Miracle-dz/UniFAR-FTUs huggingface dataset:
Newly Discovered Bright z ∼ 9–10 Galaxies and Improved Constraints on Their Prevalence Using the Full CANDELS Area

We report the results of an expanded search for z ∼ 9–10 candidates over the ∼883 arcmin2 CANDELS+ERS fields. This study adds 147 arcmin2 to the search area we consider over the Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey (CANDELS) COSMOS, UDS, and EGS fields, while expanding our selection to include sources with bluer J125 − H160 colors than our previous J125 − H160 > 0.5 mag selection. In searching for new z ∼ 9–10 candidates, we make full use of all available Hubble Space Telescope (HST), Spitzer/IRAC, and ground-based imaging data. As a result of our expanded search and use of broader color criteria, three new candidate z ∼ 9–10 galaxies are identified. We also find again the z = 8.683 source previously confirmed by Zitrin et al. This brings our sample of probable z ∼ 9–11 galaxy candidates over the CANDELS+ERS fields to 19 sources in total, equivalent to one candidate per 47 arcmin2 (one per 10 WFC3/IR fields). To be comprehensive, we also discuss 28 mostly lower likelihood z ∼ 9–10 candidates, including some sources that seem to be reliably at z > 8 using the HST+IRAC data alone, but which the ground-based data show are much more likely at z < 4. One case example is a bright z ∼ 9.4 candidate, COS910-8, which seems instead to be at z ∼ 2. Based on this expanded sample, we obtain a more robust luminosity function (LF) at z ∼ 9 and improved constraints on the volume density of bright z ∼ 9 and z ∼ 10 galaxies. Our improved z ∼ 9–10 results again reinforce previous findings for strong evolution in the UV LF at z > 8, with a factor of ∼10 evolution seen in the luminosity density from z ∼ 10 to z ∼ 8.
Arrow Contraction and Expansion in Tropical Diagrams

Arrow contraction applied to a tropical diagram of probability spaces is a modification of the diagram, replacing one of the morphisms with an isomorphism while preserving other parts of the diagram. It is related to the rate regions introduced by Ahlswede and Körner. In a companion article, we use arrow contraction to derive information about the shape of the entropic cone. Arrow expansion is the inverse operation to the arrow contraction.
Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice

Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ∼70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly. SIGNIFICANCE STATEMENT Aging is a major risk factor for the structure and function of the nervous system. Here we show that peripheral nerves of 24-month-old aging mice show similar degenerative alterations as nerves from aging human individuals. Both in mice and humans, these alterations were accompanied by endoneurial macrophages. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by blocking a cytokine receptor, essential for macrophage survival. The treatment strongly reduced macrophage numbers and substantially improved nerve structure and muscle strength. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may be helpful for treatment weakness and reduced mobility in the elderly.
Effect of MALP-2, a Lipopeptide fromMycoplasma fermentans, on Bone Resorption In Vitro

ABSTRACT Mycoplasmas may be associated with rheumatoid arthritis in various animal hosts. In humans, mycoplasma arthritis has been recorded in association with hypogammaglobulinemia. Mycoplasma fermentans is one mycoplasma species considered to be involved in causing arthritis. To clarify which mycoplasmal compounds contribute to the inflammatory, bone-destructive processes in arthritis, we used a well-defined lipopeptide, 2-kDa macrophage-activating lipopeptide (MALP-2) from M. fermentans, as an example of a class of macrophage-activating compounds ubiquitous in mycoplasmas, to study its effects on bone resorption. MALP-2 stimulated osteoclast-mediated bone resorption in murine calvaria cultures, with a maximal effect at around 2 nM. Anti-inflammatory drugs inhibited MALP-2-mediated bone resorption by about 30%. This finding suggests that MALP-2 stimulates bone resorption partially by stimulating the formation of prostaglandins. Since interleukin-6 (IL-6) stimulates bone resorption, we investigated IL-6 production in cultured calvaria. MALP-2 stimulated the liberation of IL-6, while no tumor necrosis factor was detectable. Additionally, MALP-2 stimulated low levels of NO in calvaria cultures, an effect which was strongly increased in the presence of gamma interferon, causing an inhibition of bone resorption. MALP-2 stimulated the bone-resorbing activity of osteoclasts isolated from long bones of newborn rats and cultured on dentine slices without affecting their number. In bone marrow cultures, MALP-2 inhibited the formation of osteoclasts. It appears that MALP-2 has two opposing effects: it increases the bone resorption in bone tissue by stimulation of mature osteoclasts but inhibits the formation of new ones.
On the Analytic Evaluation of Schedules via Max-Plus Algebra for DSE of Multi-Core Architectures

Dataflow modeling is well suited for a wide variety of applications for multi-core architectures, e.g. signal processing and control domain. Additionally, Design Space Exploration (DSE) can be used to explore the distribution of tasks to resources and their scheduling to obtain optimized trade-off solutions between throughput and resource costs. However, the performance evaluation of an implementation candidate in particular via compilation and throughput measurement on the target hardware is prohibitively time-consuming. Thus, we propose to use a max-plus algebra-based analytic throughput calculation method in the initial DSE phase where a fast evaluation with low accuracy is sufficient to guide the search through the design space. However, this analysis neglects some real-world concerns like cache effects and scheduling overhead. Thus, a hybrid DSE is proposed where throughput measurements are taken later in the DSE to get more accurate throughput results for real-world platforms. Results show that our approach is able to find much higher throughput multi-core solutions within a given exploration time compared to a state-of-the-art DSE approach.
The “Usual Suspects”: Genes for Inflammation, Fibrosis, Regeneration, and Muscle Strength Modify Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD), the most severe form of dystrophinopathy, is quite homogeneous with regards to its causative biochemical defect, i.e., complete dystrophin deficiency, but not so much with regards to its phenotype. For instance, muscle weakness progresses to the loss of independent ambulation at a variable age, starting from before 10 years, to even after 16 years (with glucocorticoid treatment). Identifying the bases of such variability is relevant for patient counseling, prognosis, stratification in trials, and identification of therapeutic targets. To date, variants in five loci have been associated with variability in human DMD sub-phenotypes: SPP1, LTBP4, CD40, ACTN3, and THBS1. Four of these genes (SPP1, LTBP4, CD40, and THBS1) are implicated in several interconnected molecular pathways regulating inflammatory response to muscle damage, regeneration, and fibrosis; while ACTN3 is known as “the gene for speed”, as it contains a common truncating polymorphism (18% of the general population), which reduces muscle power and sprint performance. Studies leading to the identification of these modifiers were mostly based on a “candidate gene” approach, hence the identification of modifiers in “usual suspect” pathways, which are already known to modify muscle in disease or health. Unbiased approaches that are based on genome mapping have so far been applied only initially, but they will probably represent the focus of future developments in this field, and will hopefully identify novel, “unsuspected” therapeutic targets. In this article, we summarize the state of the art of modifier loci of human dystrophin deficiency, and attempt to assess their relevance and implications on both clinical management and translational research.
Alagille Syndrome: A Novel Mutation in JAG1 Gene

Alagille syndrome is an autosomal dominant multisystem disorder with variable phenotypic penetrance, caused by heterozygous mutations in JAG1 or NOTCH2, encoding for the components of the Notch signaling pathway. In this paper, we described a novel mutation not yet reported in literature. This 3-years old male child was referred to our Clinical Genetics Unit because of delayed psychomotor development, systolic murmur, dysmorphic facial features, and hypertransaminasemia. The novel JAG1 heterozygous c.2026delT variant in exon 16 was found. JAG1 mutations are classified as protein truncating and non-protein truncating, without any genotype-phenotype correlation. The detected mutation determines a stop codon (p.Cys676AlafsTer67) in the gene sequence, encoding a truncated protein. Our report broadens the spectrum of JAG1 gene mutations.
A case report and literature review

Rationale: Herpes zoster is characterized by unilateral vesicular eruption and it most often affects the trigeminal nerve. We would like to report a rare case of abducens and vagus nerves palsy caused by varicella zoster virus (VZV) without the typical vesicular rash. Patient concerns: A 71-year-old woman presented with diplopia. Three days previously, she had experienced sore throat and hoarseness. Diagnosis: At presentation, the prism cover test revealed esotropia of 10 prism diopters at primary gaze, and abduction was restricted in the right eye. No vesicular rash was observed on the patient’s face, andmagnetic resonance imaging of the brain showed no pathology. Flexible fiberoptic laryngoscopy revealed multiple ulcerations on the right side of the larynx—from the epiglottis to the arytenoid. After 1 day of hospitalization, a diffuse skin rash occurred on the patient’s trunk, and polymerase chain reaction for VZV DNA was positive at the skin lesion. The patient was diagnosed as having herpes zoster associated with vagus and sixth nerve palsy. Intervention and outcomes: She received famciclovir at a dose of 500mg 3 times daily for 7 days and coadministered methylprednisolone. At the 4-month follow-up, her diplopia and eye movement had resolved completely. Lessons: In patients with abducens nerve palsy without typical vesicular lesion, herpes zoster may not be detected early. In that case, systemic examination is very important for diagnosing herpes zoster. Abbreviations: PCR = polymerase chain reaction, VZV = varicella zoster virus.
A New Animal Model of Thrombophilia Confirms that High Plasma Factor VIII Levels Are Thrombogenic

Summary The thrombotic risk associated with elevated plasma levels of clotting factor VIII (FVIII) was investigated in a mouse model of thrombophilia. After the intravenous injection of recombinant human FVIII and/or of purified FVIII-free human von Willebrand factor (vWF), a controlled mild injury was inflicted on the carotid artery of FVB mice by irradiation with filtered green light in combination with intravenous injection of the dye rose bengal. Formation of a platelet-rich thrombus was continuously monitored for 40 min via transillumination and the thrombus size was measured via image analysis. Administration of recombinant human FVIII at 40 g/kg led to initial FVIII plasma activities equivalent to 250% of normal human plasma FVIII activity and significantly enhanced thrombus size. Immunohistochemical staining illustrated the accumulation of FVIII within the thrombi. Human vWF, even at 10 mg/kg, had no effect on thrombus formation. The thrombotic tendency induced by FVIII was significantly inhibited by the administration of human vWF in a dose-dependent manner. Separate plasma measurements revealed that human FVIII has comparable affinities for human and murine vWF but that human vWF does not effectively bind murine platelets. The inhibition by human vWF of the thrombotic tendency induced by human FVIII could therefore be explained by a lack of accumulation of FVIII within the developing thrombus because of the reduced affinity of human vWF for murine platelets and the reduced occupancy of murine von Willebrand factor by human FVIII after injection of human vWF. These results show that vWF actively participates in FVIII accumulation in the arterial thrombus and provide experimental evidence for epidemiological findings that elevated plasma FVIII levels are associated with an increased thrombotic risk, also in arteries.
Electrophysiological properties of human mesenchymal stem cells

Human mesenchymal stem cells (hMSC) have gained considerable interest due to their potential use for cell replacement therapy and tissue engineering. One strategy is to differentiate these bone marrow stem cells in vitro into cardiomyocytes prior to implantation. In this context ion channels can be important functional markers of cardiac differentiation. At present there is little information about the electrophysiological behaviour of the undifferentiated hMSC. We therefore investigated mRNA expression of 26 ion channel subunits using semiquantitative RT‐PCR and recorded transmembrane ion currents with the whole‐cell voltage clamp technique. Bone marrow hMSC were obtained from healthy donors. The cells revealed a distinct pattern of ion channel mRNA with high expression levels for some channel subunits (e.g. Kv4.2, Kv4.3, MaxiK, HCN2, and α1C of the L‐type calcium channel). Outward currents were recorded in almost all cells. The most abundant outward current rapidly activated at potentials positive to +20 mV. This current was identified as a large‐conductance voltage‐ and Ca2+‐activated K+ current, conducted by MaxiK channels, due to its high sensitivity to tetraethylammonium (IC50= 340 μm) and its inhibition by 100 nm iberiotoxin. A large fraction of cells also demonstrated a more slowly activating current at potentials positive to –30 mV. This current was selectively inhibited by clofilium (IC50= 0.8 μm). Ba2+ inward currents, stimulated by 1 μm BayK 8644 were found in a few cells, indicating the expression of functional L‐type Ca2+ channels. Other inward currents such as sodium currents or inward rectifier currents were absent. We conclude that undifferentiated hMSC express a distinct pattern of ion channel mRNA and functional ion channels that might contribute to physiological cell function.
Impact of Colon-Specific DNA Methylation-Regulated Gene Modules on Colorectal Cancer Patient Survival

Background Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females and the third in males worldwide. Although existing evidence explained some critical functions of the single genetic abnormality in the pathogenesis of CRC, the function of interactors involved in the colon-specific regulatory network, especially DNA methylation regulated network is still poorly understood. Material/Methods In this work, matched gene expression and DNA methylation samples of CRC patients were retrieved. Differential gene expression and methylation analyses were performed. In addition, gene expression and DNA methylation were integrated into a colon-specific regulatory gene network, detecting the epigenetically regulated gene modules which drive CRC through an underlying epigenetic mechanism. Finally, the colon-specific DNA methylation-regulated gene modules were validated using an independent set of CRC patients. Results Differential gene expression analysis demonstrated the upregulation of the cell cycle and DNA replication and downregulation of cGMP-PKG signaling pathway and calcium signaling pathway in CRC. Differentially methylated regions (DMRs) showed the different levels of methylation in promoters, CpG islands, and genes in CRC. In addition, gene expression and DNA methylation were integrated into a colon-specific regulatory gene network, detecting 8 epigenetically regulated gene modules which drive CRC through an underlying epigenetic mechanism. Interestingly, 2 of the colon-specific DNA methylation-regulated gene modules showed a significant predictive ability for the survival of an independent set of CRC patients. Conclusions The results of this study could open a new era and aid the development of novel therapeutic targets for the treatment of CRC patient.
First Steps Towards an Imprecise Poisson Process

The Poisson process is the most elementary continuous-time stochastic process that models a stream of repeating events. It is uniquely characterised by a single parameter called the rate. Instead of a single value for this rate, we here consider a rate interval and let it characterise two nested sets of stochastic processes. We call these two sets of stochastic process imprecise Poisson processes, explain why this is justified, and study the corresponding lower and upper (conditional) expectations. Besides a general theoretical framework, we also provide practical methods to compute lower and upper (conditional) expectations of functions that depend on the number of events at a single point in time.
Glutamate Dehydrogenase Is Required by Mycobacterium bovis BCG for Resistance to Cellular Stress

We recently reported on our success to generate deletion mutants of the genes encoding glutamate dehydrogenase (GDH) and glutamine oxoglutarate aminotransferase (GOGAT) in M. bovis BCG, despite their in vitro essentiality in M. tuberculosis. We could use these mutants to delineate the roles of GDH and GOGAT in mycobacterial nitrogen metabolism by using M. bovis BCG as a model for M. tuberculosis specifically. Here, we extended our investigation towards the involvement of GDH and GOGAT in other aspects of M. bovis BCG physiology, including the use of glutamate as a carbon source and resistance to known phagosomal stresses, as well as in survival inside macrophages. We find that gdh is indispensable for the utilization of glutamate as a major carbon source, in low pH environments and when challenged with nitric oxide. On the other hand, the gltBD mutant had increased viability under low pH conditions and was unaffected by a challenge with nitric oxide. Strikingly, GDH was required to sustain M. bovis BCG during infection of both murine RAW 264.7 and bone-marrow derived and macrophages, while GOGAT was not. We conclude that the catabolism of glutamate in slow growing mycobacteria may be a crucial function during infection of macrophage cells and demonstrate a novel requirement for M. bovis BCG GDH in the protection against acidic and nitrosative stress. These results provide strong clues on the role of GDH in intracellular survival of M. tuberculosis, in which the essentiality of the gdh gene complicates knock out studies making the study of the role of this enzyme in pathogenesis difficult.
Risk Stratification of Patients With Acute Symptomatic Pulmonary Embolism Based on Presence or Absence of Lower Extremity DVT: Systematic Review and Meta-analysis.

BACKGROUND For patients diagnosed with acute pulmonary embolism (PE), the prognostic significance of concomitant DVT lacks clarity. METHODS We performed a meta-analysis of studies that enrolled patients with acute PE to assess the prognostic value of concomitant DVT for the primary outcome of 30-day all-cause mortality and the secondary outcome of 90-day PE-related adverse events. We conducted unrestricted searches of PubMed and Embase from 1980 through September 30, 2014, and used the terms "deep vein thrombosis," "pulmonary embolism," and "prognos*. " We used a random-effects model to pool study results, Begg rank-correlation method to evaluate for publication bias, and I(2) testing to assess for heterogeneity. RESULTS The meta-analysis included a total of nine studies (10 cohorts, as one study had two cohorts) with 8,859 patients. Of the seven cohorts with 7,868 participants who had PE and provided results on the primary outcome, 4,379 (56%) had concomitant DVT; 272 of 4,379 (6.2%) patients with concomitant DVT died 30 days after the diagnosis of PE compared with 133 of 3,489 (3.8%) without DVT. Concomitant DVT had a significant association with 30-day all-cause mortality in all patients (seven cohorts; OR, 1.9; 95% CI, 1.5-2.4; I(2) = 0%). Concomitant DVT was not significantly associated with 90-day PE-related adverse outcomes (five cohorts; OR, 1.6; 95% CI, 0.8-3.4; I(2) = 75%). CONCLUSIONS In patients diagnosed with acute symptomatic PE, concomitant DVT was significantly associated with an increased risk of death within 30 days of PE diagnosis.
Control of Invasion by Epithelial-to-Mesenchymal Transition Programs during Metastasis

Epithelial-to-mesenchymal transition (EMT) programs contribute to the acquisition of invasive properties that are essential for metastasis. It is well established that EMT programs alter cell state and promote invasive behavior. This review discusses how rather than following one specific program, EMT states are diverse in their regulation and invasive properties. Analysis across a spectrum of models using a combination of approaches has revealed how unique features of distinct EMT programs dictate whether tumor cells invade as single cells or collectively as cohesive groups of cells. It has also been shown that the mode of collective invasion is determined by the nature of the EMT, with cells in a trailblazer-type EMT state being capable of initiating collective invasion, whereas cells that have undergone an opportunist-type EMT are dependent on extrinsic factors to invade. In addition to altering cell intrinsic properties, EMT programs can influence invasion through non-cell autonomous mechanisms. Analysis of tumor subpopulations has demonstrated how EMT-induced cells can drive the invasion of sibling epithelial populations through paracrine signaling and remodeling of the microenvironment. Importantly, the variation in invasive properties controlled by EMT programs influences the kinetics and location of metastasis.