A classical analog of the quantum Zeeman effect.

We extend a recent classical mechanical analog of Bohr's atom consisting of a scalar field coupled to a massive point-like particle [P. Jamet and A. Drezet, "A mechanical analog of Bohr's atom based on de Broglie's double-solution approach," Chaos 31, 103120 (2021)] by adding and studying the contribution of a uniform weak magnetic field on their dynamics. In doing so, we are able to recover the splitting of the energy levels of the atom called Zeeman's effect within the constraints of our model and in agreement with the semiclassical theory of Sommerfeld. This result is obtained using Larmor's theorem for both the field and the particle, associating magnetic effects with inertial Coriolis forces in a rotating frame of reference. Our work, based on the old "double solution" theory of de Broglie, shows that a dualistic model involving a particle guided by a scalar field can reproduce the normal Zeeman effect.

A mechanical analog of Bohr's atom based on de Broglie's double-solution approach.

Motivated by recent developments of hydrodynamical quantum mechanical analogs [J. W. M. Bush, Annu. Rev. Fluid Mech. 47, 269-292 (2015)], we provide a relativistic model for a classical particle coupled to a scalar wave field through a holonomic constraint. In the presence of an external Coulomb field, we define a regime where the particle is guided by the wave in a way similar to the old de Broglie phase-wave proposal. Moreover, this dualistic mechanical analog of the quantum theory is reminiscent of the double-solution approach suggested by de Broglie in 1927 and is able to reproduce the Bohr-Sommerfeld semiclassical quantization formula for an electron moving in an atom.

[Use of indicators of fluid responsiveness in septic shock: a survey in public emergency departments]. / Indices de réponse au remplissage vasculaire lors de la prise en charge d'un choc septique : utilisation par les médecins urgentistes.

INTRODUCTION: Fluid therapy is one of the major elements of severe sepsis and septic shock management. A systematic initial fluid bolus is recommended before evaluation of left ventricular filling pressure by the use of indicators of fluid responsiveness, preferentially dynamic ones. A massive fluid therapy could be damaging for the patient. Dynamic indicators of fluid responsiveness are not often relevant in the emergency department. This study was aimed to evaluate the use of indicators of fluid responsiveness by emergency practitioners during septic shock management. STUDY DESIGN: Cross sectional survey using anonymous self-questionnaire. METHODS: We included all practitioners working in public emergency department of Languedoc-Roussillon (France). Primary-end point was the use of one indicator of fluid responsiveness at least. Uni- and multivariate analysis was conducted to find associated factors. RESULTS: Of 232 practitioners included, we collected 149 questionnaires (response rate=64%). Hundred and eight practitioners (72% [64-79%]) used at least one indicator of fluid responsiveness. Fifty-six practitioners (38% [30-46%]) used echocardiography, 54 practitioners (36% [29-44%]) used blood lactate concentration, 45 practitioners (30% [23-38%]) used passive leg raising. The use of indicators of fluid responsiveness is associated with easy access to echography device (odd ratio=2.94 [1.16-7.62], P=0.03). CONCLUSION: Emergency practitioners use preferentially less invasive and less time-consuming indicators of fluid responsiveness.

Implication of gene distribution in the bacterial chromosome for the bacterial cell factory.

As bacterial genome sequences accumulate, more and more pieces of data suggest that there is a significant correlation between the distribution of genes along the chromosome and the physical architecture of the cell, suggesting that the map of the cell is in the chromosome. Considering sequences and experimental data indicative of cell compartmentalisation, mRNA folding and turnover, as well as known structural features of protein and membrane complexes, we show that preliminary in silico analysis of whole genome sequences strongly substantiates this hypothesis. If there is a correlation between the genome sequence and the cell architecture, it must derive from some selection pressure in the organisms growing in the wild. As a consequence, the underlying constraints should be optimised in genetically modified organisms if one is to expect high product yields. Consequences in terms of gene expression for biotechnology are straightforward: knocking genes out and in genomes should not be randomly performed, but should follow the rules of chromosome organisation.

Mapping the bacterial cell architecture into the chromosome.

A genome is not a simple collection of genes. We propose here that it can be viewed as being organized as a 'celluloculus' similar to the homunculus of preformists, but pertaining to the category of programmes (or algorithms) rather than to that of architectures or structures: a significant correlation exists between the distribution of genes along the chromosome and the physical architecture of the cell. We review here data supporting this observation, stressing physical constraints operating on the cell's architecture and dynamics, and their consequences in terms of gene and genome structure. If such a correlation exists, it derives from some selection pressure: simple and general physical principles acting at the level of the cell structure are discussed. As a first case in point we see the piling up of planar modules as a stable, entropy-driven, architectural principle that could be at the root of the coupling between the architecture of the cell and the location of genes at specific places in the chromosome. We propose that the specific organization of certain genes whose products have a general tendency to form easily planar modules is a general motor for architectural organization in the bacterial cell. A second mechanism, operating at the transcription level, is described that could account for the efficient building up of complex structures. As an organizing principle we suggest that exploration by biological polymers of the vast space of possible conformation states is constrained by anchoring points. In particular, we suggest that transcription does not always allow the 5'-end of the transcript to go free and explore the many conformations available, but that, in many cases, it remains linked to the transcribing RNA polymerase complex in such a way that loops of RNA, rather than threads with a free end, explore the surrounding medium. In bacteria, extension of the loops throughout the cytoplasm would therefore be mediated by the de novo synthesis of ribosomes in growing cells. Termination of transcription and mRNA turnover would accordingly be expected to be controlled by sequence features at both the 3'- and 5'-ends of the molecule. These concepts are discussed taking into account in vitro analysis of genome sequences and experimental data about cell compartmentalization, mRNA folding and turnover, as well as known structural features of protein and membrane complexes.

A symbolic-numeric approach to find patterns in genomes. Application to the translation initiation sites of E. coli.

DNA sequence data provided by genome sequencing programs open new research prospects. In this respect, computational investigations are of major importance to discover new 'functional/structural patterns' and to improve biological process knowledge. For example, even though the principal steps of translation initiation in prokaryotes are known, it is difficult to point out the exact pattern of the mRNA that is recognized by the ribosome. In this study, we have carried out a systematic context analysis of the complete genome of E. coli, around codons in competition for translation initiation. Using a combinatorial approach, we first show that it is possible to accurately define the initiation site by looking for the localization of patterns representing various combinations of trinucleotides. We have combined this approach with a statistical analysis based on the frequencies of these patterns. This leads to a decision tree, able to discriminate true and false starts with a recognition level near 90%. Our method may help to precisely localize the beginning of open reading frames, and point to likely mistakes for some genes in the database. The method may be included as a component of a gene recognition system, is not restricted to a particular genome or a two-classes discrimination, and may be applied to a broader class of biological patterns.

Indigo: a World-Wide-Web review of genomes and gene functions.

The present article describes a genome database reviewing gene-related knowledge of two model bacteria, Bacillus subtilis and Escherichia coli. The database, Indigo, is open through the World-Wide Web (http://indigo.genetique.uvsq.fr). The concept used for organising the data, the concept of neighbourhood, allows one to explore the database content in an efficient although somewhat unusual way. Here, genes are related to each other by a variety of neighbourhoods, including proximity in the chromosome, phylogenetic kinship, participation in a common metabolic pathway, common presence in an article of the literature, or similar use of the genetic code. Several examples illustrate how this concept of neighbourhood permits one to review the available knowledge about a given gene or gene family, and elaborate unexpected, but revealing, analyses about gene functions.

High relapse rate among lepromatous leprosy patients treated with rifampin plus ofloxacin daily for 4 weeks.

Fifty-one lepromatous leprosy patients, all of whom had relapsed after previous dapsone (DDS) monotherapy, were treated between 1990 and 1991 with 600 mg of rifampin (RMP) plus 400 mg of ofloxacin (OFLO) daily for 4 weeks, and the great majority of the patients were followed up at least once a year after completion of the treatment. After only 173 patient-years of follow-up, 5 relapses had been detected; the overall relapse rate was 10.0% (confidence limits, 1.7 and 18.3%), or 2.9 relapses (confidence limits, 0.4 and 5.4) per 100 patient-years. The unacceptably high relapse rate indicated that 4 weeks of treatment with daily RMP-OFLO was unable to reduce the number of viable Mycobacterium leprae organisms to a negligible level. In addition, the M. leprae from one of the relapses were proved to have multiple resistance to DDS, RMP, and OFLO. To avoid further relapses, the follow-up was terminated and the great majority of the patients were retreated with the standard 2-year multidrug therapy from 1994. No further relapse has been diagnosed since the beginning of retreatment.

Using codon usage to predict genes origin: is the Escherichia coli outer membrane a patchwork of products from different genomes?

Analysis of the codon usage of genes coding for the structural components of the outer membrane in Escherichia coli, is consistent with the requirement for high expression of these genes. Because porins (which constitute the major protein component of the outer membrane), and LPS (which constitute the major outermost constituent of the outer membrane), are synthesized from genes displaying widely different codon usage, it is possible to investigate the origin of the outer membrane. The analysis predicts that the outer membrane might originate from a genome other than the genome coding for the major part of the cell. Such a special origin would explain in structural terms, the likely lethality of porins if they were inadvertently inserted within the inner membrane, giving rise to the Gram-negative bacterial type, having an envelope comprising two membranes, instead of a single cytoplasmic membrane and a murein sacculus.

SAMBA: hardware accelerator for biological sequence comparison.

MOTIVATION: SAMBA (Systolic Accelerator for Molecular Biological Applications) is a 128 processor hardware accelerator for speeding up the sequence comparison process. The short-term objective is to provide a low-cost board to boost PC or workstation performance on this class of applications. This paper places SAMBA amongst other existing systems and highlights the original features. RESULTS: Real performance obtained from the prototype is demonstrated. For example, a sequence of 300 amino acids is scanned against SWISS-PROT-34 (21 210 389 residues) in 30 s using the Smith and Waterman algorithm. More time-consuming applications, like the bank-to-bank comparison, are computed in a few hours instead of days on standard workstations. Technology allows the prototype to fit onto a single PCI board for plugging into any PC or workstation. AVAILABILITY: SAMBA can be tested on the WEB server at URL http://www.irisa.fr/SAMBA/.

Effect of HIV infection on leprosy: a three-year survey in Bamako, Mali.

From February 1992 until June 1994, all patients with histologically proven leprosy examined at the Leprology Unit of the Institut Marchoux in Bamako, Mali, were screened for HIV serology. In total, 740 leprosy patients have been tested; 553 known, previously treated leprosy cases and 187 new cases, mainly self-reporting and referred cases. The global seroprevalence in the sample was 1.5% (11/740), and increased from 1.3% in 1992 to 3.1% in 1994. HIV seroprevalence was higher in paucibacillary (PB) than in multibacillary (MB) cases (3.8% versus 0.8%, p < 0.05), and was slightly higher in new cases than in known, already treated cases (2.1% versus 1.3%), although not significantly. Among the 553 known, already treated leprosy patients, 1 out of 7 HIV-seropositive patients relapsed, as opposed to 34 out of 546 HIV-seronegative cases (14.2% versus 6.2%, p = 0.36). Among the new cases, none of the 37 patients with reaction and/or neuritis was HIV positive. In known, treated leprosy cases, there was no difference in the frequency of reactions and/or neuritis between HIV-positive and HIV-negative cases. Migration in a neighboring country appeared to be a risk factor for HIV seropositivity in our sample (chi 2 = 4.5, p = 0.04). In order to estimate the association of HIV with leprosy as compared to the general population, a control group of blood donors was set up, matched for age and sex. There was, however, no difference in HIV seroprevalence between the control group (9/735, 1.2%) and the leprosy group (1.5%). Although leprosy patients recruited for this study constitute a highly selected sample, it appears that HIV infection has little effect on leprosy, particularly on the PB/MB ratio, leprosy reactions and neuritis, but there is a suggestion the HIV infection might be associated with increased frequency of relapse.

PIP: HIV infection is a major risk factor for tuberculosis and other mycobacteria, but its association with leprosy remains unclear. From February 1992 to June 1994, all leprosy patients examined at the Leprology Unit of the Institut Marchoux, a reference center for leprosy in Mali, were screened for HIV infection. 740 leprosy patients were tested over the period; 553 known, previously treated cases and 187 newly diagnosed leprosy cases. 584 patients were multibacillary (MB) cases and 156 were paucibacillary (PB), with a large majority of MB cases among the known cases, due to the selected recruitment of those patients. There were 539 men of mean age 39.3 years and 201 women of mean age 37.7. New and known cases were of mean ages 30.7 and 41.6 years. Overall, 1.5% (11/740) were identified as HIV seropositive, increasing from 1.3% in 1992 to 3.1% in 1994. HIV seroprevalence was 3.8% among PB cases and 0.8% among MB cases, and was slightly higher in new cases than in known, already treated cases. Among the 553 known, already treated leprosy cases, 1 out of 7 HIV-seropositive patients relapsed, compared to 34 of 546 HIV-seronegative cases. Among the new cases, none of the 37 patients with reaction and/or neuritis was HIV positive. It appears that HIV infection has little effect upon leprosy, especially upon the PB/MB ratio, leprosy reactions and neuritis, but HIV infection may be associated with increased frequency of relapse.

Bactericidal activity of single dose of clarithromycin plus minocycline, with or without ofloxacin, against Mycobacterium leprae in patients.

Fifty patients with newly diagnosed lepromatous leprosy were allocated randomly to one of five groups and treated with either a month-long standard regimen of multidrug therapy (MDT) for multibacillary leprosy, a single dose of 600 mg of rifampin, a month-long regimen with the dapsone (DDS) and clofazimine (CLO) components of the standard MDT, or a single dose of 2,000 mg of clarithromycin (CLARI) plus 200 mg of minocycline (MINO), with or without the addition of 800 mg of ofloxacin (OFLO). At the end of 1 month, clinical improvement accompanied by significant decreases of morphological indexes in skin smears was observed in about half of the patients of each group. A significant bactericidal effect was demonstrated in the great majority of patients in all five groups by inoculating the footpads of mice with organisms recovered from biopsy samples obtained before and after treatment. Rifampin proved to be a bactericidal drug against Mycobacterium leprae more potent than any combination of the other drugs. A single dose of CLARI-MINO, with or without OFLO, displayed a degree of bactericidal activity similar to that of a regimen daily of doses of DDS-CLO for 1 month, suggesting that it may be possible to replace the DDS and CLO components of the MDT with a monthly dose of CLARI-MINO, with or without OFLO. However, gastrointestinal adverse events were quite frequent among patients treated with CLARI-MINO, with or without OFLO, and may be attributed to the higher dosage of CLARI or MINO or to the combination of CLARI-MINO plus OFLO. In future trials, therefore, we propose to reduce the dosages of the drugs to 1,000 mg of CLARI, 100 mg of MINO, and 400 mg of OFLO.

Searching for a family of orphan sequences with SAMBA, a parallel hardware dedicated to biological applications.

A significant proportion of coding sequences or open reading frames discovered in the course of sequencing projects do not show any similarity with other sequences deposited with the protein databanks. In such cases the search for similarities must be performed with as many comparison algorithms as possible, so as to increase the chance of finding weak relationships. A specialised parallel hardware (SAMBA) implementing the Smith & Waterman algorithm has been developed at the 'Institut de Recherche en Informatique et Systèmes Aléatoìres' (IRISA). It makes it possible to scan protein databanks at a speed comparable with that of BLAST or FASTA. We report here a study performed with SAMBA on 814 orphan sequences from S cerevisiae and compare the results with those from BLAST and FASTA.

[Anatomopathologic study of five cases of leprosy in HIV seropositive patients]. / Etude anatomopathologique de 5 cas de lèpre chez des sujets séropositifs pour le virus de l'immunodéficience humaine (VIH).

In an effort to establish whether the human immunodeficiency virus (HIV) modifies the histological image of lepromatous skin lesion, a comparative study was conducted in 1994 at the Marchoux Institute in Bamako, Mali, on persons newly suffering from leprosy who had been tested seropositive and seronegative for the HIV virus. These new leprosy patients had never been treated and could be grouped as follows: 5 HIV-positive (1 TT, 1 BT, 1 BL, 2 LL) and 10 controls testing HIV-negative, selected according to the following criteria: each seropositive leprosy subject was matched with two seronegative controls having the same clinical features, same stage under the Ridley classification system, same age and sex. No discordance between the clinical classifications and the histological features in the subjects testing HIV-positive has been observed. They display features similar to those testing negative, with the presence of histiocytes, in particular epithelioid cells and giant cells in normal proportion depending on the form of leprosy. The only remarkable difference was a greater incidence of oedema in the subjects testing seropositive, compared with patients testing seronegative. In conclusion, HIV infection does not appear to cause major modifications in cellular response to Mycobacterium leprae, and no changes should be made in leprosy control programmes.

Relapse after long-term follow up of multibacillary patients treated by WHO multidrug regimen. Marchoux Chemotherapy Study Group.

Thirty-five multibacillary (MB) leprosy patients were treated with 2 years of multidrug therapy (MDT) and followed up regularly for relapse. Relapse was defined as: a) an increase of the bacterial index (BI) by 2+ over the previous value from any single site of old lesions and b) the occurrence of definite new skin lesion(s) which demonstrated a higher BI than any pre-existing lesion. After a mean duration of 72.7 +/- 17.3 months of follow up per patient, seven relapses were diagnosed; the mean incubation period of relapse was 62.7 +/- 18.7 months. The overall relapse rate was 20.0% (or 3.3 per 100 patient-years), very significantly higher than the figures obtained from the same group of patients analyzed 2 1/2 years earlier, indicating that relapses occurred late (at least 5 +/- 2 years) after stopping MDT. Further analysis indicated that the relapse rate was closely correlated with the bacterial load of the patient, occurring far more frequently among patients with a BI of > or = 4.0 before MDT or with a BI of > or = 3.0 at the end of MDT. To avoid the alarmingly high relapse rate, it is proposed that the duration of MDT be doubled to 4 years in patients with an average BI of > or = 4.0 before MDT.