Miracle-dz/UniFAR-FTUs huggingface dataset:
Systems Biology – A Guide for Understanding and Developing Improved Strains of Lactic Acid Bacteria

Lactic Acid Bacteria (LAB) are extensively employed in the production of various fermented foods, due to their safe status, ability to affect texture and flavor and finally due to the beneficial effect they have on shelf-life. More recently, LAB have also gained interest as production hosts for various useful compounds, particularly compounds with sensitive applications, such as food ingredients and therapeutics. As for all industrial microorganisms, it is important to have a good understanding of the physiology and metabolism of LAB in order to fully exploit their potential, and for this purpose, many systems biology approaches are available. Systems metabolic engineering, an approach that combines optimization of metabolic enzymes/pathways at the systems level, synthetic biology as well as in silico model simulation, has been used to build microbial cell factories for production of biofuels, food ingredients and biochemicals. When developing LAB for use in foods, genetic engineering is in general not an accepted approach. An alternative is to screen mutant libraries for candidates with desirable traits using high-throughput screening technologies or to use adaptive laboratory evolution to select for mutants with special properties. In both cases, by using omics data and data-driven technologies to scrutinize these, it is possible to find the underlying cause for the desired attributes of such mutants. This review aims to describe how systems biology tools can be used for obtaining both engineered as well as non-engineered LAB with novel and desired properties.
Multi-Sensor Fusion for UAV Collision Avoidance

The market for low-cost unmanned aerial vehicles (UAVs) is rapidly increasing. For example, the systems can be equipped with high-resolution digital cameras for inspection flights of buildings or industrial facilities like wind power plants. To support the pilot during these flights a collision avoidance system is presented in this paper. It is based on a sensor fusion of ultrasonic sensors and a laser scanner within an occupancy grid map. Different ultrasonic and laser scanning sensors were examined and the sound radiation of a multi-copter was evaluated.
Alterations in Anatomical Covariance in the Prematurely Born

Abstract Preterm (PT) birth results in long‐term alterations in functional and structural connectivity, but the related changes in anatomical covariance are just beginning to be explored. To test the hypothesis that PT birth alters patterns of anatomical covariance, we investigated brain volumes of 25 PTs and 22 terms at young adulthood using magnetic resonance imaging. Using regional volumetrics, seed‐based analyses, and whole brain graphs, we show that PT birth is associated with reduced volume in bilateral temporal and inferior frontal lobes, left caudate, left fusiform, and posterior cingulate for prematurely born subjects at young adulthood. Seed‐based analyses demonstrate altered patterns of anatomical covariance for PTs compared with terms. PTs exhibit reduced covariance with R Brodmann area (BA) 47, Broca's area, and L BA 21, Wernicke's area, and white matter volume in the left prefrontal lobe, but increased covariance with R BA 47 and left cerebellum. Graph theory analyses demonstrate that measures of network complexity are significantly less robust in PTs compared with term controls. Volumes in regions showing group differences are significantly correlated with phonological awareness, the fundamental basis for reading acquisition, for the PTs. These data suggest both long‐lasting and clinically significant alterations in the covariance in the PTs at young adulthood.
Overcoming Resistance to Selective Serotonin Reuptake Inhibitors: Targeting Serotonin, Serotonin-1A Receptors and Adult Neuroplasticity

Major depressive disorder (MDD) is the most prevalent mental illness contributing to global disease burden. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are the first-line treatment for MDD, but are only fully effective in 30% of patients and require weeks before improvement may be seen. About 30% of SSRI-resistant patients may respond to augmentation or switching to another antidepressant, often selected by trial and error. Hence a better understanding of the causes of SSRI resistance is needed to provide models for optimizing treatment. Since SSRIs enhance 5-HT, in this review we discuss new findings on the circuitry, development and function of the 5-HT system in modulating behavior, and on how 5-HT neuronal activity is regulated. We focus on the 5-HT1A autoreceptor, which controls 5-HT activity, and the 5-HT1A heteroreceptor that mediates 5-HT actions. A series of mice models now implicate increased levels of 5-HT1A autoreceptors in SSRI resistance, and the requirement of hippocampal 5-HT1A heteroreceptor for neurogenic and behavioral response to SSRIs. We also present clinical data that show promise for identifying biomarkers of 5-HT activity, 5-HT1A regulation and regional changes in brain activity in MDD patients that may provide biomarkers for tailored interventions to overcome or bypass resistance to SSRI treatment. We identify a series of potential strategies including inhibiting 5-HT auto-inhibition, stimulating 5-HT1A heteroreceptors, other monoamine systems, or cortical stimulation to overcome SSRI resistance.
An outbreak investigation of scrub typhus in Western Province, Solomon Islands, 2014

Objective To identify the etiology and risk factors of undifferentiated fever in a cluster of patients in Western Province, Solomon Islands, May 2014. Methods An outbreak investigation with a case control study was conducted. A case was defined as an inpatient in one hospital in Western Province, Solomon Islands with high fever (> 38.5 °C) and a negative malaria microscopy test admitted between 1 and 31 May 2014. Asymptomatic controls matched with the cases residentially were recruited in a ratio of 1:2. Serum samples from the subjects were tested for rickettsial infections using indirect micro-immunofluorescence assay. Results Nine cases met the outbreak case definition. All cases were male. An eschar was noted in five cases (55%), and one developed pneumonitis. We did not identify any environmental factors associated with illness. Serum samples of all five follow-up cases (100%) had strong-positive IgG responses to scrub typhus. Nine out of ten controls were negative for ST antibodies. Four controls had low levels of antibodies against spotted fever group rickettsia, and only one had a low-level response to typhus group rickettsia. Discussion This outbreak represents the first laboratory-confirmed outbreak of scrub typhus in the Western Province of Solomon Islands. The results suggest that rickettsial infections are more common than currently recognized as a cause of an acute febrile illness. A revised clinical case definition for rickettsial infections and treatment guidelines were developed and shared with provincial health staff for better surveillance and response to future outbreaks of a similar kind.
Modulations in Oscillatory Activity of Globus Pallidus Internus Neurons During a Directed Hand Movement Task—A Primary Mechanism for Motor Planning

Globus pallidus internus (GPi) neurons in the basal ganglia are traditionally thought to play a significant role in the promotion and suppression of movement via a change in firing rates. Here, we hypothesize that a primary mechanism of movement control by GPi neurons is through specific modulations in their oscillatory patterns. We analyzed neuronal spiking activity of 83 GPi neurons recorded from two healthy nonhuman primates executing a radial center-out motor task. We found that, in directionally tuned neurons, the power in the gamma band is significantly (p < 0.05) greater than that in the beta band (a “cross-over” effect), during the planning stages of movements in their preferred direction. This cross-over effect is not observed in the non-directionally tuned neurons. These data suggest that, during movement planning, information encoding by GPi neurons may be governed by a sudden emergence and suppression of oscillatory activities, rather than simply by a change in average firing rates.
Multi-Path Transport for RDMA in Datacenters

RDMA is becoming prevalent because of its low latency, high throughput and low CPU overhead. However, current RDMA remains a single path transport which is prone to failures and falls short to utilize the rich parallel paths in datacenters. Unlike previous multipath approaches, which mainly focus on TCP, this paper presents a multi-path transport for RDMA, i.e. MPRDMA, which efﬁciently utilizes the rich network paths in datacenters. MP-RDMA employs three novel techniques to address the challenge of limited RDMA NICs on-chip memory size: 1) a multi-path ACK-clocking mechanism to distribute trafﬁc in a congestion-aware manner without incurring per-path states; 2) an out-of-order aware path selection mechanism to control the level of out-of-order delivered packets, thus minimizes the meta data required to them; 3) a synchronise mechanism to ensure in-order memory update whenever needed. With all these techniques, MP-RDMA only adds 66B to each connection state compared to single-path RDMA. Our evaluation with an FPGA-based prototype demonstrates that compared with single-path RDMA, MPRDMA can signiﬁcantly improve the robustness under failures (2x∼4x higher throughput under 0.5%∼10% link loss ratio) and improve the overall network utilization by up to 47%.
Comparison between 22G aspiration and 22G biopsy needles for EUS-guided sampling of pancreatic lesions: A meta-analysis

Background and Objective: Robust data in favor of clear superiority of 22G fine-needle biopsy (FNB) over 22G FNA for an echoendoscopic-guided sampling of pancreatic masses are lacking. The objective of this study is to compare the diagnostic outcomes and sample adequacy of these two needles. Materials and Methods: Computerized bibliographic search on the main databases was performed and restricted to only randomized controlled trials. Summary estimates were expressed regarding risk ratio (RR) and 95% confidence interval. Results: A total of 11 trials with 833 patients were analyzed. The two needles resulted comparable in terms of diagnostic accuracy (RR 1.02, 0.97–1.08; P = 0.46), sample adequacy (RR 1.01, 0.96–1.06; P = 0.61), and histological core procurement (RR 1.01, 0.89–1.15; P = 0.86). Pooled sensitivity in the diagnosis of pancreatic cancer was 93.1% (87.9%–98.4%) and 90.4% (86.3%–94.5%) with biopsy and aspirate, respectively, whereas specificity for detecting pancreatic cancer was 100% with both needles. Analysis of the number of needle passes showed a nonsignificantly positive trend in favor of FNB (mean difference: −0.32, −0.66–0.02; P = 0.07). Conclusion: Our meta-analysis stands for a nonsuperiority of 22G FNB over 22G FNA; hence, no definitive recommendations on the use of a particular device can be made.
Immunocytochemical and ultrastructural evidence of glial cells and hyalocytes in internal limiting membrane specimens of idiopathic macular holes.

PURPOSE To provide new information on epiretinal cell proliferation and the cells' origin in idiopathic macular holes and to overcome the effects of embedding and sectioning preparation procedures on cell-distribution patterns. METHODS Interference and phase-contrast microscopy, immunocytochemistry, and scanning and transmission electron microscopy were performed on surgically excised whole-mounted internal limiting membrane (ILM) specimens removed from 60 eyes with idiopathic macular holes. Cell distribution and cell morphology were correlated with immunocytochemical staining characteristics. Twelve cell type-specific antibodies were used to detect glial cells, hyalocytes, retinal pigment epithelial cells, retinal ganglion cells, and immune cells. Cell viability was analyzed. RESULTS Epiretinal cell proliferation was found in all ILM specimens, irrespective of the stage of the macular hole. Cell density showed a broad variety. Immunocytochemistry frequently revealed simultaneous expression of GFAP/CD45, GFAP/CD64, GFAP/CD68, GFAP/CRALBP, and GFAP/CD90. Some cells presented with intracellular contractile filaments (anti-αSMA); others were not immunoreactive to any antibody examined. The percentage of viable cells showed a broad variety with a mean of 73% (SD 29%). Electron microscopy demonstrated glial cells, hyalocytes, and myofibroblast-like cells. CONCLUSIONS The presence of epiretinal cells at the ILM in all macular hole stages strongly suggests a substantial involvement of cell migration and proliferation in the course of macular hole development. Glial cells and hyalocytes play the predominant role in epiretinal cell proliferation. Given the co-expression of glial cell and hyalocyte markers, transdifferentiation of epiretinal cells needs further elucidation, especially with respect to αSMA-positive cells leading to traction at the vitreoretinal interface.
Addressing the Challenges of Recruitment and Retention in Sleep and Circadian Clinical Trials

ABSTRACT Objective/Background: Sleep and circadian disorders are prevalent worldwide and frequently comorbid with physical and mental illnesses. Thus, recruiting and retaining samples for sleep and circadian research are high priorities. The aims of this paper are to highlight barriers to recruitment and retention for participants with sleep or circadian dysfunction, and to share strategies used across two randomized controlled trials (RCTs) testing the efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) to address these challenges. Participants: The first RCT recruited 176 adolescents with an evening circadian chronotype, who were at risk in at least one of five health domains: behavioral, cognitive, emotional, physical, and social. The second RCT recruited 121 low-income, racial or ethnic minority adults diagnosed with severe mental illness (SMI) and comorbid sleep or circadian dysfunction. Methods: The current study examined participant, environment, and research factors that impacted recruitment and retention of participants with sleep or circadian dysfunction, and identified strategies to enhance recruitment and retention. Results: Strategies used to recruit participants included community-based recruiting, reducing stigma, and alleviating burdensome sleep data collection. Strategies used to retain participants in our studies included flexible scheduling, mitigating participant barriers, building rapport with participants through empathic and positive interactions, creative problem solving, consulting participant networks, and utilizing incentives and other positive engagement tools. Conclusion: Both at-risk adolescents and low-income, minority adults with comorbid SMI and sleep or circadian dysfunction experience significant barriers to research participation. Recruitment and retention strategies were creatively tailored to meet the unique barriers of these diverse populations.
Efficacy of 7‐benzyloxyindole and other halogenated indoles to inhibit Candida albicans biofilm and hyphal formation

Certain pathogenic bacteria and yeast form biofilms on biotic and abiotic surfaces including medical devices and implants. Hence, the development of antibiofilm coating materials becomes relevant. The virulence of those colonizing pathogens can be reduced by inhibiting biofilm formation rather than killing pathogens using excessive amounts of antimicrobials, which is touted as one of the main reasons for the development of drug resistance. Candida albicans is an opportunistic fungal pathogen, and the transition of yeast cells to hyphal cells is believed to be a crucial virulence factor. Previous studies have shown that indole and its derivatives possess antivirulence properties against various bacterial pathogens. In this study, we used various indole derivatives to investigate biofilm‐inhibiting activity against C. albicans. Our study revealed that 7‐benzyloxyindole, 4‐fluoroindole and 5‐iodoindole effectively inhibited biofilm formation compared to the antifungal agent fluconazole. Particularly, 7‐benzyloxyindole at 0.02 mM (4.5 μg ml−1) significantly reduced C. albicans biofilm formation, but had no effect on planktonic cells, and this finding was confirmed by a 2,3‐bis‐(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide (XTT) assay and three‐dimensional confocal laser scanning microscopy. Scanning electron microscopy analyses revealed that 7‐benzyloxyindole effectively inhibited hyphal formation, which explains biofilm inhibition. Transcriptomic analysis showed that 7‐benzyloxyindole downregulated the expressions of several hypha/biofilm‐related genes (ALS3, ECE1, HWP1 and RBT1). A C. albicans‐infected Caenorhabditis elegans model system was used to confirm the antivirulence efficacy of 7‐benzyloxyindole.
CYP51 as drug targets for fungi and protozoan parasites: past, present and future

Abstract The efficiency of treatment of human infections with the unicellular eukaryotic pathogens such as fungi and protozoa remains deeply unsatisfactory. For example, the mortality rates from nosocomial fungemia in critically ill, immunosuppressed or post-cancer patients often exceed 50%. A set of six systemic clinical azoles [sterol 14α-demethylase (CYP51) inhibitors] represents the first-line antifungal treatment. All these drugs were discovered empirically, by monitoring their effects on fungal cell growth, though it had been proven that they kill fungal cells by blocking the biosynthesis of ergosterol in fungi at the stage of 14α-demethylation of the sterol nucleus. This review briefs the history of antifungal azoles, outlines the situation with the current clinical azole-based drugs, describes the attempts of their repurposing for treatment of human infections with the protozoan parasites that, similar to fungi, also produce endogenous sterols, and discusses the most recently acquired knowledge on the CYP51 structure/function and inhibition. It is our belief that this information should be helpful in shifting from the traditional phenotypic screening to the actual target-driven drug discovery paradigm, which will rationalize and substantially accelerate the development of new, more efficient and pathogen-oriented CYP51 inhibitors.
A method for rapid quantitative assessment of incomplete integral contrast for complex images

The problem of no-reference quantitative estimation (measurement) of contrast of complex (multi-element) monochrome images for assessment of their objective quality is considered. Different approaches to the quantitative assessment of the incomplete integral contrast of complex image on the basis of an analysis of the contrast values of its elements relative to a preset level of adaptation are considered. A new method for measuring the incomplete integral contrast of a complex image is proposed on the basis of estimates of contrast values for a number of elementary (two-element) images of its elements (objects) which are located on a homogeneous background and of estimate of the distribution of the brightness values at the boundaries of the image elements. A comparative analysis of the proposed and known methods of measuring the incomplete integral contrast of monochrome images is carried out.
Cyber Threat Intelligence – Issue and Challenges

Today threat landscape evolving at the rapid rate with many organization continuously face complex and malicious cyber threats. Cybercriminal equipped by better skill, organized and well-funded than before. Cyber Threat Intelligence (CTI) has become a hot topic and being under consideration for many organization to counter the rise of cyber-attacks. The aim of this paper is to review the existing research related to CTI. Through the literature review process, the most basic question of what CTI is examines by comparing existing definitions to find common ground or disagreements. It is found that both organization and vendors lack a complete understanding of what information is considered to be CTI, hence more research is needed in order to define CTI. This paper also identified current CTI product and services that include threat intelligence data feeds, threat intelligence standards and tools that being used in CTI. There is an effort by specific industry to shared only relevance threat intelligence data feeds such as Financial Services Information Sharing and Analysis Center (FS-ISAC) that collaborate on critical security threats facing by global financial services sector only. While research and development center such as MITRE working in developing a standards format (e.g.; STIX, TAXII, CybOX) for threat intelligence sharing to solve interoperability issue between threat sharing peers. Based on the review for CTI definition, standards and tools, this paper identifies four research challenges in cyber threat intelligence and analyses contemporary work carried out in each. With an organization flooded with voluminous of threat data, the requirement for qualified threat data analyst to fully utilize CTI and turn the data into actionable intelligence become more important than ever. The data quality is not a new issue but with the growing adoption of CTI, further research in this area is needed.
Relationship between human leukocyte antigen (HLA)-DQA1*0102/HLA-DQB1*0602 polymorphism and preeclampsia

Background: Preeclampsia is a condition associated with systemic disorders in the mother and the fetus. However, the exact causes of preeclampsia are unknown, but several genetics and environmental factors play role in development of this disease. Major histocompatibility complex role is very important during pregnancy through which the fetus is not rejected by mother’s immune system. Objective: In this study, we investigated the relationship of the human leukocyte antigen (HLA)-DQA1*0102/HLA-DQB1*0602 polymorphism with preeclampsia. Materials and Methods: Genomic DNA of 181 pregnant women with a history of preeclampsia as the case group and 228 pregnant women with no history of preeclampsia as the controls were extracted. The HLA-DQA1*0102/HLA-DQB1*0602 polymorphisms of all DNA samples were identified by the SSP-PCR method. Frequencies difference of variables between case and control groups were calculated by Chi-square test. The ethnic origin of the participants in this study was extracted from their medical records. Results: There was a significant association between preeclampsia and Sistani ethnic group (p=0.031). Moreover, there was a significant association between preeclampsia and frequencies of allele HLA-DQB1*0602 (p<0.001), and genotypes of heterozygote (+0102/-0602) (p<0.001) and negative homozygote (-0102/-0602) (p=0.005). There also was an association between allele HLA-DQB1*0602 and preeclampsia in Fars ethnic group (p=0.028). Conclusion: It seems that immune incompatibility may have an important role in preeclampsia predisposition. According to our results, the lack of locus HLA-DQB1*0602 may be a risk factor for preeclampsia.
Identification of Sparse Continuous-Time Linear Systems with Low Sampling Rate: Optimization Approaches

This paper addresses identification of sparse linear and noise-driven continuous-time state-space systems, i.e., the right-hand sides in the dynamical equations depend only on a subset of the states. The key assumption in this study, is that the sample rate is not high enough to directly infer the continuous time system from the data. This assumption is relevant in applications where sampling is expensive or requires human intervention (e.g., biomedicine applications). We propose an iterative optimization scheme with $l_1$-regularization, where the search directions are restricted those that decrease prediction error in each iteration. We provide numerical examples illustrating the proposed method; the method outperforms the least squares estimation for large noise.