Monolithic Silicon EUV Collector

A collector optic assembly for a EUV radiation source. The collector optic assembly includes an elliptical meniscus having a reflective Si/Mo coating for collecting and reflecting EUV radiation generated by the source. The meniscus is machined from a single piece of silicon. The collector optic assembly further includes a heat exchanger that includes cooling channels through which flows a liquid coolant. The heat exchanger is fabricated from a plurality of machined silicon sections fused together by a glass frit bonding process. The meniscus is fused to a front side of the heat echanger by a glass frit bonding process. A liquid coolant inlet manifold and a liquid coolant outlet manifold are also each machined from a single silicon block and are mounted to a back side of the heat exchange

Structure of the axonal surface recognition molecule neurofascin and its relationship to a neural subgroup of the immunoglobulin superfamily

The chick axon-associated surface glycoprotein neurofascin is implicated in axonal growth and fasciculation as revealed by antibody perturbation experiments. Here we report the complete cDNA sequence of neurofascin. It is composed of four structural elements: At the NH2 terminus neurofascin contains six Ig-like motifs of the C2 subcategory followed by four fibronectin type III (FNIII)-related repeats. Between the FNIII-like repeats and the plasma membrane spanning region neurofascin contains a domain 75-amino acid residues-long rich in proline, alanine and threonine which might be the target of extensive O-linked glycosylation. A transmembrane segment is followed by a 113-amino acid residues-long cytoplasmic domain. Sequence comparisons indicate that neurofascin is most closely related to chick Nr-CAM and forms with L1 (Ng-CAM) and Nr-CAM a subgroup within the vertebrate Ig superfamily. Sequencing of several overlapping cDNA probes reveals interesting heterogeneities throughout the neurofascin polypeptide. Genomic Southern blots analyzed with neurofascin cDNA clones suggest that neurofascin is encoded by a single gene and its pre-mRNA might be therefore alternatively spliced. Northern blot analysis with domain specific probes showed that neurofascin mRNAs of about 8.5 kb are expressed throughout development in embryonic brain but not in liver. Isolation of neurofascin by immunoaffinity chromatography results in several molecular mass components. To analyze their origin the amino-terminal sequences of several neurofascin components were determined. The NH2-terminal sequences of the 185, 160, and 110-135 kD components are all the same as the NH2 termini predicted by the cDNA sequence, whereas the other neurofascin components start with a sequence found in a putative alternatively spliced segment between the Ig- and FNIII-like part indicating that they are derived by proteolytic cleavage. A combination of enzymatic and chemical deglycosylation procedures and the analysis of peanut lectin binding reveals O- and N-linked carbohydrates on neurofascin components which might generate additional heterogeneity

Stabilizing A Vascularized Autologous Matrix with Flexible Magnesium Scaffolds to Reconstruct Dysfunctional Left Ventricular Myocardium in a Large-Animal Feasibility Study

The surgical reconstruction of dysfunctional myocardium is necessary for patients with severe heart failure. Autologous biomaterials, such as vascularized patch materials, have a regenerative potential due to in vivo remodeling. However, additional temporary mechanical stabilization of the biomaterials is required to prevent aneurysms or rupture. Degradable magnesium scaffolds could prevent these life-threatening risks. A left ventricular transmural defect was reconstructed in minipigs with a piece of the autologous stomach. Geometrically adaptable and degradable scaffolds made of magnesium alloy LA63 were affixed on the epicardium to stabilize the stomach tissue. The degradation of the magnesium structures, their biocompatibility, physiological remodeling of the stomach, and the heart’s function were examined six months after the procedure via MRI (Magnetic Resonance Imaging), angiography, µ-CT, and light microscopy. All animals survived the surgery. Stable physiological integration of the stomach patch could be detected. No ruptures of the grafts occurred. The magnesium scaffolds showed good biocompatibility. Regenerative surgical approaches for treating severe heart failure are a promising therapeutic alternative to the currently available, far from optimal options. The temporary mechanical stabilization of viable, vascularized grafts facilitates their applicability in clinical scenarios

Primary melanoma of the prostate: case report and review of the literature

Background: Primary melanoma of the prostate has an extremely rare incidence. Only five cases have been reported in the literature and prognosis is poor. The most likely origin of prostatic melanoma is the transitional epithelium of the prostatic urethra. Surgical care for primary melanoma of mucosal sites is less well established than for primary cutaneous melanoma, but excision of the primary is recommended if the patient has no systemic disease. Case presentation: Here, we describe a case of primary malignant melanoma of the prostate. A 37-year-old male patient with history of both chemo- and radiation therapy for Hodgkin’s disease was admitted to the University Hospital Heidelberg on suspicion of pleomorphic sarcoma of the bladder. In-house diagnostic work-up revealed a malignant melanoma of the prostate. We then performed radical prostatectomy with extended lymphadenectomy. Despite presumably curative surgery, the patient suffered from early relapse of disease with pulmonary metastasis. Systemic chemotherapy and subsequent immuno-oncologic treatment was thereafter initiated. Conclusion: Since prostatic melanoma is a rare disease and a melanoma metastasis of unknown primary is the differential diagnosis, a multidisciplinary approach including early imaging to rule out possible metastases and to search for another potentially existing primary is advisable. To prevent complications related to local tumor progression and to receive tissue for mutational analysis, we recommend complete surgical resection to reduce the tumor mass. Novel immune and targeted oncologic therapies can lead to an improved survival in some cases and support of clinical trials is needed

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder

Background: The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Method: Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. Results: BD individuals scored significantly higher on these spectrum measures than healthy individuals (p < 0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p < 0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p < 0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p < 0.02) and neutral faces (p < 0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BD individuals. Limitations: Small sample size of predominantly medicated BD individuals. Conclusion: This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD

Brain metastasis and survival outcomes after first-line therapy in metastatic melanoma: a multicenter DeCOG study on 1704 patients from the prospective skin cancer registry ADOREG

Background Despite the availability of effective systemic therapies, a significant number of advanced melanoma patients develops brain metastases. This study investigated differences in incidence and time to diagnosis of brain metastasis and survival outcomes dependent on the type of first-line therapy.Methods Patients with metastatic, non-resectable melanoma (AJCCv8 stage IIIC–V) without brain metastasis at start of first-line therapy (1L-therapy) were identified from the prospective multicenter real-world skin cancer registry ADOREG. Study endpoints were incidence of brain metastasis, brain metastasis-free survival (BMFS), progression-free survival (PFS), and overall survival (OS).Results Of 1704 patients, 916 were BRAF wild-type (BRAFwt) and 788 were BRAF V600 mutant (BRAFmut). Median follow-up time after start of 1L-therapy was 40.4 months. BRAFwt patients received 1L-therapy with immune checkpoint inhibitors (ICI) against CTLA-4+PD-1 (n=281) or PD-1 (n=544). In BRAFmut patients, 1L-therapy was ICI in 415 patients (CTLA-4+PD-1, n=108; PD-1, n=264), and BRAF+MEK targeted therapy (TT) in 373 patients. After 24 months, 1L-therapy with BRAF+MEK resulted in a higher incidence of brain metastasis compared with PD-1±CTLA-4 (BRAF+MEK, 30.3%; CTLA-4+PD-1, 22.2%; PD-1, 14.0%). In multivariate analysis, BRAFmut patients developed brain metastases earlier on 1L-therapy with BRAF+MEK than with PD-1±CTLA-4 (CTLA-4+PD-1: HR 0.560, 95% CI 0.332 to 0.945, p=0.030; PD-1: HR 0.575, 95% CI 0.372 to 0.888, p=0.013). Type of 1L-therapy, tumor stage, and age were independent prognostic factors for BMFS in BRAFmut patients. In BRAFwt patients, tumor stage was independently associated with longer BMFS; ECOG Performance status (ECOG-PS), lactate dehydrogenase (LDH), and tumor stage with OS. CTLA-4+PD-1 did not result in better BMFS, PFS, or OS than PD-1 in BRAFwt patients. For BRAFmut patients, multivariate Cox regression revealed ECOG-PS, type of 1L-therapy, tumor stage, and LDH as independent prognostic factors for PFS and OS. 1L-therapy with CTLA-4+PD-1 led to longer OS than PD-1 (HR 1.97, 95% CI 1.122 to 3.455, p=0.018) or BRAF+MEK (HR 2.41, 95% CI 1.432 to 4.054, p=0.001), without PD-1 being superior to BRAF+MEK.Conclusions In BRAFmut patients 1L-therapy with PD-1±CTLA-4 ICI resulted in a delayed and less frequent development of brain metastasis compared with BRAF+MEK TT. 1L-therapy with CTLA-4+PD-1 showed superior OS compared with PD-1 and BRAF+MEK. In BRAFwt patients, no differences in brain metastasis and survival outcomes were detected for CTLA-4+PD-1 compared with PD-1