According to the ejection fraction, patients with heart failure may be divided into two different groups: heart failure with preserved or reduced ejection fraction. In recent years, accumulating studies showed that increased mortality and morbidity rates of these two groups are nearly equal. More importantly, despite decline in mortality after treatment in regard to current guideline in patients with heart failure with reduced ejection fraction, there are still no trials resulting in improved outcome in patients with heart failure with preserved ejection fraction so far. Thus, novel pathophysiological mechanisms are under development, and other new viewpoints, such as multiple comorbidities resulting in increased non-cardiac deaths in patients with heart failure and preserved ejection fraction, were presented recently. In this review, we will focus on the tested as well as the promising therapeutic options that are currently studied in patients with heart failure with preserved ejection fraction, along with a brief discussion of pathophysiological mechanisms and diagnostic options that are helpful to increase our understanding of novel therapeutic strategies.


Background:
 Endocrine dysfunction, including thyroid function, has been known to affect cerebral vascular dysfunction. Hypothyroidism has been shown to cause mucopolysaccharide deposition which has been associated with the weakening of blood vessel walls and aneurysm formation in some case reports. However, the connection between hypothyroidism and cerebral aneurysm has not been well studied. We hypothesized that hypothyroidism maybe associated with occurrence of cerebral aneurysms.

 Methods:
 We performed a retrospective case-control study of consecutive patients receiving cerebral angiography at our tertiary-care academic medical center. Inclusion criteria included undergoing 3-vessel angiography. Exclusion criteria included any ruptured aneurysm or previous intracranial hemorrhage. Medical history of hypothyroidism was noted along with all other risk factors. The control group of patients did not have any intra-cranial abnormality on angiography. Patients with cerebral aneurysm were matched with controls for known risk factors of cerebral aneurysm, including: age, hypertension, and smoking history. Cases were further subdivided base on gender given females are known to have higher incidence of hypothyroidism.

 Results:
 From 2008 through 2013, 82 female and 59 male patients with aneurysms were identified for this study and were matched with equal numbers of controls. Among women, hypothyroidism was present in 20.7% (17/82) among patients with cerebral aneurysms vs. in only 6.1% (5/82) among matched controls: odds ratio (OR) 4.03 (95% CI 1.41-11.51, p=0.01). Among men, 8.5% (5/59) cases and 0/59 controls had hypothyroidism, showing no significant association, with an odds ratio of 12.01 (95% CI 0.65-222.3, p=0.095).

 Conclusion:
 We found a significant association of history of hypothyroidism with cerebral aneurysm in women in our patient cohort. Given the potential pathophysiologic connection between hypothyroidism and vascular wall dysfunction, this should be explored further.


Hepatocytes incubated at a pO2 of 0 mm Hg (N2/CO2, 95%/5%) loose their intracellular ATP content and their ability to synthesize RNA and proteins. Protein synthesis is virtually inhibited from the beginning of the incubation, while ATP content is gradually lost, thus suggesting a primary response of the cell to the absence of O2 rather than to ATP depletion. Such an early decrease of protein synthesis (as estimated as the incorporation of [14C]Leu into cell proteins) is unlikely the result of inhibition of amino acids uptake, enhanced protein degradation, or decreased RNA synthesis. Reoxygenation of such previously hypoxic cells with O2/CO2 at 95%/5% (pO2 of 700 mm Hg), leads to the recovery of both ATP and protein synthesis, even better the hypoxic period is not longer than 30 min. In hepatocytes incubated for 30 min under a pO2 of 700, 80, or 50 mm Hg, cell survival and ADP content are almost identical. Incorporation of radiolabelled leucine is linear in cells incubated under 700 mm Hg O2, but it rather stops at a pO2 of 80 or 50 mm Hg. The time course of both ATP and GTP content behaves in a similar way: it is fairly constant at a pO2 of 700 mm Hg, but a depletion is initiated after 20 min of incubation at a pO2 of 50 or 80 mm Hg. Finally, incubation of hepatocytes either at 700 or 0 mm Hg O2, in the presence of fructose (10 mM), shows that ATP content is maintained at the same level whatever the pO2 level. AMP content is increased only in cells incubated at 0 mm Hg O2 in the absence of fructose. Incorporation of radiolabelled leucine is stopped in such hypoxic cells incubated or not in the presence of fructose. From these results it appears that the presence or the absence of O2 might represent a turn on/off signal to which hepatocytes respond immediately by important metabolic changes like the inhibition of protein synthesis.


Claoxylon and Micrococca are the only Euphorbiaceae genera that have rough dried leaves (fresh ones are smooth) because of protruding styloid (needle-like) crystals more or less perpendicular to the leaf surface, which perforate the epidermis and cuticle. A broad leaf anatomical study of the subtribes Claoxylinae, the monogeneric Lobaniliinae, and Mercurialis of the Mercurialinae (95 of a possible 235 species in all six genera) showed that styloids are present in Claoxylon, Discoclaoxylon, Erythrococca, Lobanilia, and Micrococca, and lacking in Claoxylopsis and Mercurialis. Contrary to Claoxylon, the dried leaves of Discoclaoxylon, Erythrococca, Lobanilia, and Micrococca are not rough, because the styloids do not perforate the epidermis during drying and therefore herbarium leaves generally remain smooth. The presence of styloids supports a clade in a recent molecular phylogenetic study that unites subtribes Claoxylinae and Lobaniliinae as Claoxylinae s.l. Mercurialis (no styloids) is sister to all other taxa (with styloids) in the monophyletic Claoxylinae s.l. The styloids form a synapomorphy for a monophyletic part of the Claoxylinae (Claoxylon, Discoclaoxylon, Erythrococca, Lobanilia, and Micrococca). Other leaf anatomical notes are provided, together with an overview of the occurrence of styloids, stomata, and druse crystals for most species in the Claoxylinae. The indumentum ranges from (virtually) absent to a sparse or dense tomentum of straight and thick- or thin-walled unicellular hairs (most common), curly hairs, or two-armed hairs ('Malpighiaceous hairs'). The last two hair types probably form diagnostic characters for species groups within the genus Claoxylon


Vessels present in the superior mediastinum are closely related and widely variable. Knowledge of their variation is necessary for cardiothoracic radiology and surgery. We present a case where left vertebral artery originated from the arch of the aorta and left subclavian artery had a narrowing at a site where a vein from the posterior thoracic wall had crossed it. This vein was found to be the accessory azygos vein which had communicated below with hemiazygos vein. The embryological and clinical implications of such a combination of vascular anomalies, probable cause of the narrowing of the subclavian artery are discussed.


This paper studies a joint optimization problem of sub-carrier assignment and power allocation in orthogonal frequency division multiple access (OFDMA) wireless networks. A major challenge in solving the optimization problem is non-convexity caused by the combinatorial nature of sub-carrier assignment problem and/or non-convex objective functions. To address the combinatorial complexity, we formulate the resource allocation problem as an optimization problem with continuous variables. We propose a novel approach based on a penalty function method and an interior point method (PM/IPM) to solve the problem. In specific, using a two-step implementation, the penalty method is applied first to convert the non-convex feasible region to a convex one. Then, the interior point method is deployed to solve the problem which is non-convex only in the objective function. To evaluate the performance of PM/IPM, we apply a genetic algorithm (GA) that achieves near optimal solutions of the problem by iterative searching.


Alternate measurement and data analysis procedures are discussed and compared for the application of reflective Nomarski differential interference contrast microscopy for the determination of surface slopes. The discussion includes the interpretation of a previously reported iterative procedure using the results of a detailed optical model and the presentation of a new procedure based on measured image intensity extrema. Surface slope determinations from these procedures are presented and compared with results from a previously reported curve fit analysis of image intensity data. The accuracy and advantages of the different procedures are discussed.


At the end of World War I, British medical officers noted that soldiers infected with malaria were more likely to die during the 1918 influenza pandemic than those without malaria. This synergistic mortality appeared to be specific to Plasmodium falciparum and has not been generally noted since 1920. A possible explanation is that a malaria-induced procoagulant state enhanced the activation of influenza virus to increase inflammation and subsequent severe clinical outcomes. Falciparum proteins bind and likely inhibit antithrombin 3 and other factors. Pathogens interact in ways that may inform pathophysiology studies of remote epidemics.


: This paper analyses the linguistic concept of justice ( pravda ) in Croatian according to the methodology of the Lublin Ethnolinguistic School. Recent monolingual dictionaries of Croatian typically list only one meaning of the lexeme pravda and lexicographic definitions focus on the social aspect of the term. The paper also analyses the relationship of this lexeme with others (synonyms, antonyms) and lists phrases and sayings related to pravda . An analysis of a corpus of Croatian texts (of the last 150 years) and the results of a survey (100 respondents) point to weaknesses in lexicographic definitions of the lexeme pravda , as well as to the complexity of the concept of pravda in Croatian. According to the results of the survey, the most important characteristics of pravda are equality and acting on merit, followed by the ethical aspect (respect, morality, truth) and the psychological aspect (satisfaction/happiness, freedom, conscience).


The mechanism of capping of cell surface receptors has been examined by a double fluorescence staining procedure that permitted simultaneous observations of the distribution of a surface-bound ligand together with intracellular actin or myosin. At an early stage in the capping of the T-25 antigen or the H2 histocompatibility antigens on mouse splenic T lymphocytes, or of concanavalin A receptors on HeLa cells, when the specific receptors in question were collected into patches that were distributed over the entire cell surface, the intracellular membrane-associated actin or myosin was also accumulated into patches that were located directly under the receptor patches. These and other results have led us to propose a general molecular mechanism for the process of capping, in which actin and myosin are directly involved. It is suggested that membrane-associated actin is directly or indirectly bound to an integral protein or class of proteins, X, in the plasma membranes of eukaryotic cells. When any receptor in the membrane is aggregated by an external multivalent ligand, the aggregate binds effectively to X, whereas unaggregated receptors do not bind to X. The receptor aggregates, linked to actin (and myosin) through X, are then actively collected into a cap by an analogue of the actin--myosin sliding filament mechanism of muscle contraction.


Labelling a plant as "weed" may seem like a simple process, but in actuality defining exactly what a weed is can be difficult. Is it possible to create a Canadian definition of "weeds?" Declaring a plant to be a weed imposes a belief or label on it, and these beliefs and labels are provided to us by our different definitions of nature. The definition of "weeds" is a product of a social construction of nature. The idea of weeds is also an anthropocentric one, as humans decide which plants should belong in nature. In Canada and the Americas weeds also have a deep historical context in their definition. European colonizers of the Americas brought with them new plant species, as well as new ideas and definitions of nature. These new meanings separated humankind from nature, and differed from Aboriginal perspectives that saw humans as living in harmony with nature. Overall, a strictly Canadian definition of weeds was not found. Defining weeds is a process left to the individual instead of the nation. Defining what a weed is depends on each individuals' own definitions and constructions of nature, and what is perceived to belong in it.


It is a promising treatment strategy to use a nanoparticlebased drug delivery system for cancer patients, which can simultaneously deliver multiple drugs or genes in combination with therapy to induce synergistic effects and suppress drug resistance to the tumor. In this study, cationic nanostructured lipid carriers (cNLC) for coloading anionic smallinterfering RNAs (siRNA) and chemotherapeutic docetaxel (DTX) were prepared from different cationic lipids based on particle distribution and loading efficiency. In order to increase the cNLC's positive targeting capacity, a novel peptide SP94 was bound to the surface of cNLC (SP94cNLC). The cNLC showed good efficiency in loading siRNA and DTX. The SP94cNLC revealed a better cytotoxicity compared with cNLC and Taxotere ® , indicating that SP94 could successfully enhance the internalization capacity of nanoparticles to the liver cancer cells. This new type of cNLC is a potential vehicle when using in codelivery of chemotherapeutics and siRNAs. The curcumin (CUR)/DTX codelivery NLC could load both CUR and DTX in high efficiency and showed a sensibilization to DTX chemotherapy. The sensibilization was more obvious when it was used in the aggressive and resistant cancer cells. This CUR/DTX codelivery system had good potential in treating cancer cells when chemotherapy drug showed little effect alone.


Soil macroproperties, such as bulk density, porosity, water conductivity, and aeration, have been utilized in order to evaluate soil structure effects on crop yields. It has been suggested that many of the limitations to crop growth can be explained by the physical properties of the aggregates. To explore some aspects of this, a method to simulate soil aggregates of different sizes and densities was developed and tested. A Collamer silt loam soil (fine-silty, mixed, mesic Glossoboric Hapludalf) was dried, crushed, sieved, and compressed to different densities (1.4, 1.6, and 1.8 Mg m -3 ). The resulting 25- and 50-mm-thick cylindrical soil slices were cut to two different cubical sizes (25- and 50-mm sides). Cylinders with continuous horizontal and vertical macropores were assembled from these artificial aggregates to make six different treatment combinations of aggregate size and density. Corn (Zea mays L.) seedlings were transplanted into the cylinders and grown in a growth chamber for 27 d. Results show that high aggregate density limits crop growth and that, at intermediate densities, aggregate size assumes more significance as a limiting factor.


Bilateral frontal lobectomy in man, with long survival, has been performed only once. The patient, A, has been the subject of previous reports, 1 the last having been made in 1936. The purpose of this paper is to report on A's status to date. He was a stockbroker, born in 1889. Both frontal lobes were removed in 1930. PHYSICAL STATUS A's physical status is exactly what it was at the time of the last report. Neurologic examination, when performed on April 1, 1938, gave normal results except that the right achilles jerk was slightly less active than any of the other tendon reflexes and the left cremasteric reflex was absent. It is possible for the first time to report on one of the plantar reflexes, examination of which A did not permit before. In the present examination he allowed the right plantar reflex to be tested; it was normal. A's


Abstract Monoclonal antibodies (mAbs) were produced to human haptoglobin by immunising with fecal extracts from patients with colon cancer. An enzyme-linked immunosorbent assay was developed with one of the mAbs (FE14.1), and its ability to diagnose colorectal carcinoma evaluated. Patients with colorectal cancer were positive (43/46 = 93.5%) compared to normal individuals (4/211 = 1.9%). The assay has a specificity 93.5% and sensitivity 98.1% and has several advantages over current fecal occult blood tests. The test is potentially useful for bowel cancer diagnosis and to quantitate the level of haptoglobin in other body fluids such as urine and in effusions.


INTRODUCTION
The nose is the most common area where malignant skin tumors occur. Repair with a flap after tumor excision provides esthetically and functionally acceptable results. In this study, we aimed to present the use of an omega (Ω) advancement flap, which can be applied in all anatomic regions of the nose, in 2 cm or smaller defects.

METHODS
Between 2015 and 2017, 18 patients underwent repair with omega (Ω) advancement flap in the nose after tumor removal. The pathology of 17 patients was basal cell carcinoma, and keratoacanthoma in 1 patient. The average defect diameter was 1.6 × 1.56 cm. The defects were in the nasal tip, nasal wing, lateral nasal wall, and supratip region. After tumors were excised from the safe margin, and were repaired using an omega advancement flap in the same session.

RESULTS
No flap necrosis, dehiscence, or infection was observed in the early postoperative period. Three patients developed hematoma under the flap, which was drained. No tumor recurrence was observed during the postoperative follow-up period. The results were satisfactory in all patients.

CONCLUSION
The omega advancement flap is a safe procedure that can be easily applied in the same session for the repair of small-to-medium-sized nasal defects.


Immune disorders such as allergy and autoimmunity are becoming increasingly common in developed
countries. Self-reactive T cells exist in both healthy and autoimmune individuals. It is generally
understood that hyperimmune disorders are caused by insufficient regulation, namely loss of activity of
regulatory T cells. Whilst regulatory T cells exist naturally it is also possible to induce them both in
vitro and in vivo. Immunotherapeutic techniques aim to provide noninflammatory exposure of antigen
to the immune system with the aim of inducing antigen-specific regulatory T cells.
Interleukin-10 (IL-10) is a cytokine with well known immunosuppressive qualities. It inhibits both the
migration and the antigen-presenting ability of dendritic cells. It also has direct effects on T cells.
Indeed, IL-10-secreting TR1 regulatory T cells were identified almost 15 years ago; their in vitro
generation being dependent on exposure to IL-10.
Particle-mediated DNA delivery (PMDD) is a promising method of immunisation and is especially
suited to vaccines intended to have greater control over the response they induce. One of the main
reasons for this is the possibility of including genes encoding immunomodulatory molecules alongside
the antigen gene.
This study utilises a mouse model involving the adoptive transfer of TCR-transgenic CD4+ T cells and
establishes the response of these cells to PMDD immunisation. The model was then used to examine
the effect of coadministration of the IL-10 gene. Its inclusion in the vaccine suppressed the response to
antigen. This effect was maximal when the IL-10 gene was expressed in the same cell as the antigen
gene. Using sequential immunisations the model was extended in order to study long-term effects,
namely tolerance and the induction of regulatory T cells. Finally a mouse model of allergic asthma was
used to examine any tolerogenic/therapeutic effects of the antigen-IL-10 vaccine. No significant longterm
tolerance to antigen was identified.
These results demonstrate that whilst the presence of IL-10 clearly inhibits the T cell response to
antigen it does not necessarily confer tolerogenic properties on these cells. This brings into question
whether IL-10 in the periphery, supplied, for example, by TR1 cells, generates fresh regulatory T cells
or merely inhibits the response to a particular antigenic challenge.


Disc based video recorders for consumers bring the possibility of virtual editing, that is, editing without making a copy of the underlying AN data. We propose a solution to support frame-accurate virtual editing that involves generating a new segment of MPEG-2 multiplex, called a bridge sequence. Within the bridge sequence, some video is re-encoded and remultiplexed to ensure that the edited sequence can be played back seamlessly. The bridge sequence is stored on disc separately from the original sequences, which remain unchanged. BRIDGE-SEQUENCE EDITING


This article develops a critique of academic globalization theory from the viewpoint of media and communications. First, it discusses the overall importance of media and communications for the core argument of globalization theory, namely that the contemporary period has witnessed a dramatic shift in the spatio-temporal constitution of society. This is followed by a reconstruction and critique of such a line of reasoning in the work of two notable globalization theorists, Manuel Castells and Arjun Appadurai. It is argued that their positions are founded on an overtly mediacentric and unhistorical treatment of globalization that lacks a critical materialist analysis of how the global media sphere has developed in the recent decades. It is further argued that such positions can be understood in the context of the rise of neoliberalism that overlaps with the development of globalization theory.


While Treg exhibit an anergic phenotype in vitro, Treg proliferate in vivo at a rate similar to memory phenotype (MP; defined as CD44hi, CD62Llo) CD4+ T cells. In short-term BrdU labeling experiments, both populations uptake the label at a rate of 6% to 10% of cells in a 24-hour period. However, MP T cells are made up of multiple cell populations that proliferate at different rates and short-term labeling experiments only label the rapidly dividing population. To address whether Treg may also consist of multiple populations of cells dividing at different rates, we conducted long-term labeling experiments by providing BrdU in the drinking water. Adult thymectomized mice were used to control for new T cell development. In mice labeled for 20 days, only ~60% of the Treg were BrdU positive suggesting that a significant population of Treg is non-proliferative. BrdU incorporation was positively correlated with the level of CD44 expression on Treg and nondividing Treg uniquely expressed the cell surface marker Ly-6C. Ly-6C positivity represented a stable phenotype of Treg, as sorted Ly-6C negative and positive Treg retained their respective Ly-6C expression following adoptive transfer into a naïve host. These findings suggest that Treg are made up of rapidly dividing and quiescent subpopulations. The functional significance of these distinct populations is being investigated.


Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid‐based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates. Freeze‐drying is used to seamlessly integrate the luminal filler into the conduit, creating a longitudinally aligned pore microarchitecture. The luminal stiffness is modulated to support Schwann cells, with laminin incorporation further enhancing bioactivity by improving cell attachment and metabolic activity. Additionally, this biphasic NGC is shown to support neurogenesis and gliogenesis of neural progenitor cells and axonal outgrowth from dorsal root ganglia. These findings highlight the paradigm that a successful NGC requires the concerted optimization of both a mechanical support phase capable of bridging a nerve defect and a neuroconductive phase with an architecture capable of supporting both Schwann cells and neurons in order to achieve functional regenerative outcome.


1-D nanowires are one of the most promising next-generation lithography technologies for 7 nm process node and beyond. The 1-D nanowire process first constructs a 1-D nanoarray through template synthesis followed by line-end cutting with additional cut masks. To achieve better yield and manufacturability, the cut patterns shall satisfy specified restricted design rules, and thus it is desirable to develop a novel routing methodology to better address the challenges arising from cut patterns. In this paper, we propose the first nanowire-aware routing system, considering high cut-mask complexity based on a two-pass, bottom-up multilevel routing framework. Experimental results show that our nanowire-aware router can effectively and efficiently reduce cut numbers, cut spacing violations, and line-end extension length.


INTRODUCTION
KRAS mutations in colon carcinomas are associated with lack of response to anti-EGFR monoclonal antibody treatment. Therefore, patients must undergo genetic testing to be eligible for treatment. Several methods for KRAS mutation analysis exist, but many are not sensitive enough to detect a mutation in samples with low fraction of malignant cells. In the present study, we developed a KRAS mutations detection method that is both simple and sensitive.

METHODS
Using a locked nucleic acid (LNA) containing oligonucleotide, we developed a PCR clamping method that preferentially amplifies the mutated over wild type KRAS. We evaluated the sensitivity of this method using serial dilutions of plasmids containing wild-type and mutated KRAS fragments. Additionally, KRAS mutation status was evaluated on 60 archived tissue samples of colon carcinoma, and compared to direct sequencing and high resolution melting (HRM) methods.

RESULTS
The PCR clamping method could detect as little as 1% mutated DNA in the sample analyzed. Of the 29 KRAS mutations identified by the PCR clamping method, only 23 (79%) were identified by standard direct sequencing. The results of PCR clamping correlated with HRM results.

CONCLUSIONS
LNA based PCR clamping method is a simple and highly sensitive method for the detection of KRAS mutations.


Single sign-on authentication systems such as OAuth 2.0 are widely used in web services. They allow users to use accounts registered with major identity providers such as Google and Facebook to login on multiple services (relying parties). These services can both identify users and access a subset of the user's data stored with the provider. We empirically investigate the end-user privacy implications of OAuth 2.0 implementations in relying parties most visited around the world. We collect data on the use of OAuth-based logins in the Alexa Top 500 sites per country for five countries. We categorize user data made available by four identity providers (Google, Facebook, Apple and LinkedIn) and evaluate popular services accessing user data from the SSO platforms of these providers. Many services allow users to choose from multiple login options (with different identity providers). Our results reveal that services request different categories and amounts of personal data from different providers, with at least one choice undeniably more privacy-intrusive. These privacy choices (and their privacy implications) are highly invisible to users. Based on our analysis, we also identify areas which could improve user privacy and help users make informed decisions.


Interdigitated gates are employed on heterostructure surfaces to induce strong and tunable lateral superlattice potentials of type II, i.e. of purely field-effect origin. The design of the heterostructures is optimized in a way that avoids statistical potential fluctuations even at very low electron densities where screening of carriers is ineffective. Single-particle electron states confined to one-dimensional electron wires are investigated with capacitance spectroscopy. The precise control of the potential as well as the homogeneity of the potential allow us to investigate 'true' quantum wire arrays, i.e. wires in which only the lowest one-dimensional subband is occupied. Furthermore, we employ interdigitated gates to investigate the optical properties of quantum wells in a type II potential superlattice. The lateral fields are sufficiently high to field-ionize optically excited electron-hole pairs. Absorption spectra of the quantum well under such strong lateral fields show the typical signatures of the Franz-Keldysh effect.


We diagnose the Southern Ocean momentum balance in a six-year, eddy permitting state estimate of the Southern Ocean. We find that 95\% of the zonal momentum input via wind stress at the surface is balanced by topographic form stress across ocean ridges, while the remaining 5\% is balanced via bottom friction and momentum flux divergences at the northern and southern boundaries of the analysis domain. While the time-mean zonal wind stress field exhibits a relatively uniform spatial distribution, time-mean topographic form stress concentrates at shallow ridges and across the continents that lie within the Antarctic Circumpolar Current (ACC) latitudes; nearly 40\% of topographic form stress occurs across South America, while the remaining 60\% occurs across the major submerged ridges that underlie the ACC. Topographic form stress can be divided into shallow and deep regimes: the shallow regime contributes most of the westward form stress that serves as a momentum sink for the ACC system, while the deep regime consists of strong eastward and westward form stresses that largely cancel in the zonal integral. The time-varying form stress signal, integrated longitudinally and over the ACC latitudes, tracks closely with the wind stress signal integrated over the same domain; at zero lag, 88\% of the variance in the six-year form stress time series can be explained by the wind stress signal, suggesting that changes in the integrated wind stress signal are communicated via rapid barotropic response down to the level of bottom topography. This article is protected by copyright. All rights reserved.


Axial compressors in aero engines are prone to suffering a breakdown of orderly flow when operating at the peak of the pressure rise characteristic. The damaging potential of separated flows is why a safe distance has to be left between every possible operating point and an operating point at which stall occurs. During earlier investigations of stall inception mechanisms, a new type of prestall instability has been found. In this study, it could be demonstrated that the prestall instability characterised by discrete flow disturbances can be clearly assigned to the subject of "Rotating Instabilities". Propagating disturbances are responsible for the rise in blade passing irregularity. If the mass flow is reduced successively, the level of irregularity increases until the prestall condition devolves into rotating stall. The primary objective of the current work is to highlight the basic physics behind these prestall disturbances by complementary experimental and numerical investigations. Before reaching the peak of the pressure rise characteristic flow, disturbances appear as small vortex tubes with one end attached to the casing and the other attached to the suction surface of the rotor blade. These vortex structures arise when the entire tip region is affected by blockage and at the same time the critical rotor incidence is not exceeded in this flow regime. Furthermore, a new stall indicator was developed by applying statistical methods to the unsteady pressure signal measured over the rotor blade tips, thus granting a better control of the safety margin.


In this study cost effective direct compression technique was used for the development and optimization of intermediate release (IntR) ketoprofen tablets using central composite design (CCRD). Fifteen different formulations (F1-F15) were developed using (X1) microcrystalline cellulose (Avicel PH-102) (18-51%), (X2) methocel K4M (0.1-25%) and (X3) starch (1.5-18%) as selected variables while responses were % friability and Carr's Index (compressibility index). Powder blends of all formulations were evaluated using Angle of Repose, Carr's Index and porosity. Results of powder blends comply with USP standards and are classified as Fair Excellent. From F1-F15 only four formulations i.e. F6, F7, F14 and F15 were selected on acceptable weight basis, micromeritic properties and on the concentration of excipients. For the assessment of physico chemical properties of the optimized formulations different tests were performed. All results were found to be adequate range. In vitro assessment of the optimized formulations were also carried out in different dissolution media i.e. pH 1.2, phosphate buffer 4.5, pH 6.8 and pH 7.5. Release behaviour of F6, F7, F14 and F15 were estimated by using one - way ANOVA, model - independent, model dependent methods. Results of f1 and f2 showed that all the test formulations i.e. F6, F7, F14 were found to be similar with the reference formulation i.e. F15 at various dissolution media. Also all the formulations followed Hixson-Crowell kinetic model. The parameter n showed Anomalous transport (non - fickian diffusion). The mean dissolution time (MDT) was found to be in the range of 2.632-2.922. Results of ANOVA indicated no significant difference within and between formulations at different dissolution media as p values were found to be >0.05. Also all the selected formulations were found to be stable at accelerated conditions.


The routing methods which used in the wireless sensor network deal with the clustering method to diminish the amount of data transmission from the energy efficiency view. However, the clustering methods cause several problems in energy consumption at the cluster head node. Dynamic clustering is a method which used to supplement a high energy consumption problem by distributing energy consumption through the re-selection of the cluster head node. But, this method changes cluster structure every time the cluster head node is re-selected, which causes energy consumption. Namely, the dynamic clustering method approaches examined in previous researches involve the repetitive processes of cluster head node selection. This consumes a high amount of energy during the set-up process of cluster generation. Consequently, this paper proposes the hybrid clustering method that fixes the cluster and selects the head node in a round-robin method. The hybrid clustering approach is an energy-efficient method that realizes consistent and balanced energy consumption in each node of a generated cluster to prevent repetitious set-up processes as in the LEACH method. The propriety of the proposed method is substantiated with a simulation experiment.


Intelligent investment in setup cost reduction and process reliability improvement is crucial to an emerging integrated lean six sigma practice today. This study examines a cost-minimizing problem of jointly determining production lot size, setup cost reduction, and process reliability improvement decisions for a manufacturer with an imperfect production process. We develop models for previously untapped discrete shipping in a supply chain context as well as continuous shipping and solve them optimally using differential calculus and nonlinear programming. We also conduct analytic and numerical sensitivity analyses to provide various important managerial insights into practices.


The present article will discuss the advantages for the space closure alternative, as well as provide some new information about optimal finishing in canine substitution cases. Factors of crucial importance for indications and contraindications will be evaluated.


The findings of this study present the results of three producing seasons of DaiLoan-mango growers per year. The results showed that season 3 was the highest technical efficiency (73.10%), the second place was season 1 (62.65%), and then season 2 (58.41%). Moreover, the independent variables that explained the technical efficiency of season 1 were the pesticide, root fertiliser, leaf fertiliser and labour; season 2 were the root fertiliser, leaf fertiliser and labour; and in season 3 were the pesticide, root fertiliser, leaf fertiliser, and labour. Besides this, the important determinants of socio-economic variables that impacted positively on technical efficiency were the land area in all three seasons, market access in season 2, and credit access in season 3. However, the constraints to DaiLoan-mango production were the farming experience in season 1, and the age in season 2. Based on these findings, policy makers should focus on effective input models that would boost technical efficiency through conducting regular workshops and orchard demonstrations on using input materials effectively for mango farmers. Moreover, farmers should be empowered in land area acquisition to apply advanced technology in large-scale production more effectively.


In this work, a human-centred steering assist controller based on dynamic allocation of control authority between driver and automatic e-copilot has been proposed for lane keeping systems. Cooperative control between driver and steering assist controller is addressed taking into consideration human driving behaviour. The vehicle steering controller for lane keeping is designed using a driver model for representation of the conflict between the driver and the controller. The steering controller is designed employing the integrated driver-vehicle model using Takagi-Sugeno control technique coupled with Lyapunov stability tools. The proposed design is robust to longitudinal speed variations and involves a trade-off between the lane following performance and ratio of negative system interference. The proposed approach was implemented on dynamic vehicle simulator SHERPA and the results presented in this study demonstrate the effectiveness of the proposed structure for cooperative control action between human driver and the steering assistance system. Based on indices such as energies spent by driver, driver satisfaction level and contradiction level between driver and autonomous controller the proposed optimal approach shows 93.48% and 89.30% reductions in expended driver energy and contradiction levels. Further, the satisfaction level of driver increased by 67.80% while performing a lane change manoeuvre.


A number of thin aggregated metal films on glass substrates are analysed in terms of the model proposed earlier (Hill 1969). It is shown that the model is consistent, and that the conductivity of a thin metal film forming an island structure can be defined in terms of the island size and spacing, and of the properties of the substrate and the film material. The potential barrier heights for electron tunnelling between particles of gold, particles of platinum , and particles of silver through soda and barium aluminosilicate glass have been determined. It is shown that the bias effect in thin metal films (Hill 1964a) can only be observed with metals of work function close to that of the substrate material and when the substrate contains free alkali ions.


In May 2020, during the lockdown in Germany and Austria due to the coronavirus pandemic,
 Manuel Zahn arranged to have an email conversation with Christine Kopf and Alejandro
 Bachmann. Since 2017, both have been a part of the project Intercultural Film Education,
 which is the central concern of the email exchange. Since the beginning of 2019, Manuel
 Zahn and his co-researcher Katja Lell have been involved with this project in the
 form of action research. The project has brought together people and institutions
 from the German-speaking field of film education, and it aims to foster an intercultural
 sensibility within that field. The conversation provides information about the history
 of the project and the project partners, as well as about the forms of work as a learning
 group. In addition, it discusses the central concepts (intercultural attitude, for
 example) and objectives of the project. This encompasses and touches upon ideas such
 as adopting an intercultural attitude as a teacher, the selection of films, the concrete
 form of seminars, the negotiation of normative concepts and the sustainable structural
 change of institutions in cultural education.


The author analyses the success rate and efficiency of Slovenian public sector companies in the course of their operations and looks into opportunities for savings and ways of attracting private investment in infrastructure. By reducing expenditures public companies achieve higher profits, from which the state in turn receives firstly, dividends as a form of budgetary revenue; and secondly, increased tax revenues, as public companies are not exempt from paying corporate income tax. By increasing the rate of return in public companies, the state therefore receives a larger slice of the budget pie on account of its two roles – as both owner and administrator, and as fiscal generator and provider. The author concludes that Slovenian companies cannot achieve identified possible savings without the efficient management of public sector companies. To this end at least two reforms should be introduced in Slovenia: firstly, the introduction of a system of contracts between the state and public sector companies on the meeting of specific pre-determined goals; and secondly, the establishment of a politically independent system of recruitment and appointment of managers based on professional references, and a management remuneration system tied to either the operating results achieved by said public companies or on the meeting of certain pre-determined goals set out in contracts between the state and public companies.


The load of airborne microorganisms in indoors depends of factors such as human occupancy, ventilation status,
cleanliness, maintenance of rooms etc. As many airborne bacteria are pathogenic, periodic sampling of air helps
to provide insight into the quality of air and also ensure the health and safety of individuals being exposed. The
objective of this work is to study the airborne bacterial load in indoor environments. The bio-aerosol samples
were collected from different classrooms and labs with the help of an LA002 Air Sampler System, on to Nutrient
Agar medium by exposing for a period of 5 minutes. The plates were incubated at 37 �C for 24 hours and
colonies developed were studied. The results revealed the prevalence of Gram negative rod shaped organisms.
The microbial load was found to be more in non-AC classrooms than AC ones, as well as more in the samples
taken during occupied state than in vacant.


Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by the expression of mutant huntingtin protein (Htt). Suppression of Htt expression, using RNA interference, might be an effective therapy. However, if reduction of wild-type protein is not well tolerated in the brain, it may be necessary to suppress just the product of the mutant allele. We present a small interfering RNA (siRNA) that selectively reduces the endogenous mRNA for a heterozygous HD donor's pathogenic allele by approximately 80% by specifically targeting a single-nucleotide polymorphism (SNP) located several thousand bases downstream from the disease-causing mutation. In addition, we show selective suppression of endogenous mutant Htt protein, using this siRNA. We further present a method, using just a heterozygous patient's own mRNA, to determine which SNP variants correspond to the mutant allele. The method may be useful in any disorder in which a targeted SNP is far downstream from the pathogenic mutation. These results indicate that allele-specific treatment for Huntington's disease may be clinically feasible and practical.


Non-carious cervical lesions (NCCLs) are defined as the loss of dental hard tissue at the cement-enamel junction. Erosion, abrasion, and attrition have been associated with this disorder. Objective: Recently, occlusal stress causing of cervical enamel cracks (abfraction) has been considered as an additional etiology for NCCLs to facilitate the erosion and abrasion mechanisms in tooth wear. Study Design: The prevalence of NNCLs and wear facets in a population with permanent dentition in absence of any clear etiological factors related to erosion and abrasion causes is evaluated. A total 295 subjects are enrolled for this study and divided into four age groups (subjects aged 15 - 27 years, 28 - 42 years, 43 - 57 years and 58 - 75 years respectively). An overall of 6629 teeth are investigated to find NCCLs and wear facets. The occlusion is analyzed in each patient. Results: An overall of 801 teeth (12%) show NCCLs and 623 of them (78%) highlight also wear facets. The higher number of teeth with NCCLs and of these with simultaneous presence also of wear facets are found on teeth of patients of group-3 (11% of all teeth examined for group and 81% respectively) and to group-4 (24.4% of all teeth examined for group and 86.5% respectively) of remaining teeth without NCCLs (5828) only 138 (2.4%) shown wear facets. Conclusion: The results of this study held the occlusal forces as the main cause of NCCLs on teeth in presence of wear facets.


OBJECTIVE: The objective of this study was to examine early-career frontline nurse managers' (FLNMs') reported educational preparedness and participation in quality improvement (QI). BACKGROUND: Frontline nurse managers are vitally important for leading QI. However, it is not well known if they have adequate knowledge and skills to lead this important function. METHODS: We examined cross-sectional survey data from 42 FLNMs using descriptive statistics. RESULTS: About 30% of FLNMs reported being very prepared across 12 measured QI skills by schools or employers and 35% reported participating in a specific clinical effort to improve patient care on their unit more than once a month. More than 50% reported having good organizational support for QI, but only about 30% reported being rewarded for their contributions to QI. CONCLUSION: Our study highlights opportunities for development in QI for FLNMs and offers some solutions for nurse executives that can bridge the educational gaps.


SUMMARY The majority of Sub-Saharan Africa's population relies on forest products for subsistence uses, cash income, or both. In the case of non-timber forest products (NTFPs), it is imperative to 1) clearly understand the socio-economic contributions that they make to rural livelihoods in order to 2) design policies, interventions, and business ventures that serve to safeguard forest assets for the poor in a targeted manner. Based on existing literature, this article highlights the quantitative contributions that NTFPs have made to rural household incomes in several forested, Sub-Saharan African countries. Reasons for a paucity of data on this front are discussed. The article then identifies five broad socioeconomic factors (location, wealth status, gender, education, and seasonality) affecting levels of dependency on NTFPs by rural households, and calls for a better understanding of the linkages between these five factors in order for targeted policies on poverty alleviation in forest-dependent communities to be developed.


This tutorial is an introduction and overview of many of the major topics that need to be considered when designing a component or system for EMC and to minimize potential SI/PI issues. The tutorial will present the foundational physics and provide an overview of the significance and relevant mathematics that need to be understood to successfully evaluate, diagnose, and solve both EMC and SI/PI issues. After the "background" material on causes of emissions is covered, specific examples of the application of the theory will be discussed in dedicated sessions on grounding, shielding, printed circuit board (PCB) design, as well as important considerations in designing for SI/PI, and the tutorial will conclude with an overview of typical EMC test equipment.


In this paper, we study the effect of adaptivity of routing algorithm on the overall performance in a hypercube multicomputer using wormhole switching. To this end, we use three accurate analytical models proposed for deterministic, fully-adaptive, and partially-adaptive routing algorithms in hypercube. Surprisingly, our analysis shows that under uniform traffic load, the partially-adaptive routing exhibits a lower performance compared to the deterministic routing with less adaptivity


Ocimum sanctum commonly called (holy basil) an herb containing medicinal, ornamental values, is often used in culinary applications. This research focuses on the improved and efficient protocol for the direct regeneration and acclimatisation of Ocimum sanctum using nodal segments. Organogenesis and multiplication from explants were observed to a maximum on Murashige and Skoog (MS) medium supplemented with 0.1 mg/L of 6-Benzyl amino purine (BAP) and 0.025 mg/L of Indole-3-acetic acid (IAA). Furthermore, same medium was found effective for the induction of roots, in the in-vitro grown plantlets. A series of experiments were conducted to optimise the acclimatisation of in-vitro grown rooted plantlets of Ocimum sanctum. For this study different types of potting mix in assorted ratios were used  to obtain best supporting media for the acclimatisation, A7 media containing soil : farmyard manure (75:25) and A1 media containing (100%) sand were found best supporting medium for the acclimatisation and hardening of Ocimum sanctum.


Cordycepin is an anticancer metabolite produces by a zombie fungus species of Cordyceps militaris. They are capable to infect and hijack insect's nervous neuron system. Hypoxic environment commonly must be faced by the pathogenic fungus during infection either this zombie fungus. They activate oxygen sensing mode, heme, siderophore, and sterol biosynthesis to overcome it. Underlined our previous study that liquid surfaced culture of C. militaris NBRC103752 produced a higher amount of cordycepin than submerged culture, suggesting that hypoxic conditions might induce it. However, when and how the mechanism of cordycepin production started in liquid surfaced culture is not understood, yet. In our present study, the combination of transcriptomics and gas chromatography-mass spectrometry were carried out during the production phases of cordycepin (5d, 12d, and 19d of incubation periods) and the mechanism of cordycepin production was figured out. The expression of genes in the fermentation pathway and the oxidative phosphorylation pathway were significantly upregulated and down regulated, respectively. Expression of four genes in the heme biosynthesis, including 5-aminolevulinic acid synthase (CCM_01504), delta-aminolevulinic acid dehydratase (CCM_00935), coproporphyrinogen III oxidase (CCM_07483) and cytochrome c oxidase15 (CCM_05057) were upregulated at the beginning of the exponential phase (12d). Further, the activation of Zn(2)-C6 transcription factor that regulates the iron acquisition and ergosterol biosynthesis significantly upregulated and a metabolite reporter adenosine was detected only at 12d. The results in the present study show the correlation between hypoxia and the accumulation of heme before cordycepin biosynthesis.


The present recovery rate of brain tumors (20% of solid tumors in children) is 50%. Besides the progress made in neurosurgery and radiotherapy, those of chemotherapy have indisputably had an impact on the improvement of the rate of recovery. Protocols in use differ according to the histologic type of the tumor (astrocytoma, glioma, medulloblastoma). Indications for therapeutic trials for phase II and III tumors will require a longer period of follow-up as well as strict analysis of the result.


The hydrolysate from the action of crude Penicillium oxalicum KUB-SN2-1 mannanase was determined by Thin Layer Chromatography (TLC). The main products that were obtained from copra meal and coffee residue after hydrolyzed by crude mannanase were mannotetraose, mannotriose, mannobiose and mannose while the product of potato peel and sugarcane bagasse was glucose. For soybean meal, the main products were glucose and galactose. Interestingly, the hydrolysate from the degradation of agricultural wastes possessed prebiotic properties in that they promoted growth of 10 strains of Lactic Acid Bacteria (LAB) including Lactobacillus plantarum TISTR 541, Lactobacillus sake TISTR 840, Lactobacillus sake TISTR 890, Lactobacillus sake TISTR 912, Lactobacillus reuteri KUB-AC-5, Lactococcus lactis ATCC 19435, Pediococcus pentosacens JCM 5885, Pediococcus acidilactici TISTR 953, Enterococcus faeclis TISTR 927 and Enterococcus faeclis JCM 5805. In addition, the same hydrolysate could inhibit the growth of pathogenic bacteria including Staphylococcus aureus TISTR 029 and Escherichia coli E010, but not Shigella DMST 1511. The hydrolysate from coffee residue effectively inhibited the growth of Staphylococcus aureus TISTR 029 at the level 76.190 ± 3.88% while the soybean meal hydrolysate moderately inhibited the growth of Staphylococcus aureus TISTR 029 as well as E. coli E010 at the level of 34.78 ± 4.35 % and 20.0 ± 9.0%, respectively. For the aspects of health benefits and value added agricultural wastes, these mannooligosaccharide products are an attractive candidate as an environmental friendly feed supplement.


This paper focuses on SIMD processor synthesis and proposes a SIMD instruction set/functional unit synthesis algorithm. Given an initial assembly code and a timing constraint, the proposed algorithm synthesizes an area-optimized processor core with optimal SIMD functional units. It also synthesizes a SIMD instruction set. The input initial assembly code is assumed to run on a full-resource SIMD processor (virtual processor) which has all the possible SIMD functional units. In our algorithm, we introduce the SIMD operation decomposition and apply it to the initial assembly code and the full-resource SIMD processor. By gradually reducing SIMD operations or decomposing SIMD operations, we can finally find a processor core with small area under the given timing constraint. The promising experimental results are also shown.


The presence of speckle in Synthetic Aperture Radar (SAR) images makes the segmentation of such images difficult. A novel method for automatic segmentation of SAR images is proposed. Firstly, a wavelet packet based texture feature set is derived. It consists of the energy of the feature sub images obtained by the over complete wavelet packet decomposition of local areas in SAR image, where the down sampling between wavelet levels is omitted. Then an improved unsupervised clustering algorithm is proposed for image segmentation, which can determine the number of classes automatically. Segmentation results on real SAR image demonstrate the effectiveness of the proposed method.


In this study, bovine serum albumin (BSA) was used as a model protein for the optimization of protein immobilization on chitin nanowhisker and chitosan nanoparticles under different conditions. Chitosan nanoparticles showed better results than chitinin this immobilization purpose. The immobilization at 15 minutes, pH 6 and 20-25°C was the optimal condition. Subsequently, glucose oxidase (GOD), enzyme used for glucose determination, was applied in order to investigate the optimum immobilization condition on chitosan nanoparticles. The optimal condition prove to...at pH 7, 30°C and 0.5 mg/ml of initial GOD concentration via immobilization at 15 minutes. Chitin nanowhisker and chitosan nanoparticles in this study had 300 and 39 nm in size, respectively. These results will be further used for the development of glucose electrodes.


Anogeissus latifolia (Combretaceae) has been used in traditional system of medicine in India for over many years, and widely used to enhance the immune system and against various ailments. During the last decade many in-vitro, in-vivo and analytical studies witnessed and justified the traditional claim of this plant. The study was aimed to evaluate the preventive effect of Anogeissus latifolia bark in insulin resistance and metabolic dyslipidemia induced by high fructose diet feeding in rats . At the end of the treatment period, the plasma from normal control, diabetic, reference standard and Anogeissus latifolia extract (300mg/kg) treated animals were subjected to estimation of insulin, lipid profile, liver marker enzymes and kidney function test. Anogeissus latifolia was found to attenuate insulin resistance and metabolic dyslipidemia induced by adverse effects of fructose. This study validates the traditional use and shows a possible beneficial effect of the plant in the treatment of diabetes mellitus. Key Words : Anogeissus latifolia, High Fructose Diet, Insulin Resistance, Metabolic Disorder.


This paper describes a new 19.2mm GaAs PHEMT chip with high gain, high power and high power-added efficiency. Devices which are packaged by internal-matching use one such FET that has been developed at 16-16.5GHz. At 16.5GHz, the device has achieved power, gain, and power-added efficiency of 39.1dBm, 6.1dB and 26.1% respectively at the 1dB gain compression point. It is first reported that high gain, PAE and output power combination have achieved by a single FET power amplifier at such high frequency


We have generated transgenic mice that contain human-sequence Ig miniloci and, because they are also homozygous for a targeted disruption of their endogenous heavy chain genes, must rely on the transgene sequences for B cell receptor expression. Although the human transgenes contain only a fraction of the intact human heavy chain locus, these defined sequences are able to at least partially restore the humoral immune system in the mouse. B cells expressing human heavy chains develop in the bone marrow, populate peripheral lymphoid tissue and respond specifically to antigen. Furthermore, the heavy chain transgenes contain both human mu and gamma 1 coding exons as well as the respective mu and gamma 1 switch regions. The sequences included within the transgene are sufficient to direct class switch recombination. Transgene sequences are also sufficient to direct somatic mutation of the class-switched heavy chain genes. These observations define the upper limit of the cis-acting sequences necessary to direct heavy chain class switching and somatic mutation.


The Cooperative Family Registry for Breast Cancer Studies (CFRBCS) is an international multisite cooperative consortium of investigators who collaborate to ascertain families at risk for breast cancer. Sufficient blood was collected from each individual participating in the CFRBCS to permit the


This work reviews the legal norms applied to science and technology in four countries, in a comparative analysis. As a first level of analysis, we consider the constitution of the countries analyzed. In a second level, se present national laws. We analyze the scope and relevance of scientific activities; constitutional provisions concerning science and technology; general laws for the educational sector; general laws regarding research and development; and general laws regarding industrial property. .


Transmission Control Protocol (TCP) is one of the protocols that work in the OSI (Open System Interconnection) modeling transport layer. TCP was designed more for wired networks. However, to meet the need for rapid development of network technology based on user needs, further development is needed for the use of TCP on wireless devices. One of the implementation of wireless-based network is mobile technology Long Term Evolution (LTE) broadband offering advantages, especially in terms of access. TCP Tahoe, TCP Reno, TCP SACK, and TCP Vegas are variants over the LTE network model with scenario. First is the view Throughput of each TCP variants when only one variant Certain working in the network. Both observe throughput All variants of TCP at the same time and have a QoS Equivalent, but with the possibility of a small congestion based on the capacity of the links made sufficient.


GBO-006 was shown to be a highly specific and selective PLK2 inhibitor that promoted mitotic arrest in various cancer cell lines, subsequently resulting in their apoptotic death.  Intraperitoneal alternate day dosing of GBO-006 using 100 % DMSO as formulation showed significant tumor regression in xenograft models, demonstrating proof of concept of PLK2 inhibition in vivo. These studies necessitated the development of a suitable and GRAS (generally considered as safe) preformulation for pharmacokinetic and efficacy studies. GBO-006 possesses challenging physicochemical and biopharmaceutical properties like poor solubility in aqueous media, low permeability and a crystalline nature. Different methods like cosolvency, complexation and micellar solubilization were employed to improve the solubility of GBO-006.  A strategy of co-solvency is used to solubilize the GBO-006 up to 10 mg/mL. A formulation with 20 % DMSO, 40 % PEG 400, 30 % of 100 mM citrate buffer (pH 3.0) and 10 % solutol displayed clear solution without any visual precipitation of the drug even after 2 weeks of storage. GBO-006 showed moderate clearance in rat and high systemic clearance in mouse and dog. It showed poor oral bioavailability across all species. Intraperitoneal dosing of GBO-006 demonstrated the linear exposure. GBO-006 showed significant inhibition of tumor progression.


Early life stress (ELS) presents an important risk factor for drug addiction and comorbid depression and anxiety through persistent effects on the mesolimbic dopamine (DA) pathways1. Using an ELS model for child neglect (a single 24 h episode of maternal deprivation, MD) in rats, recent published works from our lab show that MD induces dysfunction in ventral tegmental area (VTA) DA neurons 2–4 and its negative controller, the lateral habenula (LHb) 5–7. In regard to LHb, MD-induced potentiation of glutamatergic synaptic transmission onto LHb neurons shifts the coordination of excitation/inhibition (E/I) balance towards excitation, resulting in an increase in the overall spontaneous neuronal activity with elevation in bursting and tonic firing, and intrinsic excitability of LHb neurons in early adolescent male rats 5–7. Here, we explored how MD affects intravenous morphine self-administration (MSA) acquisition and sucrose preference as well as glutamatergic synaptic function in LHb neurons of adult male rats self-administering morphine. We found that MD-induced increases in LHb neuronal and glutamatergic synaptic activity and E/I ratio persisted into adulthood. Moreover, MD significantly reduced morphine intake, triggered anhedonia-like behavior in the sucrose preference test (SPT), and was associated with persistent glutamatergic potentiation 24h after the last MSA session. MSA also triggered postsynaptic glutamatergic potentiation in LHb neurons of control rats during this time period. Our data highlights that ELS-induced glutamatergic plasticity in LHb may dampen the positive reinforcing properties of natural rewards and opioids, and contribute to the development of anhedonic and dysphoric states associated with opioids.


"P53 is a protein that is part of the cell cycle and acts as a checkpoint for DNA to ensure there is not damage. Currently, it is known that there are P53 mutants in over 50% of cancers," said Dr. Montgomery. Dr. Montgomery explained that an enzyme called HDAC, histone deacetylase, acts to silence genes and decrease transcription, which is the coding for new DNA copies. An HDAC inhibitor acts to overexpress genes resulting in a decreased amount of DNA available and cell cycle arrest. HDAC inhibitors have been introduced into therapeutic drugs and could potentially have anti-inflammatory properties.


OBJECTIVE
To evaluate the morbidity of living donor kidney harvesting and the long-term medical consequences and impact on quality of life (QoL).

MATERIAL AND METHODS
Retrospective analysis of medical and surgical data for 114 living kidney donors in a single teaching hospital between 1977 and 2005. Complications were evaluated in relation to the surgical approach and body mass index (BMI) using a Chi-square test or Fisher's exact test. Changes in renal function (serum creatinine, creatinine clearance), proteinuria and blood pressure (BP) were studied by Student's t test or a Mann-Whitney U or Wilcoxon nonparametric test. Long-term QoL was evaluated by the MOS SF-36 questionnaire and a local questionnaire and was then compared to that of the French general population.

RESULTS
The median follow-up was 63 months. The morbidity of kidney harvesting was significantly correlated with the surgical approach (p = 0.018) and a BMI > or = 25 kg/m2 (p = 0.014). No mortality was observed in this series. A moderate elevation of serum creatinine was observed during follow-up (mean serum creatinine increased from 82.2 micromol/l [+/- 16.3] to 104.5 micromol/l [+/- 19.9]), and mean creatinine clearance decreased from 113.4 ml/min [+/- 27.6] to 76 ml/min [+/- 29.9]. Little impact was observed on proteinuria and BP and QoL was not altered by kidney harvesting.

CONCLUSION
The perioperative complication rate is correlated with BMI and a flank incision. Kidney harvesting lowers glomerular filtration, but clearance remained stable during follow-up. Macroalbuminuria or hypertension may be observed, but their frequency is not higher than in the general population. The QoL of living donors is not altered. Clear information for the general public would allow promotion of living donor transplantation.


When individual consumers develop products for their own use, they in part expect to be rewarded by the use value of what they are creating (utilitarian user motives), and in part expect to be rewarded intrinsically by such things as the fun and learning experience derived from creating it (hedonic user motives). This paper shows a first-of-type study to understand the relationship between individual consumers' motives to innovate and the novelty and utility of the solutions they develop. The theoretical framework integrates self-determination theory and goal-setting theory.

The major findings of this study are that utilitarian user motives positively affect the utility of user-developed innovations. In contrast, hedonic user motives drive solution novelty; the more an innovator is "in it for fun," the more novel the solution developed. However, hedonic user motives also have an inverted U-shaped relationship with solution utility. When the dominant motive for developing an innovation is the joy of the creative process rather than use value, the utility of what is developed is negatively affected. These findings are of research interest, and can be of significant practical interest to producers hoping to benefit from user-developed innovations. For the first time, it has been possible to show that the adjustment of hedonic rewards, for example by means such as gamification, can affect the nature and utility of solutions individuals create.


This paper considers the application of neural network with distributed dynamics to the identification of nonlinear systems. The main intention is to provide a simulation tool to the development engineer. The identification of the thermal plant is accomplished without any a priori knowledge about the nonlinear structure or the dynamics of the plant. Identification results of two different neural nets are shown and compared. The application area is boilers for building energy management systems.


Only a fraction of scholarly work in public relations has been devoted to theoretical development, with scholars unable to agree upon any one single theoretical framework from which to view public relations. This literature review and analysis pose the case for symbolic interactionism as an appropriate theoretical origin for public relations, as initially suggested by Gordon (1997) and furthers a definition of public relations from the symbolic interactionist perspective. The paper specifically builds on Gordon's work by identifying some key shared concepts between public relations and symbolic interactionism ( communication, relationships, adaptation, shared meaning or consubstantiality, the creation of definition and social constructivism ), supporting Gordon's argument and strengthening the link. This work also builds on Gordon's definition of public relations and proposes that public relations is the intentional participation in the social construction of meaning to achieve organizational or brand reputation goals. By conceptualizing and positioning public relations within the theoretical framework of symbolic interactionism, the field can find more cohesion and also work toward a more universal definition.  ©Journal of Professional Communication, all rights reserved.


This paper describes the responses of undergraduate nursing students to an ethical clinical case study. Students in a baccalaureate program were given a case study before a lecture on ethical principles and the same case study after this lecture. These responses raise questions about the content of nursing ethics classes in Japan. The place of individual patient rights and the role of the family in a situation of non-disclosure about diagnosis and prognosis were major issues for the students. The responses reveal the problem of the 'nurse-in-the-middle' between the patient and others whose values differ. Students' post-lecture responses emphasized communication among the people involved.


Iron-biofortification of crops is a strategy that alleviates iron deficiency. The common bean (Phaseolus vulgaris L.) is an attractive candidate for biofortification. However, beans are high in polyphenols that may inhibit iron absorption. In vitro studies have shown that iron bioavailability from white beans is higher than that from colored beans. In this study, our objective was to determine if white beans contain more bioavailable iron than red beans and to determine if the in vitro observations of bean-iron bioavailability would be evident in an in vivo feeding trial. We compared iron bioavailability between diets containing either white (Matterhorn) or red (Merlot) beans, which differ in polyphenol content. One-week-old chicks (Gallus gallus) were divided into four groups: 1. "WB": 40% white-bean diet; 2. "RB" :40% red-bean diet; 3. "WB+Fe": 40% white-bean diet; 4. "RB+Fe": 40% red-bean diet (51, 47, 179, and 175 ppm iron, respectively). Diets 1 and 2 had no supplemental iron; whereas 125 µg/g iron was added to diets 3 and 4. For 8 weeks, hemoglobin, feed consumption, and body weights were measured. Divalent metal transporter 1 (iron-uptake-transporter), duodenal-cytochrome-B (iron reductase), and ferroportin (iron-exporter) expressions were higher (p<0.05), villus-surface-area (tissue iron-deficiency adaptation) was greater in the "RB" group vs. other groups. Cecal microflora was similar between treatments. Hemoglobin, body-hemoglobin iron, and body weights were lower in the "RB" group vs. other groups (p<0.05). In vitro analysis showed lower ferritin formation (less bioavailable iron) in cells exposed to the "RB" diet. We conclude that the in vivo results support the in vitro observations; i. e., white beans contain more bioavailable iron than red beans.


The coupling of unusually hot and dry weather have led to global increases in the occurrence of megafires. Despite the conventional wisdom that extreme heat and aridity overwhelm the controls on burn severity patterns (i.e., vegetation mortality), we hypothesize that wind is the main driver of megafire events in temperate mesic forests with climate-restricted fire regimes, yet that fuels and topography remain important influences on burn severity patterns. The infrequent occurrence of large high-severity wildfire in these forests means that contemporary empirical data (e.g., remote sensing) from past megafires are largely missing. During the extraordinary 2020 fire season, ca. 0.8 million ha burned in the North American Pacific Northwest (PNW) over two weeks under record-breaking fuel aridity and winds, representing the first modern example of megafires that characterize disturbance regimes west of the region's Cascade Mountains. Considering increasing concern and uncertainty surrounding the drivers of megafire events in temperate mesic forests, our objective was to understand the relative influence of, and potential interactions between, weather, fuels, and topography on high-severity (> 75% tree mortality) fire probability among five synchronous megafires in the western Cascade Mountains. To assess the influence of several potential drivers of high-severity fire and whether these relationships varied with land use and ownership, we developed remotely sensed fire extent and burn severity maps for two periods of the explosive 2020 PNW fire season: (1) during extreme winds and (2) after the extreme winds subsided. The area burned during the windstorm accounted for 90% of the total fire sizes and saw a 2.5-times greater proportion of high-severity fire than during the period without winds. Our results suggest that wind is the major driver of megafires in forests with climate-limited fire regimes, yet that fuels and topography shape burn severity patterns even under extreme fuel aridity and winds. The relative influence of topography on burn severity outweighed fuels during the windstorm, while fuels outweighed the influence of topography after winds subsided. Early-seral forests primarily concentrated on private lands, burned more severely than their older and taller counterparts, regardless of topography, over the entire megafire event. Meanwhile, mature stands burned severely only under extreme winds and especially on steeper slopes. Although climate change and land-use legacies may prime mesic temperate forests to burn more frequently and at higher severities than historically observed, and especially among early-seral forests, our work suggests that future high-severity megafires are only likely to occur during coinciding periods of heat, fuel aridity, and extreme winds.


Abstract Sapajus libidinosus members of the Pedra Furada group, living in the Serra da Capivara National Park, use stone tools in a wider variety of behaviors than any other living animal, except humans. To rescue the evolutionary history of the Caatinga S. libidinosus and identify factors that may have contributed to the emergence and maintenance of their tool-use culture, we conducted fieldwork seasons to obtain biological samples of these capuchin monkeys. UsingCYTBsequences, we show a discrete but constant population growth from the beginning of the Holocene to the present, overlapping the emergence of the Caatinga biome. Our habitat suitability reconstruction reports the presence of plants whose hard fruits, seeds, or roots are processed by capuchins using tools. TheS. libidinosusindividuals in the Caatinga were capable of dynamically developing and maintaining their autochthonous culture thanks to: a) cognitive capacity to generate and execute innovation under selective pressure; b) tolerance favoring learning and cultural inheritance; c) an unknown genetic repertoire that underpins the adaptive traits; d) a high degree of terrestriality; e) presence and abundance of natural resources, which makes some places "hot spots" for innovation, and cultural diversification within a relatively short time.


Optimum nozzle design exploiting the method of characteristic(M.O.C) has been in application as an efficient design methodology targeting a less weighted and short expansion nozzle. This paper treats the optimum nozzle design and the analysis of the inviscid compressible flow inside. Based on traditional Rao's method, the optimum nozzle design is coded with minor modifications for the identification of the control surface across which the mass flux should be conserved. Internal flow field is simulated numerically by M.O.C and implicit/explicit Taylor-Galerkin finite element method(F.E.M) with the aid of adaptive remeshing to capture the shock wave, hence improve the accuracy. Designed and calculated flow fields due to the separate analyses show that the mass flux predicted by optimum nozzle design with M.D.C is not conserved across the control surface and the sonic line should be located upstream of the nozzle throat. Rao's optimum nozzle design methodology exaggerates the momentum thrust and tends to overemphasize the engine performance loss.


Somatosensory evoked potentials provide a measure of cortical neuronal activation in response to various types of sensory stimuli. In order to prevent flooding of the cortex with redundant information various sensory stimuli are gated cortically such that response to stimulus 2 (S2) is significantly reduced in amplitude compared to stimulus 1 (S1). Upper airway protective mechanisms, such as swallowing and cough, are dependent on sensory input for triggering and modifying their motor output. Thus, it was hypothesized that central neural gating would be absent for paired-air puff stimuli applied to the oropharynx. Twenty-three healthy adults (18–35 years) served as research participants. Pharyngeal sensory evoked potentials (PSEPs) were measured via 32-electrode cap (10–20 system) connected to SynAmps2 Neuroscan EEG System. Paired-pulse air puffs were delivered with an inter-stimulus interval of 500 ms to the oropharynx using a thin polyethylene tube connected to a flexible laryngoscope. Data were analyzed using descriptive statistics and a repeated measures analysis of variance. There were no significant differences found for the amplitudes S1 and S2 for any of the four component PSEP peaks. Mean gating ratios were above 0.90 for each peak. Results supports our hypothesis that sensory central neural gating would be absent for component PSEP peaks with paired-pulse stimuli delivered to the oropharynx. This may be related to the need for constant sensory monitoring necessary for adequate airway protection associated with swallowing and coughing.


Diaphorina citri, a vector of citrus huanglongbing (HLB) disease, frequently leads to HLB outbreaks and reduces Rutaceae crop production. Recent studies have investigated the effects of RNA interference (RNAi) targeting the Vitellogenin (Vg4) and Vitellogenin receptor (VgR) genes, which are involved in egg formation in this pest, providing a theoretical foundation for developing new strategies to manage D. citri populations. This study presents RNAi methods for Vg4 and VgR gene expression interference and reveals that dsVgR is more effective than dsVg4 against D. citri. We demonstrated that dsVg4 and dsVgR persisted for 3–6 days in Murraya odorifera shoots when delivered via the in-plant system (IPS) and effectively interfered with Vg4 and VgR gene expression. Following Vg4 and VgR gene expression interference, egg length and width in the interference group were significantly smaller than those in the negative control group during the 10–30-day development stages. Additionally, the proportion of mature ovarian eggs in the interference group was significantly lower than that in the negative control group at the 10, 15, 20, 25, and 30-day developmental stages. DsVgR notably suppresses oviposition in D. citri, with fecundity decreasing by 60–70%. These results provide a theoretical basis for controlling D. citri using RNAi to mitigate the spread of HLB disease.


Objective The present study was designed to evaluate the neuroprotective effects of D-(-)-quinic acid on aluminum chloride- (AlCl3-) induced neurobehavioral and biochemical changes in rats. This study showed the behavioral and biochemical effects of D-(-)-quinic acid on rats with particular emphasis on the hippocampus and frontal cortex which are associated with memory. Materials and Methods Chronic administration of aluminum chloride at a dose of 175 mg/kg, p.o. for a period of 25 days markedly increased the level of acetylcholinesterase (AChE) activity and reduced the levels of antioxidant enzymes in the brain. Two doses of D-(-)-quinic acid (200 mg/kg and 400 mg/kg) were selected based on previous safety/toxicity studies and administered orally from the 26th day to the 36th day of the trial. Behavioral parameters were assessed using the Morris water maze test and an actophotometer in rats. Biochemical parameter content and histology of brain tissue were assessed on the final day of the experiment. Results D-(-)-Quinic acid (200 mg/kg and 400 mg/kg) orally administered alongside AlCl3 rescued AChE activity and the behavioral impairments caused by aluminum. There was significant inhibition of MAO-B in D-(-)-quinic acid-treated rats. Histopathological studies in the hippocampus and cortex of the rat brain also supported that D-(-)-quinic acid markedly reduced the toxicity of AlCl3 and preserved the normal histoarchitecture pattern of the hippocampus and cortex. These results indicate that D-(-)-quinic acid can reverse memory loss caused by aluminum intoxication by attenuating AChE activity and rescuing the deleterious effect of AlCl3.


Dickkopf-1 (Dkk1), a negative regulator of the Wnt signaling pathway, is implicated in tumorigenesis in several types of cancer. The purpose of this study was to determine the involvement of Dkk1 in oral squamous cell carcinoma (OSCC). We found that Dkk1 is frequently upregulated in OSCC-derived cell lines and primary OSCCs compared with normal counterparts. Unexpectedly, Dkk1-positive cases were correlated significantly (P<0.05) with a low risk of regional lymph node metastasis. We also found that cellular migration and invasiveness increased in Dkk1 knockdown cells and decreased in Dkk1 overexpressed cells. Furthermore, we investigated the relationship between the expression of Dkk1 and distribution of β-catenin in OSCC cells, since the Wnt signaling pathway is related closely to β-catenin. Whereas alteration of the β-catenin levels was not observed in each subcellular fractionation, the phosphorylated β-catenin levels in nuclei increased in Dkk1 knockdown cells and decreased in Dkk1 overexpressed cells. These data indicated that the high phosphorylation level of β-catenin in nuclei was correlated with a high risk of tumor invasiveness. The current study suggested that Dkk1 plays an important role in regulating cellular migration and invasiveness, making Dkk1 a potential biomarker for early detection of lymph node metastasis in OSCCs.


Due to the complexity of unconventional reservoir measurement, log data acquired are often incomplete, which results in inaccurate formation evaluation and higher operational risks. Common solutions, such as coring, are typically high cost related while not being sufficiently representative. In recent years, neural network has received increasing attention given its strong ability in data prediction. Nevertheless, most neural networks only focus on one specific feature of the selected data, thus prohibiting their prediction accuracy for reservoir logs where data are often dominated by more than one key feature. To address this challenge, a novel multi-channel hybrid Long Short-Term Memory (LSTM) neural network for effective acoustic log prediction is proposed. The network combines Convolutional Neural Network (CNN) and LSTM, where CNN is used to extract spatial features of the logs and LSTM network extracts temporal features with the assistance of an adaptive attention mechanism implemented for key feature recognition. In addition, the strong heterogeneity of unconventional reservoirs also increases the difficulty of prediction. Therefore, according to the characteristics of the unconventional reservoir, we designed three feature enhancement methods to mine the hidden information of logs. To prove the performance of the proposed network, a case study is presented with data acquired from Jimusar Oilfield, one of the largest unconventional reservoirs in China. Four groups of experiments are conducted, and the proposed network is employed for acoustic log prediction. The predicted results are validated against measurement (R2: 92.27%, 91.42%, 93.31%, and 92.03%; RMSE: 3.32%, 3.92%, 3.06%, and 3.53%). The performance of the proposed network is compared to other networks such as CNN, LSTM, CNN-LSTM, and random forest (RF). The comparisons show that the proposed network has the highest accuracy level of prediction, which means it provides an effective approach to complement missing data during complicated unconventional reservoir measurement and, therefore, could be of significant potential in energy exploration.


The initial experience suggested that kidney transplantation could be hazardous for patients on peritoneal dialysis due to the high risk of peritonitis and a possible high incidence of acute rejection. In this paper we have presented our experience with kidney transplantation in these patients. During the last four years kidney transplantation was performed in 9 patients on peritoneal dialysis. The average time spent on peritoneal dialysis was 20.6 +/- 7.6 months. In all patients peritoneal catheter was removed during the surgery. During the posttransplantation period a triple immunosuppressive therapy including steroids, cyclosporin and azathioprineor mycophenolate mofetil was administered in all patients. In comparison to patients on hemodialysis no significant difference in the incidence of acute rejection episodes, delayed graft function, graft arterial thrombosis and graft function recovery was observed. Patients on peritoneal dialysis had significantly greater and longer wound drainage in comparison to patients on hemodialysis. It was concluded that peritoneal dialysis had no negative influence on short-term outcome of kidney transplantation.


ABSTRACT A wastewater-fed, partly indoor aquaculture plant (36 basins, 360 m2 and 420 m3 in total) was designed in Otelfingen/Zurich, Switzerland. It was charged with the effluent from a methanization plant processing organic household waste and started operation in spring 1998. The aim of the successive arrangement of the different modules and steps was to efficiently recycle water-borne nutrients in the form of aquatic biomass products, such as floating (ornamental) macrophytes, fish, zoo- and phytoplankton, suitable for selling on the Swiss market. Besides treating the effluent (total organic carbon [TOC], total nitrogen, nitrate [NO3-N], ammonium [NH4-N], and total phosphorus concentrations being 670 g/m3, 255 g/m3, 150 g/m3, 95 g/m3, and 52 g/m3, respectively) according to Swiss law requirements, the research focused on the search for suitable aquatic organisms and their testing at different environmental conditions. During the 16-week experimental period, a total of 2,150kg fresh weight (FW) ofbiomass (97% as floatingmacrophytes) was harvested. This way, 176 g/week nitrogen and 47 g/week phosphorus wereeliminated by assimilation, corresponding to 25-35% of the system's inflow. Due to relatively high evapotranspiration rates (on average 35.4 mm/week) and for water reconditioning purpose in the fish stocking basins, fresh water was added. Nevertheless, the system's final effluent was very low (21% of total inflow plus rainfall) and was carrying only about 2% and 0.5% of the input loads of nitrogen and phosphorus, respectively. Hence, the elimination rate was significantly above the average performance of a conventional system normally applied in Middle Europe, althoughthe concentration values of most parameters in the outflow were comparable. Macrophyte production (and thus nutrient assimilation) was close to theoretical maxima in basins with high nutrient levels. Both plankton and fish growth were, at their best, only moderately satisfying. The semi-continual planktonic microalgae culture, and therefore also zooplankton culture, could be improved if the light absorbing humic substances were removed in a pre-treatment. Under given conditions (i.e., temperate climate) fish would rather play an accompanying role in the ecological production process. A wastewater-fed aquaculture facility resembles an integrated production plant rather than a wastewater disposal site. In addition to that, it has potential to prove advantageous over the highly developed conventional wastewater treatment plants established in Middle Europe. Further research in this field is essential and also recommended, considering political programs like Agenda 21, which contemplate the need for sustainable strategies for handling resources.


In dogs, the surgical techniques and other technical considerations for the transplantation of most tissues and organs in the body are well established. The last remaining obstacle to uniformly safe and successful organ transplantation is the immune response to foreign tissue antigen and our present inability to completely suppress this response in a specific and safe manner. Immunosuppressive techniques currently available are largely non-specific and unfortunately cause many potentially fatal side effects. As a result graft recipients must be constantly monitored so that enough immunosuppressive treatment is given to prevent rejection but not so much that the recipient develops life threatening complications. The enormous cost and the services necessary to provide this attention in view of the relatively poor survival rates of tissue and organ grafts in dogs will continue to prevent organ transplantation becoming a reality in veterinary practice. Hopefully future advances in tissue-typing and the induction of specific immunological adaption in dogs by ensuring consistently safe and successful transplantation will ead to minimal postoperative attention.


The authors studied the literature for similar findings in order to try to classify the different types of pneumoperitoneum when they had a case of pneumoperitoneum of genital origin. They then went on to study the mechanism by which these rare cases of genital pneumoperitoneum occurred: the insufflation or aspiration of air through the tubes, tubal antiperistalsis and uterine or vaginal perforations. From the clinical angle it is essential to eliminate pneumoperitoneum secondary to perforation of a hollow organ, and then to look for signs of peritonitis which only occur in genital pneumoperitoneum due to uterine perforation. The case usually cures spontaneously but recurrences are not uncommon. If there are no signs of peritonitis expectant treatment should usually be undertaken.


S U M M A R Y Tectonic deformation in the NE Basin and Range Province of the western United States is concentrated in two zones, the N-S trending northern part of the Intermountain seismic belt in northern Utah, SE Idaho and SW Wyoming and the E-W trending Central Idaho seismic zone, which converge at Yellowstone in NW Wyoming. Accepting the popular view that the Yellowstone volcanic field is above an upwelling plume from the deep mantle, I explore the possibility that deformation of the brittle upper crust in these two seismic zones may be caused by return flow from this plume. This return flow is assumed sheared SW in the direction of motion of the North American plate relative to Yellowstone. The Snake River Plain (SRP), a linear outcrop of Neogene and Quaternary basalt that trends SW from Yellowstone for more than 400 km, bisecting the angle between the two seismic zones, may be a trail formed as the plate moves SW across the upwelling plume. Beyond -150 km from Yellowstone, slip vectors on active normal faults in both deforming zones are oriented inwards at -45" towards the SW azimuth along the SRP. Normal slip rates on these faults are typically 1 mm yr-', implying extensional strain rate -lo-'' SKI. Proportions of normal slip and strike slip suggest faults in the Intermountain seismic belt are rotating anticlockwise at -2" Myr-' around vertical axes, and faults in the central Idaho seismic zone are rotating clockwise at similar rates. Within -100 km of Yellowstone, observed sense of rotation around vertical axes in both zones appears reversed. Tilt rates of hanging wall beds suggest most faults in both zones are rotating at -2"Myr-' (also -lO-"s-') around horizontal axes oriented NW. The relative size of rotation rate around vertical axes and horizontal extensional strain rate is shown to imply that velocity in the underlying deforming 'fluid' is small in the direction perpendicular to the axis of the SRP. In an initial model, this velocity is set to zero, enabling the two-dimensional pattern of flow at the horizontal upper boundary of this deforming fluid to be solved straightforwardly. This approximation enables observed rates and senses of horizontal extension and rotation around a vertical axis to be explained as consequences of the pattern of horizontal gradients of velocity parallel to the axis of the SRP in the deforming fluid beneath the brittle layer. A refinement suggests that velocity perpendicular to the SRP near the upper boundary of the deforming 'fluid' is small but inward towards the SRP from both sides, and is accompanied by downwelling beneath the SRP beyond -100 km SW of Yellowstone. This pattern of flow will act to move magma in the uppermost mantle beneath the SRP from its sides. It may thus reconcile petrological observations that SRP basalts do not show deep mantle characteristics expected had they been extruded from the Yellowstone plume, with the existence of this plume nearby. Conservation of angular momentum around horizontal axes perpendicular to the SRP for the combined system of the plume interacting with the North American plate leads to the deduction that the plume radius is -50 km, consistent with results of other investigations, and its upwelling velocity is -60 mm yr-'.


Background: Fecal occult blood testing (FOBT) is the recommended first line screening for the detection of colorectal cancer (CRC). To improve the detection of CRC we evaluated serum markers and combinations of serum markers as an alternative approach. Methods: Applying Lasso Regression, a specialized form of penalized logistic regression, we selected six markers for an evaluation in a collective of 857 patients including 301 CRC patients, 143 patients with adenoma, 266 healthy controls and 147 disease controls. For each marker and marker combination the performance was assessed. Results: We tested a total of 22 biomarkers for the detection of CRC from serum. Of these six markers were selected for a marker combination by Lasso Regression. Included were the well-known tumor markers CEA and CYFRA21-1 as well as novel markers or markers that are less routinely used for the detection of CRC: ferritin, osteopontin, anti-p53 and seprase. CEA showed the best sensitivity of all markers with 43.9 % at 95% specificity, followed by seprase (42.4%), CYFRA21-1 (35.5%), osteopontin (30.2%), ferritin (23.9%) and anti-p53 (20.0%). When these markers were combined a sensitivity of 72.3% was reached at a corresponding specificity of 95% and of 62.1% at 98% specificity. Focusing on more screening relevant stages, UICC stages 0-III, reduced the sensitivity slightly to 68.0% and 53.3%, respectively. In a sub-collective where matched stool samples were available (75 CRC cases and 234 controls) the sensitivity of the marker combination was comparable to fecal immunochemical testing (FIT) with 82.4% and 68.9% vs. 81.8% and 72.7% at 95% and 98% specificity, respectively. Conclusion: When six markers were combined to detect CRC from serum, the combination reached a performance that was comparable to FIT. This provides a novel tool for CRC screening to trigger a follow-up colonoscopy for a final diagnosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2738.


Modeling and simulation are recognized as important aspects of the scientific method for more than 70 years but its adoption in biology has been slow. Debates on its representativeness, usefulness, and whether the effort spent on such endeavors is worthwhile, exist to this day. Here, I argue that most of learning is modeling; hence, arriving at a contradiction if models are not useful. Representing biological systems through mathematical models can be difficult but the modeling procedure is a process in itself that follows a semi-formal set of rules. Although seldom reported, failure in modeling is not a rare event but I argue that this is usually a result of erroneous underlying knowledge or mis-application of a model beyond its intended purpose. I argue that in many biological studies, simulation is the only experimental tool. In others, simulation is a means of reducing possible combinations of experimental work; thereby, presenting an economical case for simulation; thus, worthwhile to engage in this endeavor. The representativeness of simulation depends on the validation, verification, assumptions, and limitations of the underlying model. This will be illustrated using the inter-relationship between population, samples, probability theory, and statistics.


Background: Although the incidence of myocardial bridge (MB) has been defined in different conventional coronary angiography (CCA) studies,the frequency of MB in radial access coronary angiography (RACA) is unknown.The aim of this study was to determine the incidence of MB in patients undergoing RACA.Method: A total of 2600 consecutive patients who underwent RACA were retrospectively investigated to detect the presence of MB.The clinical,laboratory, and angiographic features of the patients with MB were analyzed. Results: MB was detected at an incidence of 10.2%, in 255/2600 patients who underwent RACA.The most involved coronary artery was the left anterior descending artery (LAD) (86.9%) and the mid segment (84.9%) was the most affected section.Co-involvement of multiple coronary arteries by MB was 7.8%. Coronary artery disease (CAD) was determined in 102 (36.2%) of the coronary arteries with MB, 82.4% which were proximal to the MB.Conclusion: These data demonstrated that the incidence of MB able to be detected on RACA was much higher than reported in previous CCA studies.