Miracle-dz/UniFAR-FTUs huggingface dataset:
Cloud Computing: Adoption Considerations for Business and Education

Cloud computing is gathering significant momentum in business and academia through the rich benefits it offers. It is apparent from the literature that both businesses and academic institutions would benefit greatly from the adoption of cloud technology, providing the challenges presented are overcome. This paper aims to review prevalent literature on cloud computing, presenting an initial comprehensive insight into how cloud technology is transforming businesses and the wider Information Technology (IT) industry in general, the service deployment models of Software as a Service (SaaS), Platform as a Service (PaaS), and Infrastructure as a Service (IaaS), and a discussion of perceived benefits and challenges of cloud adoption. The paper's core focus addresses the domain of Education as an area of cloud application with a cloud based e-learning system developed to demonstrate the capabilities and effectiveness of cloud technology. The last section of the paper offers a conclusion, discussing how cloud computing will evolve hereafter along with recommendations for furthering our research work.
Ontogenetic and Among-Individual Variation in Foraging Strategies of Northeast Pacific White Sharks Based on Stable Isotope Analysis

There is growing evidence for individuality in dietary preferences and foraging behaviors within populations of various species. This is especially important for apex predators, since they can potentially have wide dietary niches and a large impact on trophic dynamics within ecosystems. We evaluate the diet of an apex predator, the white shark (Carcharodon carcharias), by measuring the stable carbon and nitrogen isotope composition of vertebral growth bands to create lifetime records for 15 individuals from California. Isotopic variations in white shark diets can reflect within-region differences among prey (most importantly related to trophic level), as well as differences in baseline values among the regions in which sharks forage, and both prey and habitat preferences may shift with age. The magnitude of isotopic variation among sharks in our study (>5‰ for both elements) is too great to be explained solely by geographic differences, and so must reflect differences in prey choice that may vary with sex, size, age and location. Ontogenetic patterns in δ15N values vary considerably among individuals, and one third of the population fit each of these descriptions: 1) δ15N values increased throughout life, 2) δ15N values increased to a plateau at ∼5 years of age, and 3) δ15N values remained roughly constant values throughout life. Isotopic data for the population span more than one trophic level, and we offer a qualitative evaluation of diet using shark-specific collagen discrimination factors estimated from a 3+ year captive feeding experiment (Δ13Cshark-diet and Δ15Nshark-diet equal 4.2‰ and 2.5‰, respectively). We assess the degree of individuality with a proportional similarity index that distinguishes specialists and generalists. The isotopic variance is partitioned among differences between-individual (48%), within-individuals (40%), and by calendar year of sub-adulthood (12%). Our data reveal substantial ontogenetic and individual dietary variation within a white shark population.
Molecular Dynamics Studies on the Enzalutamide Resistance Mechanisms Induced by Androgen Receptor Mutations

The second‐generation antiandrogen enzalutamide, targeting androgen receptor (AR), was approved to treat castration resistant prostate cancer (CRPC) in 2012. Its resistance was observed when it was in the clinical research stage. AR mutation is the main factor of enzalutamide resistance. AR F876L and F876L_T877A mutations were reported to switch enzalutamide from AR antagonist to agonist, but W741C cannot. There are various mutations in the ligand binding domain of AR LBD, such as L701H, W741L, H874Y, T877A, and M895T, if these mutations can lead to drug resistance problem or not is not known. In this work, molecular dynamics (MD) simulations and molecular mechanics Generalized Born (GB) surface area (MM‐GBSA) calculations were employed to explore the interaction mechanisms between enzalutamide and wild‐type (WT)/mutant ARs. The simulation results indicate that helix 12 (H12), which lies on the top of the AR LBD like a cover, plays a vital role for the function of enzalutamide. When C‐ring of enzalutamide locates near to H12, the distance between enzalutamide and H12 is reduced, which prevents H12 from closing and distort the coactivator binding site, resulting in the inactivation of transcription. In this case, enzalutamide acts as an AR antagonist. However, when the C‐ring of enzalutamide is near to helix H11 or the Loop 11–12, H12 tends to close to form a coactivator binding site to facilitate transcription, enzalutamide acts as an AR agonist. Moreover, per‐residue free energy decomposition analysis indicates that M895 and I899 are key residues in the antagonist mechanism of enzalutamide. J. Cell. Biochem. 118: 2792–2801, 2017. © 2017 Wiley Periodicals, Inc.
Methods for diagnosing onychomycosis: a comparative study and review of the literature.

OBJECTIVE To identify the sensitivity of several readily available diagnostic tests for onychomycosis. DESIGN Cross-sectional study. SETTING Dermatology and podiatry departments at a teaching hospital. PATIENTS Sixty-three adult men and women with a clinical examination highly suggestive of onychomycosis. MAIN OUTCOME MEASURES Sensitivity of each test and of several test combinations. RESULTS Nail samples underwent 6 diagnostic tests. Routine histopathologic examination with periodic acid-Schiff stain (PAS) (PATHPAS) was 85% sensitive. Sensitivities for potassium hydroxide dissolution and centrifugation combined with PAS, fluorescent brightener, or chlorazol black E were 57%, 53%, and 53%, respectively. Culture on Sabouraud agar withchloramphenicol and cycloheximide (Mycosel agar) was 32% sensitive; on Littman-oxgall agar, 23% sensitive. The most sensitive combination of tests, both culture methods plus PATHPAS, was 94% sensitive (not statistically different from the sensitivity of PATHPAS alone [P = .26]). CONCLUSIONS When onychomycosis is suspected clinically, PATHPAS of the nail is the single most sensitive of the diagnostic tests we evaluated. Because it is quickly performed and relatively operator independent, PATHPAS is practical for clinical and research purposes. Further study is needed to determine if sensitivity may be enhanced by combining PATHPAS with cultures obtained by several collection methods (clipping, curettage, and shaving). Such combinations may serve as sensitive and efficient strategies for diagnosing onychomycosis.
Inappropriate Intensive Care Unit admissions: Nigerian doctors' perception and attitude.

BACKGROUND Nonclinical factors are said to influence decisions to admit patients into the Intensive Care Unit (ICU). We therefore assessed the perception and attitude of Nigerian doctors working in the ICU about inappropriate admissions and request for admission in the setting of a full ICU. METHODS An anonymous, self-administered questionnaire survey was carried out among doctors working in the ICU of 17 University Teaching Hospitals, in Nigeria. A score of 0 (least usual reason) to 5 (most usual reason) was ascribed to some factors that can influence ICU admission. In addition, each of the 4 possible actions in the setting of a full ICU was graded from 0 (least likely) to 5 (most likely). The result was analyzed as appropriate. RESULTS Sixty-four doctors participated in the survey. Inappropriate admissions were acknowledged by 96% of respondents. Perceived reasons included pressure from superiors (93.7%), referring clinicians (89.1%), and hospital management (87.5%). If confronted with request for admission in the setting of a full ICU, respondents will arrange for the discharge of fit ICU patients to the ward (95.3%), transfer patients not receiving acute care to high dependency unit or recovery room (70.3%), or create additional ICU beds (42.2%). Chi-square test showed a significant difference between single and married respondents with regard to clinical doubt (P = 0.01) and pressure from referring clinician (P = 0.02) as reasons for inappropriate admission. Respondents' gender, marital status, professional activity, and number of ICU admissions per year did not affect possible steps in the setting of a full ICU. CONCLUSION Inappropriate ICU admissions were perceived as a common event and were mainly attributed to pressure from seniors, referring clinicians, and hospital management. Further work is necessary to determine the impact of such admissions on ICU efficiency.
CD90 Expression Controls Migration and Predicts Dasatinib Response in Glioblastoma

Purpose: CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear. Experimental Design: The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines, in vivo orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells. Results: We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes in vivo. Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion in vivo and killed CD90high primary GSC lines. Conclusions: Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90high GBM patients. Clin Cancer Res; 23(23); 7360–74. ©2017 AACR.
Structural basis for DNA recognition by STAT6

Significance STAT6 is a transcription factor and plays a predominant role in IL-4/IL-13 and virus-mediated signaling pathways. Extensive studies have linked malfunctions of STAT6 to pathological features of asthma and cancer. Targeting the function of STAT6 has become an attractive therapy. Understanding the molecular mechanisms of STAT6 transcriptional regulation is still scarce. Here, we report the atomic-level structures of the phosphorylated STAT6 core fragment homodimer, both in DNA-free and complexed with N4 or N3 site DNA, uncovering both a larger dimer interface intersection angle and the unique residue H415 of STAT6 as important factors for discrimination of N4 from N3 site DNA. This study uncovers a dramatic conformational change in STAT6 dimer for recognizing and preferring N4 site DNA. STAT6 participates in classical IL-4/IL-13 signaling and stimulator of interferon genes-mediated antiviral innate immune responses. Aberrations in STAT6-mediated signaling are linked to development of asthma and diseases of the immune system. In addition, STAT6 remains constitutively active in multiple types of cancer. Therefore, targeting STAT6 is an attractive proposition for treating related diseases. Although a lot is known about the role of STAT6 in transcriptional regulation, molecular details on how STAT6 recognizes and binds specific segments of DNA to exert its function are not clearly understood. Here, we report the crystal structures of a homodimer of phosphorylated STAT6 core fragment (STAT6CF) alone and bound with the N3 and N4 DNA binding site. Analysis of the structures reveals that STAT6 undergoes a dramatic conformational change on DNA binding, which was further validated by performing molecular dynamics simulation studies and small angle X-ray scattering analysis. Our data show that a larger angle at the intersection where the two protomers of STAT meet and the presence of a unique residue, H415, in the DNA-binding domain play important roles in discrimination of the N4 site DNA from the N3 site by STAT6. H415N mutation of STAT6CF decreased affinity of the protein for the N4 site DNA, but increased its affinity for N3 site DNA, both in vitro and in vivo. Results of our structure–function studies on STAT6 shed light on mechanism of DNA recognition by STATs in general and explain the reasons underlying STAT6’s preference for N4 site DNA over N3.
Origin, Diversification, and Classification of the Australasian Genus Dracophyllum (Richeeae, Ericaceae)1

Abstract The genus Dracophyllum Labill. (Ericaceae) has a fragmented distribution in Australasia, but reaches the greatest level of species richness and morphological diversity in New Zealand. We investigated evolutionary processes that contribute to this disparity in species richness by comparing DNA sequences from members of Dracophyllum, its close relatives Richea Labill. and Sphenotoma R. Br. ex Sweet (together constituting tribe Richeeae Crayn & Quinn), along with more distant relatives in the Ericaceae. We created complementary data sets for the chloroplast-encoded genes matK and rbcL. Parsimony, Bayesian, and maximum likelihood analyses were conducted to assess the robustness of our phylogenetic inferences. The results were largely congruent and, when analyzed in combination, provided greater resolution. In our analyses, tribe Richeeae formed a monophyletic group that diverged during the Eocene (at least 33.3 million years ago [Ma]) with a crown radiation during the Early Miocene (at least 16.5 Ma) that resulted in two disjunct lineages. This date corresponds roughly to the onset of aridification in central Australia. The southern Western Australian genus Sphenotoma formed an isolated evolutionary lineage, while Dracophyllum and Richea together formed a second lineage restricted to eastern Australia, Lord Howe Island, New Caledonia, and New Zealand. The relationships of the Tasmanian endemic, D. milliganii Hook. f. , remain an enigma. It was ambiguously placed as sister to Sphenotoma or to the Dracophyllum–Richea clade. We recovered two distinct lineages, traditionally recognized as Richea sect. Cystanthe (R. Br.) Benth. and Richea sect. Dracophylloides Benth. , which were nested within Dracophyllum. The Lord Howe Island endemic, D. fitzgeraldii F. Muell. , emerged as sister to an eastern Australian clade of Dracophyllum. Our evidence suggests that the New Caledonian and New Zealand species of Dracophyllum dispersed from Australia; we document two independent episodes of long-distance dispersal in the Late Miocene to Early Pliocene. Low levels of sequence divergence suggest a rapid and recent species radiation in these two island archipelagos largely within the last three to six million years. This radiation accompanied Pliocene uplift of the New Zealand Southern Alps and episodes of glaciation during the Pleistocene. Because Dracophyllum is paraphyletic and Richea is polyphyletic, the taxonomic circumscription of these genera requires revision.
MHC Class II Expression Restricted to CD8α+ and CD11b+ Dendritic Cells Is Sufficient for Control of Leishmania major

Control of the intracellular protozoan, Leishmania major, requires major histocompatibility complex class II (MHC II)–dependent antigen presentation and CD4+ T cell T helper cell 1 (Th1) differentiation. MHC II–positive macrophages are a primary target of infection and a crucial effector cell controlling parasite growth, yet their function as antigen-presenting cells remains controversial. Similarly, infected Langerhans cells (LCs) can prime interferon (IFN)γ–producing Th1 CD4+ T cells, but whether they are required for Th1 responses is unknown. We explored the antigen-presenting cell requirement during primary L. major infection using a mouse model in which MHC II, I-Aβ b, expression is restricted to CD11b+ and CD8α+ dendritic cells (DCs). Importantly, B cells, macrophages, and LCs are all MHC II–negative in these mice. We demonstrate that antigen presentation by these DC subsets is sufficient to control a subcutaneous L. major infection. CD4+ T cells undergo complete Th1 differentiation with parasite-specific secretion of IFNγ. Macrophages produce inducible nitric oxide synthase, accumulate at infected sites, and control parasite numbers in the absence of MHC II expression. Therefore, CD11b+ and CD8α+ DCs are not only key initiators of the primary response but also provide all the necessary cognate interactions for CD4+ T cell Th1 effectors to control this protozoan infection.
Tertiary alphabet for the observable protein structural universe

Significance Proteins fold into intricate 3D structures, determined by their amino acid sequences. Different proteins can fold into drastically different structures, and the space of all possible structures appears hopelessly complex. However, this is precisely the space that needs to be described to understand how sequence encodes structure. In this paper, we decompose the set of known protein structures into standard reusable building blocks, which we call tertiary structural motifs (TERMs). Strikingly, we find that only ∼600 TERMs describe 50% of the known protein structural universe at sub-Angstrom resolution. Furthermore, we find the natural utilization of TERMs gives us a means of uncovering sequence–structure relationships. These insights can be harnessed for protein structure prediction, protein design, and other applications. Here, we systematically decompose the known protein structural universe into its basic elements, which we dub tertiary structural motifs (TERMs). A TERM is a compact backbone fragment that captures the secondary, tertiary, and quaternary environments around a given residue, comprising one or more disjoint segments (three on average). We seek the set of universal TERMs that capture all structure in the Protein Data Bank (PDB), finding remarkable degeneracy. Only ∼600 TERMs are sufficient to describe 50% of the PDB at sub-Angstrom resolution. However, more rare geometries also exist, and the overall structural coverage grows logarithmically with the number of TERMs. We go on to show that universal TERMs provide an effective mapping between sequence and structure. We demonstrate that TERM-based statistics alone are sufficient to recapitulate close-to-native sequences given either NMR or X-ray backbones. Furthermore, sequence variability predicted from TERM data agrees closely with evolutionary variation. Finally, locations of TERMs in protein chains can be predicted from sequence alone based on sequence signatures emergent from TERM instances in the PDB. For multisegment motifs, this method identifies spatially adjacent fragments that are not contiguous in sequence—a major bottleneck in structure prediction. Although all TERMs recur in diverse proteins, some appear specialized for certain functions, such as interface formation, metal coordination, or even water binding. Structural biology has benefited greatly from previously observed degeneracies in structure. The decomposition of the known structural universe into a finite set of compact TERMs offers exciting opportunities toward better understanding, design, and prediction of protein structure.
Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome

Significance Understanding neurophysiological correlates of neurodevelopmental disorders is one of the pressing challenges of neuroscience. By analyzing a mouse model of Rett syndrome (RTT), we show that cortical pyramidal neurons in methyl-CpG binding protein 2 (MeCP2) mutant mice have reduced excitatory as well as inhibitory synaptic drive. Thus, neuronal response reliability and selectivity, features that arise from excitatory/inhibitory processing circuits within cortex, are reduced. MeCP2 deletion crucially regulates inhibition via two complementary mechanisms: reducing responses of parvalbumin-expressing (PV+) inhibitory neurons and altering the polarity of GABAergic inhibition in pyramidal neurons. Treating mutant mice with recombinant human insulin-like growth factor-1 (rhIGF1) restores GABAergic polarity along with PV+ and pyramidal neuron responses, thus providing a mechanistic basis of action of rhIGF1 in RTT. Rett syndrome (RTT) arises from loss-of-function mutations in methyl-CpG binding protein 2 gene (Mecp2), but fundamental aspects of its physiological mechanisms are unresolved. Here, by whole-cell recording of synaptic responses in MeCP2 mutant mice in vivo, we show that visually driven excitatory and inhibitory conductances are both reduced in cortical pyramidal neurons. The excitation-to-inhibition (E/I) ratio is increased in amplitude and prolonged in time course. These changes predict circuit-wide reductions in response reliability and selectivity of pyramidal neurons to visual stimuli, as confirmed by two-photon imaging. Targeted recordings reveal that parvalbumin-expressing (PV+) interneurons in mutant mice have reduced responses. PV-specific MeCP2 deletion alone recapitulates effects of global MeCP2 deletion on cortical circuits, including reduced pyramidal neuron responses and reduced response reliability and selectivity. Furthermore, MeCP2 mutant mice show reduced expression of the cation-chloride cotransporter KCC2 (K+/Cl− exporter) and a reduced KCC2/NKCC1 (Na+/K+/Cl− importer) ratio. Perforated patch recordings demonstrate that the reversal potential for GABA is more depolarized in mutant mice, but is restored by application of the NKCC1 inhibitor bumetanide. Treatment with recombinant human insulin-like growth factor-1 restores responses of PV+ and pyramidal neurons and increases KCC2 expression to normalize the KCC2/NKCC1 ratio. Thus, loss of MeCP2 in the brain alters both excitation and inhibition in brain circuits via multiple mechanisms. Loss of MeCP2 from a specific interneuron subtype contributes crucially to the cell-specific and circuit-wide deficits of RTT. The joint restoration of inhibition and excitation in cortical circuits is pivotal for functionally correcting the disorder.
Continuous stereo camera calibration in urban scenarios

The quality of a 3D reconstruction obtained from stereo images depends on the accuracy of the stereo camera calibration. Continuous online camera calibration is key to enable a long maintenance-free operation of autonomous vehicles. Conventional algorithms for online calibration usually assume a static world. This, however, is often violated in urban scenarios. In this paper an algorithm is presented that determines the twelve degrees-of-freedom (12-DoF) extrinsic calibration of a stereo camera system in dynamic, urban scenarios. An Extended Kalman Filter (EKF) continuously estimates the extrinsic stereo camera calibration by tracking the position of salient points in 3D space that are observed in both cameras. The EKF predicts the 3D position of tracked points based on the estimated calibration and the vehicle's motion, which is estimated using an inertial navigation system (INS) and odometry sensors. However, only static points can be reliable predicted. A convolutional neural network (CNN) is applied to segment camera images on a pixel level. These segmented images are further converted to binary images labeling static and potentially dynamic pixels. Only salient points which are labeled as static are retained for estimation of the stereo camera calibration. While the stereo camera's extrinsic parameters are only observable under transformation and two independent rotations of the vehicle, we present a robust filter update scheme, that enables estimation of the 12-DoF extrinsic stereo camera calibration even in the absence of significant rotations. Test on urban roads show that minor road imperfections are sufficient to estimate all 12-DoF extrinsic parameters over time.