Miracle-dz/UniFAR-FTUs huggingface dataset:
Forman curvature for directed networks

A goal in network science is the geometrical characterization of complex networks. In this direction, we (arXiv:1603.00386; J. Stat. Mech. (2016) P063206) have recently introduced the Forman's discretization of Ricci curvature to the realm of undirected networks. Investigation of Forman curvature in diverse model and real-world undirected networks revealed that this measure captures several aspects of the organization of complex undirected networks. However, many important real-world networks are inherently directed in nature, and the Forman curvature for undirected networks is unsuitable for analysis of such directed networks. Hence, we here extend the Forman curvature for undirected networks to the case of directed networks. The simple mathematical formula for the Forman curvature in directed networks elegantly incorporates node weights, edge weights and edge direction. By applying the Forman curvature for directed networks to a variety of model and real-world directed networks, we show that the measure can be used to characterize the structure of complex directed networks. Furthermore, our results also hold in real directed networks which are weighted or spatial in nature. These results in combination with our previous results suggest that the Forman curvature can be readily employed to study the organization of both directed and undirected complex networks.
Autosomal Recessive Nonsyndromic Hearing Impairment due to a Novel Deletion in the RDX Gene

The RDX gene anchors cytoskeletal actin of stereocilia to hair cell transmembrane and is responsible for autosomal recessive nonsyndromic hearing impairment (ARNSHI) due to DFNB24. A genome scan was performed using DNA samples from a consanguineous Pakistani family with ARNSHI. A significant maximum two-point LOD score of 4.5 (θ = 0) and multipoint LOD score of 5.8 were achieved at marker D11S1998 (chr11 : 117.20 Mb). The region of homozygosity is bounded by markers D11S2000 (105.06 Mb) and D11S4464 (123.13 Mb) and contains the NSHI genes TECTA and RDX. Although no potentially causal variants were identified in the TECTA gene, within the RDX gene a novel deletion c. 1076_1079delTTAA (p.Ile359Lysfs∗6) was identified. The RDX deletion segregates with ARNSHI within the family and was not observed in 500 control chromosomes. It is predicted to cause premature truncation of radixin at the α-helical domain and to result in nonfunctional transcripts within the cochlea. RDX isoforms which encode the coiled-coil region of the α-helical domain are deemed necessary for proper function of hair cell stereocilia.
Global and Site-Specific Changes in 5-Methylcytosine and 5-Hydroxymethylcytosine after Extended Post-mortem Interval

There has been a growing interest in the study of epigenetic mechanisms to elucidate the molecular bases of human brain-related diseases and disorders. Frequently, researchers utilize post-mortem tissue with the assumption that post-mortem tissue decay has little or no effect on epigenetic marks. Although previous studies show no effect of post-mortem interval on certain epigenetic marks, no such research has been performed on cytosine modifications. In this study, we use DNA from the brains of adult Sprague Dawley rats subjected to post-mortem intervals at room temperature, ranging from 0 to 96 h, to assess the stability of cytosine modifications, namely 5-methycytosine and 5-hydroxymethylcytosine. Our results indicate that neither global nor site-specific levels of 5-methycytosine and 5-hydroxymethylcytosine are affected by the post-mortem intervals we studied. As such, the use of post-mortem tissue to study cytosine modifications in the context of neurological or neuropsychiatric disorders is appropriate.
Energy Conversion: Solid‐State Lighting

Artificial illumination is a catalyst for development and improves the quality of life, but it also consumes a large fraction of the world’s energy resources [1]. Lighting has been one of the earliest applications of electric power and today utilizes approximately 20% of the world’s grid-based electricity production. The inefficiency of existing light sources that waste most of the power they consume is the reason for this large share. The worldwide demand for lighting is increasing rapidly, in particular in the developing world, and is projected to compound its strain on available energy sources. Therefore, there is a strong motivation for improving the efficiency of light sources and mitigating their effect on worldwide energy consumption and global climate change. Historically, electric light bulbs have been of the incandescent type. Although this technology was developed more than 100 years ago, it is still in use today. Incandescent light bulbs operate by heating a tungsten wire in a vacuum bulb to a temperature of 3500 K. As a result of resistive heating, the wire glows white hot and emits a broad black-body radiation spectrum that covers the entire visible
Diffusion approximation of state dependent G-networks under heavy traffic

This paper is concerned with the characterization of weak-sense limits of state-dependent G-network under heavy traffic. It is shown that, for a certain class of networks (which includes a two layer feedforward network and two queues in tandem), it is possible to approximate the number of customers in the queue by a reflected stochastic differential equation. The benefits of such an approach are that it describes the transient evolution of these queues and allows the introduction of controls, inter alia. We illustrate the application of the results with numerical experiments.
The preservation of bacteria and fungi on anhydrous silica gel: an assessment of survival over four years.

The preservation method of Perkins (1962) using suspensions in skim-milk was used to preserve 33 bacteria and 22 fungi on anhydrous silica gel. During storage at room temperature, 64% of the bacteria and 77% of the fungi survived 1 year or more. Storage at 4° often increased the survival period c. 2- to 3-fold: 73% of the bacteria and all 12 of the fungi tested at 4° survived > 1 year. At the last testing, 60% of the bacteria and 36% of the fungi were still viable after storage at 4° for periods between 3 and 4 years. The Gram positive bacilli tended to survive the silica gel preservation process better than most Gram negative bacilli. Some factors influencing survival after preservation on silica gel are discussed; the results support the use of a closed storage tube.
O-antigen and Virulence Profiling of Shiga Toxin-Producing Escherichia coli by a Rapid and Cost–Effective DNA Microarray Colorimetric Method

Shiga toxin-producing Escherichia coli (STEC) is a leading cause of foodborne illness worldwide. The present study developed the use of DNA microarrays with the ampliPHOX colorimetric method to rapidly detect and genotype STEC strains. A low-density 30-mer oligonucleotide DNA microarray was designed to target O-antigen gene clusters of 11 E. coli serogroups (O26, O45, O91, O103, O104, O111, O113, O121, O128, O145, and O157) that have been associated with the majority of STEC infections. In addition, the DNA microarray targeted 11 virulence genes, encoding adhesins, cytotoxins, proteases, and receptor proteins, which have been implicated in conferring increased ability to cause disease for STEC. Results from the validation experiments demonstrated that this microarray-based colorimetric method allowed for a rapid and accurate genotyping of STEC reference strains from environmental and clinical sources and from distinct geographical locations. Positive hybridization signals were detected only for probes targeting serotype and virulence genes known to be present in the STEC reference strains. Quantification analysis indicated that the mean pixel intensities of the signal for probes targeting O-antigen or virulence genes were at least three times higher when compared to the background. Furthermore, this microarray-based colorimetric method was then employed to genotype a group of E. coli isolates from watershed sediment and animal fecal samples that were collected from an important region for leafy-vegetable production in the central coast of California. The results indicated an accurate identification of O-type and virulence genes in the tested isolates and confirmed that the ampliPHOX colorimetric method with low-density DNA microarrays enabled a fast assessment of the virulence potential of STEC using low-cost reagents and instrumentation.
FTY720, A Novel Immunomodulator: Efficacy and Safety Results from the First Phase 2A Study in de novo Renal Transplantation

Background. FTY720 is the first of a new drug class: sphingosine-1-phosphate receptor agonist. Its effect relates to the modulation of lymphocytes trafficking from blood and peripheral tissues to lymph nodes. This is the first study to evaluate the efficacy and safety of FTY720 in de novo renal transplantation. Methods. This phase 2a, multicenter, open-label, dose-finding study compared FTY720 (0.25, 0.5, 1.0, or 2.5 mg) with mycophenolate mofetil (MMF), in combination with cyclosporine and corticosteroids. Patients (n=208) received FTY720 (n=167) or MMF (n=41) for 3 months followed by a 3-month follow-up. Results. The incidence of biopsy-confirmed acute rejection at month 3 was 23.3%, 34.9%, 17.5%, and 9.8%, respectively, with FTY720 at doses of 0.25, 0.5, 1.0, and 2.5 mg, versus 17.1% with MMF. The incidence for the composite endpoint (biopsy-confirmed acute rejection, graft loss, or death) was lowest with FTY720 at a dose of 2.5 mg at month 3 (14.6%) compared with FTY720 at doses of 0.25 mg (25.6%), 0.5 mg (34.9%), and 1.0 mg (17.5%), and MMF (19.5%). Safety was comparable between FTY720 and MMF group. The main difference in tolerability was a mild and transient reduction in heart rate. A decrease in peripheral lymphocytes occurred in patients receiving FTY720, as expected from the mode of action, and this was reversible after treatment cessation. Conclusions. FTY720 at 2.5 mg was found to be as effective as MMF in combination with cyclosporine for the prevention of acute rejection after renal transplantation. FTY720 was well tolerated and not associated with the side effects commonly observed with immunosuppressant therapies.
Biofilm Growth Increases Phosphorylcholine Content and Decreases Potency of Nontypeable Haemophilus influenzae Endotoxins

ABSTRACT Nontypeable Haemophilus influenzae (NTHI) is a common respiratory commensal and opportunistic pathogen. NTHI is normally contained within the airways by host innate defenses that include recognition of bacterial endotoxins by Toll-like receptor 4 (TLR4). NTHI produces lipooligosaccharide (LOS) endotoxins which lack polymeric O side chains and which may contain host glycolipids. We recently showed that NTHI biofilms contain variants with sialylated LOS glycoforms that are essential to biofilm formation. In this study, we show that NTHI forms biofilms on epithelial cell layers. Confocal analysis revealed that sialylated variants were distributed throughout the biofilm, while variants expressing phosphorylcholine (PCho) were found within the biofilm. Consistent with this observation, PCho content of LOS purified from NTHI biofilms was increased compared to LOS from planktonic cultures. Hypothesizing that the observed changes in endotoxin composition could affect bioactivity, we compared inflammatory responses to NTHI LOS purified from biofilm and planktonic cultures. Our results show that endotoxins from biofilms induced weaker host innate responses. While we observed a minimal effect of sialylation on LOS bioactivity, there was a significant decrease in bioactivity associated with PCho substitutions. We thus conclude that biofilm growth increases the proportion of PCho+ variants in an NTHI population, resulting in a net decrease in LOS bioactivity. Thus, in addition to their well-documented resistance phenotypes, our data show that biofilm communities of NTHI bacteria contain variants that evoke less potent host responses.
pipsqueak Encodes a Factor Essential for Sequence-Specific Targeting of a Polycomb Group Protein Complex

ABSTRACT The Polycomb (Pc) group (Pc-G) of repressors is essential for transcriptional silencing of homeotic genes that determine the axial development of metazoan animals. It is generally believed that the multimeric complexes formed by these proteins nucleate certain chromatin structures to silence promoter activity upon binding to Pc-G response elements (PRE). Little is known, however, about the molecular mechanism involved in sequence-specific binding of these complexes. Here, we show that an immunoaffinity-purified Pc protein complex contains a DNA binding activity specific to the (GA) n motif in a PRE from the bithoraxoid region. We found that this activity can be attributed primarily to the large protein isoform encoded by pipsqueak (psq) instead of to the well-characterized GAGA factor. The functional relevance of psq to the silencing mechanism is strongly supported by its synergistic interactions with a subset of Pc-G that cause misexpression of homeotic genes.
Modafinil‐induced conditioned place preference via dopaminergic system in mice

Modafinil, a psychostimulant, is used in the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea. Preclinical and clinical studies suggest that modafinil may have reinforcing effects. However, a possible rewarding property of modafinil has not been fully investigated. In this study, we assessed the potential rewarding property of modafinil using the conditioned place preference (CPP) paradigm in mice. Using radiolabeled ligands, we observed changes in dopamine, glutamate, and GABA receptor binding in the brains of mice after treatment with modafinil. Modafinil produced significant CPP in mice at an intraperitoneal (i.p.) dose of 125 mg kg−1 and prevented normal body weight gain of mice in a dose‐dependent manner. A significant reduction in normal body weight gain was observed when mice were administrated 125 mg kg−1 modafinil. In addition, there were widespread changes in receptor binding in the brains of modafinil‐treated mice; Dopamine D1 binding was increased in the caudate putamen, the accumbens, and the substantia nigra, while dopamine D2 binding was decreased in the caudate putamen and the accumbens. Dopamine transporter (DAT) binding was increased in the prefrontal cortex, the caudate putamen, and the nucleus accumbens. No changes were observed in NMDA and GABAA receptor binding. These data indicate that modafinil had a significant rewarding property and could be abused as a recreational drug. Dopamine systems may play a key role in the rewarding property of modafinil. Synapse, 2011. © 2010 Wiley‐Liss, Inc.
Potential masking effect on dyspnoea perception by short- and long-acting β2-agonists in asthma

Asthma patients evaluate the effect of medication treatment through the degree of their asthma symptoms, which might be affected by their ability to perceive these symptoms. It has been suggested that β2-agonists may mask the effects of an increase in airway inflammation. This study compared the perception of histamine-induced bronchoconstriction during monotherapy with short- or long-acting β2-agonists. Asthmatic patients (68 male and 60 female, mean age 35±11 yrs, forced expiratory volume in one second (FEV1) 86±15% of the reference value, provocative concentration causing a 20% fall in FEV1 (PC20) geometric mean 0.97 mg·mL−1 (95% confidence interval (CI): 0.73–1.30)) were selected and randomly allocated to use either a short-acting (salbutamol, n=41) or long-acting β2-agonist (formoterol, n=46) or placebo (n=41) for 12 weeks. Perception of dyspnoea provoked by histamine-induced bronchoconstriction was measured at the start and every 4 weeks thereafter. Subjects quantified their sensation of breathlessness during the challenge tests on a modified Borg scale at the start of the study and every 4 weeks thereafter. The sensitivity to changes in FEV1 was analysed by the linear regression slope (α) Borg versus % fall in FEV1. The absolute perceptual magnitude (PS20) was determined by the perception score at the 20% fall in FEV1. Although the geometric mean PC20 decreased significantly within the group using short-acting β2-agonists (in the group with initial PC20 ≥2 mg·mL−1 there was a drop from 5.26–1.94 mg·mL−1; p=0.013), repeated measurement analysis showed no difference in the course of time of perception (both slope α and PS20) between the three medication groups. This study showed that chronic use of short- or long-acting β2-agonists in asthmatics for a period of 12 weeks, did not significantly change the perception of histamine-induced bronchoconstriction compared with placebo. Further investigation is required to establish whether this suggests that these drugs do not mask a deterioration of asthma.
Activating Transcription Factor 3 Is Integral to the Eukaryotic Initiation Factor 2 Kinase Stress Response

ABSTRACT In response to environmental stress, cells induce a program of gene expression designed to remedy cellular damage or, alternatively, induce apoptosis. In this report, we explore the role of a family of protein kinases that phosphorylate eukaryotic initiation factor 2 (eIF2) in coordinating stress gene responses. We find that expression of activating transcription factor 3 (ATF3), a member of the ATF/CREB subfamily of basic-region leucine zipper (bZIP) proteins, is induced in response to endoplasmic reticulum (ER) stress or amino acid starvation by a mechanism requiring eIF2 kinases PEK (Perk or EIF2AK3) and GCN2 (EIF2AK4), respectively. Increased expression of ATF3 protein occurs early in response to stress by a mechanism requiring the related bZIP transcriptional regulator ATF4. ATF3 contributes to induction of the CHOP transcriptional factor in response to amino acid starvation, and loss of ATF3 function significantly lowers stress-induced expression of GADD34, an eIF2 protein phosphatase regulatory subunit implicated in feedback control of the eIF2 kinase stress response. Overexpression of ATF3 in mouse embryo fibroblasts partially bypasses the requirement for PEK for induction of GADD34 in response to ER stress, further supporting the idea that ATF3 functions directly or indirectly as a transcriptional activator of genes targeted by the eIF2 kinase stress pathway. These results indicate that ATF3 has an integral role in the coordinate gene expression induced by eIF2 kinases. Given that ATF3 is induced by a very large number of environmental insults, this study supports involvement of eIF2 kinases in the coordination of gene expression in response to a more diverse set of stress conditions than previously proposed.
Pregnancy, maternal exposure to analgesic medicines, and leukemia in Brazilian children below 2 years of age

Childhood leukemia etiology, and mainly the interactions of genetic and environmental risk factors, remains largely unexplored. This national hospital-based case–control study was carried out in Brazil among children aged 0–23 months who were recruited at cancer and general hospitals in 13 states. Maternal medicine intake during pregnancy, including analgesic intake, was assessed by face-to-face interviews with the mothers of 231 leukemia patients and 411 controls. Unconditional logistic regression was used to ascertain crude and adjusted odds ratios (ORs), and their 95% confidence intervals (CIs) for the association between maternal analgesic use during pregnancy and early age leukemia. Acetaminophen use during the first trimester of pregnancy showed an OR=0.39 (95% CI 0.17–0.93) for acute lymphocytic leukemia and an OR=0.37 (95% CI 0.16–0.88) for use in the second trimester. For acute myeloid leukemia, an OR=0.11 (95% CI 0.02–0.97) was found following acetaminophen use in the second trimester. For acute lymphocytic leukemia, the exclusive use of dipyrone during preconception showed an OR=1.63 (95% CI 1.06–2.53) and dipyrone intake during lactation showed an OR=2.00 (95% CI 1.18–3.39). These results suggest that acetaminophen use during pregnancy may protect against development of early age leukemia in the offspring, whereas dipyrone use may act as a risk factor for such an outcome.
Pancreas Segmentation in Abdominal CT Scan: A Coarse-to-Fine Approach

Deep neural networks have been widely adopted for automatic organ segmentation from CT-scanned images. However, the segmentation accuracy on some small organs (e.g., the pancreas) is sometimes below satisfaction, arguably because deep networks are easily distracted by the complex and variable background region which occupies a large fraction of the input volume. In this paper, we propose a coarse-to-fine approach to deal with this problem. We train two deep neural networks using different regions of the input volume. The first one, the coarse-scaled model, takes the entire volume as its input. It is used for roughly locating the spatial position of the pancreas. The second one, the fine-scaled model, only sees a small input region covering the pancreas, thus eliminating the background noise and providing more accurate segmentation especially around the boundary areas. At the testing stage, we first use the coarse-scaled model to roughly locate the pancreas, then adopt the fine-scaled model to refine the initial segmentation in an iterative manner to obtain increasingly better segmentation. We evaluate our algorithm on the NIH pancreas segmentation dataset with 82 volumes, and outperform the state-of-the-art [18] by more than 4% measured by the Dice-Sorensen Coefficient (DSC). In addition, we report 62.43% DSC for our worst case, significantly better than 34.11% reported in [18].
Some new aspects of the Langerhans cell.

Electron microscopic examination showed varying numbers of typical Langerhans cells in the dermis in normal human skin, pityriasis rosea, reticulum cell sarcoma, and Letterer-Siwe disease as well as among the stromal and parenchymal cells of several benign appendage tumors. Langerhans cells were observed crossing the basement membrane and an epidermal Langerhans cell in mitosis was seen. These findings suggest that Langerhans cells are not directly related to epidermal melanocytes and may constitute a self-perpetuating "intraepidermal phagocytic system" to which histiocytes from the dermis are added from time to time.
Novel Centromeric Loci of the Wine and Beer Yeast Dekkera bruxellensis CEN1 and CEN2

The wine and beer yeast Dekkera bruxellensis thrives in environments that are harsh and limiting, especially in concentrations with low oxygen and high ethanol. Its different strains’ chromosomes greatly vary in number (karyotype). This study isolates two novel centromeric loci (CEN1 and CEN2), which support both the yeast’s autonomous replication and the stable maintenance of plasmids. In the sequenced genome of the D. bruxellensis strain CBS 2499, CEN1 and CEN2 are each present in one copy. They differ from the known “point” CEN elements, and their biological activity is retained within ~900–1300 bp DNA segments. CEN1 and CEN2 have features of both “point” and “regional” centromeres: They contain conserved DNA elements, ARSs, short repeats, one tRNA gene, and transposon-like elements within less than 1 kb. Our discovery of a miniature inverted-repeat transposable element (MITE) next to CEN2 is the first report of such transposons in yeast. The transformants carrying circular plasmids with cloned CEN1 and CEN2 undergo a phenotypic switch: They form fluffy colonies and produce three times more biofilm. The introduction of extra copies of CEN1 and CEN2 promotes both genome rearrangements and ploidy shifts, with these effects mediated by homologous recombination (between circular plasmid and genome centromere copy) or by chromosome breakage when integrated. Also, the proximity of the MITE-like transposon to CEN2 could translocate CEN2 within the genome or cause chromosomal breaks, so promoting genome dynamics. With extra copies of CEN1 and CEN2, the yeast’s enhanced capacities to rearrange its genome and to change its gene expression could increase its abilities for exploiting new and demanding niches.