Search for Light Dark Matter with NA64 at CERN.

Thermal dark matter models with particle χ masses below the electroweak scale can provide an explanation for the observed relic dark matter density. This would imply the existence of a new feeble interaction between the dark and ordinary matter. We report on a new search for the sub-GeV χ production through the interaction mediated by a new vector boson, called the dark photon A^{'}, in collisions of 100 GeV electrons with the active target of the NA64 experiment at the CERN SPS. With 9.37×10^{11} electrons on target collected during 2016-2022 runs NA64 probes for the first time the well-motivated region of parameter space of benchmark thermal scalar and fermionic dark matter models. No evidence for dark matter production has been found. This allows us to set the most sensitive limits on the A^{'} couplings to photons for masses m_{A^{'}}≲0.35 GeV, and to exclude scalar and Majorana dark matter with the χ-A^{'} coupling α_{D}≤0.1 for masses 0.001≲m_{χ}≲0.1 GeV and 3m_{χ}≤m_{A^{'}}.

Air pollution-induced tanning of human skin.

BACKGROUND: Melanism is more frequent in animals living in polluted areas on urban-industrial sites. Given that an increasing number of people are exposed to elevated air pollution levels, it is possible that environmental pollutants affect melanogenesis in human skin. Epidemiological studies have shown that exposure to traffic-related air pollutants such as diesel exhaust particles (DEP) is associated with more clinical signs of hyperpigmentation. However, mechanistic evidence linking DEP exposure to pigmentation has been elusive. OBJECTIVES: To develop an ex␣vivo skin model to allow for repetitive topical application of relevant ambient DEP, and to provide proof of concept in humans. METHODS: We measured skin pigmentation, melanin and pigmentation-associated gene expression, and evaluated oxidative stress. RESULTS: Repetitive exposure of ex␣vivo skin to DEP at nontoxic concentrations increased skin pigmentation. This increase was visible to the naked eye, time dependent, and associated with an increase in melanin content and the transcription of genes involved in de novo melanin synthesis. Similarly, in healthy participants (n = 76), repetitive topical application of DEP at nontoxic concentrations increased skin pigmentation. DEP-induced pigmentation was mediated by an oxidative stress response. After the application of DEP, epidermal antioxidants were depleted, lipid peroxidation and oxidative DNA damage were enhanced, and in a vehicle-controlled, double-blind clinical study DEP-induced pigmentation was prevented by the topical application of an antioxidant mixture. CONCLUSIONS: Similar to solar radiation, air pollutants cause skin tanning. As eumelanin is an antioxidant, it is proposed that this response serves to protect human skin against air pollution-induced oxidative stress.

Metasurface-bounded open cavities supporting virtual absorption: free-space energy accumulation in lossless systems.

We investigate an anomalous scattering phenomenon exhibited by a lossless system based on metasurfaces. Electromagnetic energy is neither reflected nor transmitted but stored within the system to be available again at a different time. We analytically derive the proper excitation conditions and verify the response of the system through a proper set of full-wave simulations, demonstrating the key role of the metasurface in enabling such a zero-scattering condition. The practical feasibility and the opportunities offered by the proposed metasurface-based system may open the door to the design of virtual absorbers with dynamic properties in energy absorbing, storing, and releasing.

The development of episodic future thinking in middle childhood.

The ability to imagine future events (episodic future thinking-EFT) emerges in preschoolers and further improves during middle childhood and adolescence. In the present study, we focused on the possible cognitive factors that affect EFT and its development. We assessed the ability to mentally project forward in time of a large cohort of 135 6- to 11-year-old children through a task with minimal narrative demands (the Picture Book Trip task adapted from Atance and Meltzoff in Cogn Dev 20(3):341-361. doi:10.1016/j.cogdev.2005.05.001, 2005) in order to avoid potential linguistic effects on children's performance. The results showed that this task can be used to assess the development of EFT at least until the age of 8. Furthermore, EFT scores correlated with measures of phonological short-term and verbal working memory. These results support the possibility that cognitive factors such as working memory play a key role in EFT.

Yeast nitrogen catabolite repression is sustained by signals distinct from glutamine and glutamate reservoirs.

Nitrogen catabolite repression (NCR) is a wide transcriptional regulation program enabling baker's yeast to downregulate genes involved in the utilization of poor nitrogen sources when preferred ones are available. Nowadays, glutamine and glutamate, the major nitrogen donors for biosyntheses, are assumed to be key metabolic signals regulating NCR. NCR is controlled by the conserved TORC1 complex, which integrates nitrogen signals among others to regulate cell growth. However, accumulating evidence indicate that the TORC1-mediated control of NCR is only partial, arguing for the existence of supplementary regulatory processes to be discovered. In this work, we developed a genetic screen to search for new players involved in NCR signaling. Our data reveal that the NADP-glutamate dehydrogenase activity of Gdh1 negatively regulates NCR-sensitive gene transcription. By determining the total, cytoplasmic and vacuolar pools of amino acids, we show that there is no positive correlation between glutamine/glutamate reservoirs and the extent of NCR. While our data indicate that glutamine could serve as initial trigger of NCR, they show that it is not a sufficient signal to sustain repression and point to the existence of yet unknown signals. Providing additional evidence uncoupling TORC1 activity and NCR, our work revisits the dogmas underlying NCR regulation.

Molecular evidence that oral supplementation with lycopene or lutein protects human skin against ultraviolet radiation: results from a double-blinded, placebo-controlled, crossover study.

BACKGROUND: Increasing evidence suggests photoprotection by oral supplementation with ß-carotene and lycopene. OBJECTIVES: To examine the capacity of lycopene-rich tomato nutrient complex (TNC) and lutein, to protect against ultraviolet (UV)A/B and UVA1 radiation at a molecular level. METHODS: In a placebo-controlled, double-blinded, randomized, crossover study two active treatments containing either TNC or lutein were assessed for their capacity to decrease the expression of UVA1 the radiation-inducible genes HO1, ICAM1 and MMP1. Sixty-five healthy volunteers were allocated to four treatment groups and subjected to a 2-week washout phase, followed by two 12-week treatment phases separated by another 2 weeks of washout. Volunteers started either with active treatment and were then switched to placebo, or vice versa. At the beginning and at the end of each treatment phase skin was irradiated and 24 h later biopsies were taken from untreated, UVA/B- and UVA1-irradiated skin for subsequent reverse transcriptase polymerase chain reaction analysis of gene expression. Moreover, blood samples were taken after the washout and the treatment phases for assessment of carotenoids. RESULTS: TNC completely inhibited UVA1- and UVA/B-induced upregulation of heme-oxygenase 1, intercellular adhesion molecule 1 and matrix metallopeptidase 1 mRNA, no matter the sequence (anova, P < 0·05). In contrast, lutein provided complete protection if it was taken in the first period but showed significantly smaller effects in the second sequence compared with TNC. CONCLUSIONS: Assuming the role of these genes as indicators of oxidative stress, photodermatoses and photoageing, these results might indicate that TNC and lutein could protect against solar radiation-induced health damage.

Deep spinal infection in instrumented spinal surgery: diagnostic factors and therapy.

AIM: Postoperative surgical site infections (SSI) are complication of spinal surgery. These complications may lead to a poor outcome with neurological deficits, spinal deformity and chronic pain. The purpose of this study is to explore the statistical value of diagnostic parameters and the proper therapy. METHOD: We retrospectively reviewed 550 patients who underwent spinal instrumentation at our department from January 2011 to December 2015. The SSI was present in 16 patients out of 550 operated. Diagnostic criteria of SSI were the positivity of the surgical wound swab or blood culture, the clinical findings, positivity of laboratory tests and radiological elements. All patients had peri-operative antibiotic prophylaxis. Diagnostic laboratory findings were compared with a homogeneous control group of 16 patients and analyzed by univariate statistical analysis with Chi-square test for the discrete variables. P<0,05 was considered statistically significant. RESULTS: Matching the SSI patients with a group of control, fever was not statistically significant for diagnosis as number of leukocytes, neutrophils and lymphocytes. On the contrary values of ESR and CRP were statistically significant with p <0, 01. The hardware was removed only in 3 patients (18%) out of 16 SSI patients. CONCLUSION: In this study the statistically significant parameters to diagnose SSI are ESR and CRP values. The leucocytes count, number of lymphocytes and presence of fever integrates the data of ESR and CRP with no statistical significance. Most patients with SSI reach clinical healing with favorable outcome by means of target antibiotic therapy without hardware removal.

Multimodal assessment of hemispheric lateralization for language and its relevance for behavior.

Although different MRI-based techniques have been proposed to assess the hemispheric lateralization for language (HLL), the agreement across methods, and its relationship with language abilities, are still a matter of debate. In the present study we obtained measures of HLL using both task-evoked activity during the execution of three different protocols and task-free methods of functional [resting state functional connectivity (rs-FC)] and anatomical [diffusion tensor imaging (DTI) tractography] connectivity. Regional analyses focusing on the perisylvian language network were conducted to assess the consistency of HLL across techniques. In addition, following a multimodal approach, we identified macro-factors of lateralization and examined their relationship with language performance. Our findings indicate the existence of a negative relationship between the structural asymmetry of the direct segment of the arcuate fasciculus (AF) and the inter-hemispheric rs-FC of key nodes of the perisylvian network. Instead, despite all the language tasks exhibited a leftward pattern of asymmetry, measures of HLL derived from task-evoked activity did not show a direct relationship with those obtained with the two task-free methods. Furthermore, a robust brain-behavioral relationship was observed only with a specific macro-factor that combined HLL measures derived from all MRI techniques. In particular, general language performance was positively related to more symmetrical structural organization, stronger inter-hemispheric communication at rest but more lateralized activation of Wernicke's territory during production tasks. Our findings, while not supporting the existence of a direct relationship between indices of hemispheric lateralization for language derived from different MRI techniques, indicate that general language performance can be indexed using combined MRI measures. The same approach might prove successful for likewise complex human behaviours.

Graphene-Based Active Random Metamaterials for Cavity-Free Lasing.

Manipulating and controlling the optical energy flow inside random media is a research frontier of photonics and the basis of novel laser designs. Here, we show that a metamaterial consisting of randomly dispersed graphene nanoflakes embedded within an optically pumped gain medium (rhodamine 6G) can operate as a cavity-free laser thanks to its extraordinarily low threshold for saturable absorption. The emitted light is self-organized into a well-determined spatial pattern, which depends on the graphene flake density and can be externally controlled through the optical pump. We provide different examples of tunable laser operation ranging from stable single-mode to chaoticlike behavior. Our metamaterial design holds great potential for the optical control of light amplification, as well as for the development of single-mode beam-engineered cavity-free lasers.

Lupus nephritis in Latin American patients: 10-year results from a single medical center in Argentina.

INTRODUCTION: Several studies have shown that Hispanic patients generally experience a worse renal prognosis than non-Hispanic white patients with lupus. To date, there is no report on American College of Rheumatology (ACR) renal response criteria (ACR-RRC) in patients from Latin America. OBJECTIVE: To evaluate treatment response in patients with proliferative and membranous lupus nephritis (LN) according to ACR-RRC. METHODS: A retrospective study (2001-2011) was performed in our hospital and the data collected included clinical information, renal assessment and immunological parameters. Details related to treatment received during induction and maintenance therapy were also recorded. RESULTS: The study included forty-three Latin American patients (37 women) from Argentina. Mean follow-up was 54 months. The regimen used for induction therapy included intravenous cyclophosphamide (IV-CYC) for six months in 36 patients and only seven received mycophenolate mofetil (MMF) given twice daily for a total dose of 2.5 ± 0.5 grams a day. For the maintenance period, six patients continued with quarterly IV-CYC, 20 patients received MMF (1.5 ± 0.5 grams a day) and 17 patients received azathioprine (AZA) 1.5 - 2 mg/kg/day. ACR-RRC observed after induction therapy was complete response in 19%, partial response in 9%, improvement in 42%, unchanged in 14%, and 16% had deterioration despite treatment. ACR-RRC observed after maintenance therapy was complete response in 30%, partial response in 23%, improvement in 19%, unchanged in 16%, and 12% had deterioration. Relapse was observed in 11 patients (25%). Ten out of 11 cases (91%) who relapsed did not achieve a complete response at the end of the induction therapy. CONCLUSION: In Latin American patients from Argentina, only 19% could achieve a complete response after induction therapy and 30% achieved a complete response after maintenance therapy. Failing to obtain a complete response after induction therapy was related to an increased risk of relapse during long-term follow-up in our study.

A new potassium-based intermediate and its role in the desorption properties of the K-Mg-N-H system.

New insights into the reaction pathways of different potassium/magnesium amide-hydride based systems are discussed. In situ SR-PXD experiments were for the first time performed in order to reveal the evolution of the phases connected with the hydrogen releasing processes. Evidence of a new K-N-H intermediate is shown and discussed with particular focus on structural modification. Based on these results, a new reaction mechanism of amide-hydride anionic exchange is proposed.

Temperature dependence of the electronic structure of semiconductors and insulators.

The renormalization of electronic eigenenergies due to electron-phonon coupling (temperature dependence and zero-point motion effect) is sizable in many materials with light atoms. This effect, often neglected in ab initio calculations, can be computed using the perturbation-based Allen-Heine-Cardona theory in the adiabatic or non-adiabatic harmonic approximation. After a short description of the recent progresses in this field and a brief overview of the theory, we focus on the issue of phonon wavevector sampling convergence, until now poorly understood. Indeed, the renormalization is obtained numerically through a slowly converging q-point integration. For non-zero Born effective charges, we show that a divergence appears in the electron-phonon matrix elements at q → Γ, leading to a divergence of the adiabatic renormalization at band extrema. This problem is exacerbated by the slow convergence of Born effective charges with electronic wavevector sampling, which leaves residual Born effective charges in ab initio calculations on materials that are physically devoid of such charges. Here, we propose a solution that improves this convergence. However, for materials where Born effective charges are physically non-zero, the divergence of the renormalization indicates a breakdown of the adiabatic harmonic approximation, which we assess here by switching to the non-adiabatic harmonic approximation. Also, we study the convergence behavior of the renormalization and develop reliable extrapolation schemes to obtain the converged results. Finally, the adiabatic and non-adiabatic theories, with corrections for the slow Born effective charge convergence problem (and the associated divergence) are applied to the study of five semiconductors and insulators: α-AlN, ß-AlN, BN, diamond, and silicon. For these five materials, we present the zero-point renormalization, temperature dependence, phonon-induced lifetime broadening, and the renormalized electronic band structure.

Ectoine-containing cream in the treatment of mild to moderate atopic dermatitis: a randomised, comparator-controlled, intra-individual double-blind, multi-center trial.

INTRODUCTION: The natural cyclic tetrahydropyrimidine, ectoine, is a low-molecular, water-binding, organic osmolyte. Previously, topical application of ectoine to healthy human skin was shown to improve skin hydration as well as skin barrier function. OBJECTIVES: We therefore speculated that topical application of ectoine would be beneficial for patients with atopic dermatitis (AD), in which a genetically defined defect in skin barrier function is of major pathogenetic relevance. We assessed the efficacy of an ectoine-containing cream (EHK02-01) in the management of 65 patients with mild to moderate AD in a randomized, intra-individual, double-blind, multi-center trial, in which the efficacy of ectoine was compared to a nonsteroidal anti-inflammatory cream previously found to primarily act on skin barrier function and therefore with a comparable mode of action. METHODS: Sixty-five patients with mild to moderate AD aged 18-65 years were enrolled. The patients applied EHK02-01 and the control cream on two symmetrical lesions twice daily for 28 days. At the beginning, after 7 and after 28 days, treated skin areas were assessed by modified, objective local SCORAD (Scoring Atopic Dermatitis) and IGA (Investigator's Global Assessment) as well as the patients' judgment of efficacy and their assessment of pruritus. RESULTS: EHK02-01 was found to be very well tolerated. Even more important, efficacy of EHK02-01 treatment was equivalent to that achieved with the reference product. CONCLUSION: These results indicate that topical treatment with EHK02-01 may represent a novel option for the treatment of patients with AD.

Graphene-clad tapered fiber: effective nonlinearity and propagation losses.

We derive a pulse propagation equation for a graphene-clad optical fiber, treating the optical response of the graphene and nonlinearity of the dielectric fiber core as perturbations in asymptotic expansion of Maxwell equations. We analyze the effective nonlinear and attenuation coefficients due to the graphene layer. Based on the recent experimental measurements of the nonlinear graphene conductivity, we predict considerable enhancement of the effective nonlinearity for subwavelength fiber core diameters.

The human Rhesus-associated RhAG protein and a kidney homologue promote ammonium transport in yeast.

The Rhesus blood-group antigens are defined by a complex association of membrane polypeptides that includes the non-glycosylated Rh proteins (RhD and RhCE) and the RHag glycoprotein, which is strictly required for cell surface expression of these antigens. RhAG and the Rh polypeptides are erythroid-specific transmembrane proteins belonging to the same family (36% identity). Despite their importance in transfusion medicine, the function of RhAG and Rh proteins remains unknown, except that their absence in Rh(null) individuals leads to morphological and functional abnormalities of erythrocytes, known as the Rh-deficiency syndrome. We recently found significant sequence similarity between the Rh family proteins, especially RhAG, and Mep/Amt ammonium transporters. We show here that RhAG and also RhGK, a new human homologue expressed in kidney cells only, function as ammonium transport proteins when expressed in yeast. Both specifically complement the growth defect of a yeast mutant deficient in ammonium uptake. Moreover, ammonium efflux assays and growth tests in the presence of toxic concentrations of the analogue methylammonium indicate that RhAG and RhGK also promote ammonium export. Our results provide the first experimental evidence for a direct role of RhAG and RhGK in ammonium transport. These findings are of high interest, because no specific ammonium transport system has been characterized so far in human.

Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase.

BACKGROUND: Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I-II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown. METHODS: Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20. RESULTS: Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS-), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS- patients receiving at least four doses at 320 IU m(-2) was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024. CONCLUSION: ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression.

Linguistic production and syntactic comprehension in schizophrenia and bipolar disorder.

OBJECTIVE: To explore linguistic abilities in schizophrenia and bipolar disorder. Specifically, the aims of this study were to: i) investigate microlinguistic (lexicon, morphology, syntax) and macrolinguistic (discourse coherence, pragmatics) dimensions of speech production and ii) evaluate syntactic comprehension skills in both schizophrenia and bipolar disorder. METHOD: Linguistic performance of 30 Italian-speaking patients with schizophrenia, 30 participants with bipolar disorder and 30 healthy controls comparable for age and educational level has been assessed using a story-telling task and a computer-based test of syntactic comprehension. RESULTS: In narrative production, compared with healthy participants, those with schizophrenia had slight problems in speech rate and deficits at both local and global discourse coherence, whereas patients with bipolar disorder showed reduced mean length of utterance. As regards syntactic comprehension, both groups of patients collected more grammatical errors than controls, but they differed with regard to the number and kind of grammatical construction they missed. CONCLUSION: Linguistic deficits have been detected in both groups of patients, being, however, more severe and generalized in schizophrenia than in bipolar disorder. Such results help us in improving our understanding of the potential psychopathological overlapping between these disorders.

Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women.

INTRODUCTION AND OBJECTIVES: In recent years there has been an increasing interest in the use of nutritional supplements to benefit human skin. Molecular evidence substantiating such effects, however, is scarce. In the present study we investigated whether nutritional supplementation of women with the standardized pine bark extract Pycnogenol® will improve their cosmetic appearance and relate these effects to expression of corresponding molecular markers of their skin. MATERIALS AND METHODS: For this purpose 20 healthy postmenopausal women were supplemented with Pycnogenol for 12 weeks. Before, during and after supplementation, their skin condition was assessed (i) by employing non-invasive, biophysical methods including corneometry, cutometry, visioscan and ultrasound analyses and (ii) by taking biopsies and subsequent PCR for gene expression analyses related to extracellular matrix homeostasis. RESULTS: Pycnogenol supplementation was well tolerated in all volunteers. Pycnogenol significantly improved hydration and elasticity of skin. These effects were most pronounced in women presenting with dry skin conditions prior to the start of supplementation. The skin-physiological improvement was accompanied by a significant increase in the mRNA expression of hyaluronic acid synthase-1 (HAS-1), an enzyme critically involved in the synthesis of hyaluronic acid, and a noticeable increase in gene expression involved in collagen de novo synthesis. CONCLUSIONS: This study provides skin-physiological and for the first time molecular evidence that Pycnogenol supplementation benefits human skin by increasing skin hydration and skin elasticity. These effects are most likely due to an increased synthesis of extracellular matrix molecules such as hyaluronic acid and possibly collagen. Pycnogenol supplementation may thus be useful to counteract the clinical signs of skin aging.

The impact of presurgical magnetic resonance in early breast cancer: an observational study.

The aim of this study was to evaluate the impact of presurgical breast magnetic resonance imaging (MRI) on the surgical management of selected patients with early-stage breast cancer who were candidates for BCT. The sample was built up according to the EUSOMA (European Society of Breast Cancer Specialists) recommendations enrolling women with unifocal unilateral early-stage breast carcinoma diagnosed by mammography, ultrasound (US) examination and in some cases also by histological analysis; all were scheduled for wider local excision. All eligible patients underwent presurgical breast MRI and findings were classified according to the BI-RADS system. In the presence of additional foci classified as BI-RADS 3-4, a targeted second-look US study was performed. If second-look US confirmed the presence of foci, needle biopsy was performed. Possible changes in the therapeutic approach resulting from preoperative MRI findings were decided upon by a multidisciplinary team. Outcome of histological examination of the surgical specimen and particularly analysis of tumor infiltration of the resection margins was the standard for determining the appropriateness of surgical strategy. A total of 123 patients underwent presurgical breast MRI. Additional foci were detected in 41.6% of patients, a greater local extension of the index lesion in 6.4%, whereas MRI confirmed local staging established by conventional imaging in 52%. However, 13.8% of additional foci were not confirmed by second-look and needle biopsy. More extensive surgery as a result of MRI findings was performed in 34.2%. This decision proved to be appropriate in 29.3% thus resulting in an over-treatment rate of 4.9%. Presurgical breast MRI resulted in confirmation of planned surgical strategy in 65.8% with an appropriateness rate of 54.5%. Surgical resection margins were positive for malignancy in 11.3% and repeated surgery was therefore required. Therapeutic strategy established on the basis of MRI was appropriate in 83.8% of cases. This study confirms the utility of MRI in presurgical workup of selected breast cancer patients. The results obtained suggest the importance of a sensitive tool such as MRI in the local staging of breast cancer before treatment planning.