Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of RAD51-like genes in the repair of DNA damage in mammalian cells

Homologous recombination (HR) is essential for the repair of severe forms of DNA damage such as double strand breaks and interstrand cross-links. The highly conserved RAD51 protein is central to this process and forms nucleoprotein filaments on ssDNA that catalyse strand exchange. In mammalian cells, five genes that share sequence homology with RAD51 have been identified; XRCC2, XRCC3, RAD5JL1, RAD51L2 and RAD51L3 . Interactions amongst the RAD51-like proteins have been demonstrated but at present little is known about their functions in HR. Progress has been hampered in the cases of RAD5lLl, -L2 and -L3, which were identified through database homology searches, because of a lack of suitable mutant cell lines in which to study them. Cultured mammalian cell lines, selected for sensitivity to DNA-damaging agents, have been used to clone and characterise the function of genes from several DNA repair pathways. The irs3 cell line was isolated from the Chinese hamster line V79-4 in a screen for radiosensitive mutants and has a unique genetic defect. irs3 cells are sensitive to X-rays (2-fold), ethyl methanesulphonate (2.5-fold) and especially mitomycin-C (MMC) (7-fold), as well as showing chromosomal instability. In this study, the sensitivity of irs3 to DNA-damaging agents was found to be substantially complemented by expression of the human RAD51L2 gene, but not other RAD51 -like genes or RAD51 itself. An increased level of spontaneous chromosome aberrations was also complemented by RAD51L2 cDNA expression. irs3 cells were found to have little or no RAD51L2 cDNA and RAD51L2 protein. This is likely due to a G → T base substitution at the first nucleotide of exon 6 in the hamster RAD51L2 gene, which encodes an amino acid change of Val to Phe and disrupts the exon 6 3' acceptor splice site. In collaboration with Dr. Jean-Yves Masson and Dr. Steve West (Cancer Research UK, Clare Hall Laboratories, London), two RAD51 -like protein complexes were shown to exist in hamster cells as they do in human cells. Strikingly, neither complex is formed in irs3. Site-directed mutagenesis of the invariant lysine in the RAD51L2 Walker A box ATP-binding domain showed that this residue is required for MMC resistance. Consistent with a role in HR, -the RAD51L2 protein was found to localise to the nucleus. This localisation was dependent on the eleven amino acids at the C-terminus of the protein. irs3 cells showed a reduced number of MMC-induced sister chromatid exchanges compared to wild type cells. irs3 cells were also found to be defective in damage-dependent RAD51 focus formation, providing the first evidence that RAD51L2 is involved in repair via RAD51-dependent HR. Using the I-Scel endonuclease to generate a double strand break, it was found that gene conversion is decreased 7-fold in irs3 compared to wild type cells. In summary, this study provides data which identify irs3 as a RAD51L2-deficient cell line and demonstrate that RAD51L2 plays a key role in RAD51-dependent HR processes.
Aerosol activation in warm clouds

C. R. Hoyle, C. S. Webster, H. E. Rieder, E. Hammer, M. Gysel, N. Bukowiecki, E. Weingartner, M. Steinbacher, and U. Baltensperger Laboratory of Atmospheric Chemistry, Paul Scherrer Institute, Villigen, Switzerland Swiss Federal Institute for Forest Snow and Landscape Research (WSL)-Institute for Snow and Avalanche Research (SLF), Davos, Switzerland Wegener Center for Climate and Global Change and IGAM/Department of Physics University of Graz, Austria Austrian Polar Research Institute, Vienna, Austria Laboratory for Air Pollution/Environmental Technology, Empa – Swiss Federal Laboratories for Materials Science and Technology, Ueberlandstrasse 129,8600 Duebendorf, Switzerland now at: Grolimund + Partner – Environmental Engineering, Thunstrasse 101a, 3006 Bern, Switzerland
Assessment of Zinc- alfa2 glycoprotein (ZAG) and Lipase Maturation Factor 1 (LMF1) concentration in children with chronic kidney disease.

ZAG (zinc-? 2-glycoprotein) - adipokine, may participate in the mechanism of malnutrition in chronic kidney disease (CKD) as cachexia factor. The transmembrane protein of the endoplasmic reticulum - lipase maturation factor 1 (LMF1) is necessary for the secretion and enzymatic activity of lipases and lowering triglycerides level. The aim of the study was to evaluate these markers - ZAG and LMF1, their potential importance in CKD in children. The study included 59 children and adolescents aged 10.7±5.0 years with CKD. Compared with healthy children, serum and urine ZAG levels were higher in children with CKD. A similar relationship was obtained in the comparison of girls and boys between the above groups. We showed a reduced serum and urine concentration of LMF1 in children with CKD. Additionally, ZAG and LMF1 levels in children below 10 years of age and above 10 were no different. There was also no correlation between these markers and serum creatinine (except negative correlation of urinary ZAG), albumin, cholesterol, triglycerides. LMF1 concentration correlated positively with vitamin D level in dialyzed patients. To conclude, elevated serum ZAG levels in children with CKD document that selective kidney damage results in the rise of ZAG concentration, however the specific role of this marker in malnutrition was not documented. Reduced serum LMF1 concentration in children with CKD, did not correlate with standard parameters used to assess lipid metabolism and severity of CKD. The usefulness of LMF1 as the marker of the lipid metabolism disturbances in children with CKD was not proven.
High-Fat-Diet–Induced Oxidative Stress Linked to the Increased Colonization of Lactobacillus sakei in an Obese Population

Lactobacillus provides many health benefits; its various species are widely used as probiotics. However, an increased abundance of Lactobacillus has been reported in obesity, and the role of Lactobacillus strains in obesity remains unknown. ABSTRACT Obesity is a major public health problem related to various chronic health conditions. Lactobacillus species has been reported in obese individuals; however, its role is unknown. We compared the abundance and composition of Lactobacillus species by analyzing feces from 64 healthy control subjects and 88 obese subjects. We isolated one Lactobacillus strain from the feces of a subject with obesity and further analyzed its genetic and molecular features. We found that an increased abundance and higher prevalence of Lactobacillus sakei distinguished the fecal microbiota of the obese group from that of healthy subjects and that it was related to the increased levels of reactive oxygen species (ROS) induced by higher fat intake. The L. sakei ob4.1 strain, isolated from the feces of a subject with obesity, showed high catalase activity, which was regulated by oxidative stress at the gene transcription level. L. sakei ob4.1 maintained colon epithelial cell adhesion ability under ROS stimulation, and treatment with saturated fatty acid increased colon epithelial ROS levels in a dose-dependent manner; however, L. sakei ob4.1 did not change the level of fat-induced colon epithelial ROS. Exposing mice to a high-fat diet revealed that high-fat-diet–induced colon ROS was associated with the increased colonization of L. sakei ob4.1 through catalase activity. Four-week supplementation with this strain in mice fed a high-fat diet did not change their body weights or ROS levels. A high-fat diet induces changes in the colon environment by increasing ROS levels, which provides a colonization benefit to an L. sakei strain with high catalase activity. IMPORTANCE Lactobacillus provides many health benefits; its various species are widely used as probiotics. However, an increased abundance of Lactobacillus has been reported in obesity, and the role of Lactobacillus strains in obesity remains unknown. We found a high abundance of the Lactobacillus sakei species in a group of obese subjects and examined its relationship with a high-fat diet and reactive oxygen species (ROS) in the feces. To find the underlying mechanism, we analyzed and characterized an L. sakei strain isolated from a severely obese individual. We found that higher gut oxidative stress could link high-fat-diet–induced obesity and L. sakei. This translational research identifies the roles of the host gut environment in the colonization and survival of L. sakei.
In Case of Invasive Nodule, Break Ground Glass

interstitial lung diseases. Am J Respir Crit Care Med 2019;199: 1249–1256. 4. Troy LK, Grainge C, Corte TJ, Williamson JP, Vallely MP, Cooper WA, et al.; Cryobiopsy versus Open Lung biopsy in the Diagnosis of Interstitial lung disease alliance (COLDICE) Investigators. Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study. Lancet Respir Med 2020;8:171–181. 5. Johannson KA, Marcoux VS, Ronksley PE, Ryerson CJ. Diagnostic yield and complications of transbronchial lung cryobiopsy for interstitial lung disease. A systematic review and metaanalysis. Ann Am Thorac Soc 2016;13:1828–1838. 6. Raghu G, Flaherty KR, Lederer DJ, Lynch DA, Colby TV, Myers JL, et al. Use of a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples: a prospective validation study. Lancet Respir Med 2019;7:487–496. 7. Richeldi L, Scholand MB, Lynch DA, Colby TV, Myers JL, Groshong SD, et al. Utility of a molecular classifier as a complement to high-resolution computed tomography to identify usual interstitial pneumonia. Am J Respir Crit Care Med 2021;203:211–220. 8. Adams DC, Hariri LP, Miller AJ, Wang Y, Cho JL, Villiger M, et al. Birefringence microscopy platform for assessing airway smooth muscle structure and function in vivo. Sci Transl Med 2016;8: 359ra131. 9. Kirby M, Ohtani K, Lopez Lisbona RM, Lee AM, Zhang W, Lane P, et al. Bronchial thermoplasty in asthma: 2-year follow-up using optical coherence tomography. Eur Respir J 2015;46:859–862. 10. Lam S, Standish B, Baldwin C, McWilliams A, leRiche J, Gazdar A, et al. In vivo optical coherence tomography imaging of preinvasive bronchial lesions. Clin Cancer Res 2008;14:2006–2011. 11. Hariri LP, Mino-Kenudson M, Lanuti M, Miller AJ, Mark EJ, Suter MJ. Diagnosing lung carcinomas with optical coherence tomography. Ann Am Thorac Soc 2015;12:193–201. 12. Hariri LP, Applegate MB, Mino-Kenudson M, Mark EJ, Medoff BD, Luster AD, et al. Volumetric optical frequency domain imaging of pulmonary pathology with precise correlation to histopathology.Chest 2013; 143:64–74. 13. Nandy S, Raphaely RA, Muniappan A, Shih A, Roop BW, Sharma A, et al. Diagnostic accuracy of endobronchial optical coherence tomography for the microscopic diagnosis of usual interstitial pneumonia. Am J Respir Crit Care Med 2021;204:1164–1179. 14. Hariri LP, Adams DC, Wain JC, Lanuti M, Muniappan A, Sharma A, et al. Endobronchial optical coherence tomography for low-risk microscopic assessment and diagnosis of idiopathic pulmonary fibrosis in vivo. Am J Respir Crit Care Med 2018;197:949–952.
Upslope migration of snow avalanches in a warming climate

Significance Snow avalanches represent a major threat in mountain environments, where they cause damage to critical infrastructure and claim hundreds of lives every year. Here, we document an unambiguous upslope migration of snow avalanches with climate change, a physical mechanism whose existence could previously not be demonstrated. In the Vosges Mountains, we show evidence that winter warming of +1.35 °C induced a sevenfold reduction in the number of avalanches, as well as a reduction of their magnitude and shortening of the avalanche season. These results show that low-to-medium elevation mountain ranges may serve as sentinels to anticipate future changes in snow processes and related risks in higher mountain environments and could thus help in the design of efficient adaptation strategies. Snow is highly sensitive to atmospheric warming. However, because of the lack of sufficiently long snow avalanche time series and statistical techniques capable of accounting for the numerous biases inherent to sparse and incomplete avalanche records, the evolution of process activity in a warming climate remains little known. Filling this gap requires innovative approaches that put avalanche activity into a long-term context. Here, we combine extensive historical records and Bayesian techniques to construct a 240-y chronicle of snow avalanching in the Vosges Mountains (France). We show evidence that the transition from the late Little Ice Age to the early twentieth century (i.e., 1850 to 1920 CE) was not only characterized by local winter warming in the order of +1.35 °C but that this warming also resulted in a more than sevenfold reduction in yearly avalanche numbers, a severe shrinkage of avalanche size, and shorter avalanche seasons as well as in a reduction of the extent of avalanche-prone terrain. Using a substantial corpus of snow and climate proxy sources, we explain this abrupt shift with increasingly scarcer snow conditions with the low-to-medium elevations of the Vosges Mountains (600 to 1,200 m above sea level [a.s.l.]). As a result, avalanches migrated upslope, with only a relict activity persisting at the highest elevations (release areas >1,200 m a.s.l.). This abrupt, unambiguous response of snow avalanche activity to warming provides valuable information to anticipate likely changes in avalanche behavior in higher mountain environments under ongoing and future warming.
Protective-Ventilation Strategies Studied by Dynamic Positron Emission Tomography

Borges, J. B. 2014. Regional Lung Kinetics of Ventilator-Induced Lung Injury and ProtectiveVentilation Strategies Studied by Dynamic Positron Emission Tomography. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1018. 68 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9003-4. Mechanical ventilation in itself can harm the lung and cause ventilator-induced lung injury (VILI), which can induce or aggravate acute respiratory distress syndrome (ARDS). Much debate remains over pivotal concepts regarding the pathophysiology of VILI, especially about the precise contribution, kinetics, and primary role of potential VILI mechanisms. Consequently, it remains largely unknown how best to design a well-timed and full-bodied mechanical ventilation strategy. Little is known also about small airways dysfunction in ARDS. Dynamic positron emission tomography (PET) with [F]fluoro-2-deoxy-D-glucose (F-FDG) can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We studied the regional evolution of inflammation using dynamic PET/CT imaging of F-FDG in VILI and during different lung-protective mechanical ventilation strategies. By dynamic CT we investigated also the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction. Piglets were submitted to an experimental model of early ARDS combining repeated lung lavages and injurious mechanical ventilation. The animals were subsequently studied during sustained VILI, or submitted to distinct approaches of lung-protective mechanical ventilation: the one recommended by the ARDS Network (ARDSNet), or to one defined as open lung approach (OLA). The normally and poorly aerated regions corresponding to intermediate gravitational zones were the primary targets of the inflammatory process accompanying early VILI, which may be attributed to the small volume of the aerated lung that receives most of ventilation. The ARDSNet strategy did not attenuate global pulmonary inflammation during 27h and led to a concentration of inflammatory activity in the upper and poorly aerated lung regions. The OLA, in comparison with the ARDSNet approach, resulted in sustained and better gas exchange and lung mechanics. Moreover, the OLA strategy resulted in less global and regional inflammation. Dynamic CT data suggested that a significant amount of airway closure and related reabsorption atelectasis occurs in acute lung injury. Whether potential distal bronchioles injury (“bronchiolotrauma”) is a critical and decisive element in ventilator-associated lung injury is a matter for future studies.
The anatomic, clinical, and physiologic correspondences of myofascial trigger points and classical acupuncture points

: Chronic musculoskeletal pain conditions are among the most common presenting complaints of patients seeking health care treatments. These chronic pain conditions result in disability, reduced quality of life, and significant health system economic burdens. Myofascial pain syndrome (MPS) is the most common chronic musculoskeletal pain condition, and its prevalence increases with age. Given the average age of individuals globally is increasing as is the average human lifespan, socioeconomic and healthcare burdens related to MPS will rise in the coming decades. The allopathic medicine standard for treating MPS is outlined in the Trigger Point Manual , which illustrates >200 of the “most common” myofascial trigger point (mTrP) locations, their clinical (pain and non-pain) indications, and their myofascial referred-pain patterns. Though early MPS practitioners typically administered local anesthetic and/or corticosteroid injections to deactivate mTrPs, the Trigger Point Manual documents dry needling of mTrPs is similarly effective. Over the past 2–3 decades In the United States, there has been significant growth of dry needling skill certification of physical and occupational therapists, who utilize acupuncture needles to deactivate mTrPs. There has been controversy since the 1970’s regarding whether any anatomic and/or physiologic relationship exists between these “most common” mTrPs and their referred-pain patterns described by allopathic researchers, and the classical acupuncture points and primary channels described by Traditional Chinese Medicine some 2,000 years previously. If these “most common” mTrPs and classical acupoints can be shown to be similar anatomically, clinically, and physiologically, this would not only allow integration of ancient and contemporary clinical and research databases to optimally treat MPS, but also would have potential importance in elucidating acupuncture’s mechanisms. This review summarizes prior literature findings regarding the anatomic, clinical, and physiologic correspondences of the “most common” mTrPs and classical acupoints, and the clinical and research implications of these relationships.
An Empirical Study on Data Validation Methods of Delphi and General Consensus

Data collection and review are the building blocks of academic research regardless of the discipline. The gathered and reviewed data, however, need to be validated in order to obtain accurate information. The Delphi consensus is known as a method for validating the data. However, several studies have shown that this method is time-consuming and requires a number of rounds to complete. Until now, there has been no clear evidence that validating data by a Delphi consensus is more significant than by a general consensus. In this regard, if data validation between both methods are not significantly different, then just using a general consensus method is sufficient, easier, and less time-consuming. Hence, this study aims to find out whether or not data validation by a Delphi consensus method is more significant than by a general consensus method. This study firstly collected and reviewed the data of sustainable building criteria, secondly validated these data by applying each consensus method, and finally made a comparison between both consensus methods. The results showed that seventeen of the valid criteria obtained from the general consensus and reduced by the Delphi consensus were found to be inconsistent for sustainable building assessments in Cambodia. Therefore, this study concludes that using the Delphi consensus method is more significant in validating the gathered and reviewed data. This experiment contributes to the selection and application of consensus methods in validating data, information, or criteria, especially in engineering fields.
Deep Layer-wise Networks Have Closed-Form Weights

There is currently a debate within the neuroscience community over the likelihood of the brain performing backpropagation (BP). To better mimic the brain, training a network $\textit{one layer at a time}$ with only a"single forward pass"has been proposed as an alternative to bypass BP; we refer to these networks as"layer-wise"networks. We continue the work on layer-wise networks by answering two outstanding questions. First, $\textit{do they have a closed-form solution? }$ Second, $\textit{how do we know when to stop adding more layers? }$ This work proves that the kernel Mean Embedding is the closed-form weight that achieves the network global optimum while driving these networks to converge towards a highly desirable kernel for classification; we call it the $\textit{Neural Indicator Kernel}$.
Low-Cost On-device Partial Domain Adaptation (LoCO-PDA): Enabling efficient CNN retraining on edge devices

With the increased deployment of Convolutional Neural Networks (CNNs) on edge devices, the uncertainty of the observed data distribution upon deployment has led researchers to to utilise large and extensive datasets such as ILSVRC'12 to train CNNs. Consequently, it is likely that the observed data distribution upon deployment is a subset of the training data distribution. In such cases, not adapting a network to the observed data distribution can cause performance degradation due to negative transfer and alleviating this is the focus of Partial Domain Adaptation (PDA). Current works targeting PDA do not focus on performing the domain adaptation on an edge device, adapting to a changing target distribution or reducing the cost of deploying the adapted network. This work proposes a novel PDA methodology that targets all of these directions and opens avenues for on-device PDA. LoCO-PDA adapts a deployed network to the observed data distribution by enabling it to be retrained on an edge device. Across subsets of the ILSVRC12 dataset, LoCO-PDA improves classification accuracy by 3.04pp on average while achieving up to 15.1x reduction in retraining memory consumption and 2.07x improvement in inference latency on the NVIDIA Jetson TX2. The work is open-sourced at \emph{link removed for anonymity}.