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Supplementary Data from Targeted Knockdown of SEPT9_v1 Inhibits Tumor Growth and Angiogenesis of Human Prostate Cancer Cells Concomitant with Disruption of Hypoxia-Inducible Factor-1 Pathway

GOAL The aim was to assess proactive specialized inflammatory bowel diseases (IBD) emergency department (ED) consultation and multidisciplinary IBD team (IBD-MDT) intervention on IBD-related patient outcomes after discharge. BACKGROUND Despite advances in patient care, IBD-related ED visits have increased and substantially contribute to the IBD burden. METHODS Consecutive patients with IBD (below 50 y) who visited the ED during November 2017 to April 2018 (intervention group) were compared with patients with IBD that visited the same ED during 2014 to 2017 (standard-care group). The primary outcomes were hospitalization and ED revisits at 30, 90, and 180 days. RESULTS The intervention group (45 patients, mean age 32.43±8.6 y, 57.8% male) and the standard-care group (237 patients) had comparable baseline characteristics, including age, sex, and IBD type, and similar rates of hospital admissions from the ED (46.7% vs. 38.8%, P=0.32). The intervention group more frequently underwent computed tomography (40% vs. 8%, P

A left ventricular assist device (LVAD) is a mechanical device that treats advanced heart failure. Patients coping with an LVAD need extensive instrumental and medical support, which is usually provided by the spouse. Therefore, it seems that dyadic coping strategies play a crucial role as either mitigators or hinderers of couples’ illness management in the context of LVADs. The aim of this research was to formulate a typology of dyadic coping strategies applied by these couples, as unfolded in their mutual and individual subjective experiences. The research was performed in collaboration with an LVAD implantation unit at a medium-sized hospital in Israel. Couples ( N = 17) participated in an in-depth dyadic interview using a semi-structured interview guide, and the data collected were analyzed using content analysis. Our findings suggest that couples coping with an LVAD develop strategies for handling fear, processing and accepting their illness narratives, adjusting their level of independence and intimacy, and utilizing humor. Moreover, our analysis showed that each couple utilized a unique mix of dyadic coping strategies. To the best of our knowledge, the current study is the first to explore the dyadic coping strategies of couples coping with an LVAD. Our results may constitute a base for developing dyadic intervention programs and clinical recommendations to improve the quality of life and relationships of patients and their spouses while coping with LVAD implementation.

In this study, we suggest combining the monitoring of actual examination time used with grades in order to assess examination time extensions in terms of access provision and expected outcome. Usin...

Security and intelligence agencies around the world invest considerable resources in preventing terrorist attacks, as these may cause strategic damage, national demoralization, infringement of sovereignty, and government instability. Recently, data-mining techniques have evolved to allow identification of patterns and associations in criminal data that were not apparent using traditional analysis. The aim of this paper is to illustrate how to use interpretable classification algorithms to identify subgroups (“patterns”) of terrorist incidents that share common characteristics and that result in mass fatalities. This approach can produce insights far beyond those of conventional macro-level studies that use hypothesis-testing and regression models. In addition to this methodological contribution, from a practical perspective, exploring the characteristics identified in the “patterns” can lead to prevention strategies, such as alteration of the physical or systemic environment. This is in line with situational crime prevention (SCP) theory. We apply our methodology to the Global Terrorism Database (GTD). We present three examples in which terror attacks that are described by a particular pattern (set of characteristics) resulted in a high probability of mass casualties, while attacks that differ in just one of these characteristics (i.e., month of attack, geographical area targeted, or type of attack) resulted in far fewer casualties. We propose exploration of the differentiating characteristic as a means of reducing the probability of mass-fatality terrorist incidents.

The pathophysiology of multiple sclerosis involves an autoimmune and a neurodegenerative mechanism. Central nervous system-infiltrating immune cells in multiple sclerosis also possess a neuroprotective activity through secretion of neurotrophins, such as brain-derived neurotrophic factor. Fingolimod was shown to slow the progression of disability and loss of brain volume. The objective of this study was to explore whether fingolimod induces secretion of neurotrophins by immune cells. Blood was drawn from 21 patients before the initiation of treatment with fingolimod and at 6 and 12 months of follow-up. The levels of the neurotrophic factors brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, β-nerve growth factor, neurotrophin-3, neurotrophin-4, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor were screened in the supernatants of separated T cells and monocyte cultures using a customized, multiplex enzyme-linked immunosorbent assay. Brain-derived neurotrophic factor levels were further validated by a specific enzyme-linked immunosorbent assay. Treatment with fingolimod significantly increased brain-derived neurotrophic factor secretion from T cells. A specific enzyme-linked immunosorbent assay confirmed these results in the supernatant of T cells after 6 and 12 months of therapy. T cells that reach the bloodstream of fingolimod-treated patients with multiple sclerosis may contribute to the neuroprotective effect of this therapy by increased secretion of brain-derived neurotrophic factor. This mechanism of action of fingolimod in patients with multiple sclerosis has not been previously reported.

The purpose of this study is to evaluate how learning disabilities (LDs), in combination with accommodations, affect the performance of a decision-tree to predict the stability of academic behaviou...

Connective tissue growth factor (CTGF/CCN2) is a proinflammatory and an oligodendrocyte-differentiating blocking agent. It is found in MS lesions, which raises the possibility of involvement in MS pathogenesis. We found that its CSF and serum levels were higher in RR-MS patients than in controls and for serum compared to PP and SP-MS. Immune cells of both RR-MS and controls secreted CTGF/CCN2, which was enhanced by CD3/CD28 stimulation or by LPS. Anti-CTGF treatment of mice with experimental autoimmune encephalitis ameliorated its clinical severity. CTGF/CCN2 may play a role in the immune pathogenesis of MS and in remyelination failure in early stages of MS.

Oligodendrocyte precursor cells (OPCs) are present in demyelinated lesions of multiple sclerosis (MS) patients. However, their differentiation into functional oligodendrocytes is insufficient, and most lesions evolve into nonfunctional astroglial scars. Blockade of bone morphogenetic protein (BMP) signaling induces differentiation of OPCs into myelin-producing oligodendrocytes. We studied the effect of specific blockade of BMP-2/4 signaling, by intravenous (IV) treatment with anti-BMP-2/4 neutralizing mAb in both the inflammatory model of relapsing experimental autoimmune encephalomyelitis (R-EAE) and the cuprizone-toxic model of demyelination in mice. Administration of anti-BMP-2/4 to R-EAE-induced mice, on day 9 post-immunization (p.i.), ameliorated R-EAE signs, diminished the expression of phospho-SMAD1/5/8, primarily within the astrocytic lineage, increased the numbers of de novo immature and mature oligodendrocytes, and reduced the numbers of newly generated astrocytes within the spinal cord as early as day 18 p.i. This effect was accompanied with elevated remyelination, manifested by increased density of remyelinating axons (0.8

The effect of the inflammatory response on regenerative processes in the brain is complex. This complexity is even greater when the cause of the tissue damage is an autoimmune response. Multiple sclerosis (MS) is an immune-mediated disease in which demyelination foci are formed in the central nervous system. The degree of repair through oligodendrocyte regeneration and remyelination is insufficient. Ephrins are membrane-bound ligands activating tyrosine kinase signaling proteins that are known to have an inhibitory effect on oligodendrocyte regeneration. In this study, we examined the expression of ephrins on immune cells of 43 patients with relapsing-remitting (RR) MS compared to 27 matched healthy controls (HC). We found an increased expression of ephrin-A2, -A3 and -B3, especially on T cell subpopulations. We also showed overexpression of ephrins on immune cells of patients with RR-MS that increases the forward signaling pathway and that expression of ephrins on immune cells has an inhibitory effect on the differentiation of oligodendrocyte precursor cells (OPCs) in vitro. Our study findings support the concept that the immune activity of T cells in patients with RR-MS has an inhibitory effect on the differentiation capacity of OPCs through the expression and forward signaling of ephrins.

Background: We aimed to identify subjects that harbor colorectal cancer and will not complete colonoscopy within six months following a positive fecal occult blood test (target population) by artificial intelligence (A.I.) based tools. Methods: We trained and validated a machine learning model based on a dataset of the Clalit Health Services. The entire population included 25,219 subjects aged 50 to 74 years with a positive FOBT result who participated in the screening program between 2011 and 2013. The target population included 202 patients (0.8% of the total cohort; 26.5% of all cancer cases). Multiple socioeconomic, administrative, and laboratory data were collected. The portion of the total population singled out by the model was termed as subjects needed to engage (SNE). Findings: Using two threshold levels the model reduced the number of SNE to 3.85% (of the entire validation cohort), identifying 25.8% of the target population [Positve Predictive Value Value (PPV) 5.1%, 95% Confidence Intrval (CI) 4.4-5.8; Negative Predictive Value (NPV) 99.4%, 95%CI 99.4-99.4; Area Under Receiver Operative Curve (AUROC) 0.74 95%CI 0.73-0.76] or reduced the number of SNE to 15.9%, identifying 55% of the target population (PPV 2.7%, 95%CI 2.4-3.0; NPV 99.5%, 95%CI 99.5-99.6; AUROC 0.74 95%CI 0.73-0.76). Interpretation: An AI-derived tool can successfully identify subjects with a positive FOBT that are at high risk for both harboring CRC and not completing colonoscopy within six months. Implementing this approach may improve FOBT-based CRC screening programs from the first day of a positive FOBT. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The CHS ethical committee authorized the study.

Demyelination, axonal loss and failure of tissue repair characterize MS lesions. Bone morphogenetic proteins (BMPs) signaling is associated with remyelination failure. Coco is one of the BMP antagonists. We found reduced Coco serum levels in relapsing-remitting MS (RR-MS) and primary progressive MS (PP-MS) patients compared to matched healthy controls (HC) and patients with rheumatoid arthritis. Exposure of P19 cells, in the presence of retinoic acid, BMP-2, or BMP-4 to Coco, at average sera level of MS patients failed to induce neuronal phenotype, in contrast to the average sera level of HC. Coco may be a player in the BMP dysregulation and the tissue repair failure in MS.

Currently machine operator interface is mainly focused on providing the operator with easy control over the production processes and easy access to related information. However, myriad of recent technological advances in variety of fields including AI, raise the question of what could be added to the operator-machine interaction capabilities and how. This article explores the possibilities to harness new capabilities in cognitive and behavioral knowledge as well as AI and “Industry 4.0” literature in order to outline the architectural framework and capabilities of future work-station‒operator interaction as a principal component of the human‒machine interaction in the “Industry 4.0” era. The proposed system is named “Workstation‒Operator Interaction 4.0” (WOI 4.0). The equipment’s capabilities allows an adaptive ongoing interaction that aims to improve operator performance, safety, well-being, and satisfaction, as well as production measures. The paper describes the main elements of the proposed WOI 4.0 architecture, and illustrates a case of smart machine‒operator interactions. The contributions, limitations, and implications of the proposed WOI 4.0 system in the “Industry 4.0” arena are discussed, and future research directions are presented.

Blockage of bone morphogenetic protein (BMP) signaling is required for differentiation of neurons and oligodendrocytes from neural stem cells (NSCs). Sera of untreated relapsing-remitting multiple sclerosis (RR-MS) patients expressed significantly higher levels of BMP-2 compared to sera of healthy controls. BMP-2 levels correlated with BMP-4 and -5 levels only in sera of untreated MS patients. Furthermore, sera of untreated patients inhibited the neuronal differentiation of RA-treated P19 cells, which was associated with induction of phospho-SMAD signaling pathway. These results suggest that BMP-2 sera levels may play a role in the failure of remyelination and neuro-regeneration in RR-MS.

// Maya Golan 1 , Nicola J. Mabjeesh 1 1 Prostate Cancer Research Laboratory, Department of Urology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Correspondence to: Nicola J. Mabjeesh, email: nicolam@tlvmc.gov.il Keywords: hypoxia-inducible factor 1α, septin 9, bimolecular fluorescence complementation, cancer, imaging Received: June 30, 2016 Accepted: March 15, 2017 Published: March 23, 2017 ABSTRACT Hypoxia-inducible factor 1 (HIF-1) is a major mediator of the hypoxic response involved in tumor progression. We had earlier described the interaction between septin 9 isoform 1 (SEPT9_i1) protein and the oxygen-regulated subunit, HIF-1α. SEPT9_i1 is a member of the conserved family of GTP-binding cytoskeleton septins. SEPT9_i1 stabilizes HIF-1α and facilitates its cytoplasmic-nuclear translocation. We utilized split yellow fluorescent protein (YFP) bimolecular fluorescence complementation (BiFC) methodology to monitor the interaction between HIF-1α and SEPT9_i1 in live cells. N-terminal (YN) and C-terminal (YC) split YFP chimeras with HIF-1α and SEPT9_i1 on both their amino and carboxyl termini were generated. HIF-1α and SEPT9_i1 chimeras were expressed in cancer cells and screened for functional complementation. SEPT9_i1-YN and YC-HIF-1α formed a long-lived highly stable complex upon interaction. The BiFC signal was increased in the presence of hypoxia-mimicking agents. In contrast, YC-ΔHLH-HIF-1α chimera, which lacked the helix-loop-helix domain that is essential for the interaction with SEPT9_i1 as well as the expression of SEPT9_i1 252-379 amino acids fragment required for the interaction with HIF-1α, significantly reduced the BiFC signal. The signal was also reduced when cells were treated with 17- N -allylamino-17-demethoxygeldanamycin, an HSP90 inhibitor that inhibits HIF-1α. It was increased with fourchlorfenuron, a small molecule that increases the interaction between HIF-1α and SEPT9_i1. These results reconfirmed the interaction between HIF-1α and SEPT9_i1 that was imaged in live cells. This BiFC system represents a novel approach for studying the real-time interaction between these two proteins and will allow high-throughput drug screening to identity compounds that disrupt this interaction.

The importance of sharing mental health issues with supervisors is well established. However, the decision to disclose such intimate information is complex and is influenced by many intrinsic and extrinsic variables. The purpose of this study is to use machine learning algorithms to develop a tool that supervisors may use to enhance disclosure of mental health issues among their employees. Several interpretable machine learning algorithms are established based on a Kaggle dataset of more than 1,400 participants that measures attitudes towards mental health and prevalence of mental health disorders in the tech workplace. The C4.5 algorithm is chosen as the best classifier of willingness to disclose a mental health disorder to supervisors, based on a variety of classification performance measures. Tailored intervention programs are applied and are shown to have the potential to increase the probability of disclosure by between 20% and 60%.

The substantial availability of hypoxia-inducible factor 1 (HIF-1) for pathophysiological states, such as malignancies and ischemia, is primarily regulated post-translationally through the ubiquitin proteolytic system. The balance between degradation and stabilization of HIF-1α protein is determined by specific E3 ligases. In our search for new E3 ligases that might affect HIF-1α protein expression, we studied the effects of beta-transducin repeat-containing protein (β-TrCP) on the hypoxic pathway in cancer cells. β-TrCP is overexpressed in many tumors and regulates various cellular processes through mediating the degradation of important targets. Unexpectedly, we found that β-TrCP overexpression increases HIF-1α protein expression level as well as HIF-1 transcriptional activity by stabilizing HIF-1α protein and preventing its ubiquitination and proteasomal degradation in prostate cancer cells. By using a proteomic approach, we succeeded in demonstrating that β-TrCP interferes with the association between HIF-1α and HSP70/CHIP, a HIF-1α established E3 ligase complex. Whereas the E3 ligase activity of β-TrCP is well known, antagonizing another E3 ligase is a new mechanism of action of this important E3. We suggest that destroying or suppressing β-TrCP and thereby interrupting the HIF-1 pathway, could be valuable antitumor therapy.

Using a grounded theory approach and real-time data capturing the expressions and behaviors of help givers and recipients in the course of their interactions at work, we generated a typology of interactive and episodic helping behaviors (both help giving and receiving) and applied it to explore if, when, and how the behavioral configurations of the two dyad partners changed from one exchange episode to the next. Our findings suggest that certain configurations of helping behavior often shifted in a rather predictable manner over the course of the helping exchange in response to the behavior of the dyad partner, whereas other configurations were “static,” tending to be repeated by dyad partners once they first appeared. By examining help giving and receiving as a pattern in a stream of dynamic, dyadic, and cross-episodic behaviors, and more importantly, developing a typology allowing scholars to differentiate between different types of dyadic patterns, our study provides important insights into the varying...

This paper suggests a new technique to facilitate consistent transition between planning and production stages of small lots of complex products (in quantities that do not justify full automation). Despite the usage of modern approaches such as design for assembly and design for manufacturing the typical product planning ends up before production planning begins, instead of having a unified seamless planning process. This paper presents a new three stage technique to fill the gap between product planning and production. The paper shows how to generate a rigorous production plan by: (1) extending the Bill-of-Materials to include additional required information, (2) constructing an assembly ‘method prototype’ and (3) using the ‘method prototype’ to calculate time standards for executing the assembly. A case study illustrates the proposed technique.

Service dominant logic (S-D logic) is a concept that has been criticized for not adopting an interactive approach to some of its fundamental premises (Vargo & Lusch, 2016). Recently, S-D logic has been modified to reflect interactive dimensions and, in particular, the construct of value co-creation (Vargo & Lusch, 2016). These modifications suggest that the service-provider?customer dynamics cannot be fully understood without utilizing interaction terminology and research methodology that afford an opportunity to study the domain from a dyadic point of view. In this chapter, Symbolic Interactionism (SI) and Social Exchange Theory (SET) perspectives are espoused in order to explore the construct of value co-creation as a dynamic qualitative process or a stable quantitative outcome, respectively, the challenges, advantages, and limitations of applying these perspectives are discussed.

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor in the hypoxic response pathway. We recently identified a novel interaction between HIF-1α and the mammalian septin family member, septin 9 protein, isoform 1 (SEPT9_i1), a protein product of septin 9 transcript variant 1 (SEPT9_v1). Septins are a highly conserved family of GTP-binding cytoskeletal proteins that are implicated in multiple cellular functions, including oncogenesis. SEPT9_i1 binds and stabilizes HIF-1α protein and stimulates HIF-1 transcriptional activity by preventing its RACK1-mediated ubiquitination and degradation. SEPT9_i1–HIF-1 activation promotes tumor growth and angiogenesis. The effect of SEPT9_v1 silencing in prostate cancer cells was studied. SEPT9_v1 stable knockdown was generated in PC-3 cells using a specific shRNA. SEPT9_v1 silencing reduced HIF-1α protein expression and inhibited HIF-1 transcriptional activity. SEPT9_v1 knockdown affected cell morphology, deregulated cell cycle, and decreased migration. The antiproliferative effect of shSEPT9_v1 was abolished in HIF-1α knockout colon cancer cells. In vivo, SEPT9_i1 depletion reduced HIF-1α protein expression, cellular proliferation, tumor growth, and angiogenesis. These results provide new insights and validation for applying SEPT9_v1 as a potential target for antitumor therapy by interrupting the HIF-1 pathway. Mol Cancer Res; 8(5); 643–52. ©2010 AACR.

Member Assistance Programs (MAPs) are peer-based Employee Assistance Programs (EAPs) that originated in the United States and have been transferred to other countries. The current case study aims at exploring the cross-cultural transferability of MAPs by comparing the first MAP established in Israel with the prototypical American program. The observed differences are explained on the basis of cross-cultural organizational theory. In addition, empirically-testable hypotheses regarding the cross-cultural variations of MAPs are developed. The implications for EAP and MAP research and practice are discussed.

Forchlorfenuron (FCF) is a synthetic plant cytokinin that has been shown to alter yeast and mammalian septin organization. Septins are a highly conserved family of GTP-binding cytoskeletal proteins. Mammalian septins are involved in diverse cellular processes including tumorigenesis. We have been studying the interaction between septin 9 isoform 1 (SEPT9_i1) and hypoxia inducible factor-1α (HIF-1α), the oxygen regulated subunit of HIF-1. HIF-1 is a key transcription factor in the hypoxic responses pathway, and its activation has been observed in carcinogenesis and numerous cancers. SEPT9_i1/HIF-1α interaction plays an important role in upregulation of HIF-1 transcriptional activity by preventing HIF-1α’s ubiquitination and degradation leading to increased tumor growth and angiogenesis. We tested the hypothesis whether FCF affects SEPT9_i1 filamentous structures and consequently HIF-1 pathway in cancer cells. We showed that FCF suppresses tumorigenic properties, including proliferation, migration and transformation, in prostate cancer cells. FCF did not alter SEPT9_i1 steady state protein expression levels but it affected its filamentous structures and subcellular localization. FCF induced degradation of HIF-1α protein in a dose- and time-dependent manner. This inhibition was also shown in other common cancer types tested. Rapid degradation of HIF-1α protein levels was accompanied by respective inhibition in HIF-1α transcriptional activity. Moreover, HIF-1α protein half-life was markedly decreased in the presence of FCF compared with that in the absence of FCF. The FCF-induced degradation of HIF-1α was mediated in a significant part via the proteasome. To the best of our knowledge, this is the first demonstration of specific manipulation of septin filaments by pharmacological means having downstream inhibitory effects on the HIF-1 pathway.

This paper describes a new technique that utilizes the typical documentation of complex products to automate the development of the assembly method to be used for production. The technique describes a structured process that gets (as its input) the standard bill of materials (BOM) with specified additional data, and develops a detailed sequential method of assembly operation as its output. This sequential assembly method could be then further automated. The paper also discusses the gap between typical assembly instructions and structured sequential specifications necessary for automating the planning of the assembly method.

Hypoxia-inducible factor 1α (HIF-1α) gene polymorphisms have been investigated for a possible role in mediating genetic predisposition to cancer. Our previous data show that men homozygous to C1772T polymorphism had 4-fold risk to develop prostate cancer. Therefore, we studied the effects of C1772T polymorphism on HIF-1α expression. HIF-1α mRNA expression levels were significantly higher in peripheral blood leukocytes of prostate cancer patients with the TT genotype compared with the CC genotype. Expression of C1772T HIF-1α in HIF-1α knockout cancer cells showed higher expression levels and stabilization of HIF-1α mRNA compared with the wild-type. Mutated HIF-1α protein half-life was similar to that of the wild-type. Hence, our data provide evidence that C1772T polymorphism causes activation of HIF-1α as a gain-of-function mechanism driven by stabilization of HIF-1α mRNA. These findings may also explain the increased risk of men homozygous to this mutation to develop prostate cancer.

Parathyroid hormone-related protein (PTHrP) expressed by human cancer cells enhances tumor cell growth and metastasis in vivo and it is considered as the major factor responsible for humoral hypercalcemia of malignancy. Hypoxia is a widespread feature of most solid tumors. Here, we studied the effects of hypoxia on PTHrP expression. We found that PTHrP is transcriptionally induced by prolonged (48 h) hypoxia in multiple human cancer and endothelial cell lines. Pharmacological up or downregulation of hypoxia-inducible factor (HIF) resulted in induction or reduction of PTHrP levels, respectively, implying that PTHrP hypoxic induction is mediated by HIF pathway. Analysis of PTHrP promoter revealed that both HIF-1α and HIF-2α subunits bind to specific hypoxia-responsive elements (HRE) within the P2 promoter of PTHrP. However, only HIF-2α can drive direct transcriptional activation, which can be abolished by mutation in the specific HRE. To the best of our knowledge, these results provide for the first time evidence that PTHrP is regulated by hypoxia in cancer and endothelial cells through the HIF-2 pathway. We suggest that HIF-2 induced by intratumoral hypoxia or by other genetic alterations may contribute to the pathogenesis of hypercalcemia of malignancy and cancer aggressiveness by stimulation of PTHrP expression.

Hypoxia is a common feature of many solid tumors that promotes tumor progression and leads to radiation and chemotherapy resistance. Hypoxia-inducible factor 1 (HIF-1), as one of the major mediators of the hypoxic response, has been shown to activate hypoxia-responsive genes, which are involved in multiple aspects of tumorigenesis and cancer progression. Previously, we have described an interaction between septin 9 isoform 1 (SEPT9_i1) protein and HIF-1α, the oxygen regulated subunit of HIF-1. SEPT9_i1 is a member of the conserved family of septins, which are GTP-binding proteins that form cytoskeleton-like filaments essential for many functions in eukaryotic organisms including neoplasia. The interaction of SEPT9_i1 with HIF-1α increases protein stability and HIF-1 transcriptional activity in vitro and promotes proliferation, tumor growth and angiogenesis in vivo. Recent data indicated that SEPT9_i1 was also involved in the trafficking of cytoplasmic HIF-1α into the nucleus by direct interaction to the nuclear transporter importin-α. Herein, we utilized split YFP bimolecular fluorescence complementation (BiFC) methodology in order to monitor HIF-1α/SEPT9_i1 interactions in vivo. First, we generated split YFP protein chimeras fused to HIF-1α and to SEPT9_i1 on both their amino and carboxyl termini. Different pairs of HIF-1α and SEPT9_i1 chimeras were tested to functional complementation of the split YFP fragments using transient transfection in HEK293 cells. The complemented proteins capable of fluorescence were identified as SEPT9_i1-YN (the amino terminus of YFP fused to the carboxyl terminal of SEPT9_i1) and YC-HIF-1α (the carboxyl terminus of YFP fused to the N-terminal of HIF-1α). This pair was selected for further studies in PC-3 human prostate cancer cells. YFP complementation fluorescence derived from these chimeras was increased in the presence of hypoxia mimicking agents, such as CoCl2 and the iron chelators deferoxamine (DFO) and dibenzoylmethane (DBM). The chimera, YCΔHLH lacking the HLH domain that is essential for the interaction with SEPT9_i1 gave a significant reduction in YFP complementation fluorescence. Furthermore, expression of SEPT9_i1 252-379aa fragment, the domain essential for the interaction with HIF-1α, abolished almost completely the YFP complementation fluorescence. These results reconfirm our previous studies on HIF-1α/SEPT9_i1 interactions and make this system attractive for identifying new compounds capable of disrupting this complex in order to inhibit tumor growth and angiogenesis. Citation Format: Maya Golan, Nicola J. Mabjeesh. In vivo molecular imaging of HIF-1α and septin 9 interaction by bimolecular fluorescence complementation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5112. doi:10.1158/1538-7445.AM2015-5112

On the 17th of August 1999, an earthquake of 7.4 magnitude on the Richter Scale struck the Marmara region in Turkey causing a massive casualties event with an estimated 2680 deaths and 5300 injuries just at the city of Adapazari alone. A field hospital was set up by the Israel Defense Forces at Adapazari in order to provide temporary medical services until regular medical forces recovered. The aim of the paper is to overview the requirements of the nursing staff at a field hospital based on our experience and analysis of the nursing activity at the field hospital at Adapazari. The methods implemented include interviewing all nurses and many of the doctors who took part in the field hospital as well as a review of medical literature about disasters. We found an inverted nurse:phycisian ratio of 1:1.77, as opposed to a 2.5–3:1 ratio in regular civilian hospitals. The nurses in our field hospital had to work longer and more intensive shifts than in a regular hospital. They had to overcome language barriers and cultural differences, and faced difficult hygiene conditions. Our overview analysis of results brought up several recommendations. Firstly, although it is not possible to predict the number and types of casualties, it is necessary to provide an adequate number of nurses (1–1.5:1 nurse:physician ratio). Furthermore, the nurses should be specialized and rotated as needed. Secondly, the language and cultural barriers should not be undermined despite the abundance of translators. Finally, the hygiene status in a field hospital requires management by nurses with active participation of all members.