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Waitlist time for kidney transplantation is long but may be shortened with the utilization of hepatitis C positive allografts. We retrospectively reviewed the course of 36 hepatitis C positive patients awaiting kidney transplantation at 2 large centers within the same health system, with near-identical care delivery models with the exception of timing of hepatitis C treatment, to determine the impact of timing of hepatitis C treatment on access to transplant, waitlist time, and treatment efficacy and tolerability. The majority of patients had hepatitis C genotype 1a or 1b, and all received direct acting antiviral therapy with 100% treatment response. One patient underwent transplantation in the pretransplant treatment group. The 1-year transplantation rate was 12.5% vs 67.9% (P = .0013) in those treated posttransplantation. The median waitlist time in the posttransplant group was 122 (interquartile range [IQR] 21.5, 531.0) days, which was significantly shorter than the center's regional and national wait time. Pathologic review revealed no difference in allograft quality. Overall treatment related adverse events were not different between the 2 groups. A strategy of posttransplant hepatitis C treatment increased access to transplant and reduced waitlist time. Delaying treatment until after transplant did not appear to adversely affect recipients' kidney allograft or overall survival.

Organ procurement organization (OPO) performance is generally evaluated by the number of organ procurement procedures divided by the number of eligible deaths (donation after brain death [DBD] donors aged70 years), whereas the number of noneligible deaths (including donation after cardiac death donors and DBD donors aged70 years) is not tracked. The present study aimed to investigate the variability in the proportion of noneligible liver donors by the 58 donor service areas (DSAs). Patients undergoing liver transplant (LT) between 2011 and 2015 were obtained from the United Network for Organ Sharing Standard Transplant Analysis and Research file. LTs from noneligible and eligible donors were compared. The proportion of noneligible liver donors by DSA varied significantly, ranging from 0% to 19.6% of total liver grafts used. In transplant programs, the proportion of noneligible liver donors used ranged from 0% to 35.3%. On linear regression there was no correlation between match Model for End-Stage Liver Disease score for programs in a given DSA and proportion of noneligible donors used from the corresponding DSA (p = 0.14). Noneligible donors remain an underutilized resource in many OPOs. Policy changes to begin tracking noneligible donors and learning from OPOs that have high noneligible donor usage are potential strategies to increase awareness and pursuit of these organs.

WOS: 000430906100002, A morphological lexicon that is a computational source should be considered together with derivational morphology especially for agglutinative languages. To the best of our knowledge, in the Turkish language there has been no study that analyzes the derivational suffixes on the lexicon in a computational paradigm. This study provides a very rich lexical resource, filling a gap in the field, and would hopefully lead to new related studies as well. The morphological lexicon can be used in morphological analysis as well as in several other tasks, such as stemming and part of speech (POS) tagging. In this study, we introduce a morphological lexicon named TrLex and present its components, preparation processes and some statistics. We observed that more than half of the single-word lemmas (56.7%) are in the derived structure. Since the word formation in Turkish prefer the morphological processes, this number is higher than the rate of compound-type words (2.7%). As a result of the work, we obtained a knowledge-intensive data table including several fields such as form, structure, semantic information. We also extracted Lexical Markup Framework (LMF) formatted file containing only morphological and POS information and made the file freely available, Anadolu University [1410F415], This work was supported by Anadolu University, Fund of Scientific Research Projects [grant number 1410F415].

Clathrin depletion by ribonucleic acid interference (RNAi) impairs mitotic spindle stability and cytokinesis. Depletion of several clathrin-associated proteins affects centrosome integrity, suggesting a further cell cycle function for clathrin. In this paper, we report that RNAi depletion of CHC17 (clathrin heavy chain 17) clathrin, but not the CHC22 clathrin isoform, induced centrosome amplification and multipolar spindles. To stage clathrin function within the cell cycle, a cell line expressing SNAP-tagged clathrin light chains was generated. Acute clathrin inactivation by chemical dimerization of the SNAP-tag during S phase caused reduction of both clathrin and ch-TOG (colonic, hepatic tumor overexpressed gene) at metaphase centrosomes, which became fragmented. This was phenocopied by treatment with Aurora A kinase inhibitor, suggesting a centrosomal role for the Aurora A–dependent complex of clathrin, ch-TOG, and TACC3 (transforming acidic coiled-coil protein 3). Clathrin inactivation in S phase also reduced total cellular levels of ch-TOG by metaphase. Live-cell imaging showed dynamic clathrin recruitment during centrosome maturation. Therefore, we propose that clathrin promotes centrosome maturation by stabilizing the microtubule-binding protein ch-TOG, defining a novel role for the clathrin–ch-TOG–TACC3 complex.

Hyperspectral remote sensing data is a powerful tool for discriminating lithological units and for the preparation of mineral maps for alteration studies. The spaceborne hyperspectral Hyperion sensor, despite its narrow swath width ∼7.5 km, possesses great potential with its 196 channels within the wavelength range 426.82–2395.50 nm. Although it has many advantages such as low cost and on-demand coverage, much uncertainty exists in the utility of its applications. For example, poor signal-to-noise ratio, the presence of sensor-specific defects and thicker atmospheric column due to its spaceborne platform makes certain environmental and geological applications difficult or impossible. In this article we demonstrate these calibration-related uncertainties, which are manifest from the preprocessing stage to the classification stage. In addition, the intimate mixing of minerals within specific targets, for example within individual outcropping lithological units or endmembers, adds uncertainty to our spectral discrimination results. The aim of this study was to develop and evaluate an approach for geological mapping of outcrops with Earth Observing-1 EO-1 Hyperion data. Atmospheric corrections and correction for cross-track illumination CTI variations smile were determined at different wavelength regions: the visible–near-infrared VNIR; 420–1000 nm and shortwave infrared SWIR; 1000–2400 nm regions. Our methodology was tested in a selected site at Central Anatolia, Turkey containing minimal vegetation cover. The results obtained from the image analyses were then compared and assessed with field observations and spectral measurements.

A robust retrieval system ensures that user experience is\ud not damaged by the presence of poorly-performing queries.\ud Such robustness can be measured by risk-sensitive evaluation\ud measures, which assess the extent to which a system\ud performs worse than a given baseline system. However, using\ud a particular, single system as the baseline suffers from\ud the fact that retrieval performance highly varies among IR\ud systems across topics. Thus, a single system would in general\ud fail in providing enough information about the real baseline\ud performance for every topic under consideration, and\ud hence it would in general fail in measuring the real risk associated\ud with any given system. Based upon the Chi-squared\ud statistic, we propose a new measure ZRisk that exhibits more\ud promise since it takes into account multiple baselines when\ud measuring risk, and a derivative measure called GeoRisk,\ud which enhances ZRisk by also taking into account the overall\ud magnitude of effectiveness. This paper demonstrates\ud the benefits of ZRisk and GeoRisk upon TREC data, and\ud how to exploit GeoRisk for risk-sensitive learning to rank,\ud thereby making use of multiple baselines within the learning\ud objective function to obtain effective yet risk-averse/robust\ud ranking systems. Experiments using 10,000 topics from the\ud MSLR learning to rank dataset demonstrate the efficacy of\ud the proposed Chi-square statistic-based objective function.

Although relatively infrequent, groin hematoma following inguinal herniorrhaphy is a morbid complication with major ramifications of mesh infection and hernia recurrence. We have sensed an increasing frequency of this complication in our tertiary referral practice and sought to determine whether or not significant risk factors could be identified. In this matched case–control study (1995–2003), we identified 53 patients with groin hematomas and paired them with 106 age- and gender-matched controls. Patient and procedure characteristics were analyzed using chi-square and both univariate and multivariable, conditional logistic regression analysis. The 53 patients developing groin hematoma following inguinal hernia repair (mean age = 65, range 22–87, 90% male) were well matched with 106 controls (mean age = 65, range 22–87, 90% male). There was no significant difference in the location (left, right, bilateral), type (direct, indirect, pantaloon, first repair, or recurrent), or technique of hernia repair (Bassini, Lichtenstein, mesh plug, endoscopic, or McVay) between groups. While univariate analysis identified Coumadin usage (P

Learning to rank techniques provide mechanisms for combining document feature values into learned models that produce effective rankings. However, issues concerning the transferability of learned models between different corpora or subsets of the same corpus are not yet well understood. For instance, is the importance of different feature sets consistent between subsets of a corpus, or whether a learned model obtained on a small subset of the corpus effectively transfer to the larger corpus? By formulating our experiments around two null hypotheses, in this work, we apply a full-factorial experiment design to empirically investigate these questions using the ClueWeb09 and ClueWeb12 corpora, combined with queries from the TREC Web track. Among other observations, our experiments reveal that Clue-Web09 remains an effective choice of training corpus for learning effective models for ClueWeb12, and also that the importance of query independent features varies among the ClueWeb09 and ClueWeb12 corpora. In doing so, this work contributes an important study into the transferability of learning to rank models, as well as empirically-derived best practices for effective retrieval on the ClueWeb12 corpus.

Early allograft dysfunction (EAD) after liver transplantation (LT) is related to ischemia-reperfusion injury and may lead to a systemic inflammatory response and extrahepatic organ dysfunction. We evaluated the effect of EAD on new-onset acute kidney injury (AKI) requiring renal replacement therapy within the first month and end-stage renal disease (ESRD) within the first year post-LT in 1325 primary LT recipients. EAD developed in 358 (27%) of recipients. Seventy-one (5.6%) recipients developed AKI and 38 (2.9%) developed ESRD. Compared with those without EAD, recipients with EAD had a higher risk of AKI and ESRD (4% vs. 9% and 2% vs. 6%, respectively, p < 0.001 for both). Multivariate logistic regression analysis showed an independent relationship between EAD and AKI as well as ESRD (odds ratio 3.5, 95% confidence interval 1.9-6.4, and odds ratio 3.1, 95% confidence interval 11.9-91.2, respectively). Patients who experienced both EAD and AKI had inferior 1-, 3-, 5-, and 10-year patient and graft survival compared with those with either EAD or AKI alone, while those who had neither AKI nor EAD had the best outcomes (p < 0.001). Post-LT EAD is a risk factor for both AKI and ESRD and should be considered a target for future intervention to reduce post-LT short- and long-term renal dysfunction.

Recipients of primary transplants from donation after cardiac death (DCD) donors (n = 40) performed from January 2005 to December 2009 were retrospectively reviewed and compared with recipients of primary transplants from donation after brain death (DBD) donors (n = 142). Patients received rabbit antithymocyte globulin induction and rapid steroid taper (RST; steroids stopped 5 days after surgery). Maintenance immunosuppression included tacrolimus and mycophenolate mofetil. Protocol kidney biopsies, creatinine (Cr), and measured glomerular filtration rate (mGFR; determined by cold iothalamate or 24-h creatinine clearance) were obtained at 1, 4, 12, and 24 months. Kidney biopsies for cause were conducted for unexplained elevated Cr, decline in mGFR, or new proteinuria. Biopsies were graded for rejection according to the Banff criteria. Graft survival at 3 years was 90.0% for DCD recipients and 86.6% for DBD recipients (P = NS). Rejection of any grade diagnosed on any biopsy through the first 2 years occurred in 18 DCD (45%) and 50 DBD (35%) recipients. Rejection of a grade more than Banff borderline occurred in 12.5% DCD and 12.7% DBD recipients. At 2 years, the mean ± SEM Cr and mGFR for DCD recipients with rejection were 1.8 ± 0.29 mg/dL and 59.2 ± 8.5 mL/min versus 1.3 ± 0.11 mg/dL and 67.0 ± 7.8 ml/min for those without rejection. For DBD recipients with rejection, Cr and mGFR at 2 years were 1.7 ± 0.12 mg/dL and 54.0 ± 4.4 mL/min versus 1.4 ± 0.11 mg/dL and 66.6 ± 3.3 ml/min for those without rejection (P = NS). Comparing DCD to DBD, there was no statistical difference in mean Cr or mGFR outcomes. Regardless of group, grafts with delayed graft function had lower 3-year survival. DCD primary kidney transplant recipients treated with rabbit antithymocyte induction and RST have short-term graft survival and function equivalent to DBD recipients. RST appears to be acceptable immunosuppression for DCD recipients.

Supramolecular clusters at the immunological synapse provide a mechanism for structuring complex communication networks between cells of the immune system. Regulating intra- and intercellular trafficking of proteins and lipids to and from the immunological synapse provides an additional level of complexity in determining the functional outcome of immune cell interactions. An emergent principle is that molecules requiring tightly regulated cell surface expression, e.g. negative regulators of cell activation or molecules promoting cytotoxicity, are trafficked to the immunological synapse from intracellular secretory as required lysosomes. Many molecules required for the early stages of the intercellular communication are already present at the cell surface, sometimes in lipid rafts, and are rapidly translocated laterally to the intercellular contact. Our understanding of these events critically depends on utilizing appropriate technologies for probing supramolecular recognition in live cells. Thus, we also present here a critical discussion of the technologies used to study lipid rafts and, more broadly, a map of the spatial and temporal dimensions covered by current live cell physical techniques, highlighting where advances are needed to exceed current spatial and temporal boundaries.

As T cells and natural killer (NK) cells survey the surface of other cells, cognate receptors and ligands are commonly organized into distinct micrometer-scale domains at the intercellular contact, creating an immune or immunological synapse (IS). We aim to address the still unanswered questions of how this organization of proteins aids immune surveillance and how these domains are biophysically constructed. Molecular mechanisms for the formation of the IS include a role for the cytoskeleton, segregation of proteins according to the size of their extracellular domains, and association of proteins with lipid rafts. Towards understanding the function of the IS, it is instructive to compare and contrast the supramolecular organization of proteins at the inhibitory and activating NK cell IS with that at the activating T cell IS. Finally, it is essential to develop new technologies for probing molecular recognition at cell surfaces. Imaging parameters other than fluorescence intensity, such as the lifetime of the fluorophore's excited state, could be used to report on protein environments.

37th Annual International ACM Special Interest Group on Information Retrieval Conference on Research and Development in Information Retrieval - JUL 06-11, 2014 - Gold Coast, AUSTRALIA Dincer, Bekir Taner/0000-0002-0660-7239; Ounis, Iadh/0000-0003-4701-3223 WOS: 000450717600003 The aim of risk-sensitive evaluation is to measure when a given information retrieval (IR) system does not perform worse than a corresponding baseline system for any topic. This paper argues that risk-sensitive evaluation is akin to the underlying methodology of the Student's t test for matched pairs. Hence, we introduce a risk-reward tradeoff measure T-Risk that generalises the existing U-Risk measure (as used in the TREC 2013 Web track's risk-sensitive task) while being theoretically grounded in statistical hypothesis testing and easily interpretable. In particular, we show that T-Risk is a linear transformation of the t statistic, which is the test statistic used in the Student's t test. This inherent relationship between T-Ri(sk) and the t statistic, turns risk-sensitive evaluation from a descriptive analysis to a fully-fledged inferential analysis. Specifically, we demonstrate using past TREC data, that by using the inferential analysis techniques introduced in this paper, we can (1) decide whether an observed level of risk for an IR system is statistically significant, and thereby infer whether the system exhibits a real risk, and (2) determine the topics that individually lead to a significant level of risk. Indeed, we show that the latter permits a state-of-the-art learning to rank algorithm (Lamb-daMART) to focus on those topics in order to learn effective yet risk-averse ranking systems. ACM Special Interest Grp Informat Retrieval, Baidu, Google, Microsoft Res, Tourism & Events Queensland, eBay, Huawei, Seznam cz, Facebook, IBM, Pivotal, Yahoo, Labs, Yandex, Queensland Univ Technol, RMIT Univ, Univ Melbourne, Univ Otago

Select liver transplantation (LT) recipients in our program are transferred from operating room to postanesthesia care unit for recovery and extubation with transfer to the ward, completely eliminating an intensive care unit (ICU) stay. Developing a reliable method to determine patients suitable for fast-tracking would be of practical benefit to centers considering this practice. The aim of this study was to create a fast-tracking probability score that could be used to predict successful assignment of care location after LT. Recipient, donor and operative characteristics were assessed for independent association with successful fast-tracking to create a probability score. Of the 1296 LT recipients who met inclusion criteria, 704 (54.3%) were successfully fast-tracked and 592 (45.7%) were directly admitted to the ICU after LT. Based on nine readily available variables at the time of LT, we created a scoring system that classified patients according to the likelihood of being successfully fast-tracked to the surgical ward, with an area under the curve (AUC) of 0.790 (95% CI: 0.765-0.816). This score was validated in an independent group of 372 LT with similar AUC. We describe a score that can be used to predict successful fast-tracking immediately after LT using readily available clinical variables.

Clathrin assembles at bacterial adhesion sites and its phosphorylation is required for actin recruitment during bacterial infection., Bacterial pathogens recruit clathrin upon interaction with host surface receptors during infection. Here, using three different infection models, we observed that host–pathogen interactions induce tyrosine phosphorylation of clathrin heavy chain. This modification was critical for recruitment of actin at bacteria–host adhesion sites during bacterial internalization or pedestal formation. At the bacterial interface, clathrin assembled to form coated pits of conventional size. Because such structures cannot internalize large particles such as bacteria, we propose that during infection, clathrin-coated pits serve as platforms to initiate actin rearrangements at bacteria–host adhesion sites. We then showed that the clathrin–actin interdependency is initiated by Dab2 and depends on the presence of clathrin light chain and its actin-binding partner Hip1R, and that the fully assembled machinery can recruit Myosin VI. Together, our study highlights a physiological role for clathrin heavy chain phosphorylation and reinforces the increasingly recognized function of clathrin in actin cytoskeletal organization in mammalian cells.

Variable interaction between the Bw4 epitope of HLA-B and the polymorphic KIR3DL1/S1 system of inhibitory and activating NK cell receptors diversifies the development, repertoire formation, and response of human NK cells. KIR3DL1*004, a common KIR3DL1 allotype, in combination with Bw4+ HLA-B, slows progression of HIV infection to AIDS. Analysis in this study of KIR3DL1*004 membrane traffic in NK cells shows this allotype is largely misfolded but stably retained in the endoplasmic reticulum, where it binds to the chaperone calreticulin and does not induce the unfolded protein response. A small fraction of KIR3DL1*004 folds correctly and leaves the endoplasmic reticulum to be expressed on the surface of primary NK and transfected NKL cells, in a form that can be triggered to inhibit NK cell activation and secretion of IFN-γ. Consistent with this small proportion of correctly folded molecules, trace amounts of MHC class I coimmunoprecipitated with KIR3DL1*004. There was no indication of any extensive intracellular interaction between unfolded KIR3DL1*004 and cognate Bw4+ HLA-B. A similarly limited interaction of Bw4 with KIR3DL1*002, when both were expressed by the same cell, was observed despite the efficient folding of KIR3DL1*002 and its abundance on the NK cell surface. Several positions of polymorphism modulate KIR3DL1 abundance at the cell surface, differences that do not necessarily correlate with the potency of allotype function. In this context, our results suggest the possibility that the effect of Bw4+ HLA-B and KIR3DL1*004 in slowing progression to AIDS is mediated by interaction of Bw4+ HLA-B with the small fraction of cell surface KIR3DL1*004.

Adult polycystic liver disease (PLD) can cause massive hepatomegaly leading to pain, caval obstruction, and hemorrhage. Many surgical techniques including aspiration, fenestration, and resection have been used to treat PLD. In addition to substantial morbidity and mortality, conservative surgery may have limited success, and palliation may be temporary. With improved results of liver transplantation, it has become the definitive treatment for PLD. We retrospectively reviewed our experience in patients with PLD between 1998 and 2007. Thirteen patients underwent liver only or liver-kidney transplantation. All surgical procedures were performed with preservation of the recipient inferior vena cava and without venovenous bypass (piggyback technique). Our patients experienced a high rate of perioperative morbidity. However, long-term patient and graft survival were excellent.

This paper reports an unusual occurrence of talon cusp on a supernumerary primary incisor, presenting on both labial and palatal sides. The tooth was scheduled for extraction due to its interference with the occlusion. Morphometric analysis of the taloned cusps was performed on digitized replicas of the tooth crown using open-source image analysis toolkit (ImageJ). Further non-destructive investigation of the taloned crown under cone-beam X-ray computed tomography revealed pulpal extensions in both talon cusps.

Supramolecular clusters at the immunological synapse provide a mechanism for structuring complex communication networks between cells of the immune system. Regulating intra- and intercellular trafficking of proteins and lipids to and from the immunological synapse provides an additional level of complexity in determining the functional outcome of immune cell interactions. An emergent principle is that molecules requiring tightly regulated cell surface expression, e.g. negative regulators of cell activation or molecules promoting cytotoxicity, are trafficked to the immunological synapse from intracellular secretory as required lysosomes. Many molecules required for the early stages of the intercellular communication are already present at the cell surface, sometimes in lipid rafts, and are rapidly translocated laterally to the intercellular contact. Our understanding of these events critically depends on utilizing appropriate technologies for probing supramolecular recognition in live cells. Thus, we also present here a critical discussion of the technologies used to study lipid rafts and, more broadly, a map of the spatial and temporal dimensions covered by current live cell physical techniques, highlighting where advances are needed to exceed current spatial and temporal boundaries.

Cell surface proteins major histocompatibility complex (MHC) class I–related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. Patches of cross-linked raft resident ganglioside GM1 colocalized with ULBP1, 2, 3, or MICA, but not CD45. Thus, ULBPs and MICA are expressed in lipid rafts at the cell surface. Western blotting revealed that glycosylphosphatidylinositol (GPI)-anchored ULBP3 but not transmembrane MICA, MHC class I protein, or transferrin receptor, accumulated in detergent-resistant membranes containing GM1. Thus, MICA may have a weaker association with lipid rafts than ULBP3, yet both proteins accumulate at an activating human NK cell immune synapse. Target cell lipid rafts marked by green fluorescent protein–tagged GPI also accumulate with ULBP3 at some synapses. Electron microscopy reveals constitutive clusters of ULBP at the cell surface. Regarding a specific molecular basis for the organization of these proteins, ULBP1, 2, and 3 and MICA are lipid modified. ULBP1, 2, and 3 are GPI anchored, and we demonstrate here that MICA is S-acylated. Finally, expression of a truncated form of MICA that lacks the putative site for S-acylation and the cytoplasmic tail can be expressed at the cell surface, but is unable to activate NK cells.

As T cells and natural killer (NK) cells survey the surface of other cells, cognate receptors and ligands are commonly organized into distinct micrometer-scale domains at the intercellular contact, creating an immune or immunological synapse (IS). We aim to address the still unanswered questions of how this organization of proteins aids immune surveillance and how these domains are biophysically constructed. Molecular mechanisms for the formation of the IS include a role for the cytoskeleton, segregation of proteins according to the size of their extracellular domains, and association of proteins with lipid rafts. Towards understanding the function of the IS, it is instructive to compare and contrast the supramolecular organization of proteins at the inhibitory and activating NK cell IS with that at the activating T cell IS. Finally, it is essential to develop new technologies for probing molecular recognition at cell surfaces. Imaging parameters other than fluorescence intensity, such as the lifetime of the fluorophore's excited state, could be used to report on protein environments.

Expression of human complement regulating factor (hCRF) in porcine organs prevents hyperacute rejection of these organs after xenotransplantation to nonhuman primates. Experiments were designed to characterize endothelial and smooth muscle function of arteries from pigs transgenic for hCD46.Arterial blood from outbred pigs transgenic for hCD46 expression and nontransgenic animals of the same lineage was analyzed for angiotensin-converting enzyme (ACE), C-type natriuretic peptide (CNP), and nitric oxide. Aortic endothelial cells were prepared for measurement of mRNA or activity for nitric oxide synthase (NOS). Rings cut from femoral and pulmonary arteries were suspended in organ chambers for measurement of isometric tension.CNP was significantly greater, ACE was similar, and nitric oxide was significantly less in plasma from transgenic compared with nontransgenic pigs. Neither mRNA nor activity of NOS differed between the groups. Endothelium-dependent relaxations to bradykinin and acetylcholine but not the calcium ionophore were shifted significantly to the left in femoral and pulmonary arteries from hCD46 transgenic pigs compared with nontransgenic pigs. The ACE-inhibitor captopril augmented relaxations similarly in both groups, but NG-monomethyl-L-arginine (L-NMMA) did not inhibit relaxations in rings from transgenic pigs.Data suggest that expression of hCD46 on endothelium of pigs selectively augments endothelium-dependent relaxations to bradykinin by increased release of endothelium-derived factors other than nitric oxide. There does not seem to be any change in activity of ACE or NOS with expression of the human protein. Increased relaxations to bradykinin may be beneficial in lowering vascular resistance when transgenic organs are used for xenotransplantation.

Udgivelsesdato: 2009-Jan We have applied fluorescence imaging of two-photon linear dichroism to measure the subresolution organization of the cell membrane during formation of the activating (cytolytic) natural killer (NK) cell immune synapse (IS). This approach revealed that the NK cell plasma membrane is convoluted into ruffles at the periphery, but not in the center of a mature cytolytic NK cell IS. Time-lapse imaging showed that the membrane ruffles formed at the initial point of contact between NK cells and target cells and then spread radialy across the intercellular contact as the size of the IS increased, becoming absent from the center of the mature synapse. Understanding the role of such extensive membrane ruffling in the assembly of cytolytic synapses is an intriguing new goal.