Miracle-dz/UniFAR-FTUs huggingface dataset:
Feasibility of a Conditional Knockout System for Chlamydia Based on CRISPR Interference

Chlamydia is an obligate intracellular bacterium and, as such, has significantly reduced its genome size and content. Although recent advances have allowed for transformation of C. trachomatis with an exogenous plasmid, genetic manipulation of Chlamydia remains challenging. In particular, the ability to create conditional knockouts has not been developed. This is particularly important given the likelihood that most genes within the small genome of Chlamydia may be essential. Here, I describe the feasibility of using CRISPR interference (CRISPRi) based on the catalytically inactive Cas9 variant (dCas9) of Staphylococcus aureus to inducibly, and reversibly, repress gene expression in C. trachomatis. CRISPRi has been developed and used successfully in a variety of bacterial organisms including E. coli and Mycobacterium tuberculosis. I first describe the creation of a single plasmid system for CRISPRi in Chlamydia, targeted to a non-essential gene, incA, that expresses a dispensable inclusion membrane protein. Control transformations of C. trachomatis serovar L2 with plasmids encoding only the dCas9, under the control of an inducible promoter, or only the guide RNA (gRNA) targeted to the 5' UTR of incA, expressed constitutively, failed to prevent expression of IncA. Importantly, expression of dCas9 alone did not have a deleterious effect on chlamydiae. Transformation of C. trachomatis with a plasmid combining the dCas9 and a gRNA targeting incA and induction of expression of the dCas9 resulted in the reversible inhibition of IncA expression. Consequently, conditional knockout mediated by CRISPRi is feasible in Chlamydia. Potential improvements and experimental concerns in using the system are also discussed.
Analysis and design of IDMA systems based on SNR evolution and power allocation

We show that the performance of an interleave-division multiple-access (IDMA) system can be assessed by tracking the signal-to-noise-ratio (SNR) evolution of the iterative chip-by-chip (CBC) detection process. Based on this we develop a power allocation technique for performance optimization. Very high throughput (say 8 bits/chip) is observed for IDMA without sophisticated channel coding.
Understanding 802.11e contention-based prioritization mechanisms and their coexistence with legacy 802.11 stations

The IEEE 802.11e task group has reached a stable consensus on two basic contention-based priority mechanisms to promote for standardization: usage of different arbitration interframe spaces and usage of different minimum/maximum contention windows. The goal of this article is to provide a thorough understanding of the principles behind their operation. To this purpose, rather than limit our investigation to high-level (e.g. throughput and delay) performance figures, we take a closer look at their detailed operation, also in terms of low-level performance metrics (e.g., the probability of accessing specific channel slots). Our investigation on one hand confirms that AIFS differentiation provides superior and more robust operation than contention window differentiation. On the other hand, it highlights performance issues related to the coexistence between 802.11e contention-based stations with legacy 802.11 stations, and provides guidelines for the 802.11e parameter settings when such a coexistence is the goal.
Magnetic resonance imaging as an instrument to assess the association between femoral neck bone geometry and strength of the proximal femur

Introduction: Hip fractures are an increasing health and economic burden. Dual energy x-ray absorptiometry (DXA) is the instrument currently used to diagnose osteoporosis, however, there are limitations associated with using D X A to predict fracture risk and to measure response to therapeutic interventions. Magnetic resonance imaging (MRI) is an emerging instrument to assess bone, however the ability of MRI measurements of femoral neck geometry to predict bone strength has not been previously assessed. Objectives: To evaluate the association of femoral neck cross-sectional geometry measured with MRI with failure load in cadaveric femora, and to compare this association with D X A and Hip Structural Analysis (HSA). The secondary objective was to compare reliability of femoral neck geometry measured with 3 Tesla (T) MRI and 1.5 T MRI systems. Methods: Thirty-six human cadaveric proximal femora underwent D X A and MRI imaging. D X A images were also analyzed with HSA. Areal B M D (aBMD) was evaluated with D X A and HSA. Cross-sectional geometry (area, second area moment of inertia Ix, and section modulus) were evaluated with MRI (femoral neck region) and HSA (narrow neck and intertrochanteric regions). Inter-analysis and inter-acquisition reliability were compared between measurements with 1.5 T and 3 T MRI systems. The femora were loaded to failure in a fall configuration. Results: Femoral neck cortical cross-sectional area and Ix, measured with MRI, were strongly associated with failure load (R 2 = 0.47 for both measures, p < 0.001). The predictive ability of Ix was lower than trochanteric aBMD (R = 0.70), p = 0.10. Ix significantly contributed to the variance explained in failure load after accounting for femoral neck aBMD (R-change = 0.14, p = 0.01), but not after accounting for trochanteric aBMD (R-change = 0.03, p = 0.23). Crosssectional geometry, e.g. Ix, measured with MRI explained similar variance in failure load (R 2 = 0.47) as cross-sectional geometry estimated with HSA (R = 0.31). Inter-acquisition and interanalysis reliability were similar for 3 T and 1.5 T MRI systems. Summary and Conclusion: Femoral neck cross-sectional geometry assessed with MRI and HSA, and aBMD by D X A were similarly associated with failure load ex vivo. MRI holds promise for the in vivo assessment of cortical bone geometry at the proximal femur, as neither D X A nor HSA are capable of measuring these parameters without major assumptions. However, a targeted program of research that aims to improve and standardize MRI image acquisition and analysis is warranted.
Phylogenetics pez : phylogenetics for the environmental sciences

Summary: pez is an R package that permits measurement, modelling and simulation of phylogenetic structure in ecological data. pez contains the ﬁrst implementation of many methods in R , and aggregates existing data structures and methods into a single, coherent package. Availability and implementation: pez is released under the GPL v3 open-source license, available on the Internet from CRAN (http://cran.r-project.org). The package is under active development, and the authors welcome contributions (see http://github.com/willpearse/pez).
Tunable switch-mode emulated inductive elements for enhanced power converter miniaturization

This work presents the emulation of tunable switch-mode inductive elements for power converters applications. Such elements are based on the concept of ideal loss-free realization by means of switch-mode circuits. A gyrator-based approach for synthesizing inductors is demonstrated. The value of the emulated inductance could be tuned by using appropriate control which would help to alleviate common undesirable properties of conventional passive implementations such as tolerance and value change over temperature and time. This approach enables monolithic circuits composed of semiconductor devices and small inductors/capacitors to be used to emulate large reactive components as a step forward for enhanced power converter miniaturization and integration.
Joint FEC coding and linear precoding for MIMO ISI channels

In this paper, we present a joint forward-error-correction (FEC) coding and linear precoding scheme for multiple-input multiple-output (MIMO) and inter-symbol interference (ISI) channels with imperfect channel state information at the transmitter (CSIT). We first study the performance of ideally coded systems. We focus on an average power gain (APG) method that can achieve capacity in the two extreme cases of no CSIT and perfect CSIT. In the more general case, the performance of the APG method improves progressively with the CSIT quality. We then consider the implementation of this APG method in a practically coded system. We propose a unified scheme involving beamforming, water-filling, and diversity coding. The core of the new scheme is a joint FEC coding and linear precoding strategy at the transmitter and an iterative detection process at the receiver. Simulation results demonstrate that the proposed scheme can achieve significant performance gain by efficiently utilizing the available CSIT.
Association between Dietary Inflammatory Index and Prostate Cancer in Shiraz Province of Iran

Background: Dietary components like food items and nutrients have been implicated to play a role in modulating inflammation and the development of prostate cancer. Studies examining this association have not been extensively explored in Middle Eastern Countries. Material and Methods: We examined the association between the dietary inflammatory index (DIITM) and prostate cancer in the Shiraz province of Iran. A total of 60 incident cases and 60 controls attending the same hospital as the cases were recruited. The energy adjusted DII (E-DIITM) was computed based on dietary intake assessed using a validated food frequency questionnaire (FFQ). Logistic regression was used to estimate odds ratios. Results: Men with higher E-DII (>0.96) were at higher risk of prostate cancer (OR = 2.55; 95% CI =1.04–6.23) compared to men with E-DII ≤0.96. Conclusion: These data suggest a pro-inflammatory diet, as indicated by increasing DII score, may be a risk factor for prostate cancer in Iranian men.
Are infectious diseases and microbiology new fields for thermal therapy research?

Abstract Antimicrobial chemotherapy and surgery are classical methods for treating infectious diseases. However, there is a need for alternative methods to cure infections caused by antibiotic-resistant pathogens, recurrent or chronic infections, and unreachable local infections in which the use of drugs or surgery is anatomically and physically restricted. Several micro-organisms are known to be sensitive to mild hyperthermia, and this sensitivity is one of the potential benefits proposed for the host during an episode of fever. Additionally, some immunological or biophysical changes occur during hyperthermia. These changes may be useful for eliminating thermo-susceptible microbial pathogens using local heat therapy. There are several experimental studies proposing the use of hyperthermia to treat local infections. The infected organs or tissues may be heated up to a temperature that can inhibit invading microorganisms. Here, it is hypothesised that local heat therapy may become an alternative or adjuvant method for curing local infections. Here, we highlight the potential for local hyperthermia in the treatment of bacterial infections caused by thermo-susceptible pathogens in a systematic plan. If the proposed thermal-microbiology concepts and local thermal therapies can be adapted to clinical microbiology and infectiology, new medical fields, such as thermo-microbiology and thermo-infectiology, may be created in the future.
Statistical Inference in the Wright–Fisher Model Using Allele Frequency Data

Abstract The Wright‐Fisher model provides an elegant mathematical framework for understanding allele frequency data. In particular, the model can be used to infer the demographic history of species and identify loci under selection. A crucial quantity for inference under the Wright‐Fisher model is the distribution of allele frequencies (DAF). Despite the apparent simplicity of the model, the calculation of the DAF is challenging. We review and discuss strategies for approximating the DAF, and how these are used in methods that perform inference from allele frequency data. Various evolutionary forces can be incorporated in the Wright‐Fisher model, and we consider these in turn. We begin our review with the basic bi‐allelic Wright‐Fisher model where random genetic drift is the only evolutionary force. We then consider mutation, migration, and selection. In particular, we compare diffusion‐based and moment‐based methods in terms of accuracy, computational efficiency, and analytical tractability. We conclude with a brief overview of the multi‐allelic process with a general mutation model.
Optimal braking control for UW-Car using sliding mode

There has been an increasing interest in a kind of underactuated mechanical systems, mobile wheeled inverted pendulum (MWIP) models, which are widely used in the field of autonomous robotics and intelligent vehicles. A novel structure including an MWIP system and a movable seat called UW-Car is proposed in the study. The dynamic model of UW-Car system running in the flat ground is obtained by applying Lagrange's motion equation. A sliding mode control (SMC) method is proposed for the dynamic model, which is capable of both handling the mismatched perturbation and keeping the body upright. An optimal braking scheme is introduced which reduces the velocity of UW-Car to zero first and adjusts the displacement of seat to the centre position. Genetic Algorithm (GA) is adopted to search the optimal parameters for sliding mode controller. The optimal braking scheme is implemented by on-line switching three sliding mode controllers. The effectiveness of the proposed methods is finally confirmed by numerical simulation.
Traffic-Aware Design of a High-Speed FPGA Network Intrusion Detection System

Security of today's networks heavily rely on network intrusion detection systems (NIDSs). The ability to promptly update the supported rule sets and detect new emerging attacks makes field-programmable gate arrays (FPGAs) a very appealing technology. An important issue is how to scale FPGA-based NIDS implementations to ever faster network links. Whereas a trivial approach is to balance traffic over multiple, but functionally equivalent, hardware blocks, each implementing the whole rule set (several thousands rules), the obvious cons is the linear increase in the resource occupation. In this work, we promote a different, traffic-aware, modular approach in the design of FPGA-based NIDS. Instead of purely splitting traffic across equivalent modules, we classify and group homogeneous traffic, and dispatch it to differently capable hardware blocks, each supporting a (smaller) rule set tailored to the specific traffic category. We implement and validate our approach using the rule set of the well-known Snort NIDS, and we experimentally investigate the emerging trade-offs and advantages, showing resource savings up to 80 percent based on real-world traffic statistics gathered from an operator's backbone.
n+ GaAs/AuGeNi-Au Thermocouple-Type RF MEMS Power Sensors Based on Dual Thermal Flow Paths in GaAs MMIC

To achieve radio frequency (RF) power detection, gain control, and circuit protection, this paper presents n+ GaAs/AuGeNi-Au thermocouple-type RF microelectromechanical system (MEMS) power sensors based on dual thermal flow paths. The sensors utilize a conversion principle of RF power-heat-voltage, where a thermovoltage is obtained as the RF power changes. To improve the heat transfer efficiency and the sensitivity, structures of two heat conduction paths are designed: one in which a thermal slug of Au is placed between two load resistors and hot junctions of the thermocouples, and one in which a back cavity is fabricated by the MEMS technology to form a substrate membrane underneath the resistors and the hot junctions. The improved sensors were fabricated by a GaAs monolithic microwave integrated circuit (MMIC) process. Experiments show that these sensors have reflection losses of less than −17 dB up to 12 GHz. At 1, 5, and 10 GHz, measured sensitivities are about 63.45, 53.97, and 44.14 µV/mW for the sensor with the thermal slug, and about 111.03, 94.79, and 79.04 µV/mW for the sensor with the thermal slug and the back cavity, respectively.
Alterations of androgen receptor-regulated enhancer RNAs (eRNAs) contribute to enzalutamide resistance in castration-resistant prostate cancer

Enzalutamide is a second-generation anti-androgen for treatment of castration-resistant prostate cancer (CPRC). It prolongs survival of CRPC patients, but its overall survival benefit is relatively modest (4.8 months) and by 24 months most patients progress on enzalutamide. To date, however, the molecular mechanisms underlying enzalutamide resistance remain elusive. Herein, we report enzalutamide treatment-induced alterations of androgen receptor (AR)-regulated enhancer RNAs (AR-eRNAs) and their roles in enzalutamide-resistant growth and survival of CRPC cells. AR chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) and RNA-seq analyses revealed that 188 and 227 AR-eRNAs were differentially expressed in enzalutamide-resistant LNCaP and C4-2 cells, respectively. The AR-eRNAs upregulated in C4-2 cells and downregulated in LNCaP cells were selected through meta-analysis. Expression of AR-eRNAs and related mRNAs in the loci of FTO, LUZP2, MARC1 and NCAM2 were further verified by real-time RT-PCR. Silencing of LUZP2 inhibited, but silencing of MARC1 increased the growth of enzalutamide-resistant C4-2 cells. Intriguingly, meta-analysis showed that expression of LUZP2 mRNA increased in primary tumors compared to normal prostate tissues, but decreased again in metastatic CRPC. Our findings suggest that eRNA alteration profiling is a viable new approach to identify functional gene loci that may not only contribute to enzalutamide-resistant growth of CRPC, but also serve as new targets for CRPC therapy.
THE PIRATA PROGRAM History, Accomplishments, and Future Directions *

The Pilot Research Moored Array in the tropical Atlantic (PIRATA) was developed as a multinational observation network to improve our knowledge and understanding of ocean-atmosphere variability in the tropical Atlantic. PIRATA was motivated by fundamental scientific issues and by societal needs for improved prediction of climate variability and its impact on the economies of West Africa, northeastern Brazil, the West Indies, and the United States. In this paper the implementation of this network is described, noteworthy accomplishments are highlighted, and the future of PIRATA in the framework of a sustainable tropical Atlantic observing system is discussed. We demonstrate that PIRATA has advanced beyond a “Pilot” program and, as such, we have redefined the PIRATA acronym to be “Prediction and Research Moored Array in the Tropical Atlantic. ”
Evidence of a Prion-Like Transmission of p53 Amyloid in Saccharomyces cerevisiae

ABSTRACT Loss of p53 function is largely responsible for the occurrence of cancer in humans. Aggregation of mutant p53 has been found in multiple cancer cell types, suggesting a role of aggregation in loss of p53 function and cancer development. The p53 protein has recently been hypothesized to possess a prion-like conformation, although experimental evidence is lacking. Here, we report that human p53 can be inactivated upon exposure to preformed fibrils containing an aggregation-prone sequence-specific peptide, PILTIITL, derived from p53, and the inactive state was found to be stable for many generations. Importantly, we provide evidence of a prion-like transmission of these p53 aggregates. This study has significant implications for understanding cancer progression due to p53 malfunctioning without any loss-of-function mutation or occurrence of transcriptional inactivation. Our data might unlock new possibilities for understanding the disease and will lead to rational design of p53 aggregation inhibitors for the development of drugs against cancer.
Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88–0.92]; P-value = 1.58 × 10−25). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08–1.17]; P-value = 7.89 × 10−09) and rs13294895 (OR = 1.09 [1.06–1.12]; P-value = 2.97 × 10−11). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06–1.18]; P-value = 2.77 × 10−05). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.
Towards Universal Health Coverage: An Evaluation of Rwanda Mutuelles in Its First Eight Years

Background Mutuelles is a community-based health insurance program, established since 1999 by the Government of Rwanda as a key component of the national health strategy on providing universal health care. The objective of the study was to evaluate the impact of Mutuelles on achieving universal coverage of medical services and financial risk protection in its first eight years of implementation. Methods and Findings We conducted a quantitative impact evaluation of Mutuelles between 2000 and 2008 using nationally-representative surveys. At the national and provincial levels, we traced the evolution of Mutuelles coverage and its impact on child and maternal care coverage from 2000 to 2008, as well as household catastrophic health payments from 2000 to 2006. At the individual level, we investigated the impact of Mutuelles' coverage on enrollees' medical care utilization using logistic regression. We focused on three target populations: the general population, under-five children, and women with delivery. At the household level, we used logistic regression to study the relationship between Mutuelles coverage and the probability of incurring catastrophic health spending. The main limitation was that due to insufficient data, we are not able to study the impact of Mutuelles on health outcomes, such as child and maternal mortalities, directly. The findings show that Mutuelles improved medical care utilization and protected households from catastrophic health spending. Among Mutuelles enrollees, those in the poorest expenditure quintile had a significantly lower rate of utilization and higher rate of catastrophic health spending. The findings are robust to various estimation methods and datasets. Conclusions Rwanda's experience suggests that community-based health insurance schemes can be effective tools for achieving universal health coverage even in the poorest settings. We suggest a future study on how eliminating Mutuelles copayments for the poorest will improve their healthcare utilization, lower their catastrophic health spending, and affect the finances of health care providers.