Biomedical subjects

J Garnier

Publications and source records attributed to J Garnier.

At least 19 recordsLinked to original sources

PubMed2006

Statistical analysis of noise-induced multiple filamentation.

The propagation of high-power large-aperture laser beams in a Kerr medium is considered. A statistical approach is developed for the growth of filaments from small-amplitude small-scale initial modulations. Closed-form expressions are derived for the intensity distribution, contrast, and maximal beam intensity, which are valid up to the blowup of the most intense filament. Numerical experiments are found to be in good agreement with theoretical predictions.

Journal Article↗

PubMed2006

Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?

This study evaluated by immunohistochemistry (IHC) immune cell response during neoadjuvant primary systemic therapy (PST) with trastuzumab in patients with HER2-positive primary breast cancer. In all, 23 patients with IHC 3+ primary breast cancer were treated with trastuzumab plus docetaxel. Pathological complete and partial responses were documented for nine (39%) and 14 (61%) patients, respectively. Case-matched controls comprised patients treated with docetaxel-based PST without trastuzumab (D; n=23) or PST without docetaxel or trastuzumab (non-taxane, non-trastuzumab, NT-NT; n=23). All surgical specimens were blind-analysed by two independent pathologists, with immunohistochemical evaluation of B and T lymphocytes, macrophages, dendritic cells and natural killer (NK) cells. Potential cytolytic cells were stained for Granzyme B and TiA1. HER2 expression was also evaluated in residual tumour cells. Trastuzumab treatment was associated with significantly increased numbers of tumour-associated NK cells and increased lymphocyte expression of Granzyme B and TiA1 compared with controls. This study supports an in vivo role for immune (particularly NK cell) responses in the mechanism of trastuzumab action in breast cancer. These results suggest that trastuzumab plus taxanes lead to enhanced NK cell activity, which may partially account for the synergistic activity of trastuzumab and docetaxel in breast cancer.

Adolescent↗

PubMed2005

Pre-operative systemic (neo-adjuvant) therapy with trastuzumab and docetaxel for HER2-overexpressing stage II or III breast cancer: results of a multicenter phase II trial.

BACKGROUND: Trastuzumab plus chemotherapy has become the standard of care for women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Trastuzumab-based pre-operative systemic (neo-adjuvant) therapy (PST) also appears promising, warranting further investigation. PATIENTS AND METHODS: Patients with HER2-positive, stage II/III non-inflammatory, operable breast cancer requiring a mastectomy (but who wished to conserve the breast) received weekly trastuzumab and 3-weekly docetaxel for six cycles before surgery. The primary end point was pathological complete response (pCR) rate, determined from surgical specimens. RESULTS: Thirty-three patients were enrolled. The majority (79%) had T2 tumors, with 42% being N1/2. Twenty-nine patients completed six cycles of therapy and one patient withdrew prematurely due to progressive disease. A complete or partial objective clinical response was seen in 96% (73% and 23%, respectively) of patients. Surgery was performed in 30 patients, breast conserving in 23 (77%). In an intention-to-treat analysis, tumor and nodal pCR was seen in 14 (47%) patients. Treatment was generally well tolerated. Grade 3/4 neutropenia occurred in 85% of patients while febrile neutropenia was encountered in 18%. Only three patients withdrew prematurely due to toxicity. No symptomatic cardiac dysfunction was reported. CONCLUSIONS: PST with trastuzumab plus docetaxel achieved promising efficacy, with a high pCR rate and good tolerability, in women with stage II or III HER2-positive breast cancer.

Adult↗

PubMed2004

Involvement of penaeidins in defense reactions of the shrimp Litopenaeus stylirostris to a pathogenic vibrio.

The present study reports for the first time the involvement of an antimicrobial peptide in the defense reactions of a shrimp infected by a pathogenic Vibrio, Vibrio penaeicida. New members of the penaeidin family were characterized in the shrimp Litopenaeus stylirostris by RT-PCR and RACE-PCR from hemocyte total RNAs, and by mass spectrometry detection and immunolocalization of mature peptides in shrimp hemocytes. In infected shrimps, bacteria and penaeidin distribution colocalized in the gills and the lymphoid organ that represented the main infected sites. Moreover, the shrimp immune response to infection involved massive hemocyte recruitment to infection sites where released penaeidin may participate in the isolation and elimination of the bacteria, We show that the ability of the shrimps to circumvent shrimp infections is closely related to a recovery phase based on the hematopoietic process.

Amino Acid Sequence↗

PubMed2003

Statistical analysis of multimode weakly nonlinear Rayleigh-Taylor instability in the presence of surface tension.

A weakly nonlinear model is proposed for the Rayleigh-Taylor instability in the presence of surface tension. The dynamics of a multimode perturbation of the interface between two incompressible, inviscid, irrotational, and immiscible fluids is analyzed. The quadratic and cubic nonlinear effects are taken into account. They include the nonlinear corrections to the exponential growths of the fundamental modulations. The role of the initial modulation spectrum is discussed. A saturation criterion in terms of the product of a local rms and a particular wave number is exhibited. It gives theoretical foundations for numerical conjectures and allows one to analyze the effects of fundamental parameters of the problem such as the dimension or the Atwood number.

Journal Article↗

PubMed2003

Weakly nonlinear theory for the ablative Rayleigh-Taylor instability.

A weakly nonlinear model is proposed for the Rayleigh-Taylor instability in the presence of ablation and thermal transport. The second harmonic generation efficiency of a single-mode disturbance is computed, as well as the nonlinear correction to the exponential growth of the fundamental modulation. Mode coupling in the spectrum of a multimode disturbance is thoroughly analyzed. The ablative stabilization can be clearly discussed because the derived formulas for the evanescent ablation rate are in agreement with previously known results for incompressible, inviscid, irrotational, and immiscible fluids [S. W. Haan, Phys. Fluids B 3, 2349 (1991)]; M. Berning and A. M. Rubenchik, Phys. Fluids 10, 1564 (1998)]].

Journal Article↗

PubMed2003

Soliton dynamics in a random Toda chain.

This paper addresses the soliton dynamics in a Toda lattice with a randomly distributed chain of masses. Applying the inverse scattering transform, we derive effective equations for the decay of the soliton amplitude that take into account radiative losses. It is shown that the soliton energy decays as approximately N(-3/2) for small-amplitude solitons and approximately exp(-N) for large-amplitude solitons. The decay rate does not depend on the incoming energy for large-amplitude soliton. An important feature is the generation of a soliton gas consisting of a large collection of small solitons (a number of the order of epsilon (-2) of solitons with momenta of the order of epsilon (2), where epsilon is the strength of fluctuations). The soliton gas plays an important role in that the changes in the conservation equations cannot be correctly understood if the soliton production is neglected. The role of the correlation length of fluctuations on the soliton decay is discussed. It is shown that in the presence of long-range correlation the Toda soliton is not backscattered, but progressively converted into forward-going radiation. The analytical predictions are confirmed by full numerical simulations.

Journal Article↗

PubMed2002

Combining the GOR V algorithm with evolutionary information for protein secondary structure prediction from amino acid sequence.

We have modified and improved the GOR algorithm for the protein secondary structure prediction by using the evolutionary information provided by multiple sequence alignments, adding triplet statistics, and optimizing various parameters. We have expanded the database used to include the 513 non-redundant domains collected recently by Cuff and Barton (Proteins 1999;34:508-519; Proteins 2000;40:502-511). We have introduced a variable size window that allowed us to include sequences as short as 20-30 residues. A significant improvement over the previous versions of GOR algorithm was obtained by combining the PSI-BLAST multiple sequence alignments with the GOR method. The new algorithm will form the basis for the future GOR V release on an online prediction server. The average accuracy of the prediction of secondary structure with multiple sequence alignment and full jack-knife procedure was 73.5%. The accuracy of the prediction increases to 74.2% by limiting the prediction to 375 (of 513) sequences having at least 50 PSI-BLAST alignments. The average accuracy of the prediction of the new improved program without using multiple sequence alignments was 67.5%. This is approximately a 3% improvement over the preceding GOR IV algorithm (Garnier J, Gibrat JF, Robson B. Methods Enzymol 1996;266:540-553; Kloczkowski A, Ting K-L, Jernigan RL, Garnier J. Polymer 2002;43:441-449). We have discussed alternatives to the segment overlap (Sov) coefficient proposed by Zemla et al. (Proteins 1999;34:220-223).

Algorithms↗

PubMed2001

Crustacean immunity. Antifungal peptides are generated from the C terminus of shrimp hemocyanin in response to microbial challenge.

We report here the isolation from plasma of two penaeid shrimp species of novel peptides/polypeptides with exclusive antifungal activities. A set of three molecules was purified with molecular masses at 2.7 kDa (Penaeus vannamei), 7.9 kDa, and 8.3 kDa (Penaeus stylirostris). Primary structure determination was performed by a combination of Edman degradation and mass spectrometry. The peptides display 95-100% sequence identity with a C-terminal sequence of hemocyanin, indicating that they are cleaved fragments of the shrimp respiratory protein. Specific immunodetection of the hemocyanin-derived (poly)peptides revealed that experimental microbial infections increase their relative concentration in plasma as compared with nonstimulated animals. Thus, the production of antifungal (poly)peptides by limited proteolysis of hemocyanin could be relevant to a shrimp immune reaction that would confer a new function to the multifunctional respiratory pigment of crustaceans.

Amino Acid Sequence↗

PubMed2001

Laplacian growth of parallel needles: a Fokker-Planck equation approach.

Using a conformal transformation to set up the iterative nonlinear equations, we study analytically the kinetics of growth of parallel needles. We establish a discrete Fokker-Planck equation for the probability of finding at time t a given distribution of needle lengths. In the linear regime, it shows a short-wavelength Laplacian instability which we investigate in detail. From the crossover of the solutions to the nonlinear regime, we deduce analytically the general scale invariance of the two-dimensional models.

Journal Article↗

PubMed2001

Role of polarization mode dispersion on modulational instability in optical fibers.

We introduce the theory of modulational instability (MI) of electromagnetic waves in fibers with random polarization mode dispersion. Applying a linear stability analysis and stochastic calculus, we show that the MI gain spectrum reads as the maximal eigenvalue of a constant effective matrix. In the limiting cases of small or large fluctuations, we give explicit expressions for the MI gain spectra. In the general configurations, we give the explicit form of the effective matrix and numerically compute the maximal eigenvalue. In the anomalous dispersion regime, polarization dispersion widens the unstable bandwidth. Depending on the type of variations of the birefringence parameters, polarization dispersion reduces or enhances the MI gain peak. In the normal dispersion regime, random effects may extend the instability domain to the whole spectrum of modulations. The linear stability analysis is confirmed by numerical simulation of the full stochastic coupled nonlinear Schrödinger equations.

Journal Article↗

PubMed2001

Propagation of solitons in a randomly perturbed Ablowitz-Ladik chain.

This paper deals with the transmission of a soliton in a discrete, nonlinear, and random medium. A random lattice nonlinear Schrödinger equation is considered, where the randomness holds in the on-site potential or in the coupling coefficients. We study the interplay of nonlinearity, randomness, and discreteness. We derive effective evolution equations for the soliton parameters by applying a perturbation theory of the inverse scattering transform and limit theorems of stochastic calculus.

Journal Article↗

PubMed2000

Correlation of the exon/intron organization to the conserved domains of the mouse transcriptional corepressor TIF1beta.

TIF1beta, a member of the transcriptional intermediary factor 1 family, has been reported to function as a corepressor for the large class of KRAB domain-containing zinc finger proteins of the Krüppel type. In this study, we report the genomic organization and nucleotide sequence of the mouse TIF1beta gene. This gene comprises 17 coding exons located within 7 kb of genomic DNA. Exon sizes vary from 37 bp (exon 10) to 901 bp (exon 1), and intron sizes range from 71 bp to 1843 bp. All introns have the conserved GT and AG dinucleotides present at the donor and acceptor sites, respectively. The functional/homology regions of the TIF1beta protein are encoded by distinct exons. The amino-terminal RING finger is encoded by two exons interrupted by a small intron. The B boxes lie within individual exons. Similarly to the RING finger, the PHD finger is encoded by two exons. Three exons constitute the carboxy-terminal bromodomain, and their position correlates well with the secondary structure elements of the domain as predicted by computer modeling. Taken together, these results will facilitate the genetic manipulation of TIF1beta for future in vivo structure-function studies.

Animals↗

PubMed1999

Estimates of early-industrial inputs of nutrients to river systems: implication for coastal eutrophication.

Although coastal eutrophication is generally recognised as a recent phenomenon related to the well-documented increase in riverine nutrient delivery during the last 30 or 40 years, a few historical records paradoxically show that, in some places like the Southern Bight of the North Sea, or the Northern Adriatic, algal proliferation as intense as presently observed was already regularly occurring at the end of the 19th century. Estimated riverine nutrient loads from diffuse sources or from domestic point sources of waste water at that time are too low to account for these observations. We attempted a retrospective evaluation of the possible contribution of industrial activity to nutrient river loading. The figures indicate that, by the end of the last century, large scale use of traditional processes in textile and paper industries, in tanneries, candles factories and others was responsible for a dominant part of the nutrient load carried by rivers in Western Europe and could have caused nutrient inputs to coastal zones similar to the present ones.

Animals↗

PubMed1999

FORESST: fold recognition from secondary structure predictions of proteins.

MOTIVATION: A method for recognizing the three-dimensional fold from the protein amino acid sequence based on a combination of hidden Markov models (HMMs) and secondary structure prediction was recently developed for proteins in the Mainly-Alpha structural class. Here, this methodology is extended to Mainly-Beta and Alpha-Beta class proteins. Compared to other fold recognition methods based on HMMs, this approach is novel in that only secondary structure information is used. Each HMM is trained from known secondary structure sequences of proteins having a similar fold. Secondary structure prediction is performed for the amino acid sequence of a query protein. The predicted fold of a query protein is the fold described by the model fitting the predicted sequence the best. RESULTS: After model cross-validation, the success rate on 44 test proteins covering the three structural classes was found to be 59%. On seven fold predictions performed prior to the publication of experimental structure, the success rate was 71%. In conclusion, this approach manages to capture important information about the fold of a protein embedded in the length and arrangement of the predicted helices, strands and coils along the polypeptide chain. When a more extensive library of HMMs representing the universe of known structural families is available (work in progress), the program will allow rapid screening of genomic databases and sequence annotation when fold similarity is not detectable from the amino acid sequence. AVAILABILITY: FORESST web server at http://absalpha.dcrt.nih.gov:8008/ for the library of HMMs of structural families used in this paper. FORESST web server at http://www.tigr.org/ for a more extensive library of HMMs (work in progress). CONTACT: valedf@tigr.org; munson@helix.nih.gov; garnier@helix.nih.gov

Computer Simulation↗

PubMed1999

Comparing protein sequence-based and predicted secondary structure-based methods for identification of remote homologs.

We have compared a novel sequence-structure matching technique, FORESST, for detecting remote homologs to three existing sequence based methods, including local amino acid sequence similarity by BLASTP, hidden Markov models (HMMs) of sequences of protein families using SAM, HMMs based on sequence motifs identified using meta-MEME. FORESST compares predicted secondary structures to a library of structural families of proteins, using HMMs. Altogether 45 proteins from nine structural families in the database CATH were used in a cross-validated test of the fold assignment accuracy of each method. Local sequence similarity of a query sequence to a protein family is measured by the highest segment pair (HSP) score. Each of the HMM-based approaches (FORESST, MEME, amino acid sequence-based HMM) yielded log-odds score for the query sequence. In order to make a fair comparison among these methods, the scores for each method were converted to Z-scores in a uniform way by comparing the raw scores of a query protein with the corresponding scores for a set of unrelated proteins. Z-Scores were analyzed as a function of the maximum pairwise sequence identity (MPSID) of the query sequence to sequences used in training the model. For MPSID above 20%, the Z-scores increase linearly with MPSID for the sequence-based methods but remain roughly constant for FORESST. Below 15%, average Z-scores are close to zero for the sequence-based methods, whereas the FORESST method yielded average Z-scores of 1.8 and 1.1, using observed and predicted secondary structures, respectively. This demonstrates the advantage of the sequence-structure method for detecting remote homologs.

Algorithms↗

PubMed1999

Modulational instability of electromagnetic waves in birefringent fibers with periodic and random dispersion.

Modulational instability (MI) of electromagnetic waves in a birefringent fiber with a periodic dispersion (two-step dispersion management scheme) is investigated. The properties of new sidebands are studied. The strong variation of dispersion leads to the decreasing of the main MI region and the suppression of additional resonance. In the random dispersion case the MI of all frequencies of modulation in the normal dispersion region is predicted. In the anomalous dispersion case the decreasing of the main MI peak is calculated and changes in the spectral bandwidth of MI gain are found. The analytical predictions are confirmed by the numerical simulations of the full coupled nonlinear Schrödinger equations with periodic coefficients.

Journal Article↗

PubMed1999

Energy distribution of the quantum harmonic oscillator under random time-dependent perturbations.

This paper investigates the evolution of a quantum particle in a harmonic oscillator driven by time-dependent forces. The perturbations are small, but they act long enough so that we can solve the problem in the asymptotic framework corresponding to a perturbation amplitude that tends to zero and a perturbation duration that tends to infinity. We describe the effective evolution equation of the state vector, which reads as a stochastic partial differential equation. We exhibit a closed-form equation for the transition probabilities, which can be interpreted in terms of a jump process. Using standard probability tools, we are then able to compute explicitly the probabilities for observing the different energy eigenstates and give the exact statistical distribution of the energy of the particle.

Journal Article↗