The ε4 allele of the Apolipoprotein E gene (APOE), one of the main allele of APOE polymorphism, is a major risk factor for the development of Alzheimer's disease. However, several data suggest that ...genetic factors, within the APOE locus, may also modulate the risk associated with this polymorphism. We look for new mutations in the APOE promoter, susceptible to modify the risk associated with the APOE ε4 allele. We characterised a G→T mutation at −186 bp of the APOE gene TATA box, named Th1/E47cs. This new polymorphism is located in a consensus sequence of a potential transcriptional (Th1/E47) factor binding site. We studied the impact of this new polymorphism with those of other markers of the APOE locus in a large case-control study and observed that Th1/E47cs modulated the influence of the APOE ε4 allele on the risk of Alzheimer's disease.
In scintillation dosimetry, a Cerenkov background signal is generated when a conventional fibre optic is exposed to radiation produced by a megavoltage linear accelerator. Three methods of measuring ...dose in the presence of Cerenkov background are compared. In the first method, a second background fibre is used to estimate the Cerenkov signal in the signal fibre. In the second method, a colour camera is used to measure the combined scintillation and Cerenkov light in two wavelength ranges and a mathematical process is used to extract the scintillation signal. In the third method, a hollow air core light guide is used to carry the scintillation signal through the primary radiation field. In this paper, the strengths and weaknesses of each dosimetry system are identified and recommendations for the optimum method for common clinical dosimetry situations are made.
We propose a new drive mechanism for carbon nanotube (CNT) motors, based upon the torque generated by a flux of electrons passing through a chiral nanotube. The structure of interest comprises a ...double-walled CNT formed from, for example, an achiral outer tube encompassing a chiral inner tube. Through a detailed analysis of electrons passing through such a "windmill," we find that the current, due to a potential difference applied to the outer CNT, generates sufficient torque to overcome the static and dynamic frictional forces that exist between the inner and outer walls, thereby causing the inner tube to rotate.
Abstract The purpose of this study was to examine the effects of feedback provided to counselors on the outcomes of patients treated at community-based substance abuse treatment programs. A version ...of the Outcome Questionnaire (OQ-45), adapted to include drug and alcohol use, was administered to patients ( N = 304) in 3 substance abuse treatment clinics. Phase I of the study consisted only of administration of the assessment instruments. Phase II consisted of providing feedback reports to counselors based on the adapted OQ-45 at every treatment session up to Session 12. Patients who were found to not be progressing at an expectable rate (i.e., “offtrack”) were administered a questionnaire that was used as a second feedback report for counselors. For offtrack patients, feedback compared with no feedback led to significant linear reductions in alcohol use throughout treatment and also in OQ-45 total scores and drug use from the point of the second feedback instrument to Session 12. The effect for improving mental health functioning was evident at only 1 of the 3 clinics. These results suggest that a feedback system adapted to the treatment of substance use problems is a promising approach that should be tested in a larger randomized trial.
This article reports the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in March 2022. The entire ICTV was invited to vote on 174 ...taxonomic proposals approved by the ICTV Executive Committee at its annual meeting in July 2021. All proposals were ratified by an absolute majority of the ICTV members. Of note, the Study Groups have started to implement the new rule for uniform virus species naming that became effective in 2021 and mandates the binomial ‘Genus_name species_epithet’ format with or without Latinization. As a result of this ratification, the names of 6,481 virus species (more than 60 percent of all species names currently recognized by ICTV) now follow this format.
Time-dependent toxicity data of specific toxicants observed against
A. fischeri
were analysed using a single time-dependent Weibull cumulative distribution function (CDF). For binary mixtures the ...individual Weibull parameters provided the marginals for a bivariate copula model, characterised by a single extra parameter, the interaction exponent,
. The copula model unites both the dose addition (DA, Loewe additivity) and dose independence (DI, Bliss independence) hypotheses of combinations into a single explicit equation and returns both hypotheses as special cases. The model predicts the linear isoboles from sham (like against like) experiments and the linear, concave, convex and mixed concave-convex isoboles from true binary mixtures. Systems are defined as being independent when
= 1, additive when min(
n
1
,
n
2
) ≤
≤ max(
n
1
,
n
2
), antagonistic when
< min(
n
1
,
n
2
) and synergistic when
> max(
n
1
,
n
2
), where
n
i
are the individual dose (concentration) exponents. More complex mixtures were analysed by developing
n
-dimensional copulas: two ternary systems were analysed using a ternary copula that returned the three bivariate marginals and the three individual marginals of the mixture. The general model can also be used for time-independent studies by simply removing the time dependency. Research into combined effects has often assumed that if both the parameters for all the individual components in a mixture and the model for combinations were known then the additive effect of the whole could be predicted. This hypothesis has been shown to be false because without knowing how the components in a mixture interact the predictions from the standard DI or DA models provide only an initial, best guess, analysis.
A new model for combination effects gives descriptions of additivity, independence, synergy and antagonism and explains the multiple shapes of isoboles.
The adsorption of neutral glycine onto amorphous silica was investigated both theoretically and experimentally. DFT calculations were performed at the BLYP‐631++G** level using a cluster approach. ...Several possible configurations involving the formation of H bonds between glycine and one, two, or three silanol groups (SiOH) were considered. The most favorable bonding of glycine with one silanol group (45 kJ mol−1) occurs through the COOH moiety, thus forming a cycle in which the CO group is an H‐bond acceptor whereas the acidic OH group is an H‐bond donor. With two or three silanol groups, additional H bonds are formed between the amine moiety and the silanol groups, which leads to an increased adsorption energy (70 and 80 kJ mol−1 for two and three silanol groups, respectively). Calculated νCO, δHNH, and δHCH values are sensitive to the adsorption mode. A bathochromic shift of νCO as compared to the νCO of free glycine (calculated in the 1755–1790 cm−1 range) is found for glycine in interaction with silanol(s). The more H bonds are formed between the COOH moiety and silanol groups, the higher the bathochromic shift. For δHNH, no shift is found for glycine adsorbed on one and two silanol groups (where the amine is either not bound or an H‐bond donor), whereas a bathochromic shift is calculated with three silanols when the amine moiety is an H‐bond acceptor. Experimental FTIR spectra performed at room temperature for glycine adsorbed at 160 °C on Aerosil amorphous silica exhibit bands at 1371, 1423, 1630, and 1699 cm−1. The experimental/calculated frequencies have their best correspondence for glycine adsorbed on two silanol groups. It is important to note that the forms giving the best correspondence to experimental frequencies are the most stable ones.
Support group: DFT calculations suggest that glycine adsorbed on amorphous silica interacts through its COOH end with one or more silanol groups, with the formation of one H‐acceptor and one H‐donor bond. The experimental and calculated frequencies for the different functional groups of glycine correspond to glycine adsorbed on two vicinal, adjacent silanols (see picture).
The sterility assurance community is facing significant challenges. A relatively recent challenge is the pressure on manufacturing supply chains resulting from the limited availability of capacity ...for terminal sterilization of healthcare products. The current challenge is finding solutions for innovative new products, especially biologics and combination products, that offer great promise for patients around the world. This challenge will become more prevalent in the future as products advance. This article frames new paradigms and tools being developed to address these challenges. Foundational principles and current realities from each sector are reviewed so that sterility assurance professionals have a solid base from which to build strategies.
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