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Significance Isolation of sufficient numbers of circulating tumor cells (CTCs) in cancer patients could provide an alternative to invasive tumor biopsies, providing multianalyte cell-based biomarkers that are not available from current plasma circulating tumor DNA sequencing. Given the average prevalence at one CTC per billion blood cells, very large blood volumes must be screened to provide enough CTCs for reliable clinical applications. By creating an ultrahigh-throughput magnetic sorter, we demonstrate the efficient removal of leukocytes from near whole blood volume equivalents. Combined with leukapheresis to initially concentrate blood mononuclear cells, this LPCTC-iChip platform will enable noninvasive sampling of cancer cells in sufficient numbers for clinical applications, ranging from real-time pharmacokinetic monitoring of drug response to tissue-of-origin determination in early-stage cancer screening., Circulating tumor cell (CTC)-based liquid biopsies provide unique opportunities for cancer diagnostics, treatment selection, and response monitoring, but even with advanced microfluidic technologies for rare cell detection the very low number of CTCs in standard 10-mL peripheral blood samples limits their clinical utility. Clinical leukapheresis can concentrate mononuclear cells from almost the entire blood volume, but such large numbers and concentrations of cells are incompatible with current rare cell enrichment technologies. Here, we describe an ultrahigh-throughput microfluidic chip, LPCTC-iChip, that rapidly sorts through an entire leukapheresis product of over 6 billion nucleated cells, increasing CTC isolation capacity by two orders of magnitude (86% recovery with 105 enrichment). Using soft iron-filled channels to act as magnetic microlenses, we intensify the field gradient within sorting channels. Increasing magnetic fields applied to inertially focused streams of cells effectively deplete massive numbers of magnetically labeled leukocytes within microfluidic channels. The negative depletion of antibody-tagged leukocytes enables isolation of potentially viable CTCs without bias for expression of specific tumor epitopes, making this platform applicable to all solid tumors. Thus, the initial enrichment by routine leukapheresis of mononuclear cells from very large blood volumes, followed by rapid flow, high-gradient magnetic sorting of untagged CTCs, provides a technology for noninvasive isolation of cancer cells in sufficient numbers for multiple clinical and experimental applications.

[This corrects the article DOI: 10.1371/journal.pone.0054014.].

Mitochondrial metabolism is an attractive target for cancer therapy1,2. Reprogramming metabolic pathways could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options, such as triple-negative breast cancer (TNBC)1,3. Here we show that BTB and CNC homology1 (BACH1)4, a haem-binding transcription factor that is increased in expression in tumours from patients with TNBC, targets mitochondrial metabolism. BACH1 decreases glucose utilization in the tricarboxylic acid cycle and negatively regulates transcription of electron transport chain (ETC) genes. BACH1 depletion by shRNA or degradation by hemin sensitizes cells to ETC inhibitors such as metformin5,6, suppressing growth of both cell line and patient-derived tumour xenografts. Expression of a haem-resistant BACH1 mutant in cells that express a short hairpin RNA for BACH1 rescues the BACH1 phenotype and restores metformin resistance in hemin-treated cells and tumours7. Finally, BACH1 gene expression inversely correlates with ETC gene expression in tumours from patients with breast cancer and in other tumour types, which highlights the clinical relevance of our findings. This study demonstrates that mitochondrial metabolism can be exploited by targeting BACH1 to sensitize breast cancer and potentially other tumour tissues to mitochondrial inhibitors. The transcription factor BACH1, which targets mitochondrial metabolism, is expressed at high levels in several types of cancer; reducing its expression in tumours makes them more susceptible to treatment with mitochondrial inhibitors.

A case report is presented of fulminant hydroxychloroquine-induced cardiomyopathy in a 57 year-old female patient with a long history of systemic lupus erythematosus. Diagnosis was established based on clinical findings, imaging (echocardiography and cardiac magnetic resonance imaging) as well as endomyocardial biopsy. Despite immediate discontinuation of the medication, the patient died from heart failure within a few days. Since the rare adverse effect described here might be reversible, early diagnosis and discontinuation of hydroxychloroquine are crucial for the prognosis of these patients.

Coproducts of n-3 fatty acid production from algae are a potential feed resource for cattle. A study was conducted evaluating feeding algal biomass to cattle. Crossbred cattle (20 steers and 20 heifers, 255 kg initial BW, SD = 14) were individually fed 4 inclusions of condensed algal residue solubles (CARS; 0, 2.5, 5, 7.5% of diet DM) displacing dry-rolled corn in the finishing diet for a minimum of 97 d. Increasing CARS inclusion in the diet quadratically increased DMI and ADG (P ≤ 0.01) and linearly increased G:F (P

Previous experimental and analytical studies comparing the performance of transonic swept rotors in single and multistage fans have demonstrated the potential of large improvements in clean inlet performance and substantial improvements in fan sensitivity with inlet distortion with forward swept blading. A two-stage, low-aspect ratio transonic fan investigation was previously conducted in the Air Force’s Compressor Research Facility, in two builds on a back-to-back test basis, using a radial and a forward swept stage 1 blade. While the forward swept stage 1 blade configuration did demonstrate superior front stage efficiency and tolerance to inlet distortion, the common second stage among the two builds prevented the overall fan from showing clean inlet performance and stability benefits with the forward swept rotor 1. To address this measured overall performance shortfall, this paper reports on the design of a new second stage blade tested in the same two-stage fan rig with the forward swept stage 1 blade configuration. The new second stage blade was designed with forward sweep to improve efficiency and operability while replicating the baseline radial rotor 2’s aerodynamic design conditions within the same flow path. The design point requirements of the forward swept rotor 2 were selected to preserve the internal stage matching with the radially stacked rotor 2. As the new stage 2 blade had to fit within the existing radial rotor 2’s physical envelope, the new blade was designed with forward sweep through lean only, which proved to be quite challenging from a mechanical growth and deflection view point. The first attempt to run the fan rig with the new stage 2 blade resulted in a leading-edge tip rub during a part speed stall event. However, even with this unfortunate event, fan mapping test results with clean inlet from part speed to 97.5% design speed showed a significant improvement in overall fan efficiency and stall margin, validating the hypothesis that in the earlier tests stage 2 was indeed the limiting stage that prevented the fan from reaching its overall performance goals. Based on this experience and the test data acquired with unstable leading-edge tip rubs during stall deflections with forward swept airfoils leaned in the direction of rotation, a process was developed to determine the acceptability criteria of such blading.

Simple Summary About 10–20 percent of patients with breast cancer are diagnosed with triple-negative breast cancer (TNBC). These tumors are named for their lack of expression of estrogen receptor (ER), progesterone receptor (PR), and amplification of human epidermal growth factor receptor 2 (HER2). These genes are targeted by therapies in other breast cancer patients. However, most TNBC patients recur within 5 years. Understanding how and why these tumors metastasize will help clinicians better treat these underserved cancer patients. TNBC tumors are highly infiltrated by tumor-associated macrophages (TAMs) that promote tumorigenesis and metastasis. Our study elucidates how the tumor co-opts macrophages recruited to the tumor through extracellular vesicles (EVs), further increasing tumor metastasis. Expression of tumor CCL5 regulates EV secretion and cargo that further alters macrophage phenotype to drive tumor metastasis. Together, our data suggest a more extensive role of EVs in the biology of tumor metastasis as well as their potential use as biomarkers. Abstract Purpose: To understand how tumor cells alter macrophage biology once they are recruited to triple-negative breast cancer (TNBC) tumors by CCL5. Method: Mouse bone marrow derived macrophage (BMDMs) were isolated and treated with recombinant CCL5 protein alone, with tumor cell conditioned media, or with tumor extracellular vesicles (EVs). Media from these tumor EV-educated macrophages (TEMs) was then used to determine how these macrophages affect TNBC invasion. To understand the mechanism, we assayed the cytokine secretion from these macrophages to determine how they impact tumor cell invasion. Tumor CCL5 expression was varied in tumors to determine its role in regulating macrophage biology through EVs. Results: Tumor EVs are a necessary component for programming naïve macrophages toward a pro-metastatic phenotype. CCL5 expression in the tumor cells regulates both EV biogenesis/secretion/cargo and macrophage EV-education toward a pro-metastatic phenotype. Analysis of the tumor EV-educated macrophages (TEMs) showed secretion of a variety of factors including CXCL1, CTLA-4, IFNG, OPN, HGF, TGFB, and CCL19 capable of remodeling the surrounding tumor stroma and immune infiltrate. Injection of tumor cells with macrophages educated by metastatic tumor cell EVs into mice increased tumor metastasis to the lung. Conclusion: These results demonstrate that tumor-derived EVs are key mediators of macrophage education and likely play a more complex role in modulating tumor therapeutic response by regulating the tumor immune infiltrate.

Coercive Measures in Child and Adolescent Psychiatry To keep the use of coercive measures in child and adolescent psychiatry low or reduce them completely, there needs to be a specific knowledge of the starting point. The study provides an overview of the current situation using a systematic literature review of published studies from the European and the outer European regions between 2005 and 2015. In summary only twelve publications addressed the topic, differentiated in four studies from inner and eight studies from outer European countries. In the studies from Europe, girls in their late adolescence experienced coercive measures more often, whereas the outer European studies identified more boys in early school age. Regarding the diagnoses of the respective patients, no distinct trend could be identified, as coercive measures were applied with a range of different diagnoses. In the European studies, coercive measures were more often used with children and adolescents fitting in the ICD-10-category F9. Results point to a lack of empirical studies concerning coercive measures in the context of child and adolescent psychiatry. Besides, clinical practice between the countries varies tremendously, resulting in difficulties comparing the findings. One possibility to address these issues might be a central register for every kind of coercive measure, as it was introduced in Baden-Wurttemberg lately and is currently in development for North Rhine-Westphalia.

Zusammenfassung Hintergrund Verdrängungswettbewerb, Kostendruck, Generation Y, Ärztemangel und Feminisierung beeinflussen das Personalmanagement in der Viszeralchirurgie. Die Einschätzung der Istsituation durch die Abteilungsleiter (AL) sowie die Übertragbarkeit von Strategien aus Industrie und Dienstleistungsgewerbe (ID) wurden bisher nicht untersucht. Material und Methoden Mittels eines standardisierten Fragebogens mit 43 Items wurden AL an Universitätskliniken und Krankenhäusern mit ≥ 800 Planbetten befragt (n = 100). Geschlossene Fragen wurden anhand einer 5-stufigen Likert-Skala gestaltet. Zehn Personalverantwortliche (PV) aus ID wurden zur Teilnahme an einem 45-minütigen Telefoninterview eingeladen. Ergebnisse An der Befragung nahmen 37 AL teil, davon 15 Lehrstuhlinhaber. Initiativbewerbung (100%) sowie Stellenanzeigen (78%) und Ansprache von PJ-Studenten (78%) waren die häufigsten Wege der Personalgewinnung. Einen standardisierten Vorbereitungsbogen für Vorstellungsgespräche nutzten nur 17% der AL. Fachkompetenz (MW 2,2 ± 0,9), Sozialkompetenz (MW 1,9 ± 0,6) und gute Deutschkenntnisse (MW 1,8 ± 0,8) wurden als bedeutsame Voraussetzungen für eine Einstellung genannt. Referenzen und Zeugnissen (MW 3,2 ± 0,9) wurde wenig Bedeutung beigemessen. Die Mitarbeiterförderung wurde für sehr wichtig gehalten (MW 1,1 ± 0,2), ein fester Zeitrahmen für die Weiterbildung jedoch nur bedingt zugesichert (MW 3,0 ± 1,5). Transparente Anforderungsprofile für einen Aufstieg (MW 2,5 ± 1,1) und unterschiedliche Karrieremodelle (MW 2,7 ± 1,2) waren wenig vorhanden. Am Telefoninterview nahmen 6 PV teil. Die Mitarbeiterabwerbung (75%), Internet-Plattformen (75%), Werbung auf Messen (75%) sowie Anwerbung von Auszubildenden (50%), Stellenanzeigen (50%) und Social Media (50%) waren häufig genannte Wege der Personalgewinnung. Fach- und Führungskarrieren sind oft voneinander getrennte Karrierepfade, wobei Sozialkompetenz entscheidend für die Besetzung von Führungspositionen ist. Schlussfolgerung In der Viszeralchirurgie sind Initiativbewerbung, Stellenanzeige und PJ-Studenten die Hauptwege zur Personalgewinnung. Diversifizierte Fach- und Führungskarrieren sind bisher nicht etabliert. In ID erfolgreiche Maßnahmen wie aktives Scouting sowie Social Media sollten ebenso evaluiert werden wie diversifizierte Karrieremodelle.

Hintergrund/Ziel: Die Patientenversorgung in der Chirurgie ist in ihrer Komplexitat erheblich gestiegen. Damit geht auch eine erhohte Arbeitsbelastung der arztlichen Mitarbeiter einher. Wir haben eine Dienstgruppe aus Medizinstudierenden eingerichtet, die auserhalb der regularen Arbeitszeiten im OP assistiert. Unser Ziel war es, die Dienstbelastung fur die Arzte sowie Personalkosten zu reduzieren und Studierende fur die Chirurgie zu motivieren. Methoden: Die Datenerhebung erfolgte als explorative Mixed-Method-Studie mit sequenziellem Vorgehen. Zunachst wurden leitfragengestutzte Interviews mit 5 Studierenden durchgefuhrt, um die Grunde fur die Arbeit als OP-Assistenz qualitativ zu evaluieren. Anschliesend wurde zur quantitativen Erhebung ein Online-Fragebogen (EvaSys®) konstruiert und an 16 aktuelle sowie ehemalige Studierende versendet. Die Arbeitsstunden und Lohnkosten der studentischen Hilfskrafte wurden errechnet und mit der Kosteneinsparung von arztlichen Mitarbeitern verglichen. Ergebnisse: In den Jahren 2013 und 2014 arbeiteten durchschnittlich 8–9 Studierende insgesamt 1063 bzw. 1211 Stunden im Operationssaal. Die Differenz im Arbeitgeberbrutto zwischen den Studierenden und arztlichen Mitarbeitern betrug 28,37 € pro Stunde, sodass sich eine Kostenersparnis von etwa 60 000 € pro Jahr ergab. Bei der Frage nach den Motiven wurde in den Interviews der finanzielle Aspekt als sekundar betont, wohingegen die Mehrheit das Sammeln von Erfahrungen favorisierte. Bei der Online-Umfrage dienten Mittelwertvergleiche anhand der 4-stufigen Likert-Skalierung (1 = hohe Zustimmung; 4 = keine Zustimmung) als Analyseinstrument. Primare Motive konnen durch Mittelwerte ≤ 1,3 definiert werden. Anhand dieser Selektion werden vor allem das Sammeln von Erfahrungen, Spas, das Interesse an der Chirurgie und die Abwechslung zum Studium als Motive fur die Studierenden deutlich. Besonders durch die Interviews wurde der Bedarf an mehr Lehr- und Lernmoglichkeiten im OP bei den Studierenden sichtbar und insbesondere die Interaktion mit dem Operateur als verbesserungswurdig betitelt. Schlussfolgerung: Die Studierenden hatten sich aktiv fur den operativen Rufdienst entschlossen. Es gab multiple Grunde, die den finanziellen Aspekt uberwogen. Insgesamt stellt das Konzept des studentischen Rufdiensts eine Win-win-Situation fur den Arbeitgeber und die Studierenden dar. Aus den Ergebnissen der Befragungen sind aber auch klare Masnahmen zur Verbesserung abzuleiten.

New architectures of transparent conductive electrodes (TCEs) incorporating graphene monolayers in di erent configurations have been explored with the aim to improve the performance of silicon-heterojunction (SHJ) cell front transparent contacts. In SHJ technology, front electrodes play an important additional role as anti-reflectance (AR) coatings. In this work, di erent transparent-conductive-oxide (TCO) thin films have been combined with graphene monolayers in di erent configurations, yielding advanced transparent electrodes specifically designed to minimize surface reflection over a wide range of wavelengths and angles of incidence and to improve electrical performance. A preliminary analysis reveals a strong dependence of the optoelectronic properties of the TCEs on (i) the order in which the di erent thin films are deposited or the graphene is transferred and (ii) the specific TCO material used. The results shows a clear electrical improvement when three graphene monolayers are placed on top on 80-nm-thick ITO thin film. This optimum TCE presents sheet resistances as low as 55 W/sq and an average conductance as high as 13.12 mS. In addition, the spectral reflectance of this TCE also shows an important reduction in its weighted reflectance value of 2???3%. Hence, the work undergone so far clearly suggests the possibility to noticeably improve transparent electrodes with this approach and therefore to further enhance silicon-heterojunction cell performance. These results achieved so far clearly open the possibility to noticeably improve TCEs and therefore to further enhance SHJ contact-technology performance.

SummaryTriple-negative breast cancers (TNBC) are highly infiltrated by tumor-associated macrophages (TAMs) that promote tumor growth, survival, metastasis and therapeutic resistance. Although cytokines such as CCL5 have been implicated in TAM recruitment to TNBC tumors, the mechanism by which tumor cells educate TAMs is not understood. Here we show that tumor EVs are both necessary and sufficient for programming TAMs toward a pro-metastatic phenotype. The mechanism involves CCL5 regulation of tumor extracellular vesicles (EVs), which activate TLR2 and TLR3, leading to secretion of a common set of cytokines that further stimulate tumor cell invasion and metastasis as well as alter the tumor microenvironment. Cytokine expression is significantly correlated to CCL5 expression and up-regulated in TNBC patient tumors. These results demonstrate for the first time that tumor EVs are key mediators of TAM education, phenocopy the pro-metastatic and drug resistant state of the tumors to TAMs, and illustrate the potential clinical relevance of these findings to TNBC patients.HighlightsTumor extracellular vesicles (EVs) are required for pro-metastatic programming of tumor-associated macrophages (TAMs)Tumor CCL5 and macrophage TLR signaling mediate tumor EV programming of TAMs in TNBCsTumor EVs mediate drug resistance in TAMs and alter recruitment of regulatory T-cells.Cytokines expressed by EV-educated TAMs are enriched and correlate with CCL5 in human TNBC patients.eTOCChemokines such as CCL5 recruit tumor-associated macrophages (TAMs) that are required for metastasis, but TAM programming is not understood. Rabe et al. show that tumor extracellular vesicles (EVs) are required for programming TAMs via Toll-like Receptors (TLRs) to phenocopy the tumor, rewire the microenvironment, drive metastasis and promote immune cell evasion.

Previous experimental and analytical studies comparing the performance of transonic swept rotors in single and multistage fans have demonstrated the potential of large improvements in clean inlet performance and substantial improvements in fan sensitivity with inlet distortion with forward swept blading. A two-stage, low-aspect ratio transonic fan investigation was previously conducted in the Air Force’s Compressor Research Facility, in two builds on a back-to-back test basis, using a radial and a forward swept stage 1 blade. While the forward swept stage 1 blade configuration did demonstrate superior front stage efficiency and tolerance to inlet distortion, the common second stage among the two builds prevented the overall fan from showing clean inlet performance and stability benefits with the forward swept Rotor 1. To address this measured overall performance shortfall, this paper reports on the design of a new second stage blade tested in the same two-stage fan rig with the forward swept stage 1 blade configuration. The new second stage blade was designed with forward sweep to improve efficiency and operability while replicating the baseline radial Rotor 2’s aerodynamic design conditions within the same flow path. The design point requirements of the forward swept Rotor 2 were selected to preserve the internal stage matching with the radially stacked Rotor 2. As the new stage 2 blade had to fit within the existing radial Rotor 2’s physical envelope, the new blade was designed with forward sweep through lean only, which proved to be quite challenging from a mechanical growth and deflection view point. The first attempt to run the fan rig with the new stage 2 blade resulted in a leading-edge tip rub during a part speed stall event. However, even with this unfortunate event, fan mapping test results with clean inlet from part speed to 97.5 percent design speed showed a significant improvement in overall fan efficiency and stall margin, validating the hypothesis that in the earlier tests stage 2 was indeed the limiting stage that prevented the fan from reaching its overall performance goals. Based on this experience and the test data acquired with unstable leadingedge tip rubs during stall deflections with forward swept airfoils leaned in the direction of rotation, a process was developed to determine the acceptability criteria of such blading.

Signaling by human hepatocyte growth factor (hHGF) via its cell surface receptor (MET) drives mitogenesis, motogenesis and morphogenesis in a wide spectrum of target cell types and embryologic, developmental and homeostatic contexts. Oncogenic pathway activation also contributes to tumorigenesis and cancer progression, including tumor angiogenesis and metastasis, in several prevalent malignancies. The HGF gene encodes full-length hHGF and two truncated isoforms known as NK1 and NK2. NK1 induces all three HGF activities at modestly reduced potency, whereas NK2 stimulates only motogenesis and enhances HGF-driven tumor metastasis in transgenic mice. Prior studies have shown that mouse HGF (mHGF) also binds with high affinity to human MET. Here we show that, like NK2, mHGF stimulates cell motility, invasion and spontaneous metastasis of PC3M human prostate adenocarcinoma cells in mice through human MET. To identify target genes and signaling pathways associated with motogenic and metastatic HGF signaling, i.e., the HGF invasive program, gene expression profiling was performed using PC3M cells treated with hHGF, NK2 or mHGF. Results obtained using Ingenuity Pathway Analysis software showed significant overlap with networks and pathways involved in cell movement and metastasis. Interrogating The Cancer Genome Atlas project also identified a subset of 23 gene expression changes in PC3M with a strong tendency for co-occurrence in prostate cancer patients that were associated with significantly decreased disease-free survival.

This paper presents a procedure for experimentally optimizing a multistage axial compressor. Due to the usual proprietary nature of such tests, a mean-line model of a nine-stage compressor with three rows of variable geometry is used instead of a real machine as a testbed for explaining the optimization method. The compressor is optimized to achieve design-intent corrected flow and pressure ratio while achieving acceptable efficiency and stage matching. The optimization is performed using a response surface methodology that leverages a full factorial design of experiments approach. The resulting empirical models of compressor performance are of high quality, with coefficients of determination exceeding 0.99. An important finding of the work is that stage interactions are important for modeling both efficiency and stage matching, much more than for corrected flow and pressure ratio. Additionally the empirical equations resulting from the design of experiments analysis provide sensitivities due to changes in the variable geometry. These sensitivities can be applied to understanding the impact of uncertainties related to rigging the variable geometry and for assessing potential new or upgraded compressor designs.

Coercive Measures in Child and Adolescent Psychiatry To keep the use of coercive measures in child and adolescent psychiatry low or reduce them completely, there needs to be a specific knowledge of the starting point. The study provides an overview of the current situation using a systematic literature review of published studies from the European and the outer European regions between 2005 and 2015. In summary only twelve publications addressed the topic, differentiated in four studies from inner and eight studies from outer European countries. In the studies from Europe, girls in their late adolescence experienced coercive measures more often, whereas the outer European studies identified more boys in early school age. Regarding the diagnoses of the respective patients, no distinct trend could be identified, as coercive measures were applied with a range of different diagnoses. In the European studies, coercive measures were more often used with children and adolescents fitting in the ICD-10-category F9. Results point to a lack of empirical studies concerning coercive measures in the context of child and adolescent psychiatry. Besides, clinical practice between the countries varies tremendously, resulting in difficulties comparing the findings. One possibility to address these issues might be a central register for every kind of coercive measure, as it was introduced in Baden-Württemberg lately and is currently in development for North Rhine-Westphalia.

The surrounding microenvironment has been implicated in the progression of breast tumors to metastasis. However, the degree to which metastatic breast tumors locally reprogram stromal cells as they disrupt tissue boundaries is not well understood. We used species-specific RNA sequencing in a mouse xenograft model to determine how the metastasis suppressor RKIP influences transcription in a panel of paired tumor and stroma tissues. We find that gene expression in metastatic breast tumors is pervasively correlated with gene expression in local stroma of both mouse xenografts and human patients. Changes in stromal gene expression elicited by tumors better predicts subtype and patient survival than tumor gene expression, and genes with coordinated expression in both tissues predict metastasis-free survival. These observations support the use of stroma-based strategies for the diagnosis and prognosis of breast cancer.

We have examined the chromatin structure around and upstream of the transcriptional start site of the human alpha2(I) collagen (COL1A2) gene. Four strong DNase I-hypersensitive sites (HS2-5) were only detected in fibroblasts, and a weaker one (HS1) was identified in type I collagen-negative cells. Another hypersensitive site potentially involved in COL1A2 silencing was found in intron 1 (HS(In)). HS1 and HS2 were mapped within conserved promoter sequences and at locations comparable to the mouse gene. HS3, HS4, and HS5 were likewise mapped approximately 20 kilobases upstream of COL1A2 at about the same position as the mouse far-upstream enhancer and within a remarkably homologous genomic segment. DNase I footprinting identified twelve areas of nuclease protection in the far-upstream region (FU1-12) and within stretches nearly identical to the mouse sequence. The region containing HS3-5 was found to confer high and tissue-specific expression in transgenic mice to the otherwise minimally active COL1A2 promoter. Characterization of the human element documented functional differences with the mouse counterpart. Enhancer activity substantially decreased without the segment containing FU1-7 and HS5, and inclusion of AluI repeats located 3' of HS3 augmented position-independent expression of the transgene. Hence, subtle differences may characterize the regulation of mammalian alpha2(I) collagen genes by evolutionarily conserved sequences.

Objective To measure Met protein content in prostate biopsies guided by fused magnetic resonance and ultrasound imaging, and to measure soluble Met (sMet) protein concentration in plasma samples from patients presenting evidence of prostate cancer. Patients and Methods 345 patients had plasma samples drawn prior to image-guided biopsy of the prostate. Of these, 32% had benign biopsies. Of the 236 that were positive for prostate adenocarcinoma (PCa), 132 treated by total prostatectomy had Gleason scores of 6 (17%), 7, (55%), 8 (16%), or 9–10 (12%). 23% had evidence of local invasion. Plasma samples were also obtained from 80 healthy volunteers. Tissue Met and plasma sMet were measured by two-site immunoassay; values were compared among clinically defined groups using non-parametric statistical tests to determine significant differences or correlations. Results PCa tumor Met correlated significantly with plasma sMet, but median values were similar among benign and malignant groups. Median plasma sMet values were also similar among those groups, although both medians were significantly above normal. Median Met content in primary PCa tumors and sMet concentrations were independent of Gleason score, final pathologic stage and age. Conclusion Plasma sMet is not predictive of PCa or its severity in patients with organ-confined or locally invasive disease. Quantitative analysis of Met protein content and activation state in PCa tumor biopsy samples was highly feasible and may have value in follow-up to genomic and/or transcriptomic-based screens that show evidence of oncogenically relevant MET gene features that occur at relatively low frequency in non-metastatic PCa.

SummaryHepatocyte growth factor (HGF) and vascular endothelial cell growth factor (VEGF) regulate normal development and homeostasis and drive disease progression in many forms of cancer. Both proteins signal by binding to receptor tyrosine kinases and heparan sulfate (HS) proteoglycans on target cell surfaces. Basic residues comprising the primary HS binding sites on HGF and VEGF provide similar surface charge distributions without underlying structural similarity. Combining three acidic amino acid substitutions in these sites in the HGF isoform NK1 or the VEGF isoform VEGF165 transformed each into potent, selective competitive antagonists of their respective normal and oncogenic signaling pathways. Our findings illustrate the importance of HS in growth factor driven cancer progression and reveal an efficient strategy for therapeutic antagonist development.

Metastatic progression of tumors is the major cause of death in patients with triple-negative breast cancer (TNBC). However, since metastasis is a multistep process, unraveling its complexity is a major challenge. One effective way of tackling this question is to study natural blockers of the metastatic process, metastasis suppressors, and identify the mechanisms by which they regulate metastasis. Raf kinase inhibitory protein (RKIP), a protein that regulates kinase activity, is a suppressor of TNBC metastasis. Although RKIP inhibits the activity of key kinases such as Raf-1, GRK2, NIK/IKK in cultured cells, the kinase targets of RKIP in tumors are not known. To address this question, we used a mass spectrometry approach involving inhibitor-conjugated beads to identify kinases that are downregulated by RKIP in human TNBC xenograft tumors. Our results identified a network of stress kinases targeted by RKIP, including kinases that have not been previously reported as RKIP targets. In order to unravel the effect of this stress network on metastatic gene expression, we investigated genes that correlate with RKIP expression in TCGA breast cancer patient data set. We identified prometastatic genes such as APC and DOCK4 as novel RKIP targets in in vitro and in vivo models of TNBC. We also demonstrated these genes are downstream of the RKIP-stress network. Finally, by using a high-throughput invasion assay, we developed a low-dose multidrug cocktail of small-molecule kinase inhibitors that mimic RKIP's antimetastatic role in TNBCs. Elucidating RKIP function at a systems level reveals the interplay between key metastatic signaling cascades, particularly in relation to cell motility and invasion. Our findings suggest that the low-dose multidrug combination that targets a network of stress kinases is a viable antimetastatic therapy for TNBC patients. Citation Format: Ali Ekrem Yesilkanal, Daniel C. Rabe, Payal Tiwari, Casey Frankenberger, Gary L. Johnson, Marsha Rosner. A novel approach for antimetastatic therapies against TNBC utilizing a physiologic suppressor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4179.

Triple-negative breast cancers (TNBC) are highly infiltrated by tumor-associated macrophages (TAMs) that promote tumor growth, survival, metastasis and therapeutic resistance. Although cytokines such as CCL5 have been implicated in TAM recruitment to TNBC tumors, the mechanism by which tumor cells educate TAMs is not understood. Here we show that tumor extracellular vesicles (EVs) are both necessary and sufficient for programming TAMs toward a pro-metastatic phenotype. The mechanism involves CCL5 regulation of tumor EVs, which activate TLR2 and TLR3, leading to secretion of a common set of cytokines that further stimulate tumor cell invasion and metastasis as well as alter the tumor microenvironment. Cytokine expression is significantly correlated to CCL5 expression and up-regulated in TNBC patient tumors. These results demonstrate for the first time that tumor EVs are key mediators of TAM education, phenocopy the pro-metastatic and drug resistant state of the tumors to TAMs, and illustrate the potential clinical relevance of these findings to TNBC patients. Citation Format: Daniel C. Rabe, Jiyoung Lee, Felicia Rustandy, Marsha R. Rosner. Tumor extracellular vesicles are required for tumor-associated macrophage programming [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1739.

Oxidative phosphorylation is an attractive target for cancer therapy. Reprogramming metabolic pathways by promoting oxidative phosphorylation could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options like triple negative breast cancer (TNBC). Here we show that BACH1, a heme-binding transcription factor whose expression is enriched in patients with TNBC, inhibits oxidative phosphorylation through direct transcriptional regulation of electron transport chain (ETC) gene expression. Treatment of cells with hemin, which induces BACH1 degradation, mimics BACH1 depletion with shRNA. Pretreatment of TNBC tumors with BACH1 shRNA or hemin overcame resistance to metformin, an anti-diabetic drug, and abolished the growth of both cell line and patient-derived tumor xenografts. BACH1 gene expression inversely correlated with ETC gene expression in breast cancer patients as well as other tumor types, highlighting the clinical relevance. This study demonstrates that oxidative phosphorylation represents an Achilles heel that can be exploited through targeting BACH1 to sensitize breast cancer and potentially other tumor tissues to mitochondrial inhibitors. Citation Format: Jiyoung Lee, Ali Yesilkanal, Casey Frankenberger, Mohamad Elbaz, Daniel Rabe, Jielin Yan, Felicia Rustandy, Peter Hart, Christie Kang, Elizabeth Grossman, Jason Locasale, Daniel Nomura, Marcelo Bonini, Marsha Rosner. Effective combination therapy for breast cancer targeting BACH1 and mitochondrial metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5497.

The formation of microemulsions in presence of toluene, pentanol, CTAB and the ionic liquid (IL) 1-ethyl-3-methylimidazolium-ethylsulfate (EMIM-EtOSO 3 ) or 1-ethyl-3-methylimidazolium-hexylsulfate (EMIM-HexOSO 3 ) was studied. Due to the interface stabilizing properties of the co-surfactant pentanol the range of the isotropic microemulsion phase and microemulsion properties can be tuned by increasing the amount of co-surfactant. In addition, the microemulsion formation process can be influenced by the temperature and the counterion hydrophobicity of the ionic liquid. Therefore, bicontinuous microemulsions become available at higher temperatures. Conductometric titrations in combination to dynamic light scattering and rheological measurements show characteristic changes in the droplet size and droplet–droplet interactions by increasing the amount of the ionic liquid in the reverse IL-in-oil microemulsions. The droplet structure can be identified by means of Cryo-Scanning Electron Microscopy.

We propose a general technique for modeling the visible road surface in front of a vehicle. The common assumption of a planar road surface is often violated in reality. A workaround proposed in the literature is the use of a piecewise linear or quadratic function to approximate the road surface. Our approach is based on representing the road surface as a general parametric B-spline curve. The surface parameters are tracked over time using a Kalman filter. The surface parameters are estimated from stereo measurements in the free space. To this end, we adopt a recently proposed road-obstacle segmentation algorithm to include disparity measurements and the B-spline road-surface representation. Experimental results in planar and undulating terrain verify the increase in free-space availability and accuracy using a flexible B-spline for road-surface modeling.

Background: Percutaneous access to the jejunum is an important approach if gastrostomy feeding is not possible. Objective: To analyze success, short- and long-term complications (STCs, LTCs) in patients with percutaneous endoscopic jejunostomy (PEJ) and jejunal access through percutaneous endoscopic gastrostomy (Jet-PEG). Methods: A retrospective analysis of endoscopically placed PEJs and Jet-PEGs. Success rates, mortality, STCs and LTCs were investigated for risk factors comprising demographic data, underlying disease, previous surgery and experience of the endoscopist. Results: 205 PEJ and 58 Jet-PEG placements were included in the study. PEJs and Jet-PEGs were successfully placed in 65.4 and 89.7%, respectively. Billroth II surgery predisposed in favor of a significantly higher success rate for PEJ placement (p = 0.014, OR = 2.27). Inexperienced examiners have a significantly (p = 0.040) lower success rate for tube insertion than examiners with a medium level of experience. STCs and LTCs occurred evenly in PEJ and Jet-PEG patients. Dislocation of the tube occurred significantly more frequently in Jet-PEG patients (33.3%, p = 0.005). Aspiration was most common for bedridden patients. Conclusion: PEJ has a significantly lower success rate for insertions, but fewer LTCs. The experience of the endoscopist correlates with the success rate of tube insertion.

Die magnetischen Verluste, welche nach dem phanomenologischen Modell von Landau Lifschitz betrachtet werden, konnen unter Nutzung der mikroskopischen und makroskopischen Werkstoffeigenschaften entwickelt werden. Jedoch beziehen sich diese Betrachtungen auf kristalline Schichten und nicht auf reale granulare Strukturen. Granulare Strukturen sollen [ 2 ] eine hohere Absorption der elektromagnetischen Energie realisieren konnen als kristalline Schichten. Ziel dieser Arbeit ist es ein Simulationsmodell unter Nutzung realer amorpher und kristalliner Schichteigenschaften aufzubauen und einen Designhinweis zur Entwicklung einer Schicht hin zu hoheren Absorptionen aufzuzeigen. Die erhohte Absorption der granularen Nanomaterialien soll in elektromagnetischer Vertraglichkeitsanwendungen (EMV) fur Leitungen und Schichten fur Entstorfolien eingesetzt werden. Eine RF – Materialanalyse, eine AFM - Schichtanalyse und EMV - Analyse schliest den Kreis zum Materialdesign und EMV zur Industrieanwendung als Absorbermaterial bzw. Entstormaterial. Granular magnetic ultrathinthin multilayer films Fe/ FeO on Al substrates, modelling of a 1 D granulare thin film for EMC applications Hematite ferrite thin films in granular structures have attracted much attention as materials with unique proper ties. One of these properties is enhanced microwave absorption for a good EMC application. This gives a possibility to absorption electro magnetic covers ( EMC ) of cable application with ultrathin thickness and granular structure. The Electromagnetic Compatibility absorption of granular Ferrite polycristalline sample is 6 - 7 dB in the GH z - range.

Triple-negative breast cancer (TNBC) patients have the highest risk of recurrence and metastasis. Because they cannot be treated with targeted therapies, and many do not respond to chemotherapy, they represent a clinically underserved group. TNBC is characterized by reduced expression of metastasis suppressors such as Raf kinase inhibitory protein (RKIP), which inhibits tumor invasiveness. Mechanisms by which metastasis suppressors alter tumor cells are well characterized; however, their ability to regulate the tumor microenvironment and the importance of such regulation to metastasis suppression are incompletely understood. Here, we use species-specific RNA sequencing to show that RKIP expression in tumors markedly reduces the number and metastatic potential of infiltrating tumor-associated macrophages (TAM). TAMs isolated from nonmetastatic RKIP+ tumors, relative to metastatic RKIP− tumors, exhibit a reduced ability to drive tumor cell invasion and decreased secretion of prometastatic factors, including PRGN, and shed TNFR2. RKIP regulates TAM recruitment by blocking HMGA2, resulting in reduced expression of numerous macrophage chemotactic factors, including CCL5. CCL5 overexpression in RKIP+ tumors restores recruitment of prometastatic TAMs and intravasation, whereas treatment with the CCL5 receptor antagonist Maraviroc reduces TAM infiltration. These results highlight the importance of RKIP as a regulator of TAM recruitment through chemokines such as CCL5. The clinical significance of these interactions is underscored by our demonstration that a signature comprised of RKIP signaling and prometastatic TAM factors strikingly separates TNBC patients based on survival outcome. Collectively, our findings identify TAMs as a previously unsuspected mechanism by which the metastasis-suppressor RKIP regulates tumor invasiveness, and further suggest that TNBC patients with decreased RKIP activity and increased TAM infiltration may respond to macrophage-based therapeutics. Cancer Res; 75(19); 4063–73. ©2015 AACR.

The Great Recession of 2008-2009 hurt almost all of the companies’ stock values in the United States. Interestingly, for Starbucks, the deterioration started a few years before the recession. From 2005 to 2007, the company’s stock price declined by approximately 40%. This case encourages students to examine the company’s return on capital, compare it to its cost of capital, and then relate this to the decline in the company’s stock price. First, they will establish a single formula for return on invested capital. Then, they will calculate the return on invested capital for Starbucks in each year. They will learn about different costs of capital including cost of common stock, cost of preferred stock, and cost of debt. Then, they will debate whether cost of debt capital, cost of equity capital, or weighted-average cost of capital is the relevant number to compare to the company’s return on invested capital. Overall, the case illustrates the importance of return on capital, the different types of cost of capital, and the overall cost of capital on a company’s value.

Sustainability efforts encompass economic, social and environmental management. After decades of promoting such causes, sustainability finally has moved up to the boardroom agenda per PricewaterhouseCooper 2012 report. As companies incorporate sustainability into business strategy, it is crucial for accountants and financial managers to capture the financial implications of those sustainable practices. This case provides an in-depth review of current reporting and measurement of sustainable practices and outlines properties of a sustainable model. Students will analyze reasons for corporations to provide sustainability reports and examine limitations of current sustainability reporting practices. Students are advised to consider what enhancement in current reporting could increase the economic value of reporting efforts and evaluate the relative contribution of sustainable practices that improve firm performance. This case illustrates development of corporate sustainability reporting, the importance of collecting relevant data, analyzing operational data, reporting in accounting and financial terms, incorporating sustainability when making strategic business decisions.

SummaryAim: To evaluate the efficacy and tolerance of iodine- 131-lipiodol (131I-lipiodol) for hepatocellular carcinoma (HCC) in German long term patients and comparison with medically treated controls. Patients, Methods: 38 courses of intra-arterial 131I-lipiodol therapy with a total activity up to 6.7 GBq were performed in 18 patients with HCC (6 with portal vein thrombosis). Liver and tumour volume and lipiodol deposition were measured by computed tomography and 131I activity by scintigraphy. Therapeutic efficacy was determined by tumour volume change and matched-pairs analysis in comparison to medically (i.e. tamoxifen or medical support) treated patients. Results: Tumour volume decreased in 20/32 index nodules (63%) after the first course. Repeated therapy frequently resulted in further tumour reduction. Overall response to treatment was partial in 11 nodules, minor response in 4 nodules, and disease was stable in 12 and progressive in 5. Significant response was associated with pretherapeutic nodule volume up to 150 ml (diameter of 6.6 cm). Survival rate after 3, 6, 9, 12, 24 and 36 months was 78, 61, 50, 39, 17, and 6%. Matched-pairs analysis of survival revealed 131I-lipiodol to be superior to medical treatment. The most important side effect was a pancreatitis-like syndrome whereas overall tolerance was good. Conclusion: The long term results confirm that HCC therapy with 131I-lipiodol is effective and probably superior to medical treatment. Tumour nodules of up to 6 cm diameter are well suited for this therapy even in the presence of portal vein thrombosis.

Summary Cross-sectional maps of stems of beech, Horse chesnut and Norway maple affected by Ganoderma adspersum (Schulz) Donk, Pleurotus ostreatus (Jaquin: Fr.) Kumm and Kretzschmaria deusta (Hoffm.: P. Martin) (=Ustulina deusta (Fr.) Petrak), respectively showing fungal decay were obtained from living trees. Zones of altered fresh- and dry- matter density were constructed, and these compared with Picus® acoustic tomograms of the same cross-sections. The studies shown demonstrate that within a sample cross-section, a zone of decay can be determined accurately for its size and moderately accurately for its position. The shape of the sample cross section influences the accuracy of the acoustic tomograms. Thus the greater the deviation from a circular outline, the poorer the accuracy. Likewise, the number of sensors naturally affects the accuracy. Wood decay caused by Kretzschmaria deusta can be detected by the Picus® acoustic tomograph. The resolution of the tomograms is still worthy of improvement as reacti...

The Department of Defense (DoD) has identified that one of the main complaints of personnel exposed to JP-8 jet fuel is irritant dermatitis. The purpose of this investigation is to describe the JP-8-induced inflammatory cytokine response in skin. JP-8 jet fuel or acetone control (300 microl) was applied to the denuded skin of rats once a day for 7 days. Skin samples from the exposed area were collected 2 and 24 h after the final exposure. Histological examination of skin biopsies showed neutrophilic inflammatory infiltrate. Reverse transcription-polymerase chain reaction (RT-PCR) was performed utilizing skin total RNA to examine the expression of various inflammatory cytokines. The CXC chemokine GROalpha was significantly upregulated at both time points, whereas GRObeta was only increased 2 h post final exposure. The CC chemokines MCP-1, Mip-1alpha, and eotaxin were induced at both time points, whereas Mip-1beta was induced only 24 h post exposure. Interleukins-1beta and -6 (IL-1beta and IL-6) mRNAs were significantly induced at both time points, while TNFalpha was not significantly different from control. Enzyme-linked immunosorbent assay (ELISA) of skin protein confirmed that MCP-1, TNFalpha, and IL-1beta were modulated as indicated by PCR analysis. However, skin IL-6 protein content was not increased 2 h post exposure, whereas it was significantly upregulated by jet fuel after 24 h. Data from the present study indicate that repeated (7 days) JP-8 exposure induces numerous proinflammatory cytokines in skin. The increased expression of these cytokines and chemokines may lead to increased inflammatory infiltrate in exposed skin, resulting in JP-8-induced irritant dermatitis.

Experiments are performed on a modern design transonic shroudless low-aspect ratio fan blisk that experienced both subsonic/transonic and supersonic stall-side flutter. High-response flush mounted miniature pressure transducers are utilized to measure the unsteady aerodynamic loading distribution in the tip region of the fan for both flutter regimes, with strain gages utilized to measure the vibratory response at incipient and deep flutter operating conditions. Numerical simulations are performed and compared with the benchmark data using an unsteady three-dimensional nonlinear viscous computational fluid dynamic (CFD) analysis, with the effects of tip clearance, vibration amplitude, and the number of time steps-per-cycle investigated. The benchmark data are used to guide the validation of the code and establish best practices that ensure accurate flutter predictions.Copyright © 2003 by ASME

Alpha-fetoprotein (AFP) is re-expressed in 60%-70% of hepatocellular carcinomas (HCC) and may therefore be a potential target for a prophylactic or therapeutic tumour-specific vaccination. A prerequisite for this approach is the possibility to induce AFP-specific T-lymphocytes in patients with HCC and/or cirrhosis.Peripheral blood was examined for the presence of AFP-specific T-lymphocytes using a FACS-based interferon-gamma secretion assay.In a group of healthy volunteers, the presence of AFP-specific CD4- and CD8-lymphocytes was demonstrated. Screening of blood of 14 cirrhotic patients without HCC and 23 cirrhotic patients with HCC showed that patients with liver diseases that represent targets for vaccination also harbour CD4-positive as well as CD8-positive AFP-specific Tlymphocytes. AFP reactivity in patients' lymphocytes was not significantly influenced by soluble serum AFP. The median stimulation factors for CD4-positive T-lymphocytes were significantly higher (P = 0.0365) in cirrhotic patients without HCC (median 2.08, range 0.50-4.40) compared to cirrhotic patients with HCC (median 1.15, range 0.24-8.50).AFP-specific T-lymphocytes that may be instrumental in HCC vaccination strategies are present in humans. This study suggests that immunopreventive vaccination of cirrhotic patients rather than immunotherapeutic vaccination of HCC patients may be preferable.

Kidney cancer was the cause of almost 13,000 deaths in the United States in 2009. Loss of function of the VHL tumor suppressor gene (von Hippel-Lindau disease) dramatically increases the risk of developing clear cell kidney cancer. The VHL protein is best understood for its regulation of hypoxia inducible factor (HIF). HIF responds to changes in oxygen levels in the cell and is responsible for mediating the transcriptional response to hypoxia. Of the three known HIFα gene products, HIF-2α appears to play a fundamental role in renal carcinoma. A high throughput screen was developed to identify small molecule inhibitors of HIF-2 gene expression. The screen was performed and yielded 153 confirmed active natural product extracts. Three of the active extracts were from marine soft corals of the order Alcyonacea: Sarcophyton sp., Lobophytum sarcophytoides and Asterospicularia laurae. Bioassay-guided fractionation led to the isolation of two new cembrane diterpenes, (4Z,8S*,9R*,12E,14E)-9-hydroxy-1-(prop-1-en-2-yl)-8,12-dimethyl-oxabicyclo[9.3.2]-hexadeca-4,12,14-trien-18-one (1), and (1E,3E,7R*,8R*,11E)-1-(2-methoxypropan-2-yl)-4,8,12-trimethyloxabicyclo[12.1.0]-pentadeca-1,3,11-triene (7), as well as eight known compounds, 2-6 and 8-10.

Under normal conditions, hepatocyte growth factor (HGF)-induced activation of its cell surface receptor, the Met tyrosine kinase (TK), is tightly regulated by paracrine ligand delivery, ligand activation at the target cell surface, and ligand activated receptor internalization and degradation. Despite these controls, HGF/Met signaling contributes to oncogenesis and tumor progression in several cancers and promotes aggressive cellular invasiveness that is strongly linked to tumor metastasis. The prevalence of HGF/Met pathway activation in human malignancies has driven rapid growth in cancer drug development programs. Pathway inhibitors can be divided broadly into biologicals and low molecular weight synthetic TK inhibitors; of these, the latter now outnumber all other inhibitor types. We review here Met structure and function, the basic properties of HGF/Met pathway antagonists now in preclinical and clinical development, as well as the latest clinical trial results. The main challenges facing the effective use of HGF/Met-targeted antagonists for cancer treatment include optimal patient selection, diagnostic and pharmacodynamic biomarker development, and the identification and testing of optimal therapy combinations. The wealth of basic information, analytical reagents and model systems available concerning HGF/Met oncogenic signaling will continue to be invaluable in meeting these challenges and moving expeditiously toward more effective disease control.

An innovative pressure-measurement technique that employs the tools of molecular spectroscopy has been widely investigated by the aerospace community. Measurements are made via oxygen-sensitive molecules attached to the surface of interest as a coating, or paint. The pressure-sensitive-paint (PSP) technique is now commonly used in stationary wind-tunnel tests; this paper presents the use of this technique in advanced turbomachinery applications. New pressure- and temperature-sensitive paints (P/TSPs) have been developed for application to a state-of-the-art transonic compressor where pressures up to 1.4 atm and surface temperatures to 90°C are expected for the suction surface of the first-stage rotor. PSP and TSP data images have been acquired from the suction surface of the first-stage rotor at 85 percent of the corrected design speed for the compressor near-stall condition. A comparison of experimental results with CFD calculations is discussed.

Summary Sunflower seedlings (Helianthus annuus L.) were grown for 3 days in darkness. After irradiation with continuous white light (WL) the apical hook unfolded. WL-induced hook opening was due to an enhancement of cell elongation on the inner side of the curved organ. Two types of acid invertase (EC 3.2.1.26) were detected in the apical hook: a soluble and a cell-wall-bound form. The activity of the soluble enzyme was enhanced by WL, whereas that of the wall-associated form was unaffected. Detailed time-course studies revealed that the activity of the soluble acid invertase increased within 2 h of WL-treatment. Concomitantly, the level of sucrose declined and that of glucose and fructose increased. WL-induced sucrolysis was activated 2 h before a change in growth could be detected (hook opening, differential elongation of the epidermal cells). We conclude that the light-dependent activation of sucrose catabolism via soluble acid invertase represents one of the key events that leads to the unfolding of the apical hook in developing sunflower seedlings.

The effects of stepped-tip gaps and clearance levels on the performance of a transonic axial-flow compressor rotor were experimentally determined. A two-stage compressor with no inlet guide vanes was tested in a modern transonic compressor research facility. The first-stage rotor was unswept and was tested for an optimum tip clearance with variations in stepped gaps machined into the casing near the aft tip region of the rotor. Nine causing geometries were investigated consisting of three step profiles at each of three clearance levels. For small and intermediate clearances, stepped tip gaps were found to improve pressure ratio, efficiency, and flow range for most operating conditions. At 100 percent design rotor speed, stepped tip gaps produced a doubling of mass flow range with as much as a 2.0 percent increase in mass flow and a 1.5 percent improvement in efficiency. This study provides guidelines for engineers to improve compressor performance for an existing design by applying an optimum casing profile.