The Subjective and Reinforcing Effects of Visual and Olfactory Stimuli in Alcohol Drinking.

Nonpharmacological cues associated with drug intake may influence subjective and reinforcing effects of those drugs. Social drinkers (N = 80) participated in 2 sessions in which they rated and then consumed ad lib their preferred beer (with participants blind to brand). Visual and olfactory stimuli were obscured during 1 session (blocked) and not obscured during the other (unblocked). Dependent measures included ratings of "liking", "want another", and "desire to drink"; subjective mood; and ad lib beer consumption (reinforcement). Most ratings and ad lib consumption were lower during the blocked versus the unblocked condition. There were no interactions of blockade condition with sex and no effect of blockade on mood. These findings show that nonpharmacological stimuli associated with alcohol consumption influence alcohol's subjective and reinforcing effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attributions and relapse in opiate addicts.

Investigated whether attributions of opiate addicts would predict both their ability to abstain from future use and their reactions to abstinence violations. Measures of generalized beliefs about responsibility for positive and negative outcomes and specific attributions about relapse episodes were elicited from 80 addicts at the time of admission for inpatient detoxification and treatment. Addicts who at admission attributed to themselves greater responsibility for negative outcomes and who attributed relapse episodes to more personally controllable factors were subsequently (at 6-mo follow-up) more likely either to be completely abstinent or to contain the effects of temporary lapses into opiate use. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Frames of Reference in Mobile Augmented Reality Displays.

In 3 experiments, the authors investigated spatial updating in augmented reality environments. Participants learned locations of virtual objects on the physical floor. They were turned to appropriate facing directions while blindfolded before making pointing judgments (e.g., "Imagine you are facing X. Point to Y"). Experiments manipulated the angular difference between the learning heading and the imagined heading and between the actual heading and the imagined heading. The effect of actual-imagined on pointing latency was observed for naive users but not for users with brief training or instructions concerning the fact that objects can move with body movements. The results indicated that naive users used an environment-stabilized reference frame to access information arrays, but with experience and instruction the nature of the representation changed from an environment stabilized to a body stabilized reference frame. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Novel Triple-Action Inhibitor Targeting B-Cell Receptor Signaling and BRD4 Demonstrates Preclinical Activity in Chronic Lymphocytic Leukemia

B-cell chronic lymphocytic leukemia (CLL) results from intrinsic genetic defects and complex microenvironment stimuli that fuel CLL cell growth through an array of survival signaling pathways. Novel small-molecule agents targeting the B-cell receptor pathway and anti-apoptotic proteins alone or in combination have revolutionized the management of CLL, yet combination therapy carries significant toxicity and CLL remains incurable due to residual disease and relapse. Single-molecule inhibitors that can target multiple disease-driving factors are thus an attractive approach to combat both drug resistance and combination-therapy-related toxicities. We demonstrate that SRX3305, a novel small-molecule BTK/PI3K/BRD4 inhibitor that targets three distinctive facets of CLL biology, attenuates CLL cell proliferation and promotes apoptosis in a dose-dependent fashion. SRX3305 also inhibits the activation-induced proliferation of primary CLL cells in vitro and effectively blocks microenvironment-mediated survival signals, including stromal cell contact. Furthermore, SRX3305 blocks CLL cell migration toward CXCL-12 and CXCL-13, which are major chemokines involved in CLL cell homing and retention in microenvironment niches. Importantly, SRX3305 maintains its anti-tumor effects in ibrutinib-resistant CLL cells. Collectively, this study establishes the preclinical efficacy of SRX3305 in CLL, providing significant rationale for its development as a therapeutic agent for CLL and related disorders.     

Nordihydroguaiaretic Acid (NDGA) Inhibits CsgA Polymerization,Bacterial Amyloid Biogenesis,and Biofilm Formation

Escherichia coli and other Enterobacteriaceae thrive in robust biofilm communities through the coproduction of curli amyloid fibers and phosphoethanolamine cellulose. Curli promote adhesion to abiotic surfaces and plant and human host tissues and are associated with pathogenesis in urinary tract infection and food-borne illness. The production of curli in the host has also been implicated in the pathogenesis of neurodegenerative diseases. We report that the natural product nordihydroguaiaretic acid (NDGA) is effective as a curlicide in E. coli. NDGA prevents CsgA polymerization in vitro in a dose-dependent manner. NDGA selectively inhibits cell-associated curli assembly and inhibits uropathogenic E. coli biofilm formation. More broadly, this work emphasizes the ability to evaluate and identify bioactive amyloid assembly inhibitors by using the powerful gene-directed amyloid biogenesis machinery in E. coli.     

Field Testing of Stabilized Soil

Remediation of a Superfund site in Stratford, Conn., involved stabilization of the subgrade with portland cement. Part of the remediation site was to be used as a parking area. The stabilized soil was to be covered with natural base∕subbase course materials and capped with an asphalt concrete cover. During the course of the remediation, a base-course layer could not be placed prior to the onset of winter. A field study was conducted to quantify any changes in the mechanical properties of the open stabilized subgrade subjected to freeze-thaw cycling during the winter of 1996–97. Field evaluation was conducted with pavement industry tools: the Clegg impact hammer and the dynamic cone penetrometer. Evaluation results show the viability of the Clegg hammer as an instrument for quality assurance and also show that there can be up to 50% loss in compressive strength of the subgrade within the uppermost layer of the material caused by freeze-thaw cycling.     

N2O emissions from streams in the Neuse river watershed, North Carolina

We present N2O emission data from 11 sites in the Neuse River watershed. Emissions were measured using a static surface enclosure technique deployed on eight sites on the main river channel and three tributary sites. Ancillary data collected included dissolved oxygen, nitrate, total nitrogen, ammonium, dissolved organic carbon, total phosphorus, and temperature. Analysis using standard linear models, and classification and regression trees (CART), indicated nitrate to be the primary driving variable associated with N2O emission, although dissolved organic carbon concentration and water temperature were positively related with N2O emission as well. Relationships between nitrate concentration and N2O emission were consistent with those found in previous studies, although the data presented here represent the lower end of the range for both variables among published studies. Using our measured N2O emission rates along with literature values for the ratio of nitrogen gas to N2O produced during denitrification, we estimate N loss via denitrification in the Neuse River is approximately 17% of the annual N load delivered to the estuary.     

Chemistry of Leichhardt's Grasshopper, Petasida ephippigera, and its Host Plants, Pityrodia jamesii, P. ternifolia, and P. pungens

Investigation of the strikingly aposematic Leichhardt's grasshopper revealed a number of host-plant-derived components. Chemical study of the three known host plants revealed a diverse array of components. Pityrodia ternifolia and P. pungens contain predominantly sesquiterpenes and sesquiterpene glycosides and P. jamesii is rich in cineole, dihydrochalcones, chalcones, and monoterpene glycosides. Feces from grasshoppers feeding on P. jamesii contain a mixture of hydroxycineoles, of which 3-hydroxycineole is the predominant isomer (68%). No evidence for previously suspected "alkaloidal" toxins was found in either the insect or host plant.     

Role of insulin-like growth factor binding protein-3 in breast cancer cell growth

The mitogenic effects of insulin-like growth factors (IGFs) are regulated by a family of insulin-like growth factor binding proteins (IGFBPs). One member of this family, IGFBP-3, mediates the growth-inhibitory and apoptosis-inducing effects of a number of growth factors and hormones such as transforming growth factor-beta, retinoic acid, and 1,25-dihydroxyvitamin D3. IGFBP-3 may act in an IGF-dependent manner by attenuating the interaction of pericellular IGFs with the type-I IGF receptor. It may also act in an IGF-independent manner by initiating intracellular signaling from a cell surface receptor, or by direct nuclear action, or both. The possibility of a membrane-bound receptor is strengthened by recent studies which have identified members of the transforming growth factor-beta receptor family as having a role, either directly or indirectly, in signaling from the cell surface by IGFBP-3. A number of growth factors and hormones stimulate the expression and secretion of cellular IGFBP-3, which then signals from the cell surface to bring about some of the effects attributed to the primary agents. Within the cell, the apoptosis-inducing tumor suppressor, p53, can also induce IGFBP-3 expression and secretion. Since IGFBP-3 upregulates the cell cycle inhibitor, p21(Waf1), and increases the ratio of proapoptotic to antiapoptotic members of the Bcl family, it appears to exert the same effects on major downstream targets of cell signaling as p53 does. The nuclear localization of IGFBP-3 has been described in a number of cell types. IGFBP-3 may act to import IGFs or other nuclear localization signal-deficient signaling molecules into the nucleus. It may also act directly in the nucleus by enhancing the activity of retinoid X receptor-alpha and thereby promote apoptosis. All of the above phenomena will be discussed with particular emphasis on the growth of breast cancer cells.     

Meta-analysis of indoor temperatures in new-build housing

ABSTRACT

Despite growing concerns about overheating, a lack of evidence exists on the scale of the problem, particularly in contemporary UK housing. This paper presents the results of a meta-analysis of indoor temperatures in selected low-energy housing. Temperature data recorded at five-minute intervals in 60 dwellings across 19 demonstration projects (2012–14) were collated and analysed to investigate the prevalence of overheating. Findings evidence high summertime temperatures, with 27% of living rooms exceeding 28°C during August. Based on the Chartered Institution of Building Services Engineers (CIBSE) threshold of 5% annual occupied hours > 25°C, 57% of bedrooms and 75% of living rooms were classified as having overheated. Overall, 30% of living rooms exceeded the adaptive comfort threshold of > 3% occupied hours ΔT?≥?1?K. The results suggest a fundamental relationship between ventilation and indoor temperatures. The higher minimum and average summertime temperatures observed in mechanical ventilation with heat recovery (MVHR) homes (p?<?0.05) and lower temperature range (p?<?0.001) suggest the need for greater attention to adequate summertime ventilation provision in airtight homes. The results demonstrate a high prevalence of overheating in exemplary housing, indicating the need for greater efforts to ensure the effective implementation of strategies to minimize overheating and improve ventilation in low-energy homes.