A way forward for fundamental physics in space.

Space-based research can provide a major leap forward in the study of key open questions in the fundamental physics domain. They include the validity of Einstein's Equivalence principle, the origin and the nature of dark matter and dark energy, decoherence and collapse models in quantum mechanics, and the physics of quantum many-body systems. Cold-atom sensors and quantum technologies have drastically changed the approach to precision measurements. Atomic clocks and atom interferometers as well as classical and quantum links can be used to measure tiny variations of the space-time metric, elusive accelerations, and faint forces to test our knowledge of the physical laws ruling the Universe. In space, such instruments can benefit from unique conditions that allow improving both their precision and the signal to be measured. In this paper, we discuss the scientific priorities of a space-based research program in fundamental physics.

Lorentz Symmetry Violations from Matter-Gravity Couplings with Lunar Laser Ranging.

The standard-model extension (SME) is an effective field theory framework aiming at parametrizing any violation to the Lorentz symmetry (LS) in all sectors of physics. In this Letter, we report the first direct experimental measurement of SME coefficients performed simultaneously within two sectors of the SME framework using lunar laser ranging observations. We consider the pure gravitational sector and the classical point-mass limit in the matter sector of the minimal SME. We report no deviation from general relativity and put new realistic stringent constraints on LS violations improving up to 3 orders of magnitude previous estimations.

Test of Special Relativity Using a Fiber Network of Optical Clocks.

Phase compensated optical fiber links enable high accuracy atomic clocks separated by thousands of kilometers to be compared with unprecedented statistical resolution. By searching for a daily variation of the frequency difference between four strontium optical lattice clocks in different locations throughout Europe connected by such links, we improve upon previous tests of time dilation predicted by special relativity. We obtain a constraint on the Robertson-Mansouri-Sexl parameter |α|≲1.1×10^{-8}, quantifying a violation of time dilation, thus improving by a factor of around 2 the best known constraint obtained with Ives-Stilwell type experiments, and by 2 orders of magnitude the best constraint obtained by comparing atomic clocks. This work is the first of a new generation of tests of fundamental physics using optical clocks and fiber links. As clocks improve, and as fiber links are routinely operated, we expect that the tests initiated in this Letter will improve by orders of magnitude in the near future.

Testing Lorentz Symmetry with Lunar Laser Ranging.

Lorentz symmetry violations can be parametrized by an effective field theory framework that contains both general relativity and the standard model of particle physics called the standard-model extension (SME). We present new constraints on pure gravity SME coefficients obtained by analyzing lunar laser ranging (LLR) observations. We use a new numerical lunar ephemeris computed in the SME framework and we perform a LLR data analysis using a set of 20 721 normal points covering the period of August, 1969 to December, 2013. We emphasize that linear combination of SME coefficients to which LLR data are sensitive and not the same as those fitted in previous postfit residuals analysis using LLR observations and based on theoretical grounds. We found no evidence for Lorentz violation at the level of 10^{-8} for s[over ¯]^{TX}, 10^{-12} for s[over ¯]^{XY} and s[over ¯]^{XZ}, 10^{-11} for s[over ¯]^{XX}-s[over ¯]^{YY} and s[over ¯]^{XX}+s[over ¯]^{YY}-2s[over ¯]^{ZZ}-4.5s[over ¯]^{YZ}, and 10^{-9} for s[over ¯]^{TY}+0.43s[over ¯]^{TZ}. We improve previous constraints on SME coefficient by a factor up to 5 and 800 compared to postfit residuals analysis of respectively binary pulsars and LLR observations.

An experimental system to study responses of Medicago truncatula roots to chitin oligomers of high degree of polymerization and other microbial elicitors.

KEY MESSAGE: A fully acetylated, soluble CO preparation of mean DP of ca. 7 was perceived with high sensitivity by M. truncatula in a newly designed versatile root elicitation assay. The root system of legume plants interacts with a large variety of microorganisms, either pathogenic or symbiotic. Understanding how legumes recognize and respond specifically to pathogen-associated or symbiotic signals requires the development of standardized bioassays using well-defined preparations of the corresponding signals. Here we describe the preparation of chitin oligosaccharide (CO) fractions from commercial chitin and their characterization by a combination of liquid-state and solid-state nuclear magnetic resonance spectroscopy. We show that the CO fraction with highest degree of polymerization (DP) became essentially insoluble after lyophilization. However, a fully soluble, fully acetylated fraction with a mean DP of ca. 7 was recovered and validated by showing its CERK1-dependent activity in Arabidopsis thaliana. In parallel, we developed a versatile root elicitation bioassay in the model legume Medicago truncatula, using a hydroponic culture system and the Phytophthora ß-glucan elicitor as a control elicitor. We then showed that M. truncatula responded with high sensitivity to the CO elicitor, which caused the production of extracellular reactive oxygen species and the transient induction of a variety of defense-associated genes. In addition, the bioassay allowed detection of elicitor activity in culture filtrates of the oomycete Aphanomyces euteiches, opening the way to the analysis of recognition of this important legume root pathogen by M. truncatula.

[Neuroradiological manifestations of primary Sjögren's syndrome]. / Manifestations neurologiques du syndrome de Sjögren primitif.

Primary Sjögren's syndrome (PSS) is considered as the most frequent connective tissue disease. Neurological complications may affect the peripheral nervous system and to a lesser extent the central nervous system. Neurological manifestations often precede or reveal SSP. Peripheral neuropathy is the most common and well-known neurological complication of PSS. Its frequency is about 20-30 percent of patients. Distal sensory or sensorimotor axonal neuropathy is the most frequent followed by sensory neuronopathy, the only neurological complication characteristic of SSP. Recently, several cases of motor neuron syndrome have been reported suggesting that it could be a neurological complication of SSP. CNS involvement consists of cerebral or spinal cord involvement and its frequency is debated. Cerebral dysfunction may be focal or multifocal according to the number and location of lesions. Its course may be acute, remittent or progressive. Cognitive dysfunction and psychiatric manifestations seem to be frequent in SSP but this needs to be confirmed by further studies. Spinal cord involvement consists of acute myelitis or progressive myelopathy. In CNS involvement, there is no correlation between clinical findings and results of CSF study or MRI which can be normal or disclose unspecific abnormalities. For all neurological complications, response to corticosteroids or immunosuppressive therapy is unpredictable. As neurological manifestations in SSP are miscellaneous, SSP diagnosis should be considered in any unexplained neurological setting because sicca syndrome is often mild or asymptomatic and immunological abnormalities or other extraglandular manifestations of PSS may be lacking.

Neurological complications of primary Sjögren's syndrome.

OBJECTIVE: To better delineate the spectrum of neurological complications of primary Sjögren's syndrome (PSS). METHODS: A detailed neurological investigation was prospectively performed in a group of 25 consecutive patients with PSS followed in an internal medicine department between June 1996 and December 1997 (Internal Medicine group). In addition, eleven patients with neurological complications of PSS were identified in the Neurological Department of the same institution during the same period (Neurological group). RESULTS: In the Internal Medicine group, neurological complications were discovered in 10/25 (40%) patients. Peripheral nervous system involvement was present in 4/25 patients from the Internal Medicine group and in 10/11 patients from the Neurological group and consisted mainly of axonal sensorimotor/sensory polyneuropathy. A motor neuron syndrome was identified in two patients. CNS involvement occurred in 7/25 patients from the Internal Medicine group and in 4/11 patients from the Neurological group. Three patients had spinal cord involvement. Cognitive dysfunction was the most frequent finding (5/25 in the Internal Medicine group, 3/11 in the Neurological group) characterized either by subcortical or corticosubcortical dysfunction. Cognitive impairment was not attributed to mood disturbance and was not associated with specific laboratory or radiological abnormalities. CONCLUSION: Neurological complications of PSS are frequent since they were present in 40% (10/25) of patients in a consecutive series of patients from a department of Internal Medicine. Although PNS involvement predominates, complications of PSS affecting the brain or spinal cord are not rare, with subcortical dysfunction as the main finding.

Modulation of presynaptic inhibition of la afferents during voluntary wrist flexion and extension in man.

Changes in presynaptic inhibition of Ia terminals directed to flexor carpi radialis (FCR) motoneurones (MNs) were investigated in normal human subjects at rest and during voluntary wrist flexion and extension. To that end, two independent methods were used: (1) the radial-induced D1 inhibition of the FCR H reflex, which assesses the excitability of PAD (primary afferent depolarisation) interneurones controlling presynaptic inhibition of Ia terminals mediating the afferent volley of the FCR H reflex; and (2) the heteronymous monosynaptic Ia facilitation induced in the FCR H reflex by intrinsic muscle Ia afferent stimulation, which assesses the ongoing presynaptic inhibition of Ia terminals. With respect to results at rest, it was found that at the onset of (and during tonic) voluntary wrist flexion, D1 inhibition was reduced and heteronymous monosynaptic Ia facilitation was increased. This suggests that, as in the lower limb, presynaptic inhibition is decreased on Ia terminals projecting to MNs involved in the voluntary contraction. In contrast with results observed in the lower limb, presynaptic inhibition of Ia terminals to FCR MNs was also found to be reduced at the onset of a voluntary contraction involving the antagonistic wrist extensors, suggesting that presynaptic inhibition of Ia terminals projecting to wrist flexors and extensors might be mediated through the same subsets of PAD interneurones. This is in keeping with other features showing that the organisation of reflex pathways between wrist flexors and extensors differs from that observed at other (elbow, ankle) joints.

Presynaptic inhibition and homosynaptic depression: a comparison between lower and upper limbs in normal human subjects and patients with hemiplegia.

Presynaptic inhibition of Ia terminals and postactivation depression at the Ia fibre-motor neuron (MN) synapses were compared in the upper and lower limbs of both sides in subjects from different populations: 49 spastic patients with hemiplegia [mainly with a lesion in the middle cerebral artery (MCA) area], two tetraplegics and 35 healthy subjects. Presynaptic inhibition was assessed using D1 inhibition of the soleus and the flexor carpi radialis (FCR) H reflexes elicited by electrical stimuli applied to the nerve supplying antagonistic muscles, and postactivation depression was explored by varying the time interval between two consecutive H reflexes. In normal subjects no right-left asymmetry was found in the amount of presynaptic Ia inhibition, homosynaptic depression or the H(max)/M(max) ratio. In the hemiplegic side of patients with MCA area lesions, the H(max)/M(max) ratio was significantly increased in the soleus but not in the FCR. Presynaptic inhibition of Ia terminals, which was significantly reduced at the cervical level on the hemiplegic side (and also, but to a lesser extent, on the unaffected side), was unchanged at the lumbar level. Homosynaptic depression was similarly reduced at the cervical and lumbar levels on the hemiplegic side but not modified on the unaffected side. It is argued that the decrease in presynaptic inhibition of Ia terminals is more a correlate of spasticity than a mechanism underlying it. The decrease in postactivation depression, which very probably contributes to the exaggeration of the stretch reflex characterizing spasticity, might be a consequence of the changes in the pattern of activation of Ia afferents and MNs following the motor impairment.

[Gougerot-Sjögren syndrome. Neurologic complications]. / Syndrome de Gougerot-Sjögren. Complications neurologiques.

PERIPHERAL NERVE INVOLVEMENT: Peripheral nerve involvement is better known than central nervous system involvement. The dominant features are sensoromotor polyneuropathies or pure sensorial polyneuropathies. CENTRAL NERVOUS SYSTEM: The manifestations are polymorphous, generally presenting as encephalitis and/or focal or multifocal involvement of the spinal cord. OTHER LOCALIZATIONS: Diffuse encephalic involvement is less common: acute aseptic meningitis, intellectual deterioration. Psychiatric manifestations are also frequently observed. THERAPEUTIC OPTIONS: Response to corticosteroid therapy or immunosuppressor therapy can be spectacular but is unpredictable.

[determining factors of depression in multiple sclerosis: review of the literature]. / Les déterminants de la dépression dans la sclérose en plaques. Revue de la littérature.

Depression is considered to occur more frequently in multiple sclerosis than in other chronic organic disorders. The determining factors of this specific association have been appraised by most authors in a dichotomic manner, confronting organic to psychogenic hypotheses. To assess these hypotheses two investigational methods have been used in the literature: either the search for correlations between depression and other parameters linked to the neurologic process, or the comparison of the course of neurologic and thymic symptoms. Systematically scrutinizing this literature enabled us to discuss its findings as well as its methodologic and conceptual limitations.

Treatment of supratentorial glioblastoma multiforme with radiotherapy and a combination of BCNU and tamoxifen: a phase II study.

From May 1990 to November 1994, 70 consecutive patients suffering from glioblastoma multiforme were treated following surgery with conventional radiotherapy and adjuvant IV BCNU administered alone or in combination with tamoxifen. Twenty-five patients received BCNU alone (control group A) while 24 patients also received 40 mg of tamoxifen (TMX) PO daily (group B) and 21 received 100 mg of TMX PO daily (group C). There were no significant differences between the 3 groups concerning age, type of resection and median post-operative Karnofsky performance status (KPS). Blood toxicity over grade II occurred in 33.5% of patients receiving TMX versus 12% of patients treated with BCNU alone (p < 0.05). Deep venous thrombosis complications were observed in 4 patients of each TMX group, whereas they were not observed in the control group (p < 0.04). Median time to tumor progression (MTTP) was 35 weeks in the control group and 27 weeks in both TMX groups B and C. Median survival time (MST) was 56, 66 and 51 weeks, respectively. These results suggest that the addition of TMX to standard treatment of glioblastomas does not affect the time to tumor progression and overall survival but may increase the risk of deep venous thrombosis or nitrosourea-induced blood toxicity.

[Neurologic manifestations of primary Gougerot-Sjögren syndrome]. / Manifestations neurologiques du syndrome de Gougerot-Sjögren primitif.

Primary Sjögren's syndrome is one of the commonest autoimmune connective tissue diseases. Neurological complications occur in about 20 p. 100 of primary Sjögren's syndrome patients. It most frequently involves the peripheral nervous system, predominantly sensorimotor and sensory polyneuropathy. Sensory neuronopathy and trigeminal nerve involvement are less frequent but quite suggestive of primary Sjögren's syndrome. Among central nervous system involvements, focal or multifocal lesions of the brain or the spinal cord are the most frequent. Diffuse encephalic involvement may present either as an aseptic meningoencephalitis or as a cognitive impairment. It is not clear whether psychiatric manifestations (mostly mood and personality disturbances) have an organic substratum or are the psychological consequence of the disability induced by a chronic disease such as Sjögren's syndrome. The response to corticosteroids or immunosuppressive therapy is unpredictable in neurological complications of primary Sjögren's syndrome. The pathophysiology of these complications remains unknown. Different mechanisms could be assumed depending on the neurological manifestations: vasculitis in polyneuropathies and multiple mononeuropathies, humoral and/or cellular mediated immune response against neurones in sensory neuronopathy. In central nervous system involvement, each of these mechanisms could occur.

[Effect of treatment with methadone on utilization of medical care by addicts seropositive for the AIDS virus. Results of a descriptive study, Bayonne, 1996]. / Influence des traitements par la méthadone dans la prise en charge médicale des toxicomanes séropositifs pour le virus du SIDA. Résultats d'une étude descriptive, Bayonne, 1996.

Since two years, 80 patients received methadone maintenance treatment in Bayonne Médecins du Monde Center. In this population, 48% are HIV positive... The aim of this study is to determine the impact of methadone maintenance treatment on the medical status of a group of HIV positive subjects. In addition to the Addiction Severity Index collected data and quality of life evaluation by the TEAQV, the following data are collected: compliance to appointments HIV clinic, CD4 status, evolution of weight, observance of HIV medicine. Preliminary results are presented, showing precisely and confirming the good influence of methadone maintenance treatment on medical care of patients with HIV and AIDS. This kind of study, before and during the maintenance treatment (base line, third month and every six months) appears as a very important stake: for this patients with HIV and AIDS, in term of personal and medical status, for us, in term of methadone treatment impact, and health public care.

Analysis of hydroxyproline and hydroxyproline-arabinosides of plant origin by high-performance anion-exchange chromatography-pulsed amperometric detection.

The plant cell wall hydroxyproline-rich glycoprotein (HRGP), also called extensin, contains arabinose and oligoarabinoside side chains O-glycosidically linked to hydroxyproline (Hyp). We present a highly sensitive method for determining both the glycosylation pattern and the Hyp content of HRGP requiring only nanomole amounts of each Hyp-compound for accurate determination. This method is based on anion-exchange chromatography followed by pulsed amperometric detection of the Hyp-oligoarabinosides and Hyp released from HRGP by 0.22 M Ba(OH)2 hydrolysis, which cleaves only peptidyl bonds. A sodium acetate gradient (0-250 mM) in 150 mM NaOH elutes Hyp and the Hyp-oligoarabinosides Hyp-(Ara)1-5 in less than 40 min. We have used this procedure to determine the glycosylation pattern of Hyp in plant cell walls, without prior isolation of HRGP.

Induction by (alpha)-L-Arabinose and (alpha)-L-Rhamnose of Endopolygalacturonase Gene Expression in Colletotrichum lindemuthianum.

The production of endopolygalacturonase (endoPG) by Colletotrichum lindemuthianum, a fungal pathogen causing anthracnose on bean seedlings, was enhanced when the fungus was grown in liquid medium with L-arabinose or L-rhamnose as the sole carbon source. These two neutral sugars are present in plant cell wall pectic polysaccharides. The endolytic nature of the enzyme was demonstrated by its specific interaction with the polygalacturonase-inhibiting protein of the host plant as well as by sugar analysis of the products released from its action on oligogalacturonides. Additional characterization of the protein was achieved with an antiserum raised against the pure endoPG of the fungus. Induction by arabinose and rhamnose was more prolonged and led to a level of enzyme activity at least five times higher than that on pectin. Northern blot experiments showed that this effect was correlated to the induction of a 1.6-kb transcript. A dose-response study indicated that the endoPG transcript level was already increased at a concentration of each sugar as low as 2.75 mM in the medium and was maximum at 55 mM arabinose and 28 mM rhamnose. Glucose, the main plant cell wall sugar residue which is also present in the apoplast, prevented endoPG gene expression, partially when added to pectin at concentrations ranging from 5 to 110 mM and totally when added at 55 mM to arabinose. Inhibition by glucose of the rhamnose-induced endoPG was correlated to nonuptake of rhamnose. This is the first report that arabinose and rhamnose stimulate endoPG gene expression in a fungus. The possible involvement of these various sugars on endoPG gene expression during pathogenesis is discussed.