The Rational Design, Synthesis, and Antimicrobial Properties of Thiophene Derivatives That Inhibit Bacterial Histidine Kinases

The emergence of multidrug-resistant bacteria emphasizes the urgent need for novel antibacterial compounds targeting unique cellular processes. Two-component signal transduction systems (TCSs) are commonly used by bacteria to couple environmental stimuli to adaptive responses, are absent in mammals, and are embedded in various pathogenic pathways. To attenuate these signaling pathways, we aimed to target the TCS signal transducer histidine kinase (HK) by focusing on their highly conserved adenosine triphosphate-binding domain. We used a structure-based drug design strategy that begins from an inhibitor-bound crystal structure and includes a significant number of structurally simplifiying “intuitive” modifications to arrive at the simple achiral, biaryl target structures. Thus, ligands were designed, leading to a series of thiophene derivatives. These compounds were synthesized and evaluated in vitro against bacterial HKs. We identified eight compounds with significant inhibitory activities against these proteins, two of which exhibited broad-spectrum antimicrobial activity. The compounds were also evaluated as adjuvants for the treatment of resistant bacteria. One compound was found to restore the sensivity of these bacteria to the respective antibiotics

Towards 500°C SPER activated devices for 3D sequential integration

session: Monolithic 3D 3International audienceThis work investigates the possibility to reduce the Solid Phase Epitaxy Regrowth (SPER) temperature for dopant activation needed in 3D sequential integration. The electrical results obtained on 28nm FDSOI devices show that 500°C SPER can yield similar performance to that of 600°C SPER and 1050°C spike anneal. This paper highlights the advantages of using a -oriented channel and tilted implantation to successfully reduce the SPER thermal budget. It also confirms that the channel can be used as a seed for the recrystallization. The analysis takes into account the SPER rate dependence on temperature, crystalline orientation, dopant type and dopant concentration

Smart solutions for efficient dual strain integration for future FDSOI generations

cited By 1International audienceWe present deep insights on the integration and physics of two new strain boosters for FDSOI CMOS. 'STRASS' and 'BOX creep' techniques (for tensily and compressively stressed channels, respectively) are for the first time integrated in a localized manner on a state-of-The-Art 14nm FDSOI route. STRASS enables to achieve +1.6 GPa in SOI active regions (w.r.t. +1.3 GPa for thin BOX sSOI). BOX creep process leads to more than +10% in hole mobility and +6% in Ieff(Ioff) plots. The BOX creep efficiency is investigated with respect to device dimensions: The electrical data evolution matches the proposed mobility model based on 2D simulated stress profiles. © 2016 IEEE

Impact of strain on access resistance in planar and nanowire CMOS devices

session 17: CMOS integrationInternational audienceWe fabricated and in-depth characterized advanced planar and nanowire CMOS devices, strained by the substrate (sSOI or SiGe channel) and by the process (CESL, SiGe source/drain). We have built a novel access resistance (R ACC ) extraction procedure, which enables us to clearly evidence the strong impact of back-bias and strain on R acc (-21% for 4 V V B and -53% for -1GPa stress on pMOS FDSOI). This is in agreement with Non-Equilibrium-Green-Functions (NEGF) simulations. This RAcc(strain) dependence has been introduced into SPICE, leading to +6% increase of the RO frequency under ε n/p =0.8%/-0.5% strain, compared to the state-of-the-art model. It is thus mandatory for predictive benchmarking and optimized IC designs

Design / technology co-optimization of strain-induced layout effects in 14nm UTBB-FDSOI CMOS: Enablement and assessment of continuous-RX designs

cited By 4International audienceWe report on the main local layout effect in 14nm Ultra-Thin Buried oxide and Body Fully Depleted Silicon On Insulator (UTBB-FDSOI) CMOS technology [1]. This effect is demonstrated by Nano-Beam Diffraction to be directly induced by the strain in the SiGe channel and reproduced by an accurate electrical compact model. An original continuous-RX design optimizes the stress management, maintaining longitudinal stress component while relaxing the transverse one. A 28% ring oscillator delay improvement is experimentally demonstrated at same leakage for 1-finger inverter at VDD=0.8V supply voltage and a frequency gain up to 15% is simulated in a critical path of an A9 core. © 2016 IEEE

Gonadotropin-releasing hormone secretion from hypothalamic neurons: stimulation by insulin and potentiation by leptin.

Insulin and leptin are peripheral metabolic factors signaling the body needs in energy to the central nervous system. Because energy homeostasis and reproductive function are closely related phenomena, we investigated the respective roles played by insulin and leptin in the hypothalamic control of GnRH secretion. We observed that increasing circulating insulin levels, by performing hyperinsulinemic clamp studies in male mice, was associated with a significant rise in LH secretion. This effect of insulin is likely mediated at the hypothalamic level, because it was also found to stimulate the secretion and the expression of GnRH by hypothalamic neurons in culture. Leptin was found to potentiate the effect of insulin on GnRH secretion in vitro but was devoid of any effect on its own. These data represent the first evidence of direct insulin sensing by hypothalamic neurons involved in activating the neuroendocrine gonadotrope axis. They also demonstrate that these neurons can integrate different hormonal signals to modulate net hypothalamic GnRH output. We propose that such integration is an essential mechanism for the adaptation of reproductive function to changes in the metabolic status of an individual