Miracle-dz/UniFAR-FTUs huggingface dataset:
Nucleostemin deletion reveals an essential mechanism that maintains the genomic stability of stem and progenitor cells

Stem and progenitor cells maintain a robust DNA replication program during the tissue expansion phase of embryogenesis. The unique mechanism that protects them from the increased risk of replication-induced DNA damage, and hence permits self-renewal, remains unclear. To determine whether the genome integrity of stem/progenitor cells is safeguarded by mechanisms involving molecules beyond the core DNA repair machinery, we created a nucleostemin (a stem and cancer cell-enriched protein) conditional-null allele and showed that neural-specific knockout of nucleostemin predisposes embryos to spontaneous DNA damage that leads to severe brain defects in vivo. In cultured neural stem cells, depletion of nucleostemin triggers replication-dependent DNA damage and perturbs self-renewal, whereas overexpression of nucleostemin shows a protective effect against hydroxyurea-induced DNA damage. Mechanistic studies performed in mouse embryonic fibroblast cells showed that loss of nucleostemin triggers DNA damage and growth arrest independently of the p53 status or rRNA synthesis. Instead, nucleostemin is directly recruited to DNA damage sites and regulates the recruitment of the core repair protein, RAD51, to hydroxyurea-induced foci. This work establishes the primary function of nucleostemin in maintaining the genomic stability of actively dividing stem/progenitor cells by promoting the recruitment of RAD51 to stalled replication-induced DNA damage foci.
Partitioned Group Password-Based Authenticated Key Exchange

Group Password-Based Authenticated Key Exchange (GPAKE) allows a group of users to establish a secret key, as long as all of them share the same password. However, in existing GPAKE protocols as soon as one user runs the protocol with a non-matching password, all the others abort and no key is established. In this paper we seek for a more flexible, yet secure, GPAKE and put forward the notion of partitioned GPAKE. Partitioned GPAKE tolerates users that run the protocol on different passwords. Through a protocol run, any subgroup of users that indeed share a password, establish a session key, factoring out the “noise” of inputs by users holding different passwords. At the same time any two keys, each established by a different subgroup of users, are pair-wise independent if the corresponding subgroups hold different passwords. We also introduce the notion of password-privacy for partitioned GPAKE, which is a kind of affiliation hiding property, ensuring that an adversary should not be able to tell whether any given set of users share a password. Finally, we propose an efficient instantiation of partitioned GPAKE building on an unforgeable symmetric encryption scheme and a PAKE by Bellare et al. [6]. Our proposal is proven secure in the random oracle/ideal cipher model, and requires only two communication rounds.
Reliability assessment of AlGaN/GaN HEMT technology on SiC for 48V applications

We present wearout reliability assessment of GaN HEMTs fabricated on SiC. Based on 3 temperature 48 V dc stress tests and using a failure criterion of 10% reduction in Idss, the 60% confidence interval on estimate of Ea was [2.00,2.94] eV and the predicted 60% confidence interval on estimate of MTTF at Tj=200 degC was [1.0 x 106, 3.0 x 107] hours. To compare the impact of dc and RF stress, additional experiments were conducted on a smaller sample set and the results indicate that the impact of dc and RF stress is not significantly different.
Planning with Incomplete Information as Heuristic Search in Belief Space

The formulation of planning as heuristic search with heuristics derived from problem representations has turned out to be a fruitful approach for classical planning. In this paper, we pursue a similar idea in the context planning with incomplete information. Planning with incomplete information can be formulated as a problem of search in belief space, where belief states can be either sets of states or more generally probability distribution over states. While the formulation (as the formulation of classical planning as heuristic search) is not particularly novel, the contribution of this paper is to make it explicit, to test it over a number of domains, and to extend it to tasks like planning with sensing where the standard search algorithms do not apply. The resulting planner appears to be competitive with the most recent conformant and contingent planners (e.g., CGP, SGP, and CMBP) while at the same time is more general as it can handle probabilistic actions and sensing, different action costs, and epistemic goals.
Efficient Polar Code Construction for Higher-Order Modulation

An efficient algorithm for the construction of polar codes for higher-order modulation is presented based on information- theoretic principles. The bit reliabilities after successive demapping are estimated using the LM-rate, an achievable rate for mismatched decoding. The successive demapper bit channels are then replaced by binary input Additive White Gaussian Noise (biAWGN) surrogate channels and polar codes are constructed using a Gaussian approximation (GA). This LM-rate Demapper GA (LM-DGA) construction is used to construct polar codes for several demapping strategies proposed in literature. For all considered demappers, the LM-DGA constructed polar codes have the same performance as polar codes constructed by Monte Carlo (MC) simulation, but the LM-DGA construction is much faster. For 64-QAM, spectral efficiency 3 bits/s/Hz, and block length 1536 bits, simulation results show that LM-DGA constructed polar codes with cyclic redundancy check and successive cancellation list decoding are 1 dB more power efficient than state-of-the-art AR4JA low-density parity- check codes.
Engineering a Novel Multifunctional Green Fluorescent Protein Tag for a Wide Variety of Protein Research

Background Genetically encoded tag is a powerful tool for protein research. Various kinds of tags have been developed: fluorescent proteins for live-cell imaging, affinity tags for protein isolation, and epitope tags for immunological detections. One of the major problems concerning the protein tagging is that many constructs with different tags have to be made for different applications, which is time- and resource-consuming. Methodology/Principal Findings Here we report a novel multifunctional green fluorescent protein (mfGFP) tag which was engineered by inserting multiple peptide tags, i.e., octa-histidine (8×His), streptavidin-binding peptide (SBP), and c-Myc tag, in tandem into a loop of GFP. When fused to various proteins, mfGFP monitored their localization in living cells. Streptavidin agarose column chromatography with the SBP tag successfully isolated the protein complexes in a native form with a high purity. Tandem affinity purification (TAP) with 8×His and SBP tags in mfGFP further purified the protein complexes. mfGFP was clearly detected by c-Myc-specific antibody both in immunofluorescence and immuno-electron microscopy (EM). These findings indicate that mfGFP works well as a multifunctional tag in mammalian cells. The tag insertion was also successful in other fluorescent protein, mCherry. Conclusions and Significance The multifunctional fluorescent protein tag is a useful tool for a wide variety of protein research, and may have the advantage over other multiple tag systems in its higher expandability and compatibility with existing and future tag technologies.
A Beta-Herpesvirus with Fluorescent Capsids to Study Transport in Living Cells

Fluorescent tagging of viral particles by genetic means enables the study of virus dynamics in living cells. However, the study of beta-herpesvirus entry and morphogenesis by this method is currently limited. This is due to the lack of replication competent, capsid-tagged fluorescent viruses. Here, we report on viable recombinant MCMVs carrying ectopic insertions of the small capsid protein (SCP) fused to fluorescent proteins (FPs). The FPs were inserted into an internal position which allowed the production of viable, fluorescently labeled cytomegaloviruses, which replicated with wild type kinetics in cell culture. Fluorescent particles were readily detectable by several methods. Moreover, in a spread assay, labeled capsids accumulated around the nucleus of the newly infected cells without any detectable viral gene expression suggesting normal entry and particle trafficking. These recombinants were used to record particle dynamics by live-cell microscopy during MCMV egress with high spatial as well as temporal resolution. From the resulting tracks we obtained not only mean track velocities but also their mean square displacements and diffusion coefficients. With this key information, we were able to describe particle behavior at high detail and discriminate between particle tracks exhibiting directed movement and tracks in which particles exhibited free or anomalous diffusion.
Endoplasmic Reticulum-Quality Control Chaperones Facilitate the Biogenesis of Cf Receptor-Like Proteins Involved in Pathogen Resistance of Tomato1[C][W]

Cf proteins are receptor-like proteins (RLPs) that mediate resistance of tomato (Solanum lycopersicum) to the foliar pathogen Cladosporium fulvum. These transmembrane immune receptors, which carry extracellular leucine-rich repeats that are subjected to posttranslational glycosylation, perceive effectors of the pathogen and trigger a defense response that results in plant resistance. To identify proteins required for the functionality of these RLPs, we performed immunopurification of a functional Cf-4-enhanced green fluorescent protein fusion protein transiently expressed in Nicotiana benthamiana, followed by mass spectrometry. The endoplasmic reticulum (ER) heat shock protein70 binding proteins (BiPs) and lectin-type calreticulins (CRTs), which are chaperones involved in ER-quality control, were copurifying with Cf-4-enhanced green fluorescent protein. The tomato and N. benthamiana genomes encode four BiP homologs and silencing experiments revealed that these BiPs are important for overall plant viability. For the three tomato CRTs, virus-induced gene silencing targeting the plant-specific CRT3a gene resulted in a significantly compromised Cf-4-mediated defense response and loss of full resistance to C. fulvum. We show that upon knockdown of CRT3a the Cf-4 protein accumulated, but the pool of Cf-4 protein carrying complex-type N-linked glycans was largely reduced. Together, our study on proteins required for Cf function reveals an important role for the CRT ER chaperone CRT3a in the biogenesis and functionality of this type of RLP involved in plant defense.
How Would You Recognise an Expert Coach if You Saw One?

Literature that frames coaching practice and specifically the formation and determination of expert coaching practice reveals a body of research that generally lacks continuity. Importantly, arguments relating to the instability of professional interpretations of coaching practice appear to stem from a penchant for subjective investigation. This analysis draws on an extensive review of peer-reviewed articles, chapters and books – all published within the last 35 years that address the notion of coaching practice. The key themes to emerge point to the idea that much of the research used to establish conceptual clarity fails to distinguish between highly organised or efficient coaching practice and expert coaching practice. This paper concludes with some suggestions from alternate paradigms and disciplines that suggest that expertise in interceptive sports coaching may be better theorised and suitably identified through a lens of the growing ideas surrounding the concept of ‘emergence’.
Residual Impact of Previous Injury on Musculoskeletal Characteristics in Special Forces Operators

Background Musculoskeletal injuries are a significant burden to United States Army Special Operations Forces. The advanced tactical skill level and physical training required of Army Special Operators highlights the need to optimize musculoskeletal characteristics to reduce the likelihood of suffering a recurrent injury. Purpose To identify the residual impact of previous injury on musculoskeletal characteristics. Study Design Cross-sectional study; Level of evidence, 3. Methods Isokinetic strength of the knee, shoulder, and back and flexibility of the shoulder and hamstrings were assessed as part of a comprehensive human performance protocol, and self-reported musculoskeletal injury history was obtained. Subjects were stratified based on previous history of low back, knee, or shoulder injury, and within-group and between-group comparisons were made for musculoskeletal variables. Results Knee injury analysis showed no significant strength or flexibility differences. Shoulder injury analysis found internal rotation strength of the healthy subjects (H) was significantly higher compared with injured (I) and uninjured (U) limbs of the injured group (H, 60.8 ± 11.5 percent body weight [%BW]; I, 54.5 ± 10.5 %BW; U, 55.5 ± 11.3 %BW) (P = .014 [H vs I] and P = .05 [H vs U]). The external rotation/internal rotation strength ratio was significantly lower in the healthy subjects compared with injured and uninjured limbs of the injured group (H, 0.653 ± 0.122; I, 0.724 ± 0.121; U, 0.724 ± 0.124) (P = .026 [H vs I] and P = .018 [H vs U]). Posterior shoulder tightness was significantly different between the injured and uninjured limb of the injured group (I, 111.6° ± 9.4°; U, 114.4° ± 9.3°; P = .008). The back injury analysis found no significant strength differences between the healthy and injured groups. Conclusion Few physical differences existed between operators with prior knee or back injury. However, operators with a previous history of shoulder injury demonstrated significantly less shoulder strength than uninjured operators as well as decreased shoulder flexibility on the injured side. All operators, regardless of prior injury, must perform the same tasks; therefore, a targeted injury rehabilitation/human performance training specifically focused on internal rotation strength and tightness of the posterior capsule may help reduce the risk for recurrence of injury. Operators presenting with musculoskeletal asymmetries and/or insufficient strength ratios may be predisposed to musculoskeletal injury. Clinical Relevance Specific fitness programs to compensate for deficiencies in strength and flexibility need to be designed that may reduce the risk of injuries in Special Forces Operators.
Forensic Casework Applications Using Y-PLEX™ 6 and Y-PLEX™ 5 Systems.

Analysis for Y-chromosome short tandem repeat (Y-STR) loci has become a useful tool in resolving difficult cases, particularly with evidence samples containing mixtures of male and female DNA. The Y-PLEX™ 6 and Y-PLEX™ 5 systems have been validated and used in forensic cases. A total of 188 samples, which included 127 evidence samples, have been analyzed using Y-PLEX™ 6 and Y-PLEX™ 5 systems. The evidence sample types included fingernails, sperm, epithelial cells, blood, and tissue. The results from five cases are discussed. The results from Y-PLEX™ 6 kits have accepted in several jurisdictions throughout the United States.
Genome Sequence of Thermophilic Bacillus licheniformis Strain 3F-3, an Efficient Pentose-Utilizing Producer of 2,3-Butanediol

ABSTRACT Bacillus licheniformis strain 3F-3 is an efficient pentose-utilizing producer of platform chemical, 2,3-butanediol. Here we present a 4.1-Mb assembly of its genome. The key genes for pentose utilization, regulation, and metabolism of 2,3-butanediol were annotated, which may provide further insights into the molecular mechanism of 2,3-butanediol production from biomass pentose.
MAINTENANCE AND LOSS OF HETEROZYGOSITY IN A THELYTOKOUS LINEAGE OF HONEY BEES (APIS MELLIFERA CAPENSIS)

An asexual lineage that reproduces by automictic thelytokous parthenogenesis has a problem: rapid loss of heterozygosity resulting in effective inbreeding. Thus, the circumstances under which rare asexual lineages thrive provide insights into the trade‐offs that shape the evolution of alternative reproductive strategies across taxa. A socially parasitic lineage of the Cape honey bee, Apis mellifera capensis, provides an example of a thelytokous lineage that has endured for over two decades. It has been proposed that cytological adaptations slow the loss of heterozygosity in this lineage. However, we show that heterozygosity at the complementary sex determining (csd) locus is maintained via selection against homozygous diploid males that arise from recombination. Further, because zygosity is correlated across the genome, it appears that selection against diploid males reduces loss of homozygosity at other loci. Selection against homozygotes at csd results in substantial genetic load, so that if a thelytokous lineage is to endure, unusual ecological circumstances must exist in which asexuality permits such a high degree of fecundity that the genetic load can be tolerated. Without these ecological circumstances, sex will triumph over asexuality. In A. m. capensis, these conditions are provided by the parasitic interaction with its conspecific host, Apis mellifera scutellata.
Monitoring of lipid storage in Caenorhabditis elegans using coherent anti-Stokes Raman scattering (CARS) microscopy

Better understanding of the fundamental mechanisms behind metabolic diseases requires methods to monitor lipid stores on single-cell level in vivo. We have used Caenorhabditis elegans as a model organism to demonstrate the limitations of fluorescence microscopy for imaging of lipids compared with coherent anti-Stokes Raman scattering (CARS) microscopy, the latter allowing chemically specific and label-free imaging in living organisms. CARS microscopy was used to quantitatively monitor the impact of genetic variations in metabolic pathways on lipid storage in 60 specimens of C. elegans. We found that the feeding-defective mutant pha-3 contained a lipid volume fraction one-third of that found in control worms. In contrast, mutants (daf-2, daf-4 dauer) with deficiencies in the insulin and transforming growth factors (IGF and TGF-β) signaling pathways had lipid volume fractions that were 1.4 and 2 times larger than controls, respectively. This was observed as an accumulation of small-sized lipid droplets in the hypodermal cells, hosting as much as 40% of the total lipid volume in contrast to the 9% for the wild-type larvae. Spectral CARS microscopy measurements indicated that this is accompanied by a shift in the ordering of the lipids from gel to liquid phase. We conclude that the degree of hypodermal lipid storage and the lipid phase can be used as a marker of lipid metabolism shift. This study shows that CARS microscopy has the potential to become a sensitive and important tool for studies of lipid storage mechanisms, improving our understanding of phenomena underlying metabolic disorders.
Barriers to treatment access for young problem gamblers

The rate of problem gambling is more than twice as high in adolescents as it is for adults (2%) (Ipsos MORI, 2009), and the younger the age of onset of problem gambling the more severe the problem can be in later life. It has been suggested that help-seeking for gambling problems is uncommon amongst young people (Gupta & Derevensky, 2000; Hardoon, Gupta & Derevensky, 2003) and a number of speculative reasons for this have been presented (Chevalier & Griffiths, 2004; Griffiths, 2001). However to date there is a paucity of empirical evidence which explore barriers to treatment access in young problem gamblers (Suurvali, 2009). The research aims were to generate empirical evidence to identify and explain barriers to treatment access for young problem gamblers in the UK. The main objectives were to i) Explore the attitudes and perceptions that young people hold towards problem gambling; ii) Investigate the potential barriers which may prevent young people from seeking treatment; and iii) To understand the salience of the identified barriers to treatment access amongst young problem gamblers. The research employed a mixed methods approach, incorporating exploratory studies, indepth interviews with problem gambling treatment professionals (n=11) and problem gamblers (n=6), and a study employing Q methodology to help understand the subjectivity of opinion on barriers to help-seeking (n=21).
Risk Factors for Persistent Cervical Intraepithelial Neoplasia Grades 1 and 2: Managed by Watchful Waiting

Objective: This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and examines whether human papillomavirus (HPV) testing predicts persistent lesions. Materials and Methods: Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed up every 3 months without treatment. Human papillomavirus genotyping, plasma levels of ascorbic acid, and red blood cell folate levels were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. Results: At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p < .001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared with HPV-negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74-2.09) were at increased risk for persistent CIN; women with HPV-16/18 had the highest risk (RRs range = 1.91-2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50-2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. Conclusions: Spontaneous regression of CIN 1 and 2 occurs frequently within 12 months. Human papillomavirus infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion.
Liveness-based garbage collection for lazy languages

We consider the problem of reducing the memory required to run lazy first-order functional programs. Our approach is to analyze programs for liveness of heap-allocated data. The result of the analysis is used to preserve only live data—a subset of reachable data—during garbage collection. The result is an increase in the garbage reclaimed and a reduction in the peak memory requirement of programs. Whereas this technique has already been shown to yield benefits for eager first-order languages, the lack of a statically determinable execution order and the presence of closures pose new challenges for lazy languages. These require changes both in the liveness analysis itself and in the design of the garbage collector. To show the effectiveness of our method, we implemented a copying collector that uses the results of the liveness analysis to preserve live objects, both evaluated and closures. Our experiments confirm that for programs running with a liveness-based garbage collector, there is a significant decrease in peak memory requirements. In addition, a sizable reduction in the number of collections ensures that in spite of using a more complex garbage collector, the execution times of programs running with liveness and reachability-based collectors remain comparable.