Search

Idea submissions in innovation contests contain a variety of information as e.g., the idea description, information on its contributor or feedback by the crowd. Raters might perceive and attend to these sources of information differently, which potentially influences the selection of the best ideas. Up to now, however, we know little about the extent to which the visual attention to such information changes during the idea selection process and what impact such changes might have on the outcome of idea selection. The goal of our experiment is to investigate the effect of two idea presentation modes on changes in visual attention to idea attributes, measured with fixations using eye-tracking over time. Preliminary results on a sample of 30 participants show that visual attention to idea attributes decreases rapidly after participants saw the first 8 ideas.

Dispersions of preexfoliated nanographene (NG) and fused electron donor–acceptor tetrathiafulvalene–perylenediimide (TTF–PDI) enable multifunctional, noncovalently functionalized NG. They were characterized by complementary spectroscopic and microscopic techniques. The design strategy of the chromophoric and electroactive molecular conjugate renders a large and planar π-extended system with a distinct localization of electron-rich and electron-poor parts at either end of the molecular conjugate. Within the in-situ formed nanohybrid, the conjugate was found to couple electronically with NG preferentially through the electron accepting PDI rather than the electron donating TTF and to lead to p-doping of graphene.

PURPOSE: To explore associations between magnetic resonance imaging (MRI) features of prostate cancer and expression levels of cell cycle genes, as assessed by the Prolaris® test. MATERIALS AND METHODS: Retrospective analysis of 118 PCa patients with genetic testing of biopsy specimen and prostate MRI from 08/2013 to 11/2015. Associations between the cell cycle risk (CCR) score and MRI features (i.e. PI-RADSv2 score, extracapsular extension (ECE), quantitative metrics) were analysed with Fisher’s exact test, nonparametric tests, and Spearman correlation coefficient. In 41 patients (34.7%), test results were compared to unfavourable features on prostatectomy specimen (i.e. Gleason group≥3, ECE, lymph node metastases). RESULTS: Fifty-four (45.8%), 60 (50.8%) and 4 (3.4%) patients had low, intermediate and high-risk cancers according to American Urological Association scoring system. Patients with ECE on MRI had significantly higher mean CCR scores (reader 1: 3.9 vs. 3.2, p=0.015; reader 2: 3.6 vs. 3.2, p=0.045). PI-RADSv2 scores and quantitative MRI features were not associated with CCR scores. In the prostatectomy subset, ECE on MRI (p=

PURPOSE N-chlorotaurine (NCT) is an anti-infective belonging to the class of chloramines and an investigative drug for the topical treatment of keratoconjunctivitis. The aim of the present study was to demonstrate its efficacy against Acanthamoeba and Candida in corneas infected ex vivo. METHODS Corneal buttons from porcine eyes were contaminated with Acanthamoeba castellanii trophozoites or Candida albicans Centraalbureau voor Schimmelcultures 5982 and incubated for 7 and 3 days, respectively. Subsequently, they were treated with 1% NCT for 5 to 120 minutes. After further incubation for 2 days in the absence of NCT in tests with A. castellanii, the buttons were homogenized, and the amoebae grown for a further 5 days before they were counted in a light microscope. For C. albicans, quantitative cultures were performed from corneal homogenates. RESULTS Incubation of 120 minutes in NCT completely inhibited the regrowth of A. castellanii and reduced the number of C. albicans colony-forming unit counts by 4 log10. In addition, at 60 minutes, significant reductions of both pathogens could be observed. Histology showed penetration of pathogens into the stroma of the corneal buttons. CONCLUSIONS NCT inactivates A. castellanii and C. albicans in corneal tissue.

A combination of a preexfoliated nanographene (NG) dispersion and fused electron donor–acceptor tetrathiafulvalene–perylenediimide (TTF–PDI) results in a noncovalent functionalization of NG. Such novel types of nanohybrids were characterized by complementary spectroscopic and microscopic techniques. The design strategy of the chromophoric and electroactive molecular conjugate renders a large and planar π-extended system with a distinct localization of electron-rich and electron-poor parts at either end of the molecular conjugate. Within the in situ formed nanohybrid, the conjugate was found to couple electronically with NG preferentially through the electron accepting PDI rather than the electron donating TTF and to form the one-electron reduced form of PDI, which corresponds to p-doping of graphene.

We lay the foundations for a model theoretic study of proalgebraic groups. Our axiomatization is based on the tannakian philosophy. Through a tensor analog of skeletal categories we are able to consider neutral tannakian categories with a fibre functor as many-sorted first order structures. The class of diagonalizable proalgebraic groups is analyzed in detail. We show that the theory of a diagonalizable proalgebraic group $G$ is determined by the theory of the base field and the theory of the character group of $G$. Some initial steps towards a comprehensive study of types are also made., Comment: 39 pages

We study the structure of the absolute differential Galois group of a rational function field over an algebraically closed field of characteristic zero. In particular, we relate the behavior of differential embedding problems to the condition that the absolute differential Galois group is free as a proalgebraic group. Building on this, we prove Matzat's freeness conjecture in the case that the field of constants is algebraically closed of countably infinite transcendence degree over the rationals. This is the first known case of the twenty year old conjecture., Comment: 16 pages. Version of Oct. 20, 2020. Expanded the discussion after Definition 2.4; added an assumption on not being finite type after the proof of Lemma 3.2

Replacing finite groups by linear algebraic groups, we study an algebraic-geometric counterpart of the theory of free profinite groups. In particular, we introduce free proalgebraic groups and characterize them in terms of embedding problems. The main motivation for this endeavor is a differential analog of a conjecture of Shafarevic., Comment: 36 pages, final accepted version

$ $We study solutions of difference equations in the rings of sequences and, more generally, solutions of equations with a monoid action in the ring of sequences indexed by the monoid. This framework includes, for example, difference equations on grids (e.g., standard difference schemes) and difference equations in functions on words. On the universality side, we prove a version of strong Nullstellensatz for such difference equations under the assuption that the cardinality of the ground field is greater than the cardinality of the monoid and construct an example showing that this assumption cannot be omitted. On the undecidability side, we show that the following problems are undecidable: $\bullet$ testing radical difference ideal membership or, equivalently, determining whether a given difference polynomial vanishes on the solution set of a given system of difference polynomials; $\bullet$ determining consistency of a system of difference equations in the ring of real-valued sequences; $\bullet$ determining consistency of a system of equations with action of $\mathbb{Z}^2$, $\mathbb{N}^2$, or the free monoid with two generators in the corresponding ring of sequences over any field of characteristic zero.

5019 Background: Preferential fat accumulation in the visceral compartment (i.e. central adiposity) increases cardiovascular risk in the general population independent of body mass index (BMI). We investigated how body fat distribution modulates the cardiometabolic risk of male germ cell tumor (GCT) survivors after cisplatin-based chemotherapy. Methods: For 456 patients in The Platinum Study enrolled at Memorial Sloan Kettering Cancer Center, visceral (VAT) and subcutaneous (SAT) adipose tissue compartments were quantified on pre-chemotherapy computed tomography (CT) scans (median time between CT and chemotherapy: 13 days, range: 0-56). The VAT/SAT ratio was calculated as a quantitative indicator of central adiposity. Endpoints were (I) post-chemotherapy cardiovascular risk as per the office-based Framingham risk calculator, and (II) incidence of post-chemotherapy cardiometabolic disease defined as need for new anti-hypertensive drugs, or lipid-lowering drugs, or medication used to treat diabetes. Changes in fat distribution after chemotherapy were analyzed in a subgroup with post-chemotherapy CTs (n = 108; median interval from chemotherapy start: 18 months, range: 7-185). Linear regression with interaction terms (endpoint 1, subgroup analysis) and Cox proportional hazard regression (endpoint 2) were applied. Results: For all 456 patients, median age at chemotherapy initiation was 31 years and median follow-up was 27 months (range: 7, 207). At baseline (pre-chemotherapy), the median BMI was 26.2 kg/m2, and 102 patients (22.4%) had a BMI of ≥30 kg/m2. The median VAT/SAT ratio at baseline CT was 0.49, and positively associated with higher post-chemotherapy Framingham risk scores after adjustment for age, BMI, and blood pressure measurements at chemotherapy start, as well as post-therapy follow-up time (adjusted β-estimate: 1.36, 95% CI: 1.15, 1.59, p < 0.001). A higher VAT/SAT ratio also inferred a higher likelihood of new onset cardiometabolic disease in patients with BMI ≥30 kg/m2 (age-adjusted HR: 3.11, 95%CI: 1.01, 9.62, p = 0.048), but not in those with BMI < 30 kg/m2. In the subgroup analysis, we observed a significant increase of BMI after chemotherapy (mean: +1.1 kg/m2, 95% CI: +0.58, +1.54; p < 0.001). Changes in BMI were positively associated with changes of the VAT/SAT ratio (β-estimate: 3.0, 95% CI: 2.23, 4.04; p < 0.001), meaning that weight gain occurred preferentially in the VAT compartment, while weight loss tended to be paralleled by an improved body fat distribution. Conclusions: In male GCT patients, central adiposity at baseline increases cardiometabolic risk after cisplatin-based chemotherapy, particularly for obese individuals. Quantification of an individual’s body fat distribution on pre-chemotherapy CT could potentially help to identify high risk individuals who may benefit from intensified risk-modulating interventions.

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and serum prostate-specific antigen (PSA) level after systemic treatment and the association between PSMA PET and overall survival in metastatic CRPC patients. PubMed, Embase, and Cochrane library databases were searched until August 2020. Studies that reported the concordance between PSMA PET and PSA response were included. PSMA PET and PSA response evaluation were dichotomized into response vs. non-response to construct two-by-two contingency tables, an ≥30% increase in PSMA PET according to PET Response Criteria in Solid Tumors 1.0 and as an increase in serum PSA level of ≥25% as per Prostate Cancer Working Group 3 guidelines were defined as non-response. The percent agreement rates were pooled using random-effect model. Ten studies (268 patients) were included. The concordance rates ranged 0.50–0.84 with a pooled proportion of 0.73 (95% confidence interval 0.67–0.79). Patients were treated with 177Lu-PSMA therapy in five, chemotherapy in three, 223Ra in one, and more than one type in one study. Various PET parameters were used: the most widely evaluated was PSMA tumor volume (PSMA-TV). Similar proportions were found across different therapeutic agents, PET response parameters, and regarding directionality of discordance (PSA response/PSMA non-response vs. PSMA response/PSA non-response). Two studies reported that a decrease in PSMA-TV was associated with better overall survival. PSMA PET and PSA response assessments were discordant in nearly a fourth of metastatic CRPC patients. Further studies are warranted to establish the clinical meaning of this discordance and define appropriate management for such clinical situation.

All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage. IMPORTANCE The conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of different antibody lineages to this site remain elusive. Studies have shown that strain-specific antibodies can evolve into broadly neutralizing antibodies or in some cases act as helper lineages. Therefore, characterizing the epitopes of strain-specific antibodies may help to inform the design of HIV-1 immunogens to elicit broadly neutralizing antibodies. In this study, we isolate a narrowly neutralizing N276 glycan-dependent antibody and use X-ray crystallography and viral deep sequencing to describe how gp120 lacking glycans in V5 might have elicited these early glycan-dependent CD4 binding site antibodies. These data highlight how glycan holes can play a role in the elicitation of B-cell lineages targeting the CD4 binding site.

MRI has emerged as the most comprehensive noninvasive diagnostic tool for focal liver lesions and diffuse hepatobiliary disorders. The introduction of hepatobiliary contrast agents, most notably gadoxetic acid (GA), has expanded the role of MRI, particularly in the functional imaging of chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD). GA-enhanced MRI (GA-MRI) may help to distinguish between the two subgroups of NAFLD, simple steatosis and nonalcoholic steatohepatitis. Furthermore, GA-MRI can be used to stage fibrosis and cirrhosis, predict liver transplant graft survival, and preoperatively estimate the risk of liver failure should major resection be undertaken. The amount of GA uptake can be estimated, using static images, by the relative liver enhancement, hepatic uptake index, and relaxometry of T1-mapping during the hepatobiliary phase. On the contrary, the hepatic extraction fraction and liver perfusion can be measured on dynamic imaging. Importantly, there is currently no clear consensus as to which of these MR-derived parameters is the most suitable for assessing liver dysfunction. This review article aims to describe the current role of GA-enhanced MRI in quantifying liver function, primarily in diffuse hepatobiliary disorders. Level of Evidence: 3 J. Magn. Reson. Imaging 2017;45:646–659.

The aim of this study was to evaluate the prognostic potential of a 3-parameter visual scoring (qualitative score [QS]) system for hepatobiliary phase gadoxetic acid-enhanced magnetic resonance imaging (MRI) in orthotopic liver transplant grafts.This retrospective study of 128 patients was approved by our institutional review board. Two readers independently assigned 3 QSs to T1-weighted MRI scans, 20 minutes after the administration of gadoxetic acid (hepatobiliary phase), based upon the following: (1) liver parenchymal enhancement (EnQS, 0-2); (2) biliary contrast excretion (ExQS, 0-2); and (3) signal intensity of the portal vein relative to the liver parenchyma, that is, the portal vein sign (PVsQS, 0-2). The functional liver imaging score (FLIS) was calculated as the sum score of these 3 parameters. The relative liver enhancement (RLE) was measured as well. Demographic, clinical, laboratory parameters, and imaging findings were included in univariate and multivariate statistical analyses. The primary end point was graft failure, that is, retransplantation or death from liver failure. The probability of graft survival was calculated by Kaplan-Meier estimates and Cox proportional hazards regression.In the univariate analysis, EnQS, ExQS, PVsQS, and FLIS scores, as well as RLE, were significantly associated with the 1- to 3-year probability of graft survival (P0.001). For a FLIS of (0), the 3-year probability of graft survival was 6.5%, whereas it was 51.3% for a FLIS of (1-3) and 100% for a FLIS of (4-6) (P0.001). In the multivariate survival models, EnQS, ExQS, and PVsQS, each independently outperformed the majority of clinical and laboratory parameters, and the FLIS did even better regarding the prediction of 1- to 3-year graft survival.In liver transplant recipients, gadoxetic acid-enhanced MRI-derived QSs (ie, EnQS, ExQS, and PVsQS), as well as the FLIS and RLE, can predict graft survival probability.

A successful paradigm shift toward personalized management strategies for patients with prostate cancer (PCa) is heavily dependent on the availability of noninvasive diagnostic tools capable of accurately establishing the true extent of disease at the time of diagnosis and estimating the risk of subsequent disease progression and related mortality. Although there is still considerable scope for improvement in its diagnostic, predictive, and prognostic capabilities, multiparametric prostate magnetic resonance imaging (MRI) is currently regarded as the imaging modality of choice for local staging of PCa. A negative MRI, that is, the absence of any MRI-visible intraprostatic lesion, has a high negative predictive value for the presence of clinically significant PCa and can substantiate the consideration of active surveillance as a preferred initial management approach. MRI-derived quantitative and semi-quantitative parameters can be utilized to noninvasively characterize MRI-visible prostate lesions and identify those patients who are most likely to benefit from radical treatment, and differentiate them from patients with benign or indolent prostate pathology that may also be visible on MRI. This literature review summarizes current strategies how MRI can be used to determine a tailored management strategy for an individual patient.

Study Design.A retrospective cohort study.Objective.The aim of this study was to assess and compare the predictive accuracy of six models designed to estimate survival of patients suffering from spinal bone metastases Just (SBMs).Summary of Background Data.On the basis of the estimated survival of patients with SBM, extent of treatment can be adjusted. To aid clinicians in the difficult task of assessing probability of survival, prognostic scoring systems have been developed by Tomita, Tokuhashi, Van der Linden, Bauer, Rades, and Bollen.Methods.All patients who were treated for SBM between 2000 and 2010 were included in this international, multicenter, retrospective study (n=1379). Medical records were reviewed for all items needed to use the scoring systems. Survival time was calculated as the difference between start of treatment for SBM and date of death. Survival curves were estimated using the Kaplan-Meier method and accuracy was assessed with the c-statistic. Survival rates of the worst prognostic groups were evaluated at 4 months.Results.Median follow-up was 6.7 years [95% confidence interval (95% CI) 5.6-7.7] with a minimum of 2.3 years and a maximum of 12.3 years. The overall median survival was 5.1 months (95% CI 4.6-5.6). The most common primary tumors were breast (n=388, 28%), lung (n=318, 23%), and prostate cancer (n=259, 19%). The Tokuhashi, Bauer, Tomita, and Van der Linden models performed similar with a c-statistic of 0.64 to 0.66 and a 4-month accuracy of 62% to 65%. The Rades model (c-statistic 0.44) and Bollen model (c-statistic 0.70) had a 4-month accuracy of 69% and 75%, respectively.Conclusion.The Bollen model performs better than the other models. However, improvements are still warranted to increase the accuracy.Level of Evidence: 3

The added value of diffusion-weighted magnetic resonance imaging (DW-MRI) for the detection, localization, and staging of primary prostate cancer has been extensively reported in original studies and meta-analyses. More recently, DW-MRI and related techniques have been used to non-invasively assess prostate cancer aggressiveness and estimate its biological behavior. The present article aims to summarize the potential applications of DW-MRI for non-invasive optimization of pretherapeutic risk assessment, patient management decisions, and evaluation of treatment response.

The epitopes defined by HIV-1 broadly neutralizing antibodies (bNAbs) are valuable templates for vaccine design, and studies of the immunological development of these antibodies are providing insights for vaccination strategies. In addition, the most potent and broadly reactive of these bNAbs have potential for clinical use. We previously described a family of 12 V1V2-directed neutralizing antibodies, CAP256-VRC26, isolated from an HIV-1 clade C-infected donor at years 1, 2, and 4 of infection (N. A. Doria-Rose et al., Nature 509:55–62, 2014, http://dx.doi.org/10.1038/nature13036 ). Here, we report on the isolation and characterization of new members of the family mostly obtained at time points of peak serum neutralization breadth and potency. Thirteen antibodies were isolated from B cell culture, and eight were isolated using trimeric envelope probes for differential single B cell sorting. One of the new antibodies displayed a 10-fold greater neutralization potency than previously published lineage members. This antibody, CAP256-VRC26.25, neutralized 57% of diverse clade viral isolates and 70% of clade C isolates with remarkable potency. Among the viruses neutralized, the median 50% inhibitory concentration was 0.001 μg/ml. All 33 lineage members targeted a quaternary epitope focused on V2. While all known bNAbs targeting the V1V2 region interact with the N160 glycan, the CAP256-VRC26 antibodies showed an inverse correlation of neutralization potency with dependence on this glycan. Overall, our results highlight the ongoing evolution within a single antibody lineage and describe more potent and broadly neutralizing members with potential clinical utility, particularly in areas where clade C is prevalent. IMPORTANCE Studies of HIV-1 broadly neutralizing antibodies (bNAbs) provide valuable information for vaccine design, and the most potent and broadly reactive of these bNAbs have potential for clinical use. We previously described a family of V1V2-directed neutralizing antibodies from an HIV-1 clade C-infected donor. Here, we report on the isolation and characterization of new members of the family mostly obtained at time points of peak serum neutralization breadth and potency. One of the new antibodies, CAP256-VRC26.25, displayed a 10-fold greater neutralization potency than previously described lineage members. It neutralized 57% of diverse clade viral isolates and 70% of clade C isolates with remarkable potency: the median 50% inhibitory concentration was 0.001 μg/ml. Our results highlight the ongoing evolution within a single antibody lineage and describe more potent and broadly neutralizing members with potential clinical utility, particularly in areas where clade C is prevalent.

The purpose of this study was to differentiate clear cell renal cell carcinoma (RCC) from other common renal cortical tumors by use of DWI.The study included 117 patients (mean age, 60 years) with 122 histopathologically confirmed renal cortical tumors who underwent 1.5-T MRI that included DWI before they underwent nephrectomy between 2006 and 2013. For each tumor, two radiologists independently evaluated apparent diffusion coefficient (ADC) values on the basis of a single ROI in a nonnecrotic area of the tumor and also by assessment of the whole tumor. The concordance correlation coefficient (CCC) was calculated to assess interreader agreement. The mean ADC values of clear cell RCC and every other tumor subtype were compared using an exact Wilcoxon rank sum test.Interreader agreement was excellent and higher in whole-tumor assessment (CCC, 0.982) than in single-ROI analysis (CCC, 0.756). For both readers, ADC values for clear cell RCC found on single-ROI assessment (2.19 and 2.08 × 10(-3) mm(2)/s) and whole-tumor assessment (2.30 and 2.32 × 10(-3) mm(2)/s) were statistically significantly higher than those for chromophobe, papillary, or unclassified RCC (p0.05) but were similar to those for oncocytoma found on single-ROI assessment (2.14 and 2.32 × 10(-3) mm(2)/s) and whole-tumor assessment (2.38 and 2.24 × 10(-3) mm(2)/s). ADC values were also higher for clear cell RCC than for angiomyolipoma, but the difference was statistically significant only in whole-tumor assessment (p0.03).ADC values were statistically significantly higher for clear cell RCC than for chromophobe, papillary, or unclassified RCC subtypes; however, differentiating clear cell RCC from oncocytoma by use of DWI remains especially challenging, because similar ADC values have been shown for these two tumor types.

During the past decade, with its breakthroughs in systems biology, precision medicine (PM) has emerged as a novel health-care paradigm. Challenging reductionism and broad-based approaches in medicine, PM is an approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. It involves integrating information from multiple sources in a holistic manner to achieve a definitive diagnosis, focused treatment, and adequate response assessment. Biomedical imaging and imaging-guided interventions, which provide multiparametric morphologic and functional information and enable focused, minimally invasive treatments, are key elements in the infrastructure needed for PM. The emerging discipline of radiogenomics, which links genotypic information to phenotypic disease manifestations at imaging, should also greatly contribute to patient-tailored care. Because of the growing volume and complexity of imaging data, decision-support algorithms will be required to help physicians apply the most essential patient data for optimal management. These innovations will challenge traditional concepts of health care and business models. Reimbursement policies and quality assurance measures will have to be reconsidered and adapted. In their 10th biannual symposium, which was held in August 2013, the members of the International Society for Strategic Studies in Radiology discussed the opportunities and challenges arising for the imaging community with the transition to PM. This article summarizes the discussions and central messages of the symposium. (C) RSNA, 2015

[This corrects the article DOI: 10.1371/journal.pone.0149725.].

The GI tract is preferentially targeted during acute/early HIV-1 infection. Consequent damage to the gut plays a central role in HIV pathogenesis. The basis for preferential targeting of gut tissues is not well defined. Recombinant proteins and synthetic peptides derived from HIV and SIV gp120 bind directly to integrin α4β7, a gut-homing receptor. Using both cell-surface expressed α4β7 and a soluble α4β7 heterodimer we demonstrate that its specific affinity for gp120 is similar to its affinity for MAdCAM (its natural ligand). The gp120 V2 domain preferentially engages extended forms of α4β7 in a cation -sensitive manner and is inhibited by soluble MAdCAM. Thus, V2 mimics MAdCAM in the way that it binds to α4β7, providing HIV a potential mechanism to discriminate between functionally distinct subsets of lymphocytes, including those with gut-homing potential. Furthermore, α4β7 antagonists developed for the treatment of inflammatory bowel diseases, block V2 binding to α4β7. A 15-amino acid V2 -derived peptide is sufficient to mediate binding to α4β7. It includes the canonical LDV/I α4β7 binding site, a cryptic epitope that lies 7-9 amino acids amino terminal to the LDV/I, and residues K169 and I181. These two residues were identified in a sieve analysis of the RV144 vaccine trial as sites of vaccine -mediated immune pressure. HIV and SIV V2 mAbs elicited by both vaccination and infection that recognize this peptide block V2-α4β7 interactions. These mAbs recognize conformations absent from the β- barrel presented in a stabilized HIV SOSIP gp120/41 trimer. The mimicry of MAdCAM-α4β7 interactions by V2 may influence early events in HIV infection, particularly the rapid seeding of gut tissues, and supports the view that HIV replication in gut tissue is a central feature of HIV pathogenesis.

We introduce the notion of differential torsors, which allows the adaptation of constructions from algebraic geometry to differential Galois theory. Using these differential torsors, we set up a general framework for applying patching techniques in differential Galois theory over fields of characteristic zero. We show that patching holds over function fields over the complex numbers. As the main application, we prove the solvability of all differential embedding problems over complex function fields, thereby providing new insight on the structure of the absolute differential Galois group, i.e., the fundamental group of the underlying Tannakian category., Documenta Mathematica, 2018, vol. 23, p. 189-240, 1431-0643

For many radiologists, requests for imaging evaluation of testicular or scrotal symptoms and physical exam findings may cause some degree of uneasiness, for two main reasons: first, the number of tumor entities and tumor-like lesions in the testes and scrotum is relatively large and their histopathologic classification is complex (Table 1) and second, case volume of scrotal studies for non-emergency indications may be relatively low in some centers. In this chapter, we provide basic strategies to extract information from imaging pertinent to some of the most commonly encountered clinical scenarios in the evaluation of the testes and scrotum.

Two zinc phthalocyanines (ZnPcs) have been equipped with Newkome-type dendritic branches of increasing size and number of terminal carboxylate functional groups. The negatively charged carboxylates render these polyelectrolytes soluble in polar media such as methanol or buffered water. Sonication of the ZnPcs with graphene allowed for pronounced non-covalent binding of the ZnPc moieties on the graphene surface. These hybrid systems were fully characterized via UV/Vis, AFM, TEM, Raman and transient absorption spectroscopy, yielding insights into the electron donating nature of the novel phthalocyanine structures.

The diagnostics of diffuse liver disease traditionally rely on liver biopsies and histopathological analysis of tissue specimens. However, a liver biopsy is invasive and carries some non-negligible risks, especially for patients with decreased liver function and those requiring repeated follow-up examinations. Over the last decades, magnetic resonance imaging (MRI) has developed into a valuable tool for the non-invasive characterization of focal liver lesions and diseases of the bile ducts. Recently, several MRI methods have been developed and clinically evaluated that also allow the diagnostics and staging of diffuse liver diseases, e.g. non-alcoholic fatty liver disease, hepatitis, hepatic fibrosis, liver cirrhosis, hemochromatosis and hemosiderosis. The sequelae of diffuse liver diseases, such as a decreased liver functional reserve or portal hypertension, can also be detected and quantified by modern MRI methods. This article provides the reader with the basic principles of functional MRI of the liver and discusses the importance in a clinical context.

Multiparametric MRI of the prostate consists of T1- and T2-weighted sequences, which provide anatomical information, and one or more ‘functional’ sequences, that is, diffusion-weighted imaging, dynamic contrast-enhanced sequences and magnetic resonance spectroscopy. Prostate MRI is the most accurate imaging method for local staging of prostate cancer and can also be used for the noninvasive evaluation of tumor aggressiveness. By magnetic resonance-guided prostate biopsy it is possible to target the most cancer-suspicious areas of the gland, especially in patients with a negative transrectal biopsy. In patients with biochemical recurrence after radical treatment, MRI is a valuable tool for the detection of local tumor recurrence and whole-body MRI can be used for the diagnosis of distant metastases.

During physical exercise, pulse transit time (PTT), expressed as the interval between ventricular electrical activity and peripheral pulse wave, may provide a surrogate estimate for blood pressure by the use of specific calibration procedures. The objective of this study was to determine systolic blood pressure (SBP) values derived from the PTT method and from an established method of non-invasive continuous blood pressure measurement based on the volume clamp technique, and to compare their agreement with sphygmomanometry during exercise tests. In 18 subjects, electrocardiogram (ECG) and finger-photoplethysmography were continuously recorded during maximal cycle exercise tests. Intermittent and continuous blood pressure measurements were simultaneously taken using automated sphygmomanometry and a Portapres Model-2 device, respectively. PTT was calculated for each ECG R-wave and the corresponding steepest upstroke slope in the photoplethysmogram, and was transformed to a continuous blood pressure estimate using multipoint nonlinear regression calibration based on the individual subject's sphygmomanometer readings. Bland-Altman limits of agreement between PTT-derived SBP estimates and sphygmomanometer values were -24.7 to 24.1 mmHg, and between Portapres and sphygmomanometer SBP values were -42.0 to 70.1 mmHg. For beat-to-beat SBP estimation during exercise, PTT measurement combined with multipoint nonlinear regression calibration based on intermittent sphygmomanometry may be an alternative to volume clamp devices.

To investigate Haralick texture analysis of prostate MRI for cancer detection and differentiating Gleason scores (GS).One hundred and forty-seven patients underwent T2- weighted (T2WI) and diffusion-weighted prostate MRI. Cancers ≥0.5 ml and non-cancerous peripheral (PZ) and transition (TZ) zone tissue were identified on T2WI and apparent diffusion coefficient (ADC) maps, using whole-mount pathology as reference. Texture features (Energy, Entropy, Correlation, Homogeneity, Inertia) were extracted and analysed using generalized estimating equations.PZ cancers (n = 143) showed higher Entropy and Inertia and lower Energy, Correlation and Homogeneity compared to non-cancerous tissue on T2WI and ADC maps (p-values:.0001-0.008). In TZ cancers (n = 43) we observed significant differences for all five texture features on the ADC map (all p-values:.0001) and for Correlation (p = 0.041) and Inertia (p = 0.001) on T2WI. On ADC maps, GS was associated with higher Entropy (GS 6 vs. 7: p = 0.0225; 6 vs.7: p = 0.0069) and lower Energy (GS 6 vs. 7: p = 0.0116, 6 vs.7: p = 0.0039). ADC map Energy (p = 0.0102) and Entropy (p = 0.0019) were significantly different in GS ≤3 + 4 versus ≥4 + 3 cancers; ADC map Entropy remained significant after controlling for the median ADC (p = 0.0291).Several Haralick-based texture features appear useful for prostate cancer detection and GS assessment.• Several Haralick texture features may differentiate non-cancerous and cancerous prostate tissue. • Tumour Energy and Entropy on ADC maps correlate with Gleason score. • T2w-image-derived texture features are not associated with the Gleason score.

Chordomas mainly arise along the axial skeleton and are characterized by their slow but destructive growth. Prognosis and quality of life are poor because treatment options are mainly limited to surgery and radiotherapy. Survivin, a member of the apoptosis inhibitor protein family, functions as a key regulator of mitosis and programmed cell death, and is overexpressed in many tumor types. The aim of this study was to determine the role of survivin in chordomas. Survivin expression was investigated in 50 chordoma samples and three chordoma cell lines using immunohistochemistry. The intensity of immunostaining was evaluated in regard to the development of recurrences. The immunohistochemical results were correlated with clinical parameters like gender, age, tumor size, and location and were performed in primary chordomas as well as in recurrent lesions. Furthermore, survivin knockdown experiments on chordoma cell lines were performed. YM155 decreased the growth behavior of chordoma cells dose- and time dependently. Transient knockdown of survivin led to a G2/M arrest, decreased proliferation, consistently induced an increase of polyploidy and morphological changes, and induced apoptosis. The resultant data from this study suggest that survivin plays a cell cycle-progressive role in chordomas. Hence, regulation of survivin by YM155 is a promising new target for the development of new therapeutic drugs.

We describe herein the preparation of novel exfoliated graphene–phthalocyanine nanohybrids, and the investigation of their photophysical properties. Pyridyl-phthalocyanines (Pcs) 1–3 are presented as novel electron accepting building blocks of variable strengths with great potential for the exfoliation of graphite via their immobilization onto the basal plane of graphene in dimethylformamide (DMF) affording single layered and turbostratic graphene based G1–G3. G1–G3 were fully characterized (AFM, TEM, Raman, steady-state and pump probe transient absorption spectroscopy) and were studied in terms of electron donor–acceptor interactions in the ground and excited states. In this context, electron transfer upon photoexcitation from graphene to the electron accepting Pcs with dynamics, for example, in G2 of