Miracle-dz/UniFAR-FTUs huggingface dataset:
A Biochemist’s Guide to C. elegans

This review is written as an introduction to those who may be contemplating a foray into the “worm world” but are not familiar with this animal or the toolbox of techniques and reagents that would be useful to get started. The goal is to provide an overview, an idea of what to consider, and where to find additional resources and necessary information. It has been slightly more than 30 years since Sydney Brenner documented the use of Caenorhabditis elegans as a model genetic organism [1]. Since that time more than 7,000 articles have been published investigating all aspects of this organism from its feeding and social behavior to very fine details of neurotransmission. After the sequence of the entire genome of C. elegans became available in 1998 [2], it became apparent that the similarity of genes between this microscopic nematode and that of humans is remarkable with approximately 40% of genes that are associated with human disease having homologs in the C. elegans genome [3]. This similarity validates Brenner’s choice of C. elegans as not only a model for general biological processes but also for understanding the pathogenesis of disease. If the 1990’s is considered the “decade of genome”, where the sequence of organism after organism was reported, the early 2000’s might be considered the “decade of genome mining” in which large scale efforts are aimed at understanding the function of the genomic content. In the C. elegans community, these efforts are directed at understanding of the function, regulation, interaction, and expression of the entire complement of genes in the genome (reviewed in [4]). All of this information is increasing the likelihood that C. elegans will be an attractive system for studying an everexpanding variety of biological problems. Indeed, a number of investigators have successfully crossed over from another organism to the worm in order to study their homolog of interest in this simple model.
Development of real-time in vivo imaging of Staphylococcus epidermidis device-related infection in mice: influence of animal immune status

SUMMARY— We constructed a bioluminescent strain of Staphylococcus epidermidis and developed a catheter-related murine infection model for real-time monitoring of biofilm-associated infection in this leading nosocomial pathogen. Additionally, we compared immune-compromised versus immune-competent mice, demonstrating a substantial effect of animal immune status on susceptibility to experimental S. epidermidis infection. Advanced modern detection techniques such as bioluminescence imaging (BLI) utilize a high sensitive optical biophotonic camera and subsequent digital quantification to measure in vivo processes. Bioluminescence results from the emission of visible light by metabolically active organisms through luciferase-catalyzed oxidation of the substrate luciferin. The bioactive process requires FMN H2 , ATP, and oxygen. Microorganisms can be engineered to produce bioluminescence by insertion of the lux genes into the bacterial genome. Thus, BLI permits visualization, quantification, and monitoring of “tagged” microorganism within intact animals (3,4,8,21). biofilm-associated factors of in vivo dynamics of
Defining the Flow Limiting Stenosis Non-Invasively for Management of Patients with CAD

Coronary artery disease (CAD) has become the number one pathologic process responsible for disease burden in the world. While traditionally the management of CAD was based on anatomic stenosis, more recently, better outcomes have been associated with revascularization of flow limiting stenoses as opposed to indications based on purely anatomical obstructions. The reference standard for defining ischemia related coronary obstructions relies in the measurement of fractional-flow reserve (FFR) in the catheterization laboratory during adenosine induced vasodilation. Indeed, FFR-guided PCI has become the standard of care for intermediate lesions with a strong body of evidence now accumulated using this paradigm (1,2).
68 th Montagna Symposium on the Biology of Skin “Decoding Complex Skin Diseases: Integrating Genetics, Genomics, and Disease Biology”

The 68 th Montagna Symposium on the Biology of the Skin was held from October 10–14, 2019, at Salishan Lodge in Gleneden Beach, Oregon. The theme of the meeting was “Decoding Complex Skin Diseases: Integrating Genetics, Genomics, and Disease Biology”. The meeting emphasized integration of multiple themes and disciplines to better understand some of the most common skin diseases, ranging from psoriasis to alopecia areata to vitiligo to lupus erythematosus to atopic dermatitis and food allergy. Promising therapeutic strategies are emerging for all of these diseases, providing clues for ways to connect the bench to the bedside. A common thread was the success of genome-wide association studies (GWAS), which have highlighted the importance of regulatory signals vs. coding variation. These diseases also share an environmental component linked to immune system function. Hence, beyond GWAS studies, this meeting focused on gene regulatory mechanisms, the “single-cell revolution”, in vivo systems for dissection of disease pathogenesis, and the relationship between genetics and environment in the context of host defense. We concluded with a “Translational Roundtable” designed to explore how these interrelated fields can best be directed towards long term disease control, and ultimately, cure.
Prospective Study Evaluating the Impact of Tissue Conﬁrmation of Metastatic Disease in Patients With Breast Cancer

Purpose Decisions about treatment for women with metastatic breast cancer are usually based on the estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) status of the primary tumor. Retrospective data suggest that discordance between primary and metastatic lesions leads to detrimental outcome. This prospective study investigated receptor status of primary tumors and metastases in the same patient and assessed the impact of discordance on patient management and survival. Patients and Methods Biopsies of suspected metastases were analyzed for ER, PgR, and HER2 . Primary tumors and metastases were analyzed using similar methodology. The treating oncologist indicated a treatment plan before and after biopsy to determine whether the result inﬂuenced management. Patients were followed up for progression or death.
Circulating Angiogenic Factors Associated with Response and Survival in Patients with Acute Graft-Versus-Host Disease: Results from BMT CTN 0302 and 0802 Biol Blood Marrow Transplant .

Circulating angiogenic factors (AF) reflect tissue healing capacity, although some AF can also contribute to inflammation and are indicative of endothelial dysfunction. The AF milieu in acute graft-versus-host disease (aGVHD) has not been broadly characterized. We hypothesized that patients with abundant AF involved in repair/regeneration vs. those mediating damage/ inflammation would have improved outcomes. Circulating AF known predominantly for repair/ regeneration (epidermal growth factor [EGF], fibroblast growth factor-1 and -2, heparin binding-EGF-like growth factor, vascular endothelial growth factor-A, -C, and -D) and for damage/ inflammation (angiopoietin-2, endothelin-1, soluble endoglin [sEng], follistatin [FS], leptin, placental growth factor [PlGF]) were measured in a discovery set of HCT recipients with grade III/IV aGVHD versus controls, then validated in two aGVHD cohorts enrolled in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials 0302 (N=105, serum) and 0802 (N=158, plasma) versus controls without aGVHD (N=53, serum). Levels of EGF and VEGF-A were lower than controls at the onset of aGVHD in both trials and higher with complete response to first-line aGVHD therapy in CTN 0802. FS and PlGF were elevated in aGVHD measured in either serum or plasma. At day 28 after initial aGVHD therapy, elevated FS was an independent negative prognostic factor for survival in both cohorts (hazard ratio 9.3 in CTN 0302, 2.8 in CTN 0802). These data suggest that circulating AF are associated with clinical outcomes after aGVHD and thus may contribute to both pathogenesis and recovery.
Neuromodulation Special Issue Transcranial electric stimulation as a neural interface to gain insight on human brain functions: current knowledge and future perspective

The use of brain stimulation approaches in social and affective science has greatly increased over the last two decades. The interest in social factors has grown along with technological advances in brain research. Transcranial electric stimulation (tES) is a research tool that allows scientists to establish contributory causality between brain functioning and social behaviour, therefore deepening our understanding of the social mind. Preliminary evidence is also starting to demonstrate that tES, either alone or in combination with pharmacological or behavioural interventions, can alleviate the symptomatology of individuals with affective or social cognition disorders. This review offers an overview of the application of tES in the field of social and affective neuroscience. We discuss the issues and challenges related to this application and suggest an avenue for future basic and translational research. the causal contribution of this region to decision-making and pain perception,transcranial magnetic stimulation (TMS) and tDCS-based perturbational approaches were applied over the primary somatosensory cortex. The integration of different neuroimaging and neuromodulation methods used in this study could represent an ideal methodological approach to correlate a brain area to social and affective cognition. thereby enhancing ecological validity without compromising internal validity. A recent pilot study on 12 veterans with warzone-related post-traumatic stress disorder (PTSD) delivered tDCS over the ventromedial PFC during six virtual reality sessions (van’t Wout-Frank et .,2019). The virtual reality setting provided combat-related multisensory information, including visual, auditory, olfactory and haptic information. Results showed that active tDCS reduced the arousal in response to PTSD-related information compared to sham. This study showed that the application of tDCS in virtual reality set-tingsis technicallyfeasibleand promising.Futurestudies should take advantage of the portability of tES and investigate the neural correlates of social cognition by immersing participants in settings that are as close as possible to real-life situations and social interactions.
Chromogenic In Situ Hybridization for (cid:1) 6 (cid:2) 4 Integrin in Breast Cancer Correlation with Protein Expression

The (cid:1) 6 (cid:2) 4 integrin is the receptor for the basement membrane protein laminin-5. Recent studies suggest that (cid:1) 6 (cid:2) 4 integrin expression in invasive breast carcinomas may be a poor prognostic factor. Because we have not had reliable results with commercially available antibodies for the immunohistochemical detection of (cid:1) 6 (cid:2) 4 integrin in archival paraffin-embedded tissues, we designed a probe to detect (cid:2) 4 integrin subunit mRNA in paraffin sections. In situ hybridization for (cid:2) 4 mRNA was performed on paraffin-embed-ded tissue sections of 25 invasive breast carcinomas using a hyperbiotinylated oligonucleotide DNA probe. Immunohistochemical staining was performed on corrresponding frozen tumor sections using two commercially available antibodies to the (cid:2) 4 integrin subunit. All cases positive for (cid:2) 4 protein by one or both antibodies were also positive for (cid:2) 4 mRNA by in situ hybridization, but three cases with (cid:2) 4 mRNA expression were negative by immunohistochemistry with both antibodies. These findings suggest that in situ hybridization appears to be a sensitive method for detecting (cid:2) 4 integrin mRNA, but it appears to identify some cases that either lack (cid:2) 4 protein or express variants not recognized with commercial antibodies directed to particular extracellular or cytoplasmic domains. (J Mol Diagn 2004, 6:10–15) Integrins are that serve as the principal cell proteins.
Case study of virtual reality in CNC machine tool exhibition

Exhibition and demonstration are generally used in the promotion and sale-assistance of manufactured products. However, the transportation cost of the real goods from the vender factory to the exposition venue is generally expensive for huge and heavy commodity. With the advancement of computing, graphics, mobile apps, and mobile hardware the 3D visibility technology is getting more and more popular to be adopted in visual-assisted communication such as amusement games. Virtual reality (VR) technology has therefore being paid great attention in emulating expensive small and/or huge and heavy equipment. Virtual reality can be characterized as 3D extension with Immersion, Interaction and Imagination. This paper was then be focused on the study of virtual reality in the assistance of CNC machine tool demonstration and exhibition. A commercial CNC machine tool was used in this study to illustrate the effectiveness and usability of using virtual reality for an exhibition. The adopted CNC machine tool is a large and heavy mill-turn machine with the width up to eleven meters and weighted about 35 tons. A head-mounted display (HMD) was attached to the developed VR CNC machine tool for the immersion viewing. A user can see around the 3D scene of the large mill-turn machine and the operation of the virtual CNC machine can be actuated by bare hand. Coolant was added to demonstrate more realistic operation while collision detection function was also added to remind the operator. The developed VR demonstration system has been presented in the 2017 Taipei International Machine Tool Show (TIMTOS 2017). This case study has shown that young engineers and/or students are very impressed by the VR-based demonstration while elder persons could not adapt themselves easily to the VR-based scene because of eyesight issues. However, virtual reality has successfully being adopted and integrated with the CNC machine tool in an international show. Another machine tool on laser-assisted milling machine motion simulation has also been successfully conducted to show the expandability of the VR based technology. One can conclude that VR will be adopted and paid more and more attention in the future in helping CNC machine tool promotion. Further study could be extended to education and training system, and also for the maintenance system, too.
Analysis of Ca v 1.2 and Ryanodine Receptor Clusters in Rat Ventricular Myocytes

We analyzed the distribution of ryanodine receptor (RyR) and Ca v 1.2 clusters in adult rat ventricular myocytes using three-dimensional object-based colocalization metrics. We found that ~75% of the Ca v 1.2 clusters and 65% of the RyR clusters were within couplons, and both were roughly two and a half times larger than their extradyadic counterparts. Within a couplon, Ca v 1.2 was concentrated near the center of the underlying RyR cluster and accounted for ~67% of its size. These data, together with previous ﬁndings from binding studies, enable us to estimate that a couplon contains 74 RyR tetramers and 10 copies of the a -subunit of Ca v 1.2. Extradyadic clusters of RyR contained ~30 tetramers, whereas the extradyadic Ca v 1.2 clusters contained, on average, only four channels. Between 80% and 85% of both RyR and Ca v 1.2 molecules are within couplons. RyR clusters were in the closest proximity, with a median nearest-neighbor distance of 552 nm; comparable values for Ca v 1.2 clusters and couplons were 619 nm and 735 nm, respectively. Extradyadic RyR clusters were signiﬁcantly closer together (624 nm) and closer to the couplons (674 nm) than the couplons were to each other. In contrast, the extradyadic clusters of Ca v 1.2 showed no preferential localization and were broadly distributed. These results provide a wealth of morphometric data that are essential for understanding intracellular Ca 2 þ regulation and modeling Ca 2 þ dynamics. A ﬂuorophore and vice versa. The are object which allows us relationship between the make up the dyad. Speciﬁcally, if the two components of the dyad overlap each other’s brightest points, they are considered to be colocalized even if the number of voxels in one component is than the From this information we derive two metrics: the are colocalized, and voxels within colocalized Nearest-neighbor distances were calculated the centers these These and methodology used to calculate them are described in detail in al. We determined the of the cell by identifying the coordinates of the cell surface using the algorithm developed by Lifshitz et al. and described detail by Scriven et al. We then directly determined the according to the of inside
Application of low tube potentials in coronary CT angiography: Results from the PROTECTION VI study

Objectives: The aim of this study was to assess the utilization of low tube potentials for coronary computed tomography angiography (CCTA) in worldwide clinical practice and its influence on radiation exposure, contrast agent volume and image quality. Background: CCTA is frequently employed in clinical practice. Lowering of tube potential is a potent method to reduce radiation exposure and to economize contrast agent volume. Methods: CCTAs of 4,006 patients from 61 international study sites were analyzed regarding very-low (≤80-kVp), low (90–100-kVp), conventional (110–120-kVp) and high (≥130-kVp) tube potentials. The impact on dose-length product (DLP) and contrast agent volume was analyzed. Image quality was determined by evaluation of the diagnostic applicability and assessment of the objective image parameters signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR). Results: When compared to conventional tube potentials, low tube potentials were used in 56% of CCTAs (≤80-kVp: 9%; 90–100-kVp: 47%), which varied among sites from 0% to 100%. Tube potential reduction was associated with low cardiovascular risk profile, low body-mass-index (BMI) and new-generation scanners. Median radiation exposure was lowered by 68% or 50%, and median contrast agent volume by 25% or 13% for tube potential protocols of ≤80-kVp or 90–100-kVp when compared to conventional tube potentials, respectively (all p<0.001). With the use of lower tube potentials, the frequency of diagnostic scans was maintained (p=0.41), while SNR and CNR significantly improved (both p<0.001). Considering BMI eligibility criteria, 58% (n=946) conventionally scanned patients would have been suitable for low tube potential protocols, and 44% (n=831) of patients scanned with 90–100-kVp would have been eligible for very-low tube potential CCTA imaging of ≤80-kVp. Conclusions: This large international registry confirms the feasibility of tube potential reduction in clinical practice leading to lower radiation exposure and lower contrast volumes. The current registry also demonstrates that this strategy is still underutilized in daily practice.
Reptation theory of ion channel gating

Reptation theory is a highly successful approach for describing polymer dynamics in entangled systems. In turn, this molecular process is the basis of viscoelasticity. We apply a modified version of reptation dynamics to develop an actual physical model of ion channel gating. We show that at times longer than microseconds these dynamics predict an a-helix-screw motion for the amphipathic protein segment that partially lines the channel pore. Such motion has been implicated in several molecular mechanics studies of both voltage-gated and transmitter-gated channels. The experimental probability density function (pdf) for this process follows t-312 which has been observed in several experimental systems. Reptation theory predicts that channel gating will occur on the milli-second time scale and this is consistent with experimental results from sin-gle-channel recording. We examine the consequences of reptation over random barriers and we show that, to first order, the pdf remains unchanged. In the case of a charged helix undergoing reptation in the presence of a transmembrane potential we show that the tail of the pdf will be exponential. We provide a list of practical experimental predictions to test the validity of this physical theory.
Tumour immune landscape of paediatric high-grade gliomas

Over the past decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumours. It has become evident that paediatric high-grade gliomas differ from those in adults with respect to multiple defining aspects including: DNA copy number, gene expression profiles, tumour locations within the CNS and genetic alterations such as somatic histone mutations. Despite these advances, clinical trials for children with gliomas have historically been based on ineffective adult regimens that fail to take into consideration the fundamental biological differences between the two. Additionally, although our knowledge of the intrinsic cellular mechanisms driving tumour progression has considerably expanded, little is known about the dynamic tumour immune microenvironment in paediatric high-grade gliomas. In this review, we explore the genetic and epigenetic landscape of these gliomas and how this drives the creation of specific tumour subgroups with meaningful survival outcomes. Further, we provide a comprehensive analysis of the paediatric high-grade glioma tumour immune microenvironment and discuss emerging therapeutic efforts aimed at exploiting the immune functions of these tumours.
SPECIAL SERIES: LOCOREGIONAL MANAGEMENT OF BREAST CANCER

The widespread adoption of screening mammography in the United States has led to an associated increase in the incidence of both ductal carcinoma in situ (DCIS; stage 0 breast cancer) and early-stage invasive breast cancer. One study has estimated that in the United States alone, the incidence of early-stage breast cancer has more than doubled in the last three decades, with this increase almost exclusively observed in women of screening age,$ 40 years. Outcomes following current treatment guidelines for stage 0 and I breast cancer are excellent; between 2009 and 2015, 62% of new breast cancer was localized to the breast at the time of diagnosis, and the 5-year mortality for these early-stage patients was 98.8%.
Active Vibration Control of Passenger Seat in Quarter Car Model using Supertwisting Controller

The objective of present study is vibartion control of passenger seat in active quarter car model having three degrees of freedom. Passenger ride comfort issues are considered under random road excitation using simulation work in time and frequency domain. The designed supertwisting controller is applied in main suspension of active quarter car model. The proposed controller showed effectiveness in vibration suppression of passenger seat acceleration and displacement responses as compared to passive one. Simulation work in graphical and mathematical results showed the superior performance of the designed supertwisting sliding mode controller.