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Efflux-mediated β-lactam resistance is a major public health concern, reducing the effectiveness of β-lactam antibiotics against many bacteria. Structural analyses show the efflux protein TolC in Gram-negative bacteria acts as a channel for antibiotics, impacting bacterial susceptibility and virulence. This study examines β-lactam drug efflux mediated by TolC using experimental and computational methods. Molecular dynamics simulations of drug-free TolC reveal essential movements and key residues involved in TolC opening. A whole-gene-saturation mutagenesis assay, mutating each TolC residue and measuring fitness effects under β-lactam selection, is performed. Here we show the TolC-mediated efflux of three antibiotics: oxacillin, piperacillin, and carbenicillin. Steered molecular dynamics simulations identify general and drug-specific efflux mechanisms, revealing key positions at TolC's periplasmic entry affecting efflux motions. Our findings provide insights into TolC's structural dynamics, aiding the design of new antibiotics to overcome bacterial efflux mechanisms. Modelling and deep mutational scanning of TolC provide insights for designing β-lactams to evade resistance, by outlining how efflux is fine-tuned for efficiency via transient hydrogen bonds with antibiotics and how allostery impacts exit site motions. [ABSTRACT FROM AUTHOR]

As recreational genomics continues to grow in its popularity, many people are afforded the opportunity to share their genomes in exchange for various services, including third-party interpretation (TPI) tools, to understand their predisposition to health problems and, based on genome similarity, to find extended family members. At the same time, these services have increasingly been reused by law enforcement to track down potential criminals through family members who disclose their genomic information. While it has been observed that many potential users shy away from such data sharing when they learn that their privacy cannot be assured, it remains unclear how potential users' valuations of the service will affect a population's behavior. In this paper, we present a game theoretic framework to model interdependent privacy challenges in genomic data sharing online. Through simulations, we find that in addition to the boundary cases when (1) no player and (2) every player joins, there exist pure-strategy Nash equilibria when a relatively small portion of players choose to join the genomic database. The result is consistent under different parametric settings. We further examine the stability of Nash equilibria and illustrate that the only equilibrium that is resistant to a random dropping of players is when all players join the genomic database. Finally, we show that when players consider the impact that their data sharing may have on their relatives, the only pure strategy Nash equilibria are when either no player or every player shares their genomic data. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to determine whether varying the magnetic field during magnetic resonance imaging would affect the development of chicken embryos and neural tube defects.Methods: Following incubation for 24 h, we exposed chicken embryos to varying magnetic fields for 10 min to assess the impact on development. Three magnetic resonance imaging devices were used, and the eggs were divided into four groups: group 1 is exposed to 1 T, group 2 is exposed to 1.5 T, group 3 is exposed to 3 T, and group 4, control group, was not exposed to magnetic field. After MRI exposure, all embryos were again put inside incubator to complete 48 h. “The new technique” was used to open eggs, a stereomicroscope was used for the examination of magnified external morphology, and each embryo was examined according to the Hamburger and Hamilton chicken embryo stages. Embryos who had delayed stages of development are considered growth retarded. Growth retardation criteria do not include small for stage.Results: Compared with embryos not exposed to a magnetic field, there was a statistically significant increase in the incidence of neural tube closure defects and growth retardation in the embryos exposed to magnetic fields (p < 0.05). However, although the incidence of neural tube closure defects was expected to increase as exposure (tesla level) increased, we found a higher rate of defects in the 1.5-T group compared with the 3-T group. By contrast, the highest incidence of growth retardation was in the 3-T group, which was consistent with our expectation that growth retardation would be more likely as tesla level increased.Conclusions: We therefore conclude that the use of magnetic resonance imaging as a diagnostic tool can result in midline closure defects and growth retardation in chicken embryos. We hypothesize that this may also be true for human embryos exposed to MRI. If a pregnant individual is to take an MRI scan, as for lumbar disc disease or any other any other reason, our results indicate that consideration should be given to an avoidance of MRI during pregnancy. [ABSTRACT FROM AUTHOR]

Search over encrypted data recently became a critical operation that raised a considerable amount of interest in both academia and industry. Especially, as outsourcing, sensitive data to cloud prove to be a strong trend to benefit from the unmatched storage and computing capacities thereof. Indeed, privacy-preserving search over encrypted data, an apt term to address privacy-related issues concomitant in outsourcing sensitive data, have been widely investigated in the literature under different models and assumptions. In this work, we propose an efficient scheme that allows privacy-preserving search over encrypted data using queries with multiple keywords. Most important contributions of this work are as follows. Firstly, using a property referred as $$\delta $$ - mean query obfuscation, the proposed scheme hides the search patterns, which are allowed to leak in many works in the literature including our preliminary work on the subject Orencik et al. (2013) []. Secondly, a two-server setting is employed to eliminate the correlation between the queries and matching documents sent to the user under the assumption that the two servers are not colluding. Thirdly, we propose a novel compression scheme that reduces both the communication cost between the two servers and the computation cost of the search operation more than 55 times compared to the standard approach. And finally, the proposed scheme also provides an effective scoring and ranking capability that is based on term frequency-inverse document frequency (tf-idf) weights of keyword-document pairs. Our analyses demonstrate that the proposed scheme is privacy-preserving, efficient and effective. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a general term for a group of complex neurodevelopmental disorders of brain development that limits a person's ability to function normally. Etiology has not been clearly defined up to date. However, gut microbiota and the bidirectional communication between the gastrointestinal tract and brain, the so-called microbiota-gut-brain axis, are hypothesized, which may be involved in the etiology of several mental disorders. Recent reports suggest that Candida, particularly Candida albicans, growth in intestines may cause lower absorption of carbohydrates and minerals and higher toxin levels which are thought to contribute autistic behaviors. The aim of this study was to identify the 3-year deposited yeasts isolated from stool samples of children with diagnosed or suspected ASD and to determine in vitro activity of nystatin and fluconazole against these isolates using Clinical Laboratory Standards Institute M27-A3 guidelines. A 17-year retrospective assessment was also done using our laboratory records. Among the species identified, intrinsically fluconazole-resistent Candida krusei (19.8 %) and Candida glabrata (14.8 %) with elevated MICs were remarkable. Overall, C. albicans (57.4 %) was the most commonly isolated species in 17 years. The species identification and/or antifungal susceptibility tests have to be performed using the strain isolated from stool sample, to select the appropriate antifungal agent, if antimycotic therapy is needed. [ABSTRACT FROM AUTHOR]

The notion of data provenance was formally introduced a decade ago and has since been investigated, but mainly from a functional perspective, which follows the historical pattern of introducing new technologies with the expectation that security and privacy can be added later. Despite very recent interests from the cyber security community on some specific aspects of data provenance, there is no long-haul, overarching, systematic framework for the security and privacy of provenance. The importance of secure provenance R&D has been emphasized in the recent report on Federal game-changing R&D for cyber security especially with respect to the theme of Tailored Trustworthy Spaces. Secure data provenance can significantly enhance data trustworthiness, which is crucial to various decision-making processes. Moreover, data provenance can facilitate accountability and compliance (including compliance with privacy preferences and policies of relevant users), can be an important factor in access control and usage control decisions, and can be valuable in data forensics. Along with these potential benefits, data provenance also poses a number of security and privacy challenges. For example, sometimes provenance needs to be confidential so it is visible only to properly authorized users, and we also need to protect the identity of entities in the provenance from exposure. We thus need to achieve high assurance of provenance without comprising privacy of those in the chain that produced the data. Moreover, if we expect voluntary large-scale participation in provenance-aware applications, we must assure that the privacy of the individuals or organizations involved will be maintained. It is incumbent on the cyber security community to develop a technical and scientific framework to address the security and privacy challenges so that our society can gain maximum benefit from this technology. In this paper, we discuss a framework of theoretical foundations, models, mechanisms and architectures that allow applications to benefit from privacy-enhanced and secure use of provenance in a modular fashion. After introducing the main components of such a framework and the notion of provenance life cycle, we discuss in details research questions and issues concerning each such component and related approaches. [ABSTRACT FROM AUTHOR]

As the popularity and usage of social media exploded over the years, understanding how social network users' interests evolve gained importance in diverse fields, ranging from sociological studies to marketing. In this paper, we use two snapshots from the Twitter network and analyze data interest patterns of users in time to understand individual and collective user behavior on social networks. Building topical profiles of users, we propose novel metrics to identify anomalous friendships, and validate our results with Amazon Mechanical Turk experiments. We show that although more than 80 % of all friendships on Twitter are created due to data interests, 83 % of all users have at least one friendship that can be explained neither by users' past interest nor collective behavior of other similar users. [ABSTRACT FROM AUTHOR]

In this paper, we study the problem of supporting multidimensional range queries on encrypted data. The problem is motivated by secure data outsourcing applications where a client may store his/her data on a remote server in encrypted form and want to execute queries using server's computational capabilities. The solution approach is to compute a secure indexing tag of the data by applying bucketization (a generic form of data partitioning) which prevents the server from learning exact values but still allows it to check if a record satisfies the query predicate. Queries are evaluated in an approximate manner where the returned set of records may contain some false positives. These records then need to be weeded out by the client which comprises the computational overhead of our scheme. We develop a bucketization procedure for answering multidimensional range queries on multidimensional data. For a given bucketization scheme, we derive cost and disclosure-risk metrics that estimate client's computational overhead and disclosure risk respectively. Given a multidimensional dataset, its bucketization is posed as an optimization problem where the goal is to minimize the risk of disclosure while keeping query cost (client's computational overhead) below a certain user-specified threshold value. We provide a tunable data bucketization algorithm that allows the data owner to control the trade-off between disclosure risk and cost. We also study the trade-off characteristics through an extensive set of experiments on real and synthetic data. [ABSTRACT FROM AUTHOR]

Background: Familial Mediterranean fever (FMF) is an auto-inflammatory disorder characterized by febrile attacks. Increased acute-phase reactants are characteristic during febrile attacks. Ghrelin is a natural G-protein that decreases secretion of pro-inflammatory cytokines and acts as anti-inflammatory agent. The aim of this study was to investigate whether there is any change in ghrelin levels and whether increases in ghrelin levels can be used as a marker in these patients. Subjects and Methods: Thirty-seven male patients and 30 healthy men as a control group were included in the study. Blood samples were obtained for ghrelin measurements both before the attacks (pre-attack period; ghrelin 1 group) and during the attacks (ghrelin 2 group). Samples were kept at −80°C until the analysis was conducted and plasma ghrelin levels were measured using an immune-sorbent assay method. Results: Mean ghrelin levels measured during the attacks were significantly higher (11.01 ± 4.78 pg/ml) as compared to pre-attack levels (5.78 ± 2.17 pg/ml; p < 0.001). Similarly, mean ghrelin levels measured in FMF patients during an attack were significantly different from that of the control group (6.57 ± 4.13 pg/ml; p < 0.001). Conclusions: In this study, high ghrelin levels were measured during attacks in FMF patients. This finding is in line with previous results regarding the fact that inflammatory response arising during an FMF attack is an acute inflammatory event. Our findings suggest that ghrelin levels measured during FMF attacks could be used as a biochemical indicator for the FMF attack in FMF patients and that it could be used for support of the diagnosis of the disease. [ABSTRACT FROM AUTHOR]

Mobile devices with global positioning capabilities allow users to retrieve points of interest (POI) in their proximity. To protect user privacy, it is important not to disclose exact user coordinates to un-trusted entities that provide location-based services. Currently, there are two main approaches to protect the location privacy of users: (i) hiding locations inside cloaking regions (CRs) and (ii) encrypting location data using private information retrieval (PIR) protocols. Previous work focused on finding good trade-offs between privacy and performance of user protection techniques, but disregarded the important issue of protecting the POI dataset D. For instance, location cloaking requires large-sized CRs, leading to excessive disclosure of POIs ( O(| D|) in the worst case). PIR, on the other hand, reduces this bound to $O(\sqrt{|D|})$, but at the expense of high processing and communication overhead. We propose hybrid, two-step approaches for private location-based queries which provide protection for both the users and the database. In the first step, user locations are generalized to coarse-grained CRs which provide strong privacy. Next, a PIR protocol is applied with respect to the obtained query CR. To protect against excessive disclosure of POI locations, we devise two cryptographic protocols that privately evaluate whether a point is enclosed inside a rectangular region or a convex polygon. We also introduce algorithms to efficiently support PIR on dynamic POI sub-sets. We provide solutions for both approximate and exact NN queries. In the approximate case, our method discloses O(1) POI, orders of magnitude fewer than CR- or PIR-based techniques. For the exact case, we obtain optimal disclosure of a single POI, although with slightly higher computational overhead. Experimental results show that the hybrid approaches are scalable in practice, and outperform the pure-PIR approach in terms of computational and communication overhead. [ABSTRACT FROM AUTHOR]

Burkitt lymphoma (BL) is a highly aggressive B cell non-Hodgkin lymphoma that has a high proliferation rate. The prognosis for BL is generally favorable, with cure rate of 75-90 % with modern chemoimmunotherapy regimens. Prompt administration of multiagent immunochemotherapy regimens is critical, because BL is almost always fatal if left untreated. Nevertheless here we report a case of BL that is still in complete remission after more than 4 years without any further treatment after surgical excision of the involved lymph node. [ABSTRACT FROM AUTHOR]

The study includes a case report and a literature review. The main objective of this study is to present a case of spondylodiscitis due to a fungal pathogen, Blastoschizomyces capitatus and to review the published literature on this emergent fungus in etiology of spondylodiscitis, and osteomyelitis. Osteoarticular involvement due to B. capitatus has been reported in six cases, and vertebral involvement has been seen in five of them. All of these cases had underlying malignancy. Infection is usually advanced at presentation. Case notes and online databases were reviewed. Organism was isolated from bone material in all of the cases and antibiotic treatment by antifungal agents cured the infection. We present another case of infectious spondylodiscitis due to B. capitaus, which is reported first in Turkey and tried to attract attendance to this emergent fungal pathogen as an etiologic agent of spine infections in cancer patients. [ABSTRACT FROM AUTHOR]