Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical evaluation of ceftolozane–tazobactam for complicated urinary tract and intra-abdominal infections

The rise in resistant Gram-negative pathogens continues to challenge clinicians treating infections. These resistant infections have inspired the development of new antimicrobial agents, including ceftolozane–tazobactam, a novel β-lactam/β-lactamase inhibitor combination approved by the US Food and Drug Administration for the treatment of complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) in combination with metronidazole. Ceftolozane exhibits bactericidal activity by inhibiting penicillin-binding proteins (PBPs), with high affinity for PBP1b, PBP1c, and PBP3. The addition of tazobactam protects ceftolozane from hydrolysis by irreversibly binding to some β-lactamase enzymes. Ceftolozane–tazobactam is active against a wide range of Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa, several streptococcal species, and Bacteroides fragilis. When anaerobic coverage is needed, it should be used in combination with metronidazole. Ceftolozane demonstrates linear pharmacokinetics, low protein binding, and minimal accumulation with repeated dosing. The major pharmacokinetic/pharmacodynamic index for ceftolozane is the percentage of the dosing interval in which the plasma free drug concentration remains higher than the minimum inhibitory concentration (%T.MIC). Phase III clinical trials for the treatment of cUTIs and cIAIs have been completed, showing that it is an effective and safe alternative for the treatment of these infections. The approved dose for cUTIs and cIAIs is 1.5 g (1 g ceftolozane and 500 mg tazobactam) infused over 1 hour every 8 hours. A higher 3 g dose is currently in Phase III trials for the treatment of ventilated nosocomial pneumonia. Dosage adjustments are necessary for patients with moderate-to-severe renal impairment. Current data suggest that ceftolozane–tazobactam is a promising carbapenem-sparing alternative agent for the treatment of cUTIs and cIAIs, including those caused by ESBL-producing Enterobacteriaceae and MDR P. aeruginosa.
Real-Time Macroeconomic Monitoring: Real Activity, Inflation, and Interactions

We sketch a framework for monitoring macroeconomic activity in real-time and push it in new directions. In particular, we focus not only on real activity, which has received most attention to date, but also on inflation and its interaction with real activity. As for the recent recession, we find that (1) it likely ended around July 2009; (2) its most extreme aspects concern a real activity decline that was unusually long but less unusually deep, and an inflation decline that was unusually deep but brief; and (3) its real activity and inflation interactions were strongly positive, consistent with an adverse demand shock.
Quantitative Analysis by Pixel Intensity and Fractal Dimensions for Imaging Diagnosis of Periapical Lesions

Aims of study: To perform quantitative analysis of periapical lesions by pixel intensity, fractal dimensions in diagnosis of periapical lesions. Subjects, Material and Methods: Twentysix patients aged between 8-40 years classified as age groups: Group 1 from 8-18 years, Group 2 from 19-29 years, Group 3 from 30- 40 years and with periapical lesion in maxillary and mandibular anterior teeth and premolars diagnosed by their clinical sign and symptoms and radiographic findings who attended to the maxillofacial unit in al Al Jamhori Teaching Hospital and Specialist Center of Dentistry/Right bank in Mosul city were include in this study. The periapical radiograph for all twenty six patients had taken by bisecting angle technique. All The periapical radiograph, then digitize to convert them to the digital form for detection pixel intensity, the developed imagej software version 1.34s software was used for image processing then found the pixel intensity for all lesions and also histogram.Periapical lesion shows fractal behavior which isquantitative evaluation of periapical area and fractal dimensions also measured.
ON THE EQUIVALENCE OF VARIOUS WEAK NOTIONS OF SOLUTIONSOF ELLIPTIC PDES WITH MEASURABLE INGREDIENTS

Section 0. Introduction In this work we outline some aspects of the \L p theory" of viscosity solutions of scalar fully nonlinear elliptic partial diierential equations of the form G(x; u(x); Du(x); D 2 u(x)) = 0 in ; (0:1) where is a bounded open set in IR n , Du corresponds to the gradient (u x 1 ; : : : ; u x n) of u, D 2 u corresponds to the Hessian matrix (u x i ;x j) of second order partial derivatives of u, N is a Lebesgue null set, and G : ((n N) IR IR n S(n) ! IR: Here S(n) denotes the set of n n real symmetric matrices; S(n) will be equipped with its usual order, that is 0 P means 0 hP; i for 2 IR n , where hh; i is the Euclidean inner-product, and X Y means 0 Y ? X. A key point in the discussion is that G(x; r; p; X) depends measurably (and not continuously) on x, and therefore the notion of viscosity solutions must be suitably adapted to this situation. Part of our concerns lie in the relations between the various ways this has been done, and we will present some new results in this direction. Other goals of this work are to provide a review of some existing results, and to improve the route to understanding them. We will rewrite (0.1) in the form
Using Routinely Reported Tuberculosis Genotyping and Surveillance Data to Predict Tuberculosis Outbreaks

We combined routinely reported tuberculosis (TB) patient characteristics with genotyping data and measures of geospatial concentration to predict which small clusters (i.e., consisting of only 3 TB patients) in the United States were most likely to become outbreaks of at least 6 TB cases. Of 146 clusters analyzed, 16 (11.0%) grew into outbreaks. Clusters most likely to become outbreaks were those in which at least 1 of the first 3 patients reported homelessness or excess alcohol or illicit drug use or was incarcerated at the time of TB diagnosis and in which the cluster grew rapidly (i.e., the third case was diagnosed within 5.3 months of the first case). Of 17 clusters with these characteristics and therefore considered high risk, 9 (53%) became outbreaks. This retrospective cohort analysis of clusters in the United States suggests that routinely reported data may identify small clusters that are likely to become outbreaks and which are therefore candidates for intensified contact investigations.
Induced Genome-Wide Binding of Three Arabidopsis WRKY Transcription Factors during Early MAMP-Triggered Immunity

Genome-wide analysis reveals the in vivo binding sites of Arabidopsis WRKY18, WRKY33, and WRKY40 transcription factors during early MTI and the consequences of WRKY18 and WRKY40 binding on transcriptional output. During microbial-associated molecular pattern-triggered immunity (MTI), molecules derived from microbes are perceived by cell surface receptors and upon signaling to the nucleus initiate a massive transcriptional reprogramming critical to mount an appropriate host defense response. WRKY transcription factors play an important role in regulating these transcriptional processes. Here, we determined on a genome-wide scale the flg22-induced in vivo DNA binding dynamics of three of the most prominent WRKY factors, WRKY18, WRKY40, and WRKY33. The three WRKY factors each bound to more than 1000 gene loci predominantly at W-box elements, the known WRKY binding motif. Binding occurred mainly in the 500-bp promoter regions of these genes. Many of the targeted genes are involved in signal perception and transduction not only during MTI but also upon damage-associated molecular pattern-triggered immunity, providing a mechanistic link between these functionally interconnected basal defense pathways. Among the additional targets were genes involved in the production of indolic secondary metabolites and in modulating distinct plant hormone pathways. Importantly, among the targeted genes were numerous transcription factors, encoding predominantly ethylene response factors, active during early MTI, and WRKY factors, supporting the previously hypothesized existence of a WRKY subregulatory network. Transcriptional analysis revealed that WRKY18 and WRKY40 function redundantly as negative regulators of flg22-induced genes often to prevent exaggerated defense responses.
Too Interconnected To Fail: Financial Contagion and Systemic Risk in Network Model of CDS and Other Credit Enhancement Obligations of US Banks

Credit default swaps (CDS) which constitute up to 98% of credit derivatives have had a unique, endemic and pernicious role to play in the current financial crisis. However, there are few in depth empirical studies of the financial network interconnections among banks and between banks and nonbanks involved as CDS protection buyers and protection sellers. The ongoing problems related to technical insolvency of US commercial banks is not just confined to the so called legacy/toxic RMBS assets on balance sheets but also because of their credit risk exposures from SPVs (Special Purpose Vehicles) and the CDS markets. The dominance of a few big players in the chains of insurance and reinsurance for CDS credit risk mitigation for banks’ assets has led to the idea of “too interconnected to fail” resulting, as in the case of AIG, of having to maintain the fiction of non-failure in order to avert a credit event that can bring down the CDS pyramid and the financial system. This paper also includes a brief discussion of the complex system Agent-based Computational Economics (ACE) approach to financial network modeling for systemic risk assessment. Quantitative analysis is confined to the empirical reconstruction of the US CDS network based on the FDIC Q4 2008 data in order to conduct a series of stress tests that investigate the consequences of the fact that top 5 US banks account for 92% of the US bank activity in the $34 tn global gross notional value of CDS for Q4 2008 (see, BIS and DTCC). The May-Wigner stability condition for networks is considered for the hub like dominance of a few financial entities in the US CDS structures to understand the lack of robustness. We provide a Systemic Risk Ratio and an implementation of concentration risk in CDS settlement for major US banks in terms of the loss of aggregate core capital. We also compare our stress test results with those provided by SCAP (Supervisory Capital Assessment Program). Finally, in the context of the Basel II credit risk transfer and synthetic securitization framework, there is little evidence that the CDS market predicated on a system of offsets to minimize final settlement can provide the credit risk mitigation sought by banks for reference assets in the case of a significant credit event. The large negative externalities that arise from a lack of robustness of the CDS financial network from the demise of a big CDS seller undermines the justification in Basel II that banks be permitted to reduce capital on assets that have CDS guarantees. We recommend that the Basel II provision for capital reduction on bank assets that have CDS cover should be discontinued.
Intra-Firm Wage Dispersion and Firm Performance: Evidence from Linked Employer-Employee Data

This paper examines the relationship between intra-firm wage dispersion and firm performance in large Belgian firms using a unique matched employer-employee data set. On the basis of the Winter-Ebmer and Zweimuller's (1999) methodology, we find a positive and significant relationship between intra-firm wage dispersion and profits per capita, even when controlling for individual and firm characteristics and addressing potential simultaneity problems. Results also suggest that the intensity of this relationship is stronger for blue-collar workers and within firms with a high degree of monitoring. These findings are more in line with the 'tournament' models than with the 'fairness, morale and cohesiveness' models.
Field evaluation of a PCR for the diagnosis of chlamydial abortion in sheep

A total of 94 vaginal swab samples and 195 serum samples collected from aborted ewes in 15 flocks were examined by pcr and a complement fixation test, respectively. In addition, 172 samples of stomach contents from fetuses from different flocks submitted for the diagnosis of abortion during the four lambing periods between 2000 and 2004 were tested by pcr. Chlamydial dna was detected in seven vaginal swabs obtained from five of the 15 flocks and in six samples of fetal stomach contents. The results of pcr and flock serology for Chlamydia were positive in five of the 15 flocks and negative in eight.
A new scheme for effective MAC-layer DiffServ supports in mobile ad hoc networks and multihop wireless LANs

We propose the multiple access collision prevention (MACP) scheme for medium access control (MAC) in ad hoc networks and multihop wireless LANs. MACP is the first and only distributed MAC scheme that can support collision-free transmissions for both control messages and data packets, even in the presence of hidden terminals. Although dual busy tone multiple access (DBTMA) can support collision-free transmissions for data packets, MACP is the first and only distributed MAC scheme that can support collision-free data packet transmissions without relying on busy tone or dual transceivers per mobile device. MACP effectively supports differentiated service through binary countdown and prioritized group activation based on the priority bits and probability density functions for their competition numbers and the distributed differentiated scheduling discipline. The differentiation capability of MACP is considerably stronger than that of IEEE 802.11e in ad hoc networks and multihop wireless LANs.
A Novel Location-Centric IoT-Cloud Based On-Street Car Parking Violation Management System in Smart Cities

Nowadays, in big cities, parking management is a critical issue from both the driver’s side and the city government’s side. From the driver’s side, how to find an available parking lot in a city is a considerable concern. As a result, smart parking systems recently have received great interest, both in academia and industry. From the city government’s side, how to manage and distribute such a limited public parking resource efficiently to give every visitor a fair chance of finding an on-street parking lot is also a considerable concern. However, existing studies of smart parking management focus only on assisting the driver’s side to find available parking spaces. This study aims to raise a new perspective on such smart parking management and to propose a novel location-centric IoT-cloud-based parking violation management system. The system is designed to assist authoritative officers in finding parking violations easily and recommends the least cost path for officers so that officers can achieve their highest productivity in finding parking violations and issuing parking tickets. Experimental results show that the system not only improves the productivity of officers in finding parking violations and issuing tickets, but also helps reduce the traveling cost of officers and to reduce the average violation period of violating cars considerably.
Genetic and pharmacological manipulations of the serotonergic system in early life: neurodevelopmental underpinnings of autism-related behavior

Serotonin, in its function as neurotransmitter, is well-known for its role in depression, autism and other neuropsychiatric disorders, however, less known as a neurodevelopmental factor. The serotonergic system is one of the earliest to develop during embryogenesis and early changes in serotonin levels can have large consequences for the correct development of specific brain areas. The regulation and functioning of serotonin is influenced by genetic risk factors, such as the serotonin transporter polymorphism in humans. This polymorphism is associated with anxiety-related symptoms, changes in social behavior, and cortical gray and white matter changes also seen in patients suffering from autism spectrum disorders (ASD). The human polymorphism can be mimicked by the knockout of the serotonin transporter in rodents, which are as a model system therefore vital to explore the precise neurobiological mechanisms. Moreover, there are pharmacological challenges influencing serotonin in early life, like prenatal/neonatal exposure to selective serotonin reuptake inhibitors (SSRI) in depressed pregnant women. There is accumulating evidence that this dysregulation of serotonin during critical phases of brain development can lead to ASD-related symptoms in children, and reduced social behavior and increased anxiety in rodents. Furthermore, prenatal valproic acid (VPA) exposure, a mood stabilizing drug which is also thought to interfere with serotonin levels, has the potency to induce ASD-like symptoms and to affect the development of the serotonergic system. Here, we review and compare the neurodevelopmental and behavioral consequences of serotonin transporter gene variation, and prenatal SSRI and VPA exposure in the context of ASD.
Mutation-Structure-Function Relationship Based Integrated Strategy Reveals the Potential Impact of Deleterious Missense Mutations in Autophagy Related Proteins on Hepatocellular Carcinoma (HCC): A Comprehensive Informatics Approach

Autophagy, an evolutionary conserved multifaceted lysosome-mediated bulk degradation system, plays a vital role in liver pathologies including hepatocellular carcinoma (HCC). Post-translational modifications (PTMs) and genetic variations in autophagy components have emerged as significant determinants of autophagy related proteins. Identification of a comprehensive spectrum of genetic variations and PTMs of autophagy related proteins and their impact at molecular level will greatly expand our understanding of autophagy based regulation. In this study, we attempted to identify high risk missense mutations that are highly damaging to the structure as well as function of autophagy related proteins including LC3A, LC3B, BECN1 and SCD1. Number of putative structural and functional residues, including several sites that undergo PTMs were also identified. In total, 16 high-risk SNPs in LC3A, 18 in LC3B, 40 in BECN1 and 43 in SCD1 were prioritized. Out of these, 2 in LC3A (K49A, K51A), 1 in LC3B (S92C), 6 in BECN1 (S113R, R292C, R292H, Y338C, S346Y, Y352H) and 6 in SCD1 (Y41C, Y55D, R131W, R135Q, R135W, Y151C) coincide with potential PTM sites. Our integrated analysis found LC3B Y113C, BECN1 I403T, SCD1 R126S and SCD1 Y218C as highly deleterious HCC-associated mutations. This study is the first extensive in silico mutational analysis of the LC3A, LC3B, BECN1 and SCD1 proteins. We hope that the observed results will be a valuable resource for in-depth mechanistic insight into future investigations of pathological missense SNPs using an integrated computational platform.
Adaptation of avian influenza A (H6N1) virus from avian to human receptor‐binding preference

The receptor‐binding specificity of influenza A viruses is a major determinant for the host tropism of the virus, which enables interspecies transmission. In 2013, the first human case of infection with avian influenza A (H6N1) virus was reported in Taiwan. To gather evidence concerning the epidemic potential of H6 subtype viruses, we performed comprehensive analysis of receptor‐binding properties of Taiwan‐isolated H6 HAs from 1972 to 2013. We propose that the receptor‐binding properties of Taiwan‐isolated H6 HAs have undergone three major stages: initially avian receptor‐binding preference, secondarily obtaining human receptor‐binding capacity, and recently human receptor‐binding preference, which has been confirmed by receptor‐binding assessment of three representative virus isolates. Mutagenesis work revealed that E190V and G228S substitutions are important to acquire the human receptor‐binding capacity, and the P186L substitution could reduce the binding to avian receptor. Further structural analysis revealed how the P186L substitution in the receptor‐binding site of HA determines the receptor‐binding preference change. We conclude that the human‐infecting H6N1 evolved into a human receptor preference.
Peripheral T cell activation and deletion induced by transfer of lymphocyte subsets expressing endogenous or exogenous mouse mammary tumor virus

Murine T cell reactivity with products of the minor lymphocyte stimulatory (Mls) locus correlates with the expression of particular variable (V) domains of the T cell receptor (TCR) beta chain. It was recently demonstrated that Mls antigens are encoded by an open reading frame (ORF) in the 3' long terminal repeat of either endogenous or exogenous mouse mammary tumor virus (MMTV). Immature thymocytes expressing reactive TCR-V beta domains are clonally deleted upon exposure to endogenous Mtv's. Mature T cells proliferate vigorously in response to Mls-1a (Mtv-7) in vivo, but induction of specific anergy and deletion after exposure to Mtv-7-expressing cells in the periphery has also been described. We show here that B cells and CD8+ (but not CD4+) T cells from Mtv-7+ mice efficiently induce peripheral deletion of reactive T cells upon transfer to Mtv-7- recipients, whereas only B cells stimulate specific T cell proliferation in vivo. In contrast to endogenous Mtv-7, transfer of B, CD4+, or CD8+ lymphocyte subsets from mice maternally infected with MMTV(SW), an infectious homologue of Mtv- 7, results in specific T cell deletion in the absence of a detectable proliferative response. Finally, we show by secondary transfers of infected cells that exogenous MMTV(SW) is transmitted multidirectionally between lymphocyte subsets and ultimately to the mammary gland. Collectively our data demonstrate heterogeneity in the expression and/or presentation of endogenous and exogenous MMTV ORF by lymphocyte subsets and emphasize the low threshold required for induction of peripheral T cell deletion by these gene products.
Trends of prevalence of primary HIV drug resistance in Germany.

BACKGROUND Primary HIV drug resistance (PDR) is associated with poor treatment outcome of first-line highly active antiretroviral therapy (HAART). The aim of the study was to observe the trend of prevalence of PDR between 2001 and 2005. METHODS In a prospective multicentre study in the state of Nordrhein-Westfalen, Germany, 831 treatment-naive chronically HIV-infected patients underwent genotypic resistance testing. RESULTS Six hundred and forty (77%) of them were male. Two-thirds of the patients (558, 67%) were infected with HIV subtype B. PDR was found in 75 of 831 [9%; 95% confidence interval (CI) 7.1-10.9] cases entering the study between January 2001 and December 2005. An increasing trend of PDR was found from 2001 (4.8%; CI 2.1-9.4) to 2005 (9.0%; CI 5.4-12.6; P = 0.08). A significant tendency to higher PDR was observed for ethnicity other than Caucasian (P = 0.04), HIV subtypes other than B (P = 0.02) and transmission routes other than homosexual (P = 0.03). CONCLUSIONS A non-significant increase in prevalence of PDR was observed from 2001 to 2005. A significant trend to higher PDR rate was detected in non-Caucasian patients, patients infected with non-B subtypes, and in patients with risk factors for acquisition of HIV other than homosexual transmission. Based on the fact that there is a trend to higher PDR rate, resistance testing in untreated HIV-infected patients starting HAART becomes more important in clinical routine. The identification of patient subgroups with a remarkable risk of PDR makes continuous monitoring of PDR mandatory.