bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicriteria optimization of the spatial dose distribution
Authors: Schlaefer Alexander , Viulet Tiberiu , Muacevic Alexander , Fürweger Christoph 
Published: November 2013

Purpose:Treatment planning for radiation therapy involves trade‐offs with respect to different clinical goals. Typically, the dose distribution is evaluated based on few statistics and dose–volume histograms. Particularly for stereotactic treatments, the spatial dose distribution represents further criteria, e.g., when considering the gradient between subregions of volumes of interest. The authors have studied how to consider the spatial dose distribution using a multicriteria optimization approach.Methods:The authors have extended a stepwise multicriteria optimization approach to include criteria with respect to the local dose distribution. Based on a three‐dimensional visualization of the dose the authors use a software tool allowing interaction with the dose distribution to map objectives with respect to its shape to a constrained optimization problem. Similarly, conflicting criteria are highlighted and the planner decides if and where to relax the shape of the dose distribution.Results:To demonstrate the potential of spatial multicriteria optimization, the tool was applied to a prostate and meningioma case. For the prostate case, local sparing of the rectal wall and shaping of a boost volume are achieved through local relaxations and while maintaining the remaining dose distribution. For the meningioma, target coverage is improved by compromising low dose conformality toward noncritical structures. A comparison of dose–volume histograms illustrates the importance of spatial information for achieving the trade‐offs.Conclusions:The results show that it is possible to consider the location of conflicting criteria during treatment planning. Particularly, it is possible to conserve already achieved goals with respect to the dose distribution, to visualize potential trade‐offs, and to relax constraints locally. Hence, the proposed approach facilitates a systematic exploration of the optimal shape of the dose distribution.
A Type III Secretion System Inhibitor Targets YopD while Revealing Differential Regulation of Secretion in Calcium-Blind Mutants of Yersinia pestis
Authors: Jessen Danielle L. , Bradley David S. , Nilles Matthew L. 
Published: November 2013

ABSTRACT

Numerous Gram-negative pathogens rely upon type III secretion (T3S) systems to cause disease. Several small-molecule inhibitors of the type III secretion systems have been identified; however, few targets of these inhibitors have been elucidated. Here we report that 2,2′-thiobis-(4-methylphenol) (compound D), inhibits type III secretion in
Yersinia pestis
,
Yersinia pseudotuberculosis
, and
Pseudomonas aeruginosa
. YopD, a protein involved in the formation of the translocon and regulatory processes of the type III secretion system, appears to play a role in the inhibition of secretion by compound D. The use of compound D in T3S regulatory mutants demonstrated a difference in secretion inhibition in the presence and absence of calcium. Interestingly, compound D was effective only under conditions without calcium, indicating that a secretion-active needle structure may be necessary for compound D to inhibit secretion.
Endovascular recanalization of complete subacute to chronic atherosclerotic occlusions of intracranial arteries
Authors: Aghaebrahim Amin , Jovin Tudor , Jadhav Ashutosh P , Noorian Alireza , Gupta Rishi , Nogueira Raul G 
Published: November 2013

Objective/backgroundSymptomatic subacute/chronic large artery intracranial occlusive disease represents a common medical dilemma. We now report a multicenter experience of endovascular recanalization of intracranial atherosclerotic occlusions refractory to medical therapy.MethodsRetrospective multicenter case series of consecutive endovascularly treated patients presenting with symptomatic (transient ischemic attack (TIA) or stroke) subacute (>48 h) or chronic complete occlusion of an intracranial artery of presumed atherosclerotic etiology. All of the patients were considered to be in the high risk category with symptomatic intracranial occlusions and progression or recurrence of their symptoms despite the best medical therapies.Results24 patients (median age 63 years; mean pretreatment National Institutes of Health Stroke Scale (NIHSS) score 10; 66% men) presenting with recurrent TIAs (n=1) or strokes (n=23) were treated in two academic centers from April 2005 to June 2012. Median time from symptoms/documented occlusion to treatment was 5 days. Periprocedural complications included one symptomatic intracranial hemorrhage, one reperfusion syndrome, three asymptomatic dissections, and one asymptomatic perforation. There were no periprocedural strokes. Immediate postprocedural improvement (NIHSS decrease ≥4 at hospital discharge) occurred in 43% (10/23) of patients. There were no recurrent TIAs or strokes in the 22 patients with clinical follow-up at 90 days. At 90 days, there were two deaths (unrelated to the procedure) and 9/22 patients with an available modified Rankin Scale (mRS) score achieved a good outcome (mRS score of 0–2).ConclusionsEndovascular recanalization can be performed with an acceptable safety profile in selected patients with symptomatic complete subacute to chronic intracranial atherosclerotic occlusion. Additional studies are warranted to investigate whether this treatment compares favorably with best medical management.
Synergistic Combination of Novel Tubulin Inhibitor ABI-274 and Vemurafenib Overcomes Vemurafenib Acquired Resistance in BRAFV600E Melanoma
Authors: Wang Jin , Chen Jianjun , Miller Duane D. , Li Wei 
Published: November 2013

Abstract
Acquired clinical resistance to vemurafenib, a selective BRAFV600E inhibitor, arises frequently after short-term chemotherapy. Because inhibitions of targets in the RAF–MEK–ERK pathway result in G0–G1 cell-cycle arrest, vemurafenib-resistant cancer cells are expected to escape this cell-cycle arrest and progress to the subsequent G2–M phase. We hypothesized that a combined therapy using vemurafenib with a G2–M phase blocking agent will trap resistant cells and overcome vemurafenib resistance. To test this hypothesis, we first determined the combination index (CI) values of our novel tubulin inhibitor ABI-274 and vemurafenib on parental human A375 and MDA-MB-435 melanoma cell lines to be 0.32 and 0.1, respectively, suggesting strong synergy for the combination. We then developed an A375RF21 subline with significant acquired resistance to vemurafenib and confirmed the strong synergistic effect. Next, we studied the potential mechanisms of overcoming vemurafenib resistance. Flow cytometry confirmed that the combination of ABI-274 and vemurafenib synergistically arrested cells in the G1–G2–M phase, and significantly increased apoptosis in both parental A375 and the vemurafenib-resistant A375RF21 cells. Western blot analysis revealed that the combination treatment effectively reduced the level of phosphorylated and total AKT, activated the apoptosis cascade, and increased cleaved caspase-3 and cleaved PARP, but had no significant influence on the level of extracellular signal–regulated kinase (ERK) phosphorylation. Finally, in vivo coadministration of vemurafenib with ABI-274 showed strong synergistic efficacy in the vemurafenib-resistant xenograft model in nude mice. Overall, these results offer a rational combination strategy to significantly enhance the therapeutic benefit in patients with melanoma who inevitably become resistant to current vemurafenib therapy. Mol Cancer Ther; 13(1); 16–26. ©2013 AACR.
Changes in Moisture Flux over the Tibetan Plateau during 1979–2011 and Possible Mechanisms
Authors: Gao Yanhong , Cuo Lan , Zhang Yongxin 
Published: November 2013

Abstract
Changes in moisture as represented by P − E (precipitation − evapotranspiration) and the possible causes over the Tibetan Plateau (TP) during 1979–2011 are examined based on the Global Land Data Assimilation Systems (GLDAS) ensemble mean runoff and reanalyses. It is found that the TP is getting wetter as a whole but with large spatial variations. The climatologically humid southeastern TP is getting drier while the vast arid and semiarid northwestern TP is getting wetter. The Clausius–Clapeyron relation cannot be used to explain the changes in P − E over the TP.
Through decomposing the changes in P − E into three major components—dynamic, thermodynamic, and transient eddy components—it is noted that the dynamic component plays a key role in the changes of P − E over the TP. The thermodynamic component contributes positively over the southern and central TP whereas the transient eddy component tends to reinforce (offset) the dynamic component over the southern and parts of the northern TP (central TP).
Seasonally, the dynamic component contributes substantially to changes in P − E during the wet season, with small contributions from the thermodynamic and transient eddy components. Further analyses reveal the poleward shift of the East Asian westerly jet stream by 0.7° and poleward moisture transport as well as the intensification of the summer monsoon circulation due to global warming, which are shown to be responsible for the general wetting trend over the TP. It is further demonstrated that changes in local circulations that occur due to the differential heating of the TP and its surroundings are responsible for the spatially varying changes in moisture over the TP.
YHap: a population model for probabilistic assignment of Y haplogroups from re-sequencing data
Authors: Zhang Fan , Chen Ruoyan , Liu Dongbing , Yao Xiaotian , Li Guoqing , Jin Yabin , Yu Chang , Li Yingrui , Coin Lachlan JM 
Published: November 2013

Abstract

Background
Y haplogroup analyses are an important component of genealogical reconstruction, population genetic analyses, medical genetics and forensics. These fields are increasingly moving towards use of low-coverage, high throughput sequencing. While there have been methods recently proposed for assignment of Y haplogroups on the basis of high-coverage sequence data, assignment on the basis of low-coverage data remains challenging.

Results
We developed a new algorithm, YHap, which uses an imputation framework to jointly predict Y chromosome genotypes and assign Y haplogroups using low coverage population sequence data. We use data from the 1000 genomes project to demonstrate that YHap provides accurate Y haplogroup assignment with less than 2x coverage.

Conclusions
Borrowing information across multiple samples within a population using an imputation framework enables accurate Y haplogroup assignment.
A secreted splice variant of the Xenopus frizzled-4 receptor is a biphasic modulator of Wnt signalling
Authors: Gorny Anne-Kathrin , Kaufmann Lilian T , Swain Rajeeb K , Steinbeisser Herbert 
Published: November 2013

Abstract

Background
Activation of the Wnt signalling cascade is primarily based on the interplay between Wnt ligands, their receptors and extracellular modulators. One prominent family of extracellular modulators is represented by the SFRP (secreted Frizzled-related protein) family. These proteins have significant similarity to the extracellular domain of Frizzled receptors, suggesting that they bind Wnt ligands and inhibit signalling. The SFRP-type protein Fz4-v1, a splice variant of the Frizzled-4 receptor found in humans and Xenopus, was shown to augment Wnt/β-catenin signalling, and also interacts with those Wnt ligands that act on β-catenin-independent Wnt pathways.

Findings
Here we show that Xenopus Fz4-v1 can activate and inhibit the β-catenin-dependent Wnt pathway. Gain-of-function experiments revealed that high Wnt/β-catenin activity is inhibited by low and high concentrations of Fz4-v1. In contrast, signals generated by low amounts of Wnt ligands were enhanced by low concentrations of Fz4-v1 but were repressed by high concentrations. This biphasic activity of Fz4-v1 was not observed in non-canonical Wnt signalling. Fz4-v1 enhanced β-catenin-independent Wnt signalling triggered by either low or high doses of Wnt11. Antisense morpholino-mediated knock-down experiments demonstrated that in early Xenopus embryos Fz4-v1 is required for the migration of cranial neural crest cells and for the development of the dorsal fin.

Conclusions
For the first time, we show that a splice variant of the Frizzled-4 receptor modulates Wnt signalling in a dose-dependent, biphasic manner. These results also demonstrate that the cystein-rich domain (CRD), which is shared by Fz4-v1 and SFRPs, is sufficient for the biphasic activity of these secreted Wnt modulators.
Multi-modal highlight generation for sports videos using an information-theoretic excitability measure
Authors: Hasan Taufiq , Bořil Hynek , Sangwan Abhijeet , L Hansen John H 
Published: November 2013

Abstract
The ability to detect and organize ‘hot spots’ representing areas of excitement within video streams is a challenging research problem when techniques rely exclusively on video content. A generic method for sports video highlight selection is presented in this study which leverages both video/image structure as well as audio/speech properties. Processing begins where the video is partitioned into small segments and several multi-modal features are extracted from each segment. Excitability is computed based on the likelihood of the segmental features residing in certain regions of their joint probability density function space which are considered both exciting and rare. The proposed measure is used to rank order the partitioned segments to compress the overall video sequence and produce a contiguous set of highlights. Experiments are performed on baseball videos based on signal processing advancements for excitement assessment in the commentators’ speech, audio energy, slow motion replay, scene cut density, and motion activity as features. Detailed analysis on correlation between user excitability and various speech production parameters is conducted and an effective scheme is designed to estimate the excitement level of commentator’s speech from the sports videos. Subjective evaluation of excitability and ranking of video segments demonstrate a higher correlation with the proposed measure compared to well-established techniques indicating the effectiveness of the overall approach.
HIV relies on neddylation for ubiquitin ligase-mediated functions
Authors: Nekorchuk Michael D , Sharifi Hamayun J , Furuya Andrea KM , Jellinger Robert , de Noronha Carlos MC 
Published: November 2013

Abstract

Background
HIV and SIV defeat antiviral proteins by usurping Cullin-RING E3 ubiquitin ligases (CRLs) and likely influence other cellular processes through these as well. HIV-2 viral protein X (Vpx) engages the cullin4-containing CRL4 complex to deplete the antiviral protein SAMHD1. Vif expressed by HIV-1 and HIV-2 taps a cullin5 ubiquitin ligase complex to mark the antiviral protein APOBEC3G for destruction. Viral Protein R of HIV-1 (Vpr) assembles with the CRL4 ubiquitin ligase complex to deplete uracil-N-glycosylase2 (UNG2). Covalent attachment of the ubiquitin-like protein side-chain NEDD8 functionally activates cullins which are common to all of these processes.

Results
The requirement for neddylation in HIV-1 and HIV-2 infectivity was tested in the presence of APOBEC3G and SAMHD1 respectively. Further the need for neddylation in HIV-1 Vpr-mediated depletion of UNG2 was probed. Treatment with MLN4924, an adenosine sulfamate analog which hinders the NEDD8 activating enzyme NAE1, blocked neddylation of cullin4A (CUL4A). The inhibitor hindered HIV-1 infection in the presence of APOBEC3G, even when Vif was expressed, and it stopped HIV-2 infection in the presence of SAMHD1 and Vpx. Consistent with these findings, MLN4924 prevented Vpx-mediated depletion of SAMHD1 in macrophages infected with Vpx-expressing HIV-2, as well as HIV-1 Vif-mediated destruction of APOBEC3G. It also stemmed Vpr-mediated UNG2 elimination from cells infected with HIV-1.

Conclusions
Neddylation plays an important role in HIV-1 and HIV-2 infection. This observation is consistent with the essential parts that cullin-based ubiquitin ligases play in overcoming cellular anti-viral defenses.
Temporal effect of HLA-B*57 on viral control during primary HIV-1 infection
Authors: Vaidya Sagar A , Streeck Hendrik , Beckwith Noor , Ghebremichael Musie , Pereyra Florencia , Kwon Douglas S , Addo Marylyn M , Rychert Jenna , Routy Jean-Pierre , Jessen Heiko , Kelleher Anthony D , Hecht Frederick , Sekaly Rafick-Pierre , Carrington Mary , Walker Bruce D , Allen Todd M , Rosenberg Eric S , Altfeld Marcus 
Published: November 2013

Abstract

Background
HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infection and establishment of the early viral load set point (VLSP).

Findings
Individuals identified during primary HIV-1 infection were HLA class I typed and followed longitudinally. Associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP were analyzed in untreated subjects. The results showed that neither HLA-B*57 nor HLA-B*27 were significantly associated with viral control during acute HIV-1 infection (Fiebig stage I-IV, n=171). HLA-B*57 was however significantly associated with a subsequent lower VLSP (p<0.001, n=135) with nearly 1 log10 less median viral load. Analysis of a known polymorphism at position 97 of HLA-B showed significant associations with both lower initial viral load (p<0.01) and lower VLSP (p<0.05). However, this association was dependent on different amino acids at this position for each endpoint.

Conclusions
The effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, which suggests the underlying mechanism of control occurs at a critical period in the first several months after HIV-1 acquisition. The risk profile of polymorphisms at position 97 of HLA-B are more broadly associated with HIV-1 viral load during primary infection and may serve as a focal point in further studies of HLA-B function.
One case of swine hepatitis E virus and porcine reproductive and respiratory syndrome virus Co-infection in weaned pigs
Authors: Mao Jingjing , Zhao Yue , She Ruiping , Xiao Peng , Tian Jijing , Chen Jian 
Published: November 2013

Abstract

Background
Using various methods, we analyzed the cause of death among weaned pigs from a pig farm in Hebei Province, China. All 300 piglets (100% fatality) were identified as moribund, with death occurring within 1 month from the onset of clinical signs.

Results
A single case exhibited obvious hemorrhagic necrotic changes with massive lymphocytic infiltration in multiple organs, in particular the liver, lungs and intestines. Dysplasia and lymphocyte deterioration were common in lymphatic organs. No visible bacterial colonies from liver and spleen were observed in nutrient, MacConkey, and blood agar plates. Using polymerase chain reaction techniques for this case, we attempted to detect a number of epidemic swine viruses in spleen and liver, including PRRSV, CSF, HEV, and PCV2. We found that this sample was positive for the presence of HEV and PRRSV.

Conclusions
We have detected HEV and PRRSV co-infection in one piglet. Severe pathologic changes were observed. The high mortality of weaned pigs which showed the similar clinical syptom was possibly a result of HEV and PRRSV co-infection, which has rarely been reported previously. We speculated that co-infection with PRRSV and HEV might lead to more serious problems.
CD20, CD3, placental malaria infections and low birth weight in an area of unstable malaria transmission in Central Sudan
Authors: Batran Samah E , Salih Magdi M , Elhassan Elhassan M , Mohmmed Ahmed A , Adam Ishag 
Published: November 2013

AbstractBackgroundMalaria during pregnancy is the main cause of low birth weight (LBW) in the tropics. There are few studies concerning B and T lymphocyte infiltrates in placental malaria infections or their potential association with LBW babies.MethodsA case–control study was conducted at the Medani Hospital, Central Sudan. Cases were women who had LBW deliveries (infants weighed < 2,500 g) and controls were parturient women with normal birth weight babies. Sociodemographic and medical characteristics were gathered from both groups of women using questionnaires. Cases and controls were investigated for malaria using microscopic blood film analysis, placental histology, and immunohistochemistry for detection of B (CD20) and T lymphocytes (CD3).ResultsThe two groups (97 in each arm) were well matched in their basic characteristics. There were no malaria-positive blood films in either the cases or the controls. Twenty-nine (30.0%)vs.24 (24.7%), P = 0.519 of the casesvs.the controls had placental malaria infections on histological examination. Three (3.1%), two (2.1%) and 24 (24.7%)vs.two (2.1%), two (2.1%) and 20 (20.6%) of the placentae showed evidence of acute, chronic and past malarial infections on histopathological examination of the two groups (case–control), respectively, while 68 (70.1%)vs.73 (75.3%) of them showed no signs of infection; P = 0.420. Women with placental malaria infections had significantly fewer CD20 cell infiltrates [6 (11.3% vs. 95 (67.4%), P < 0.001)] and higher numbers of CD3 cell infiltrates [50 (94.3%) vs. 42 (29.8%), P < 0.001] than those without placental malaria infection. Logistic regression analysis showed that neither placental malaria infections nor CD3 or CD20 were associated with LBW.ConclusionsSignificantly higher rates of CD3 T cells and lower rates of CD20 B cells were found in women with placental malaria infections compared with those without such infections. Neither placental malaria infection nor CD3 or CD20 are associated with LBW.Virtual slideshttp://www.diagnosticpathology.diagnomx.eu/vs/6879723961063755