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Alzheimer’s disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly in the early stages of functional impairment, and how they relate to disease progression in the brain remain largely unknown. To better understand the pathological features of AD in the retina, we conducted an extensive histopathological and biochemical investigation of postmortem retina and brain tissues from 86 human donors. Quantitative examination of superior and inferior temporal retinas from mild cognitive impairment (MCI) and AD patients compared to those with normal cognition (NC) revealed significant increases in amyloid β-protein (Aβ42) forms and novel intraneuronal Aβ oligomers (AβOi), which were closely associated with exacerbated retinal macrogliosis, microgliosis, and tissue atrophy. These pathologies were unevenly distributed across retinal layers and geometrical areas, with the inner layers and peripheral subregions exhibiting most pronounced accumulations in the MCI and AD versus NC retinas. While microgliosis was increased in the retina of these patients, the proportion of microglial cells engaging in Aβ uptake was reduced. Female AD patients exhibited higher levels of retinal microgliosis than males. Notably, retinal Aβ42, S100 calcium-binding protein B+ macrogliosis, and atrophy correlated with severity of brain Aβ pathology, tauopathy, and atrophy, and most retinal pathologies reflected Braak staging. All retinal biomarkers correlated with the cognitive scores, with retinal Aβ42, far-peripheral AβOi and microgliosis displaying the strongest correlations. Proteomic analysis of AD retinas revealed activation of specific inflammatory and neurodegenerative processes and inhibition of oxidative phosphorylation/mitochondrial, and photoreceptor-related pathways. This study identifies and maps retinopathy in MCI and AD patients, demonstrating the quantitative relationship with brain pathology and cognition, and may lead to reliable retinal biomarkers for noninvasive retinal screening and monitoring of AD.

Alzheimer’s disease (AD) pathologies were discovered in the easily accessible neurosensory retina. Yet, their specific nature, topographical distribution, and relationship with disease status remain undefined. Here, we histologically determined burden and spatial distribution of amyloid β-protein (Aβ42), intraneuronal scFvA13+-Aβ species, macro- and microgliosis, and atrophy in superior- and inferior-temporal retinas of human donors with mild cognitive impairment (MCI) or AD versus normal cognition. AD and MCI patients had enhanced retinopathy, predominantly affecting inner layers and peripheral subregions, which quantitatively correlated with severity of cerebral amyloid, tau, and neurodegeneration, and cognitive scores. In advanced clinical stages AD retinopathy further affected central outer segments. Increased retinal macrogliosis and Aβ-phagocytosing microglia were detected in MCI and AD patients. Further, distinct proteome profiles of AD retinas were identified, displaying greater overlap with the temporal cortices than with hippocampi or cerebella. AD retinas exhibited upregulated inflammatory and neurodegenerative processes and downregulated oxidative-phosphorylation/mitochondrial, and photoreceptor-related pathways. This study identifies and maps AD retinopathy, demonstrating the quantitative relationship with brain pathology and cognition.

Background Hypertension is considered a major risk factor for the progression of diabetic kidney disease. Type 2 diabetes is associated with increased renal sodium reabsorption and salt-sensitive hypertension. Clinical studies show that men have higher risk than premenopausal women for the development of diabetic kidney disease. However, the renal mechanisms that predispose to salt sensitivity during diabetes and whether sexual dimorphism is associated with these mechanisms remains unknown. Methods Female and male db/db mice exposed to a high-salt diet were used to analyze the progression of diabetic kidney disease and the development of hypertension. Results Male, 34-week-old, db/db mice display hypertension when exposed to a 4-week high-salt treatment, whereas equivalently treated female db/db mice remain normotensive. Salt-sensitive hypertension in male mice was associated with no suppression of the epithelial sodium channel (ENaC) in response to a high-salt diet, despite downregulation of several components of the intrarenal renin-angiotensin system. Male db/db mice show higher levels of proinflammatory cytokines and more immune-cell infiltration in the kidney than do female db/db mice. Blocking inflammation, with either mycophenolate mofetil or by reducing IL-6 levels with a neutralizing anti-IL-6 antibody, prevented the development of salt sensitivity in male db/db mice. Conclusions The inflammatory response observed in male, but not in female, db/db mice induces salt-sensitive hypertension by impairing ENaC downregulation in response to high salt. These data provide a mechanistic explanation for the sexual dimorphism associated with the development of diabetic kidney disease and salt sensitivity.

Background Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is used increasingly when performing a prophylactic mastectomy. Few prospective studies have reported on complication rates. This complementary trial to the French prospective multicentre MAPAM trial aimed to evaluate the nipple–areola complex (NAC) necrosis rate in prophylactic NSM with IBR. Methods Patient characteristics and surgical data were recorded. Morbidity after prophylactic NSM with a focus on NAC necrosis was analysed. Results Among 59 women undergoing prophylactic NSM, 19 (32 per cent) of the incisions were partly on the NAC. Reconstructions were performed with 46 definitive implants and 13 expanders. The crude rate of postoperative complications was 25 per cent (15 patients). Complete NAC necrosis was reported in two women (3 per cent) and partial or total necrosis in nine (15 per cent). No NAC resection was necessary. Median BMI was lower in women with total or partial NAC necrosis compared with the others (20.0 versus 21.3 kg/m2 respectively; P = 0.034). Conclusion Results of this prospective study confirm that prophylactic NSM with IBR is associated with a low risk of total NAC necrosis.

In most scenarios where detonations in fuel–air mixtures can present a hazard, such as in industrial accidents, or where they can be used for practical purposes, like detonative propulsion applications, the mixture is essentially non-uniform. For industrial accidents, it is important to understand what fraction of the mixture can detonate in order to limit the consequences of an explosion event by ensuring proper separation distances to critical facilities and personnel. For propulsion applications, mixture non-uniformities directly affect the performance of the device by limiting the detonable portion of the mixture. While it is known that detonation limits depend on mixture composition, geometry, and concentration gradients, these limits have only been defined for either uniform mixtures, or for detonation propagation in the direction of a smooth concentration gradient. In this study, a model is developed to generalize these classic detonation limits to consider arbitrary concentration distributions and is compared with experimental data for detonation propagation in non-uniform mixtures. The model is then applied to representative concentration distributions corresponding to two practical examples, a high-pressure hydrogen jet and a large-scale vapor cloud explosion (VCE). For both distributions, the model illustrates how a non-uniform mixture composition significantly limits the detonable portion of the flammable mixture created by a realistic release.

Les douleurs neuropathiques (DN) restent très difficiles à soulager. Plusieurs recommandations ont été proposées au cours de ces dernières années, mais aucune n’a pris en compte à ce jour l’ensemble des approches thérapeutiques disponibles. Nous avons réalisé une revue systématique portant sur toutes les études concernant le traitement des DN périphériques et centrales de l’adulte et de l’enfant, publiées jusqu’en janvier 2018 et avons évalué la qualité des études et le niveau de preuve des traitements au moyen du système GRADE. Les principaux critères d’inclusion étaient l’existence d’une DN chronique (≥ 3 mois), une méthodologie contrôlée et randomisée, un suivi supérieur ou égal à trois semaines, un nombre de patients supérieur ou égal à dix par groupe et une évaluation en double insu pour les traitements pharmacologiques. Sur la base du GRADE, nous recommandons en première intention les antidépresseurs inhibiteurs mixtes de recapture des monoamines (duloxétine et venlafaxine), les antidépresseurs tricycliques, la gabapentine pour toute DN, et les emplâtres de lidocaïne 5 % et la stimulation électrique transcutanée pour les DN périphériques localisées. Nous recommandons en deuxième intention la prégabaline, le tramadol (avec les précautions d’emploi afférentes aux opioïdes) et certaines associations pharmacologiques (antidépresseurs et gabapentine ou prégabaline) pour toute DN, et les patchs de haute concentration de capsaïcine (8 %) et la toxine botulique de type A (en milieu spécialisé) pour les DN périphériques localisées. Nous recommandons en troisième intention la stimulation magnétique transcrânienne répétitive à haute fréquence du cortex moteur (en milieu spécialisé) et les opioïdes forts (en l’absence d’alternative et en respectant les précautions d’emploi afférentes aux opioïdes) pour toute douleur neuropathique, et la stimulation médullaire pour les douleurs radiculaires chroniques postchirurgicales et la polyneuropathie diabétique douloureuse. La psychothérapie (thérapie cognitivocomportementale et thérapie de pleine conscience) peut être recommandée en deuxième intention en association avec les traitements précédents.

Neuropathic pain remains a significant unmet medical need. Several recommendations have recently been proposed concerning pharmacotherapy, neurostimulation techniques and interventional management, but no comprehensive guideline encompassing all these treatments has yet been issued. We performed a systematic review of pharmacotherapy, neurostimulation, surgery, psychotherapies and other types of therapy for peripheral or central neuropathic pain, based on studies published in peer-reviewed journals before January 2018. The main inclusion criteria were chronic neuropathic pain for at least three months, a randomized controlled methodology, at least three weeks of follow-up, at least 10 patients per group, and a double-blind design for drug therapy. Based on the GRADE system, we provide weak-to-strong recommendations for use and proposal as a first-line treatment for SNRIs (duloxetine and venlafaxine), gabapentin and tricyclic antidepressants and, for topical lidocaine and transcutaneous electrical nerve stimulation specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a second-line treatment for pregabalin, tramadol, combination therapy (antidepressant combined with gabapentinoids), and for high-concentration capsaicin patches and botulinum toxin A specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a third-line treatment for high-frequency rTMS of the motor cortex, spinal cord stimulation (failed back surgery syndrome and painful diabetic polyneuropathy) and strong opioids (in the absence of an alternative). Psychotherapy (cognitive behavioral therapy and mindfulness) is recommended as a second-line therapy, as an add-on to other therapies. An algorithm encompassing all the recommended treatments is proposed.

Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal vascular Aβ40 and Aβ42 burden. Decreased vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased vascular amyloidosis in Alzheimer’s retina implies compromised blood–retinal barrier integrity and provides new targets for AD diagnosis and therapy. Electronic supplementary material The online version of this article (10.1007/s00401-020-02134-w) contains supplementary material, which is available to authorized users.

Despite growing evidence for the characteristic signs of Alzheimer's disease (AD) in the neurosensory retina, our understanding of retina–brain relationships, especially at advanced disease stages and in response to therapy, is lacking. In transgenic models of AD (APPSWE/PS1∆E9; ADtg mice), glatiramer acetate (GA) immunomodulation alleviates disease progression in pre‐ and early‐symptomatic disease stages. Here, we explored the link between retinal and cerebral AD‐related biomarkers, including response to GA immunization, in cohorts of old, late‐stage ADtg mice. This aged model is considered more clinically relevant to the age‐dependent disease. Levels of synaptotoxic amyloid β‐protein (Aβ)1–42, angiopathic Aβ1–40, non‐amyloidogenic Aβ1–38, and Aβ42/Aβ40 ratios tightly correlated between paired retinas derived from oculus sinister (OS) and oculus dexter (OD) eyes, and between left and right posterior brain hemispheres. We identified lateralization of Aβ burden, with one‐side dominance within paired retinal and brain tissues. Importantly, OS and OD retinal Aβ levels correlated with their cerebral counterparts, with stronger contralateral correlations and following GA immunization. Moreover, immunomodulation in old ADtg mice brought about reductions in cerebral vascular and parenchymal Aβ deposits, especially of large, dense‐core plaques, and alleviation of microgliosis and astrocytosis. Immunization further enhanced cerebral recruitment of peripheral myeloid cells and synaptic preservation. Mass spectrometry analysis identified new parallels in retino‐cerebral AD‐related pathology and response to GA immunization, including restoration of homeostatic glutamine synthetase expression. Overall, our results illustrate the viability of immunomodulation‐guided CNS repair in old AD model mice, while shedding light onto similar retino‐cerebral responses to intervention, providing incentives to explore retinal AD biomarkers., In this study, Doustar et al. revealed that retinal Abeta burden predicts its brain levels in old, late‐stage murine models of Alzheimer's disease and further in response to immunotherapy. Substantial therapeutic effects are detected even at such advanced disease stage; immunomodulation effectively mitigates vascular and parenchymal amyloid‐beta deposition, diminishes neuroinflammation, as well as restores synaptic density and retino‐cerebral glutamine synthetase levels.

Targeted overexpression of angiotensin-converting enzyme (ACE), an amyloid-β protein degrading enzyme, to brain resident microglia and peripheral myelomonocytes (ACE10 model) substantially diminished Alzheimer’s-like disease in double-transgenic APPSWE/PS1ΔE9 (AD+) mice. In this study, we explored the impact of selective and transient angiotensin-converting enzyme overexpression on macrophage behaviour and the relative contribution of bone marrow-derived ACE10 macrophages, but not microglia, in attenuating disease progression. To this end, two in vivo approaches were applied in AD+ mice: (i) ACE10/GFP+ bone marrow transplantation with head shielding; and (ii) adoptive transfer of CD115+-ACE10/GFP+ monocytes to the peripheral blood. Extensive in vitro studies were further undertaken to establish the unique ACE10-macrophage phenotype(s) in response to amyloid-β1-42 fibrils and oligomers. The combined in vivo approaches showed that increased cerebral infiltration of ACE10 as compared to wild-type monocytes (∼3-fold increase; P < 0.05) led to reductions in cerebral soluble amyloid-β1-42, vascular and parenchymal amyloid-β deposits, and astrocytosis (31%, 47–80%, and 33%, respectively; P < 0.05–0.0001). ACE10 macrophages surrounded brain and retinal amyloid-β plaques and expressed 3.2-fold higher insulin-like growth factor-1 (P < 0.01) and ∼60% lower tumour necrosis factor-α (P < 0.05). Importantly, blood enrichment with CD115+-ACE10 monocytes in symptomatic AD+ mice resulted in pronounced synaptic and cognitive preservation (P < 0.05–0.001). In vitro analysis of macrophage response to well-defined amyloid-β1-42 conformers (fibrils, prion rod-like structures, and stabilized soluble oligomers) revealed extensive resistance to amyloid-β1-42 species by ACE10 macrophages. They exhibited 2–5-fold increased surface binding to amyloid-β conformers as well as substantially more effective amyloid-β1-42 uptake, at least 8-fold higher than those of wild-type macrophages (P < 0.0001), which were associated with enhanced expression of surface scavenger receptors (i.e. CD36, scavenger receptor class A member 1, triggering receptor expressed on myeloid cells 2, CD163; P < 0.05–0.0001), endosomal processing (P < 0.05–0.0001), and ∼80% increased extracellular degradation of amyloid-β1-42 (P < 0.001). Beneficial ACE10 phenotype was reversed by the angiotensin-converting enzyme inhibitor (lisinopril) and thus was dependent on angiotensin-converting enzyme catalytic activity. Further, ACE10 macrophages presented distinct anti-inflammatory (low inducible nitric oxide synthase and lower tumour necrosis factor-α), pro-healing immune profiles (high insulin-like growth factor-1, elongated cell morphology), even following exposure to Alzheimer’s-related amyloid-β1-42 oligomers. Overall, we provide the first evidence for therapeutic roles of angiotensin-converting enzyme-overexpressing macrophages in preserving synapses and cognition, attenuating neuropathology and neuroinflammation, and enhancing resistance to defined pathognomonic amyloid-β forms.

Explosion isolation systems provide critical protection for interconnected vessels and work areas, preventing the spread of explosions through interconnecting pipes and ducts. These systems not only prevent propagating events, but also mitigate the elevated explosion hazards of interconnected vessels, related to pressure piling and enhanced turbulence. Explosion isolation systems can, however, fail catastrophically when they are not properly designed for a use case. Evaluating the performance of explosion isolation systems includes assessing their pressure resistance, flame-barrier efficacy, and determining appropriate installation distances, which typically requires extensive testing. To predict the performance of a system for use cases outside the tested conditions, models are needed to reliably predict both the explosion dynamics and the isolation system response. In this study, a physics-based model for explosion dynamics in vented vessel-pipe systems is developed and validated. An extensive series of large-scale validation experiments were conducted, including tests using an 8 m3 vessel with attached pipes, varying the pipe dimensions, ignition location, and mixture reactivity. The model accurately captures the effects of experimental parameters and predicts the time available for isolation systems to form a flame barrier. This model can help to predict installation distances and reduce the number of tests needed to comprehensively evaluate explosion isolation systems and their use cases.

Background Mechanical ventilation is strongly associated with cognitive decline after critical illness. This finding is particularly evident among older individuals who have pre-existing cognitive impairment, most commonly characterized by varying degrees of cerebral amyloid-β accumulation, neuroinflammation, and blood-brain barrier dysfunction. We sought to test the hypothesis that short-term mechanical ventilation contributes to the neuropathology of cognitive impairment by (i) increasing cerebral amyloid-β accumulation in mice with pre-existing Alzheimer’s disease pathology, (ii) increasing neurologic and systemic inflammation in wild-type mice and mice with pre-existing Alzheimer’s disease pathology, and (iii) increasing hippocampal blood-brain barrier permeability in wild-type mice and mice with pre-existing Alzheimer’s disease pathology. Methods We subjected double transgenic Alzheimer’s disease (APP/PSEN1) and wild-type mice to mechanical ventilation for 4 h and compared to non-mechanically ventilated Alzheimer’s disease model and wild-type mice. Cerebral soluble/insoluble amyloid-β1–40/amyloid-β1–42 and neurological and systemic markers of inflammation were quantified. Hippocampal blood-brain barrier permeability was quantified using a novel methodology that enabled assessment of small and large molecule permeability across the blood-brain barrier. Results Mechanical ventilation resulted in (i) a significant increase in cerebral soluble amyloid-β1–40 (p = 0.007) and (ii) significant increases in neuroinflammatory cytokines in both wild-type and Alzheimer’s disease mice which, in most cases, were not reflected in the plasma. There were (i) direct correlations between polymorphonuclear cells in the bronchoalveolar fluid and cerebral soluble amyloid-β1–40 (p = 0.0033), and several Alzheimer’s disease-relevant neuroinflammatory biomarkers including cerebral TNF-α and IL-6; (iii) significant decreases in blood-brain barrier permeability in mechanically ventilated Alzheimer’s disease mice and a trend towards increased blood-brain barrier permeability in mechanically ventilated wild-type mice. Conclusions These results provide the first evidence that short-term mechanical ventilation independently promotes the neuropathology of Alzheimer’s disease in subjects with and without pre-existing cerebral Alzheimer’s disease pathology. Future studies are needed to further clarify the specific mechanisms by which this occurs and to develop neuroprotective mechanical ventilation strategies that mitigate the risk of cognitive decline after critical illness. Electronic supplementary material The online version of this article (10.1186/s13054-019-2356-2) contains supplementary material, which is available to authorized users.

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A series of large-scale field trials to better understand the explosion characteristics of silane–air was conducted by the G-13 Silane Task Group under the direction of the Compressed Gas Association (CGA) and its guidelines. Silane was released from a high-pressure source into the open atmosphere, and overpressure measurements of unconfined silane–air explosions were taken at different locations away from the explosion centre. It was found that significant blast effects can result from relatively small releases of silane (around 0.1 kg). It is possible to achieve these small releases during an accidental discharge from a “pigtail” connection (a small-diameter coiled tube that connects a silane tube trailer to a process). Therefore, accidental silane explosions should be recognized as significant and possible events when handling silane. These results were also used in the proposed revision of ANSI/CGA G-13 Storage and Handling of Silane and Silane Mixtures.

In early 2011, the G-13 Silane Modeling Task Force of the Compressed Gas Association (CGA) proposed a series of tests to better define pyrophoric behavior during unintentional, large-scale releases of silane. The tests were conducted in two phases under the direction of CGA and its guidelines. Phase I took place from June 27 to June 30, 2011, focusing primarily on thermal radiation and the heat transfer from flame impingement due to silane release from a fully open pressure relief device (PRD) on a tonner. Phase II took place on June 19 and 20, 2012, focusing on thermal radiation and explosion overpressure. The results were subsequently utilized to revise CGA G-13 guidelines on the safe handling of silane. In the present two-part papers, the results from the tests are summarized in order to highlight the key findings. The first part of summary described the results of the flame impingement and thermal radiation tests. Three different test series were conducted, including shakedown tests using nitrogen instead of silane, silane flame-impingement tests onto an adjacent target tonner, and heat-flux tests. For comparison with known values in the published literature, thermal radiation of ethylene flame jets was also measured. In addition, metallurgical analyses of the target tonner indicated that the metallurgical properties of the cylinder material were not altered by the flame impingement. The steel surface temperature at the point of impingement was estimated to be below 853.15 K and definitely did not exceed 950.15 K. Thus, the combination of internal pressure and vessel metal temperature was unlikely to exceed the rupture pressure of the ton cylinder.

In the present investigation, laminar burning velocities (LBVs) were measured for several different silane fuels (i.e., trichlorosilane, trimethylchlorosilane, methyldichlorosilane, dimethylchlorosilane, and tetramethylsilane) in order to evaluate their potential for vapour cloud explosions (VCEs). Laminar burning velocities were determined from constant-volume explosions in a closed vessel; the pressure rise of the initial portion of flame propagation was used to calculate the laminar burning velocity. The LBVs for the different silane compounds were found to be in the range of 43 cm/s (for dimethylchlorosilane) to 124 cm/s (for trichlorosilane). These values were then used to estimate blast effects of VCEs resulting from a 25,000 kg release of each fuel. In particular, the VCE severity of trichlorosilane was compared to that of propane and ethylene for a given release mass. It was found that a trichlorosilane VCE would produce greater overpressures than propane and ethylene in the near field but the pressure would decay more rapidly with increasing distance from the explosion centre. Moreover, the impulse from a trichlorosilane VCE would be considerably lower than that of propane and ethylene.

A complete multiple-scale solution is constructed for the one-dimensional problem of an oscillating flame in a tube, ignited at a closed end, with the second end open. The flame front moves into the unburnt mixture at a constant burning velocity relative to the mixture ahead, and the heat release is constant. The solution is based upon the assumption that the propagation speed multiplied by the expansion ratio is small compared with the speed of sound. This approximate solution is compared with a numerical solution for the same physical model, assuming a propagation speed of arbitrary magnitude, and the results are close enough to confirm the validity of the approximate solution. Because ignition takes place at the closed end, the effect of thermal expansion is to push the column of fluid in the tube towards the open end. Acoustics set in motion by the impulsive start of the column of fluid play a crucial role in the oscillation. The analytical solution also captures the subsequent interaction between acoustics and the reaction front, the effect of which does not appear to be as significant as that of the impulsive start, however.

A subset of neutrino-induced upward through-going muons in the Super-Kamiokande detector consists of high energy muons which lose energy through radiative processes such as bremsstrahlung, e^{+} e^{-} pair production and photonuclear interactions. These ``upward showering muons'' comprise an event sample whose mean parent neutrino energy is approximately 1 TeV. We show that the zenith angle distribution of upward showering muons is consistent with negligible distortion due to neutrino oscillations, as expected of such a high-energy neutrino sample. We present astronomical searches using these high energy events, such as those from WIMP annihilations in the Sun, Earth and Galactic Center, some suspected point sources, as well as searches for diffuse flux from the interstellar medium., Comment: Submitted for publication to Astroparticle Physics. Fig 12 has slightly higher resolution in the version submitted to the journal

2Although there is strong theoretical support that na-ture can be described by a grand uni ed theory (GUT) [1,2], there is currently no direct experimental evidence.One of the most powerful ways to test grand uni cationis to look for proton (or bound neutron) decay. MostGUTs have an unstable proton; in the absence of anobservation, setting experimental limits on the protonlifetime can provide useful constraints on the nature ofgrand uni ed theories. Observation, on the other hand,would be tantalizing evidence of new physics beyond theStandard Model.One of the more simple but interesting candidates forgrand uni cation is SO(10), where the Standard Model’sSU(3), SU(2), and U(1) are contained within the largergauge group. The class of models based on SO(10) uni- cation generally make predictions for neutrino massesand mixing that are broadly in accord with all knownneutrino mixing data [3, 4]. The minimal supersym-metric SO(10) model with a 126 Higgs eld describedin Ref. [3] is the particular motivation for the analysispresented here. In addition to predicting neutrino massand mixing in agreement with observations, it leaves R-parity unbroken, which guarantees the existence of stabledark matter. For some region of its allowed parameterspace, this model predicts that the dominant nucleon de-cay modes will be p! ˇ

Diaporthe helianthi, the causal agent of sunflower stem canker, a serious pathogen of sunflower in Europe, is sporadically recorded in Italy. A comparison of pathogen populations from different countries can be performed in order to detect genetically different biotypes. Our approach was turned to study molecular variability in genomic coding and non coding regions among D.helianthi isolates from different geographic origin. A set of isolates from different countries have been used to evaluate genomic variability in endo-polygalacturonase (endo-PG) genic portions and IGS region of rDNA. A PCR analysis with Fusarium moniliforme endo-PG degenerated primers produced variable amplification profiles between isolates in relation to their geographic origin. French and Yugoslavian isolates (countries where the pathogen is most aggressive) showed conserved patterns, while Italian isolates showed highly variable patterns. Primers for speciation studies in filamentous ascomycetes were used for the amplification of a portion of IGS region of rDNA. Amplification products were purified and sequenced in both directions. Phylogenetic analysis separated the isolates into two main clusters: i) all isolate from France and Yugoslavia; ii) all isolates from Italy. This investigation pointed out a good correlation between data obtained by the two different molecular approaches in order to detect intraspecific genetic variability in D.helianthi.

Diaporthe helianthi (Phomopsis helianthi), agente del cancro dello stelo, è uno dei più importanti patogeni del girasole in Europa, ma non risulta particolarmente aggressivo in Italia. I funghi fitopatogeni producono uno spettro di enzimi che degradano la parete cellulare vegetale, tra i quali le pectinasi svolgono un ruolo importante, poiché degradano uno dei principali componenti della parete cellulare e della lamella mediana. Al momento in letteratura non è disponibile alcuna informazione circa la produzione di specifici enzimi pectinolitici in D.helianthi. In questo studio abbiamo confrontato 12 isolati di D.helianthi di origine geografica diversa, per i quali sono note anche differenze di virulenza sul girasole, al fine di individuare la presenza di geni per l’endo-poligalatturonasi (endo-PG) e di valutarne la variabilità. A questo scopo sono stati condotti esperimenti di PCR, utilizzando una coppia di oligonucleotidi degenerati costruiti sulla sequenza del gene endo-PG (pgA) di Fusarium moniliforme. I profili di amplificazione ottenuti sono risultati interessanti in quanto diversi tra gli isolati, in relazione all’origine geografica. In particolare i pattern degli amplificati derivati da DNA genomico di isolati francesi ed yugoslavi risultano simili, mentre quelli ottenuti con DNA di isolati italiani, rumeni o argentini sono molto variabili. Sono stati quindi effettuati esperimenti di Southern blot per confermare l’identità dei prodotti di amplificazione, utilizzando come sonda il gene clonato per l’endo-PG (pgA) di F.moniliforme. La sonda ha ibridato con la maggior parte dei prodotti di amplificazione, anche se con livelli di riconoscimento diversi. Il prodotto di amplificazione principale degli isolati francesi ed yugoslavi è stato selezionato come rappresentativo delle sequenze conservate in questo gruppo di isolati. Uno degli isolati francesi è stato scelto per avviare l’analisi di sequenza. Dal confronto del prodotto di amplificazione di D.helianthi con le sequenze note di endo-PG in letteratura emerge un allineamento variabile, in accordo con la divergenza riscontrata tra questi geni nelle varie specie fungine. Inoltre una ricerca in banca dati evidenzia una omologia significativa tra la sequenza di D.helianthi e un gene di Aspergillus terreus per una polichetide sintasi, come già descritto in letteratura per un gene endo-PG di Botrytis cinerea (BcPGA2). Lavoro svolto nell’ambito del Programma di Ricerca di Interesse Nazionale (MURST, finanziamento 1999) “Diaporte helianthi – girasole: studio di un patosistema”.

We have searched for proton into muon plus neutral kaon using data from a 91.7 kiloton-year exposure of Super-Kamiokande-I, a 49.2 kiloton-year exposure of Super-Kamiokande-II, and a 31.9 kiloton-year exposure of Super-Kamiokande-III. The number of candidate events in the data was consistent with the atmospheric neutrino background expectation and no evidence for proton decay in this mode was found. We set a partial lifetime lower limit of 1.6x10^33 years at the 90% confidence level.

Searches for a nucleon decay into a charged anti-lepton (e^+ or {\mu}^+) plus a light meson ({\pi}^0, {\pi}^-, {\eta}, {\rho}^0, {\rho}^-, {\omega}) were performed using the Super-Kamiokande I and II data. Twelve nucleon decay modes were searched for. The total exposure is 140.9 kiloton \cdot years, which includes a 91.7 kiloton \cdot year exposure (1489.2 live days) of Super-Kamiokande-I and a 49.2 kiloton \cdot year exposure (798.6 live days) of Super-Kamiokande-II. The number of candidate events in the data was consistent with the atmospheric neutrino background expectation. No significant evidence for a nucleon decay was observed in the data. Thus, lower limits on the nucleon partial lifetime at 90% confidence level were obtained. The limits range from 3.6 \times 10^31 to 8.2 \times 10^33 years, depending on the decay modes., Comment: 25 pages, 18 figures

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, A new Super-Kamiokande search for supernova relic neutrinos was conducted using 2853 live days of data. Sensitivity is now greatly improved compared to the 2003 Super-Kamiokande result, which placed a flux limit near many theoretical predictions. This more detailed analysis includes a variety of improvements such as increased efficiency, a lower energy threshold, and an expanded data set. New combined upper limits on supernova relic neutrino flux are between 2.8 and 3.1ν̄e cm-2 s-1 > 16 MeV total positron energy (17.3 MeV Eν), The Super-Kamiokande experiment has been built and operated from funding by the Japanese Ministry of Education, Culture, Sports, Science and Technology, the United States Department of Energy, and the U.S. National Science Foundation. Some of us have been supported by funds from the Korean Research Foundation (BK21), the National Research Foundation of Korea (NRF- 20110024009), the Japan Society for the Promotion of Science, and the National Natural Science Foundation of China (Grants No. 10875062 and No. 10911140109)

In this paper we study non-standard neutrino interactions as an example of physics beyond the standard model using atmospheric neutrino data collected during the Super-Kamiokande I(1996-2001) and II(2003-2005) periods. We focus on flavor-changing-neutral-currents (FCNC), which allow neutrino flavor transitions via neutral current interactions, and effects which violate lepton non-universality (NU) and give rise to different neutral-current interaction-amplitudes for different neutrino flavors. We obtain a limit on the FCNC coupling parameter, varepsilon_{mu tau}, |varepsilon_{mu tau}, 12 Pages, 14 figures. To be submitted to Phys. Rev. D

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, The results of the third phase of the Super-Kamiokande solar neutrino measurement are presented and compared to the first and second phase results. With improved detector calibrations, a full detector simulation, and improved analysis methods, the systematic uncertainty on the total neutrino flux is estimated to be ± 2.1%, which is about two thirds of the systematic uncertainty for the first phase of Super-Kamiokande. The observed 8B solar flux in the 5.0 to 20 MeV total electron energy region is 2.32 ± 0.04 (stat.) ± 0.05 (sys.) x 10^6 cm^-2sec^-1, under the assumption of pure electron-flavor content, in agreement with previous measurements. A combined oscillation analysis is carried out using SK-I, II, and III data, and the results are also combined with the results of other solar neutrino experiments. The best-fit oscillation parameters are obtained to be sin^2 {\theta}12 = 0.30+0.02-0.01(tan^2 {\theta}12 = 0.42+0.04 -0.02) and {\Delta}m2_21 = 6.2+1.1-1.9 *10^-5eV^2. Combined with KamLAND results, the best-fit oscillation parameters are found to be sin^2 {\theta}12 = 0.31±0.01 (tan^2 {\theta}12 = 0.44±0.03) and {\Delta}m2_21 = 7.6 ± 0.2 x 10^-5 eV^2. The 8B neutrino flux obtained from global solar neutrino experiments is 5.3 ± 0.2 (stat + sys) x 10^6cm^-2s^-1, while the 8B flux becomes 5.1 ± 0.1 (stat +sys ) x 10^6cm^-2s^-1 by adding KamLAND result. In a three-flavor analysis combining all solar neutrino experiments, the upper limit of sin^2 {\theta}13 is 0.060 at 95% C.L.. After combination with KamLAND results, the upper limit of sin^2 {\theta}13 is found to be 0.059 at 95% C.L., The authors gratefully acknowledge the cooperation of the Kamioka Mining and Smelting Company. Super-K has been built and operated from funds provided by the Japanese Ministry of Education, Culture, Sports, Science and Technology, the U.S. Department of Energy, and the U.S. National Science Foundation. This work was partially supported by the Research Foundation of Korea (BK21 and KNRC), the Korean Ministry of Science and Technology, the National Science Foundation of China, and the Spanish Ministry of Science and Innovation (Grants No. FPA2009- 13697-C04-02 and No. Consolider-Ingenio-2010/CPAN)

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, We present a search for differences in the oscillations of antineutrinos and neutrinos in the Super-Kamiokande-I, -II, and -III atmospheric neutrino sample. Under a two-flavor disappearance model with separate mixing parameters between neutrinos and antineutrinos, we find no evidence for a difference in oscillation parameters. Best-fit antineutrino mixing is found to be at (Δm̄2,sin22θ̄)=(2.0×10−3 eV2,1.0) and is consistent with the overall Super-K measurement, We gratefully acknowledge the cooperation of the Kamioka Mining and Smelting Company. The Super- Kamiokande experiment has been built and operated from funding by the Japanese Ministry of Education, Culture, Sports, Science and Technology, the United States Department of Energy, and the U.S. National Science Foundation. Some of us have been supported by funds from the Korean Research Foundation (BK21), and the Korea Research Foundation Grants (MOEHRD, Basic Research Promotion Fund), (KRF-2008-521-c00072). Some of us have been supported by the State Committee for Scientific Research in Poland (Grant No. 1757/B/H03/ 2008/35). Some collaborators have been supported by the National Natural Science Foundation of China under Grants No. 10875062 and No. 10911140109

We present a search for non-zero theta_{13} and deviations of sin^2 theta_{23} from 0.5 in the oscillations of atmospheric neutrino data from Super-Kamiokande -I, -II, and -III. No distortions of the neutrino flux consistent with non-zero theta_{13} are found and both neutrino mass hierarchy hypotheses are in agreement with the data. The data are best fit at Delta m^2 = 2.1 x 10^-3 eV^2, sin^2 theta_{13} = 0.0, and sin^2 theta_{23} =0.5. In the normal (inverted) hierarchy theta_{13} and Delta m^2 are constrained at the one-dimensional 90% C.L. to sin^2 theta_{13} < 0.04 (0.09) and 1.9 (1.7) x 10^-3 < Delta m^2 < 2.6 (2.7) x 10^-3 eV^2. The atmospheric mixing angle is within 0.407, 17 Pages, 14 figures. To be submitted to Phys. Rev. D Minor update to text after referee comments. Figures modified for better grayscale printing.

We report the development of a proton identification method for the Super-Kamiokande detector. This new tool is applied to the search for events with a single proton track, a high purity neutral current sample of interest for sterile neutrino searches. After selection using a neural network, we observe 38 events in the combined SK-I and SK-II data corresponding to 2285.1 days of exposure, with an estimated signal to background ratio of 1.6 to 1. Proton identification was also applied to a direct search for charged-current quasi-elastic (CCQE) events, obtaining a high precision sample of fully kinematically reconstructed atmospheric neutrinos, which has not been previously reported in water Cherenkov detectors. The CCQE fraction of this sample is 55%, and its neutrino (as opposed to anti-neutrino) fraction is 91.7+/-3%. We selected 78 mu-like and 47 e-like events in the SK-I and SK-II data set. With this data, a clear zenith angle distortion of the neutrino direction itself is reported in a sub-GeV sample of muon neutrinos where the lepton angular correlation to the incoming neutrino is weak. Our fit to nu_mu->nu_tau oscillations using the neutrino L/E distribution of the CCQE sample alone yields a wide acceptance region compatible with our previous results and excludes the no-oscillation hypothesis at 3 sigma., Comment: 23 pages, 22 figures. Corrected typos, replaced some figures. Version accepted for publication in Phys. Rev. D