Miracle-dz/UniFAR-FTUs huggingface dataset:
Supporting Online Material Materials and Methods Figs. S1 to S7 Tables S1 to S4 References Mutations in the Fus/tls Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders. A myotrophic lateral sclerosis (ALS) is a progressive, uniformly fatal, age-dependent degenerative disorder of motor neurons. Its incidence (0.6 to 2.6 per 100,000 humans) peaks in the sixth decade of life (1). Death from ALS is typically 2 to 5 years after onset and is usually a consequence of respiratory paralysis. Familial cases account for about 10% of ALS. Of these, about 20% are caused by mutations in the superoxide dismutase 1 (SOD1) gene (2). A small number of both familial and apparently sporadic cases are caused by mutations in various other genes, including TAR DNA-binding protein 43 (TDP43) (3–5), although in the majority of familial ALS (FALS) cases the causative gene is unknown. In a family of Cape Verdean origin (F577) (fig. S1A), four members developed distinctive ALS with onset in the proximal upper extremities and spreading to the lower extremities, but not the bulbar region. The maternal grandparents of the proband were first cousins; the family originates from a small island of roughly 6000 inhabitants , raising the possibility that the inheritance pattern is recessive. To pursue this, we conducted loss-of-heterozygosity (LOH) mapping and identified a major LOH cluster within a previously reported chromosome 16 ALS locus. Five smaller regions of homozygosity were observed in other chromosomal regions (table S1). The major LOH cluster spanned approximately 4 Mb and contained 56 candidate ALS genes. Genomic sequencing of these genes revealed a sequence variant in the index ALS cases in exon 15 of the fused in sarcoma/translated in lipo-sarcoma (FUS/TLS) gene (6). This variant, a base pair C1551G missense mutation (7), substituting glutamine for histidine at amino acid residue 517 (Table 1), was heterozygously present in asymptomatic individuals and homozygously …
The evolution of X-ray-selected narrow-emission-line galaxies

We examine the cosmological evolution of X-ray-selected narrow-emission-line galaxies (NELGs), using a sample of 35 such objects identified in the combined ROSAT UK Deep Survey and RIXOS. This sample is entirely independent of those previously used to investigate the X-ray evolution of NELGs.We detect evolution which is at a similar rate to the evolution found in the optical luminosity function of blue galaxies. The lack of high-redshift (z > 0.6) NELGs detected in X-ray surveys, and the small, well-defined number of X-ray sources which are not optically identified indicate that the evolution of NELGs is probably not the same as the X-ray evolution of QSOs: NELG evolution is slower than the evolution of QSOs and/or ends at a lower redshift.
Multi-wavelength observations of IGR J17544-2619 from quiescence to outburst

In this paper we report on a long multi-wavelength observational campaign of the supergiant fast X-ray transient prototype IGR J17544-2619. A 150 ks-long observation was carried out simultaneously with XMM-Newton and NuSTAR, catching the source in an initial faint X-ray state and then undergoing a bright X-ray outburst lasting approximately 7 ks. We studied the spectral variability during outburst and quiescence by using a thermal and bulk Comptonization model that is typically adopted to describe the X-ray spectral energy distribution of young pulsars in high mass X-ray binaries. Although the statistics of the collected X-ray data were relatively high, we could neither confirm the presence of a cyclotron line in the broad-band spectrum of the source (0.5−40 keV), nor detect any of the previously reported tentative detections of the source spin period. The monitoring carried out with Swift /XRT during the same orbit of the system observed by XMM-Newton and NuSTAR revealed that the source remained in a low emission state for most of the time, in agreement with the known property of all supergiant fast X-ray transients being significantly sub-luminous compared to other supergiant X-ray binaries. Optical and infrared observations were carried out for a total of a few thousand seconds during the quiescence state of the source detected by XMM-Newton and NuSTAR. The measured optical and infrared magnitudes were slightly lower than previous values reported in the literature, but compatible with the known micro-variability of supergiant stars. UV observations obtained with the UVOT telescope on-board Swift did not reveal significant changes in the magnitude of the source in this energy domain compared to previously reported values.
ANK6, a mitochondrial ankyrin repeat protein, is required for male-female gamete recognition in Arabidopsis thaliana

Double fertilization in angiosperms involves several successive steps, including guidance and reception of the pollen tube and male-female gamete recognition. Each step entails extensive communication and interaction between two different reproductive cell or tissue types. Extensive research has focused on the pollen tube, namely, its interaction with the stigma and reception by maternal cells. Little is known, however, about the mechanism by which the gametes recognize each other and interact to form a zygote. We report that an ankyrin repeat protein (ANK6) is essential for fertilization, specifically for gamete recognition. ANK6 (At5g61230) was highly expressed in the male and female gametophytes before and during but not after fertilization. Genetic analysis of a T-DNA insertional mutant suggested that loss of function of ANK6 results in embryonic lethality. Moreover, male-female gamete recognition was found to be impaired only when an ank6 male gamete reached an ank6 female gamete, thereby preventing formation of homozygous zygotes. ANK6 was localized to the mitochondria, where it interacted with SIG5, a transcription initiation factor previously found to be essential for fertility. These results show that ANK6 plays a central role in male-female gamete recognition, possibly by regulating mitochondrial gene expression.
Regulation of protein synthesis and the role of eIF 3 in cancer

Maintenance of cell homeostasis and regulation of cell proliferation depend importantly on regulating the process of protein synthesis. Many disease states arise when disregulation of protein synthesis occurs. This review focuses on mechanisms of translational control and how disregulation results in cell malignancy. Most translational controls occur during the initiation phase of protein synthesis, with the initiation factors being the major target of regulation through their phosphorylation. In particular, the recruitment of mRNAs through the m7G-cap structure and the binding of the initiator methionyl-tRNAi are frequent targets. However, translation, especially of specific mRNAs, may also be regulated by sequestration into processing bodies or stress granules, by trans-acting proteins or by microRNAs. When the process of protein synthesis is hyper-activated, weak mRNAs are translated relatively more efficiently, leading to an imbalance of cellular proteins that promotes cell proliferation and malignant transformation. This occurs, for example, when the cap-binding protein, eIF4E, is overexpressed, or when the methionyltRNAi-binding factor, eIF2, is too active. In addition, enhanced activity of eIF3 contributes to oncogenesis. The importance of the translation initiation factors as regulators of protein synthesis and cell proliferation makes them potential therapeutic targets for the treatment of cancer.
A Review of Phytate, Iron, Zinc, and Calcium Concentrations in Plant-Based Complementary Foods Used in Low-Income Countries and Implications for Bioavailability

Plant-based complementary foods often contain high levels of phytate, a potent inhibitor of iron, zinc, and calcium absorption. This review summarizes the concentrations of phytate (as hexa- and penta-inositol phosphate), iron, zinc, and calcium and the corresponding phytate:mineral molar ratios in 26 indigenous and 27 commercially processed plant-based complementary foods sold in low-income countries. Phytate concentrations were highest in complementary foods based on unrefined cereals and legumes (∼600 mg/100 g dry weight), followed by refined cereals (∼100 mg/100 g dry weight) and then starchy roots and tubers (< 20 mg/100 g dry weight); mineral concentrations followed the same trend. Sixty-two percent (16/26) of the indigenous and 37% (10/27) of the processed complementary foods had at least two phytate:mineral molar ratios (used to estimate relative mineral bioavailability) that exceeded suggested desirable levels for mineral absorption (i.e., phytate:iron < 1, phytate:zinc < 18, phytate:calcium < 0.17). Desirable molar ratios for phytate:iron, phytate:zinc, and phytate:calcium were achieved for 25%, 70%, and 57%, respectively, of the complementary foods presented, often through enrichment with animal-source foods and/or fortification with minerals. Dephytinization, either in the household or commercially, can potentially enhance mineral absorption in high-phytate complementary foods, although probably not enough to overcome the shortfalls in iron, zinc, and calcium content of plant-based complementary foods used in low-income countries. Instead, to ensure the World Health Organization estimated needs for these minerals from plant-based complementary foods for breastfed infants are met, dephytinization must be combined with enrichment with animal-source foods and/or fortification with appropriate levels and forms of mineral fortificants.
Screening for colorectal cancer with an immunological faecal occult blood test: 2‐Year follow‐up

This study is a 2‐year follow‐up of an average‐risk population Offered screening with both Haemoccult and Hemeselect tests to determine the interval cancer rate, and thus sensitivity. The effect on compliance with Hemeselect of testing over 1 day rather than 3 days was investigated in a separate cohort. In the first study, 3948 subjects received tests; 1489 (37·7 per cent) completed both tests and 148 had a positive result, 17 (1·1 per cent) were Haemoccult positive and 145 (9·7 per cent) were Hemeselect positive. Investigation of 142 patients revealed ten with cancer (Dukes stage A, seven; B, one; C, two). All were detected by Hemeselect but only one was Haemoccult positive. After a median follow‐up of 35 (range 26–43) months, seven further patients developed colorectal cancer (stage A, one; B, three; C, three) but none followed a negative Hemeselect test (100 per cent sensitivity). In the second study 2703 subjects were offered Hemeselect tests. Compliance for testing over 1 day (48·6 per cent) was significantly better than that over 3 days (43·1 per cent) (χ2 = 8·1, 1 d.f., P<0·01). Hemeselect is a promising screening test for the early detection of colorectal cancer.
Sex-role attitudes, social comparison, and satisfaction with relationships

In the present study, we were interested in whether satisfaction with relationships is related more strongly to equity comparison with the partner or with a reference group. We tested two non-exclusive hypotheses derived from social comparison theory. First, we expected that the association between satisfaction and comparison with the partner would be stronger among individuals with egalitarian sex-role beliefs, whereas among individuals adhering to traditional sex-role beliefs, satisfaction would be related more closely to comparison with a reference group (the similarity hypothesis). Second, we predicted that comparisons with others, including the partner, would be related more strongly to satisfaction among individuals who feel uncertain about how things are going in their relationship (the uncertainty reduction hypothesis)
Applications of High-Capacity Crossbar Memories in Cryptography

This paper proposes a new approach for the construction of highly secure physical unclonable functions (PUFs). Instead of using systems with medium information content and high readout rates, we suggest to maximize the information content of the PUF while strongly reducing its readout frequency. We show that special, passive crossbar arrays with a very large random information content and inherently limited readout speed are suited to implement our approach. They can conceal sensitive information over long time periods and can be made secure against invasive physical attacks. To support our feasibility study, circuit-level simulations and experimental data are presented. Our design allows the first PUFs that are secure against computationally unrestricted adversaries, and which remain so in the face of weeks or even years of uninterrupted adversarial access. We term the new design principle a “SHIC PUF,” where the acronym SHIC stands for super high information content.
Heterogeneous Distribution of Microbial Activity in Methanogenic Aggregates: pH and Glucose Microprofiles

Methanogenic aggregates, harvested from an upflow anaerobic sludge blanket reactor treating potato starch wastewater, were acclimatized to either glucose or a mixture of sugars and organic nitrogen compounds (i.e., diluted molasses). Both types of granules exhibited internal pH and substrate concentration gradients in mineral medium (pH 7.0, 30°C) as was measured with microelectrodes. Glucose-acclimatized granules suspended in a mineral medium lacking glucose exhibited a distinct internal pH decrease of about 1 U within the granule, suggesting strong metabolism by the acidogenic bacteria. Molasses-acclimatized and aged granules suspended in mineral medium did not exhibit such a pH decrease, suggesting the importance of the metabolic state of these acidogens. The pH gradient did not occur in deactivated granules and was not observable in strongly buffered media (mineral medium containing 33 mM phosphate or reactor liquid). When glucose (0.5 to 5.0 mM) was added to the mineral medium, granules exhibited a convex pH profile. Glucose consumption was located exclusively in the outer 200 to 300 μm of the aggregates (mean diameter = 1.5 mm). The addition of 20 mM 2-bromoethanesulfonic acid to the mineral medium indicated that the higher pH levels in the centre of the granule appeared to be related to the activity of methanogens. It is suggested that acidogenic activity occurs predominantly in the outer 200 to 300 μm of the aggregate and methanogenic activity occurs predominantly in the center of the investigated granules.
Mobility-aware MAC protocol for delay-sensitive wireless sensor networks

Most of the MAC protocols proposed for the wireless sensor networks (WSN) assume sensor nodes to be static and therefore they usually fail or provide very bad network performance in mobile sensor networks. Since WSN mobile applications have become popular nowadays, there is a need for MAC protocols that consider mobility. In this paper, we propose a mobility-aware MAC protocol for WSN that can work with satisfactory performance in both stationary and mobile sensor networks. Furthermore, most of the WSN mobile applications are considered critical ones (e.g. a patient assistance system which monitors patients' health via wearable bio-sensors). Such applications require very quick responses. So, in addition to handling mobility, the proposed MAC protocol considers the problem of latency as well. In summary, this paper proposes a WSN MAC protocol (MD-SMAC) that is considered to be mobility-aware, delay-sensitive and provides satisfactory level of energy efficiency. In addition, we study the performance of the proposed MD-SMAC protocol by simulating it using the NS-2 simulator and comparing it to other WSN MAC protocols. The results show that the MD-SMAC protocol outperforms other existing WSN MAC protocols in terms of mobility-handling, delay-reduction, and energy-efficiency in scenarios involving mobile sensors.
Supercomplexes in the respiratory chains of yeast and mammalian mitochondria

Around 30–40 years after the first isolation of the five complexes of oxidative phosphorylation from mammalian mitochondria, we present data that fundamentally change the paradigm of how the yeast and mammalian system of oxidative phosphorylation is organized. The complexes are not randomly distributed within the inner mitochondrial membrane, but assemble into supramolecular structures. We show that all cytochrome c oxidase (complex IV) of Saccharomyces cerevisiae is bound to cytochrome c reductase (complex III), which exists in three forms: the free dimer, and two supercomplexes comprising an additional one or two complex IV monomers. The distribution between these forms varies with growth conditions. In mammalian mitochondria, almost all complex I is assembled into supercomplexes comprising complexes I and III and up to four copies of complex IV, which guided us to present a model for a network of respiratory chain complexes: a ‘respirasome’. A fraction of total bovine ATP synthase (complex V) was isolated in dimeric form, suggesting that a dimeric state is not limited to S.cerevisiae, but also exists in mammalian mitochondria.
Linked Chromosome 16q13 Chemokines, Macrophage-Derived Chemokine, Fractalkine, and Thymus- and Activation-Regulated Chemokine, Are Expressed in Human Atherosclerotic Lesions

Abstract—Chemokines are important mediators of macrophage and T-cell recruitment in a number of inflammatory pathologies, and chemokines expressed in atherosclerotic lesions may play an important role in mononuclear cell recruitment and macrophage differentiation. We have analyzed the expression of the linked chromosome 16q13 genes that encode macrophage-derived chemokine (MDC/CCL22), thymus- and activation-regulated chemokine (TARC/CCL17), and the CX3C chemokine fractalkine (CX3CL1) in primary macrophages and human atherosclerotic lesions by reverse transcription–polymerase chain reaction and immunohistochemistry. We show that macrophage expression of the chemokines MDC, fractalkine, and TARC is upregulated by treatment with the Th2-type cytokines interleukin-4 and interleukin-13. High levels of MDC, TARC, and fractalkine mRNA expression are seen in some, but not all, human arteries with advanced atherosclerotic lesions. Immunohistochemistry shows that MDC, fractalkine, and TARC are expressed by a subset of macrophages within regions of plaques that contain plaque microvessels. We conclude that MDC, fractalkine, and TARC, which are chromosome 16q13 chemokines, could play a role in mononuclear cell recruitment into atherosclerotic lesions and influence the subsequent inflammatory response. Macrophage-expressed chemokines upregulated by interleukin-4 may be useful surrogate markers for the presence of Th2-type immune responses in human atherosclerotic lesions.
Insecticide‐treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast

New tools to prevent malaria morbidity and mortality are needed to improve child survival in sub‐Saharan Africa. Insecticide treated bednets (ITBN) have been shown, in one setting (The Gambia, West Africa), to reduce childhood mortality. To assess the impact of ITBN on child survival under different epidemiological and cultural conditions we conducted a community randomized, controlled trial of permethrin treated bednets (0.5 g/m2) among a rural population on the Kenyan Coast.
Hip Resurfacing Arthroplasty

Abstract Hip resurfacing arthroplasty is a type of hip replacement that involves capping the femoral head and preserving bone of the proximal femur. Metal‐on‐metal surface replacements have been manufactured since the early 1990s. Recent studies indicate excellent clinical results with low failure rates at 1‐ to 5‐year follow‐up. Although these early results are encouraging, resurfacing devices must be used with caution because less is known about their long‐term safety and efficacy. The best candidates for resurfacing are patients younger than age 60 years with good bone stock. The surgical approach is similar to that for standard total hip replacements, but with slightly more dissection because the femoral head must be preserved and displaced to visualize the acetabulum. To reduce complications, resurfacing arthroplasty should be performed by surgeons who have received training specifically in this technique.
A systematic method for scoping core assets in product line engineering

Product line engineering (PLE) is an effective reuse methodology where common features among members are captured into core assets and applications are produced by reusing the core assets, reducing development cost while increasing productivity. To maximize the reusability of core assets, optimal scoping of core assets is essential. If the scope is excessively broad, it results in high cost of asset development while lowering reusability. On the other hand, if the scope is too narrow, it results in a limited applicability, only supporting a small number of members in the domain. In this paper, we propose a process for domain analysis and economical analysis of core asset scope. Then, we define guidelines for each activity of the process. Since variability often occurs in PLE, we significantly treat the variability of features among members. By applying our scoping framework, one can develop core assets of which scope provide the most economical value.
Human leukocytes regulate ganglioside expression in cultured micro-pig aortic endothelial cells

Gangliosides are ubiquitous components of the membranes of mammalian cells that are thought to play important roles in various cell functions such as cell-cell interaction, cell adhesion, cell differentiation, growth control, and signaling. However, the role that gangliosides play in the immune rejection response after xenotransplantation is not yet clearly understood. In this study, the regulatory effects of human leukocytes on ganglioside expression in primary cultured micro-pig aortic endothelial cells (PAECs) were investigated. To determine the impact of human leukocytes on the expression of gangliosides in PAECs, we performed high-performance thin layer chromatography (HPTLC) in PAECs incubated with FBS, FBS containing human leukocytes, human serum containing human leukocytes, and FBS containing TNF-α. Both HPTLC and immunohistochemistry analyses revealed that PAECs incubated with FBS predominantly express the gangliosides GM3, GM1, and GD3. However, the expression of GM1 significantly decreased in PAECs incubated for 5 h with TNF-α (10 ng/mL), 10% human serum containing human leukocytes, and 10% FBS containing human leukocytes. Taken together, these results suggest that human leukocytes induced changes in the expression profile of ganglioside GM1 similar to those seen upon treatment of PAECs with TNF-α. This finding may be relevant for designing future therapeutic strategies intended to prolong xenograft survival.