Engineering of a Bispecific Nanofitin with Immune Checkpoint Inhibitory Activity Conditioned by the Cross-Arm Binding to EGFR and PDL1.

Re-education of the tumor microenvironment with immune checkpoint inhibitors (ICI) has provided the most significant advancement in cancer management, with impressive efficacy and durable response reported. However, low response rates and a high frequency of immune-related adverse events (irAEs) remain associated with ICI therapies. The latter can be linked to their high affinity and avidity for their target that fosters on-target/off-tumor binding and subsequent breaking of immune self-tolerance in normal tissues.

[Unmet medical need in RSV prevention and future prevention strategies].

Each year, there are more than 45.000 hospitalizations in France attributable to RSV. The development of a maternal vaccine and long half-life monoclonal antibodies against RSV suggests a change in prevention strategy from a small group of very high-risk children (extreme preterm infants, newborn with hemodynamically significant congenital heart disease or with other rare conditions) to all newborns in the pre-epidemic and epidemic periods or throughout all the year.

Airy theory revisited with the method combining vectorial complex ray model and physical optics.

Airy published his theory in the 1830s to remedy the problem of infinite intensity in the rainbow angles of a spherical droplet predicted by geometrical optics. This theory has been studied by mathematicians and physicists since then from different points of view. In what concerns the scattering diagram around the rainbow angles, Airy theory has been improved by researchers in order to predict correctly the intensity of the supernumerary bows.

Acousto-optically driven lensless single-shot ultrafast optical imaging.

Driven by many applications in a wide span of scientific fields, a myriad of advanced ultrafast imaging techniques have emerged in the last decade, featuring record-high imaging speeds above a trillion-frame-per-second with long sequence depths. Although bringing remarkable insights into various ultrafast phenomena, their application out of a laboratory environment is however limited in most cases, either by the cost, complexity of the operation or by heavy data processing. We then report a versatile single-shot imaging technique combining sequentially timed all-optical mapping photography (STAMP) with acousto-optics programmable dispersive filtering (AOPDF) and digital in-line holography (DIH).

DockNmine, a Web Portal to Assemble and Analyse Virtual and Experimental Interaction Data.

Scientists have to perform multiple experiments producing qualitative and quantitative data to determine if a compound is able to bind to a given target. Due to the large diversity of the potential ligand chemical space, the possibility of experimentally exploring a lot of compounds on a target rapidly becomes out of reach. Scientists therefore need to use virtual screening methods to determine the putative binding mode of ligands on a protein and then post-process the raw docking experiments with a dedicated scoring function in relation with experimental data.

Ultrafast high-repetition imaging of fuel sprays using picosecond fiber laser.

Modern diesel injectors operate at very high injection pressures of about 2000 bar resulting in injection velocities as high as 700 m/s near the nozzle outlet. In order to better predict the behavior of the atomization process at such high pressures, high-resolution spray images at high repetition rates must be recorded. However, due to extremely high velocity in the near-nozzle region, high-speed cameras fail to avoid blurring of the structures in the spray images due to their exposure time.

Collinear, two-color optical Kerr effect shutter for ultrafast time-resolved imaging.

Imaging with ultrashort exposure times is generally achieved with a crossed-beam geometry. In the usual arrangement, an off-axis gating pulse induces birefringence in a medium exhibiting a strong Kerr response (commonly carbon disulfide) which is followed by a polarizer aligned to fully attenuate the on-axis imaging beam. By properly timing the gate pulse, imaging light experiences a polarization change allowing time-dependent transmission through the polarizer to form an ultrashort image.

DNA polymorphisms of the KiSS1 3' untranslated region interfere with the folding of a G-rich sequence into G-quadruplex.

KISS1R and its ligand, the kisspeptins, are key hypothalamic factors that regulate GnRH hypothalamic secretion and therefore the pubertal timing. During studies analysing KiSS1 as a candidate gene in pubertal onset disorders, two SNP and one nucleotide insertion were observed in a 23 nucleotides G-rich sequence located 65 nucleotides downstream of the stop codon. The polymorphisms formed four haplotypes.

Vectorial complex ray model and application to two-dimensional scattering of plane wave by a spheroidal particle.

A vectorial complex ray model is introduced to describe the scattering of a smooth surface object of arbitrary shape. In this model, all waves are considered as vectorial complex rays of four parameters: amplitude, phase, direction of propagation, and polarization. The ray direction and the wave divergence/convergence after each interaction of the wave with a dioptric surface as well as the phase shifts of each ray are determined by the vector Snell law and the wavefront equation according to the curvatures of the surfaces.

Time gate, optical layout, and wavelength effects on ballistic imaging.

A method to distinguish a hidden object from a perturbing environment is to use an ultrashort femtosecond pulse of light and a time-resolved detection. To separate ballistic light containing information on a hidden object from multiscattered light coming from the surrounding environment that scrambles the signal, an optical Kerr gate can be used. It consists of a carbon disulfide (CS(2)) cell in which birefringence is optically induced.

[Congenital hypogonadotropic hypogonadism].

Congenital hypogonadotropic hypogonadism is defined by reduced steroid hormone synthesis and secretion due to low LH and FSH secretion. It is a rare disease with an unknown prevalence (about 1/5000). It results from a fetal defect in GnRH neuron migration, a defect of pituitary development or from a functional defect of the hypothalamopituitary axis between GnRH neurons and gonadotropic cells.

Ultrashort pulse propagation through a strongly scattering medium: simulation and experiments.

Forward light scattering of femtosecond pulses through strongly scattering media is investigated experimentally and numerically. Computations are based on a semi-Monte Carlo method including polarization effects when experiments depend on a Ti:sapphire regenerative amplifier (100 fs, 1 kHz, 1 mJ@ 800 nm). The temporal separation between ballistic light and scattered light is exhibited and used to perform optical depth measurements up to 22 (transmission factor of approximately 10(-10)).

Four-flux model for a multilayer, plane absorbing and scattering medium: application to the optical degradation of white paint in a space environment.

We generalize the four-flux radiative transfer model to the case of a multilayer medium. A concrete application, that of the study of the optical degradation of white paint in a simulated space environment, is presented. The degraded material is decomposed in a damaged layer and in an unaffected layer, and we assume that the degradation is due to a variation Dkappa of the imaginary part of the refractive index in the damaged layer.

Comparison of iterative and monte carlo methods for calculation of the Aureole about a point source in the earth's atmosphere.

Point sources in the atmosphere are surrounded by aureoles because of atmospheric scattering. The properties of an aureole were calculated by use of a Monte Carlo approach and an iterative method for an isotropic source and an axially symmetric emission source inside an infinite homogeneous atmosphere. The influence of single-scattering albedo, optical depth between source and observer, and source intensity anisotropy were studied from both approaches.

Predictors of late menarche and adult height in children with anorexia nervosa.

Objectives: The onset of anorexia nervosa (AN) during childhood can affect the timing of puberty and adult height. The aim of the study was to evaluate the determinants of late menarche and adult height in children with AN.

Patients And Methods: We carried out a retrospective, longitudinal, university hospital-based study.

Carbonylbisphosphonate and (diazomethylene)bisphosphonate analogues of AZT 5(')-diphosphate.

A novel nucleotide analogue is described, in which the alpha,beta-phosphoric anhydride oxygen of a nucleoside 5(')-diphosphate is replaced by a carbonyl group: the carbonylbisphosphonate analogue 5 of 2('),3(')-dideoxy-3(')-azidothymidine 5(')-diphosphate (AZT 5(')-diphosphate). 5 was synthesized from tetramethyl (diazomethylene)bisphosphonate 1 via the trimethyl ester 4 of the corresponding AZT 5(')-(diazomethylene)bisphosphonate 6, which is also a new type of nucleotide analogue. The ultimate product 5 was isolated by reverse-phase HPLC, and characterized by 31P, 13C, and 1H NMR; and by high-resolution mass spectrometry.

Modulation of exocrine pancreatic secretion by leptin through CCK(1)-receptors and afferent vagal fibres in the rat.

In this report, we determined whether leptin could modify the exocrine pancreatic secretion of anaesthetized rats in vivo. Intravenous injection of recombinant murine leptin resulted in a time- and dose-dependent stimulation of exocrine pancreatic secretion, maximally observed with 30 nmol/kg of leptin. This stimulation of pancreatic water, bicarbonate, and protein output was abolished by atropine, hexamethonium, L364,718 ([3S(-)-N-(1,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine]), a cholecystokinin CCK(1) receptor antagonist or perivagal capsaicin pretreatment, but unaffected by the CCK(2) receptor antagonist L365,260 ([3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3yl)-N'-(3-methylphenyl)urea]).

Vasoactive intestinal peptide is involved in the inhibitory effect of interleukin-1 beta on the jejunal contractile response induced by acetylcholine.

Unlabelled: Although previous studies have shown that interleukin-1 beta (IL-1 beta) decreases acetylcholine (ACh)-induced intestinal contraction by an action on the enteric nervous system, the neuromediator(s) involved are still unknown.

Aim: To determine the role of nitric oxide (NO), vasoactive intestinal peptide (VIP) and/or adenosine triphosphate (ATP) in mediating this inhibitory effect.

Methods: The effects of NO synthase inhibitors, VIP and ATP antagonists on motor response to the ACh were investigated before and after 90-min exposure of a rat preparation of jejunal longitudinal muscle-myenteric plexus to IL-1 beta.

In vivo absorption of water and electrolytes in mouse intestine. Application to villin -/- mice.

This study was done to establish and validate a single-pass perfusion method for measuring the absorption of water and electrolytes by the mouse small intestine. The method was then used to study intestinal absorption in mice whose villin gene had been invalidated (v-/-). The single-pass perfusion of the jejunum measures the absorption of water, Cl(-), Na(+), K(+), HCO, and glucose in anesthetized wild-type and v-/- mice in vivo.

PepT1-mediated epithelial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine.

Dietary proteins are mostly absorbed as di- and tripeptides by the intestinal proton-dependent transporter PepT1. We have examined the effects of leptin on PepT1 function in rat jejunum and in monolayers of the human enterocyte-like 2 cell Caco-2. Leptin is produced by the stomach and secreted in the gut lumen.

Role of nonesterified fatty acids in necrotizing pancreatitis: an in vivo experimental study in rats.

Introduction: In acute pancreatitis, nonesterified fatty acids (NEFA) might be released by lipase and cause tissue necrosis by their detergent properties, but this has not been established in vivo.

Aims: To measure the release of NEFA in the blood stream, pancreatic tissue, and peritoneal cavity during taurocholate-induced acute necrotizing pancreatitis in rats.

Methodology: Ascites and blood were repeatedly sampled; after 24 hours, pancreatic lesions were scored, and NEFA were measured in the pancreas.

The peptide YY-preferring receptor mediating inhibition of small intestinal secretion is a peripheral Y(2) receptor: pharmacological evidence and molecular cloning.

A peptide YY (PYY)-preferring receptor [PYY > neuropeptide Y (NPY)] was previously characterized in rat small intestinal crypt cells, where it mediates inhibition of fluid secretion. Here, we investigated the possible status of this receptor as a peripheral Y(2) receptor in rats. Typical Y(2) agonists (PYY(3-36), NPY(3-36), NPY(13-36), C2-NPY) and very short PYY analogs (N-alpha-Ac-PYY(22-36) and N-alpha-Ac-PYY(25-36)) acting at the intestinal PYY receptor were tested for their ability to inhibit the binding of (125)I-PYY to membranes of rat intestinal crypt cells and of CHO cells stably transfected with the rat hippocampal Y(2) receptor cDNA.