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We report on fabrication of spatially-coherent columnar plasmonic nanostructure superlattice-type thin films with high porosity and strong optical anisotropy using glancing angle deposition. Subsequent and repeated depositions of silicon and gold lead to nanometer-dimension subcolumns with controlled lengths. We perform generalized spectroscopic ellipsometry measurements and finite element method computations to elucidate the strongly anisotropic optical properties of the highly-porous Si-Au slanted columnar heterostructures. The occurrence of a strongly localized plasmonic mode with displacement pattern reminiscent of a dark quadrupole mode is observed in the vicinity of the gold subcolumns. We demonstrate tuning of this quadrupole-like mode frequency within the near-infrared spectral range by varying the geometry of Si-Au slanted columnar heterostructures. In addition, coupled-plasmon-like and inter-band transition-like modes occur in the visible and ultra-violet spectral regions, respectively. We elucidate an example for the potential use of Si-Au slanted columnar heterostructures as a highly porous plasmonic sensor with optical read out sensitivity to few parts-per-million solvent levels in water. Funding Agencies|National Science Foundation (NSF) through the Nebraska Materials Research Science and Engineering Center (MRSEC) [DMR-1420645, CMMI 1337856, EAR 1521428, DMR 1808715]; German Research Foundation [FE 1532/1-1]; Air Force Research Office [FA9550-18-1-0360]; American Chemical Society [ACS PRF 59374-ND5]; University of Nebraska-Lincoln; J.A. Woollam Co., Inc.; J.A. Woollam Foundation

Electron-beam evaporation at a glancing angle of 85° is utilized to fabricate highly ordered, spatially coherent titanium slanted columnar thin films. Prior to deposition of the slanted columnar thin films, a titanium nucleation layer is deposited using electron-beam deposition at normal incidence with various intended nucleation layer thicknesses of 0 nm, 5 nm, 7.5 nm, 10 nm, 20 nm, and 50 nm. Structural and optical properties of the anisotropic porous thin films are studied by scanning electron microscopy, atomic force microscopy, and Mueller matrix generalized spectroscopic ellipsometry in the near infrared to ultra-violet spectral regions. An anisotropic effective medium approximation is employed for analysis of the ellipsometry data in order to determine slanting angle and porosity model parameters. We find that the slanting angle and titanium volume fraction are strongly influenced by the nucleation layer thickness. Structural parameters of SCTFs deposited on 50 nm nucleation layers are similar to those from SCTFs with no nucleation layer. For small nucleation layer thicknesses, the corresponding SCTF slanting angle and titanium volume fraction decrease reaching a minimum of ≈33° and ≈12%, respectively, at 10 nm nucleation layer thickness. In accordance with the strong decrease in volume fraction we observe substantial reduction of the effective anisotropic thin film optical constants. We find the slanting angle and porosity variation reproducible and suggest use of a nucleation layer for control of slanting angle and porosity of slanted columnar thin films.

The anisotropic optical dielectric functions of a metal (cobalt) slanted columnar thin film deposited by electron-beam glancing angle deposition are reported for the terahertz (THz) frequency domain before and after the slanted columnar thin film was passivated by a conformal alumina coating. A simple effective medium dielectric function homogenization approach which describes isolated, electrically conductive columns rendering the thin film biaxial (orthorhombic) is used to model the observed optical responses. Upon passivating the slanted columnar thin film with a 3 nm thick alumina film an increase of both the real and the imaginary part of the dielectric function for all major polarizability directions is found and attributed to screening effects within the spatially coherent metal nanocolumns.

Optical and structural properties of sequential Co-column–NiFe-column slanted columnar heterostructure thin films with an Al 2 O 3 passivation coating are reported. Electron-beam evaporated glancing angle deposition is utilized to deposit the sequential multiple-material slanted columnar heterostructure thin films. Mueller matrix generalized spectroscopic ellipsometry data is analyzed with a best-match model approach employing the anisotropic Bruggeman effective medium approximation formalism to determine bulk-like and anisotropic optical and structural properties of the individual Co and NiFe slanted columnar material sub-layers. Scanning electron microscopy is applied to image the Co-NiFe sequential growth properties and to verify the results of the ellipsometric analysis. Comparisons to single-material slanted columnar thin films and optically bulk solid thin films are presented and discussed. We find that the optical and structural properties of each material sub-layer of the sequential slanted columnar heterostructure film are distinct from each other and resemble those of their respective single-material counterparts.

This paper discusses existing communication standards in the field of medicine and their applicability for a telemonitoring system for a mobile circulatory module. This module hosts an explanted porcine lung during transportation from the explantation site to a laboratory environment. The telemonitoring modules must enable to assess the wellbeing of the lung and the survival of the tissue as expressed in basic parameters that are measured in the circulation and nutrition module like liquid pressure, liquid flow and temperature. The parameter readings need to be displayed for monitoring purposes on a tablet-PC. Thresholds for parameters shall be set remotely and exceedance of these thresholds shall trigger the transfer of alarm messages to the tablet-PC. The goal of this work is to evaluate existing interoperability standards according to these requirements in order to select a set of standards that will then be used for implementation of the system. Standards that have identified and examined are ISO/IEEE 11073-20601, HL7 Version 2.x and ANT+. It was found that existing standards support large parts of the requirements. However detailed gap analysis will be necessary as the implementation continues.

With satellite communications on a continuous rise the geostationary arc and orbital slots as well as the frequency spectrum available becomes increasingly crowed. This directly influences the design of the spacecraft antennas as gain and isolation requirements are tightened to be compatible with this environment. Typically, two distinctly different antenna designs emerge depending on the requirements. For more regional type coverages with one shaped beam and with polarisation isolation requirements the shaped reflector antenna is often chosen. The multifeed reflector antennas fulfil the needs of multibeam antennas with stringent isolation requirements between beams that are spatially isolation. State-of-the-art designs continue to be provident by Dornier Satellitensysteme GmbH. For the shaped reflector antenna past and several on-going programmes at Dornier Satellitensysteme employ this type of design among them the INSAT-2E shaped reflector antennas which were delivered to ISRO in early 1997. For the mu...

From the interosseous membrane of the forearm a tract extends to the dorsal capsule of the distal radioulnar joint. The structure and function of this tract have been investigated. The tract originates from the radius 22 mm proximal to the distal dorsal corner of the sigmoid notch. Central fibres are attached there with fibrous cartilage and superficial bundles mix with the periosteum. The tract is 8 mm wide, 31 mm long and 1 mm thick. Distally it inserts at the capsule of the distal radioulnar joint between the tendon sheaths of extensor digiti minimi and extensor carpi ulnaris. Deep fibres insert directly at the triangular fibrocartilage. The tract of the interosseous membrane is taut in pronation and loose in supination. It strengthens the dorsal capsule of the distal radioulnar joint. During pronation the tract protects the ulnar head in a sling. Its attachment at the triangular fibrocartilage influences the distal radioulnar joint. Its insertion at the triangular fibrocartilage and the support of the weakest part of the dorsal capsule are of interest.

// Wen Liu 1, 2, * , Julia Beck 3, * , Laura C. Schmidt 1, 2 , Catrin Roolf 1 , Anahit Pews-Davtyan 4 , Barbara C. Rutgen 5 , Sabine Hammer 6 , Saskia Willenbrock 2 , Anett Sekora 1 , Arndt Rolfs 7, 8 , Matthias Beller 4 , Bertram Brenig 9 , Ingo Nolte 2 , Christian Junghanss 1 , Ekkehard Schutz 3, 9, * , Hugo Murua Escobar 1, 2, * 1 Department of Medicine, Clinic III - Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany 2 Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Germany 3 Chronix Biomedical, Gottingen, Germany 4 Leibniz-Institute for Catalysis at the University of Rostock, Rostock, Germany 5 Clinical Pathology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria 6 Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria 7 Albrecht-Kossel-Institute for Neuroregeneration (Akos), Center for Mental Health, University of Rostock, Rostock, Germany 8 Centogene AG, Rostock, Germany 9 Institute of Veterinary Medicine, Georg-August-University Gottingen, Gottingen, Germany * The authors contributed equally Correspondence to: Hugo Murua Escobar, email: hugo.murua.escobar@med.uni-rostock.de Keywords: PDA, arylindolylmaleimides, canine lymphoma, transcriptome sequencing Received: September 14, 2015 Accepted: April 02, 2016 Published: May 12, 2016 ABSTRACT Protein kinase inhibitors are widely used in chemotherapeutic cancer regimens. Maleimide derivatives such as SB-216763 act as GSK-3 inhibitor targeting cell proliferation, cell death and cell cycle progression. Herein, the two arylindolylmaleimide derivatives PDA-66 and PDA-377 were evaluated as potential chemotherapeutic agents on canine B-cell lymphoma cell lines. Canine lymphoma represents a naturally occurring model closely resembling the human high-grade non-Hodgkin’s lymphoma (NHL). PDA-66 showed more pronounced effects on both cell lines. Application of 2.5μM PDA-66 resulted in a significant induction of apoptosis (approx. 11 %), decrease of the metabolic activity (approx. 95 %), anti-proliferative effect (approx. 85 %) and cell death within 48h. Agent induced mode of action was characterized by whole transcriptome sequencing, 12 h and 24 h post-agent exposure. Key PDA-66-modulated pathways identified were cell cycle, DNA replication and p53 signaling. Expression analyses indicated that the drug acting mechanism is mediated through DNA replication and cycle arrest involving the spindle assembly checkpoint. In conclusion, both PDA derivatives displayed strong anti-proliferation activity in canine B-cell lymphoma cells. The cell and molecular PDA-induced effect characterization and the molecular characterization of the agent acting mechanism provides the basis for further evaluation of a potential drug for canine lymphoma serving as model for human NHL.

Introduction: Aberrant methylation of tumor suppressor gene promoters is frequently observed in acute lymphoblastic leukemia (ALL). Decitabine (DAC) and Azacitidine (AZA) are methyltransferase inhibitors (hypomethylating agents, HMA) which partially reverse aberrant DNA methylation. Recently, it was reported that DNA methylation patterns are regulated by casein kinase 2 (CK2) mediated phosphorylation of DNMT3a. CK2 is a key regulator of cell proliferation and survival and modulates hematopoiesis associated signaling cascades by phosphorylation of PTEN and AKT. Elevated CK2 expression has been demonstrated in hematological malignancies and plays a significant role in cell survival. However, it is not yet clear if CK2 inhibition is effective in ALL cells. Therefore, we examined the impact of conventional cytostatics, demethylation and CK2 inhibition on B- and T-ALL cells in single application and in combination. We hypothesized that demethylation and inhibition of CK2 act synergistically inducing greater impact on DNA hypomethylation and ALL cell proliferation. Methods: Several B- and T-ALL cell lines (SEM, RS4;11, Jurkat, CEM) as well as de novo ALL cells were treated with DAC and AZA in mono application. Further, DAC was combined with AraC, Doxorubicin (Doxo) or a CK2 inhibitor for up to 72 h. Cell proliferation and metabolism were determined (trypan blue staining & WST-1 assay). Methylation patterns of bisulfite converted DNA samples were examined using methylation specific qPCR on LINE-1 and the CDH13 gene. For in vivo studies, the SEM cell line was stably transfected with a dual firefly luciferase (ffluc) and GFP expression plasmid. NOD scid gamma (NSG) mice were intravenously injected with 2.5x106 SEM-ffluc-GFP cells. Starting on day (d) 7, mice were treated intraperitoneal. with a vehicle (saline: d7-d10), daily 0.5 mg/kg DAC (d7-d10), daily with 150 mg/kg AraC (d7, d8), or both. Leukemic engraftment and drug response were investigated weekly by flow cytometry (GFP) and bioluminescence imaging (ffluc) for up to 31 days, respectively. Additionally, for therapy monitoring 18F-FDG metabolism of spleen was evaluated using PET/CT on d21 and d28. Results : Mono application of HMA reduced metabolic activity and proliferation significantly (p Moreover, we evaluated the in vivo efficacy of DAC and DAC+AraC. Transplantation of SEM-ffluc-GFP into NSG mice resulted in stable engraftment of ALL cells. Using bioluminescence imaging, leukemic organ infiltration in bone marrow, spleen, lung, liver and brain increased in saline treated mice from d7: 3.0x107 ± 2.3x107 to d31: 6.2x109 ± 5.7x108 ph/s (n=9) continuously. In contrast, treatment with DAC alone or in combination with AraC significantly inhibited the engraftment of ALL cells in vivo. Notably, strongest anti-leukemic effects were induced with DAC alone and not in combination with AraC (d31: DAC: 3.1 x109 ± 1.7 x109 ph/s; n=11 vs. DAC+ AraC: 4.8 x109 ± 1.7 x109 ph/s, n=11). In addition, metabolic spleen volume determined by 18F-FDG-PET/CT on d28 was also markedly reduced in DAC-treated (DAC: 22.8 ± 15.5 mm3, DAC+AraC: 48.7 ± 15.4 mm3) compared to saline treated mice (81.1 ± 21.8 mm3). In vitro combination of DAC with an CK2 inhibitor (CX-4945) induced strong synergistic effects. Here, metabolic activity decreased significantly after 72 h (DAC+CX-4945: 32.2 ± 2.4 % compared to DAC: 72.6 ± 6.4 % and CX-4945: 68.6 ± 8.4 %; DMSO-control: 100 %). The efficacy of DAC and CK2 inhibition in an ALL-xenograft model is currently evaluated. In conclusion, we have shown that HMA significantly inhibit ALL cell proliferation (DAC more than AZA). Further, in vivo combination of DAC with AraC was less effective than DAC alone pointing at antagonistic effects. Of note, our in vitro data indicate that treatment with DAC and CK2 inhibition is synergistic and reveals significant anti-leukemic effects which have to be further elucidated. Disclosures No relevant conflicts of interest to declare.

This paper describes the design of equipment for measuring and temperature control solutions with an accuracy of temperature measurement to ± 0.2 °C from 25 °C to 45 °C. It describes the basic blocks of the proposed facility and the results obtained in testing the liquid volume to 2 litre. The proposed facility is designed as an autonomous system, but allows setting and displaying the control on your compute. The device implements two algorithms and autonomic control of the PSD and the tri-state control. Designed and implemented system for temperature control solutions is fully operational and immediately applicable to real requirements in practice. DOI: http://dx.doi.org/10.5755/j01.eee.18.10.3056

The effect of vibrations and static deformations on aerospace platforms and their influence on the performance of radar, navigation or communication systems are currently studied in the scope of the NATO Research Task Groups SET-131. The deformations may be caused by different effects, e.g. aerodynamic loads, vehicle motion, moving parts such as rudders or turbines, or the impact of a collision. Depending on their strength and the function of the wireless system, they may have a significant impact on the system performance. Structural aspects of the platform such as mechanical or thermal stability, aerodynamics or outer appearance are of great importance. The present paper gives an overview of the scope of work of the group and on-going investigations on system performance analysis and compensation methods such as adaptive signal processing or electronic phase compensation for military key applications such as RADAR, Communication, Electronic Support Measures (ESM) or Command and Control (C2). In addition, the development of an antenna array demonstrator with active vibration compensation using piezo sensors and actuators and control algorithms will be shown, including simulated as well as experimental results.

Structure integrated or conformal antenna arrays consist of several spatially distributed patches. Integrated in aircraft fuselages the array is excited by inherent engine and turbulent boundary layer induced vibrations. These disturbances lead to distortions of single patch orientation and thus to unknown phase differences in the patch signals. Smart-structures technology is the key to overcome this problem. Structure integrated sensors and actuators measure structural vibrations and induce annihilating vibrations which are calculated by a controller. This paper presents a closed-loop sub-space identification combined with a self-tuning controller approach. The objective is to identify the controlled plant operating in closed-loop in flight. Thereby, changes in the vibration behavior of the supporting structure due to temperature gradients e.g. are monitored. A subsequent re-synthesis of the controller by self-tuning guarantees optimal performance during the entire flight. For identification a two stage LQ decomposition is combined with a sequential LQ decomposition in order to handle large data sets. In experiments on an active plate demonstrator a parameter study leads to good identification results without degrading controller performance.

Context Morphine sulfate and naltrexone hydrochloride extended release capsules contain extended-release pellets of morphine with a sequestered naltrexone core (MS-sNT). Taken whole, as intended, morphine is released to provide pain relief; if tampered with by crushing, naltrexone is released to mitigate subjective effects of morphine. Objectives This open-label study assessed long-term (12-month) safety of MS-sNT in patients with chronic, moderate to severe pain. Methods Safety assessments included determining adverse events (AEs), laboratory assessments, and the Clinical Opiate Withdrawal Scale (COWS). Analgesic efficacy was assessed (diary) as worst, least, average, and current pain using an 11-point numeric scale (0=none; 10=worst). Results Of 465 patients receiving one or more doses, 160 completed the study. Most patients (81.3%) experienced one or more AEs, most commonly constipation (31.8%) or nausea (25.2%). Thirty-three patients (7.1%) reported serious AEs; one patient's severe gastrointestinal inflammation and colitis were considered possibly study drug-related. Most discontinuations (30%) occurred in the first month, most often because of AEs (23.7%). There were no clinically relevant changes in laboratory results or vital signs, and no clinically significant electrocardiogram changes deemed study drug-related. During each visit after Week 1, 5% or fewer patients had COWS scores indicating mild withdrawal symptoms (range, 0%–4.8%). Five patients, who did not take the study drug as instructed, had scores consistent with moderate withdrawal. MS-sNT yielded statistically significant improvements from baseline in mean scores for all pain diary items for all visits, except Week 1 for least pain. Conclusion In this study population, when MS-sNT was taken as directed for chronic, moderate to severe pain for up to 12 months, most AEs were typical opioid-related side effects. Mean COWS scores remained low, indicating lack of withdrawal symptoms and appropriate transition off the study drug at completion.

Recently, the elder abuse professional community has developed various models of multi-disciplinary team (M-teams) to handle difficult cases of elder abuse and neglect: hospital-based, family-practice, consortium, and community-based. Some professional literature is available about the hospital and family-practice models but none exists to date about consortium or community M-teams. This paper uses job analysis to describe one community-based M-team affiliated with four elder abuse agencies in Illinois. From the results, a picture of M-teams emerges in terms of the responsibilities, knowledge, and resources needed by teams to do their "jobs."

Monophasic action potential (MAP) can be recorded from the heart surface by optical method via fluorescence measurement. The motion of isolated heart during experiment caused additional noise in recorded signal. The motion artifact can be eliminated by ratiometric fluorescence emission measurements. This study is based on experiments in which a new ratiometric recording setup is used for recording MAPs from isolated rabbit hearts perfused according to Langendorff. MAPs recorded by new ratiometric recording setup are compared with simple optical MAP measurement without ratiometry.

Chronic myeloproliferative neoplasms (CMPN) are a group of hematopoietic stem cell disorders associated with abnormal blood cell production and bone marrow (BM) morphology. Myeloid cells from the majority of polycythemia vera (PV) patients and approximately half of essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients carry the JAK2 V617F mutation.1-3 Recent proposed revisions to the World Health Organization (WHO) diagnostic criteria for these disorders include the presence of JAK2V617F mutation as a major criterion for diagnosis.4 Although various studies have shown that JAK2 mutation testing can be successfully performed on peripheral blood (PB),1-3 bone marrow aspirate (BMA),5 or BM biopsy,6, 7 comparison of results across different sample types has not been performed.

We use generalized spectroscopic ellipsometry to characterize the biaxial optical properties of porous polymer and slanted nanocolumnar template thin films. The porous polymer with inverse columnar structure was prepared via infiltrating polymer into the voids of the slanted nanocolumnar film and selectively removing the column material (cobalt). The anisotropic Bruggeman effective medium approximation was employed to analyze the ellipsometry data of the porous polymer film and nanocolumnar template. The classification and structure of optical anisotropy are found to be identical for both samples. The interchangeable optical behaviors between two complementary structures are attributed to the equivalency in their anisotropic polarizabilities.

Introduction: Successful engraftment following hematopoietic stem cell transplantation (HSCT) depends on factors like immunosuppression, graft composition and number of infused HSC. Whereas the immunosuppression as well as the type and composition of the graft are influenceable low numbers of available HSCs i.e. “weak grafts” remain a clinical challenge. Weak grafts are accompanied by increased graft failure rates and longer cytopenias associated with increased morbidity. Intra bone marrow (IBM) infusion of HSC might be an approach to overcome these problems. Studies in rodents demonstrated faster engraftment with an IBM HSCT approach compared to intravenous (IV) HSCT following myeloablative conditioning. Studies of IBM HSCT following non-myeloablative or reduced intensity conditioning (RIC) are missing. Aims: Exploring the feasibility and efficiency of IBM allogeneic HSCT in comparison to IV HSCT in dog leukocyte antigen (DLA) identical canine littermates using a RIC regimen. Methods: DLA-identical siblings were used as donor/recipient pairs for HSCT. Recipient dogs were conditioned with 4.5 Gy total body irradiation before HSCT (d0) and received 15 mg/kg Cyclosporin A BID as pre- and postgrafting immunosuppression (d-1 to d+35). BM grafts were harvested at d0. In the control group (CON, n=7) unmodified BM was transplanted IV. In the IBM group (n=7) BM harvests were centrifuged and buffy coat of the BM was then transfused simultaneously into the recipient humeri and femura (50 ml, 10 min). 10 dogs are currently evaluable. Chimerism of the peripheral blood mononuclear cells (PBMC) and granulocytes (G) were tested weekly until week 8 and afterwards in larger intervals. Blood cell counts and clinical toxicities such as weight loss were monitored. Results: Infusion of BM directly into the bone was feasible. All animals engrafted. Median number of infused total nucleated cells was 4.0*108/kg (range 2.3-6.0*108/kg, IBM) and 3.3*108/kg (range 1.9-5.0*108/kg, CON, IBM vs CON: p=0.4). Median CD34+ numbers infused were 3.1*106/kg (range:1.2-10.0*106/kg, IBM) and 3.9*106/kg (range: 1.0-7.2*106/kg, CON; IBM vs CON: p= 0.8). Hematopoietic recovery in the IBM and CON groups were similar. Leukocytes recovery (>1.0*109/l) occurred at median d+11 (range: d+10 - d+16, IBM) and d+10 (range: d+9-d+12, CON; IBM vs CON: p=0.3). Median leukocytes nadirs amounted to 0.23*109/l (IBM) and 0.28*109/l (CON; IBM vs CON: p=0.3) and median duration of leukopenia ( Chimerism analyses showed an early and fast increase in donor chimerism in both groups. The PBMC donor chimerism at d+14, d+28 and d+56 were 46% (range: 30-53%), 57% (range: 40-73%), 64% (range: 60-83%) for IBM. Results in CON were 37% (range: 17-93%), 60% (range: 49-100%), 57% (range: 40-100%) (IBM vs CON, p=n.s. (all time points)). The G chimerism values at that specific points were 95% (range: 53-100%), 100% (range: 53-100%), 96% (range: 88-100%) for IBM and 100% (range: 93-100%), 99% (range: 92-100%), 98% (range: 93-100%) for CON (IBM vs CON, p=n.s. (all time points)). Primary goal of the study was the feasibility of the IBM approach. Ethics regulations did not allow to use weak grafts (≤2.0*106/kg) intentionally. However, 4 animals received weak grafts (CON n=2, 1.0 and 2.0*106/kg; IBM n=2, 1.2 and 1.3 *106/kg). Of interest, comparing data of these dogs showed that durations of leukopenia were similar (median 10 days, both groups), but duration of thrombocytopenia were different (median 8 days, IBM vs 22 days, CON). Additionally, long term donor chimerism was higher in the IBM (median 80% PBMC, 100% G) vs CON (median 61% PBMC, 42% G). Conclusion: First, IBM HSCT is a feasible and effective method to deliver HSC directly into the bone marrow following RIC in a canine HSCT model. Second, our preliminary data suggest that IBM HSCT reveals advantageous engraftment differences in regards to platelet recovery and donor chimerism kinetics compared to the IV HSCT when grafts with low HSC numbers were infused. Follow up data of this study and future studies will have to clarify these observations further. Disclosures No relevant conflicts of interest to declare.

Abstract 3711 Introduction: Successful engraftment following transplantation of hematopoietic stem cells (HSCT) depends mainly on pre- and posttransplant immunosuppression, graft type and composition as well as on the HSC numbers infused. Whereas some of the aforementioned parameters can be influenced in the clinical setting, the latter one is more difficult to address. HSCTs of grafts with limited HSC numbers are accompanied by increased graft failure rates, longer cytopenias and increased morbidity. Current concepts to overcome low HSC numbers include the combination of two unrelated grafts, expansion techniques, modification of the graft composition or the site of graft infusion. In preliminary rodent studies intra-bone marrow (IBM) compared to intravenous (IV) HSCT led to faster engraftment which might be explained by closer location of the HSC to the stem cell niches. Aims: To investigate the feasibility and efficiency of IBM-HSCT following a non-myeloablative conditioning regimen in a dog-leukocyte antigen (DLA) identical canine HSCT model. Method: DLA-identical siblings were used as donor/recipient pairs for HSCTs. Recipients received a single dose of 2 Gy total body irradiation before HSCT (day 0). Pre- and postgrafting immunosuppression consisted of CSA (d-1 to d+35) and MMF (d0 to d+27). Two IBM-HSCT cohorts were investigated and data compared to IV controls (CON). BM-grafts of the respective donors were infused unmodified IV (CON, n=9) or IBM after HSC enrichment using a buffy coat followed by ficoll density centrifugation (IBM-I, n=6; 5ml total volume) or IBM after HSC enrichment using buffy coat centrifugation only (IBM-II, n=6; 25 ml total volume). In the CON group the graft was infused in the cubital vein. In the IBM-groups the grafts were infused through a BM aspiration needle into the BM of the left humerus and femur over a period of 5 minutes. In 4 IBM animals graft migration analyses were performed using technecium99 marking. Chimerism and BM cellularity were determined at injection and opposite sides. Analyses of chimerism were performed via polymorphic nucleotide repeat analyses weekly. BM cellularity was determined biweekly. Complete blood count was performed daily. Result: Infusion of grafts directly into the BM was feasible: both volumes (5ml, 25ml) could be infused without any leakage at the injection sites. Tc99-marked BM cells stayed predominately at the injection site for the first 24 hours. All animals engrafted. Mean TNC numbers infused were 2.6 ×108/kg (range: 1.6–11.4; CON), 1.6 ×108/kg (range: 1–2.4; IBM-I), 3.7 ×108/kg (range: 2.1–5.8; IBM-II) (IBM-I vs CON: p=0.08, IBM-II vs CON: p=0.9, IBM-I vs II: p Conclusion: Infusion of HSC grafts up to volumes of 25ml directly into the BM is feasible and allows successful donor engraftment following non-myeloablative conditioning. Duration of cytopenias following IBM-HSCT is still significant, perhaps due to the loss of precursor cells during graft preparation. Further studies are warranted to determine optimal graft preparation and IBM application techniques. Disclosures: No relevant conflicts of interest to declare.

A short review is given of the development of the theory and of the new experimental technique of x-ray low-angle scattering. The study of human γ-globulin leads to a cylindrical particle of about elliptical cross section with axes of 19 and 57 A. and with a length of 230–240 A. The volume is found to be 1.98 × 105 A.3, which involves a molecular weight of 1.62 × 105 in satisfactory agreement with the value found by ultracentrifuge measurements.

Background Prognosis of adult patients suffering from acute lymphoblastic leukemia (ALL) is still unsatisfactory. Targeted therapy via inhibition of deregulated signaling pathways appears to be a promising therapeutic option for the treatment of ALL. Herein, we evaluated the influence of a novel arylindolylmaleimide (PDA-66), a potential GSK3β inhibitor, on several ALL cell lines. Methods ALL cell lines (SEM, RS4;11, Jurkat and MOLT4) were exposed to different concentrations of PDA-66. Subsequently, proliferation, metabolic activity, apoptosis and necrosis, cell cycle distribution and protein expression of Wnt and PI3K/Akt signaling pathways were analyzed at different time points. Results PDA-66 inhibited the proliferation of ALL cells significantly by reduction of metabolic activity. The 72 h IC50 values ranged between 0.41 to 1.28 μM PDA-66. Additionally, caspase activated induction of apoptosis could be detected in the analyzed cell lines. PDA-66 influenced the cell cycle distribution of ALL cell lines differently. While RS4;11 and MOLT4 cells were found to be arrested in G2 phase, SEM cells showed an increased cell cycle in G0/1 phase. Conclusion PDA-66 displays significant antileukemic activity in ALL cells and classifies as candidate for further evaluation as a potential drug in targeted therapy of ALL.

Two different collimating systems have been used to obtain small angle X-ray scattering data from the same colloidal silica suspension. Because of the different collimation conditions, the two uncorrected scattering curves are quite different. However, after collimation corrections are applied, the corrected curves are almost identical. This close agreement provides evidence for the reliability of the collimation correction procedures.