Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Genomics of Early-Diverging Brucella Strains Reveals a Novel Lipopolysaccharide Biosynthesis Pathway

ABSTRACT Brucella species are Gram-negative bacteria that infect mammals. Recently, two unusual strains (Brucella inopinata BO1T and B. inopinata-like BO2) have been isolated from human patients, and their similarity to some atypical brucellae isolated from Australian native rodent species was noted. Here we present a phylogenomic analysis of the draft genome sequences of BO1T and BO2 and of the Australian rodent strains 83-13 and NF2653 that shows that they form two groups well separated from the other sequenced Brucella spp. Several important differences were noted. Both BO1T and BO2 did not agglutinate significantly when live or inactivated cells were exposed to monospecific A and M antisera against O-side chain sugars composed of N-formyl-perosamine. While BO1T maintained the genes required to synthesize a typical Brucella O-antigen, BO2 lacked many of these genes but still produced a smooth LPS (lipopolysaccharide). Most missing genes were found in the wbk region involved in O-antigen synthesis in classic smooth Brucella spp. In their place, BO2 carries four genes that other bacteria use for making a rhamnose-based O-antigen. Electrophoretic, immunoblot, and chemical analyses showed that BO2 carries an antigenically different O-antigen made of repeating hexose-rich oligosaccharide units that made the LPS water-soluble, which contrasts with the homopolymeric O-antigen of other smooth brucellae that have a phenol-soluble LPS. The results demonstrate the existence of a group of early-diverging brucellae with traits that depart significantly from those of the Brucella species described thus far. IMPORTANCE This report examines differences between genomes from four new Brucella strains and those from the classic Brucella spp. Our results show that the four new strains are outliers with respect to the previously known Brucella strains and yet are part of the genus, forming two new clades. The analysis revealed important information about the evolution and survival mechanisms of Brucella species, helping reshape our knowledge of this important zoonotic pathogen. One discovery of special importance is that one of the strains, BO2, produces an O-antigen distinct from any that has been seen in any other Brucella isolates to date. This report examines differences between genomes from four new Brucella strains and those from the classic Brucella spp. Our results show that the four new strains are outliers with respect to the previously known Brucella strains and yet are part of the genus, forming two new clades. The analysis revealed important information about the evolution and survival mechanisms of Brucella species, helping reshape our knowledge of this important zoonotic pathogen. One discovery of special importance is that one of the strains, BO2, produces an O-antigen distinct from any that has been seen in any other Brucella isolates to date.
Diagnosing Pulmonary Embolism: New Computed Tomography Applications

Computed tomographic pulmonary angiography has become the standard of care for the evaluation of patients with suspected pulmonary embolism (PE). In addition to the direct depiction or exclusion of a pulmonary embolus in suspected PE, a number of predictive markers have been established to evaluate the patient's prognosis in acute and in chronic PE. An accurate risk stratification based on CT findings is crucial because optimal management, monitoring, and therapeutic strategies depend on the prognosis. With the recent introduction of the so-called “dual-source” CT scanners, that is, a scanner consisting of 2 tubes and 2 detectors mounted orthogonally to each other, different tube voltages can be used simultaneously, resulting in different energies of the emitted x-ray spectra (dual-energy CT; DECT). Initial results have shown that DECT is capable of iodine mapping of the pulmonary parenchyma, reliably depicting the segmental defects in iodine distribution in locations corresponding to embolic vessel occlusions. This study deals with a number of actual topics on PE imaging with multidetector CT and DECT, including the discussion of the relevant imaging findings to assess the patient's prognosis, the potential and additional benefit of dual-energy information on the parenchymal iodine distribution, the optimization of scan protocols including low-radiation dose chest pain protocols, and the discussion on future perspectives of CT in PE patients, such as the role of computer-aided diagnostic tools or the potential of ventilation imaging with DECT.
Two Saccharomyces cerevisiae Genes Which Control Sensitivity To G1 Arrest Induced by Kluyveromyces lactis Toxin

The Kluyveromyces lactis toxin causes an arrest of sensitive yeast cells in the G1 phase of the cell division cycle. Two complementary genetic approaches have been undertaken in the yeast Saccharomyces cerevisiae to understand the mode of action of this toxin. First, two sequences conferring toxin resistance specifically in high copy number have been isolated and shown to encode a tRNA(Glu3) and a novel polypeptide. Disruption of the latter sequence in the yeast genome conferred toxin resistance and revealed that it was nonessential, while the effect of the tRNA(Glu)3 was highly specific and mediated resistance by affecting the toxin's target. An alpha-specific, copy number-independent suppressor of toxin sensitivity was also isolated and identified as MATa, consistent with the observation that diploid cells are partially resistant to the toxin. Second, in a comprehensive screen for toxin-resistant mutants, representatives of 13 complementation groups have been obtained and characterized to determine whether they are altered in the toxin's intracellular target. Of 10 genes found to affect the target process, one (KTI12) was found to encode the novel polypeptide previously identified as a multicopy resistance determinant. Thus, both loss of KTI12 function and elevated KTI12 copy number can cause resistance to the K. lactis toxin.
Somatization in cancer

Somatic symptoms can occur in disease-free cancer patients. The causes of such symptoms in cancer can be many and varied. These could be due to anxiety, depression, somatization or a manifestation of illness behaviour. Somatic symptoms can also arise out of treatments for the cancer like radiation treatment or chemotherapy. Cancer related somatic symptoms have cognitive, psychological, and physiological causes, each of which is amenable to treatment. The occurrence of somatoform disorders in cancer patients is likely to complicate the treatment and outcome of the cancer. Common somatic symptoms in cancer have been found to be pain, fatigue, anorexia, tiredness or exhaustion, weakness, reduced energy, lethargy, and tremors. Breathlessness, muscle pain, dizziness, and palpitation are common symptoms of anxiety and panic attack which have also been noted in cancer patients. Somatic concern and preoccupation are also common. These symptoms create difficulty in diagnosing depression and anxiety in cancer patients, and leads to the need for modification of the standard diagnostic criteria. Somatic symptoms in cancer respond to counselling and psychopharmacotherapy. More research are needed on this area to understand the process of somatization in a somatic disease.
Real-time adjustment of power management policy for a time-based power control architecture

As state-of-the-art mobile devices are demanded for high performance and attractive designs, system-on-chips have been integrated with many functional blocks into a single chip to reduce the chip size, cost, and power consumption. In this paper, to reduce power consumption of heterogeneous processor, a power management algorithm is proposed with a time-based power control architecture which autonomously performs voltage/clock scaling operations without the intervention of the processors. The proposed algorithm has adaptively adjusted time-threshold levels for voltage/clock control to minimize the power consumption and work in severe time-constraints for real-time processing. The real-time adjustment makes robust performance of the power consumption guarantee regardless of patterns of data traffic and diverse application programs. To show performance of the proposed, they are adopted to an application processor integrated with a communication processor for smartphones. Via electronic system-level simulation, it is shown that the proposed algorithm reduces the power consumption by approximately 40%.
Endotoxin uptake in mouse liver is blocked by endotoxin pretreatment through a suppressor of cytokine signaling‐1–dependent mechanism

The liver is the main organ that clears lipopolysaccharide (LPS) and hepatocytes are a major cell‐type involved in LPS uptake. LPS tolerance, or desensitization, is important in negative regulation of responses to LPS, but little is known about its mechanisms in hepatocytes. Primary isolated C57BL/6 hepatocytes, and liver in vivo, internalized fluorescent LPS, and this was dependent on Toll‐like receptor 4 (TLR4) at the cell surface but not on TLR4‐TIR signaling through MyD88. LPS clearance from plasma was also TLR4‐dependent. Pretreatment of C57BL/6 hepatocytes with LPS prevented uptake of LPS 24 hours later and this LPS‐mediated suppression was dependent on TLR4 signaling through MyD88. Many regulators of TLR4 signaling have been identified and implicated in LPS desensitization, including suppressor of cytokine signaling 1 (SOCS1). SOCS1 mRNA and protein expression increased after LPS stimulation in hepatocytes and in whole liver. LPS uptake in hepatocytes and liver was significantly reduced following infection with adenoviral vectors overexpressing SOCS1. Similarly, inhibition of SOCS1 using small interfering (si)RNA‐mediated knockdown prevented LPS desensitization in hepatocytes. SOCS1 is known to interact with Toll/IL‐1 receptor associated protein (TIRAP) and cause TIRAP ubiquitination and degradation, which regulates TLR signaling. We have also shown previously that TIRAP regulates LPS uptake in hepatocytes. SOCS1 coimmunoprecipitated with TIRAP in wild type hepatocyte cell lysates up to 8 hours after LPS stimulation, but not at later times. In the same samples, ubiquitinated TIRAP was detected after 4 hours and up to 8 hours after LPS stimulation, but not at later times. Conclusion: These data indicate hepatocytes are desensitized by LPS in a TLR4 signaling‐dependent manner. LPS‐induced SOCS1 upregulation increases degradation of TIRAP and prevents subsequent LPS uptake. The exploitation of these mechanisms of LPS desensitization in the liver may be important in future sepsis therapies. (HEPATOLOGY 2009.)
Identification of Constitutive Phosphorylation Sites on the Epstein-Barr Virus ZEBRA Protein*

ZEBRA, the product of the Epstein-Barr virus gene bzlf1, and a member of the AP-1 subfamily of basic zipper (bZIP) transcription factors, is necessary and sufficient to disrupt viral latency and to initiate the viral lytic cycle. Two serine residues of ZEBRA, Ser167 and Ser173, are substrates for casein kinase 2 (CK2) and are constitutively phosphorylated in vivo. Phosphorylation of ZEBRA at its CK2 sites is required for proper temporal regulation of viral gene expression. Phosphopeptide analysis indicated that ZEBRA contains additional constitutive phosphorylation sites. Here we employed a co-migration strategy to map these sites in vivo. The cornerstone of this strategy was to correlate the migration of 32P- and 35S-labeled tryptic peptides of ZEBRA. The identity of the peptides was revealed by mutagenesis of methionine and cysteine residues present in each peptide. Phosphorylation sites within the peptide were identified by mutagenesis of serines and threonines. ZEBRA was shown to be phosphorylated at serine and threonine residues, but not tyrosine. Two previously unrecognized phosphorylation sites of ZEBRA were identified in the NH2-terminal region of the transactivation domain: a cluster of weak phosphorylation sites at Ser6, Thr7, and Ser8 and a strong phosphorylation site at Thr14. Thr14 was embedded in a MAP kinase consensus sequence and could be phosphorylated in vitro by JNK, despite the absence of a canonical JNK docking site. Thus ZEBRA is now known to be constitutively phosphorylated at three distinct sites.
The Sinuous Dragon: Economic Freedom and Economic Growth in China

With sinuous reforms and economic openness over the last four decades, China has enjoyed substantial economic development. Though still a developing country, its GDP per capita has grown over 10% annually, from $183(US) in 1977 to $7,590 (US) in 2014. This miracle in economic growth is attributed by some to a series of pro-market policies and reforms. Although the general trend is greater economic freedom, China has experienced brief periods of decreasing or stagnant economic freedom that correspond with slowdowns in the growth rate. In this paper we trace these changes in economic freedom in China and discuss prospects for future improvement.
A Qualitative Perspective of Family Resources Among Low Income, African American Grandmother–Caregivers

ABSTRACT This ethnographic study describes a group of 7 low-income, African American, grandmother–caregivers' perceptions of family resources. An ethnographic design, enhanced by a genogram, captured those who were available and unavailable to provide support to the grandmother. The analysis used a constant comparative method to thematically capture grandmothers' perceptions of family support resources as absent, unavailable, dependent, and reliable support, and the circumstances that led to that status. The findings reveal that many African American grandmothers are rearing children with little family support, owing mainly to the devastation of negative social and economic conditions. The results suggest areas for improvement in social work assessment and intervention.
Seasonal Variation in Nymphal Blacklegged Tick Abundance in Southern New England Forests

Abstract In the northeastern United States, risk of human exposure to tick transmitted disease is primarily a function of the abundance of the blacklegged tick, Ixodes scapularis Say. We assessed seasonal variability in the abundance of nymphal stage I. scapularis over 13 yr, collected from several forested areas throughout Rhode Island. Specifically, we examined intraseasonal differences by using two temporally distinct tick collections made during the peak nymphal tick season. Intraseasonal factors significantly impacted tick abundance, with the June tick rate (mean = 40.42, SD = 14.79) significantly more abundant than the July tick rate (mean = 27.64, SD = 15.47). The greater variability in July (coefficient of variation: June, 36.61%; July, 55.95%) lead us to conclude June tick rates are relatively stable from year to year, whereas July tick rates contribute more to intraseasonal and yearly variation.
The mast cell-committed progenitor. In vitro generation of committed progenitors from bone marrow.

Mast cell-committed progenitors are detected in the unique microenvironment of the mesenteric lymph node (MLN) of Nippostrongylus brasiliensis-infected mice but not in naive bone marrow. We have determined that MLN cells, after infection, produce high levels of IL-3, IL-4, and IgE, presumably in the form of immune complexes with antigens produced by the infecting helminth. After N. brasiliensis infection, peak production of these factors occurs several days before the peak appearance of mast cell-committed progenitors in the MLN. To determine if these factors play a role in mast cell commitment, we recreated these conditions, in vitro. Naive bone marrow cells were cultured with combinations of IL-3, IL-4, and IgE immune complexes, or on IgE-coated plates, and then assayed for acquisition of the ability to form mast cell colonies when supplemented with fibroblast-conditioned medium alone. IL-3 and IgE immune complexes, and, unexpectedly, IgE immune complexes alone were found to be capable of producing mast cell-committed progenitors, i.e., cells responsive to fibroblast-conditioned medium alone, from bone marrow, whereas IL-4 did not enhance production of mast cell-committed progenitors from bone marrow. Production of IFN-gamma peaked at the same time point as committed progenitor activity and may be responsible for down regulating the response.
A Unified Theory of Insider Trading Law

When an insider trades in his own corporation’s stock while in possession of material non-public information, courts apply what is called the “classical theory” of insider trading. This theory is the foundation of U.S. insider trading law. It has been invoked in every court opinion on the subject for the past three decades. Yet, this Article argues that the theory is an unqualified failure. The reason? Because the theory fails to do what a theory must, which is to explain settled law and provide answers to unsettled law that are intuitively appealing. We need a new theory for the classic case of insider trading, and the best candidate for the job is staring us in the face – the misappropriation theory, which historically has only applied to insider trading involving corporate “outsiders,” is superior to the classical theory. It does a better job explaining what courts actually do in classical insider trading cases. And with respect to those issues that are still open, it yields results that are more intuitively appealing. Replacing the classical theory with the misappropriation theory would have the effect of unifying insider trading law, resulting in a single theory applicable to both insiders and outsiders alike. To be sure, for some commentators, the misappropriation theory's main drawback is its so-called “brazen fiduciary problem,” the fact that, under that theory, the trader can avoid insider trading liability by simply pre-disclosing to the board an intention to trade. However, I argue that this infirmity can be largely mitigated with a simple disclosure rule, promulgated by the SEC, which would require boards of public companies to disclose any such notice received by the board. The unified (misappropriation) theory of insider trading law that I argue for here would bring much needed clarity to this doctrinal area. It would also promote values, including consistency and predictability, which are essential for the rule of law.
The 6-Kilodalton Early Secreted Antigenic Target-Responsive, Asymptomatic Contacts of Tuberculosis Patients Express Elevated Levels of Interleukin-4 and Reduced Levels of Gamma Interferon

ABSTRACT It is well known that the majority of healthy individuals exposed to Mycobacterium tuberculosis do not become clinically ill. We have previously shown that in recently exposed healthy contacts of tuberculosis (TB) patients, a strong immune response to the M. tuberculosis 6-kDa early secreted antigenic target (ESAT-6) virulence factor correlated with a higher risk of subsequent disease, although the mechanism was unclear at that time. Inspired by recent reports that elevated expression of interleukin-4 (IL-4) in health care workers exposed to M. tuberculosis also correlated with a higher risk of their subsequently developing disease, we examined expression of IL-4, its competitive antagonist IL-4δ2, and gamma interferon (IFN-γ) in healthy household contacts of TB patients from Ethiopia. We then compared cytokine expression to their recognition of ESAT-6 (which is largely restricted to members of the tuberculosis complex and which serves as a reliable marker of infection) or to Ag85A (an antigen that is conserved among the mycobacteria and serves as a nonspecific control). Our study shows that in these recently exposed individuals, there is a correlation between a strong response to ESAT-6 and elevated expression of IL-4. Further, elevated expression of IL-4 is associated with lower expression of its antagonistic splice variant IL-4δ2 and with the Th1 cytokine IFN-γ, suggesting that in these at-risk individuals, immunity is skewed away from a protective Th1 response, even before the development of clinical symptoms.
Association between Functional CYP2D6 Polymorphisms and Susceptibility to Autoimmune Diseases: A Meta-Analysis

ABSTRACT Objective: This study aimed to explore whether functional CYP2D6 polymorphisms are associated with susceptibility to autoimmune diseases. Methods: A meta-analysis was conducted on associations between autoimmune diseases and functional CYP2D6*4 1934 A/G and *3 polymorphisms and CYP2D6 phenotypes. Results: Twelve studies with 1,472 patients and 3,328 controls were included. Autoimmune disease and the CYP2D6 1934 A allele were significantly associated in the overall group, consistent with the Hardy–Weinberg equilibrium (OR = 1.227, 95% CI = 1.071–1.406, p = 0.003); stratification by ethnicity indicated that the CYP2D6 1934 A allele and autoimmune diseases were associated in Caucasians (OR = 1.225, 95% CI = 1.010–1.485, p = 0.039). The CYP2D6*3 allele was also associated with autoimmune diseases in Caucasians (OR = 1.977, 95% CI = 1.125–3.472, p = 0.018). Stratified by autoimmune disease type revealed that the CYP2D6 1934 AA genotype was associated with systemic lupus erythematosus (SLE; OR = 2.007, 95% CI = 1.170–3.442, p = 0.011) and ankylosing spondylitis (AS; OR = 2.317, 95% CI = 1.422–3.774, p = 0.001). The CYP2D6 PM+IM phenotype was significantly associated with autoimmune diseases in Caucasians (OR = 1.526, 95% CI = 1.038–2.246, p = 0.032) and with SLE (OR = 1.778, 95% CI = 1.249–2.532, p = 0.001). Conclusions: This meta-analysis indicates that CYP2D6*4 and *3 polymorphisms and the CYP2D6 phenotype are associated with susceptibility to autoimmune diseases in Caucasians; particularly, the CYP2D6*4 polymorphism and CYP2D6 PM+IM phenotype are risk factors for SLE development.
An Efficient Online Approach for Direction-Preserving Trajectory Simplification with Interval Bounds

The prevalence of GPS devices has facilitated collection of large-scale trajectories. Fresh positions of moving objects can be sampled periodically and sent to servers for data analytics and query processing. Online trajectory simplification is a compression task usually conducted at the sensor side and serves as a key component to reduce network communication overhead. In this paper, we study a new trajectory simplification problem which is direction-preserving and works in an online fashion. An efficient simplification algorithm is proposed, which is guaranteed to be error-bounded and achieves O(n) time and O(1) space complexity. In an extensive experimental evaluation with two real datasets, our approach exhibits superior performance on both running time and compression rate.