Miracle-dz/UniFAR-FTUs huggingface dataset:
Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution

To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I–hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements. Despite pervasive evolutionary remodeling of the location and content of individual cis-regulatory regions, within orthologous mouse and human cell types the global fraction of regulatory DNA bases encoding recognition sites for each TF has been strictly conserved. Our findings provide new insights into the evolutionary forces shaping mammalian regulatory DNA landscapes. Mouse-to-human genomic comparisons illuminate conserved transcriptional programs despite regulatory rewiring. Rewiring the gene regulatory landscape DNAse I hypersensitive sites (DHSs) correlate with genomic locations that control where messenger RNA is to be produced. DHSs differ, depending on the cell type, developmental stage, and species. Viestra et al. compared mouse and human genome-wide DHS maps. Approximately one-third of the DHSs are conserved between the species, which separated approximately 550 million years ago. Most DHSs fell into tissue-specific cohorts; however, these were generally not conserved between the human and mouse. It seems that the majority of DHSs evolve because of changes in the sequence that gradually change how the region is regulated. Science, this issue p. 1007
Mitosis and Hypertrophy of Intercalated Duct Cells and Endothelial Cells in the Isoproterenol-treated Rat Parotid Gland

Chronic treatment of rats with isoproterenol (IPR) induces mitosis and differentiation of intercalated duct cells, and mitosis and hypertrophy of endothelial cells of the microvasculature in the parotid gland. Mitoses occurred in duct cells situated at or near the acinar-intercalated duct junction, and were most numerous after six IPR injections. These cells increased in size, contained numerous electronlucent granules, and were incorporated into the hypertrophic acini. The granules contained branching filamentous or finely reticulated material, and did not react with histochemical stains for carbohydrate. Capillary and venule endothelial cell mitoses were frequently seen after four to six IPR injections. The endothelial cells increased in thickness, contained abundant cytoplasmic organelles, lacked fenestrations, and had few pinocytotic vesicles. These results demonstrate the extensive nature of the response to chronic IPR treatment, and are consistent with the concept that the intercalated ducts have an important role in salivary gland physiology.
E-VSM: Novel text representation model to capture contex-based closeness between two text documents

In many applications of Information Retrieval and Text Mining, there is need for an intelligent system to calculate the closeness between two text documents. In this, representation of text document in terms of mathematical object plays vital role. Vector Space Model is most popular method to represent text document in mathematical form but it is lossy, loses ordering of terms in text document in turn the context of it. Existing measures of closeness between two text documents are Cosine Similarity, Euclidean Distance etc. which are efficient but lacks in consideration of context of document. Through this paper we propose E-VSM: Enhanced-Vector Space Model to overcome limitations of original Vector Space Model and new `Density-based Clustering' approach to calculate context-based closeness between two text documents which outperforms state of art in terms of accuracy. Experiments show good results specially when text document to be compared is very much close to a particular region of target text document.
Energy-Efficient Channel Management Scheme for Cognitive Radio Sensor Networks

In designing a cognitive radio sensor network (CRSN), we need to take account of energy both efficiency and primary user (PU) protection since the CRSN consumes additional energy to support CR functionality such as channel sensing and switching, which can shorten the network lifetime. In this paper, we propose a new channel management scheme for CRSNs, which heightens the energy efficiency while not greatly disturbing a PU. The CRSN with the proposed scheme adaptively selects its operation mode among channel sensing, channel switching, and data transmission/reception, according to the channel-sensing outcome. Considering that the sensing outcome can be erroneous due to noise uncertainty, we design the proposed scheme on the basis of the partially observable Markov decision process framework. The simulation results show that the proposed scheme energy-efficiently operates while properly protecting a PU.
Cross-talk between the mitogen activated protein kinase and bone morphogenetic protein/hemojuvelin pathways is required for the induction of hepcidin by holotransferrin in primary mouse hepatocytes

The circulating hormone hepcidin plays a central role in iron homeostasis. The findings of this study show that transcriptional activation of hepcidin by holotransferrin occurs in primary mouse hepatocytes through both BMP/HJV and TFR2/ERK pathways. Background The circulating hormone hepcidin plays a central role in iron homeostasis. Our goal was to establish an ex vivo iron-sensing model and to characterize the molecular mechanisms linking iron to hepcidin. Design and Methods Murine hepatocytes were isolated by the collagenase method, either from wild type or HFE knockout mice, and cultured 42 h without serum before treatments. Results After 42 h of serum-free culture, hepcidin gene expression was undetectable in the hepatocytes. Hepcidin gene expression could, however, be re-activated by an additional 24 h of incubation with 10% serum. Interestingly, addition of 30 μM holotransferrin consistently increased serum-dependent hepcidin levels 3- to 5-fold. The effects of serum and serum+holotransferrin were direct, transcriptional, independent of de novo protein synthesis and required the presence of bone morphogenetic protein. Transferrin receptor-2 activation by its ligand holotransferrin led to extracellular signal regulated kinase (ERK)/mitogen activated protein kinase pathway stimulation and the ERK specific inhibitor U0-126 blunted holotransferrin-mediated induction of hepcidin. ERK activation by holotransferrin provoked increased levels of phospho-Smad1/5/8 highlighting cross-talk between the bone morphogenetic protein/hemojuvelin and ERK1/2 pathways. Finally, we demonstrated, using hepatocytes isolated from Hfe−/− mice, that HFE was not critical for the hepcidin response to holotransferrin but important for basal hepcidin expression. Conclusions We demonstrate that hepatocytes are liver iron-sensor cells and that transferrin receptor-2, by signaling through the ERK1/2 pathway, and bone morphogenetic protein/hemojuvelin, by signaling through the Smad pathways, coordinately regulate the iron-sensing machinery linking holotransferrin to hepcidin.
Development of Anti‐Retroviral Resistance of HIV‐1 Infected Individuals on Therapy: Is it inevitable?

Highly active antiretroviral therapy directed against HIV‐1 has dramatically modified morbidity and mortality in infected individuals. Enthusiasm for the success of these medications have been tempered by an inability to clear virus from the infected host leaving a virus poised to leverage any advantage into one of productive survival. One mechanism used to accomplish escape from suppression secondary to antiretroviral therapy is by developing mutations. The goal of therapy has been to diminish viral replication, thereby effectively abrogating the development of these resistance‐bearing mutations. This strategy has met with significant success but numerous host‐viral factors impact on the ability of the clinician to persistently suppress viral load, thereby providing a window of opportunity for the virus to mutate. In particular we review evidence for ongoing viral replication in the face of suppressive antiretroviral therapy and viral replication in tissue compartments. We discuss whether viral resistance can develop during transient elevations in viral load (viral blips) or as a function of the rate of viral load decay while on therapy. Finally, we touch on the therapeutic strategy that diminished viral replication capacity of mutational species can maintain host immunity. IUBMB Life, 56: 301‐307, 2004
Transcription of the mammalian mitochondrial genome.

PERSPECTIVES AND SUMMARY 573 GENOMIC ORGANIZATION 574 TRANSCRIPTIONAL MAPPING 576 INITIATION, ELONGATION, AND TERMINATION OF TRANSCRIPTION 578 I n Vivo Transcription 578 In Vitro Transcription 581 PROCESSING OF PRIMARY TRANSCRIPTS 582 POST-TRANSCRIPTIONAL MODIFICATION AND MATURATION OF RNA . •. • ••. • 584 Ribosomal RN As 584 Transfer RNAs 586 Messenger RNAs 587 "7S RNA" 588 OVERALL MODE OF TRANSCRIPTION 590 CONCLUSIONS AND PROSPECTS 592
Studying Vulnerable Populations: Lessons From the Roma Minority

There are important disparities in health outcomes between racial/ethnic minorities and majorities in all countries where minority health has been investigated. This holds true for the largest minority population of Europe, the Roma, although research data related to Roma are scarcer and more contested than for other minorities. We discuss major obstacles that hinder or prevent the collection of reliable data in Roma and other minorities. The definitions and classification systems on race/ethnicity vary widely, pointing to the social construction of both race and ethnicity. Imprecision in taxonomy and definition of target groups is compounded by challenges in data collection, analysis, and interpretation, along with ethnocentricity that shapes the perspectives and approaches of the researchers. However, administrative data collection on race/ethnicity serves legitimate purposes although such data must comply with less-stringent quality requirements as opposed to data meant for scientific analysis. Research on minorities should consider race/ethnicity as proxy indicators of complex health determinants, and should aim at dissecting these determinants into separate items. Careful documentation of methodology and active involvement of the minorities themselves can increase trust between the investigators and the research subjects, which can in turn improve research on minority health.
Predictors of heavy drinking after liver transplantation for alcoholic liver disease in Denmark (1990–2013): a nationwide study with competing risks analyses

Abstract Objective. Heavy drinking following liver transplantation decreases survival. Little is known of predictors of heavy drinking, which should guide clinicians identifying patients at high risk of return to heavy drinking after transplantation. Material and methods. We calculated the cumulative incidence of heavy drinking among patients transplanted for alcoholic liver disease in Denmark 1990–2013. We then analyzed pre-transplant demographic and psychiatric characteristics as predictors of post-transplant heavy drinking. Information was obtained from medical records, from nationwide registries and by interview. Results. Among 156 liver-transplanted patients, the cumulative incidence of heavy drinking was 18%, 24% and 27% after 5, 10 and 15 years post-transplant. In univariate analyses of pre-transplant predictors of heavy drinking after transplantation, younger age (p < 0.001), being retired (p = 0.007), anxiety (p = 0.04), personality disorder (p = 0.05) and no lifetime diagnosis of alcohol dependence (p = 0.03) were associated with heavy drinking after transplantation. Smoking (p = 0.06) tended to be associated, whereas depression (p = 0.7) or being married was not (p = 0.7). In the multivariate analysis, only younger age (p = 0.03), being retired (p = 0.007) and no lifetime diagnosis of alcohol dependence (p = 0.003) remained significant predictors. Heavy drinking after transplantation decreased survival beyond 5 years post-transplant (p = 0.004). Conclusions.There is a high incidence of heavy drinking after liver transplantation for alcoholic cirrhosis in Denmark. Younger age, being retired and no lifetime diagnosis of alcohol dependence were predictors of heavy drinking after transplantation.
MOJAVE. XII. ACCELERATION AND COLLIMATION OF BLAZAR JETS ON PARSEC SCALES

We report on the acceleration properties of 329 features in 95 blazar jets from the MOJAVE Very Long Baseline Array program. Nearly half the features and three-quarters of the jets show significant changes in speed and/or direction. In general, apparent speed changes are distinctly larger than changes in direction, indicating that changes in the Lorentz factors of jet features dominate the observed speed changes rather than bends along the line of sight. Observed accelerations tend to increase the speed of features near the jet base, ≲ 10–20 pc projected, and decrease their speed at longer distances. The range of apparent speeds at a fixed distance in an individual jet can span a factor of a few, indicating that shock properties and geometry may influence the apparent motions; however, we suggest that the broad trend of jet features increasing their speed near the origin is due to an overall acceleration of the jet flow out to deprojected distances of the order of 102 pc, beyond which the flow begins to decelerate or remains nearly constant in speed. We estimate intrinsic rates of change of the Lorentz factors in the galaxy frame of the order of to 10−2 yr−1, which can lead to total Lorentz factor changes of a factor of a few on the length scales observed here. Finally, we also find evidence for jet collimation at projected distances of ≲ 10 pc in the form of the non-radial motion and bending accelerations that tend to better align features with the inner jet.
A link between long-term natalizumab dosing in MS and PML

When an infectious serious adverse event is linked with a therapy for an underlying disease, it usually is seen in a few weeks or months, not years. This is not the case with the effective monoclonal antibody therapy for patients with multiple sclerosis (MS) natalizumab (Tysabri), the α4 integrin inhibitor preventing inflammatory T cells entering the brain. The infectious adverse event in patients with MS is another demyelinating disease, progressive multifocal leukoencephalopathy (PML), caused by lytic infection of oligodendrocytes with JC virus (JCV), a ubiquitous agent in the population. Although cases of PML are seen in patients with MS after receiving as few as 7 monthly doses, the highest incidence of PML, 1/75 or higher,1 occurs after 24 monthly doses. Other risk factors for PML in these patients implicate prior exposure to JCV infection evidenced by presence of antiviral antibody as well as previous immunosuppressive treatments.2
Occurrence of tetracycline, chlortetracyclin, and oxytetracycline residues in raw cow's milk.

The objective of this study was the detection of tetracycline, chlortetracycline and oxytetracycline residues in raw cow's milk. When analysing bulk milk (n = 57) and tanker trailer'a (n = 113) samples, two methods were used simultaneously: a specific rapid test Milk Tetrasensor Kit and high performance liquid chromatography (HPLC) with ultraviolet detection and isocratic elution. For HPLC analysis, Breeze (Waters, USA), a liquid chromatographic system, was used. The samples underwent solid phase extraction before the HPLC analysis. The Nova Pack C8 column (3.9 x 150 mm, 4 μm, Waters) and mobile phase (0.8 ml/min) consisting of acetonitrile, methanol, and 0.05 mol/l of oxalic acid in a 13:13:74 ratio were used. None of the samples analysed with the use of the specific rapid test displayed the presence of tetracycline antibiotics. In all of the samples analysed by means of HPLC, low concentrations of tetracycline antibiotics residues were detected. None of the samples displayed the presence of chlortetracycline. All of the analysed samples displayed residues of tetracycline. Oxytetracycline residues were detected only in 50.6% of analysed samples.
Analyzing Schedule Delay of Mega Project: Lessons Learned From Korea Train Express

In 2004, Korea became the fifth country in the world to own and operate a high-speed railway called Korea Train eXpress (KTX). Numerous uncertainties and challenges during planning and managing phase resulted in schedule delays and cost overruns. The delay causes of each activity along the 412 km Korea high-speed railway route were very difficult to identify because KTX project consisted of 11&nbsp;141 different activities. This paper evaluates challenges, obstacles, and performances of KTX project. First, critical sections in the railway route that influenced significant delays to project completion were identified. Then, delay causes of these critical sections were investigated thoroughly. The analysis discovered five major delay causes for KTX project. They are lack of owner's abilities and strategies to manage hi-tech oriented mega project; frequent changes of routes triggered by conflicts between public agencies and growing public resistance from environmental concerns; the inappropriate project delivery system; a lack of proper scheduling tool tailored for a linear mega project; and redesign and change orders of main structures and tunnels for high-speed railway, which is fundamentally different from the traditional railway construction. Based on the in-depth analysis of KTX project, through which a conceptual framework was established to identify the various facets of mega projects, this paper suggests lessons learned for engineers to better prepare and respond to potential causes of schedule delays for mega projects.
Cutaneous necrosis in a young woman

A 21-year-old woman presented with a 1-week history of rapidly spreading skin rash involving her arms and legs. Her medical history was unremarkable. She had erythematous dusky-coloured patches on the lateral aspect of both calves, upper thighs and arms. Laboratory investigations revealed thrombocytopenia [platelet count of 50 · 10 ⁄ L, normal range (NR) 140– 400 · 10 ⁄ L], international normalized ratio (INR) of 1.3 (NR 0.85–1.25), and activated partial thromboplastin time ratio of 2.24 (NR 075–1.35), which was partially corrected to 1.7 following administration of a 50: 50 mixture of normal plasma. Within days, the erythematous rash developed into large areas of fullthickness cutaneous necrosis (Fig. 1a).
Properties of RNA Polymerase Bypass Mutants

The bacterial nutritional and stress alarmone ppGpp and its co-factor DksA directly bind RNA polymerase to regulate its activity at certain σ70-dependent promoters. A number of promoters that are dependent on alternative σ-factors function poorly in the absence of ppGpp. These include the Pseudomonas-derived σ54-dependent Po promoter and several other σ54-promoters, the transcription from which is essentially abolished in Escherichia coli devoid of ppGpp and DksA. However, ppGpp and DksA have no apparent effect on reconstituted in vitro σ54-transcription, which suggests an indirect mechanism of control. Here we report analysis of five hyper-suppressor mutants within the β- and β′-subunits of core RNA polymerase that allow high levels of transcription from the σ54-Po promoter in the absence of ppGpp. Using in vitro transcription and competition assays, we present evidence that these core RNA polymerase mutants are defective in one or both of two properties that could combine to explain their hyper-suppressor phenotypes: (i) modulation of competitive association with σ-factors to favor σ54-holoenzyme formation over that with σ70, and (ii) reduced innate stability of RNA polymerase-promoter complexes, which mimics the essential effects of ppGpp and DksA for negative regulation of stringent σ70-promoters. Both these properties of the mutant holoenzymes support a recently proposed mechanism for regulation of σ54-transcription that depends on the potent negative effects of ppGpp and DksA on transcription from powerful stringent σ70-promoters, and suggests that stringent regulation is a key mechanism by which the activity of alternative σ-factors is controlled to meet cellular requirements.
Pulse-based feature extraction for hardware-efficient neural recording systems

Current brain-machine interfaces have two machine learners-one for spike sorting and the second for intention decoding that acts on the sorted spatio-temporal spike train. In this paper, we propose a pulse-based feature extractor that can enable these two machine learners to be combined into one. We show from simulations and measurements that the information about the spike shape is still retained in the pulse counts-hence, the circuit can also be used as a traditional feature extractor. The proposed circuit also has the advantage of sharing several blocks with spike detector designs reducing system level cost. Fabricated in 65nm CMOS and operating from Vdd = 1V, the feature extractor dissipates roughly 2μW of power for an input spike rate of 100Hz.
Role in Calcineurin Inhibitors for Inflammatory Bowel Disease in the Biologics Era: When and How to Use

Abstract:Ulcerative colitis and Crohn's disease, which is the 2 major forms of inflammatory bowel disease, are chronic relapsing and remitting inflammatory disorder of the gastrointestinal tract. During the last 30 years, the therapy for patients with refractory inflammatory bowel diseases is still challenging despite the fact that morbidity and mortality rates have been obviously reduced. The conventional management with corticosteroids has been modified by the introduction of calcineurin inhibitors and biologics. In this review, we focus on role in calcineurin inhibitors for patients with inflammatory bowel disease in the currently clinical practice.
Incorporating Mental Health into Bioterrorism Response Planning

Despite some recent improvements in public health preparedness in many communities, efforts to incorporate mental health plans and services into bioterrorism response planning remain in their infancy. A recent report from the Institute of Medicine recommended that “to address the prevention, health care, and promotion needs related to psychological consequences of terrorism, this area must be integrated into national, state, and local planning. ”1
Immunohistochemical and molecular characterizations in urothelial carcinoma of bladder in patients less than 45 years

Bladder tumours in early-onset patients are rare and seem to exhibit unique clinicopathological features. Only few studies have investigated somatic alterations in this specific age of onset group and evidence is accumulating of a distinct molecular behaviour of early-onset bladder tumours. We collected the largest cohort of early-onset tumours of patients 45 years old or younger and aimed to test genomic alterations typically found in bladder cancer. Tumours of 118 early-onset patients were compared with a consecutive group of 113 cases. Immunohistochemistry of TP53, CK20 and Ki-67 was carried out. Molecular analysis was conducted to test for loss of heterozygosity of chromosome 9 and 17, as well as TP53 and FGFR3 mutations. Fisher´s exact and chi-squared test were appropriately used. No differences in grade/stage characteristics were observed. Overexpressed TP53 was differentially distributed between the two groups. TP53 nuclear accumulation was significantly more frequent in early-onset papillomas, PUNLMPs and pTa low-grade tumours compared to the consecutive cohort (p=0.005). Moreover, chromosome 9 deletions (29.5% vs. 44.6%) and FGFR3 mutations (34.5% vs. 63.7%) were less often detected in early-onset patients (p=0.05 and p<0.0001). By comparing the largest cohort of early-onset bladder cancer patients with an unselected group, we demonstrated that the typical molecular features are not independent of age at diagnosis. Our study supports the hypothesis of a distinct biological behaviour in early-onset tumours.