Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytokine inhibition in the treatment of COPD

Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD), including the chronic inflammatory process, emphysema, and altered innate immune response. Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP), and growth factors such as transforming growth factor-β. The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations. While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable. In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines. The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor. Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in COPD. The two largest studies that have been reported in the literature involve the use of blocking antibody to TNFα and CXCL8 (IL-8), and neither has provided benefit. Blocking the actions of CXCL8 through its CXCR2 receptor blockade was not successful either. Studies of antibodies against IL-17, IL-18, IL-1β, and TSLP are currently either being undertaken or planned. There is a need to carefully phenotype COPD and discover good biomarkers of drug efficacy for each specific target. Specific groups of COPD patients should be targeted with specific anticytokine therapy if there is evidence of high expression of that cytokine and there are features of the clinical expression of COPD that will respond.
Depth Estimation of Submerged Aquatic Vegetation in Clear Water Streams Using Low-Altitude Optical Remote Sensing

UAVs and other low-altitude remote sensing platforms are proving very useful tools for remote sensing of river systems. Currently consumer grade cameras are still the most commonly used sensors for this purpose. In particular, progress is being made to obtain river bathymetry from the optical image data collected with such cameras, using the strong attenuation of light in water. No studies have yet applied this method to map submergence depth of aquatic vegetation, which has rather different reflectance characteristics from river bed substrate. This study therefore looked at the possibilities to use the optical image data to map submerged aquatic vegetation (SAV) depth in shallow clear water streams. We first applied the Optimal Band Ratio Analysis method (OBRA) of Legleiter et al. (2009) to a dataset of spectral signatures from three macrophyte species in a clear water stream. The results showed that for each species the ratio of certain wavelengths were strongly associated with depth. A combined assessment of all species resulted in equally strong associations, indicating that the effect of spectral variation in vegetation is subsidiary to spectral variation due to depth changes. Strongest associations (R2-values ranging from 0.67 to 0.90 for different species) were found for combinations including one band in the near infrared (NIR) region between 825 and 925 nm and one band in the visible light region. Currently data of both high spatial and spectral resolution is not commonly available to apply the OBRA results directly to image data for SAV depth mapping. Instead a novel, low-cost data acquisition method was used to obtain six-band high spatial resolution image composites using a NIR sensitive DSLR camera. A field dataset of SAV submergence depths was used to develop regression models for the mapping of submergence depth from image pixel values. Band (combinations) providing the best performing models (R2-values up to 0.77) corresponded with the OBRA findings. A 10% error was achieved under sub-optimal data collection conditions, which indicates that the method could be suitable for many SAV mapping applications.
The rat sperm proteome characterized via IPG strip prefractionation and LC‐MS/MS identification

Proteomics represents a powerful tool for the analysis of mammalian spermatozoa, since these terminally differentiated cells are transcriptionally inactive and exhibit a limited dynamic range of protein expression. Here we report the identification of 5123 peptides, leading to 829 unambiguous and 2215 redundant gene products found to be present within rat spermatozoa derived from the cauda epididymis. Bioinformatics demonstrated that 60 proteins appeared to be specifically expressed in the genitourinary tract, including pyruvate dehydrogenase 1, ropporin, testis‐specific serine kinase 4, testis‐specific transporter, and retinol dehydrogenase 14. We also identified eight members of the ADAM family, seven of which have previously been detected in spermatozoa (ADAM2, ‐3, ‐4, ‐5, ‐6, ‐7, and ‐30) while ADAM34 has been identified in the sperm proteome for the first time. Approximately 21 gene products were found to possess isomerase activity including peptidylprolyl cis/trans isomerases that are known to be involved in germ cell differentiation and protein disulfide isomerases that have been implicated in sperm–oocyte fusion. Furthermore, 51 gene products clustered into ion‐transporter activity. This inventory of gene products, the first ever 2‐D LC‐MS/MS analysis of rat spermatozoa, will be invaluable in directing future research into the molecular mechanisms that drive these highly specialized cells.
Identification of coagulase-negative staphylococci with the API staph system

A kit for the identification of staphylococci based on the biochemical criteria proposed by Kloos and Schleifer (W.E. Kloos and K.H. Schleifer, J. Clin. Microbiol., 1:82-88, 1975) is now available commercially. The system was used to identify 100 strains of coagulase-negative staphylococci isolated from various body sites as the primary etiological agent of clinical infection. The increasing importance of staphylococci and their resistance to antibiotics provided the rationale for such an investigation. Over 90% of the Staphylococcus isolates were easily identified as to their species on the basis of their reaction profile to 19 biochemical tests included in the kit. The remainder, which showed minor variations, could also be assigned to the various species. Identification of the isolates was as follows: S. epidermidis, 54; S. haemolyticus, 5; S. simulans, 2; S. hominis, 1; S. capitis, 4; S. cohnii, 2; S. warneri, 2; S. xylosus, 8; and S. saprophyticus, 22. Antibiotic sensitivity patterns were determined for each of the isolates. Novobiocin resistance was detected in strains of S. saprophyticus and S. xylosus, a property hitherto recognized in Micrococcus sp. type 3 causing bacteriuria in young women. Resistance to penicillin was widespread among strains of several species, whereas resistance to tetracycline was mainly confined to strains of S. epidermidis. General resistance to sulfamethoxazole and nalidixic acid was found among all strains, with almost uniform sensitivity to the other drugs tested.
Water Main Break Rates in the USA and Canada: A Comprehensive Study, April 2012

Modern societies base their economic prosperity on a standard of living which includes a complex network of infrastructure, both above and below ground. Quality drinking water brought to the tap through elaborate underground distribution systems is a critical component to our public health and economic well-being. In the USA and Canada, it has been the hallmark of our industry and cooperation. Our water infrastructure is now in decline after decades of service. The signs of distress surface daily as water mains break, creating floods and sink holes. The loss of water service is more than an inconvenience, since it causes significant social and economic disruptions and jeopardizes public health. One factor used to quantify the occurrences of failing underground pipe networks is water main break rates. Water main break rates are calculated for all pipe materials used in the transport of water to create a measurement to judge pipe performance and durability. Water main break rates can vary year to year and by utility. However, in aggregate, break rates produce a compelling story which can aid our prudent decision making as it relates to repairing and replacing our underground pipes. This Comprehensive Water Main Break Rate Study for the USA and Canada compiles the collective experience of 188 utilities which can be used for making future critical pipe replacement decisions. It is the desire of the researchers and participants to offer data and analysis that utility managers and elected officials can apply to the circumstances of their own operations. Highlights of the Comprehensive Water Main Break Study include a new national metric for citizens served per one mile of pipe, aggregate data on pipe material break rates, analysis of age and corrosion in failure modes, and related observations on pressure, temperature and trenchless technology practices.
Recovery from Incorrect knowledge in Soar

Incorrect knowledge can be a problem for any intelligent system. Soar is a proposal for the underlying architecture that supports intelligence. It has a single representation of long-term memory and a single learning mechanism called chunking. This paper investigates the problem of recovery from incorrect knowledge in Soar. Recovery is problematic in Soar because of the simplicity of chunking: it does not modify existing productions, nor does it analyze the long-term memory during learning. In spite of these limitations, we demonstrate a domain-independent approach to recovery from incorrect control knowledge and present extensions to this approach for recovering from all types of incorrect knowledge. The key idea is to correct decisions instead of long-term knowledge. Soar's architecture allows this corrections to occur in parallel with normal processing. This approach does not require any changes to the Soar architecture and because of Soar's uniform representations for tasks and knowledge, this approach can be used for all tasks and sub-tasks in Soar.
Impacts of northern Tibetan Plateau on East Asian summer rainfall via modulating midlatitude transient eddies

Roles of the Tibetan Plateau (TP) in forming and changing the seasonal Asian climate system have been widely explored. However, little is known about modulation effects of the TP on extratropical transient eddies (TEs) and subsequent synoptic responses of the East Asian rainfall. In this study, the Community Atmosphere Model version 5.1 coupled with a slab ocean model is employed to highlight the important role of the TP in regulating the upper‐tropospheric transient wave train. Comparison between sensitivity experiments with and without the TP shows that the northern TP excites a strong anomalous anticyclone, which shifts the upper‐level East Asian westerly jet northward and helps transfer barotropic and baroclinic energy from the mean flow to the synoptic TE flow. The transient wave train is primarily shifted northward by northern TP and is forced to propagate southeastward along the eastern flank of the TP until reaching eastern China. Before the strengthening of monsoonal southerlies, the TP‐modulated transient wave train cools the troposphere, which decreases the static stability over northern China. Meanwhile, the associated anomalous warm advection induces ascending motion, leading to excessive rainfall by releasing unstable energy as the southerly strengthens. Due to the southeastward propagation of the wave train, anomalous heavy rainfall subsequently appears over eastern China from north to south, which increases day‐to‐day rainfall variation in this region. Additionally, occurrence of this upper‐tropospheric transient wave train associated with low‐level southerly peak is substantially increased by northern TP.
Latent Effects of Hsp90 Mutants Revealed at Reduced Expression Levels

In natural systems, selection acts on both protein sequence and expression level, but it is unclear how selection integrates over these two dimensions. We recently developed the EMPIRIC approach to systematically determine the fitness effects of all possible point mutants for important regions of essential genes in yeast. Here, we systematically investigated the fitness effects of point mutations in a putative substrate binding loop of yeast Hsp90 (Hsp82) over a broad range of expression strengths. Negative epistasis between reduced expression strength and amino acid substitutions was common, and the endogenous expression strength frequently obscured mutant defects. By analyzing fitness effects at varied expression strengths, we were able to uncover all mutant effects on function. The majority of mutants caused partial functional defects, consistent with this region of Hsp90 contributing to a mutation sensitive and critical process. These results demonstrate that important functional regions of proteins can tolerate mutational defects without experimentally observable impacts on fitness.
Starvation mitigation for dense WLANs through distributed channel selection: Potential game approach

A potential game based distributed channel selection scheme is proposed in this paper to mitigate the flow-in-the-middle (FIM) throughput starvation problem that frequently occurs in dense wireless local area networks (WLANs). The FIM throughput starvation occurs when neighbors of a given node are not within the carrier sense ranges of each other. Since they spatially reuse the channel and at least one of them transmits with a high probability, the node in the middle would detect the channel being occupied for a prolonged time and therefore experience extremely low throughput. The basic idea of the proposed scheme is to let each access point (AP) select the channel that reduces the number of three-node chain topologies on its two-hop neighborhood contention graph. The proposed scheme is proved to be a potential game, i.e., the proposed scheme is guaranteed to converge. Graph-based simulation shows that starvation occurs on 20% of nodes when nodes randomly select their frequency channels. The proposed scheme significantly reduces the number of starved nodes along with iterations, outperforming the compared traditional potential game based scheme.
Immunovirological and Biochemical Changes in Nigerian Patients with Hepatitis B Coinfection on Antiretroviral Therapy

Hepatitis B virus (HBV) co-infection with HIV is high among Nigerians. Some studies have suggested impaired CD4 recovery among coinfected patients compared to the HIV mono infected. This retrospective study of treatment-naive HIV infected patients was aimed at determining the trend of changes in CD4+ counts, HIV-RNA and renal and liver function tests in response to combined antiretroviral therapy (CART). A questionnaire was utilised to extract clinical and laboratory data of HBV co infected HIV/AIDS patients before treatment and at six, twelve and eighteen months of therapy with CART. Findings were compared to those of HIV mono infected. Relevant statistical instruments were used to analyse for comparisons of means of Log10 HIV viral load and CD4 count using SPSS package 15.0. All levels of sig-nificance were at 5 %. Two thousand five hundred and sixty two patients were analysed. Of these, 354(13.8%) were HBsAg positive. Majority (63.1%) were females. Most of the recruited patients were on combivir and nevirapine. The median CD4 count for the HBsAg negative was 104 cells/mm3 (IQR 34 – 171) and it was significantly higher than those of the positive (91 cells/mm3) (p < 0.05). ALT and AST were higher among HBsAg positives, while urea and creatinine levels were similar. The median change in CD4 count from baseline and during the course of therapy were similar in the two groups. Similarly, virological responses were not different in the two groups at the various time points. In con-clusion no significant difference in the rate of CD4 recovery and HIV-RNA decline in among coinfected and monoin-fected HIV patients at different stages of therapy.
Statistical properties of seismicity of fault zones at different evolutionary stages

SUMMARY We perform a systematic parameter space study of the seismic response of a large fault with different levels of heterogeneity, using a 3-D elastic framework within the continuum limit. The fault is governed by rate-and-state friction and simulations are performed for model realizations with frictional and large scale properties characterized by different ranges of size scales. We use a number of seismicity and stress functions to characterize different types of seismic responses and test the correlation between hypocenter locations and the employed distributions of model parameters. The simulated hypocenters are found to correlate significantly with small L values of the rate-and-state friction. The final sizes of earthquakes are correlated with physical properties at their nucleation sites. The obtained stacked scaling relations are overall self-similar and have good correspondence with properties of natural earthquakes.
Septin 7 Interacts with Centromere-associated Protein E and Is Required for Its Kinetochore Localization*

Chromosome segregation in mitosis is orchestrated by dynamic interaction between spindle microtubules and the kinetochore. Septin (SEPT) belongs to a conserved family of polymerizing GTPases localized to the metaphase spindle during mitosis. Previous study showed that SEPT2 depletion results in chromosome mis-segregation correlated with a loss of centromere-associated protein E (CENP-E) from the kinetochores of congressing chromosomes (1). However, it has remained elusive as to whether CENP-E physically interacts with SEPT and how this interaction orchestrates chromosome segregation in mitosis. Here we show that SEPT7 is required for a stable kinetochore localization of CENP-E in HeLa and MDCK cells. SEPT7 stabilizes the kinetochore association of CENP-E by directly interacting with its C-terminal domain. The region of SEPT7 binding to CENP-E was mapped to its C-terminal domain by glutathione S-transferase pull-down and yeast two-hybrid assays. Immunofluorescence study shows that SEPT7 filaments distribute along the mitotic spindle and terminate at the kinetochore marked by CENP-E. Remarkably, suppression of synthesis of SEPT7 by small interfering RNA abrogated the localization of CENP-E to the kinetochore and caused aberrant chromosome segregation. These mitotic defects and kinetochore localization of CENP-E can be successfully rescued by introducing exogenous GFP-SEPT7 into the SEPT7-depleted cells. These SEPT7-suppressed cells display reduced tension at kinetochores of bi-orientated chromosomes and activated mitotic spindle checkpoint marked by Mad2 and BubR1 labelings on these misaligned chromosomes. These findings reveal a key role for the SEPT7-CENP-E interaction in the distribution of CENP-E to the kinetochore and achieving chromosome alignment. We propose that SEPT7 forms a link between kinetochore distribution of CENP-E and the mitotic spindle checkpoint.
Relapse pattern and second-line treatment following multimodality treatment for malignant pleural mesothelioma.

OBJECTIVES To analyse the relapse pattern and influence of second-line treatment after recurrence of malignant pleural mesothelioma (MPM) in patients who had previously undergone multimodality treatment. METHODS Between September 1999 and December 2013, 136 patients underwent macroscopic complete resection (MCR) by extrapleural pneumonectomy after induction chemotherapy for MPM. We analysed 106 patients who presented with recurrent disease until October 2014. Data were retrieved from our mesothelioma database, with additional information regarding precise localization gathered by reviewing the imaging and medical records. RESULTS The overall recurrence rate was 78% (106/136 patients). The median freedom from recurrence was 9 months after surgery [95% confidence interval (95% CI) 7-10]. Local recurrence only was observed in 33 patients (31%), distant metastases only in 27 patients (26%) and simultaneous distant and local recurrence in 46 patients (43%). Local recurrence was observed significantly less frequently in patients having received adjuvant radiotherapy (19 vs 47%, P = 0.003), but there was no significant impact on overall survival (OS) [radiation: 22 months (95% CI 19-24); no-radiation: 23 months (95% CI 18-27), P = 0.6]. The median OS was 22 months (95% CI 21-24), median post-recurrence survival (PRS) was 7 months (95% CI 5-9) and patients with local recurrence only survived significantly longer (12 months, 95% CI 8-16) compared with patients with distant recurrence only (5 months, 95% CI 2-8) or distant plus local relapse (6 months, 95% CI 3-9; P = 0.04). A total of 78 patients received a second-line therapy after tumour recurrence: chemotherapy (n = 48), local radiotherapy (n = 9), surgery (n = 10) or a combination thereof (n = 11). Patients undergoing second-line treatment survived significantly longer compared with patients not receiving therapy (P < 0.0005). The median PRS after surgery was significantly longer than that of patients receiving chemo-, radio- or chemo-radiotherapy (P = 0.04). CONCLUSIONS Local recurrence of MPM remains the most frequent type of relapse even after multimodality treatment including MCR. In the present cohort, active treatment seems beneficial to the patient since surgical excision of local tumour relapse has good long-term outcome in selected patients. Thus, second-line treatment may prolong PRS; however, these results need to be confirmed in a prospective manner.
O-GlcNAc-Specific Antibody CTD110.6 Cross-Reacts with N-GlcNAc2-Modified Proteins Induced under Glucose Deprivation

Modification of serine and threonine residues in proteins by O-linked β-N-acetylgulcosamine (O-GlcNAc) glycosylation is a feature of many cellular responses to the nutritional state and to stress. O-GlcNAc modification is reversibly regulated by O-linked β-N-acetylgulcosamine transferase (OGT) and β-D-N-acetylgulcosaminase (O-GlcNAcase). O-GlcNAc modification of proteins is dependent on the concentration of uridine 5′-diphospho-N-acetylgulcosamine (UDP-GlcNAc), which is a substrate of OGT and is synthesized via the hexosamine biosynthetic pathway. Immunoblot analysis using the O-GlcNAc-specific antibody CTD110.6 has indicated that glucose deprivation increases protein O-GlcNAcylation in some cancer cells. The mechanism of this paradoxical phenomenon has remained unclear. Here we show that the increased glycosylation induced by glucose deprivation and detected by CTD110.6 antibodies is actually modification by N-GlcNAc2, rather than by O-GlcNAc. We found that this induced glycosylation was not regulated by OGT and O-GlcNAcase, unlike typical O-GlcNAcylation, and it was inhibited by treatment with tunicamycin, an N-glycosylation inhibitor. Proteomics analysis showed that proteins modified by this induced glycosylation were N-GlcNAc2-modified glycoproteins. Furthermore, CTD110.6 antibodies reacted with N-GlcNAc2-modified glycoproteins produced by a yeast strain with a ts-mutant of ALG1 that could not add a mannose residue to dolichol-PP-GlcNAc2. Our results demonstrated that N-GlcNAc2-modified glycoproteins were induced under glucose deprivation and that they cross-reacted with the O-GlcNAc-specific antibody CTD110.6. We therefore propose that the glycosylation status of proteins previously classified as O-GlcNAc-modified proteins according to their reactivity with CTD110.6 antibodies must be re-examined. We also suggest that the repression of mature N-linked glycoproteins due to increased levels of N-GlcNAc2-modifed proteins is a newly recognized pathway for effective use of sugar under stress and deprivation conditions. Further research is needed to clarify the physiological and pathological roles of N-GlcNAc2-modifed proteins.