The Pfaffian-Grassmannian equivalence revisited

We give a new proof of the 'Pfaffian-Grassmannian' derived equivalence between certain pairs of non-birational Calabi-Yau threefolds. Our proof follows the physical constructions of Hori and Tong, and we factor the equivalence into three steps by passing through some intermediate categories of (global) matrix factorizations. The first step is global Knoerrer periodicity, the second comes from a birational map between Landau-Ginzburg B-models, and for the third we develop some new techniques.Comment: Improved exposition, minor corrections. 32 page

Four-year monthly sediment deposition on turbid southwestern Atlantic coral reefs, with a comparison of benthic assemblages

A sedimentação é freqüentemente relacionada a estresse em recifes de coral. Os recifes do Atlântico sul ocidental possuem grande sedimentação, entretanto carecem de séries temporais das taxas de deposição de sedimento. Foram avaliadas estas taxas e a composição carbonática do sedimento, além da cobertura de corais e zoantídeos em seis recifes brasileiros durante quatro anos consecutivos. A deposição variou de zero a 233 mg cm-2 dia-1, com picos entre agosto e dezembro e médias anuais variando de nove a 104 mg cm-2 dia-1. As taxas de deposição apresentaram correlação com o vento, indicando que a ressuspensão deve ser o fator preponderante. A contribuição do carbonato variou de 38% a 90%, com dois locais apresentando diferenciação sazonal. As comunidades bênticas foram similares entre locais, entretanto as análises sugerem freqüencias diferenciadas para cada local. Não houve correlação significativa entre sedimentação e a comunidade bêntica. Entretanto, maior cobertura de Palythoa caribaeorum normalmente ocorreu em áreas de maior sedimentação. Nossos resultados não corroboraram resultados prévios sugerindo que 10 mg cm-2 dia-1 seria "limite crítico para sobrevivência" dos corais. Recifes brasileiros podem estar associados a ambientes de alta deposição de sedimento com elevadas frações carbonáticas, o que não impede o desenvolvimento das comunidades recifais do Atlântico sul ocidental.High sedimentation is often related to stress in coral reef communities. Most southwestern Atlantic reefs are characterized by high sedimentation. However, there are no temporal series of sediment deposition rates. We evaluated sediment deposition, the sediment carbonate composition and coral and zoanthid covers on six reefs in Brazil over four-years. Sediment deposition rates varied from near zero to 233 mg cm-2 day-1, with peaks between August and December, and yearly averages ranging from nine to 104 mg cm-2 day-1. Deposition rates presented site-specific correlations with wind, indicating that resuspension must be a major factor. The presence of carbonates varied from 38% to 90%, with two sites showing seasonal differences. Benthic communities were fairly similar among sites, but the analyses suggested particular frequencies at each site. There was no significant correlation between sediment and benthic communities. However, Palythoa caribaeorum usually occur in high sediment deposition areas. Our results did not corroborate previous data that suggested that a 10 mg cm-2 day-1 would be a "critical limit for coral survival". Some coral reefs may be associated with high sedimentation environments including carbonatic fractions, but which does not per se hinder the development of southwestern Atlantic coral reef communities

Intracranial symptomatic giant arachnoid cyst

Intracranial arachnoid cysts are congenital compartments. They are frequently localized in the middle fossa and are intimately bordered by the arachnoid membrane. (1,2) Clinical symptoms appear commonly at an early age. Cases of symptomatic arachnoid cysts are rare in the elderly. (1,3,4) In this case report, we describe clinical and radiological signs of a 66 year old patient presenting with a giant suprasellar arachnoid cyst. Treatment options are discussed

Cobertura e Recrutamento de Corais Recifais (Cnidaria: Scleractinia E Milleporidae) nos Recifes Itacolomis, Brasil

The Itacolomis Reefs (Brazil – 16°55’ S) were almost unknown until recently. In this study, reef cover, especially corals and zoanthids, coral recruitment, and sediment deposition were sampled in six localities of these reefs. Comparisons of coral and zoanthid cover indicated that the sampled localities have different communities. However, usually the composition and abundance of species in each locality were comparatively more homogeneous among its stations than between localities. Recruitment plates showed 1227 recruits.m-2. Families considered brooders had higher recruitment, dominated by Poritidae and Agariciidae, than broadcasters and/or families with both reproductive modes. The recruitment of Milleporidae occurred, unexpectedly, in a single locality. The recruitment of Siderastreidae had a positive significant correlation with its adult cover; and a negative significant correlation with adult cover of Mussidae, which confirms a previous study with colonies of these families in the Abrolhos Archipelago. The recruitment of Mussidae had a negative significant correlation with the cover of Agariciidae. There were not significant correlations between estimated sediment deposition rates and coral cover and/or recruitment rates. The sediment deposition rate in locality 2 was statistically different than the rates of other stations. This locality was the only one that exhibited a heterogeneous composition and abundance of species among stations. Specific studies are necessary to determine if the significant correlations found represent a cause-effect relation or if they are simultaneously under the influence of external factors. The fact that the same locality exhibited the higher sediment deposition rate and heterogeneous communities should be investigated.Os Recifes Itacolomis (Brasil – 16°55’ S) permaneceram praticamente desconhecidos até recentemente. Neste trabalho, foram amostradas as coberturas do fundo, especialmente corais e zoantídeos, o recrutamento de corais e a deposição de sedimentos em seis locais destes recifes. As comparações das coberturas de corais e zoantídeos mostraram que os locais amostrados possuem comunidades diferentes. Porém, em sua maioria, a composição e abundância de espécies de cada local foram comparativamente mais próximas entre si que entre locais. As placas de recrutamento apresentaram 1227 recrutas.m-2. Houve maior recrutamento das famílias consideradas incubadoras de larvas, especialmente Poritidae e Agariciidae, do que das liberadoras de gametas e das que apresentam os dois modos de reprodução. A família Milleporidae apresentou, inesperadamente, recrutas em apenas um dos locais. O recrutamento de Siderastreidae apresentou correlação positiva e significativa com sua cobertura adulta; e negativa e significativa com a cobertura de Mussidae, corroborando estudo anterior com colônias destas famílias no Arquipélago dos Abrolhos. O recrutamento de Mussidae apresentou correlação significativa negativa com a cobertura de Agariciidae. Não houve correlações significativas entre as estimativas das taxas de deposição de sedimentos e cobertura coralínea e/ou recrutamento. A taxa de deposição de sedimentos do local 2 apresentou-se estatisticamente diferente daquelas dos demais locais. Este local foi o único a apresentar heterogeneidade na composição e abundância de espécies entre suas estações. Estudos específicos são necessários para definir se as variáveis que apresentaram correlações significativas possuem relação causa-efeito, ou se fatores externos estão atuando simultaneamente sobre estas variáveis. O fato de o local de maior deposição de sedimentos ser também o de maior heterogeneidade de comunidades deve ser mais bem investigado

VSOP/Hv1 proton channels sustain calcium entry, neutrophil migration, and superoxide production by limiting cell depolarization and acidification

Neutrophils kill microbes with reactive oxygen species generated by the NADPH oxidase, an enzyme which moves electrons across membranes. Voltage-gated proton channels (voltage-sensing domain only protein [VSOP]/Hv1) are required for high-level superoxide production by phagocytes, but the mechanism of this effect is not established. We show that neutrophils from VSOP/Hv1−/− mice lack proton currents but have normal electron currents, indicating that these cells have a fully functional oxidase that cannot conduct protons. VSOP/Hv1−/− neutrophils had a more acidic cytosol, were more depolarized, and produced less superoxide and hydrogen peroxide than neutrophils from wild-type mice. Hydrogen peroxide production was rescued by providing an artificial conductance with gramicidin. Loss of VSOP/Hv1 also aborted calcium responses to chemoattractants, increased neutrophil spreading, and decreased neutrophil migration. The migration defect was restored by the addition of a calcium ionophore. Our findings indicate that proton channels extrude the acid and compensate the charge generated by the oxidase, thereby sustaining calcium entry signals that control the adhesion and motility of neutrophils. Loss of proton channels thus aborts superoxide production and causes a severe signaling defect in neutrophils

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci

Intrinsic flexibility of B-DNA: the experimental TRX scale

B-DNA flexibility, crucial for DNA–protein recognition, is sequence dependent. Free DNA in solution would in principle be the best reference state to uncover the relation between base sequences and their intrinsic flexibility; however, this has long been hampered by a lack of suitable experimental data. We investigated this relationship by compiling and analyzing a large dataset of NMR 31P chemical shifts in solution. These measurements reflect the BI ↔ BII equilibrium in DNA, intimately correlated to helicoidal descriptors of the curvature, winding and groove dimensions. Comparing the ten complementary DNA dinucleotide steps indicates that some steps are much more flexible than others. This malleability is primarily controlled at the dinucleotide level, modulated by the tetranucleotide environment. Our analyses provide an experimental scale called TRX that quantifies the intrinsic flexibility of the ten dinucleotide steps in terms of Twist, Roll, and X-disp (base pair displacement). Applying the TRX scale to DNA sequences optimized for nucleosome formation reveals a 10 base-pair periodic alternation of stiff and flexible regions. Thus, DNA flexibility captured by the TRX scale is relevant to nucleosome formation, suggesting that this scale may be of general interest to better understand protein-DNA recognition

Nutrition and Inflammatory Biomarkers in Chronic Pancreatitis Patients

BackgroundChronic pancreatitis (CP) patients frequently experience malabsorption and maldigestion, leading to micronutrient and macronutrient deficiencies. Comorbid diabetes and lifestyle habits, such as alcohol consumption, may impact nutrition status.MethodsWe compared micronutrient antioxidant, bone metabolism, serum protein, and inflammatory marker levels in 301 CP patients and 266 controls with no known pancreatic disease. We analyzed serum prealbumin and retinol binding protein; vitamins A, D, E, and B12; osteocalcin; tumor necrosis factor‐α; and C‐reactive protein (CRP). We also evaluated biomarkers among subsets of patients, examining factors including time since diagnosis, body mass index, alcohol as primary etiology, diabetes mellitus, vitamin supplementation, and pancreatic enzyme replacement.ResultsAfter correcting for multiple comparisons, CP patients had significantly lower levels than controls of the following: vitamin A (40.9 vs 45.4 μg/dL) and vitamin E (α‐tocopherol [8.7 vs 10.3 mg/L] and γ‐tocopherol [1.8 vs 2.2 mg/L]), as well as osteocalcin (7.9 vs 10 ng/mL) and serum prealbumin (23 vs 27 mg/dL). Both patients and controls who took vitamin supplements had higher serum levels of vitamins than those not taking supplements. Compared with controls, in controlled analyses, CP patients had significantly lower levels of vitamins A, D, and E (both α‐tocopherol and γ‐tocopherol). CP patients also had significantly lower levels of osteocalcin, serum prealbumin, and retinol binding protein, and higher CRP.ConclusionsCP patients demonstrated lower levels of selected nutrition and bone metabolism biomarkers than controls. Diabetes and alcohol did not impact biomarkers. Vitamin supplements and pancreatic enzyme replacement therapy improved nutrition biomarkers in CP patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149272/1/ncp10186-sup-0001-TableS1-S4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149272/2/ncp10186.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149272/3/ncp10186_am.pd

The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial

BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system-penetrant, type II RAF inhibitor tovorafenib (420 mg m$^{-}$$^{2}$ once weekly; 600 mg maximum) in patients with BRAF-altered, relapsed/refractory pLGG. Arm 2 (n = 60) is an extension cohort, which provided treatment access for patients with RAF-altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n = 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≥3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485