Miracle-dz/UniFAR-FTUs huggingface dataset:
Isothermal Aging Effects on the Thermal reliability Performance of Lead-Free Solder Joints

Electronics assemblies containing solder joints are often exposed to elevated temperatures for prolonged periods of time. The time-at-temperature stress impacts the overall package reliability of the assembled circuitry due to evolving materials, microstructural, and mechanical properties. It is especially important to understand the impact of isothermal aging on the long term behavior of lead (Pb)-free solder joints which operate in harsh environments. In this study, we have explored the effects of elevated temperature isothermal aging on the reliability of Sn-Ag-Cu (SAC) assemblies on board level packages. As the isothermal aging temperature increases, the Weybull characteristic lifetime for SAC 105 and 305 solder joints is drastically reduced compared to Sn-37Pb.In parallel mechanical studies on bulk solder specimens, the creep rate for SAC105, 305 rapidly increases with aging. A full test matrix with varying aging temperatures and solder alloys was considered. Package sizes ranged from 19mm, 0.8mm pit.
Lanthanide-dependent cross-feeding of methane-derived carbon is linked by microbial community interactions

Significance A great challenge in microbial ecology lies in determining the underlying mechanisms that drive interactions in complex natural communities. In this study we used bacterial isolates from Lake Washington sediment that are important for the utilization of the greenhouse gas methane. We show how simple cocultures can be used to identify mechanisms involved in cross-feeding in microbial communities; these mechanisms cannot be deduced from pure cultures alone. We demonstrate that the presence of one species alters gene expression and metabolism in another species such that the second species excretes a carbon and energy source to sustain the cross-fed species. This mode of cross-feeding based on partner-induced altered gene expression may have important implications for microbial interactions in the environment. The utilization of methane, a potent greenhouse gas, is an important component of local and global carbon cycles that is characterized by tight linkages between methane-utilizing (methanotrophic) and nonmethanotrophic bacteria. It has been suggested that the methanotroph sustains these nonmethanotrophs by cross-feeding, because subsequent products of the methane oxidation pathway, such as methanol, represent alternative carbon sources. We established cocultures in a microcosm model system to determine the mechanism and substrate that underlay the observed cross-feeding in the environment. Lanthanum, a rare earth element, was applied because of its increasing importance in methylotrophy. We used co-occurring strains isolated from Lake Washington sediment that are involved in methane utilization: a methanotroph and two nonmethanotrophic methylotrophs. Gene-expression profiles and mutant analyses suggest that methanol is the dominant carbon and energy source the methanotroph provides to support growth of the nonmethanotrophs. However, in the presence of the nonmethanotroph, gene expression of the dominant methanol dehydrogenase (MDH) shifts from the lanthanide-dependent MDH (XoxF)-type, to the calcium-dependent MDH (MxaF)-type. Correspondingly, methanol is released into the medium only when the methanotroph expresses the MxaF-type MDH. These results suggest a cross-feeding mechanism in which the nonmethanotrophic partner induces a change in expression of methanotroph MDHs, resulting in release of methanol for its growth. This partner-induced change in gene expression that benefits the partner is a paradigm for microbial interactions that cannot be observed in studies of pure cultures, underscoring the importance of synthetic microbial community approaches to understand environmental microbiomes.
Long-Lived Termite Queens Exhibit High Cu/Zn-Superoxide Dismutase Activity

In most organisms, superoxide dismutases (SODs) are among the most effective antioxidant enzymes that regulate the reactive oxygen species (ROS) generated by oxidative energy metabolism. ROS are considered main proximate causes of aging. However, it remains unclear if SOD activities are associated with organismal longevity. The queens of eusocial insects, such as termites, ants, and honeybees, exhibit extraordinary longevity in comparison with the nonreproductive castes, such as workers. Therefore, the queens are promising candidates to study the underlying mechanisms of aging. Here, we found that queens have higher Cu/Zn-SOD activity than nonreproductive individuals of the termite Reticulitermes speratus. We identified three Cu/Zn-SOD sequences and one Mn-SOD sequence by RNA sequencing in R. speratus. Although the queens showed higher Cu/Zn-SOD activity than the nonreproductive individuals, there were no differences in their expression levels of the Cu/Zn-SOD genes RsSOD1 and RsSOD3A. Copper (Cu2+ and Cu+) is an essential cofactor for Cu/Zn-SOD enzyme activity, and the queens had higher concentrations of copper than the workers. These results suggest that the high Cu/Zn-SOD activity of termite queens is related to their high levels of the cofactor rather than gene expression. This study highlights that Cu/Zn-SOD activity contributes to extraordinary longevity in termites.
Architecture of the yeast Elongator complex

The highly conserved eukaryotic Elongator complex performs specific chemical modifications on wobble base uridines of tRNAs, which are essential for proteome stability and homeostasis. The complex is formed by six individual subunits (Elp1‐6) that are all equally important for its tRNA modification activity. However, its overall architecture and the detailed reaction mechanism remain elusive. Here, we report the structures of the fully assembled yeast Elongator and the Elp123 sub‐complex solved by an integrative structure determination approach showing that two copies of the Elp1, Elp2, and Elp3 subunits form a two‐lobed scaffold, which binds Elp456 asymmetrically. Our topological models are consistent with previous studies on individual subunits and further validated by complementary biochemical analyses. Our study provides a structural framework on how the tRNA modification activity is carried out by Elongator.
Social status alters immune regulation and response to infection in macaques

Status alters immune function in macaques Rhesus macaques experience variable levels of stress on the basis of their position in the social hierarchy. To examine how stress affects immune function, Snyder-Mackler et al. manipulated the social status of individual macaques (see the Perspective by Sapolsky). Social status influenced the immune system at multiple levels, from immune cell numbers to gene expression, and altered signaling pathways in a model of response to infection. Macaques possess a plastic and adaptive immune response wherein social subordination promotes antibacterial responses, whereas high social status promotes antiviral responses. Science, this issue p. 1041; see also p. 967 Manipulation of social status in macaques affects cell-specific immune gene regulation. Social status is one of the strongest predictors of human disease risk and mortality, and it also influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined genomics with a social status manipulation in female rhesus macaques to investigate how status alters immune function. We demonstrate causal but largely plastic social status effects on immune cell proportions, cell type–specific gene expression levels, and the gene expression response to immune challenge. Further, we identify specific transcription factor signaling pathways that explain these differences, including low-status–associated polarization of the Toll-like receptor 4 signaling pathway toward a proinflammatory response. Our findings provide insight into the direct biological effects of social inequality on immune function, thus improving our understanding of social gradients in health.
Forkhead Box Protein O3 Transcription Factor Negatively Regulates Autophagy in Human Cancer Cells by Inhibiting Forkhead Box Protein O1 Expression and Cytosolic Accumulation

FoxO proteins are important regulators in cellular metabolism and are recognized to be nodes in multiple signaling pathways, most notably those involving PI3K/AKT and mTOR. FoxO proteins primarily function as transcription factors, but recent study suggests that cytosolic FoxO1 participates in the regulation of autophagy. In the current study, we find that cytosolic FoxO1 indeed stimulates cellular autophagy in multiple cancer cell lines, and that it regulates not only basal autophagy but also that induced by rapamycin and that in response to nutrient deprivation. These findings illustrate the importance of FoxO1 in cell metabolism regulation independent of its transcription factor function. In contrast to FoxO1, we find the closely related FoxO3a is a negative regulator of autophagy in multiple cancer cell lines, a previously unrecognized function for this protein, different from its function in benign fibroblast and muscle cells. The induction of autophagy by the knockdown of FoxO3a was found not to be mediated through the suppression of mTORC1 signaling; rather, the regulatory role of FoxO3a on autophagy was determined to be through its ability to transcriptionally suppress FoxO1. This complicated interplay of FoxO1 and FoxO3a suggests a complex checks- and balances-relationship between FoxO3a and FoxO1 in regulating autophagy and cell metabolism.
Sorption of antibiotics onto montmorillonite and kaolinite: competition modelling

ABSTRACT Antibiotic contaminants, which are generally present in bi-solute systems, can be competitively adsorbed onto clays. Single- and bi-solute sorptions of sulfadiazine (SDZ) and ciprofloxacin (CIP) onto montmorillonite and kaolinite were investigated at pH values of 5 and 8. Freundlich and Langmuir models were used and fit the experimental data well for single-solute sorption. The sorption isotherms were nonlinear (NF = 0.265–0.730), and the maximum sorption capacities (qmL) of the SDZ and CIP onto montmorillonite were higher than those onto kaolinite. The octanol–water distribution ratio (Dow), cation exchange capacity (CEC), Brunauer–Emmett–Teller (BET) surface area (ABET), pore size, point of zero charge (pHPZC), and basal spacing predominantly affected the Freundlich constant (KF) and qmL of SDZ0 and CIP+ at pH 5 more than SDZ− and CIP± at pH 8. For bi-solute sorption, the presence of CIP inhibited the SDZ sorption onto montmorillonite and kaolinite. Competitive sorption models such as Sheindorf–Rebhun–Sheintuch (SRS), Murali–Aylmore (M–A) and the modified extended Langmuir model (MELM) were used; of these, the MELM provided the best prediction with SDZ sorption onto montmorillonite at pH 8 and CIP onto kaolinite at pH 5 and 8 in SDZ/CIP system occurring synergistically, whereas others occurred antagonistically. The distribution coefficient (Kd) of the bi-solute sorption decreased with increasing pH in the order cationic > neutral > anionic for SDZ and cationic > zwitterionic > anionic for CIP, which resembled the Kd of single-solute sorption. Fourier transform infrared spectroscopy (FT-IR) spectra indicated that amine in SDZ and keto oxygen in CIP were responsible for the interactions with the montmorillonite and kaolinite. GRAPHICAL ABSTRACT
Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans.

It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po2 and Pco2 or if coronary vascular responses are the result of concomitant increases in myocardial O2 consumption/demand ([Formula: see text]). We hypothesized that the coronary vascular response to Po2 and Pco2 would be attenuated in healthy men when [Formula: see text] was attenuated with β1-adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β1-adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized crossover study and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and after 5 min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LADV; Doppler echocardiography), heart rate, and arterial blood pressure. LADV values at the end of each hypoxic condition were compared between esmolol and placebo. The rate-pressure product (RPP) and left ventricular mechanical energy (MELV) were calculated as indexes of [Formula: see text]. All gas manipulations augmented RPP, MELV, and LADV, but only RPP and MELV were attenuated (4-18%) after β1-adrenergic receptor blockade ( P < 0.05). Despite attenuated RPP and MELV responses, β1-adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response compared with placebo during poikilocapnic hypoxia (29.4 ± 2.2 vs. 27.3 ± 1.6 cm/s) and isocapnic hypoxia (29.5 ± 1.5 vs. 30.3 ± 2.2 cm/s). Hypercapnic hypoxia elicited a feedforward coronary dilation that was blocked by β1-adrenergic receptor blockade. These results indicate a direct influence of arterial Po2 on coronary vascular regulation that is independent of [Formula: see text]. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an increase in epicardial coronary artery blood velocity. β1-Adrenergic receptor blockade did not diminish the hypoxemic coronary response despite reduced myocardial O2 demand. These data indicate hypoxemia can regulate coronary blood flow independent of myocardial O2 consumption. A plateau in the mean left anterior descending coronary artery blood velocity-rate-pressure product relationship suggested β1-adrenergic receptor-mediated, feedforward epicardial coronary artery dilation. In addition, we observed a synergistic effect of Po2 and Pco2 during hypercapnic hypoxia.
Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual's risk of non‐communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig's potential to enhance clinical therapeutic innovation to improve human health.
CONSISTENCY OF THE EFFECTS OF FEMALE EDUCATION ON FERTILITY ACROSS THE NORTH–SOUTH DEMOGRAPHIC DIVIDE IN NIGERIA, 2003–2013

Summary Most studies examining the association between female education and fertility have reported an inverse association. However, little is known about the consistency of the relationship, or what level of education triggers an inverse association. This study examined the consistency of the association between female education and fertility across the north–south demographic divide in Nigeria. Data on women aged 40–49 were taken from the 2003, 2008 and 2013 Nigerian DHS data sets. The results showed that female education remained significantly and consistently inversely related to fertility in both the north and south of Nigeria. Women with secondary or higher level of education reported a lower number of children ever born (CEB) than those with primary or no education in both the north and south (p<0.05). The findings suggest that female education has a more effective negative effect on fertility in the south, where the level of female schooling is higher, than in the north, with its limited level of female education. Primary-level female education appeared to be ineffective in reducing fertility in the study sample. Women with primary schooling reported a slightly higher CEB than those who did not have any formal education. Also, age at marriage and child mortality were found to be consistent and significant predictors of fertility in both the north and south (p<0.001). Women who married at relatively higher ages and those who had never lost a child reported a smaller CEB consistently in both the north and south (p<0.001). Therefore, to attain sustainable fertility decline throughout Nigeria, it is imperative that policies aimed at increasing the prevalence and quality of female education are pursued, and there must be a focus on social, physical, environmental and cultural factors influencing age at marriage and child mortality.
In vivo CRISPR screening unveils histone demethylase UTX as an important epigenetic regulator in lung tumorigenesis

Significance Tumor suppressor genes (TSGs) play important roles in lung cancer initiation, progression, and even metastasis. Here, we take advantage of the clustered regularly interspaced short palindromic repeats/Cas9-mediated screening in vivo technique to identify multiple tumor suppressor genes contributing to lung cancer malignant progression. Using genetically engineered mouse models, we further confirm the tumor-suppressive role of epigenetic regulator UTX and provide therapeutic implications for UTX-deficient lung tumors. Thus, our work provides a systematic screening of TSGs in vivo and demonstrates UTX functions as the important epigenetic regulator in lung tumorigenesis. Lung cancer is the leading cause of cancer-related death worldwide. Inactivation of tumor suppressor genes (TSGs) promotes lung cancer malignant progression. Here, we take advantage of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated somatic gene knockout in a KrasG12D/+ mouse model to identify bona fide TSGs. From individual knockout of 55 potential TSGs, we identify five genes, including Utx, Ptip, Acp5, Acacb, and Clu, whose knockout significantly promotes lung tumorigenesis. These candidate genes are frequently down-regulated in human lung cancer specimens and significantly associated with survival in patients with lung cancer. Through crossing the conditional Utx knockout allele to the KrasG12D/+ mouse model, we further find that Utx deletion dramatically promotes lung cancer progression. The tumor-promotive effect of Utx knockout in vivo is mainly mediated through an increase of the EZH2 level, which up-regulates the H3K27me3 level. Moreover, the Utx-knockout lung tumors are preferentially sensitive to EZH2 inhibitor treatment. Collectively, our study provides a systematic screening of TSGs in vivo and identifies UTX as an important epigenetic regulator in lung tumorigenesis.
Crystallization of the rice immune receptor RGA5A_S with the rice blast fungus effector AVR1-CO39 prepared via mixture and tandem strategies.

RGA5 is a component of the Pia resistance-protein pair (RGA4/RGA5) from Oryza sativa L. japonica. It acts as an immune receptor that directly recognizes the effector AVR1-CO39 from Magnaporthe oryzae via a C-terminal non-LRR domain (RGA5A_S). The interaction between RGA5A_S and AVR1-CO39 relieves the repression of RGA4, leading to effector-independent cell death. To determine the structure of the complex of RGA5A_S and AVR1-CO39 and to understand the details of this interaction, the complex was prepared by fusing the proteins together, by mixing them in vitro or by co-expressing them in one host cell. Samples purified via the first two strategies were crystallized under two different conditions. A mixture of AVR1-CO39 and RGA5A_S (complex I) crystallized in 1.1 M ammonium tartrate dibasic, 0.1 M sodium acetate-HCl pH 4.6, while crystals of the fusion complex RGA5A_S-TEV-AVR1-CO39 (complex II) were grown in 2 M NaCl. The crystal of complex I belonged to space group P3121, with unit-cell parameters a = b = 66.2, c = 108.8 Å, α = β = 90, γ = 120°. The crystals diffracted to a Bragg spacing of 2.4 Å, and one molecule each of RGA5A_S and AVR1-CO39 were present in the asymmetric unit of the initial model. The crystal of complex II belonged to space group I4, with unit-cell parameters a = b = 137.4, c = 66.2 Å, α = β = γ = 90°. The crystals diffracted to a Bragg spacing of 2.72 Å, and there were two molecules of RGA5A_S and two molecules of AVR1-CO39 in the asymmetric unit of the initial model. Further structural characterization of the interaction between RGA5A_S and AVR1-CO39 will lead to a better understanding of the mechanism underlying effector recognition by R proteins.
Topical Community Detection in Event-based Social Network

Event-based services have recently witnessed a rapid growth driving the way people explore and share information of interest. They host a huge amount of users' activities including explicit RSVP, shared photos, comments and social connections. Exploiting these activities to detect communities of similar users is a challenging problem. In reality, a community in event-based social network (ESBN) is a group of users not only sharing common events and friends, but also having similar topical interests. However, such community could not be detected by most of existing methods which mainly draw on link analysis in the network. To address this problem, there is a need to capitalize on the semantics of shared objects along with the structural properties, and to generate overlapping communities rather than disjoint ones. In this paper, we propose to leverage the users' activities around events with the aim to detect communities based on topical clustering and link analysis that maximize a new form of semantic modularity. We particularly highlight the difference between online and offline social interactions, and the influence of event categories to detect communities. Experimental results on real datasets showed that our approach was able to detect semantically meaningful communities compared with existing state of the art methods.