Miracle-dz/UniFAR-FTUs huggingface dataset:
Host metabolites stimulate the bacterial proton motive force to enhance the activity of aminoglycoside antibiotics

Antibiotic susceptibility of bacterial pathogens is typically evaluated using in vitro assays that do not consider the complex host microenvironment. This may help explaining a significant discrepancy between antibiotic efficacy in vitro and in vivo, with some antibiotics being effective in vitro but not in vivo or vice versa. Nevertheless, it is well-known that antibiotic susceptibility of bacteria is driven by environmental factors. Lung epithelial cells enhance the activity of aminoglycoside antibiotics against the opportunistic pathogen Pseudomonas aeruginosa, yet the mechanism behind is unknown. The present study addresses this gap and provides mechanistic understanding on how lung epithelial cells stimulate aminoglycoside activity. To investigate the influence of the local host microenvironment on antibiotic activity, an in vivo-like three-dimensional (3-D) lung epithelial cell model was used. We report that conditioned medium of 3-D lung cells, containing secreted but not cellular components, potentiated the bactericidal activity of aminoglycosides against P. aeruginosa, including resistant clinical isolates, and several other pathogens. In contrast, conditioned medium obtained from the same cell type, but grown as conventional (2-D) monolayers did not influence antibiotic efficacy. We found that 3-D lung cells secreted endogenous metabolites (including succinate and glutamate) that enhanced aminoglycoside activity, and provide evidence that bacterial pyruvate metabolism is linked to the observed potentiation of antimicrobial activity. Biochemical and phenotypic assays indicated that 3-D cell conditioned medium stimulated the proton motive force (PMF), resulting in increased bacterial intracellular pH. The latter stimulated antibiotic uptake, as determined using fluorescently labelled tobramycin in combination with flow cytometry analysis. Our findings reveal a cross-talk between host and bacterial metabolic pathways, that influence downstream activity of antibiotics. Understanding the underlying basis of the discrepancy between the activity of antibiotics in vitro and in vivo may lead to improved diagnostic approaches and pave the way towards novel means to stimulate antibiotic activity.
The Rate-Distortion Function for Product of Two Sources With Side-Information at Decoders

This paper investigates a lossy source coding problem, in which two decoders can access their respective side-information. The correlated sources are a product of two component correlated sources, and we exclusively investigate the case such that each component is degraded. We show the rate-distortion function for that case and give the following observations. When the components are degraded in matched order, the rate-distortion function of the product sources is equal to the sum of the componentwise rate-distortion functions. On the other hand, the former is strictly smaller than the latter when the component sources are degraded in mismatched order. The converse proof for the mismatched case is motivated by the enhancement technique used for broadcast channels. For binary Hamming and Gaussian examples, we evaluate the rate-distortion functions.
Stress-Dependent Expression of a Polymorphic, Charged Antigen in the Protozoan Parasite Entamoeba histolytica

ABSTRACT We have identified a novel stress inducible gene, Ehssp1 in Entamoeba histolytica, the causative agent of amebiasis. Ehssp1 belongs to a polymorphic, multigene family and is present on multiple chromosomes. No homologue of this gene was found in the NCBI database. Sequence alignment of the multiple copies, and genomic PCR data restricted the polymorphism to the central region of the gene. This region contains a polypurine stretch that encodes a domain rich in acidic and basic amino acids. Under normal culture conditions only one copy of this multigene family is expressed, as observed by Northern blot and RT-PCR analysis. The size of this copy of the gene is 1,077 nucleotides, encoding a protein of 359 amino acids. The polymorphic domain in this copy is 64 nucleotides long. However, on exposure of cells to stress conditions such as heat shock or oxidative stress, multiple polymorphic copies of the gene are expressed, suggesting a possible role of this gene in adaptation of cells to stress conditions. The gene copy expressed under normal conditions, and the expression profile of cells under heat stress was identical in two different strains of E. histolytica tested. Interestingly, the extent of polymorphism in this gene was very less in E. dispar, a nonpathogenic sibling species of E. histolytica. Ehssp1 was found to be antigenic in invasive amebiasis patients.
New Non-Volatile Memory Structures for FPGA Architectures

A new set of programmable elements (PEs) using a new non-volatile device for use with routing switches and logical elements within a field-programmable gate array (FPGA) is described. The PEs have small area, can be combined with components that use low operational voltage on the same CMOS logic process, are non-volatile, enable the use of fast thin-oxide pass transistors, and are reprogrammable. A novel non-volatile flip-flop for use within the logical elements is presented as well. In combination, these methods enable programmable logic devices with improved area efficiency, the speed advantages of SRAM-based FPGAs, and a wide range of opportunities for power down strategies.
The Trilemma of Network Analysis

The recent interest in network analysis is caused by the unprecedented accessibility to large datasets: there are huge, publicly available databases on protein-protein-interactions, air transportation, and street maps which easily lend themselves to a network representation. Once a network is created, all types of path-based network analytic measures can be easily applied: typical examples are centrality measures, but also some clustering algorithms and robustness analysis rely on path-based measures. Borgatti has claimed that centrality measures basically simulate dissemination processes of goods which use a certain subset of paths on the given network [1]; they can thus only be used to describe processes which rely on the same type of good and the same subset of paths. Later, Butts pointed out that the results of a chosen network analytic method strongly vary with modeling decisions taken when turning raw data into networks [2]. In this article we combine these two insights to the trilemma of network analysis which states that the network process of interest, the network representation, and the network analytic method cannot be chosen independently. We discuss on two real-world examples in the realm of air transportation networks how to choose a distance based measure with respect to the context of the data, re-computing similar analyses by Guimer'a et al. [3] and Dall'Asta et al. [4]. In both cases, the path-based measures matching the network process of interest change the interpretation of the previous findings, which shows the potential in regarding the trilemma of network analysis.
Automatic Tissue Differentiation Based on Confocal Endomicroscopic Images for Intraoperative Guidance in Neurosurgery

Diagnosis of tumor and definition of tumor borders intraoperatively using fast histopathology is often not sufficiently informative primarily due to tissue architecture alteration during sample preparation step. Confocal laser microscopy (CLE) provides microscopic information of tissue in real-time on cellular and subcellular levels, where tissue characterization is possible. One major challenge is to categorize these images reliably during the surgery as quickly as possible. To address this, we propose an automated tissue differentiation algorithm based on the machine learning concept. During a training phase, a large number of image frames with known tissue types are analyzed and the most discriminant image-based signatures for various tissue types are identified. During the procedure, the algorithm uses the learnt image features to assign a proper tissue type to the acquired image frame. We have verified this method on the example of two types of brain tumors: glioblastoma and meningioma. The algorithm was trained using 117 image sequences containing over 27 thousand images captured from more than 20 patients. We achieved an average cross validation accuracy of better than 83%. We believe this algorithm could be a useful component to an intraoperative pathology system for guiding the resection procedure based on cellular level information.
Volume-Outcome Relationships and Abdominal Aortic Aneurysm Repair

Background— There is a well-established literature relating procedure volume to outcomes, but incorporating such information into clinical decision making is problematic when there is >1 treatment option for a condition. Methods and Results— We used data from the Medicare program to investigate the relationship between institutional volume for open and endovascular abdominal aortic aneurysm (AAA) repair and outcomes, examine trends in volume, and explore the implications for physicians making referrals for AAA repair. Trends in institutional volume were measured for the time period 2001–2006, whereas outcomes were assessed with the use of a previously assembled propensity score-matched cohort covering the time period 2001–2004. Between 2001 and 2006, there were a total of 230 736 repairs of either an intact or ruptured AAA for traditional Medicare beneficiaries. During this time, the proportion of endovascular cases increased from ≈22% in 2001 to >50% of AAA repairs in 2006, but there was little shift in procedure volume to high-volume institutions. For endovascular repair, adjusted mortality by quintile showed a marked decrease between the first and second quintile, with continued smaller decreases over quintiles 3 to 5. For open repair, adjusted mortality showed a steady decrease across the quintiles of volume. Conclusions— We found a steady increase in survival with increasing volume of open repair but relatively little improvement after reaching a relatively low threshold for endovascular repair. Because hospital experience with one repair method does not translate into improved outcomes for the alternative method, referring clinicians must consider both treatment options when making referral decisions.
A survey on web services composition

Due to the web services' heterogeneous nature, which stems from the definition of several XML-based standards to overcome platform and language dependence, web services have become an emerging and promising technology to design and build complex inter-enterprise business applications out of single web-based software components. To establish the existence of a global component market, in order to enforce extensive software reuse, service composition experienced increasing interest in doing a lot of research effort. This paper discusses the urgent need for service composition, the required technologies to perform service composition. It also presents several different composition strategies, based on some currently existing composition platforms and frameworks, re-presenting first implementations of state-of the-art technologies, and gives an outlook to essential future research work.
Association Studies of the GPR103 and BCL2L15 Genes in Autoimmune Thyroid Disease in the Japanese Population

While the past genome-wide association study (GWAS) for autoimmune thyroid diseases (AITDs) was done in Caucasians, a recent GWAS in Caucasian patients with both AITD and type 1 diabetes [a variant of autoimmune polyglandular syndrome type 3 (APS3v)] identified five non-HLA genes: BCL2L15, MAGI3, PHTF1, PTPN22, and GPR103. The aim of our study was to replicate these associations with AITD in a Japanese population. Since analyzing the rs2476601 single-nucleotide polymorphism (SNP) within the PTPN22 gene revealed no polymorphism in the Japanese, we analyzed four SNPs, rs2358994 (in BCL2L15), rs2153977 (in MAGI3), rs1111695 (in PHTF1), and rs7679475 (in GPR103) genotypes in a case–control study based on 447 Japanese AITD patients [277 Graves’ disease (GD) and 170 Hashimoto’s thyroiditis (HT) patients] and 225 matched Japanese controls using the high-resolution melting and unlabeled probe methods. Case–control association studies were performed using the χ2 and Fisher’s exact tests with Yates correction. The G allele of rs7679475 (A/G) was associated with HT compared with controls [P = 0.022, odds ratio (OR) = 0.69]. GD showed no significant associations with any SNPs. However, when patients with GD were stratified according to Graves’ ophthalmopathy (GO), the G allele of rs2358994 (A/G) was associated with GO vs. controls (P = 0.018, OR = 1.52). These findings suggest that in the Japanese population the GPR103 gene may contribute to the pathogenesis of HT. Moreover, this study demonstrated that the SNP rs2358994 within BCL2L15 gene is associated with GO in the Japanese population.
Time-Frequency Multiplex Estimator and Low Complexity Equalizer Design for Multi-Carrier Systems with TX/RX IQ Imbalance, CFO and Multipath Fading Channels

A low complexity time-frequency multiplex estimator and low complexity equalizer transceiver design is proposed to combat the RF impairment problems for the zero-IF transceiver of multi- carrier systems. Moreover, the proposed preamble can estimate and compensate the transmitter/receiver (Tx/Rx) in-phase and quadrature-phase (IQ) imbalance, carrier frequency offset (CFO), and channel impulse response parameters. There are two parts in the proposed system. Firstly, all parameters of impairments are estimated by the proposed time-frequency multiplex estimator design. Secondly, the estimated parameters are used to equalize the above problems and detect the transmitted signal with low complexity advantage. Simulation results confirm that the proposed estimator can provide reliable performance over the severe Tx/Rx IQ imbalance, CFO, and multipath fading channel environments.
A high-order MRTD technique with Laguerre-polynomial-based time-integration

A new unconditionally stable method is derived as a modified version of the scaling function based-multiresolution time domain (S-MRTD), by replacing the customary explicit leapfrog time scheme with marching in order of weighted Laguerre polynomials. This paper proposes the use of high-order finite differences in space, in the sense of the S-MRTD technique. Thus, cell sizes close to the Nyquist limit can be used, that can still provide for satisfactory numerical dispersion properties, due to the high linearity of the S-MRTD dispersion. The methodology for the derivation of the proposed Laguerre-MRTD technique is shown and a numerical study of the this technique is provided.
Phenotypic Pattern-Based Assay for Dynamically Monitoring Host Cellular Responses to Salmonella Infections

The interaction between mammalian host cells and bacteria is a dynamic process, and the underlying pathologic mechanisms are poorly characterized. Limited information describing the host-bacterial interaction is based mainly on studies using label-based endpoint assays that detect changes in cell behavior at a given time point, yielding incomplete information. In this paper, a novel, label-free, real-time cell-detection system based on electronic impedance sensor technology was adapted to dynamically monitor the entire process of intestinal epithelial cells response to Salmonella infection. Changes in cell morphology and attachment were quantitatively and continuously recorded following infection. The resulting impedance-based time-dependent cell response profiles (TCRPs) were compared to standard assays and showed good correlation and sensitivity. Biochemical assays further suggested that TCRPs were correlated with cytoskeleton-associated morphological dynamics, which can be largely attenuated by inhibitions of actin and microtubule polymerization. Collectively, our data indicate that cell-electrode impedance measurements not only provide a novel, real-time, label-free method for investigating bacterial infection but also help advance our understanding of host responses in a more physiological and continuous manner that is beyond the scope of current endpoint assays.
Research Statement Caner Kazanci Statistical Properties of Large Biochemical Networks

Extensive work has been done in mathematical modeling of biological systems, focusing on small subsystems that can be described using only a few differential equations. With recent advances in experimental techniques in biology, there is a need to extend mathematical modeling to include larger systems. One of the major challenges is understanding how cells and other large biological systems work. It is clear that only a few differential equations are not sufficient to capture the complexity of such systems. New mathematical and computational tools need to be developed.
Verifying linearizability with hindsight

We present a proof of safety and linearizability of a highly-concurrent optimistic set algorithm. The key step in our proof is the Hindsight Lemma, which allows a thread to infer the existence of a global state in which its operation can be linearized based on limited local atomic observations about the shared state. The Hindsight Lemma allows us to avoid one of the most complex and non-intuitive steps in reasoning about highly concurrent algorithms: considering the linearization point of an operation to be in a different thread than the one executing it. The Hindsight Lemma assumes that the algorithm maintains certain simple invariants which are resilient to interference, and which can themselves be verified using purely thread-local proofs. As a consequence, the lemma allows us to unlock a perhaps-surprising intuition: a high degree of interference makes non-trivial highly-concurrent algorithms in some cases much easier to verify than less concurrent ones.
Gestational age, birth weight, and the risk of hyperkinetic disorder

Aims: To study the association between gestational age and birth weight and the risk of clinically verified hyperkinetic disorder. Methods: Nested case-control study of 834 cases and 20 100 controls with incidence density sampling. Results: Compared with children born at term, children born with gestational ages of 34–36 completed weeks had a 70% increased risk of hyperkinetic disorder (rate ratio (RR) 1.7, 95% confidence interval (CI) 1.2 to 2.5). Children with gestational ages below 34 completed weeks had an almost threefold increased risk (RR 2.7, 95% CI 1.8 to 4.1). Children born at term with birth weights of 1500–2499 g had a 90% increased risk of hyperkinetic disorder (RR 1.9, 95% CI 1.2 to 2.9), and children with birth weights of 2500–2999 g had a 50% increased risk (RR 1.5, 95% CI 1.2 to 1.8) compared with children born at term with birth weights above 2999 g. The results were adjusted for socioeconomic status of the parents, family history of psychiatric disorders, conduct disorders, comorbidity, and maternal smoking during pregnancy. Results related to birth weight were unchanged after adjusting for differences in gestational age. Conclusions: Children born preterm, also close to term, and children born at term with low birth weights (1500–2499 g) have an increased risk of clinically verified hyperkinetic disorder. These findings have important public health perspectives because the majority of preterm babies are born close to term.
Field programmable analog arrays enable analog signal processing education

In a laboratory environment, the practicality and scope of experiments is constrained by time and financial resources. In the digital hardware design arena, t he development of programmable logic devices, such as field–programmable gate arrays (FPGAs), has greatly enha nced the students ability to design and synthesize complete systems within a short period of time and at a reason able cost. Unfortunately, analog circuit design and signal processing have not enjoyed similar advances. Howev er, new advances in field–programmable analog arrays (FPAAs) have created many new opportunities in analog circu it design and signal processing education. This paper will investigate the usefulness of these FPAAs as viable ped agogical tools. It will also explore the new methodologies in analog signal processing education that are available wh n FPAAs are brought into the classroom.
A Conceptual Model for Digital Libraries Evolution

The evolution and preservation of digital libraries are not simply a matter of technological decisions, but they can be better understood if treated as the integration of three complementary dimensions (based on the informational, technological and social domains). These dimensions together form a conceptual framework suitable to characterize the whole digital library concept. In this paper, starting from the experience and the lessons learned in the realization of the EU-India E-Dvara project, we propose such framework, providing motivational examples and discussing opportune solutions. More in particular, we discuss the issues concerned the technical infrastructure adaptation, the coordination of different user roles, and the data evolution in order to select the dimensions along which we base our
Microwave-Based Chemical Synthesis of Co-Alloyed Nd-Fe-B Hard Magnetic Powders

Modern high-energy-product permanent magnets derive their superior properties from nanoscale interactions, which are a sensitive function of the crystal size. Further property improvements require novel synthesis techniques to control the crystal size. Hence, we report a cost-effective and facile technique, i.e., microwave-based synthesis, to produce Co-alloyed Nd-Fe-B-based magnetic nanostructured powder. Dedicated microwave synthesis equipment with an optical pyrometer attachment was used to synthesize mixed metal oxides, followed by reduction diffusion to produce Nd-Fe-Co-B magnetic nanoparticles. Nanosized mixed oxide powders were formed in a single-step combustion after ignition, which was completed within a few seconds. In the reduction diffusion process, a two-step reaction was observed. Co and Fe oxides were first reduced to Fe and Co as the temperature reached <inline-formula><tex-math notation="LaTeX">$350\, ^\circ {\text{C}}$</tex-math></inline-formula>. Nd oxide was partially reduced to <inline-formula><tex-math notation="LaTeX">${\text{NdH}}_{\text{2}}$</tex-math></inline-formula> at <inline-formula><tex-math notation="LaTeX">${350\, ^\circ \text{C}}$</tex-math> </inline-formula> and finally to Nd when the temperature reached <inline-formula><tex-math notation="LaTeX">${740\, ^\circ \text{C}}$</tex-math></inline-formula>, when the desired <inline-formula><tex-math notation="LaTeX">${\text{Nd}}_{\text{2}}{\text{(Fe,Co)}}_{\text{14}}{\text{B}}$</tex-math></inline-formula> phase was also obtained. This reaction sequence matched thermodynamic calculations. Microwave power played a crucial role in controlling combustion temperature, crystal size, and coercivity of the <inline-formula><tex-math notation="LaTeX">${\text{Nd}}_{\text{2}}{\text{(Fe,Co)}}_{\text{14}}{\text{B}}$</tex-math></inline-formula> nanoparticles. The coercivity of these nanoparticles increased from 4.6kOe to 8kOe as the mean crystal size increased from 20 to 60nm. The saturation magnetization was 106emug.