bluuebunny/crossref_metadata_2025 huggingface dataset:
*Cages:
Authors: García Francisco González , Paradinas Teresa , Coll Narcís , Patow Gustavo
Published: July 2013

Cage-based deformation has been one of the main approaches for mesh deformation in recent years, with a lot of interesting and active research. The main advantages of cage-based deformation techniques are their simplicity, relative flexibility, and speed. However, to date there has been no widely accepted solution that provides both user control at different levels of detail and high-quality deformations. We present *Cages (star-cages), a significant step forward with respect to traditional single-cage coordinate systems, and which allows the usage of multiple cages enclosing the model for easier manipulation while still preserving the smoothness of the mesh in the transitions between them. The proposed deformation scheme is extremely flexible and versatile, allowing the usage of heterogeneous sets of coordinates and different levels of deformation, ranging from a whole-model deformation to a very localized one. This locality allows faster evaluation and a reduced memory footprint, and as a result outperforms single-cage approaches in flexibility, speed, and memory requirements for complex editing operations.
Analytic displacement mapping using hardware tessellation
Authors: Nießner Matthias , Loop Charles
Published: July 2013

Displacement mapping is ideal for modern GPUs since it enables high-frequency geometric surface detail on models with low memory I/O. However, problems such as texture seams, normal recomputation, and undersampling artifacts have limited its adoption. We provide a comprehensive solution to these problems by introducing a smooth analytic displacement function. Coefficients are stored in a GPU-friendly tile-based texture format, and a multiresolution mip hierarchy of this function is formed. We propose a novel level-of-detail scheme by computing per-vertex adaptive tessellation factors and select the appropriate prefiltered mip levels of the displacement function. Our method obviates the need for a precomputed normal map since normals are directly derived from the displacements. Thus, we are able to perform authoring and rendering simultaneously without typical displacement map extraction from a dense triangle mesh. This not only is more flexible than the traditional combination of discrete displacements and normal maps, but also provides faster runtime due to reduced memory I/O.
A Master Theorem for Discrete Divide and Conquer Recurrences
Authors: Drmota Michael , Szpankowski Wojciech
Published: July 2013

Divide-and-conquer
recurrences are one of the most studied equations in computer science. Yet, discrete versions of these recurrences, namely for some known sequence
a
n
and given
b
j
,
b
j
,
p
j
and
δ
j
,
δ
j
, present some challenges. The discrete nature of this recurrence (represented by the floor and ceiling functions) introduces certain oscillations not captured by the traditional Master Theorem, for example due to Akra and Bazzi [1998] who primary studied the continuous version of the recurrence. We apply powerful techniques such as Dirichlet series, Mellin-Perron formula, and (extended) Tauberian theorems of Wiener-Ikehara to provide a complete and precise solution to this basic computer science recurrence. We illustrate applicability of our results on several examples including a popular and fast arithmetic coding algorithm due to Boncelet for which we estimate its average redundancy and prove the Central Limit Theorem for the phrase length. To the best of our knowledge,
discrete
divide and conquer recurrences were not studied in this generality and such detail; in particular, this allows us to compare the redundancy of Boncelet’s algorithm to the (asymptotically) optimal Tunstall scheme.
A partition-based method for string similarity joins with edit-distance constraints
Authors: Li Guoliang , Deng Dong , Feng Jianhua
Published: July 2013

As an essential operation in data cleaning, the similarity join has attracted considerable attention from the database community. In this article, we study string similarity joins with edit-distance constraints, which find similar string pairs from two large sets of strings whose edit distance is within a given threshold. Existing algorithms are efficient either for short strings or for long strings, and there is no algorithm that can efficiently and adaptively support both short strings and long strings. To address this problem, we propose a new filter, called
the segment filter
. We partition a string into a set of segments and use the segments as a filter to find similar string pairs. We first create inverted indices for the segments. Then for each string, we select some of its substrings, identify the selected substrings from the inverted indices, and take strings on the inverted lists of the found substrings as candidates of this string. Finally, we verify the candidates to generate the final answer. We devise efficient techniques to select substrings and prove that our method can minimize the number of selected substrings. We develop novel pruning techniques to efficiently verify the candidates. We also extend our techniques to support normalized edit distance. Experimental results show that our algorithms are efficient for both short strings and long strings, and outperform state-of-the-art methods on real-world datasets.
A comparative study on IP prefixes and their origin ases in BGP and the IRR
Authors: Khan Akmal , Kim Hyun-chul , Kwon Taekyoung , Choi Yanghee
Published: July 2013

The IRR is a set of globally distributed databases with which ASes can register their routing and address-related information. It is often believed that the quality of the IRR data is not reliable since there are few economic incentives for the ASes to register and update their routing information timely. To validate these negative beliefs, we carry out a comprehensive analysis of (IP prefix, its origin AS) pairs in BGP against the corresponding information registered with the IRR, and vice versa. Considering the BGP and IRR practices, we propose a methodology to match the (IP prefix, origin AS) pairs between the IRR and BGP. We observe that the practice of registering IP prefi xes and origin ASes with the IRR is prevalent. However, the quality of the IRR data can vary substantially depending on routing registries, regional Internet registries (to which ASes belong), and AS types. We argue that the IRR can help improve the security level of BGP routing by making BGP routers selectively rely on the corresponding IRR data considering these observations.
Making sense of internet censorship
Authors: Burnett Sam , Feamster Nick
Published: July 2013

Free and open access to information on the Internet is at risk: more than 60 countries around the world practice some form of Internet censorship, and both the number of countries practicing censorship and the proportion of Internet users who are subject to it are likely to increase. We posit that, although it may not always be feasible to guarantee free and open access to information, citizens have the right to know when their access has been obstructed, restricted, or tampered with, so that they can make informed decisions on information access. We motivate the need for a system that provides accurate, verifiable reports of censorship and discuss the challenges involved in designing such a system. We place these challenges in context by studying their applicability to OONI, a new censorship measurement platform.
The 5th workshop on active internet measurements (AIMS-5) report
Authors: claffy kc
Published: July 2013

On February 6-8, 2013, CAIDA hosted the fifth Workshop on Active Internet Measurements (AIMS-5) as part of our series of Internet Statistics and Metrics Analysis (ISMA) workshops. As with previous AIMS workshops, the goals were to further our understanding of the potential and limitations of active measurement research and infrastructure in the wide-area Internet, and to promote cooperative solutions and coordinated strategies to address future data needs of the network and security operations and research communities. The workshop focus this year was on creating, managing, and analyzing annotations of large longitudinal active Internet measurement data sets. Due to popular demand, we also dedicated half a day to large-scale active measurement (performance/topology) from mobile/cellular devices. This report describes topics discussed at this year's workshop. Materials related to the workshop are available at http://www.caida.org/workshops/.
Sex and vasodilator responses to hypoxia at rest and during exercise
Authors: Casey Darren P. , Shepherd John R. A. , Joyner Michael J.
Published: July 2013

In humans, β-adrenergic receptor activation causes a substantial portion of hypoxic vasodilation in skeletal muscle at rest and during forearm exercise. Recent evidence suggests that β-adrenergic receptors are either more sensitive or upregulated in young women vs. men. Therefore, we examined whether sex influences hypoxic vasodilation in 31 young subjects (15 women/16 men; 26 ± 1 yr). We also examined whether potential sex-related differences existed in a group of older adults (6 women/5 men; 61 ± 2 yr). All subjects performed forearm exercise at 10 and 20% of maximum under normoxic and hypoxic [80% arterial O2 saturation (So2)] conditions. Forearm vascular conductance (FVC; ml·min−1·100 mmHg−1) was calculated from blood flow (ml/min) and blood pressure (mmHg). At rest, young women demonstrated a greater vasodilator response to hypoxia compared with men (39 ± 12 vs. 13 ± 6%, P < 0.05). The absolute compensatory vasodilator response (hypoxic FVC-normoxic FVC) during exercise was similar between sexes, but the relative change was greater in young women at 10% (28 ± 5 vs. 17 ± 3%, P < 0.05) and 20% exercise (29 ± 4% vs. 15 ± 3%, P < 0.01). Additionally, the absolute changes in vasodilation after normalizing the response to forearm volume or workload were greater in young women during exercise ( P < 0.05). Interestingly, the compensatory vasodilator responses between older women and men were similar at 10 and 20% exercise, regardless of whether the response is expressed as absolute, relative, or absolute change normalized for forearm volume or workload ( P = 0.054–0.97). Our data suggest that the compensatory vasodilator response to hypoxic exercise is greater in young women compared with men. However, sex-specific differences appear to be lost with aging.
Baroreflex-mediated cardiovascular responses to hyperbaric oxygen
Authors: Demchenko Ivan T. , Zhilyaev Sergei Y. , Moskvin Alexander N. , Krivchenko Alexander I. , Piantadosi Claude A. , Allen Barry W.
Published: July 2013

The cardiovascular system responds to hyperbaric hyperoxia (HBO2) with vasoconstriction, hypertension, bradycardia, and reduced cardiac output (CO). We tested the hypothesis that these responses are linked by a common mechanism—activation of the arterial baroreflex. Baroreflex function in HBO2 was assessed in anesthetized and conscious rats after deafferentation of aortic or carotid baroreceptors or both. Cardiovascular and autonomic responses to HBO2 in these animals were compared with those in intact animals at 2.5 ATA for conscious rats and at 3 ATA for anesthetized rats. During O2 compression, hypertension was greater after aortic or carotid baroreceptor deafferentation and was significantly more severe if these procedures were combined. Similarly, the hyperoxic bradycardia observed in intact animals was diminished after aortic or carotid baroreceptor deafferentation and replaced by a slight tachycardia after complete baroreceptor deafferentation. We found that hypertension, bradycardia, and reduced CO—the initial cardiovascular responses to moderate levels of HBO2—are coordinated through a baroreflex-mediated mechanism initiated by HBO2-induced vasoconstriction. Furthermore, we have shown that baroreceptor activation in HBO2 inhibits sympathetic outflow and can partially reverse an O2-dependent increase in arterial pressure.
Self in motion: sensorimotor and cognitive mechanisms in gait agency
Authors: Kannape O. A. , Blanke O.
Published: July 2013

Acting in our environment and experiencing ourselves as conscious agents are fundamental aspects of human selfhood. While large advances have been made with respect to understanding human sensorimotor control from an engineering approach, knowledge about its interaction with cognition and the conscious experience of movement (agency) is still sparse, especially for locomotion. We investigated these relationships by using life-size visual feedback of participants' ongoing locomotion, thereby extending agency research previously limited to goal-directed upper limb movements to continuous movements of the entire body. By introducing temporal delays and cognitive loading we were able to demonstrate distinct effects of bottom-up visuomotor conflicts as well as top-down cognitive loading on the conscious experience of locomotion (gait agency) and gait movements. While gait agency depended on the spatial and temporal congruency of the avatar feedback, gait movements were solely driven by its temporal characteristics as participants nonconsciously attempted to synchronize their gait with their avatar's gait. Furthermore, gait synchronization was suppressed by cognitive loading across all tested delays, whereas gait agency was only affected for selective temporal delays that depended on the participant's step cycle. Extending data from upper limb agency and auditory gait agency, our results are compatible with effector-independent and supramodal control of agency; they show that both mechanisms are dissociated from automated sensorimotor control and that cognitive loading further enhances this dissociation.
Characterising Cytokine Gene Expression Signatures in Patients with Severe Sepsis
Authors: Grealy Robert , White Mary , Stordeur Patrick , Kelleher Dermot , Doherty Derek G. , McManus Ross , Ryan Thomas
Published: July 2013

Introduction. Severe sepsis in humans may be related to an underlying profound immune suppressive state. We investigated the link between gene expression of immune regulatory cytokines and the range of illness severity in patients with infection and severe sepsis.Methods. A prospective observational study included 54 ICU patients with severe sepsis, 53 patients with infection without organ failure, and 20 healthy controls. Gene expression in peripheral blood mononuclear cells (PBMC) was measured using real-time polymerase chain reaction.Results. Infection differed from health by decreased expression of the IL2, and IL23 and greater expression of IL10 and IL27. Severe sepsis differed from infection by having decreased IL7, IL23, IFNγ, and TNFαgene expression. An algorithm utilising mRNA copy number for TNFα, IFNγ, IL7, IL10, and IL23 accurately distinguished sepsis from severe sepsis with a receiver operator characteristic value of 0.88. Gene expression was similar with gram-positive and gram-negative infection and was similar following medical and surgical severe sepsis. Severity of organ failure was associated with serum IL6 protein levels but not with any index of cytokine gene expression in PBMCs.Conclusions. Immune regulatory cytokine gene expression in PBMC provides a robust method of modelling patients’ response to infection.
Prostasin: An Epithelial Sodium Channel Regulator
Authors: Aggarwal Shakti , Dabla Pradeep K. , Arora Sarika
Published: July 2013

Prostasin is a glycophosphatidylinositol-anchored protein which is found in prostate gland, kidney, bronchi, colon, liver, lung, pancreas, and salivary glands. It is a serine protease with trypsin-like substrate specificity which was first purified from seminal fluid in 1994. In the last decade, its diverse roles in various biological and physiological processes have been elucidated. Many studies done to date suggest that prostasin is one of several membrane peptidases regulating epithelial sodium channels in mammals. A comprehensive literature search was conducted from the websites of Pubmed Central, the US National Library of Medicine’s digital archive of life sciences literature and the National Library of Medicine. The data was also assessed from journals and books that published relevant articles in this field. Understanding the mechanism by which prostasin and its inhibitors regulate sodium channels has provided a new insight into the treatment of hypertension and some other diseases like cystic fibrosis. Prostasin plays an important role in epidermal growth factor receptor (EGFR) signal modulation. Extracellular proteases have been implicated in tumor metastasis and local tissue invasion because of their ability to degrade extracellular matrices.
Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis
Authors: Lohner Ralph , Schwederski Markus , Narath Carolin , Klein Johanna , Duerr Georg D. , Torno Alexandra , Knuefermann Pascal , Hoeft Andreas , Baumgarten Georg , Meyer Rainer , Boehm Olaf
Published: July 2013

Background. Aim was to elucidate the role of toll-like receptor 9 (TLR9) in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis.Methods. Sepsis was induced via colon ascendens stent peritonitis (CASP) in C57BL/6 wild-type (WT) and TLR9-deficient (TLR9-D) mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h. Eighteen hours after CASP cardiac function was monitoredin vivo. Sarcomere length of isolated cardiomyocytes was measured at 0.5 to 10 Hz after incubation with heat-inactivated bacteria.Results. CASP led to continuous release of bacteria into the peritoneal cavity, an increase of cytokines, and differential regulation of receptors of innate immunity in the heart. Eighteen hours after CASP WT mice developed septic heart failure characterised by reduction of end-systolic pressure, stroke volume, cardiac output, and parameters of contractility. This coincided with reduced cardiomyocyte sarcomere shortening. TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function. This was consistent with reduced mortality in TLR9-D compared to WT mice.Conclusions. In polymicrobial sepsis TLR9 signalling is pivotal to cardiac inflammation and septic heart failure.
Haplogroup T Is an Obesity Risk Factor: Mitochondrial DNA Haplotyping in a Morbid Obese Population from Southern Italy
Authors: Nardelli Carmela , Labruna Giuseppe , Liguori Rosario , Mazzaccara Cristina , Ferrigno Maddalena , Capobianco Valentina , Pezzuti Massimo , Castaldo Giuseppe , Farinaro Eduardo , Contaldo Franco , Buono Pasqualina , Sacchetti Lucia , Pasanisi Fabrizio
Published: July 2013

Mitochondrial DNA (mtDNA) haplogroups have been associated with the expression of mitochondrial-related diseases and with metabolic alterations, but their role has not yet been investigated in morbid obese Caucasian subjects. Therefore, we investigated the association between mitochondrial haplogroups and morbid obesity in patients from southern Italy. The mtDNA D-loop of morbid obese patients (n=500; BMI > 40 kg/m2) and controls (n=216; BMI < 25 kg/m2) was sequenced to determine the mtDNA haplogroups. The T and J haplogroup frequencies were higher and lower, respectively, in obese subjects than in controls. Women bearing haplogroup T or J had twice or half the risk of obesity. Binomial logistic regression analysis showed that haplogroup T and systolic blood pressure are risk factors for a high degree of morbid obesity, namely, BMI > 45 kg/m2and in fact together account for 8% of the BMI. In conclusion, our finding that haplogroup T increases the risk of obesity by about two-fold, suggests that, besides nuclear genome variations and environmental factors, the T haplogroup plays a role in morbid obesity in our study population from southern Italy.
Behçet’s Disease and Intracardiac Thrombosis: A Report of Three Cases
Authors: Düzgün Nurşen , Küçükşahin Orhan , Atasoy Kayhan Çetin , Togay Işıkay Canan , Gerede Demet Menekşe , Erden Ayşe , Şahap Seda Kaynak , İbiş Muhammed Arif , Ateş Aşkın
Published: July 2013

We present three patients with Behçet’s disease associated with intracardiac thrombus and pulmonary vascular involvement. One of these patients had also Budd-Chiari syndrome. All patients were treated with corticosteroid plus monthly intravenous cyclophosphamide as first line treatment and with no recurrences. Immunosuppressive therapy was successful in the treatment of intracardiac thrombus and also in the regression of pulmonary vascular thromboses in these patients. Intracardiac thrombus in Behçet’s disease is rarely seen. Behçet’s disease should be remembered in the differential diagnosis of the patients with intracardiac mass, especially in patients from the Mediterranean and Middle East populations.
Objective versus Subjective Assessment of Laparoscopic Skill
Authors: van Empel Pieter J. , van Rijssen Lennart B. , Commandeur Joris P. , Verdam Mathilde G. E. , Huirne Judith A. , Scheele Fedde , Bonjer H. Jaap , Meijerink W. Jeroen
Published: July 2013

Background. The equality of subjective- and objective-assessment methods in laparoscopic surgery are unknown. The aim of this study was to compare a subjective assessment method to an objective assessment method to evaluate laparoscopic skill. Methods. A prospective observational cohort study was conducted. Seventy-two residents completed a basic laparoscopic suturing task on a box trainer at two consecutive assessment points. Laparoscopic skill was rated subjectively using the Objective Structured Assessment of Technical Skills (OSATS) list and objectively using the TrEndo, an augmented-reality simulator. Results. TrEndo scores between the two assessment points correlated. OSATS scores did not correlate between the two assessment points. There was a correlation between TrEndo and OSATS scores at the first assessment point, but not at the second assessment point. Overall, OSATS scores correlated with TrEndo scores. There was a greater spread within OSATS scores compared to TrEndo scores. Conclusion. OSATS scores correlated with TrEndo scores. The TrEndo may be more responsive at rating individual’s laparoscopic skill, as demonstrated by a smaller overall spread in TrEndo scores. The additional value of objective assessment methods over conventional assessment methods as provided by laparoscopic simulators should be investigated.
The Adaptive Nature of the Bone-Periodontal Ligament-Cementum Complex in a Ligature-Induced Periodontitis Rat Model
Authors: Lee Ji-Hyun , Lin Jeremy D. , Fong Justine I. , Ryder Mark I. , Ho Sunita P.
Published: July 2013

The novel aspect of this study involves illustrating significant adaptation of a functionally loaded bone-PDL-cementum complex in a ligature-induced periodontitis rat model. Following 4, 8, and 15 days of ligation, proinflammatory cytokines (TNF-αand RANKL), a mineral resorption indicator (TRAP), and a cell migration and adhesion molecule for tissue regeneration (fibronectin) within the complex were localized and correlated with changes in PDL-space (functional space). At 4 days of ligation, the functional space of the distal complex was widened compared to controls and was positively correlated with an increased expression of TNF-α. At 8 and 15 days, the number of RANKL(+) cells decreased near the mesial alveolar bone crest (ABC) but increased at the distal ABC. TRAP(+) cells on both sides of the complex significantly increased at 8 days. A gradual change in fibronectin expression from the distal PDL-secondary cementum interfaces through precementum layers was observed when compared to increased and abrupt changes at the mesial PDL-cementum and PDL-bone interfaces in ligated and control groups. Based on our results, we hypothesize that compromised strain fields can be created in a diseased periodontium, which in response to prolonged function can significantly alter the original bone and apical cementum formations.
Chemopreventive Activity of Plant Flavonoid Isorhamnetin in Colorectal Cancer Is Mediated by Oncogenic Src and β-Catenin
Authors: Saud Shakir M. , Young Matthew R. , Jones-Hall Yava L. , Ileva Lilia , Evbuomwan Moses O. , Wise Jennifer , Colburn Nancy H. , Kim Young S. , Bobe Gerd
Published: July 2013

Analysis of the Polyp Prevention Trial showed an association between an isorhamnetin-rich diet and a reduced risk of advanced adenoma recurrence; however, the mechanism behind the chemoprotective effects of isorhamnetin remains unclear. Here, we show that isorhamnetin prevents colorectal tumorigenesis of FVB/N mice treated with the chemical carcinogen azoxymethane and subsequently exposed to colonic irritant dextran sodium sulfate (DSS). Dietary isorhamnetin decreased mortality, tumor number, and tumor burden by 62%, 35%, and 59%, respectively. MRI, histopathology, and immunohistochemical analysis revealed that dietary isorhamnetin resolved the DSS-induced inflammatory response faster than the control diet. Isorhamnetin inhibited AOM/DSS–induced oncogenic c-Src activation and β-catenin nuclear translocation, while promoting the expression of C-terminal Src kinase (CSK), a negative regulator of Src family of tyrosine kinases. Similarly, in HT-29 colon cancer cells, isorhamnetin inhibited oncogenic Src activity and β-catenin nuclear translocation by inducing expression of csk, as verified by RNA interference knockdown of csk. Our observations suggest the chemoprotective effects of isorhamnetin in colon cancer are linked to its anti-inflammatory activities and its inhibition of oncogenic Src activity and consequential loss of nuclear β-catenin, activities that are dependent on CSK expression. Cancer Res; 73(17); 5473–84. ©2013 AACR.
Defining Risks of Taxane Neuropathy: Insights from Randomized Clinical Trials
Authors: Kudlowitz David , Muggia Franco
Published: July 2013

Sensory neuropathy is a common but difficult to quantify complication encountered during treatment of various cancers with taxane-containing regimens. Docetaxel, paclitaxel, and its nanoparticle albumin-bound formulation have been extensively studied in randomized clinical trials comparing various dose and schedules for the treatment of breast, lung, and ovarian cancers. This review highlights differences in extent of severe neuropathies encountered in such randomized trials and seeks to draw conclusions in terms of known pharmacologic factors that may lead to neuropathy. This basic knowledge provides an essential background for exploring pharmacogenomic differences among patients in relation to their susceptibility of developing severe manifestations. In addition, the differences highlighted may lead to greater insight into drug and basic host factors (such as age, sex, and ethnicity) contributing to axonal injury from taxanes. Clin Cancer Res; 19(17); 4570–7. ©2013 AACR.
MET and ERBB2 Are Coexpressed in ERBB2+ Breast Cancer and Contribute to Innate Resistance
Authors: Paulson Amanda K. , Linklater Erik S. , Berghuis Bree D. , App Colleen A. , Oostendorp Leon D. , Paulson Jayne E. , Pettinga Jane E. , Melnik Marianne K. , Vande Woude George F. , Graveel Carrie R.
Published: July 2013

Breast cancer displays significant intratumoral heterogeneity, which has been shown to have a substantial impact on both innate and acquired resistance to tyrosine kinase inhibitors. The heterogeneous expression of multiple receptor tyrosine kinases (RTK) in cancers supports tumor signaling robustness and plays a significant role in resistance to targeted inhibition. Recent studies have revealed interactions between the MET receptor and the ERBB receptor family in the therapeutic resistance of several cancers. In this study, the relationship between MET expression/activity and the expression/activity of the ERBB receptor family in human breast cancer was interrogated. Importantly, a significant percentage of ERBB2+ tumors coexpressing MET and ERBB2 were observed and displayed significant heterogeneity with subpopulations of cells that are MET−/ERBB2+, MET+/ERBB2−, and MET+/ERBB2+. In a MET+/ERBB2+ breast cancer cell line, MET depletion resulted in increased ERBB2 activation, and conversely, ERBB2 depletion resulted in increased MET activation. Neither EGFR nor ERBB3 compensated for MET or ERBB2 knockdown. The loss of either MET or ERBB2 led to a decrease in PI3K/AKT signaling and increased dependency on MAPK. These data show that a subset of ERBB2+ breast cancers express MET and contain MET+/ERBB2+ subpopulations. Moreover, analysis of RTK activation during ERBB2 knockdown indicated that MET signaling is a compensatory pathway of resistance.

Implications: ERBB2+ breast cancers with MET+/ERBB2+ subpopulations may have an innate resistance to ERBB2 inhibition and may benefit from combined MET and ERBB2 inhibition. Mol Cancer Res; 11(9); 1112–21. ©2013 AACR.
Early Biochemical and Hematological Response to Intramuscular Cyanocobalamin Therapy in Vitamin B12-Deficient Patients
Authors: Mansoor M. Azam , Stea Tonje Holte , Schneede Jørn , Reine Andreas
Published: July 2013

Background: Data on early biochemical and hematological responses to cobalamin therapy in vitamin B12-deficient patients are scarce. Therefore, we investigated whether cobalamin injections would include prompt biochemical and hematological responses in vitamin B12-deficient patients. Subjects and Methods: Seven female patients (mean age: 69.4 years, range: 61-78) with a mean serum cobalamin level of 104 ± 38 pmol/l mean ± SD and 7 male patients (mean age: 67.0 years, range: 53-78) with a mean serum cobalamin level of 84 ± 40 (±SD) participated in the study. They were administered 1 mg i.m. cyanocobalamin per week for 3 weeks. Blood samples were collected before and 1, 3, 7, 14 and 21 days after cobalamin injection. The concentrations of plasma aminothiols and serum methylmalonic acid (MMA) were measured with high-performance liquid chromatography and gas chromatography/mass spectrometry, respectively, and hematological parameters were determined with a hematological analyzer. Results: Already 1 day after intramuscular Cobalamin injections, the concentrations of serum vitamin B12 and plasma total cysteine were significantly increased while the concentrations of serum folate, plasma total homocysteine and serum MMA were decreased. Mean cell volume was also significantly decreased first after 14 days of therapy. Conclusion: Intramuscular cobalamin administration causes swift and significant changes in plasma aminothiols, whereas the first change in hematological parameters was detected only after 14 days.
Early Intervention with Probiotic Lactobacillus paracasei F19 Has No Long-Term Effect on Caries Experience
Authors: Hasslöf P. , West C.E. , Karlsson Videhult F. , Brandelius C. , Stecksén-Blicks C.
Published: July 2013

The aim of the study was to evaluate possible long-term effects of a cereal diet supplemented with Lactobacillus paracasei F19 (LF19) during weaning on caries experience, mutans streptococci (MS) and lactobacilli (LBC) in a group of 9-year-old children. A secondary aim was to evaluate if the intervention resulted in the permanent integration of LF19 as part of the oral microbiota. The study followed up on a double-blind placebo-controlled randomised trial. Among 179 infants that were randomised to a daily diet that included cereals with or without LF19 from 4 to 13 months of age, 56 from the probiotic group and 62 from the placebo group participated in the follow-up at 9 years. Data were collected by oral clinical examination and questionnaires. MS and LBC levels were assessed with conventional cultivation; LF19 was detected by using randomly amplified polymerase chain reactions (RAPD-PCR). At the follow-up, neither decayed, missing and filled surfaces for primary teeth (dmfs) nor decayed, missing and filled surfaces for permanent teeth (DMFS) differed significantly between the probiotic and placebo groups (p > 0.05). MS and LBC levels were similar in both groups (p > 0.05). RAPD-PCR showed no evidence of oral colonisation with LF19 in the study group. It is concluded that an early intervention with LF19 did not affect the frequency of dental caries, MS or LBC. LF19 did not establish itself as a permanent facet of the oral microbiota in any of the subjects included in this study.
Bevacizumab with Erlotinib as First-line Therapy in Asian Patients with Advanced Hepatocellular Carcinoma: A Multicenter Phase II Study
Authors: Hsu Chih-Hung , Kang Yoon Koo , Yang Tsai-Shen , Shun Chia-Tung , Shao Yu-Yun , Su Wu-Chou , Sandoval-Tan Jennifer , Chiou Tzeon-Jye , Jin Kate , Hsu Chiun , Cheng Ann-Lii
Published: July 2013

Objectives: The bevacizumab/erlotinib combination was reported with high clinical activity for advanced hepatocellular carcinoma (HCC) by a phase II study conducted in the USA. This multicenter study across several Asian countries was to evaluate the safety and efficacy of the combination in this population. Methods: Patients with histology-proven HCC, advanced disease and Child-Pugh class A liver function received bevacizumab 5 mg/kg intravenously every 2 weeks and erlotinib 150 mg/day orally as first-line therapy. The primary end point was progression-free survival at 16 weeks (PFS-16W). The expression of epidermal growth factor receptor (EGFR), phospho-AKT and vascular endothelial growth factor, the microvessel density and the EGFR gene copy number in HCC tissues were correlated with treatment efficacy. Results: Fifty-one patients were enrolled. The PFS-16W was 35.3% (95% CI 22.4-49.9), the median PFS was 2.9 months (95% CI, 1.3-4.4) and the median overall survival was 10.7 months (95% CI, 6.2-15.2). Grade 3/4 toxicities were uncommon, including rash, acne (10% each), diarrhea (6%) and gastrointestinal bleeding (4%). None of the evaluated biomarkers correlated with disease control or PFS. Conclusions: Bevacizumab plus erlotinib showed good tolerability and modest activity in this Asian cohort. Further studies are warranted to identify the predictive biomarkers of this combination.
Smooth Muscle Contractile Plasticity in Rat Mesenteric Small Arteries: Sensitivity to Specific Vasoconstrictors, Distension and Inflammatory Cytokines
Authors: Tuna Bilge Guvenc , Schoorl Marieke J.C. , Bakker Erik N.T.P. , de Vos Judith , VanBavel Ed
Published: July 2013

Small artery remodeling may involve a shift in the diameter-dependent force generating capacity of smooth muscle cells (SMC). We tested to what extent and under which conditions such contractile plasticity occurs. Rat mesenteric arteries were mounted on isometric myographs. Active diameter-tension relations were determined after application of several stimuli for 16 or 40 h at 40 or 110% of the passive diameter at 100 mm Hg. At 40%, 16-hour incubation with endothelin-1 (ET-1) but not U46619 shifted force capacity towards smaller diameters. Inflammatory cytokines (TNF-α, IL-1β, IFN-γ), TGF-β or serum neither induced such shift nor augmented the effect of ET-1. The ET-1-mediated change was not affected by superoxide dismutase and catalase. Inward matrix remodeling in the presence of ET-1 was slower, occurring after 40 h. Arteries maintained at 110% showed a shift of force capacity to larger diameters, which was prevented by ET-1 but not by U46619. In the active but not the passive state, SMC had altered nuclear lengths after incubation at 40%. These data demonstrate contractile plasticity in small arteries, where chronic strain is an outward drive and specifically ET-1 an inward drive, acting through mechanisms that do not seem to relate to oxidative stress, inflammatory pathways or major reorganization of the SMC.
Inhibitor κB Kinase 2 Is a Myosin Light Chain Kinase in Vascular Smooth Muscle
Authors: Ying Zhekang , do Carmo Jussara M. , Xiang Lusha , da Silva Alexandre A. , Chen Minjie , Ryan Michael J. , Ostrowski Michael , Rajagopalan Sanjay , Hall John E.
Published: July 2013

Rationale:

Myosin light chain (MLC) phosphorylation determines vascular contractile status. In addition to the classic Ca
2+
-dependent MLC kinase (MLCK), another unidentified kinase(s) also contributes to MLC phosphorylation in living cells. Inhibitor κB kinase 2 (IKK2)–deficient mouse embryonic fibroblasts demonstrate abnormal morphology and migration, suggesting that IKK2 may be involved in MLC phosphorylation.

Objective:

Therefore, we tested whether IKK2 is an MLCK in living cells and the role of IKK2 in mediating vasoconstriction and blood pressure regulation.

Methods and Results:

In the present study, we showed that recombinant IKK2–phosphorylated MLC and intact myosin in vitro, and the kinetic parameters were comparable with those of the classic MLCK. Overexpression of IKK2 increased cellular MLC phosphorylation level, and pharmacological inhibition of IKK2 markedly decreased vascular smooth muscle cell MLC phosphorylation, suggesting that IKK2 is an MLCK in living cells. IKK2 inhibitors dose- and time-dependently attenuated vasoconstriction elicited by diverse agonists, suggesting the physiological importance of IKK2 as an MLCK. Vascular smooth muscle cell-specific IKK2-deficient mice had decreased aortic contractile responses, and reduced hypertensive responses to several vasoconstrictors, compared with wild-type mice, confirming the physiological importance of IKK2 as an MLCK.

Conclusions:

Our data provide a novel mechanism whereby IKK2 regulates MLC phosphorylation as an MLCK and, thus, vascular function and blood pressure.
Modifications of Chromatin Dynamics Control Smad2 Pathway Activation in Aneurysmal Smooth Muscle Cells
Authors: Gomez Delphine , Kessler Ketty , Michel Jean-Baptiste , Vranckx Roger
Published: July 2013

Rationale
:

The activation of the Smad2 signaling pathway is thought to play an important role in human aneurysmal diseases as described by an important body of research. We previously showed that constitutive Smad2 activation is associated with Smad2 mRNA overexpression in aneurysmal vascular smooth muscle cells (VSMCs), which is dependent on epigenetic regulation of the
SMAD2
promoter involving histone modifications. However, the underlying molecular mechanisms controlling Smad2 overexpression are currently unknown.

Objective
:

The aim of the present study is to understand the mechanisms regulating the constitutive Smad2 overexpression in VSMCs by identification of the histone-modifying enzymes, transcription factors, and cofactors responsible for Smad2 promoter activation in aneurysmal disease.

Methods and Results
:

This study was performed on medial tissue extracts and primary cultures of VSMCs of human thoracic aneurysms (n=17) and normal thoracic aortas (n=10). Here, we demonstrate that the activation of
SMAD2
promoter is driven by the recruitment of a multipartner complex, including the transcription factor p53 and histone acetyltransferases. Remarkably, the transcriptional regulatory network of the
SMAD2
promoter is dramatically altered in human aneurysmal VSMCs in vitro and in situ with a switch from Myc-dependent repression of
SMAD2
in normal vessel to a p53-dependent activation of
SMAD2
in aneurysms. Furthermore, histone acetyltransferases p300 and P300/CBP-associated protein play a major role in
SMAD2
promoter activation by acting on histone acetylation, p53 recruitment, and acetylation.

Conclusions
:

These results provide evidence for a major role of p53 and the complex composed of p300 and p300/CBP-associated protein in Smad2 activation in human aneurysmal VSMCs.
Comprehensive Cardiac Magnetic Resonance Imaging and Spectroscopy Reveal a High Burden of Myocardial Disease in HIV Patients
Authors: Holloway Cameron J. , Ntusi Ntobeko , Suttie Joseph , Mahmod Masliza , Wainwright Emma , Clutton Genevieve , Hancock Gemma , Beak Philip , Tajar Abdelouahid , Piechnik Stefan K. , Schneider Jurgen E. , Angus Brian , Clarke Kieran , Dorrell Lucy , Neubauer Stefan
Published: July 2013

Background—

HIV infection continues to be endemic worldwide. Although treatments are successful, it remains controversial whether patients receiving optimal therapy have structural, functional, or biochemical cardiac abnormalities that may underlie their increased cardiac morbidity and mortality. The purpose of this study was to characterize myocardial abnormalities in a contemporary group of HIV-infected individuals undergoing combination antiretroviral therapy.

Methods and Results—

Volunteers with HIV who were undergoing combination antiretroviral therapy and age-matched control subjects without a history of cardiovascular disease underwent cardiac magnetic resonance imaging and spectroscopy for the determination of cardiac function, myocardial fibrosis, and myocardial lipid content. A total of 129 participants were included in this analysis. Compared with age-matched control subjects (n=39; 30.23%), HIV-infected subjects undergoing combination antiretroviral therapy (n=90; 69.77%) had 47% higher median myocardial lipid levels (
P
<0.003) and 74% higher median plasma triglyceride levels (both
P
<0.001). Myocardial fibrosis, predominantly in the basal inferolateral wall of the left ventricle, was observed in 76% of HIV-infected subjects compared with 13% of control subjects (
P
<0.001). Peak myocardial systolic and diastolic longitudinal strain were also lower in HIV-infected individuals than in control subjects and remained statistically significant after adjustment for available confounders.

Conclusions—

Comprehensive cardiac imaging revealed cardiac steatosis, alterations in cardiac function, and a high prevalence of myocardial fibrosis in a contemporary group of asymptomatic HIV-infected subjects undergoing combination antiretroviral therapy. Cardiac steatosis and fibrosis may underlie cardiac dysfunction and increased cardiovascular morbidity and mortality in subjects with HIV.
Factor Xa Activation of Factor V Is of Paramount Importance in Initiating the Coagulation System
Authors: Schuijt Tim J. , Bakhtiari Kamran , Daffre Sirlei , DePonte Kathleen , Wielders Simone J.H. , Marquart J. Arnoud , Hovius Joppe W. , van der Poll Tom , Fikrig Erol , Bunce Matthew W. , Camire Rodney M. , Nicolaes Gerry A.F. , Meijers Joost C.M. , van ‘t Veer Cornelis
Published: July 2013

Background—

Generation of active procoagulant cofactor factor Va (FVa) and its subsequent association with the enzyme activated factor X (FXa) to form the prothrombinase complex is a pivotal initial event in blood coagulation and has been the subject of investigative effort, speculation, and controversy. The current paradigm assumes that FV activation is initiated by limited proteolysis by traces of (meizo) thrombin.

Methods and Results—

Recombinant tick salivary protein TIX-5 was produced and anticoagulant properties were studied with the use of plasma, whole blood, and purified systems. Here, we report that TIX-5 specifically inhibits FXa-mediated FV activation involving the B domain of FV and show that FXa activation of FV is pivotal for plasma and blood clotting. Accordingly, tick feeding is impaired on TIX-5 immune rabbits, displaying the in vivo importance of TIX-5.

Conclusions—

Our data elucidate a unique molecular mechanism by which ticks inhibit the host’s coagulation system. From our data, we propose a revised blood coagulation scheme in which direct FXa-mediated FV activation occurs in the initiation phase during which thrombin-mediated FV activation is restrained by fibrinogen and inhibitors.
JOLANTA BROŻEK (2013) A comparison of external and internal maxilla and mandible morphology of water bugs (Hemiptera: Heteroptera: Nepomorpha). Zootaxa, 3635(4), 340–378.
Authors: BROŻEK JOLANTA
Published: July 2013

Page 375 line 30 to read as:-Insufficient data were obtained on the monophyly of the Naucoridae, due to the output of the Cheirochelinae (one autapomorphy was indicated), and lack of synapomorphy in all subfamilies of the Naucoridae. The monophyly of Naucoridae had been indicated in a previous study by Hebsgaard et al., (2004).
Faculty-Led Study Abroad in Atmospheric Science Education
Authors: Kahl Jonathan D. W. , Cerón Julia G.
Published: July 2013

For several years the University of Wisconsin–Milwaukee's Atmospheric Science group has offered the faculty-led study abroad program Mexico: Air Pollution and Ancient Cultures. In this course, open to both atmospheric science majors and nonmajors as well as to students attending other colleges and universities, participating students learn about the corrosive effects of acid deposition on the limestone surfaces of Mesoamerican archaeological sites. The course content includes not only the science aspects of acid rain and environmental corrosion, but also aspects of Mesoamerican history and anthropology, as well as personal reflection on a variety of social science topics via journaling. The academic content is delivered via lectures and laboratories, guided tours of museums and archaeological sites, visits to Mexican universities, and hands-on measurements and analysis. Postprogram surveys indicate that participating students consider the program to be quite valuable in terms of both academic and personal growth.
Prognostic Equation for Radar Radial Velocity Derived by Considering Atmospheric Refraction and Earth Curvature
Authors: Xu Qin , Wei Li
Published: July 2013

The prognostic equation for the radial velocity field observed with a Doppler radar is derived to include the effects of atmospheric refraction and earth curvature on radar-beam height and slope angle. The derived equation, called the radial velocity equation, contains a high-order small term that can be truncated. The truncated radial velocity equation is shown to be much more accurate than its counterpart radial velocity equation derived without considering the effects of atmospheric refraction and earth curvature. The truncated equation has the same concise form as its counterpart radial velocity equation but remains to be sufficiently accurate as a useful dynamic constraint for radar wind analysis and assimilation (in normal situations) even up to the farthest 300-km radial range of operational Weather Surveillance Radar-1988 Doppler (WSR-88D) scans where its counterpart radial velocity equation becomes erroneous.
Different Pacific Ocean Warming Decaying Types and Northwest Pacific Tropical Cyclone Activity
Authors: Ha Yao , Zhong Zhong , Yang Xiuqun , Sun Yuan
Published: July 2013

This study focuses on statistical analysis of anomalous tropical cyclone (TC) activities and the physical mechanisms behind these anomalies. Different patterns of decaying of the warm sea surface temperature anomaly (SSTA) over the equatorial central-eastern Pacific are categorized into three types: eastern Pacific warming decaying to La Niña (EPWDL), eastern Pacific warming decaying to a neutral phase (EPWDN), and a central Pacific warming decaying year (CPWD). Differences in TC activity over the western North Pacific (WNP) corresponding to the above three types are discussed, and possible mechanisms are proposed. For EPWDL, TC genesis shows a significant positive (negative) anomaly over the northwestern (southeastern) WNP and more TCs move westward and make landfall over the southern East Asian coast. This is attributed primarily to the combined modulation of La Niña and the warm equatorial east Indian Ocean SSTA. For EPWDN, enhanced TC genesis is observed over the northeastern WNP, and suppressed TC activity is located mainly in the zonal region extending from the Philippine Sea to the eastern WNP, close to 160°E. Most of the TCs formed over the eastern WNP experience early recurvature east of 140°E, then move northeastward; hence, fewer TCs move northwestward to make landfall over the East Asian coast. For CPWD, the enhanced TC activity appears over the western WNP. This is due to the weak anomalous cyclonic circulation over the Philippines, primarily caused by the weaker, more westward-shifting warm SSTA compared to that in the previous warming year over the central Pacific.