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Perturbations to the in utero environment can dramatically change the trajectory of offspring neurodevelopment. Insults commonly encountered in modern human life such as infection, toxins, high-fat diet, prescription medications, and others are increasingly linked to behavioral alterations in prenatally-exposed offspring. While appreciation is expanding for the potential consequence that these triggers can have on embryo development, there is a paucity of information concerning how the crucial maternal-fetal interface (MFI) responds to these various insults and how it may relate to changes in offspring neurodevelopment. Here, we found that the MFI responds both to an inflammatory state and altered serotonergic tone in pregnant mice. Maternal immune activation (MIA) triggered an acute inflammatory response in the MFI dominated by interferon signaling that came at the expense of ordinary development-related transcriptional programs. The major MFI compartments, the decidua and the placenta, each responded in distinct manners to MIA. MFIs exposed to MIA were also found to have disrupted sex-specific gene expression and heightened serotonin levels. We found that offspring exposed to MIA had sex-biased behavioral changes and that microglia were not transcriptionally impacted. Moreover, the combination of maternal inflammation in the presence of pharmacologic inhibition of serotonin reuptake further transformed MFI physiology and offspring neurobiology, impacting immune and serotonin signaling pathways alike. In all, these findings highlight the complexities of evaluating diverse environmental impacts on placental physiology and neurodevelopment.

Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders and can modulate neurodevelopment and behavior. While this has sparked great interest in the meninges, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one week post-injury. Then, using bulk RNA sequencing, we assessed the differential long-term outcomes between young and aged mice following a TBI. In our scRNA-seq studies, we found that mild head trauma leads to an activation of type I interferon (IFN) signature genes in meningeal macrophages as well as the mobilization of multiple distinct sub-populations of meningeal macrophages expressing hallmarks of either classically activated or wound healing macrophages. We also revealed that dural fibroblasts in the meningeal compartment are highly responsive to TBI, and pathway analysis identified differential expression of genes linked to various neurodegenerative diseases. For reasons that remain poorly understood, the elderly are especially vulnerable to head trauma, where even mild injuries can lead to rapid cognitive decline and devastating neuropathology. To better understand the differential outcomes between the young and the elderly following brain injury, we performed bulk RNA-seq on young and aged meninges from mice that had received a mild TBI or Sham treatment 1.5 months prior. Notably, we found that aging alone induced massive upregulation of meningeal genes involved in antibody production by B cells and type I IFN signaling. Following injury, the meningeal transcriptome had largely returned to its pre-injury signature in young mice. In stark contrast, aged TBI mice still exhibited massive upregulation of immune-related genes and markedly reduced expression of genes involved in extracellular matrix remodeling and maintenance of cellular junctions. Overall, these findings illustrate the dynamic and complex transcriptional response of the meninges to mild head trauma. Moreover, we also reveal how aging modulates the meningeal response to TBI.

Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders, however, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one-week post-injury. Then, using bulk RNA-seq, we assessed the differential long-term outcomes between young and aged mice following TBI. In our scRNA-seq studies, we highlight injury-related changes in differential gene expression seen in major meningeal cell populations including macrophages, fibroblasts, and adaptive immune cells. We found that TBI leads to an upregulation of type I interferon (IFN) signature genes in macrophages and a controlled upregulation of inflammatory-related genes in the fibroblast and adaptive immune cell populations. For reasons that remain poorly understood, even mild injuries in the elderly can lead to cognitive decline and devastating neuropathology. To better understand the differential outcomes between the young and the elderly following brain injury, we performed bulk RNA-seq on young and aged meninges 1.5 months after TBI. Notably, we found that aging alone induced upregulation of meningeal genes involved in antibody production by B cells and type I IFN signaling. Following injury, the meningeal transcriptome had largely returned to its pre-injury signature in young mice. In stark contrast, aged TBI mice still exhibited upregulation of immune-related genes and downregulation of genes involved in extracellular matrix remodeling. Overall, these findings illustrate the dynamic transcriptional response of the meninges to mild head trauma in youth and aging.

The final explosive fate of massive stars, and the nature of the compact remnants they leave behind (black holes and neutron stars), are major open questions in astrophysics. Many massive stars are stripped of their outer hydrogen envelopes as they evolve. Such Wolf-Rayet (W-R) stars emit strong and rapidly expanding (v_wind>1000 km/s) winds indicating a high escape velocity from the stellar surface. A fraction of this population is also helium depleted, with spectra dominated by highly-ionized emission lines of carbon and oxygen (Types WC/WO). Evidence indicates that the most commonly-observed supernova (SN) explosions that lack hydrogen and helium (Types Ib/Ic) cannot result from massive WC/WO stars, leading some to suggest that most such stars collapse directly into black holes without a visible supernova explosions. Here, we present observations of supernova SN 2019hgp, discovered about a day after explosion. The short rise time and rapid decline place it among an emerging population of rapidly-evolving transients (RETs). Spectroscopy reveals a rich set of emission lines indicating that the explosion occurred within a nebula composed of carbon, oxygen, and neon. Narrow absorption features show that this material is expanding at relatively high velocities (>1500 km/s) requiring a compact progenitor. Our observations are consistent with an explosion of a massive WC/WO star, and suggest that massive W-R stars may be the progenitors of some rapidly evolving transients., Unedited author version, Nature in press

Background: In Europe, BEV is approved with either paclitaxel (PAC) or capecitabine (CAP) as 1st-line therapy for HER2-negative aBC. These regimens are being evaluated in routine oncology practice in the German AVANTI (ML22452) observational study. Methods: Eligible pts had received no prior chemotherapy (CT) for aBC and had no BEV contraindications. CT schedule, diagnostics and frequency of follow-up are at the physician's discretion. Data are collected for 1 y after starting BEV, with 6-monthly follow-up for 1.5 y thereafter. QoL is assessed using EORTC QLQ-C30. Data cutoff for the 3rd interim analysis was Dec 1, 2016. Results: Between Oct 2009 and Feb 2015, 2056 eligible pts at >300 centers began treatment with BEV+PAC (n=1658) or BEV+CAP (n=398). Median follow-up was 12.7 (range Table 1. PFS by subgroupPtsNo. of events/pts (%)Median PFS (95% CI), moAll1121/2042 (55)14.2 (13.5–15.3)BEV+PAC902/1646 (55)15.2 (14.0–16.2)BEV+CAP219/396 (55)10.9 (10.1–13.4)TNBC187/429 (44)12.6 (10.7–14.3)Non-TNBC677/1486 (46)14.7 (13.6–16.1) Table 2. Mean QoL scores over time, selected scalesScaleTimepointAll pts Conclusions: More mature results from AVANTI show median PFS of 14.2 mo, favorable tolerability and maintained QoL, supporting 1st-line use of BEV for aBC. The subgroup with prolonged disease control (PFS >15 mo) was heterogeneous; further analyses of these pts are ongoing. Citation Format: Müller V, Jakob A, Aktas B, Grafe A, März W, Fett W, Bruch H-R, Klare P, Hoefflin S, Schneeweiss A. Effectiveness, safety and quality of life (QoL) results from the German multicenter AVANTI study of 1st-line bevacizumab (BEV)-containing therapy in >2000 patients (pts) with advanced breast cancer (aBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-11-01.

Background: The multicenter AVANTI observational study is evaluating the safety and effectiveness of EU-approved BEV-containing regimens (BEV + paclitaxel [PAC] or BEV + capecitabine [CAP]) as first-line therapy for HER2-negative aBC in German routine oncology practice. Methods: Eligible patients (pts) had received no prior chemotherapy (CT) for aBC and had no BEV contraindications. CT schedule, diagnostics, and frequency of follow-up visits are at the physician's discretion. Data are collected for 1 year after starting BEV, with 6-monthly follow-up for 1.5 years thereafter. We explored treatment outcomes in pts with triple-negative aBC (TNBC), pts considered at high risk according to a simple prognostic index for OS in BEV-treated pts [Llombart, 2014], and subgroups defined by timing of BEV+CT initiation. Results: Between Oct 2009 and Feb 2015, 2168 pts treated at 331 centers received BEV+PAC (n=1774) or BEV+CAP (n=394). Of these, 445 (21%) had TNBC and 306 (14%) met the high-risk criteria. Within the hormone receptor-positive (HR+) subgroup, pts receiving endocrine therapy (ET) before BEV+CT were older than pts starting BEV+CT immediately (median age 65 vs 60 years, respectively) and included a smaller proportion with ECOG performance status 0 (39% vs 47%), visceral metastases (70% vs 77%), or prior (neo)adjuvant CT exposure (46% vs 57%). In all subgroups, median BEV treatment duration was longer than median CT duration. At the data cutoff for this interim analysis (Mar 1, 2015), median duration of observation was 10.8 (range table 1 All pts (n=2168)TNBC (n=445)aHR+ with immediate BEV+CT (n=1260)a,bHR+ with ET before BEV+CT (n=309)a,bHigh riskc (n=306)bBEV+PAC, n (%)1774 (82)352 (79)b1062 (84)238 (77)229 (75)Treated until PD, n (%)b,d640 (30)180 (40)314 (25)104 (34)125 (41)BEV+CT until PD449 (21)143 (32)210 (17)61 (20)99 (32)Single-agent BEV until PD191 (9)37 (8)104 (8)43 (14)26 (8)Median BEV duration, months (95% CI)5.9 (5.6–6.3)5.1 (4.9–5.6)6.4 (5.9–7.0)5.6 (5.1–6.5)5.1 (4.6–5.6)Median CT duration, months4.6 (4.4–4.9)3.9 (3.5–4.2)4.9 (4.6–5.1)4.6 (4.2–5.1)3.9 (3.3–4.4)No. of PFS events/pts (%)e1238/2154 (57)302/441 (68)667/1255 (53)187/307 (61)210/306 (69)Median PFS, months (95% CI)10.1 (9.7–10.7)7.2 (6.2–8.0)11.5 (10.8–12.3)9.0 (8.3–10.0)6.4 (5.9–7.4)a154 pts could not be classified as TNBC or HR+ because of missing HR status information. bPost hoc analysis. c≥3 of the 5 risk factors (disease-free interval ≤24 months; ECOG performance status ≥2; liver metastases and/or ≥3 metastatic organ sites; TNBC; prior (neo)adjuvant anthracycline and/or taxane). dData available only in pts with documented end of treatment. ePFS data missing in 14 pts. Conclusions: Interim results from this large observational study indicate that first-line BEV+CT is an effective therapy in all risk subgroups of a general population of pts with HER2-negative aBC treated in routine oncology practice, including pts with a particularly poor prognosis. Results of these exploratory subgroup analyses suggest that BEV+CT could be considered irrespective of HR status. Citation Format: Mueller V, Jakob A, Aktas B, Pott D, Grafe A, Jungberg P, Maerz W, Fett W, Bruch H-R, Klare P, Boller E, Hoefflin S, Schneeweiss A. Efficacy of first-line bevacizumab (BEV)-containing therapy for poor-prognosis advanced breast cancer (aBC): Subgroup analyses of the German AVANTI observational study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-13-02.

Bendamustine has demonstrated clinical activity and a favorable safety profile as monotherapy or in combination with rituximab in lymphoid malignancies. As interventional trials do not always reflect clinical reality, we were interested in the treatment modalities and the outcome of bendamustine-based first-line therapy in patients with advanced indolent non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL) in routine practice. Between April 2010 and October 2011, 324 patients were enrolled in a prospective non-interventional multicenter study. Choice of the bendamustine regimen was at the treating physician's discretion. Effectiveness was assessed by best response. Mean age at onset of therapy was 69 years. The majority (94 %) of the patients was treated with bendamustine in combination with rituximab at a median bendamustine dose of 177 mg/m(2) per cycle. Most often, bendamustine was administered on days 1 and 2 (87 %) at 4-week intervals over a median of 6 cycles. Two hundred eighty-one patients qualified for evaluation of response. The overall response rate was 86 % (complete response 43 %, partial response 43 %, stable disease 10 %, progressive disease 4 %). Side effects of all grades were documented for 161 of the 323 patients (50 %), most frequently affecting blood/bone marrow (35 %). Fifty-four (17 %) patients experienced side effects of grade 3 (15 %) or grade 4 (2 %), and two patients grade 5 toxicities. Bendamustine-based first-line treatment of patients with advanced indolent NHL and MCL in clinical routine practice was assessed as effective and well tolerated in our study. Response was comparable to results from interventional clinical trials.

Background Guidelines for metastatic non-small cell lung cancer recommend stratified treatment by biomarker test results. We used CRISP to evaluate treatment and outcome of patients (pts) in whom neither targetable molecular alterations nor any PD-L1 expression were detected. Methods Currently 163 sites in Germany have recruited >3700 pts at start of 1st-line who will be followed until death or end of project. Data from 2204 pts recruited by 133 sites from 12/2015 to 06/2018 was analyzed. These pts started treatment prior approval of immune checkpoint inhibitors (ICI) for this group of pts. Progression-free survival (PFS) was determined in pts ≥1 year under observation (recruited until 06/2017 (n = 906), outcome sample (ous)). Results 6% of pts with non-squamous (nsq) and 35% with squamous (sq) tumors received no type of biomarker testing prior to start of 1st-line, and in 49% and 36% no targetable alterations or any PD-L1 expression were detected. Thus, 55% and 71% of pts (nsq/sq) were eligible for chemotherapy (ctx) but no type of targeted therapy at start of 1st-line. Median age at start of 1st-line was 66 and 68 years (nsq/sq). 29%/23% had ECOG=0 and 82%/90% ≤1 comorbidity. 10%/6% were never-smokers. In 1st-line, pts received carboplatin- (55%) or cisplatin-based ctx (24%), 13% targeted therapy (e.g. ICI in trial, switch to TKI but test result not yet documented). At database cut, 33% of all pts had started 2nd-line, 24% had died prior to a 2nd-line and remaining pts were still in 1st-line. In the ous, median PFS was 5.0 months (66% events, 95%-CI 4.5-5.5 months, n = 457) for nsq tumors and 4.5 months (66% events, 95%-CI 3.4-5.3 months, n = 154) for sq tumors. In total 55% of pts with nsq and 53% of pts with sq tumors had died. Conclusions CRISP presents current real life data from Germany. Despite break-throughs with targeted therapies and high test rates in routine care, the majority of pts do not qualify for targeted therapy because no targetable alterations are found. First outcome results indicate that prognosis is poor in these pts. Outcome will hopefully improve in the cohort now treated with ctx-ICI combination. Clinical trial identification NCT02622581. Legal entity responsible for the study AIO-Studien-gGmbH. Funding AstraZeneca GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Bristol-Myers Squibb GmbH & Co. KGaA, Celgene GmbH, MSD Sharp & Dohme GmbH, Lilly Deutschland GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, Roche Pharma AG, and Takeda Pharma Vertriebs GmbH & Co. KG. Disclosure F. Griesinger: Honoraria (self), Advisory / Consultancy: Ariad; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myer-Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (self), Advisory / Consultancy: Clovis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck-Sharp-Dome; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche. N.W. Marschner: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution): MSD Sharp & Dohme ; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: iOMEDICO. M. Janicke: Leadership role, Full / Part-time employment: iOMEDICO. A. Fleitz: Full / Part-time employment: iOMEDICO. L. Spring: Full / Part-time employment: iOMEDICO. J. Sahlmann: Leadership role, Full / Part-time employment: iOMEDICO. A. Karatas: Research grant / Funding (institution): AstraZeneca ; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Takeda. A. Hipper: Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): AstraZeneca. M. Sebastian: Advisory / Consultancy: Bristol-Myers Squibb ; Advisory / Consultancy: MSD Sharp & Dohme ; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim Pharma; Advisory / Consultancy: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer. M. Thomas: Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Sharp & Dohme ; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb ; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca ; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis. All other authors have declared no conflicts of interest.

We characterize and compare four different types of focusing optics for hard X-rays, suitable for femtosecond X-ray diffraction experiments, using a tabletop femtosecond laser-based plasma source. We demonstrate a 23 µm focus with a toroidally bent Ge single crystal. A maximum flux of 7 × 10 8 photons/(s mm 2 ) is generated in a 32 µm focus using a multi-layer mirror. An elliptical glass capillary yields the highest number of photons per Bragg angle (2 × 10 5 photons/(s mrad)). The largest number of photons (3 × 10 6 photons/s) per second is obtained in the 105 µm focus of a poly-capillary optical lens system. All numbers are given for characteristic Cu Kα photons.

We have studied high resolution beryllium Auger electron spectra in the 120–160 eV projectile electron energy range following intermediate energies (1.2 and 1.5 a.u. impact velocities) in Be + + CH 4 ion–molecule single collisions [Comments At. Mol. Phys. D 14 (1984) 117]. The major focus of this study is the double K-shell excitation of the Be + projectile forming triply excited BeII*** states (hollow atoms) and BeIII** K shell ionization plus excitation of BeII doubly excited states with two inner shell vacancies. In such intermediate velocity ion-molecular collisions, the CH 4 target plays an important role in the enhancement of the population of BeII*** triply excited states when compared to a more tightly bound He (1s 2 ) 1 S ground state target. Due to the pioneering theoretical work of Gou and Chung [Phys. Rev. A 29 (1996) 6103] most line structures can now be unambiguously identified. The main triply excited states are associated with the 2s 2 2p, 2s2p 2 and 2p 3 and 2 l 2 l ′ n ′ l ″ ( n =3 and 4) configurations decaying to different final BeIII (1snl) ionic states. The line identification method used here is based on Auger energy levels, decay channels and branching ratios.

Rationale:This report describes interdisciplinary rehabilitation for a 51-year-old male recovering from incomplete cervical spinal cord injury (SCI) and multiple comorbidities following an automobile accident.Patient concerns:The patient was admitted to a rehabilitation specialty hospital ap

The incidence of incisional hernias after laparoscopic surgery is evaluated by analysing our own cases and reviewing the literature. Summarised data show the incidence is 1 in 550 cases. The most frequent complication is intestinal incarceration, with a high proportion of Richter's hernias. To avoid post-laparoscopic hernias, it is important to suture the fascia when the trocar diameter exceeds 5 mm. When external suturing of the fascia is impossible, a laparoscopic technique, using the Reverdin needle, is suitable for fascial closure after minimally invasive surgery.

The excitation energies and the probabilities for radiative and radiationless decays of hollow atom states belonging to the 2s22p, 2s2p2 and 2p3 configurations have been calculated on the basis of perturbation theory method (1/Z-expansion) in a broad range of values of atomic number Z. Our results agree well with the first observation of these states and the theoretical and experimental results obtained recently for neutral Li atoms. It should be noted that the 1/Z expansion method gives more accurate results for ions than for neutral systems, because of the limited number of coefficients of 1/Z expansion calculated in this work. In this case the good agreement provided by our results for neutral system allows us to believe that our data for the same triply excited states with Z>3 should be used for prediction of new experiments with these states.

We have developed new types of experimental methods for high-temperature plasma diagnostics based on both glass capillary converters (GCCs) and multilayer mirrors (MLMs), where the optical GCC device provides guiding, focusing, and polarization analysis of short wavelength radiation with a large bandwidth, and the MLM elements are used for dispersing, focusing, and polarization sensitive studies of radiation within a narrow bandwidth. In particular, we report here for the first time, to the best of our knowledge, the development and testing of such new optical diagnostic devices for: (i) pinhole chamber with GCC, (ii) GCC converter for time-resolved x-ray measurements, (iii) polarimeters–spectrometers with GCC and MLM for measurements of polarization and spectral characteristics of short wavelength radiation, and (iv) high sensitivity extreme ultraviolet spectrometers.

Cross sections have been measured for the production of He{sup +} ({ital np}){sup 2}{ital P}{sup {ital o}} states, {ital n}=2,3,4, by proton impact on helium over a projectile velocity range of 1.42{endash}2.45 a.u. (50 {le}{ital E}{le}150 keV). Cross sections were determined by measuring the extreme ultraviolet photons emitted from excited He{sup +} ions. The data indicate a lower energy than expected for the maximum cross section. A comparison of the present results in terms of projectile energy dependance with the cross sections for excitation to He (1{ital snp}){sup 1}{ital P}{sup {ital o}}, ionization, and total electron capture suggests the primary mechanism for the production of excited He{sup +} at low energies is transfer excitation, with ionization excitation being the dominant mechanism at higher energies. {copyright} {ital 1996 The American Physical Society.}

The perturbation theory method was used for the calculation of atomic energy levels of autoionization states for Be-like ions. Correlation, relativistic and radiative effects are taken into account. The resulting theoretical wavelengths (1s2s22p−1s22s2, 1s2s2p2−1s2s2p, 1s2p3−1s22p2) are compared with available experimental data along the isoelectronic sequence to identify irregularities in the experimental data and to predict wavelengths of ions whose values are unknown or uncertain.

The cross section for ionization-excitation of the Lyman series HeII (1s−np, n = 2–5) following proton and electron impact on He has been measured. At projectile velocities between 3.5 and 8 a.u. the cross section for electron impact exceeds that for protons by a factor of up to about 3. The cross section ratio σ(e − ) σ(p) and the difference σ(e−)−σ(p) may be sensitive to interference effects between first and second order terms in the scattering amplitude.

The proposed technology platform allows the fabrication of disposable volume-optical measurement devices in combination with microfluidic channels and reservoirs at an affordable price. The sensor can be easily integrated into more complex polymer based Lab-on-Chips to increase their functionality towards integrated volume-optical sensing. Its possible applications can be found not only in biomedical sensing, but also in monitoring of chemical reaction in micro chambers as well as in the fields of food and environmental control.

We experimentally demonstrate a stable and reproducible generation of long concatenated high-density plasma channels in air by a single femtosecond laser pulse. Each segment of the plasma channel is created by a plasma filament left in the wake of the same single high power laser pulse. Our method enables a control of a few millimeters over the position of each segment as well as exact temporal synchronization between them. The combined plasma channel can extend up to several meters long. The plasma density along the entire concatenated plasma channels is measured to be above 1015 cm−3. The demonstrated approach can be further extrapolated to a higher number of filament segments, thus to much longer high-density plasma channels.

In this study we report new results on the changes in optical properties of glass surfaces induced during wet photolithography using Oblique Incidence Reflectivity Difference Ellipsometry (OI-RD). A novel wet UV-photolithographic method for patterning phospholipid bilayers into two-dimensional arrays of voids and patches on hydrophilic glass substrates is presented. Especially, this technique involves etching the glass substrate fused with lipid vesicle solution and subsequently illuminated with short-wavelength UV light through a photo mask thus creating voids in the irradiated regions. The effects of the chemical etching and subsequent UV irradiation on the surfaces of microscope glass slides are investigated using the OI-RD technique. In this study, we have observed that the UV irradiation after chemical etching further changes the properties of the surface, even in the absence of the lipid bilayer. As a result, irradiating the chemically etched surface before the UV photolithography step renders the whole surface homogenous. Furthermore, fluorescence recovery after photobleaching (FRAP) experiments have been conducted on such homogenized surfaces which reveal that the fluidic properties of the membranes are retained. The created patterns are suitable to study protein-DNA interactions in the lipid environment. Our long term goal is to utilize this technique as a new screening approach for testing drug interactions above and below the cell surface.

A permanent magnet 6.4 GHz microwave plasma generator has been designed and constructed at Plasma and Ion Source Technology group at Lawrence Berkeley National Laboratory for applications in Extreme Ultraviolet Lithography (EUVL). In order to produce 13.5 nm EUV light, Xenon plasma was formed with the goal of producing Xe10+ ions, which are associated with the formation of 13.5 nm radiation. The goal was to diagnose the source plasma by extracting Xe‐ ions from the source plasma and by measuring the EUV light spectrum with a grazing incidence monochromator. 13.5 nm light was observed in the measurements indicating that Xe10+ existed in the plasma.

New types of focusing optical devices based on glass‐capillary converters (GCCs) for the extreme ultraviolet (EUV) region have been constructed and tested. The EUV spectra of He II (np‐1s) line radiation have been recorded in the spectral region from 23.0 to 30.6 nm both with and without GCC. Experimentally an enhancement of EUV radiation by a factor of 4–5 has been demonstrated for a small solid angle of the detection system. Theoretically, a computer simulation has been performed producing an enhancement coefficient of about 30–50 for optimal conditions of such experiments.

The treatment of colorectal cancer with administration of a 2-h infusion of calcium folinate followed by a 24-h infusion of 5-fluorouracil (5-FU) is a standard therapy. Based on newly published data we have applied an infusion of both compounds, 5-FU and calcium folinate, mixed together in an ambulatory pump.We report on a patient suffering from metastatic rectal cancer. After first and second line chemotherapy we started third line chemotherapy consisting of calcium folinate (1,000 mg) and 5-FU (4,000 mg) mixed together in a total volume of 240 ml in an ambulatory pump and administered over a period of 24 h. After a total of 11 applications the patient developed a port thrombosis resistant to lysis with urokinase. The blocked catheter was surgically explanted and the firm material inside was analyzed.The material from inside the lumen of the catheter was analyzed using x-ray spectroscopy and a scanning electron microscopy. Both analyses confirmed that the isolated material is calcium carbonate.This case and the results of the analyses are in accordance with the described problems and results published earlier. A physical and/or chemical in vitro compatibility of 5-FU and calcium folinic acid, without validated clinical data is not sufficient to use this mixture in routine clinical practice.

In this paper we demonstrate the development of a new microspectrometer system for the mid-infrared range (2.5 - 6 /spl mu/m). Micromechanical components are used for the system, therefore a very compact and economical spectroscopic device has been realized. First measurement results are reported as well as the functional ability of the device.

Experimental cross sections in the extreme ultraviolet (EUV) wavelength range for the excitation of helium following electron and H+, H2+, and H3+ ion impact are presented for HeI (1snp) 1Po states with n=2–5. These measurements extend over a large velocity range from 3.8–8.5 a.u. for electrons, 1.4–7.5 a.u. for protons, and 1.4–4.0 a.u. for H2+ and H3+ ions, and they represent the most complete data set obtained so far in the EUV. Furthermore, the convergent close coupling (CCC) and R-matrix with pseudo-states (RMPS) methods have been used here to predict excitation cross sections for the HeI (1snp) 1Po states following electron impact and the atomic-orbitals close coupling expansion (AOCC) for proton impact. In particular, our theoretical results are presented and compared with our EUV experimental cross sections for equal projectile velocities together with previous experimental results including cross sections derived from scaling procedures.

We present the first EUV emission spectra following single and multiple-electron capture for the 80 keV Ar8++N2 multi charged ion-molecular collision system. Our analysis provides evidence of single and double capture processes leading to radiative deexcitation of Ar7+*(nl) n=3–6 and Ar6+*(3lnl′) n=3–5 projectile states. Furthermore we have identified numerous Nq+ (q=2,3) ionic target lines in the EUV spectral range (10–18 nm), owing to multiple ionization of the N2 molecule and consecutive dissociation plus excitation of the fragments. The subsequent photon emission arises from high lying states of the target such as N2+*(1s22s2lnl′) 2,4L,n=2–10 and N3+*(1s22lnl′) 1,3L,n=2–5 with excitation energies up to 52 eV and 78 eV, respectively. The N2+ and N3+ excited dissociated fragments are due to multiply electron capture processes involving up to six electrons.

Neben ballaststoffarmer Ernahrung und Bindegewebsveranderungen der Darmwand gelten intestinale Motilitatsstorungen als Ursache der Divertikelkrankheit (DK). Da die Vermittlung intestinaler Motilitat masgeblich dem enterischen Nervensystem unterliegt, wurden die intramuralen Nervengeflechte von Patienten mit DK und einer Kontrollgruppe untersucht. Die Beurteilung der immunhistochemisch (PGP 9,5) dargestellten Nervenplexus erfolgte an Schnitt- und Schichtpraparaten der Darmwand. Bei 25% der Patienten mit DK fand sich eine oligoneuronale Hypoganglionose des Plexus myentericus. 41,6% zeigten hypertrophe submukose Nervenfaserstrange auf, 16,6% zusatzlich Riesenganglien. Die Befunde belegen, dass die DK mit intestinalen Innervationsstorungen assoziiert ist. Daher sollten insbesondere bei Divertikeltragern mit obstipativer Symptomatik und einem hyperkontraktilen Kolon Fehlbildungen des enterischen Nervensystems atiologisch berucksichtigt werden.

In this study, we present high resolution electron spectra and new identifications of numerous triply excited states of the Li-isoelectronic sequence produced by intermediate velocity Li+ and Be+ projectiles interacting with CH4 molecules under single collision conditions. In particular, we show here as typical examples high resolution lithium and beryllium projectile Auger electron spectra following double K-shell excitation in 200 keV Li++CH4 and 300 keV Be++CH4 collisions. For the beryllium case, the impact velocity is 1.15 a.u. Many new lines appearing in these spectra have been assigned to triply excited Li and Be+ and doubly excited Li+ and Be2+ states. Only recently due to the pioneering theoretical predictions by Chung and coworkers (1), such collisional line structures can now be unambiguously identified. We have not only identified the lowest lying, most prominent 2s22p, 2s2p2 and 2p3 triply excited states (2), but also new excitation and deexcitation channels of higher lying 2l2l′nl′ hollow ato...

Ionization-excitation cross sections of He have been measured following bombardment by fast H+, H+2 and H+3 particles (v = 1.4−8 a.u.). Cross sections for populating different He+ (np, n = 2−5) states have been determined as a function of the projectile velocity, mass, atomic and molecular structure, and number of interacting electrons. It is found that ionization-excitation cross sections obtained are largest for H+3 molecular ions and smallest for protons, roughly in accord with a simple scaling relation.

Absolute EUV emission cross sections for simultaneous ionization and excitation of helium by H+ and C6+ projectiles have been measured for impact energies between 0.83 and 2.3 MeV/u. In this energy range the mass, charge and velocity dependence of the ionization-excitation cross sections is compared for the He+(np) Rydberg states for n ≤5. It is found that the experimental cross sections vary approximately as Z p 3 .

The purpose of this study is to isolate pure biochemical compounds' eigenspectra and to classify skin cancer tumors.Fourier transform infrared fiberoptic evanescent wave (FTIR-FEW) spectra, in the middle infrared (MIR) region, of human normal skin tissue and cancer tumors were analyzed using chemical factor analysis.Eigenspectra of biochemical species were isolated and some of the eigenspectra have been preliminarily identified as due to protein peptide bond and lipid carbonyl vibrations. Cluster analysis was used for classification and good agreement with prior pathological classifications, specifically for normal skin tissue and melanoma tumors, has been found. However the cluster analysis suggests substantial variability in basaloma tumor biochemical characteristics. In addition this study has demonstrated that chemical factor analysis can be carried out directly on raw data to extract biochemical component eigenspectra and classify skin states. Most importantly, it has been demonstrated that the combination of FTIR-FEW technique and chemical factor analysis has potential as a clinical diagnostic tool.

A new multilayer mirror (MLM) polarimeter has been designed, constructed and optimized to analyze polarization in the extreme ultraviolet (EUV) wavelength range. In particular, a MLM polarimeter with a resolving power of about 6 at 304 A (Lyman α of He+) has been developed and fully characterized for detailed polarization studies at wavelengths of 256 A (HeII (3p→1s) and 304 A (HeII (2p→1s). The MLM has also been used as a single flat surface mirror polarimeter for the analysis of longer wavelength, from 517 to 584 A for HeI(1snp)1P0→(1s2)1S transitions.

New experimental results are presented on the degree of linear polarization of the extreme ultraviolet (EUV) emission of the neutral and ionized helium following electron impact excitation and ionization-excitation of He atoms. The polarization of the photon emission from decay of the He (1snp) 1P0 states with wavelengths of 51.7 to 58.4 nm has been measured for electron impact energies ranging from 30 to 1500 eV. In addition, the polarization for the He+ (2p) 2P0 and He+ (3p) 2P0 states with wavelengths of 30.4 and 25.6 nm, respectively, has been obtained from threshold (66 eV and 73 eV) to 1500 eV. Furthermore, a comparison of the experimental results with theoretical calculations is provided.

Treatment of acute viral hepatitis B is symptomatic, fulminant cases may require liver transplantation. In chronic hepatitis B interferon (IFN)-alpha will induce sustained response rates of 30-40%. Nucleoside analogues such as famciclovir or lamivudine appear to be promising for treatment in non-responders or cirrhotic and immunosuppressed patients. IFN-alpha may reduce the rate of chronic courses in acute hepatitis C infections. Chronic hepatitis C patients with elevated ALT activities, positive serum HCV RNA and portal or bridging fibrosis on biopsy are recommended for treatment with IFN-alpha. Sustained responses are observed in less than 20% of treated patients. Retreatment with IFN-alpha may be indicated in non-responders or in case of relapse. Combination therapy of IFN-alpha plus ribavirin may emerge as treatment of choice for patients with a relapse in the near future.

We have applied a new more efficient diagnostic method for studies of extreme ultraviolet (EUV) radiation produced by multicharged ions interacting with He gas. Following single and double electron capture and one electron capture plus target-ion excitation in He2++He collisions the subsequent emitted EUV photons are analyzed with a high-resolution 2.2 m grazing incidence monochromator in conjunction with a new type of glass capillary converter (GCC), specifically designed for the EUV wavelength region (10.0 nm

We have created new concepts of experimental instrumentation for diagnostics of hot plasma and studies of interaction of ion beams with matter (atoms, molecules, microstructures, surfaces and solids) based on both glass capillary converters (GCCs) and multilayer mirrors (MLMs) or crystals, where the optical GCC devices provide guiding, focusing and polarization analysis of short wavelength radiation with a large bandwidth and the MLM, or crystal optical elements are used for dispersing, focusing and polarization sensitive studies of radiation within a narrow bandwidth. In particular, we report here for the first time about the development and test of such new optical devices for (i) studies of fundamental collision processes involving multicharged ions, (ii) compact polarimeter-spectrometers with GCC and MLM (crystals) for measurements of polarization and spectral characteristics of short wavelength radiation and (iii) compact high sensitivity EUV spectrometers. This type of micro instrumentation is very suitable also for 2D and 3D as well as multi parameter applications.

Die fruhe Endotoxintoleranz ist ein seit langem bekanntes Phanomen bei hoheren Wirbeltieren. Neben seiner letalen Toxizitat und Pyrogenitat weist Endotoxin fur den Organismus auch nutzliche biologische Aktivitaten auf wie z. B. die Induktion eines nekrotisierenden Effektes bei Tumoren und die Steigerung einer unspezifischen Resistenz gegenuber Infektionen. Die fruhe Endotoxintoleranz wird hervorgerufen durch die Applikation subletaler Endotoxindo-sen uber 3–4 Tage, ist unspezifisch, d.h. betrifft alle verschiedenartigen Endotoxine diverser gramnegativer Keime, und halt bis zur Bildung spezifischer Antikorper fur ungefahr eine Woche an [1].

Spin‐nonconserving electron transfer processes violating the ‘‘Wigner rule’’ have been studied for slow multiply charged ion‐atom collisions. Experimentally a strong population of highly metastable sodium‐like quartet states in low energy Fe17+ + He single collision events has been observed. The possibility of double‐electron capture plus spin‐flip mechanisms has been discussed experimentally and theoretically, Our theoretical model using time dependent perturbation theory predicts that spin‐flip processes are as likely as no spin flip under the conditions of our experiment.

Laser plasmas produced at intensities of up to 1014 W/cm2 expand towards a secondary target a few millimeters away. The intense x‐ray emission during the interaction plasma‐target was recorded spectrally, spatially and time‐resolved. A number of processes, like recombination and charge transfer may account for this strong radiation. The implications of these experiments to the design of a charge transfer x‐ray laser are discussed.

State‐selective cross sections σ+*(nl) have been measured for ionization‐excitation of helium in collisions with fully stripped ions. The energies of the H+, Li3+, B5+, and C6+ were .83 MeV/u and 1.60 MeV/u. These relate to collision velocities of 5.8 and 8.0 a.u. Data for the Lyman series, He+(np→1s), have been measured by observation of the extreme ultra‐violet spectra in the 22 to 31 nm wavelength range. The 2p‐ 1s data is presented and analyzed in terms of a simple power law dependence on the projectile charge state, Zpn. For the two equivelocity series of cross sections the powers, n, derived from least squares fits to the data were 2.89±0.3 and 2.83±0.4.