles fragmentation or agglomerates spreading at lower compaction pressures. Mixtures with increased plasticity (MC/CC/PVP and MC/CC/PVP/MS) showed an increased compactibility, which was more evident at higher compaction pressures and higher CC proportions, presumably due to higher deformation and erosion of PVP particles. Inclusion of about 40% CC in a MC/PVP/MS mixture showed 60% recovery of the original MC tablet tensile strength. Lower MS proportions are expected to allow a higher recovery.

Antacids↗
PubMed2003

Compactibility of agglomerated mixtures of calcium carbonate and microcrystalline cellulose.

The tablet tensile strength (T) of agglomerated mixtures of microcrystalline cellulose-Avicel PH 102 (MC), calcium carbonate (CC) and polyvinylpyrrolidone (Povidone, PVP), lubricated with magnesium stearate (MS), and formed under a compaction pressure (P(c)) ranging up to 618MPa has been determined. The compactibility was defined through: ln(-ln(1-T/T(max)))=Slope x lnP(c)+Intercept. MC/CC mixtures added of an agglutinant, before and after lubrication, show an important positive effect on their tablet tensile strength compared to a lineal relationship. This positive effect becomes smaller with decreasing compaction pressures. By different mixing methods, the higher the mixing efficiency the higher the compactibility, following the order: spray-dried>wet massing>tumble mixing. The compactibility of MC/CC/PVP spray-dried mixtures with calcium carbonate content from 20 to 60% was equal to or greater than that of pure microcrystalline cellulose. After lubrication with 2% MS the compactibility decreased, only the mixture with the maximal tablet tensile strength attained the tensile strength of pure microcrystalline cellulose. The presence of the binder, the lubricant and higher compaction pressures allow the accommodation of higher calcium carbonate proportions in the mixtures, at the maximal tablet tensile strength of the series. The lubricant decreases in a greater extent the compactibility of mixtures with a continuous phase of MC/PVP than that of CC/PVP. This is attributed to the plastic behavior of the MC/PVP continuous phase compared to a calcium carbonate continuous phase able to disrupt the Povidone and the possible lubricant coatings allowing a stronger interparticle interaction.

Calcium Carbonate↗
PubMedDate not supplied

Mechanistic information from analysis of molecular weight distributions of starch.

A methodology is developed for interpreting the molecular weight distributions of debranched amylopectin, based on techniques developed for quantitatively and qualitatively finding mechanistic information from the molecular weight distributions of synthetic polymers. If the only events occurring are random chain growth and stoppage (i.e., the rates are independent of degree of polymerization over the range in question), then the number of chains of degree of polymerization N, P(N), is linear in ln P(N) with a negative slope, where the slope gives the ratio of the stoppage and growth rates. This starting point suggests that mechanistic inferences can be made from a plot of lnP against N. Application to capillary electrophoresis data for the P(N) of debranched starch from across the major taxa, from bacteria (Escherichia coli), green algae (Chlamydomonas reinhardtii), mammals (Bos), and flowering plants (Oryza sativa, rice; Zea mays, maize; Triticum aestivum, wheat; Hordeum vulgare, barley; and Solanum tuberosum, potato), gives insights into the biosynthetic pathways, showing the differences and similarities of the alpha-1,4-glucans produced by the various species. Four characteristic regions for storage starch from the higher plants are revealed: (1) an initial increasing region corresponding to the formation of new branches, (2) a linear ln P region with negative slope, indicating random growth and stoppage, (3) a region corresponding to the formation of the crystalline lamellae and subsequent elongation of chains, and (4) a second linear ln P with negative slope region. Each region can be assigned to specific enzymatic processes in starch synthesis, including determining the ranges of degrees of polymerization which are subject to random and nonrandom processes.

Animals↗
PubMed2023

Lung SORT LNPs enable precise homology-directed repair mediated CRISPR/Cas genome correction in cystic fibrosis models.

Approximately 10% of Cystic Fibrosis (CF) patients, particularly those with CF transmembrane conductance regulator (CFTR) gene nonsense mutations, lack effective treatments. The potential of gene correction therapy through delivery of the CRISPR/Cas system to CF-relevant organs/cells is hindered by the lack of efficient genome editor delivery carriers. Herein, we report improved Lung Selective Organ Targeting Lipid Nanoparticles (SORT LNPs) for efficient delivery of Cas9 mRNA, sgRNA, and donor ssDNA templates, enabling precise homology-directed repair-mediated gene correction in CF models. Optimized Lung SORT LNPs deliver mRNA to lung basal cells in Ai9 reporter mice. SORT LNP treatment successfully corrected the CFTR mutations in homozygous G542X mice and in patient-derived human bronchial epithelial cells with homozygous F508del mutations, leading to the restoration of CFTR protein expression and chloride transport function. This proof-of-concept study will contribute to accelerating the clinical development of mRNA LNPs for CF treatment through CRISPR/Cas gene correction.

Humans↗
PubMed2025

A pan-beta-coronavirus vaccine bearing conserved and asymptomatic B- and T-cell epitopes protects against highly pathogenic Delta and highly transmissible Omicron SARS-CoV-2 variants.

Over the last five years of the COVID-19 pandemic, the repetitive mutations and deletions in the SARS-CoV-2 genome, primarily targeting the Spike gene, resulted in the emergence of multiple viral variants and sub-variants. The non-updated mismatched Spike-based sub-unit vaccines are less effective due to the ability of these SARS-CoV-2 variants and sub-variants to evade vaccine-induced humoral immunity. To reduce reliance on neutralizing antibodies and prevent potential mismatches between circulating variants, sub-variants, and the vaccines, we have identified highly conserved Spike and non-Spike viral epitopes associated with protective asymptomatic B- and T-cell immune responses, respectively. We demonstrated that unvaccinated asymptomatic patients with COVID-19 recognized these conserved B- and T-cell epitopes. Using the mRNA-LNP-based antigen delivery system, we developed a multi-epitope vaccine that incorporates the conserved B-cell epitopes, CD4+ T-cell epitopes, and CD8+ T-cell epitopes. To assess the efficacy of this "asymptomatic" multi-epitope vaccine, we used the HLA-A*02:01/HLA-DRB1*&#x2009;01:01-hACE-2 triple transgenic mouse model. We demonstrated that this "asymptomatic" multi-epitope vaccine conferred robust protection against infection and disease caused by the SARS-CoV-2 Delta (B.1.617.2) and Omicron (XBB.1.5) variants as assessed by: (i) prevention of weight loss, (ii) reduction of virus replication, and (iii) lung pathology. This protection was associated with: (i) strong antibody responses; and (ii) high frequency of anti-viral IFN-&#x3b3;-producing CD4+ and CD8+ T-cells. These findings illustrate the possibility of developing a pan-beta-coronavirus vaccine to induce broad-spectrum protective immunity against SARS-CoV-2 variants and sub-variants by targeting highly conserved "asymptomatic" B- and T-cell epitopes identified from both structural and non-structural viral proteins.

Epitopes, T-Lymphocyte↗
PubMed2001

Effect of temperature on cuticular transpiration of isolated cuticular membranes and leaf discs.

Cuticular transpiration was measured in the temperature range between 10 degrees C and 55 degrees C using tritiated water and five species (Vinca major L., Prunus laurocerasus L., Forsythia intermedia L., Citrus aurantium L., and Hedera helix L.). Cuticular water permeabilities measured with isolated cuticular membranes were not different from cuticular water permeabilities measured with leaf discs. Depending on the species cuticular water permeabilities increased by factors between 12 (V. major) to 264 (H. helix) when temperature was increased from 10 degrees C to 55 degrees C. Arrhenius plots (lnP versus 1/T) of all investigated species were characterized by phase transitions occurring in the temperature range of 30-39 degrees C. Activation energies for water permeability across plant cuticles below and above the midpoint of phase transition were calculated from Arrhenius plots. Depending on the species they varied between 26 (F. intermedia) to 61 kJ mol(-1) (H. helix) below the phase transition and from 67 (V. major) to 122 kJ mol(-1) (F. intermedia) above the phase transition. Since the occurrence of phase transitions always lead to significantly increased rates of cuticular transpiration it is argued that temperatures higher than 35 degrees C caused structural defects to the transport-limiting barrier of the plant cuticles of all species investigated.

Cell Membrane↗
PubMed1994

Protein side-chain conformational entropy derived from fusion data--comparison with other empirical scales.

The loss of conformational entropy of protein side-chains is a major effect in the energetics of folding. The simplest approach is to enumerate the number of freely rotatable bonds. Recently, two scales of side-chain conformational entropy have been proposed based on the definition of entropy as the Boltzmann sampling over all accessible states (S = -R sigma p(i)lnp(i), where p(i) is the probability of being in a rotameric state). In one scale, derived only for aliphatic and aromatic side-chains, the values of p(i) were obtained from Monte Carlo simulations. In the other scale, the observed frequencies of different rotameric states in a database of protein crystal structures yielded an estimate for p(i). Here an empirical estimation of the fusion entropy of the side-chains is used to derive a third scale. The fusion entropy is obtained as a sum of empirically derived contributions from component hydrocarbon and functional groups. There is a good agreement between the fusion scale and the other two scales. This suggests that the magnitude of conformational entropy is being correctly established.

Computer Simulation↗
PubMed2001

Fluctuations of the correlation dimension at metal-insulator transitions.

We investigate numerically the inverse participation ratio, P(2), of the 3D Anderson model and of the power-law random banded matrix (PRBM) model at criticality. We found that the variance of lnP(2) scales with system size L as sigma(2)(L) = sigma(2)(infinity)-AL(-D(2)/2d), with D(2) being the correlation dimension and d the system dimension. Therefore the concept of a correlation dimension is well defined in the two models considered. The 3D Anderson transition and the PRBM transition for b = 0.3 (see the text for the definition of b) are fairly similar with respect to all critical magnitudes studied.

Journal Article↗