Channel Estimation for Diffusive Molecular Communications

In molecular communication (MC) systems, the \textit{expected} number of molecules observed at the receiver over time after the instantaneous release of molecules by the transmitter is referred to as the channel impulse response (CIR). Knowledge of the CIR is needed for the design of detection and equalization schemes. In this paper, we present a training-based CIR estimation framework for MC systems which aims at estimating the CIR based on the \textit{observed} number of molecules at the receiver due to emission of a \textit{sequence} of known numbers of molecules by the transmitter. Thereby, we distinguish two scenarios depending on whether or not statistical channel knowledge is available. In particular, we derive maximum likelihood (ML) and least sum of square errors (LSSE) estimators which do not require any knowledge of the channel statistics. For the case, when statistical channel knowledge is available, the corresponding maximum a posteriori (MAP) and linear minimum mean square error (LMMSE) estimators are provided. As performance bound, we derive the classical Cramer Rao (CR) lower bound, valid for any unbiased estimator, which does not exploit statistical channel knowledge, and the Bayesian CR lower bound, valid for any unbiased estimator, which exploits statistical channel knowledge. Finally, we propose optimal and suboptimal training sequence designs for the considered MC system. Simulation results confirm the analysis and compare the performance of the proposed estimation techniques with the respective CR lower bounds.Comment: to be appeared in IEEE Transactions on Communications. arXiv admin note: text overlap with arXiv:1510.0861

DNA binding by Corynebacterium glutamicum TetR-type transcription regulator AmtR

<p>Abstract</p> <p>Background</p> <p>The TetR family member AmtR is the central regulator of nitrogen starvation response in <it>Corynebacterium glutamicum</it>. While the AmtR regulon was physiologically characterized in great detail up to now, mechanistic questions of AmtR binding were not addressed. This study presents a characterization of functionally important amino acids in the DNA binding domain of AmtR and of crucial nucleotides in the AmtR recognition motif.</p> <p>Results</p> <p>Site-directed mutagenesis, the characterization of corresponding mutant proteins by gel retardation assays and surface plasmon resonance and molecular modelling revealed several amino acids, which are directly involved in DNA binding, while others have more structural function. Furthermore, we could show that the spacing of the binding motif half sites is crucial for repression of transcription by AmtR.</p> <p>Conclusion</p> <p>Although the DNA binding domain of TetR-type repressors is highly conserved and a core binding motif was identified for AmtR and TetR(D), the AmtR binding domain shows individual properties compared to other TetR proteins. Besides by distinct amino acids of AmtR, DNA binding is influenced by nucleotides not only of the conserved binding motif but also by spacing nucleotides in <it>C. glutamicum</it>.</p

Primary processes: from atoms to diatomic molecules and clusters

International audienceThis article presents a short review of the main progresses achieved at the GANIL facilities during the last thirty years in the field of ion-atom and ion-diatomic molecule collisions. Thanks to the wide range of projectile energies and species available on the different beam lines of the facility, elementary processes such as electron capture, ionization and excitation have been extensively studied. Beside primary collision mechanisms, the relaxation processes of the collision partners after the collision have been another specific source of interest. Progresses on other fundamental processes such as Young type interferences induced by ion-molecule collisions or shake off ionization resulting from nuclear beta decay are also presented. 1. Introduction For the electronic structures of atoms and molecules, precise theoretical knowledge and high-resolution experimental data are available. But the complete understanding of dynamic processes in atomic collisions remains a challenge, due to large theoretical problems in describing time-dependent many-particle reactions, and to experimental difficulties in performing complete experiments in which all relevant quantities are accessible. Elementary collisions involving ions, atoms and molecules play an important role in many gaseous and plasma environments, where they provide both the heating and cooling mechanisms. The study of such collisions is thus not only of fundamental importance, it is also essential for the understanding of large-scale systems such as astrophysical plasmas, planetary atmospheres, gas discharge lasers, semiconductor processing plasmas, and fusion plasmas. Collisions between ions and atoms (or simple molecules) give also access to the elementary processes responsible for energy transfer in ion-matter and ion-biological molecule collisions. Complete knowledge of these elementary processes is thus of primordial importance for ion induced modification of materials as well as for radiolysis, radiotherapy and biological damages due to radiation exposure

Subcutaneous Rituximab-MiniCHOP compared with subcutaneous Rituximab-MiniCHOP plus Lenalidomide in diffuse large B-Cell lymphoma for patients age 80 years or older.

peer reviewedPURPOSE The prognosis of elderly patients with diffuse large B-cell lymphoma (DLBCL) is worse than that of young patients. An attenuated dose of chemotherapy—cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-miniCHOP)—is a good compromise between efficacy and safety in very elderly patients. In combination with R-CHOP (R2-CHOP), lenalidomide has an acceptable level of toxicity and may mitigate the negative prognosis of the non–germinal center B-cell–like phenotype. The Lymphoma Study association conducted a multicentric, phase III, open-label, randomized trial to compare R-miniCHOP and R2- miniCHOP. PATIENTS AND METHODS Patients of age 80 years or older with untreated DLBCL were randomly assigned into the R-miniCHOP21 group or the R2-miniCHOP21 group for six cycles and stratified according to CD10 expression and age. The first cycle of rituximab was delivered by IV on D1 after a prephase and then delivered subcutaneously on D1 of cycles 2-6. Lenalidomide was delivered at a dose of 10 mg once daily on D1-D14 of each cycle. The primary end point was overall survival (OS). RESULTS A total of 249 patients with new DLBCL were randomly assigned (127 R-miniCHOP and 122 R2- miniCHOP). The median age was 83 years (range, 80-96), and 55% of the patients were classified as non-GCB. The delivered dose for each R-miniCHOP compound was similar in both arms. Over a median follow-up of 25.1 months, the intention-to-treat analysis revealed that R2-miniCHOP did not improve OS (2-year OS 66% in R-miniCHOP and 65.7% in R2-miniCHOP arm, P5 .98) in the overall population or in the non-GCB population. Grade 3-4 adverse events occurred in 53% of patients with R-miniCHOP and in 81% of patients with R2- miniCHOP. CONCLUSION The addition of lenalidomide to R-miniCHOP does not improve OS. Rituximab delivered subcutaneously was safe in this population

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Edifices carbonés et borocarbonés en chimie moléculaire et de l'état solide (étude théorique)

Ce manuscrit regroupe un ensemble d'études réalisées sur des édifices carbonés et borocarbonés rencontrés en chimie moléculaire et de l'état solide. Il est divisé en trois parties. La première partie aborde l'étude de l'arrangement structural de borocarbures de métaux de transition de terre rare. Des composés sont présentés dans lesquels les atomes non métalliques forment des chaînes infinies unidimensionnelles ou de taille finie. Leur mode de liaison est analysé de manière qualitative, puis quantitative au moyen des méthodes de Hückel étendue (EH-TB) et de la fonctionnelle de la densité (DFT). Le mécanisme de la réaction de métathèse d'oléfine catalysée par un complexe carbène est présenté dans la deuxième partie. Les différents mécanismes proposés pour cette réaction ont été étudiés en DFT. Les résultats montrent que l'étape d'initiation est " dissociative ". La prise en compte du solvant de façon explicite est nécessaire pour avoir un bon accord avec les résultats des mesures de cinétique en solution. La troisième partie concerne la structure électronique de composés moléculaires mono-dimésityl-boryles de type " push-pull " et bis-dimésityl-boryles. Un regard particulier est porté à l'influence de différents groupements donneurs et du pont organique sur les fragments accepteurs dimésityl-boryles. Ces composés présentent des propriétés en optique non linéaire avec des hyperpolarisabilités élevées sous l'effet d'un champ électrique. Les hyperpolarisabilités du deuxième ordre ont été évaluées au moyen de méthodes semi-empiriques et ab initio Hartree-Fock.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Voltage‐gated proton channels in polyneopteran insects

Voltage‐gated proton channels (H(V)1) are expressed in eukaryotes, including basal hexapods and polyneopteran insects. However, currently, there is little known about H(V)1 channels in insects. A characteristic aspartate (Asp) that functions as the proton selectivity filter (SF) and the RxWRxxR voltage‐sensor motif are conserved structural elements in H(V)1 channels. By analysing Transcriptome Shotgun Assembly (TSA) databases, we found 33 polyneopteran species meeting these structural requirements. Unexpectedly, an unusual natural variation Asp to glutamate (Glu) at SF was found in Phasmatodea and Mantophasmatodea. Additionally, we analysed the expression and function of H(V)1 in the phasmatodean stick insect Extatosoma tiaratum (Et). EtH(V)1 is strongly expressed in nervous tissue and shows pronounced inward proton conduction. This is the first study of a natural occurring Glu within the SF of a functional H(V)1 and might be instrumental in uncovering the physiological function of H(V)1 in insects

Gd5Si2B8: A Ternary Rare-Earth-Metal Silicide Boride Compound

International audienc

A New Family of Heavy-fermion Compounds - U4TGa12 (T = Fe, Co, Rh and Pd)

U4TGa12 (T = Fe, Co, Rh and Pd) compounds represent a new family of isostructural heavy-fermion materials. They crystallize in the cubic structure typeY4PdGa12 (Im 3m) which consists of the doubling of the UGa3 (AuCu3-type, Pm 3m) elementary cell with a partial ordered occupancy (1/4) of the gallium octahedra by the transition metal atoms. Their magnetic and electronic properties (resistivity, magnetization and specific heat) have been investigated. All compounds display a moderately enhanced value of the Sommerfeld coefficient γ (80–140 mJ/molUK2) whereas only U4PdGa12 shows the occurrence of an antiferromagnetic order below TN =43K.JRC.E.6-Actinides researc