Scattering three closed strings off a Dp-brane in pure spinor formalism

We compute the disk amplitude of three closed strings in the pure spinor formalism. Among others, this amplitude probes tree-level gravitational interactions in the presence of Dp-branes. After disentangling holomorphic and anti-holomorphic closed string coordinates on the disk by means of introducing monodromy phases we find a compact expression for the disk amplitude of three closed strings in terms of open superstring six-point amplitudes. Furthermore, we provide the low-energy expansion (in the inverse string tension) of our amplitude and discuss some relevant Dp-brane couplings associated to it. Finally, we write down an expression for the general structure of the disk amplitude of any number n_c of closed strings in terms of pure open string amplitudes involving 2n_c open strings.Comment: 64 pages, 11 figure

Renal AA-amyloidosis in intravenous drug users - a role for HIV-infection?

Background: Chronic renal disease is a serious complication of long-term intravenous drug use (IVDU). Recent reports have postulated a changing pattern of underlying nephropathy over the last decades. Methods: Retrospective investigation including all patients with prior or present IVDU that underwent renal biopsy because of chronic kidney disease between 01.04.2002 and 31.03.2012 in the city of Frankfurt/Main, Germany. Results: Twenty four patients with IVDU underwent renal biopsy because of progressive chronic kidney disease or proteinuria. Renal AA-amyloidosis was the predominant cause of renal failure in 50% of patients. Membranoproliferative glomerulonephritis (GN) was the second most common cause found in 21%. Patients with AA-amyloidosis were more likely to be HIV infected (67 vs.17%; p=0.036) and tended to have a higher rate of repeated systemic infections (92 vs. 50%; p=0.069). Patients with AA-amyloidosis presented with progressive renal disease and nephrotic-range proteinuria but most patients had no peripheral edema or systemic hypertension. Development of proteinuria preceded the decline of GFR for approximately 1--2 years. Conclusions: AA-amyloidosis was the predominant cause of progressive renal disease in the last 10 years in patients with IVDU. The highest rate of AA-amyloidosis observed was seen in HIV infected patients with IVDU. We speculate that chronic HIV-infection as well as the associated immunosuppression might promote development of AA-amyloidosis by increasing frequency and duration of infections acquired by IVDU

VIS-NIR/SWIR Spectral Properties of H2O Ice Depending on Particle Size and Surface Temperature

Laboratory measurements were performed to study the spectral signature of H2O ice between 0.4 and 4.2 µm depending on varying temperatures between 70 and 220 K. Spectral parameters of samples with particle sizes up to ~1360 µm, particle size mixtures, and different particle shapes were analyzed. The band depth (BD) of the major H2O-ice absorptions at 1.04, 1.25, 1.5, and 2 µm offers an excellent indicator for varying particle sizes in pure H2O ice. The spectral changes due to temperature rather, but not exclusively, affect the H2O-ice absorptions located at 1.31, 1.57, and 1.65 µm and the Fresnel reflection peaks at 3.1 and 3.2 µm, which strongly weaken with increasing temperature. As the BDs of the H2O-ice absorptions at 1.31, 1.57, and 1.65 µm increase, the band centers (BCs) of the H2O-ice absorptions at 1.25 and 1.5 µm slightly shift to shorter wavelengths. However, the BCs of the strong H2O-ice absorptions can also be affected by saturation in the case of large particles. The collected spectra provide a useful spectral library for future investigations of icy satellites such as Ganymede and Callisto, the major targets of ESA’s JUICE mission

Fluxbrane Inflation

As a first step towards inflation in genuinely F-theoretic setups, we propose a scenario where the inflaton is the relative position of two 7-branes on holomorphic 4-cycles. Non-supersymmetric gauge flux induces an attractive inter-brane potential. The latter is sufficiently flat in the supergravity regime of large volume moduli. Thus, in contrast to brane-antibrane inflation, fluxbrane inflation does not require warping. We calculate the inflaton potential both in the supergravity approximation and via an open-string one-loop computation on toroidal backgrounds. This leads us to propose a generalisation to genuine Calabi-Yau manifolds. We also comment on competing F-term effects. The end of inflation is marked by the condensation of tachyonic recombination fields between the 7-branes, triggering the formation of a bound state described as a stable extension along the 7-brane divisor. Hence our model fits in the framework of hybrid D-term inflation. We work out the main phenomenological properties of our D-term inflaton potential. In particular, our scenario of D7/D7 inflation avoids the familiar observational constraints associated with cosmic strings.Comment: 49 pages, 3 figures; v3: refs adde

Biallelic ADAM22 pathogenic variants cause progressive encephalopathy and infantile-onset refractory epilepsy

Pathogenic variants in A Disintegrin And Metalloproteinase (ADAM) 22, the postsynaptic cell membrane receptor for the glycoprotein leucine-rich repeat glioma-inactivated protein 1 (LGI1), have been recently associated with recessive developmental and epileptic encephalopathy. However, so far, only two affected individuals have been described and many features of this disorder are unknown. We refine the phenotype and report 19 additional individuals harboring compound heterozygous or homozygous inactivating ADAM22 variants, of whom 18 had clinical data available. Additionally, we provide follow-up data from two previously reported cases. All affected individuals exhibited infantile-onset, treatment-resistant epilepsy. Additional clinical features included moderate to profound global developmental delay/intellectual disability (20/20), hypotonia (12/20), delayed motor development (19/20). Brain MRI findings included cerebral atrophy (13/20), supported by post-mortem histological examination in patient-derived brain tissue, cerebellar vermis atrophy (5/20), and callosal hypoplasia (4/20). Functional studies in transfected cell lines confirmed the deleteriousness of all identified variants and indicated at least three distinct pathological mechanisms: defective cell membrane expression (1), impaired LGI1-binding (2), and/or impaired interaction with the postsynaptic density protein PSD-95 (3). We reveal novel clinical and molecular hallmarks of ADAM22 deficiency and provide knowledge that might inform clinical management and early diagnostics

Biallelic ADAM22 pathogenic variants cause progressive encephalopathy and infantile-onset refractory epilepsy

Pathogenic variants in A Disintegrin And Metalloproteinase (ADAM) 22, the postsynaptic cell membrane receptor for the glycoprotein leucine-rich repeat glioma-inactivated protein 1 (LGI1), have been recently associated with recessive developmental and epileptic encephalopathy. However, so far, only two affected individuals have been described and many features of this disorder are unknown. We refine the phenotype and report 19 additional individuals harbouring compound heterozygous or homozygous inactivating ADAM22 variants, of whom 18 had clinical data available. Additionally, we provide follow-up data from two previously reported cases. All affected individuals exhibited infantile-onset, treatment-resistant epilepsy. Additional clinical features included moderate to profound global developmental delay/intellectual disability (20/20), hypotonia (12/20) and delayed motor development (19/20). Brain MRI findings included cerebral atrophy (13/20), supported by post-mortem histological examination in patient-derived brain tissue, cerebellar vermis atrophy (5/20), and callosal hypoplasia (4/20). Functional studies in transfected cell lines confirmed the deleteriousness of all identified variants and indicated at least three distinct pathological mechanisms: (i) defective cell membrane expression; (ii) impaired LGI1-binding; and/or (iii) impaired interaction with the postsynaptic density protein PSD-95. We reveal novel clinical and molecular hallmarks of ADAM22 deficiency and provide knowledge that might inform clinical management and early diagnostics. Van der Knoop et al. describe the clinical features of 21 individuals with biallelic pathogenic variants in ADAM22 and confirm the deleteriousness of the variants with functional studies. Clinical hallmarks of this rare disorder comprise progressive encephalopathy and infantile-onset refractory epilepsy.Peer reviewe

Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies