Vibration Alert Bracelet for Notification of the Visually and Hearing Impaired

This paper presents the prototype of an electronic vibration bracelet designed to help the visually and hearing impaired to receive and send emergency alerts. The bracelet has two basic functions. The first function is to receive a wireless signal and respond with a vibration to alert the user. The second function is implemented by pushing one button of the bracelet to send an emergency signal. We report testing on a prototype system formed by a mobile application and two bracelets. The bracelets and the application form a complete system intended to be used in retirement apartment communities. However, the system is flexible and could be expanded to add new features or to serve as a research platform for gait analysis and location services. The medical and professional potential of the proposed system is that it offers a simple, modular, and cost-effective alternative to all the existing medical devices with similar functionality currently on the market. The proposed system has an educational potential as well: it can be used as a starting point for capstone projects and demonstration purposes in schools to attract students to STEM disciplines

CYP450 phenotyping and metabolite identification of quinine by accurate mass UPLC-MS analysis: a possible metabolic link to blackwater fever

BACKGROUND: The naturally occurring alkaloid drug, quinine is commonly used for the treatment of severe malaria. Despite centuries of use, its metabolism is still not fully understood, and may play a role in the haemolytic disorders associated with the drug. METHODS: Incubations of quinine with CYPs 1A2, 2C9, 2C19, 2D6, and 3A4 were conducted, and the metabolites were characterized by accurate mass UPLC-MS(E) analysis. Reactive oxygen species generation was also measured in human erythrocytes incubated in the presence of quinine with and without microsomes. RESULTS: The metabolites 3-hydroxyquinine, 2’-oxoquininone, and O-desmethylquinine were observed after incubation with CYPs 3A4 (3-hydroxyquinine and 2’-oxoquininone) and 2D6 (O-desmethylquinine). In addition, multiple hydroxylations were observed both on the quinoline core and the quinuclidine ring system. Of the five primary abundance CYPs tested, 3A4, 2D6, 2C9, and 2C19 all demonstrated activity toward quinine, while 1A2 did not. Further, quinine produced robust dose-dependent oxidative stress in human erythrocytes in the presence of microsomes. CONCLUSIONS: Taken in context, these data suggest a CYP-mediated link between quinine metabolism and the poorly understood haemolytic condition known as blackwater fever, often associated with quinine ingestion

Shining Light on Merging Galaxies I: The Ongoing Merger of a Quasar with a `Green Valley' Galaxy

Serendipitous observations of a pair z = 0.37 interacting galaxies (one hosting a quasar) show a massive gaseous bridge of material connecting the two objects. This bridge is photoionized by the quasar (QSO) revealing gas along the entire projected 38 kpc sightline connecting the two galaxies. The emission lines that result give an unprecedented opportunity to study the merger process at this redshift. We determine the kinematics, ionization parameter (log U ~ -2.5 +- 0.03), column density (N_H ~ 10^{21} cm^{-2}), metallicity ([M/H] ~ -0.20 +- 0.15), and mass (~ 10^8 Msun) of the gaseous bridge. We simultaneously constrain properties of the QSO-host (M_DM>8.8x 10^{11} Msun) and its companion galaxy (M_DM>2.1 x 10^{11} Msun; M_star ~ 2 x 10^{10} Msun; stellar burst age=300-800 Myr; SFR~6 Msun/yr; and metallicity 12+log (O/H)= 8.64 +- 0.2). The general properties of this system match the standard paradigm of a galaxy-galaxy merger caught between first and second passage while one of the galaxies hosts an active quasar. The companion galaxy lies in the so-called `green valley', with a stellar population consistent with a recent starburst triggered during the first passage of the merger and has no detectable AGN activity. In addition to providing case-studies of quasars associated with galaxy mergers, quasar/galaxy pairs with QSO-photoionized tidal bridges such as this one offer unique insights into the galaxy properties while also distinguishing an important and inadequately understood phase of galaxy evolution.Comment: 23 pages, 12 figures, 5 tables, Submitted to ApJ, revised to address referee's comment

Comparative Genomics Suggests that the Fungal Pathogen Pneumocystis Is an Obligate Parasite Scavenging Amino Acids from Its Host's Lungs

Pneumocystis jirovecii is a fungus causing severe pneumonia in immuno-compromised patients. Progress in understanding its pathogenicity and epidemiology has been hampered by the lack of a long-term in vitro culture method. Obligate parasitism of this pathogen has been suggested on the basis of various features but remains controversial. We analysed the 7.0 Mb draft genome sequence of the closely related species Pneumocystis carinii infecting rats, which is a well established experimental model of the disease. We predicted 8’085 (redundant) peptides and 14.9% of them were mapped onto the KEGG biochemical pathways. The proteome of the closely related yeast Schizosaccharomyces pombe was used as a control for the annotation procedure (4’974 genes, 14.1% mapped). About two thirds of the mapped peptides of each organism (65.7% and 73.2%, respectively) corresponded to crucial enzymes for the basal metabolism and standard cellular processes. However, the proportion of P. carinii genes relative to those of S. pombe was significantly smaller for the “amino acid metabolism” category of pathways than for all other categories taken together (40 versus 114 against 278 versus 427, P<0.002). Importantly, we identified in P. carinii only 2 enzymes specifically dedicated to the synthesis of the 20 standard amino acids. By contrast all the 54 enzymes dedicated to this synthesis reported in the KEGG atlas for S. pombe were detected upon reannotation of S. pombe proteome (2 versus 54 against 278 versus 427, P<0.0001). This finding strongly suggests that species of the genus Pneumocystis are scavenging amino acids from their host's lung environment. Consequently, they would have no form able to live independently from another organism, and these parasites would be obligate in addition to being opportunistic. These findings have implications for the management of patients susceptible to P. jirovecii infection given that the only source of infection would be other humans

Female-Biased Dispersal and Gene Flow in a Behaviorally Monogamous Mammal, the Large Treeshrew (Tupaia tana)

Background: Female-biased dispersal (FBD) is predicted to occur in monogamous species due to local resource competition among females, but evidence for this association in mammals is scarce. The predicted relationship between FBD and monogamy may also be too simplistic, given that many pair-living mammals exhibit substantial extra-pair paternity. Methodology/Principal Findings: I examined whether dispersal and gene flow are female-biased in the large treeshrew (Tupaia tana) in Borneo, a behaviorally monogamous species with a genetic mating system characterized by high rates (50%) of extra-pair paternity. Genetic analyses provided evidence of FBD in this species. As predicted for FBD, I found lower mean values for the corrected assignment index for adult females than for males using seven microsatellite loci, indicating that female individuals were more likely to be immigrants. Adult female pairs were also less related than adult male pairs. Furthermore, comparison of Bayesian coalescent-based estimates of migration rates using maternally and bi-parentally inherited genetic markers suggested that gene flow is female-biased in T. tana. The effective number of migrants between populations estimated from mitochondrial DNA sequence was three times higher than the number estimated using autosomal microsatellites. Conclusions/Significance: These results provide the first evidence of FBD in a behaviorally monogamous species without mating fidelity. I argue that competition among females for feeding territories creates a sexual asymmetry in the costs an

Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication

Pharmacological targeting of metabolic processes in cancer must overcome redundancy in biosynthetic pathways. Deoxycytidine (dC) triphosphate (dCTP) can be produced both by the de novo pathway (DNP) and by the nucleoside salvage pathway (NSP). However, the role of the NSP in dCTP production and DNA synthesis in cancer cells is currently not well understood. We show that acute lymphoblastic leukemia (ALL) cells avoid lethal replication stress after thymidine (dT)-induced inhibition of DNP dCTP synthesis by switching to NSP-mediated dCTP production. The metabolic switch in dCTP production triggered by DNP inhibition is accompanied by NSP up-regulation and can be prevented using DI-39, a new high-affinity small-molecule inhibitor of the NSP rate-limiting enzyme dC kinase (dCK). Positron emission tomography (PET) imaging was useful for following both the duration and degree of dCK inhibition by DI-39 treatment in vivo, thus providing a companion pharmacodynamic biomarker. Pharmacological co-targeting of the DNP with dT and the NSP with DI-39 was efficacious against ALL models in mice, without detectable host toxicity. These findings advance our understanding of nucleotide metabolism in leukemic cells, and identify dCTP biosynthesis as a potential new therapeutic target for metabolic interventions in ALL and possibly other hematological malignancies