Highly Dispersive Spin Excitations in the Chain Cuprate Li2CuO2

We present an inelastic neutron scattering investigation of Li2CuO2 detecting the long sought quasi-1D magnetic excitations with a large dispersion along the CuO2-chains studied up to 25 meV. The total dispersion is governed by a surprisingly large ferromagnetic (FM) nearest-neighbor exchange integral J1=-228 K. An anomalous quartic dispersion near the zone center and a pronounced minimum near (0,0.11,0.5) r.l.u. (corresponding to a spiral excitation with a pitch angle about 41 degree point to the vicinity of a 3D FM-spiral critical point. The leading exchange couplings are obtained applying standard linear spin-wave theory. The 2nd neighbor inter-chain interaction suppresses a spiral state and drives the FM in-chain ordering below the Ne'el temperature. The obtained exchange parameters are in agreement with the results for a realistic five-band extended Hubbard Cu 3d O 2p model and L(S)DA+U predictions.Comment: 6 pages, 4 figures, submitted to Europhys. Let

Brain glucose utilization in systemic lupus erythematosus with neuropsychiatric symptoms: A controlled positron emission tomography study

In contrast to morphological imaging [such as magnetic resonance imaging (MRI) or computed tomography], functional imaging may be of advantage in the detection of brain abnormalities in cases of neuropsychiatric systemic lupus erythematosus (SLE). Therefore, we studied 13 patients (aged 40±14 years, 11 female, 2 male) with neuropsychiatric SLE who met four of the American Rheumatism Association criteria for the classification of SLE. Ten clinically and neurologically healthy volunteers served as controls (aged 40±12 years, 5 female, 5 male). Both groups were investigated using fluorine-18-labelled fluorodeoxyglucose brain positron emission tomography (PET) and cranial MRI. The normal controls and 11 of the 13 patients showed normal MRI scans. However, PET scan was abnormal in all 13 SLE patients. Significant group-to-group differences in the glucose metabolic index (GMI=region of interest uptake/global uptake at the level of the basal ganglia and thalamus) were found in the parieto-occipital region on both sides: the GMI of the parieto-occipital region on the right side was 0.922±0.045 in patients and 1.066±0.081 in controls (P<0.0001, Mann WhitneyU test), while on the left side it was 0.892±0.060 in patients and 1.034±0.051 in controls (P=0.0002). Parietooccipital hypometabolism is a conspicuous finding in mainly MRI-negative neuropsychiatric SLE. As the parieto-occipital region is located at the boundary of blood supply of all three major arteries, it could be the most vulnerable zone of the cerebrum and may be affected at an early stage of the cerebrovascular diseas

Challenges and Progress in improving Safety and Managing Radioactive Wastes at Chornobyl NPP and in the Chornobyl Exclusion Zone

The commissioning of the New Safe Confinement at the Chornobyl Nuclear Plant Unit 4 site will mark the achievement of one important milestone within the process “conversion of the Chornobyl Unit 4 into safe ecologic conditions”. New radioactive waste management facilities have been developed at Chornobyl Nuclear Plant and at Vektor Complex to ensure the safe management of radioactive wastes in the Chornobyl Exclusion Zone. The continued investigations and safety assessments of different legacy waste sites which were created as part of the accident response measures confirm the efficiency of the measures of the past are and consolidate the basis for the strategy for the safe management of legacy wastes. All these together demonstrates that the national and international efforts vested to manage the consequences of the Chornobyl accident have achieved substantial and visible progress in safety and long term safety will be achieved by their consistent continuation.Уведення в експлуатацію нового безпечного конфайнмента на майданчику № 4 ЧАЕС ознаменує досягнення однієї важливої віхи у процесі перетворення чорнобильського енергоблока № 4 на екологічну безпечну систему. Нові об'єкти з поводження з радіоактивними відходами були розроблені на ЧАЕС і в комплексі "Вектор" для забезпечення безпечного поводження з радіоактивними відходами в чорнобильській зоні відчуження. Тривалі дослідження та оцінки безпеки різних майданчиків відходів, що були створені в рамках робіт із мінімізації наслідків катастрофи, підтверджують ефективність заходів, проведених у минулому та формують основу стратегії безпечного поводження з відходами, що залишились у спадщину. Усе це разом показує, що національні та міжнародні зусилля, спрямовані на контроль впливу наслідків Чорнобильської аварії, досягли суттєвого й помітного прогресу в галузі безпеки, і довгострокова безпека буде досягнута завдяки їхньому послідовному продовженню.Введение в эксплуатацию нового безопасного конфайнмента на площадке № 4 ЧАЭС ознаменует достижение важной вехи в процессе преобразования чернобыльского энергоблока № 4 в экологически безопасную систему. Новые объекты по обращению с радиоактивными отходами были построены на ЧАЭС и в комплексе "Вектор" для обеспечения безопасного обращения с радиоактивными отходами в чернобыльской зоне отчуждения. Длительные исследования и оценки безопасности различных наследственных площадок отходов, которые были созданы в рамках мероприятий по реагированию на катастрофу, подтверждают эффективность мер прошлого и закрепляют основу стратегии безопасного обращения с наследственными отходами. Все это вместе показывает, что национальные и международные усилия, направленные на контроль над воздействиями последствий Чернобыльской аварии, достигли существенного и заметного прогресса в области безопасности, и долгосрочная безопасность будет достигнута благодаря их последовательному продлению

Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia

In common with other chronic pain conditions, there is an unmet clinical need in the treatment of inherited erythromelalgia (IEM). TheSCN9Agene encoding the sodium channel Nav1.7 expressed in the peripheral nervous system plays a critical role in IEM. A gain-of-function mutation in this sodium channel leads to aberrant sensory neuronal activity and extreme pain, particularly in response to heat. Five patients with IEM were treated with a new potent and selective compound that blocked the Nav1.7 sodium channel resulting in a decrease in heat-induced pain in most of the patients. We derived induced pluripotent stem cell (iPSC) lines from four of five subjects and produced sensory neurons that emulated the clinical phenotype of hyperexcitability and aberrant responses to heat stimuli. When we compared the severity of the clinical phenotype with the hyperexcitability of the iPSC-derived sensory neurons, we saw a trend toward a correlation for individual mutations. The in vitro IEM phenotype was sensitive to Nav1.7 blockers, including the clinical test agent. Given the importance of peripherally expressed sodium channels in many pain conditions, our approach may have broader utility for a wide range of pain and sensory conditions

Translational models for vascular cognitive impairment: a review including larger species.

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water

PURPOSE: Quantification of myocardial blood flow (MBF) with generator-produced (82)Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate (82)Rb-measured MBF in relation to that measured using (15)O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). METHODS: MBF was measured at rest and during adenosine-induced hyperaemia with (82)Rb and (15)O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment (82)Rb model with ventricular spillover correction was used. The (82)Rb flow-dependent extraction rate was derived from (15)O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ (c) (measuring both precision and accuracy) were used. RESULTS: Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF (r = 0.90, [(82)Rb-(15)O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = -1.26 to 1.33 ml/min/g, ρ(c) = 0.88) and MFR (range 1.79-5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = -0.99 to 1.28, ρ(c) = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for (15)O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for (82)Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for (15)O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for (82)Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p &gt; 0.31). CONCLUSION: Quantification of MBF with (82)Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using (15)O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. (82)Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine

The Chromatin Remodeling Factor SMARCB1 Forms a Complex with Human Cytomegalovirus Proteins UL114 and UL44

Background: Human cytomegalovirus (HCMV) uracil DNA glycosylase, UL114, is required for efficient viral DNA replication. Presumably, UL114 functions as a structural partner to other factors of the DNA-replication machinery and not as a DNA repair protein. UL114 binds UL44 (HCMV processivity factor) and UL54 (HCMV-DNA-polymerase). In the present study we have searched for cellular partners of UL114. Methodology/Principal Findings: In a yeast two-hybrid screen SMARCB1, a factor of the SWI/SNF chromatin remodeling complex, was found to be an interacting partner of UL114. This interaction was confirmed in vitro by coimmunoprecipitation and pull-down. Immunofluorescence microscopy revealed that SMARCB1 along with BRG-1, BAF170 and BAF155, which are the core SWI/SNF components required for efficient chromatin remodeling, were present in virus replication foci 24–48 hours post infection (hpi). Furthermore a direct interaction was also demonstrated for SMARCB1 and UL44. Conclusions/Significance: The core SWI/SNF factors required for efficient chromatin remodeling are present in the HCMV replication foci throughout infection. The proteins UL44 and UL114 interact with SMARCB1 and may participate in the recruitment of the SWI/SNF complex to the chromatinized virus DNA. Thus, the presence of the SWI/SNF chromatin remodeling complex in replication foci and its association with UL114 and with UL44 might imply its involvement i