Forecasting daily cash receipts and disbursements : a general statistical approach

Includes bibliographical references (p. 21-22)

Profiles of cash flow components

Includes bibliographical references (p. 20-22)

Characterization of a monothiol glutaredoxin encoded by Chlorella virus PBCV-1

Annotation of the 330-kb Chlorella virus PBCV-1 genome identified a 237 nucleotide gene (a438l) that codes for a protein with ~35% amino acid identity to glutaredoxins (Grx) found in other organisms. The PBCV-1 protein resembles classical Grxs in both size (9 kDa) and location of the active site (N-terminus). However, the PBCV-1 Grx is unusual because it contains a monothiol active site (CPYS) rather than the typical dithiol active site (CPYC). To examine this unique active site, four sitespecific mutants (CPYC, CPYA, SPYC, and SPYS) were constructed to determine if the N-terminal cysteine is necessary for enzyme activity. Wild type and both mutants containing N-terminal cysteines catalyzed the reduction of disulfides in a coupled system with GSH, NADPH, and glutathione reductase. However, both mutants with an altered N-terminal cysteine were inactive. The grx gene is common in the Chlorella viruses. Molecular phylogenetic analyses of the PBCV-1 enzyme support its relatedness to those from other Chlorella viruses and yet demonstrate the divergence of the Grx molecule

Does Access to Health Care Impact Survival Time after Diagnosis of AIDS?

Lack of access to health care is often blamed for poor health outcomes, but this effect is not supported by existing HIV/AIDS literature. The authors examined the association between access to care and survival time after progression to AIDS, using survival analysis methods. This study combined data from two CDC sponsored studies of HIV-infected persons, a cross-sectional interview study and a longitudinal medical record review study. Study subjects included 752 persons who progressed to AIDS before December 31, 1999, and were patients at either of two major HIV care facilities in Detroit, MIchigan. Separate statistical models were used to test associations between survival time after meeting the criteria for AIDS and two indicators of access to health care: (1) perceived access to health care and (2) health care utilization patterns. Perceived access was not associated with survival time after AIDS, but patterns of health care utilization were significantly associated with survival time after AIDS (HR = 2.04, p < 0.001). Individuals who received a greater proportion of their care in the ER had a worse survival prognosis than those who received more of their health care in an outpatient clinic setting. It is crucial that we provide HIV-infected populations with tools that enable them to access a regular source of health care.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63272/1/10872910252972276.pd

Immunofluorescent spectral analysis reveals the intrathecal cannabinoid agonist, AM1241, produces spinal anti-inflammatory cytokine responses in neuropathic rats exhibiting relief from allodynia

During pathological pain, the actions of the endocannabinoid system, including the cannabinoid 2 receptor (CB2R), leads to effective anti-allodynia and modifies a variety of spinal microglial and astrocyte responses. Here, following spinal administration of the CB2R compound, AM1241, we examined immunoreactive alterations in markers for activated p38 mitogen-activated protein kinase, interleukin-1β (IL-1β), the anti-inflammatory cytokine, interleukin-10 (IL-10) as well as degradative endocannabinoid enzymes, and markers for altered glial responses in neuropathic rats. In these studies, the dorsal horn of the spinal cord and dorsal root ganglia were examined. AM1241 produced profound anti-allodynia with corresponding immunoreactive levels of p38 mitogen-activated kinase, IL-1β, IL-10, the endocannabinoid enzyme monoacylglycerol lipase, and astrocyte activation markers that were similar to nonneuropathic controls. In contrast, spinal AM1241 did not suppress the increased microglial responses observed in neuropathic rats. The differences in fluorescent markers were determined within discrete anatomical regions by applying spectral analysis methods, which virtually eliminated nonspecific signal during the quantification of specific immunofluorescent intensity. These data reveal expression profiles that support the actions of intrathecal AM1241 control pathological pain through anti-inflammatory mechanisms by modulating critical glial factors, and additionally decrease expression levels of endocannabinoid degradative enzymes

Miles to go (mtgo) encodes FNDC3 proteins that interact with the chaperonin subunit CCT3 and are required for NMJ branching and growth in Drosophila.

Analysis of mutants that affect formation and function of the Drosophila larval neuromuscular junction (NMJ) has provided valuable insight into genes required for neuronal branching and synaptic growth. We report that NMJ development in Drosophila requires both the Drosophila ortholog of FNDC3 genes; CG42389 (herein referred to as miles to go; mtgo), and CCT3, which encodes a chaperonin complex subunit. Loss of mtgo function causes late pupal lethality with most animals unable to escape the pupal case, while rare escapers exhibit an ataxic gait and reduced lifespan. NMJs in mtgo mutant larvae have dramatically reduced branching and growth and fewer synaptic boutons compared with control animals. Mutant larvae show normal locomotion but display an abnormal self-righting response and chemosensory deficits that suggest additional functions of mtgo within the nervous system. The pharate lethality in mtgo mutants can be rescued by both low-level pan- and neuronal-, but not muscle-specific expression of a mtgo transgene, supporting a neuronal-intrinsic requirement for mtgo in NMJ development. Mtgo encodes three similar proteins whose domain structure is most closely related to the vertebrate intracellular cytosolic membrane-anchored fibronectin type-III domain-containing protein 3 (FNDC3) protein family. Mtgo physically and genetically interacts with Drosophila CCT3, which encodes a subunit of the TRiC/CCT chaperonin complex required for maturation of actin, tubulin and other substrates. Drosophila larvae heterozygous for a mutation in CCT3 that reduces binding between CCT3 and MTGO also show abnormal NMJ development similar to that observed in mtgo null mutants. Hence, the intracellular FNDC3-ortholog MTGO and CCT3 can form a macromolecular complex, and are both required for NMJ development in Drosophila

Consumer Attitudes and Use of Antibiotics

Recent antibiotic use is a risk factor for infection or colonization with resistant bacterial pathogens. Demand for antibiotics can be affected by consumers’ knowledge, attitudes, and practices. In 1998–1999, the Foodborne Diseases Active Surveillance Network (FoodNet) conducted a population-based, random-digit dialing telephone survey, including questions regarding respondents’ knowledge, attitudes, and practices of antibiotic use. Twelve percent had recently taken antibiotics; 27% believed that taking antibiotics when they had a cold made them better more quickly, 32% believed that taking antibiotics when they had a cold prevented more serious illness, and 48% expected a prescription for antibiotics when they were ill enough from a cold to seek medical attention. These misguided beliefs and expectations were associated with a lack of awareness of the dangers of antibiotic use; 58% of patients were not aware of the possible health dangers. National educational efforts are needed to address these issues if patient demand for antibiotics is to be reduced

Dengue viruses cluster antigenically but not as discrete serotypes.

The four genetically divergent dengue virus (DENV) types are traditionally classified as serotypes. Antigenic and genetic differences among the DENV types influence disease outcome, vaccine-induced protection, epidemic magnitude, and viral evolution. We characterized antigenic diversity in the DENV types by antigenic maps constructed from neutralizing antibody titers obtained from African green monkeys and after human vaccination and natural infections. Genetically, geographically, and temporally, diverse DENV isolates clustered loosely by type, but we found that many are as similar antigenically to a virus of a different type as to some viruses of the same type. Primary infection antisera did not neutralize all viruses of the same DENV type any better than other types did up to 2 years after infection and did not show improved neutralization to homologous type isolates. That the canonical DENV types are not antigenically homogeneous has implications for vaccination and research on the dynamics of immunity, disease, and the evolution of DENV.This research was supported in part by the Intramural Research Program of the US NIH, National Institute of Allergy and Infectious Diseases, European Union (EU) FP7 programs EMPERIE (223498) and ANTIGONE (278976), Human Frontier Science Program (HFSP) program grant P0050/2008, the NIH Director’s Pioneer Award DP1-OD000490-01, the FIRST program from the Bill and Melinda Gates Foundation and the Instituto Carlos Slim de la Salud (E.H.). The antigenic cartography toolkit was in part supported by NIAID-NIH Centers of Excellence for Influenza Research and Surveillance contracts HHSN266200700010C and HHSN272201400008C for use on influenza virus. L.C.K. was supported by the Gates Cambridge Scholarship and the NIH Oxford Cambridge Scholars Program. J.M.F. was supported by an MRC Fellowship (MR/K021885/1) and a Junior Research Fellowship from Homerton College Cambridge. E.C.H. was supported by an NHMRC Australia Fellowship. N.V. and R.B.T were supported by NIH contract HHSN272201000040I/HHSN27200004/D04.This is the author accepted manuscript. The final version is available from AAAS via http://dx.doi.org/10.1126/science.aac501