bluuebunny/crossref_metadata_2025 huggingface dataset:
GPU-optimized volume ray tracing for massive numbers of rays in radiotherapy
Authors: Zhou Bo , Xiao Kai , Chen Danny Z. , Hu X. Sharon
Published: December 2013

Ray tracing within a uniform grid volume is a fundamental process invoked frequently by many applications, especially radiation-dose calculation methods in radiotherapy. However, the conflicting features between the GPU memory architecture and the memory-accessing patterns of volume ray tracing lead to inefficient usage of GPU memory bandwidth and waste of capability of modern GPUs. To improve the ray tracing performance on GPU, we propose a lookup-table-based ray tracing method which is specially optimized towards the GPU memory system for processing a massive number of rays. The proposed method is based on a key observation that many of these applications normally involves a massive number of rays, but their ray tracing may not need to follow a specific execution order. Therefore, we divide the 3D space into many regions (called pyramids) and group together the rays falling into the same pyramid. For each ray group, the volume is rotated and resampled for their raytracing. This divide-and-rotate strategy allows the memory access of the ray tracing process to adopt a table-lookup approach and leads to better memory coalescing on GPU. Our proposed method was thoroughly evaluated in four volume setups with randomly-generated rays. The collapsed-cone convolution/superposition (CCCS) dose calculation method is also implemented with/without the proposed approach to verify the feasibility of our method. Compared with the direct GPU implementation of the popular 3DDDA algorithm, our method provides a speedup in the range of 1.91--2.94X for the volume settings we used. Major performance factors, including ray origins, volume size, and pyramid size, are also analyzed. The proposed technique was also found to be able to give a speedup of 1.61--2.17X over the original GPU implementation of the CCCS algorithm. Our experiment results indicate that the proposed approach is capable of offering better coalesced memory access which eventually boosts the raytracing performance on GPU. Moreover, our approach is conceptually simple and can be readily included into various applications.
An analytical approach for fast and accurate design space exploration of instruction caches
Authors: Liang Yun , Mitra Tulika
Published: December 2013

Application-specific system-on-chip platforms create the opportunity to customize the cache configuration for optimal performance with minimal chip area. Simulation, in particular trace-driven simulation, is widely used to estimate cache hit rates. However, simulation is too slow to be deployed in design space exploration, especially when there are hundreds of design points and the traces are huge. In this article, we propose a novel analytical approach for design space exploration of instruction caches. Given the program control flow graph (CFG) annotated only with basic block and control flow edge execution counts, we first model the cache states at each point of the CFG in a probabilistic manner. Then, we exploit the structural similarities among related cache configurations to estimate the cache hit rates for multiple cache configurations in one pass. Experimental results indicate that our analysis is 28--2,500 times faster compared to the fastest known cache simulator while maintaining high accuracy (0.2% average error) in estimating cache hit rates for a large set of popular benchmarks. Moreover, compared to a state-of-the-art cache design space exploration technique, our approach achieves 304--8,086 times speedup and saves up to 62% (average 7%) energy for the evaluated benchmarks.
Flexible filters in stream programs
Authors: Collins Rebecca L. , Carloni Luca P.
Published: December 2013

The stream-processing model is a natural fit for multicore systems because it exposes the inherent locality and concurrency of a program and highlights its separable tasks for efficient parallel implementations. We present
flexible filters
, a load-balancing optimization technique for stream programs. Flexible filters utilize the programmability of the cores in order to improve the data-processing throughput of individual bottleneck tasks by “borrowing” resources from neighbors in the stream. Our technique is distributed and scalable because all runtime load-balancing decisions are based on point-to-point handshake signals exchanged between neighboring cores. Load balancing with flexible filters increases the system-level processing throughput of stream applications, particularly those with large dynamic variations in the computational load of their tasks. We empirically evaluate flexible filters in a homogeneous multicore environment over a suite of five real-word stream programs.
A regression test selection technique for embedded software
Authors: Biswas Swarnendu , Mall Rajib , Satpathy Manoranjan
Published: December 2013

The current approaches for regression test selection of embedded programs are usually based on data- and control-dependency analyses, often augmented with human reasoning. Existing techniques do not take into account additional execution dependencies which may exist among code elements in such programs due to features such as tasks, task deadlines, task precedences, and intertask communications. In this context, we propose a model-based regression test selection technique for such programs. Our technique first constructs a graph model of the program; the proposed graph model has been designed to capture several characteristics of embedded programs, such as task precedence order, priority, intertask communication, timers, exceptions and interrupt handlers, which we consider important for regression-test selection. Our regression test selection technique selects test cases based on an analysis of the constructed graph model. We have implemented our technique to realize a prototype tool. The experimental results obtained using this tool show that, on average, our approach selects about 28.33% more regression test cases than those selected by a traditional approach. We observed that, on average, 36.36% of the fault-revealing test cases were overlooked by the existing regression test selection technique.
The benefits of using variable-length pipelined operations in high-level synthesis
Authors: Ben-Asher Yosi , Rotem Nadav
Published: December 2013

Current high-level synthesis systems synthesize arithmetic units of a fixed known number of stages, and the scheduler mainly determines when units are activated. We focus on scheduling techniques for the high-level synthesis of pipelined arithmetic units where the number of stages of these operations is a free parameter of the synthesis. This problem is motivated by the ability to automatically create pipelined functional units, such as multipliers, with different pipe lengths. These units have different characteristics in terms of parallelism level, clock latency, frequency, etc. This article presents the Variable-length Pipeline Scheduler (VPS). The ability to synthesize variable-length pipelined units expands the known scheduling problem of high-level synthesis to include a search for a minimal number of hardware units (operations) and their desired number of stages. The proposed search procedure is based on algorithms that find a local minima in a
d
-dimensional grid, thus avoiding the need to evaluate all possible points in the space. We have implemented a C language compiler for VPS targeting FPGAs. Our results demonstrate that using variable-length pipeline units can reduce the overall resource usage and improve the execution time when synthesized onto an FPGA. The proposed search is sufficiently fast, taking only a few seconds, allowing an interactive mode of work. A comparison with xPilot shows a significant saving of hardware resources while maintaining comparable execution times of the resulting circuits. This work is an extension of a previous paper [Ben-Asher and Rotem 2008]
A resource-driven DVFS scheme for smart handheld devices
Authors: Chang Yu-Ming , Hsiu Pi-Cheng , Chang Yuan-Hao , Chang Che-Wei
Published: December 2013

Reducing the energy consumption of the emerging genre of smart handheld devices while simultaneously maintaining mobile applications and services is a major challenge. This work is inspired by an observation on the resource usage patterns of mobile applications. In contrast to existing DVFS scheduling algorithms and history-based prediction techniques, we propose a resource-driven DVFS scheme in which resource state machines are designed to model the resource usage patterns in an online fashion to guide DVFS. We have implemented the proposed scheme on Android smartphones and conducted experiments based on real-world applications. The results are very encouraging and demonstrate the efficacy of the proposed scheme.
A hardware architecture for real-time object detection using depth and edge information
Authors: Kyrkou Christos , Ttofis Christos , Theocharides Theocharis
Published: December 2013

Emerging embedded 3D vision systems for robotics and security applications utilize object detection to perform video analysis in order to intelligently interact with their host environment and take appropriate actions. Such systems have high performance and high detection-accuracy demands, while requiring low energy consumption, especially when dealing with embedded mobile systems. However, there is a large image search space involved in object detection, primarily because of the different sizes in which an object may appear, which makes it difficult to meet these demands. Hence, it is possible to meet such constraints by reducing the search space involved in object detection. To this end, this article proposes a depth and edge accelerated search method and a dedicated hardware architecture that implements it to provide an efficient platform for generic real-time object detection. The hardware integration of depth and edge processing mechanisms, with a support vector machine classification core onto an FPGA platform, results in significant speed-ups and improved detection accuracy. The proposed architecture was evaluated using images of various sizes, with results indicating that the proposed architecture is capable of achieving real-time frame rates for a variety of image sizes (271 fps for 320 × 240, 42 fps for 640 × 480, and 23 fps for 800 × 600) compared to existing works, while reducing the false-positive rate by 52%.
QoS-Aware scheduling in heterogeneous datacenters with paragon
Authors: Delimitrou Christina , Kozyrakis Christos
Published: December 2013

Large-scale datacenters (DCs) host tens of thousands of diverse applications each day. However, interference between colocated workloads and the difficulty of matching applications to one of the many hardware platforms available can degrade performance, violating the quality of service (QoS) guarantees that many cloud workloads require. While previous work has identified the impact of heterogeneity and interference, existing solutions are computationally intensive, cannot be applied online, and do not scale beyond a few applications.

We present Paragon, an online and scalable DC scheduler that is heterogeneity- and interference-aware. Paragon is derived from robust analytical methods, and instead of profiling each application in detail, it leverages information the system already has about applications it has previously seen. It uses collaborative filtering techniques to quickly and accurately classify an unknown incoming workload with respect to heterogeneity and interference in multiple shared resources. It does so by identifying similarities to previously scheduled applications. The classification allows Paragon to greedily schedule applications in a manner that minimizes interference and maximizes server utilization. After the initial application placement, Paragon monitors application behavior and adjusts the scheduling decisions at runtime to avoid performance degradations. Additionally, we design ARQ, a multiclass admission control protocol that constrains application waiting time. ARQ queues applications in separate classes based on the type of resources they need and avoids long queueing delays for easy-to-satisfy workloads in highly-loaded scenarios. Paragon scales to tens of thousands of servers and applications with marginal scheduling overheads in terms of time or state.

We evaluate Paragon with a wide range of workload scenarios, on both small and large-scale systems, including 1,000 servers on EC2. For a 2,500-workload scenario, Paragon enforces performance guarantees for 91% of applications, while significantly improving utilization. In comparison, heterogeneity-oblivious, interference-oblivious, and least-loaded schedulers only provide similar guarantees for 14%, 11%, and 3% of workloads. The differences are more striking in oversubscribed scenarios where resource efficiency is more critical.
Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing
Authors: Tomlinson Ryan E. , Shoghi Kooresh I. , Silva Matthew J.
Published: December 2013

Despite the strong connection between angiogenesis and osteogenesis in skeletal repair conditions such as fracture and distraction osteogenesis, little is known about the vascular requirements for bone formation after repetitive mechanical loading. Here, established protocols of damaging (stress fracture) and nondamaging (physiological) forelimb loading in the adult rat were used to stimulate either woven or lamellar bone formation, respectively. Positron emission tomography was used to evaluate blood flow and fluoride kinetics at the site of bone formation. In the group that received damaging mechanical loading leading to woven bone formation (WBF),15O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas18F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF),15O water and18F fluoride flow rates in loaded limbs were not significantly different from nonloaded limbs at any time point. The early increase in blood flow rate after WBF loading was associated with local vasodilation. In addition, Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs. The nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester was used to suppress NO generation, resulting in significant decreases in early blood flow rate and bone formation after WBF loading. These results demonstrate that NO-mediated vasodilation is a key feature of the normal response to stress fracture and precedes woven bone formation. Therefore, patients with impaired vascular function may heal stress fractures more slowly than expected.
Cytokine-Induced Killer Cells Eradicate Bone and Soft-Tissue Sarcomas
Authors: Sangiolo Dario , Mesiano Giulia , Gammaitoni Loretta , Leuci Valeria , Todorovic Maja , Giraudo Lidia , Cammarata Cristina , Dell'Aglio Carmine , D'Ambrosio Lorenzo , Pisacane Alberto , Sarotto Ivana , Miano Sara , Ferrero Ivana , Carnevale-Schianca Fabrizio , Pignochino Ymera , Sassi Francesco , Bertotti Andrea , Piacibello Wanda , Fagioli Franca , Aglietta Massimo , Grignani Giovanni
Published: December 2013

Unresectable metastatic bone sarcoma and soft-tissue sarcomas (STS) are incurable due to the inability to eradicate chemoresistant cancer stem–like cells (sCSC) that are likely responsible for relapses and drug resistance. In this study, we investigated the preclinical activity of patient-derived cytokine-induced killer (CIK) cells against autologous bone sarcoma and STS, including against putative sCSCs. Tumor killing was evaluated both in vitro and within an immunodeficient mouse model of autologous sarcoma. To identify putative sCSCs, autologous bone sarcoma and STS cells were engineered with a CSC detector vector encoding eGFP under the control of the human promoter for OCT4, a stem cell gene activated in putative sCSCs. Using CIK cells expanded from 21 patients, we found that CIK cells efficiently killed allogeneic and autologous sarcoma cells in vitro. Intravenous infusion of CIK cells delayed autologous tumor growth in immunodeficient mice. Further in vivo analyses established that CIK cells could infiltrate tumors and that tumor growth inhibition occurred without an enrichment of sCSCs relative to control-treated animals. These results provide preclinical proof-of-concept for an effective strategy to attack autologous sarcomas, including putative sCSCs, supporting the clinical development of CIK cells as a novel class of immunotherapy for use in settings of untreatable metastatic disease. Cancer Res; 74(1); 119–29. ©2013 AACR.
Urinary 3,3′-Diindolylmethane: A Biomarker of Glucobrassicin Exposure and Indole-3-Carbinol Uptake in Humans
Authors: Fujioka Naomi , Ainslie-Waldman Cheryl E. , Upadhyaya Pramod , Carmella Steven G. , Fritz Vincent A. , Rohwer Charles , Fan Yunhua , Rauch Diane , Le Chap , Hatsukami Dorothy K. , Hecht Stephen S.
Published: December 2013

Background: Brassica vegetable consumption may confer a protective effect against cancer, possibly attributable to their glucosinolates. Glucobrassicin is a predominant glucosinolate and is the precursor of indole-3-carbinol (I3C), a compound with anticancer effects. However, objective assessments of I3C uptake from Brassica vegetables have not been successful.

Methods: We conducted a randomized, crossover trial to test whether 3,3′-diindolylmethane (DIM, a metabolite of I3C) excreted in the urine after consumption of raw Brassica vegetables with divergent glucobrassicin concentrations is a marker of I3C uptake from such foods. Twenty-five subjects were fed 50 g of either raw “Jade Cross” Brussels sprouts (high glucobrassicin concentration) or “Blue Dynasty” cabbage (low glucobrassicin concentration) once daily for 3 days. All urine was collected for 24 hours after vegetable consumption each day. After a washout period, subjects crossed over to the alternate vegetable. Urinary DIM was measured using a novel liquid chromatography-electrospray ionization-tandem mass spectrometry–selected reaction monitoring (LC-ESI-MS/MS-SRM) method with [2H2]DIM as internal standard.

Results: Urinary DIM was consistently and significantly higher after Brussels sprouts feeding than after cabbage feeding, as evidenced by an average difference of 8.73 pmol/mg creatinine (95% confidence interval, 5.36–12.10; P = 0.00002).

Conclusion: We have successfully quantified urinary DIM after uptake of I3C from food, and demonstrated that differences in glucobrassicin exposure are reflected in urinary DIM levels.

Impact: Our LC-ESI-MS/MS-SRM method and the results of our study indicate urinary DIM is a measure of I3C uptake from Brassica vegetables, a finding that can be utilized in prospective epidemiologic and chemoprevention studies. Cancer Epidemiol Biomarkers Prev; 23(2); 282–7. ©2013 AACR.
The Effect of Photoimmunotherapy Followed by Liposomal Daunorubicin in a Mixed Tumor Model: A Demonstration of the Super-Enhanced Permeability and Retention Effect after Photoimmunotherapy
Authors: Sano Kohei , Nakajima Takahito , Choyke Peter L. , Kobayashi Hisataka
Published: December 2013

In general, de novo solid tumors are composed of phenotypically and functionally heterogeneous malignant cells. This heterogeneity interferes with the effectiveness of targeted molecular cancer therapies. Even if most of the tumor is killed by a targeted treatment, recurrences are common and can be lethal. In this study, a mixed tumor model, which is predominantly a population of epidermal growth factor receptor (EGFR)-positive A431 cells combined with a smaller population of EGFR-negative Balb3T3/DsRed cells, was established. This mixed tumor was then treated with photoimmunotherapy, a newly developed target-cell–selective cancer therapy using a monoclonal antibody (mAb)–photosensitizer (IR700 fluorescence dye) conjugate and exposure of near-infrared light. Although photoimmunotherapy successfully treated EGFR-positive A431 cells in the mixed tumor, EGFR-negative Balb/DsRed cells were not responsive. However, photoimmunotherapy also induced a large increase in tumor permeability, known as the super-enhanced permeability and retention (SUPR) effect, which allowed a 5-fold increase in the accumulation of a liposomal chemotherapy (DaunoXome) and resulted in more effective therapy than either photoimmunotherapy or liposomal daunorubicin alone. The liposomal daunorubicin, administered 1 hour after EGFR-targeted photoimmunotherapy, was homogeneously distributed, allowing delivery to tiny surviving nests of EGFR-negative Balb3T3/DsRed cells, resulting in prolonged survival of mice. Mol Cancer Ther; 13(2); 426–32. ©2013 AACR.
Antiangiogenic Therapies: Going beyond Their Limits
Authors: Moserle Lidia , Jiménez-Valerio Gabriela , Casanovas Oriol
Published: December 2013

Tumor growth requires induction of an angiogenic program, and targeting of this program with antiangiogenic drugs shows an impact on tumor progression. However, although they are effective at reducing angiogenesis, these therapies have not produced widespread or enduring clinical benefit, which openly exposes their limitations. Here, we describe the current limitations of these therapies, including the known mechanisms and current controversies. Further, we present some of the recent approaches to predict these limitations and strategies to overcome them. With the development of meaningful predictive biomarkers and effective treatments that impede these limitations, longer and more robust efficacies will be achieved for a wider population of patients.

Significance: The clinical benefit of antiangiogenic drugs is restricted because of intrinsic and acquired limitations. Acknowledging and understanding these limitations will not only allow the development of effective predictive biomarkers but also help in devising new therapeutic strategies that achieve longer efficacies for a wider population of patients. Cancer Discov; 4(1); 31–41. ©2013 AACR.
Mesothelin-Specific Chimeric Antigen Receptor mRNA-Engineered T Cells Induce Antitumor Activity in Solid Malignancies
Authors: Beatty Gregory L. , Haas Andrew R. , Maus Marcela V. , Torigian Drew A. , Soulen Michael C. , Plesa Gabriela , Chew Anne , Zhao Yangbing , Levine Bruce L. , Albelda Steven M. , Kalos Michael , June Carl H.
Published: December 2013

Off-target toxicity due to the expression of target antigens in normal tissue represents a major obstacle to the use of chimeric antigen receptor (CAR)-engineered T cells for treatment of solid malignancies. To circumvent this issue, we established a clinical platform for engineering T cells with transient CAR expression by using in vitro transcribed mRNA encoding a CAR that includes both the CD3-ζ and 4-1BB costimulatory domains. We present two case reports from ongoing trials indicating that adoptive transfer of mRNA CAR T cells that target mesothelin (CARTmeso cells) is feasible and safe without overt evidence of off-tumor on-target toxicity against normal tissues. CARTmeso cells persisted transiently within the peripheral blood after intravenous administration and migrated to primary and metastatic tumor sites. Clinical and laboratory evidence of antitumor activity was shown in both patients, and the CARTmeso cells elicited an antitumor immune response revealed by the development of novel antiself antibodies. These data show the potential of using mRNA-engineered T cells to evaluate, in a controlled manner, potential off-tumor on-target toxicities and show that short-lived CAR T cells can induce epitope spreading and mediate antitumor activity in patients with advanced cancer. Thus, these findings support the development of mRNA CAR-based strategies for carcinoma and other solid tumors. Cancer Immunol Res; 2(2); 112–20. ©2013 AACR.
Baha-Mediated Rehabilitation of Patients with Unilateral Deafness: Selection Criteria
Authors: Saroul N. , Akkari M. , Pavier Y. , Gilain L. , Mom T.
Published: December 2013

The aim of our study was to identify clinical criteria for optimizing rehabilitation of patients with unilateral deafness using the Baha device. We made a retrospective study of 102 patients with unilateral deafness requesting auditory rehabilitation over a period of 5 years. All subjects underwent a series of stereo audiometric tests, with and without Baha worn on a headband, and were then referred to a hearing care specialist for a real life trial of 15 days. The Glasgow Health Status Inventory (GHSI) questionnaire was administered. Patients refusing the implantation were retrospectively submitted to a questionnaire specifically designed to ask the reasons for refusal. We measured stereo audiometric test results, age, aetiology of deafness, duration of auditory deprivation on the rehabilitated ear, and GHSI score. At the conclusion of testing, the implantation rate was 29%. During preoperative testing, the improvement in understanding of speech-in-noise was 22 ± 11% for patients agreeing to the implantation versus 13 ± 11% for patients refusing the implantation. Age, aetiology of deafness and duration of auditory deprivation had no influence on the implantation decision. Speech-in-noise testing and aided stereo audiometric gain were the only two measures showing statistically significant differences between the groups agreeing to and refusing the implantation. There were multiple reasons for refusal of the implantation. Among these, the four principal reasons were: absence of perceived benefit during stereo audiometric testing (59%), requirement for surgery (35%), cost of the solution (44%), and aesthetics (41%). Hence, no other criteria except the preoperative improvement in understanding of speech-in-noise and the aided gain from Baha worn on a headband were found to be predictive of the patient's acceptance of surgical implantation of a bone-anchored implant/abutment for Baha. Speech-in-noise testing with and without Baha worn on a headband has a role to play in deciding on the implantation of a bone-anchored hearing solution.
Pre-Emptive Replacement of Water Treatment Components Improves Responsiveness to Erythropoiesis-Stimulating Agents in Maintenance Haemodialysis Patients: A Quality Improvement Report
Authors: Singh Seema K. , Loucaidou Marina , Power Albert , Beagle Simon , Nevin Margaret , Edwards Claire , Corbett Richard , Ashby Damien R. , Duncan Neill , Choi Peter
Published: December 2013

Hypo-responsiveness to erythropoiesis-stimulating agents (ESAs) has been associated with increased mortality. We examined the effect of water treatment component replacement on declining ESA responsiveness in the absence of chemical or microbiological standards failure. Pre-emptive renewal of the water treatment system supplying 802 standard-flux haemodialysis patients resulted in a significant rise in haemoglobin from (mean ± SD) 12.1 ± 1.2 to 12.3 ± 1.0 g/dl (p < 0.0001), accompanied by a significant decrease in prescribed dose of darbepoetin alfa from 47.9 ± 27.3 to 44.7 ± 27.6 μg/week (p < 0.0001). ESA responsiveness improved significantly from 0.060 ± 0.041 to 0.055 ± 0.040 μg/kg/g·dl-1 (p < 0.0001) and the number of patients no longer requiring ESA therapy increased threefold. These benefits were derived in the absence of haemolysis or significant changes in water quality. Renewal of water system components should be conducted even in the absence of proven microbiological and chemical failure.
A High Incidence of Adjacent-1 Meiotic Segregation Pattern, Revealed by Multicolor Sperm FISH, in a Carrier Boar of a New Reciprocal Translocation t(6;16)(p13;q23)
Authors: Kociucka B. , Szczerbal I. , Bugaj S. , Orsztynowicz M. , Switonski M.
Published: December 2013

Reciprocal translocations pose a serious problem in pig breeding due to the reduced fertility of the carriers. This paper presents a new reciprocal translocation in a phenotypically normal, but hypoprolific (20% reduction) boar. Chromosome banding as well as the FISH technique with the use of BAC and telomeric probes was applied for a detailed characterization of this chromosome rearrangement. The karyotype of the studied boar was described as 38,XY,t(6;16)(p13;q23). The meiotic segregation of the quadrivalent was studied in 1,071 sperms by multicolor FISH. The most frequent segregation patterns were alternate (47.5%) and adjacent 1 (41.9%), while adjacent 2 and 3:1 were less frequent at 1.2 and 9.2%, respectively. Surprisingly, the frequency of the adjacent-1 segregation appeared to be relatively high, when compared with human and pig reciprocal translocations studied by sperm FISH. Our study, along with a review of the literature, shows that a reduction of fertility in the carriers and the incidence of different segregation patterns of the quadrivalent may vary within a broad range, and both aspects seem to be unrelated. A need for obligatory karyotype screening programs of artificial insemination boars is emphasized.
Perfusion Disturbances of Kidney Graft Parenchyma Evaluated with Contrast-Enhanced Ultrasonography in the Immediate Period following Kidney Transplantation
Authors: Grzelak P. , Kurnatowska I. , Nowicki M. , Marchwicka-Wasiak M. , Podgórski M. , Durczyński A. , Strzelczyk J. , Stefańczyk L.
Published: December 2013

Purpose: Graft parenchyma perfusion disturbances (GPPD) in transplanted kidneys are common in the early postoperative period. Rapid and accurate diagnosis can guide proper treatment, preventing graft dysfunction. Methods: One hundred and eighty patients, who underwent kidney transplantation (KTx), were examined in the immediate postoperative period using real-time ultrasonography (B-mode) with color and power Doppler (US-CD/PD) and B-flow ultrasound, as well as with an additional protocol of contrast-enhanced ultrasonography (CE-US). Regions of GPPD were localized and measured. The number and size of these areas were compared between the two acquisition techniques. Follow-up examinations were carried out 6 months postoperatively. Results: CE-US revealed more GPPDs and showed them more precisely than the B+US-CD/PD/B-flow technique. Moreover, in the CE-US examination, ischemic foci had statistically significant higher echogenicity in comparison to normal parenchyma, were larger and better visualized (better circumscribed) than in B+US-CD/PD/B-flow. Conclusion: CE-US allows the visualization of GPPD caused by occlusion of small arteries. It is a noninvasive, safe, real-time method, which has many advantages over standard B+US-CD/PD/B-flow examinations, and we recommend it as a routine diagnostic procedure in the early postoperative period following KTx.
Prevalence and Clinical Relevance of Allergic Rhinitis in Patients with Classic Asthma and Cough Variant Asthma
Authors: Tajiri Tomoko , Niimi Akio , Matsumoto Hisako , Ito Isao , Oguma Tsuyoshi , Otsuka Kojiro , Takeda Tomoshi , Nakaji Hitoshi , Inoue Hideki , Iwata Toshiyuki , Nagasaki Tadao , Mishima Michiaki
Published: December 2013

Background: A clinically relevant relationship between classic asthma and allergic rhinitis has been reported. However, the possible link between cough variant asthma (CVA) and allergic rhinitis remains unknown. Objectives: To clarify the prevalence and clinical relevance of perennial allergic rhinitis or seasonal allergic rhinitis in CVA patients compared to classic asthma patients. Methods: We retrospectively studied adult patients with classic asthma (n = 190) and those with CVA (n = 83). The prevalence of perennial allergic rhinitis or seasonal allergic rhinitis and associations of concomitant perennial or seasonal allergic rhinitis with asthma severity, forced expiratory volume in 1 s (% predicted), fractional exhaled nitric oxide (FeNO) levels, and eosinophil proportions in sputum and blood were analyzed in the two groups. Results: The prevalence of perennial allergic rhinitis and/or seasonal allergic rhinitis was significantly higher in classic asthma patients than in CVA patients (all p < 0.05). Concomitant perennial allergic rhinitis was associated with higher FeNO levels and eosinophil proportions in sputum and blood in classic asthma patients (p = 0.035, p = 0.036, and p = 0.008, respectively) and with higher asthma severity, FeNO levels, and sputum eosinophil proportions in CVA patients (p = 0.031, p = 0.007, and p = 0.010, respectively). Concomitant seasonal allergic rhinitis was only associated with higher sputum eosinophil proportions in CVA patients with active rhinitis symptoms during the sensitized pollen season (p = 0.025). Conclusions: Perennial allergic rhinitis may be relevant for CVA patients as well as classic asthma patients by consistently augmenting eosinophilic lower airway inflammation.
Methylation Status of Immune Response Genes Promoters in Cell-Free DNA Differs in Hemodialyzed Patients with Diabetic Nephropathy According to the Intensity of Anemia Therapy
Authors: Korabecna Marie , Pazourkova Eva , Horinek Ales , Mokrejsova Magdalena , Tesar Vladimir
Published: December 2013

Background: Anemia is a major complication of end-stage renal disease. Hemodialysis itself is regarded as a stimulus activating inflammation. Pro-inflammatory cytokines are able to suppress erythropoiesis. In this pilot study, we analyzed the changes in methylation status of promoters of immune response genes in cell-free DNA to detect the differences between diabetic subjects (n = 18) with different therapeutic doses of recombinant erythropoietin. Methods: The extent of promoter methylation of 24 genes in plasma cell-free DNA was examined before and after hemodialysis using EpiTect Methyl qPCR Array Inflammatory Response and Autoimmunity (Qiagen). Results: The patients with higher methylation status of gene sequences IL13RA1, IL15, EDG3 and INHA in interdialytic interval were significantly overrepresented in the group with none or mild anemia therapy. Conclusion: The results are in agreement with the fact that IL13 and IL15 are known inhibitors of erythropoiesis and with considered immunomodulatory role of cell-free DNA.
Elimination of Middle-Sized Uremic Solutes with High-Flux and High-Cut-Off Membranes: A Randomized in vivo Study
Authors: Kneis C. , Beck W. , Boenisch O. , Klefisch F. , Deppisch R. , Zickler D. , Schindler R.
Published: December 2013

The elimination of substances between 10 and 50 kDa by conventional high-flux membranes is not satisfactory. We investigated in vivo the elimination of middle-sized uremic solutes by conventional polyflux (PF) and modified high-cut-off (HCO) membranes. All 12 patients underwent four treatments, two with the HCO dialyzer and two with the PF dialyzer, each in either a haemodialysis (HD) or haemodiafiltration (HDF) mode. The reduction ratio of urea, creatinine, β2-microglobulin (β2M), leptin, soluble TNF-RI, complement factor D, IL-6, sIL-6 receptor, advanced glycation end-products (AGEs) and albumin was determined. In addition, the amount removed was determined in the dialysate for β2M, complement factor D, AGEs and albumin. Treatment with HCO removed β2M, sTNF-RI, factor D, and high molecular AGE significantly better than conventional high-flux membranes. The albumin loss was higher when using HCO membranes. HCO membranes are a promising approach to improve removal of uremic toxins not affected by conventional high-flux membranes.
Effect of Different Hemodialyzers on Serum Levels of Interleukin-6, Interleukin-10 and Interleukin-18
Authors: Shu Kuo-Hsiung , Cheng Chi-Hung , Wu Ming-Ju , Chen Cheng-Hsu , Yu Tung-Min , Chuang Ya-Wen , Huang Shih-Ting , Tsai Shang-Feng , Lo Ying-Chih
Published: December 2013

Background: The blood and membrane contact during dialysis may elicit an immune reaction. The current study looked at the impact of different dialyzers on blood levels of cytokines. Methods: During the first month, randomly selected patients were treated with one dialyzer (PF-170H) and then crossed over to another dialyzer (FLX-18GW) during the next month. Pre- and postdialysis blood samples were assayed for interleukin (IL)-6, IL-10 and IL-18. Results: A significant drop of postdialysis systolic blood pressure (pre vs. post 156.4 ± 31.8 vs. 143.1 ± 24.8 mm Hg, p = 0.014) and diastolic pressure (80.7 ± 12.7 vs. 73.4 ± 10.9 mm Hg, p = 0.002) were found when patients were dialyzed with PF-170H. A significant increase of postdialysis IL-18 levels was found in both groups (pre vs. post 605.5 ± 278.6 vs. 690.6 ± 315.3 pg/ml, p = 0.016, for PF-170H and 556.4 ± 231.0 vs. 647.3 ± 282.6 pg/ml, p = 0.067, for FLX-18GW). There was a positive correlation between IL-6 and IL-10 levels (p < 0.0001). Conclusion: We demonstrated a significant increase of postdialysis serum IL-18 level when either dialyzer was used. There is a strong correlation between serum levels of IL-6 and IL-10.
Improvement in Glaucoma Patient Quality of Life by Therapy Switch to Preservative-Free Timolol/Dorzolamide Fixed Combination
Authors: Abegão Pinto Luís , Vandewalle Evelien , Gerlier Laetitia , Stalmans Ingeborg ,   The CosoptUD Switch Study Group
Published: December 2013

Purpose: To assess a change in visual-related quality of life (QoL) in glaucoma patients after switching from preservative-containing medical therapy to preservative-free unit dose timolol/dorzolamide fixed combination (TDFC UD). Methods: Prospective, noninterventional, multicenter 8-week study. Primary outcome was a change in visual symptoms at week 8, as assessed by the Glaucoma Symptom Scale (GSS). Results: 80 patients completed the study. There was a clinically significant increase in the scores of all GSS-related categories at week 8 when compared to baseline (GSS symptom week 8: +21.15 ± 37.9%, GSS function week 8: +10.3 ± 31.6%, both p < 0.001 vs. baseline). Comparison between patients taking only TDFC UD and patients taking TDFC UD plus concomitant medications did not detect differences in any GSS category (p > 0.50 in all comparisons). Conclusions: Switching to TDFC UD significantly improved the self-reported QoL of glaucoma patients. This can be seen even in patients who are taking concomitant ocular treatments.
Analysis of Facial Skin-Resident Microbiota in Japanese Acne Patients
Authors: Numata Shigeki , Akamatsu Hirohiko , Akaza Narifumi , Yagami Akiko , Nakata Satoru , Matsunaga Kayoko
Published: December 2013

Objectives: We investigated the facial skin microbiota of Japanese acne patients. Methods: Skin swab samples were obtained from 100 acne patients and 28 healthy controls to evaluate Propionibacterium and Staphylococcus spp. using a culture method. Malassezia spp. were evaluated using a nonculture method. Antibiotic resistance of Propionibacterium spp. was also examined. Results: Acne patients and controls did not show significant differences in Propionibacterium and Staphylococcus spp. populations. However, the number of Malassezia globosa from patients was greater than that from controls. Moreover, the number of Propionibacterium spp. from patients carrying antibiotic-resistant strains was significantly greater than that from patients not carrying them. Conclusions: The present study characterized the facial skin microbiota of Japanese acne patients, suggesting a correlation between acne and quantitative differences in Malassezia microbiota. It was also found that the antibiotic resistance of Propionibacterium spp. may affect its abundance in the skin.
Extensive Cartilaginous Metaplasia of Recurrent Posterior Fossa Ependymoma: Case Report and Review of the Literature
Authors: Boukas Alexandros , Joshi Abhijit , Jenkins Alistair , Holliman Damian
Published: December 2013

Cartilaginous metaplasia in ependymomas is extremely rare and only few cases have been reported in the literature. We describe a case of a 5-year-old patient with a 5th recurrence of 4th ventricle ependymoma. He was previously treated with 4 resections, chemotherapy and radiotherapy. Histopathology revealed well-differentiated chondroid tissue occupying almost the entire lesion. Near total resection was achieved for the 5th time, but the patient died 3 months later achieving a total survival of 48 months, the 3rd longest reported in literature. Multiple resections of tumour recurrence provided a new insight in this very rare tumour, as it gave us the opportunity to observe the progression of tumour aggressiveness from grade II to grade III and finally to chondroid metaplasia. Cartilaginous metaplasia in posterior fossa ependymomas is a very atypical and challenging tumour with poor overall prognosis.
Effects of Prochlorperazine on Normal Vestibular Ocular and Perceptual Responses: A Randomised, Double-Blind, Crossover, Placebo-Controlled Study
Authors: Patel M. , Nigmatullina Y. , Seemungal B.M. , Golding J.F. , Bronstein A.M.
Published: December 2013

Background: The present study investigated whether prochlorperazine affects vestibulo-ocular reflex (VOR) and vestibulo-perceptual function. Methods: We studied 12 healthy naïve subjects 3 h after a single dose of oral prochlorperazine 5 mg in a randomised, placebo-controlled, double-blind, crossover study in healthy young subjects. Two rotational tests in yaw were used: (1) a threshold task investigating perceptual motion detection and nystagmic thresholds (acceleration steps of 0.5°/s2) and (2) suprathreshold responses to velocity steps of 90°/s in which vestibulo-ocular and vestibuloperceptual time constants of decay, as well as VOR gain, were measured. Results: Prochlorperazine had no effect upon any measure of nystagmic or perceptual vestibular function compared to placebo. This lack of effects on vestibular-mediated motion perception suggests that the drug is likely to act more as an anti-emetic than as an antivertiginous agent.
Free Radicals: How Do We Stand Them? Anaerobic and Aerobic Free Radical (Chain) Reactions Involved in the Use of Fluorogenic Probes and in Biological Systems
Authors: Liochev Stefan I.
Published: December 2013

Biologically significant conclusions have been based on the use of fluorogenic and luminogenic probes for the detection of reactive species. The basic mechanisms of the processes involved have not been satisfactorily elucidated. In the present work, the mechanism of the enzyme and photosensitized oxidation of NAD(P)H by resorufin is analyzed and appears to involve both aerobic and anaerobic free radical chain reactions. There are two major fallouts of this analysis. Many of the conclusions about the participation of radicals based on the use of probes such as resorufin and Amplex red need reevaluation. It is also concluded that anaerobic free radical reactions may be biologically significant, and the possible existence of enzymatic systems to eliminate certain free radicals is discussed.
Sex Determination Mechanisms in the Calliphoridae (Blow Flies)
Authors: Scott M.J. , Pimsler M.L. , Tarone A.M.
Published: December 2013

The Calliphoridae or blow flies are a family of insects that occupy diverse habitats and perform important ecological roles, particularly the decomposition of animal remains. Some Calliphoridae species are also important in the forensic sciences, in agriculture (e.g. as livestock pests) and in medicine (e.g. maggot therapy). Calliphoridae provide striking examples in support of the hypothesis that sex determination regulatory gene hierarchies evolve in the reverse order, with the gene at the top being the most recently added. Unlike the model fly Drosophila melanogaster, where sex is determined by the number of X chromosomes, in the Australian sheep blow fly (Lucilia cuprina) sex is determined by a Y-linked male-determining gene (M). A different regulatory system appears to operate in the hairy maggot blow fly (Chrysomya rufifacies) where the maternal genotype determines sex. It is hypothesized that females heterozygous for a dominant female-determining factor (F/f) produce only female offspring and homozygous f/f females produce only sons. The bottom of the regulatory hierarchy appears to be the same in D. melanogaster and L. cuprina, with sex-specific splicing of doublesex transcripts being controlled by the female-specific Transformer (TRA) protein. We discuss a model that has been proposed for how tra transcripts are sex-specifically spliced in calliphorids, which is very different from D. melanogaster.
Genomic Imprinting and Maternal Effect Genes in Haplodiploid Sex Determination
Authors: van de Zande L. , Verhulst E.C.
Published: December 2013

The research into the Drosophila melanogaster sex-determining system has been at the basis of all further research on insect sex determination. This further research has made it clear that, for most insect species, the presence of sufficient functional Transformer (TRA) protein in the early embryonic stage is essential for female sexual development. In Hymenoptera, functional analysis of sex determination by knockdown studies of sex-determining genes has only been performed for 2 species. The first is the social insect species Apis mellifera, the honeybee, which has single-locus complementary sex determination (CSD). The other species is the parasitoid Nasonia vitripennis, the jewel wasp. Nasonia has a non-CSD sex-determining system, described as the maternal effect genomic imprinting sex determination system (MEGISD). Here, we describe the arguments that eventually led to the formulation of MEGISD and the experimental data that supported and refined this model. We evaluate the possibility that DNA methylation lies at the basis of MEGISD and briefly address the role of genomic imprinting in non-CSD sex determination in other Hymenoptera.
Transcriptomic Analysis of Sexual Differentiation in Somatic Tissues of Drosophila melanogaster: Successes and Caveats
Authors: Samson M.-L. , Rabinow L.
Published: December 2013

The advent of high-throughput technologies to analyze RNA expression levels and transcript structure has brought renewed attention to the age-old question of what differentiates males from females. In Drosophila, the characterized somatic sex determination cascade includes proteins implicated in the regulation of pre-mRNA splicing as well as at least 2 transcription factors at its base. Both DNA microarrays and RNA-Seq have been applied in a number of studies to determine the identities, expression levels and structure of transcripts expressed differentially in the 2 sexes, with remarkably divergent results in the number, structure and identity of affected transcripts. We briefly summarize these reports and discuss the reasons for the apparent discrepancies based upon the different conditions used for sample preparation and data analysis.
The Neuroprotection Exerted by Memantine, Minocycline and Lithium, against Neurotoxicity of CSF from Patients with Amyotrophic Lateral Sclerosis, Is Antagonized by Riluzole
Authors: Yáñez Matilde , Matías-Guiu Jorge , Arranz-Tagarro Juan-Alberto , Galán Lucía , Viña Dolores , Gómez-Pinedo Ulises , Vela Álvaro , Guerrero Antonio , Martínez-Vila Eduardo , García Antonio G.
Published: December 2013

In a recent study we found that cerebrospinal fluids (CSFs) from amyotrophic lateral sclerosis (ALS) patients caused 20-30% loss of cell viability in primary cultures of rat embryo motor cortex neurons. We also found that the antioxidant resveratrol protected against such damaging effects and that, surprisingly, riluzole antagonized its protecting effects. Here we have extended this study to the interactions of riluzole with 3 other recognized neuroprotective agents, namely memantine, minocycline and lithium. We found: (1) by itself riluzole exerted neurotoxic effects at concentrations of 3-30 µM; this cell damage was similar to that elicited by 30 µM glutamate and a 10% dilution of ALS/CSF; (2) memantine (0.1-30 µM), minocycline (0.03-1 µM) and lithium (1-80 µg/ml) afforded 10-30% protection against ALS/CSF-elicited neurotoxicity, and (3) at 1-10 µM, riluzole antagonized the protection afforded by the 3 agents. These results strongly support the view that at the riluzole concentrations reached in the brain of patients, the neurotoxic effects of this drug could be masking the potential neuroprotective actions of new compounds being tested in clinical trials. Therefore, in the light of the present results, the inclusion of a group of patients free of riluzole treatment may be mandatory in future clinical trials performed in ALS patients with novel neuroprotective compounds.