We study open and closed string amplitudes at tree-level in string perturbation theory using the methods of single-valued integration which were developed in the prequel to this paper (Brown and Dupont in Single-valued integration and double copy, 2020). Using dihedral coordinates on the moduli spaces of curves of genus zero with marked points, we define a canonical regularisation of both open and closed string perturbation amplitudes at tree level, and deduce that they admit a Laurent expansion in Mandelstam variables whose coefficients are multiple zeta values (resp. single-valued multiple zeta values). Furthermore, we prove the existence of a motivic Laurent expansion whose image under the period map is the open string expansion, and whose image under the single-valued period map is the closed string expansion. This proves the recent conjecture of Stieberger that closed string amplitudes are the single-valued projections of (motivic lifts of) open string amplitudes. Finally, applying a variant of the single-valued formalism for cohomology with coefficients yields the KLT formula expressing closed string amplitudes as quadratic expressions in open string amplitudes.

A recent genome-wide association meta-analysis for Alzheimer's disease (AD) identified 19 risk loci (in addition to APOE) in which the functional genes are unknown. Using Drosophila, we screened 296 constructs targeting orthologs of 54 candidate risk genes within these loci for their ability to modify Tau neurotoxicity by quantifying the size of >6000 eyes. Besides Drosophila Amph (ortholog of BIN1), which we previously implicated in Tau pathology, we identified p130CAS (CASS4), Eph (EPHA1), Fak (PTK2B) and Rab3-GEF (MADD) as Tau toxicity modulators. Of these, the focal adhesion kinase Fak behaved as a strong Tau toxicity suppressor in both the eye and an independent focal adhesion-related wing blister assay. Accordingly, the human Tau and PTK2B proteins biochemically interacted in vitro and PTK2B co-localized with hyperphosphorylated and oligomeric Tau in progressive pathological stages in the brains of AD patients and transgenic Tau mice. These data indicate that PTK2B acts as an early marker and in vivo modulator of Tau toxicity.

This INDYGO trial assesses the feasibility of intraoperative 5-aminolevulinic acid PDT, a novel seamless approach to treat GBM. The technology is easily embeddable within the reference treatment at a low-incremental cost. The safety of this new treatment modality is a preliminary requirement before a multicenter randomized clinical trial can be further conducted to assess local control improvement by treating infiltrating and nonresected GBM cells.

We develop a model for the cohomology of the complement of a hypersurface arrangement inside a smooth projective complex variety. This generalizes the case of normal crossing divisors, discovered by P. Deligne in the context of the mixed Hodge theory of smooth complex varieties. Our model is a global version of the Orlik-Solomon algebra, which computes the cohomology of the complement of a union of hyperplanes in an affine space. The main tool is the complex of logarithmic forms along a hypersurface arrangement, and its weight filtration. Connections with wonderful compactifications and the configuration spaces of points on curves are also studied.for a more precise statement). Here H • (C n \ L) denotes the cohomology of the complement C n \ L with rational coefficients. Theorem 1.1 (Brieskorn-Orlik-Solomon). We have an isomorphism of graded algebrasOne may define an Orlik-Solomon algebra A • (L) for L any hypersurface arrangement inside a complex manifold X. We still have a direct sum decomposition (1), with S • (L) the graded poset of strata of L, as well as product maps (2) and natural morphisms (3). As in the local case, the Orlik-Solomon algebra A • (L) only depends on the poset of strata of L. It is functorial with respect to (X, L) in the sense that any holomorphic map ϕ :• Geometry: the Gysin long exact sequence. For a smooth hypersurface V inside a smooth projective variety X over C, the Gysin morphisms of the inclusion V ⊂ X are the morphisms H k−2 (V )(−1) → H k (X) , where (−1) denotes a Tate twist, obtained as the Poincaré duals of the natural morphisms H 2n−k (X) → H 2n−k (V ) where n = dim C (X). They fit into a long exact sequence, called the Gysin long exact sequence:It is worth noting that the connecting homomorphisms H k (X \ V ) → H k−1 (V )(−1) are residue morphisms, which are easily described using logarithmic forms. We can now state our main theorem (see Theorem 4.8 for more precise statements). Theorem 1.2. Let X be a smooth projective variety over C and L be a hypersurface arrangement in X.(1) For integers q and n let us considerwhere (n − q) is a Tate twist, viewed as a pure Hodge structure of weight q. Then the direct sumhas the structure of a differential graded algebra (dga) in the (semi-simple) category of split mixed Hodge structures over Q. The product in M • (X, L) is induced by the product maps (2) of the Orlik-Solomon algebra and the cup-product on the cohomology of the strata. The differential in M • (X, L) is induced by the natural morphisms (3) and the Gysin morphismsof the inclusions of strata S ⊂ S ′ . The dga M • (X, L) is functorial with respect to (X, L) in the sense explained above.(2) The dga M • (X, L) is a model for the cohomology of X \ L in the following sense: we have isomorphisms of pure Hodge structures over Q L)) which are compatible with the algebra structures, and functorial with respect to (X, L).The precise definition of the Orlik-Solomon model M • (X, L) is given in §4.4. Theorem 1.2 generalizes the case of normal crossing divisors, which is due to P. Del...

Purpose Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The unfavorable prognosis despite maximal therapy relates to high propensity for recurrence. Thus, overall survival (OS) is quite limited and local failure remains the fundamental problem. Here, we present a safety and feasibility trial after treating GBM intraoperatively by photodynamic therapy (PDT) after 5-aminolevulinic acid (5-ALA) administration and maximal resection. Methods Ten patients with newly diagnosed GBM were enrolled and treated between May 2017 and June 2018. The standardized therapeutic approach included maximal resection (near total or gross total tumor resection (GTR)) guided by 5-ALA fluorescence-guided surgery (FGS), followed by intraoperative PDT. Postoperatively, patients underwent adjuvant therapy (Stupp protocol). Follow-up included clinical examinations and brain MR imaging was performed every 3 months until tumor progression and/or death. Results There were no unacceptable or unexpected toxicities or serious adverse effects. At the time of the interim analysis, the actuarial 12-months progression-free survival (PFS) rate was 60% (median 17.1 months), and the actuarial 12-months OS rate was 80% (median 23.1 months). Conclusions This trial assessed the feasibility and the safety of intraoperative 5-ALA PDT as a novel approach for treating GBM after maximal tumor resection. The current standard of care remains microsurgical resection whenever feasible, followed by adjuvant therapy (Stupp protocol). We postulate that PDT delivered immediately after resection as an add-on therapy of this primary brain cancer is safe and may help to decrease the recurrence risk by targeting residual tumor cells in the resection cavity. Trial registration NCT number: NCT03048240. EudraCT number: 2016-002706-39.

In this paper, we study a single-valued integration pairing between differential forms and dual differential forms which subsumes some classical constructions in mathematics and physics. It can be interpreted as a p-adic period pairing at the infinite prime. The single-valued integration pairing is defined by transporting the action of complex conjugation from singular to de Rham cohomology via the comparison isomorphism. We show how quite general families of period integrals admit canonical single-valued versions and prove some general formulae for them. This implies an elementary “double copy” formula expressing certain singular volume integrals over the complex points of a smooth projective variety as a quadratic expression in ordinary period integrals of half the dimension. We provide several examples, including non-holomorphic modular forms, archimedean Néron–Tate heights on curves, single-valued multiple zeta values and polylogarithms. The results of the present paper are used in [F. Brown and C. Dupont, Single-valued integration and superstring amplitudes in genus zero, preprint 2019, https://arxiv.org/abs/1910.01107] to prove a recent conjecture of Stieberger which relates the coefficients in a Laurent expansion of two different kinds of periods of twisted cohomology on the moduli spaces of curves {\mathcal{M}_{0,n}} of genus zero with n marked points. We also study a morphism between certain rings of “motivic” periods, called the de Rham projection, which provides a bridge between complex periods and single-valued periods in many situations of interest.

The Bridging Integrator 1 (BIN1) gene is a major susceptibility gene for Alzheimer’s disease (AD). Deciphering its pathophysiological role is challenging due to its numerous isoforms. Here we observed in Drosophila that human BIN1 isoform1 (BIN1iso1) overexpression, contrary to human BIN1 isoform8 (BIN1iso8) and human BIN1 isoform9 (BIN1iso9), induced an accumulation of endosomal vesicles and neurodegeneration. Systematic search for endosome regulators able to prevent BIN1iso1-induced neurodegeneration indicated that a defect at the early endosome level is responsible for the neurodegeneration. In human induced neurons (hiNs) and cerebral organoids, BIN1 knock-out resulted in the narrowing of early endosomes. This phenotype was rescued by BIN1iso1 but not BIN1iso9 expression. Finally, BIN1iso1 overexpression also led to an increase in the size of early endosomes and neurodegeneration in hiNs. Altogether, our data demonstrate that the AD susceptibility gene BIN1, and especially BIN1iso1, contributes to early-endosome size deregulation, which is an early pathophysiological hallmark of AD pathology.

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