Illusory Essences: A Bias Holding Back Theorizing in Psychological Science.

The reliance in psychology on verbal definitions means that psychological research is unusually moored to how humans think and communicate about categories. Psychological concepts (e.g., intelligence, attention) are easily assumed to represent objective, definable categories with an underlying essence. Like the "vital forces" previously thought to animate life, these assumed essences can create an illusion of understanding. By synthesizing a wide range of research lines from cognitive, clinical, and biological psychology and neuroscience, we describe a pervasive tendency across psychological science to assume that essences explain phenomena. Labeling a complex phenomenon can appear as theoretical progress before there is sufficient evidence that the described category has a definable essence or known boundary conditions. Category labels can further undermine progress by masking contingent and contextual relationships and obscuring the need to specify mechanisms. Finally, we highlight examples of promising methods that circumvent the lure of essences and suggest four concrete strategies for identifying and avoiding essentialist intuitions in theory development.

Mechanisms of vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34 in rat bone resistance arteries.

UNLABELLED: Parathyroid hormone (PTH) augments bone metabolism and bone mass when given intermittently. Enhanced blood flow is requisite to support high tissue metabolism. The bone arteries are responsive to all three PTH analogs, which may serve to augment skeletal blood flow during intermittent PTH administration. INTRODUCTION: PTH augments bone metabolism. Yet, mechanisms by which PTH regulates bone blood vessels are unknown. We deciphered (1) endothelium-dependent and endothelium-independent vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34, (2) the signaling pathways (i.e., endothelial nitric oxide synthase [eNOS], cyclooxygenase [COX], protein kinase C [PKC], and protein kinase A [PKA]), and (3) receptor activation. METHODS: Femoral principal nutrient arteries (PNAs) were given cumulative doses (10(-13)-10(-8) M) of PTH 1-84, PTH 1-34, and PTHrP 1-34 with and without signaling pathway blockade. Vasodilation was also determined following endothelial cell removal (i.e., denudation), PTH 1 receptor (PTH1R) inhibition and to sodium nitroprusside (SNP; a nitric oxide [NO] donor). RESULTS: Vasodilation was lowest to PTH 1-34, and maximal dilation was highest to PTHrP 1-34. Inhibition of eNOS reduced vasodilation to PTH 1-84 (-80 %), PTH 1-34 (-66 %), and PTHrP 1-34 (-48 %), evidencing the contribution of NO. Vasodilation following denudation was eliminated (PTH 1-84 and PTHrP 1-34) and impaired (PTH 1-34, 17 % of maximum), highlighting the importance of endothelial cells for PTH signaling. Denuded and intact PNAs responded similarly to SNP. Both PKA and PKC inhibition diminished vasodilation in all three analogs to varying degrees. PTH1R blockade reduced vasodilation to 1, 12, and 12 % to PTH 1-84, PTH 1-34, and PTHrP 1-34, respectively. CONCLUSIONS: Vasodilation of femoral PNAs to the PTH analogs occurred via activation of the endothelial cell PTH1R for NO-mediated events. PTH 1-84 and PTHrP 1-34 primarily stimulated PKA signaling, and PTH 1-34 equally stimulated PKA and PKC signaling.

Identification of candidate circulating cisplatin-resistant biomarkers from epithelial ovarian carcinoma cell secretomes.

BACKGROUND: The majority of patients diagnosed with advanced epithelial ovarian carcinoma (EOC) relapse with resistant disease, and there are no biomarkers that possess clinical utility to identify or monitor these patients. This study aimed to identify secreted proteins ('secretome') collected from human EOC cell lines that differ in their inherent platinum sensitivity. METHODS: Secreted proteins collected from conditioned medium from ovarian cancer cell lines that vary in their sensitivity to cisplatin were digested with trypsin and analysed by liquid chromatography-tandem mass spectrometry for peptide identification. RESULTS: Of the 1688 proteins identified, 16 possessed significant differential abundances (P<0.05) between the platinum-resistant and -sensitive cell lines. A number of these were verified by immunoblot, including COL11A1, which was also found to be associated with worse progression-free survival (PFS; N=723) and overall survival (OS; N=1183) as assessed from publicly available transcript expression data from ovarian cancer tumour specimens. CONCLUSION: Secretome proteomics of EOC cells resulted in the identification of a novel candidate biomarker, COL11A1. The expression level of COL11A1 correlates to worse PFS and OS, and is predicted to reside in peripheral circulation making this an attractive candidate for validation in sera as a biomarker of cisplatin resistance and poor outcome.

Theoretical Investigation of Optical Detection and Recognition of Single Biological Molecules Using Coherent Dynamics of Exciton-Plasmon Coupling.

We use quantum coherence in a system consisting of one metallic nanorod and one semi-conductor quantum dot to investigate a plasmonic nanosensor capable of digital optical detection and recognition of single biological molecules. In such a sensor the adsorption of a specific molecule to the nanorod turns off the emission of the system when it interacts with an optical pulse having a certain intensity and temporal width. The proposed quantum sensors can count the number of molecules of the same type or differentiate between molecule types with digital optical signals that can be measured with high certainty. We show that these sensors are based on the ultrafast upheaval of coherent dynamics of the system and the removal of coherent blockage of energy transfer from the quantum dot to the nanorod once the adsorption process has occurred.

ORION laser target diagnostics.

The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

An overview of the Central Queensland University self-contained evapotranspiration beds.

The Central Queensland University (CQU) has championed a self-contained concrete lined evapotranspiration channel. Any non-transpired effluent returns to a holding tank and is recirculated through the evapotranspiration channel until it is used. This paper examines the results from the Rockhampton trial site. Nutrient ions in the effluent were quantified over time and found not to accumulate in solution. Microbial analysis of the treated effluent was performed and was found to be within the ranges required by the relevant legislative codes. Citrus fruit grown in the evapotranspiration channel were sampled and no elevated levels of faecal coliforms were recorded. Macronutrients and micronutrients of the soil in the channels were measured over a 5-year period. No toxic accumulations or nutrient deficiencies in the soil occurred. Levels of salinity and sodicity in the evapotranspiration channel soil were quantified. Salinity rose slightly, as did sodium. Concentrations of salts and sodium did not reach unsustainable levels. The aim of the trial was to develop an on-site treatment and reuse system that is sustainable and protects public and environmental health.

Paediatric narcolepsy: complexities of diagnosis.

Narcolepsy is a sleep disorder that is characterized by excessive daytime sleepiness and the inappropriate intrusion of aspects of rapid eye movement sleep into wakefulness. While the disorder emerges from an interplay of genetic and environmental factors, recent findings suggest that abnormalities in the neurotransmission of hypocretin may be implicated in its pathogenesis. Although narcolepsy has typically been associated with adulthood, there is a growing evidence base for the emergence of the disorder in childhood. We report suspected narcolepsy in early infancy, highlighting both the complexities of presentation and subsequent diagnosis associated with paediatric narcolepsy, and the significant psychosocial difficulties experienced by children and families managing this disorder.

An incremental approach to a Web-based computerized medical record.

Acceptance of an electronic medical record within physician practices is a challenge that the Everett Clinic and the Wenatchee Valley Clinic in Washington State have chosen to approach incrementally. These two independent clinics, with 180 physicians each, joined forces in 1995 to form an information service organization, CliniTech Information Resources, to consolidate operation of their practice management and lab systems. With that done, in 1997 they asked CliniTech to come up with a solution to give physicians online access to clinical data in a way that didn't interrupt their work-flow or decrease their productivity--not a small order. The first HTML application was On Line Transcription, for viewing chart notes and radiology reports. Next, the On Line Patient Profile was developed to replace the face sheet. On Line Lab Results followed as a way to view results from the clinics' internal and reference lab systems. A single user interface was created in 2000 to link these components to the physician's schedule and clinical references. The new computerized medical record (CMR) has been embraced by the clinics' physicians (currently at 70 percent usage) and will continue to grow with additional results and images. Electronic signature capabilities for transcription and results are also slated for 2001 and will be the first change to how the physician practices.

Is visual search really like foraging?

The visual-search paradigm provides a controlled and easy to implement experimental situation in which to study the search process. However, little work has been carried out in humans to investigate the extent to which traditional visual-search tasks are similar to more general search or foraging. Here we report results from a task in which search involves walking around a room and leaning down to inspect individual locations. Consistent with more traditional search tasks, search time increases linearly with display size, and the target-present to target-absent search slope is 1:2. However, although rechecking of locations did occur, compared to more traditional search it was relatively rare, suggesting an increased role for memory.

Characterization of the recombinant IKK1/IKK2 heterodimer. Mechanisms regulating kinase activity.

Nuclear factor kappa B (NF-kappaB) is a ubiquitous, inducible transcription factor that regulates the initiation and progression of immune and inflammatory stress responses. NF-kappaB activation depends on phosphorylation and degradation of its inhibitor protein, IkappaB, initiated by an IkappaB kinase (IKK) complex. This IKK complex includes a catalytic heterodimer composed of IkappaB kinase 1 (IKK1) and IkappaB kinase 2 (IKK2) as well as a regulatory adaptor subunit, NF-kappaB essential modulator. To better understand the role of IKKs in NF-kappaB activation, we have cloned, expressed, purified, and characterized the physiological isoform, the rhIKK1/rhIKK2 heterodimer. We compared its kinetic properties with those of the homodimers rhIKK1 and rhIKK2 and a constitutively active rhIKK2 (S177E, S181E) mutant. We demonstrate activation of these recombinantly expressed IKKs by phosphorylation during expression in a baculoviral system. The K(m) values for ATP and IkappaBalpha peptide for the rhIKK1/rhIKK2 heterodimer are 0.63 and 0.60 micrometer, respectively, which are comparable to those of the IKK2 homodimer. However, the purified rhIKK1/rhIKK2 heterodimer exhibits the highest catalytic efficiency (k(cat)/K(m)) of 47.50 h(-1) micrometer(-1) using an IkappaBalpha peptide substrate compared with any of the other IKK isoforms, including rhIKK2 (17.44 h(-1) micrometer(-1)), its mutant rhIKK2 (S177E, S181E, 1.18 h(-1) micrometer(-1)), or rhIKK1 (0.02 h(-1) micrometer(-1)). Kinetic analysis also indicates that, although both products of the kinase reaction, ADP and a phosphorylated IkappaBalpha peptide, exhibited competitive inhibitory kinetics, only ADP with the low K(i) of 0.77 micrometer may play a physiological role in regulation of the enzyme activity.

Predicting the outcomes of physical events: two-year-olds fail to reveal knowledge of solidity and support.

Two-year-olds' (N = 153) knowledge of solidity was tested in four search tasks adapted from infant looking-time experiments. In Experiment 1, 2-year-olds failed to search in the correct location for a falling ball after a hidden shelf that blocked its trajectory had been inserted in the apparatus. Experiment 2 extended this finding by showing that 2-year-olds failed to take into account the effects of either removing or inserting a shelf in their search for a toy dropped behind a screen. Experiment 3 examined sensitivity to the constraint provided by a solid barrier on horizontal motion. In all three experiments, 2-year-old children searched initially at the location where they saw the object during familiarization. Experiment 4, using multiple test trials but no familiarization to a pretest location, also showed that 2-year-olds failed to take the presence or absence of a barrier into account when planning where to search for a toy they had seen dropped behind a screen. In all of these studies, 2-year-olds showed no evidence of representing solidity and support constraints on the trajectories of falling objects. Experiments 1 and 3 also included 2 1/2-year-olds (N = 31), who succeeded on these search tasks. The implications of the poor performance of 2-year-olds, in the face of success by very young infants on looking-time measures of sensitivity to similar constraints on object motion, are discussed.

Human lens coloration and aging. Evidence for crystallin modification by the major ultraviolet filter, 3-hydroxy-kynurenine O-beta-D-glucoside.

The human lens becomes increasingly yellow with age and thereby reduces our perception of blue light. This coloration is associated with lens proteins (crystallins), but its molecular basis was unknown. Here we show that the coloration occurs because of the interaction of crystallins with a UV filter compound, 3-hydroxykynurenine glucoside (3-OHKG). Crystallin modification results from deamination of the 3-OHKG amino acid side chain, yielding an unsaturated ketone that is susceptible to nucleophilic attack by cysteine, histidine, and lysine residues. This novel protein modification contributes to age-related lens coloration and may play a role in human nuclear cataractogenesis.

Eikenella corrodens phase variation involves a posttranslational event in pilus formation.

The human pathogen Eikenella corrodens synthesizes type IV pili and exhibits a phase variation involving the irreversible transition from piliated to nonpiliated variants. On solid medium, piliated variants form small (S-phase), corroding colonies whereas nonpiliated variants form large (L-phase), noncorroding colonies. We are studying the molecular basis of this phase variation in the clinical isolate E. corrodens VA1. A genomic fragment encoding the major type IV pilin was cloned from the S-phase variant of strain VA1. Sequence analysis of the fragment revealed four tandemly arranged potential open reading frames (ORFs), designated pilA1, pilA2, pilB, and hagA. Both pilA1 and pilA2 predict a type IV pilin. The protein predicted by pilB shares sequence identity with the Dichelobacter nodosus FimB fimbrial assembly protein. The protein predicted by hagA resembles a hemagglutinin. The region containing these four ORFs was designated the pilA locus. DNA hybridization and sequence analysis showed that the pilA locus of an L-phase variant of strain VA1 was identical to that of the S-phase variant. An abundant pilA1 transcript initiating upstream of pilA1 and terminating at a predicted hairpin structure between pilA1 and pilA2 was detected by several assays, as was a less abundant read-through transcript encompassing pilA1, pilA2, and pilB. Transcription from the pilA locus was nearly indistinguishable between S- and L-phase variants. Electron microscopy and immunochemical analysis showed that S-phase variants synthesize, export, and assemble pilin into pili. In contrast, L-phase variants synthesize pilin but do not export and assemble it into pili. These data suggest that a posttranslational event, possibly involving an alteration in pilin export and assembly, is responsible for phase variation in E. corrodens.

Two intact executive capacities in children with autism: implications for the core executive dysfunctions in the disorder.

Many studies have shown that children with autism perform at a much lower level than control subjects on tests of executive functioning, defined as tasks requiring subjects to hold information in mind while suppressing a prepotent response. These tasks have invariably required subjects to (a) follow arbitrary and novel rules and (b) make a nonverbal response. We report that when one of these features is absent, children with autism are not impaired relative to controls. They perform at a similar level to normally developing children on the "tubes" task (containing no arbitrary and novel rules) and on the day/night task (in which the output is verbal). Results are consistent, at least, with the hypothesis that children with autism are challenged by executive tasks because they are unlikely to encode rules in a verbal form.

Fascioloidiasis in game-ranched elk from Montana.

The distribution of Fascioloides magna in game-ranched elk and the potential for spread of the parasite through movement of infected animals was examined in Montana (USA). Fecal samples (n = 448) collected from captive elk on 29 game ranches were examined for eggs of F. magna by fecal sedimentation. Eggs were detected in elk on 5 ranches. This suggests that F. magna has been translocated by infected game-ranched elk. The wide distribution of snail intermediate hosts for F. magna in Montana indicates a potential to spread the parasite to other captive cervids domestic livestock or free-ranging wildlife.

Metamemory in narcolepsy.

People with narcolepsy consistently report diminished memory function attributable to the disorder, however, objective evaluations of memory performance in this clinical group remain inconclusive. Previous evaluations of these subjective experiences have been primarily anecdotal with subjects required to provide global assessments of their memory function. The present study aimed to evaluate subjective assessments of memory dysfunction more extensively comparing responses by narcoleptics, subjects experiencing excessive daytime sleepiness, and controls, on the Metamemory in Adulthood (MIA) questionnaire. The results of the study indicate that subjects with narcolepsy have lower self efficacy for memory performance than either of the comparison groups, despite there being no significant difference between groups in relation to knowledge based aspects of memory functioning. This lowered self efficacy in narcolepsy is expressed through increased anxiety about memory function, decreased evaluations of memory capacity and increased perceptions of memory decline in relation to the comparison groups. It is argued that the negative cognitive self evaluations of narcoleptics potentially arise as a consequence of global psychosocial adjustment difficulties.

Believing what you feel: using proprioceptive feedback to reduce unilateral neglect.

Unilateral spatial neglect declines when participants reach to grip the center of long metal rods compared with when they point to the perceived center, suggesting that visuomotor control systems are less affected by neglect than other representational systems (I. H. Robertson, D. Nico, & B. Hood, 1995). In this study, 16 participants with unilateral left neglect actually picked up rods, and we predicted short-term improvements in neglect because of induced conflict between a phenomenally symmetrical visual world on the one hand and a proprioceptively conveyed rightward-biased world on the other. With participants serving as their own controls, significant short-term improvements in neglect were found on 2 out of 4 neglect tasks after participants experienced proprioceptive feedback discrepant from the judgments they made on the basis of visual information alone.

Sleepiness and performance in narcolepsy.

Previous attempts to investigate the relationship between sleepiness and performance for subjects with narcolepsy have been limited by both the ability of narcoleptic subjects to contain their sleepiness for brief testing periods and the potential lack of sensitivity of routine performance tasks to sleepiness induced changes. The present study developed a research protocol which allowed subjects with narcolepsy to express states of sleepiness and non sleepiness and to then compare the performance of subjects with narcolepsy to age, gender and IQ matched controls on tasks evaluating automatic, attentional and complex cognitive functioning. The results indicated that at high arousal subjects with narcolepsy performed as well as controls on automatic tasks suggesting that the capacity to perform for narcolepsy subjects is not restricted by physiological factors but is secondary to the effects of sleepiness. Comparison of both the within subject effects for narcolepsy subjects of the transition between high and low arousal states, and the between subject effects of low arousal for narcolepsy subjects compared to controls indicate that complex cognitive tasks are the most sensitive to arousal fluctuation. This study provides support for the subjective experiences of subjects with narcolepsy of diminished cognitive function associated with the disorder.

The intention to act improves unilateral left neglect: two demonstrations.

Unilateral neglect involves a spatial bias to one side of space, usually to the right. Perceptual and motor systems interact in the manifestation of this disorder, and there is also evidence that motor manipulative responses may have access to unique streams of information not available for non-motoric judgements. It is therefore predicted that the manifestation of neglect may be alterable by changing the purpose of otherwise very similar responses to spatially extended objects. In Experiment 1, neglect-based deviation to the right of centre was significantly less when subjects reached towards metal rods as if to pick them up in the centre, compared to when they pointed to their centres. In Experiment 2, subjects pointed to the centre of a rectangular box with a swivelled lid. They were then asked to place a coin at the centre of this lid, in a position sufficiently central to prevent the lid tilting and the coin falling into the box; in fact, the lid was fixed and subjects never received feedback. Responses were significantly more central with the balancing response than with the pointing one. These results suggest that prehensive movements towards objects allow 'leakage' of information about their spatial extent, via an unaffected stream of information available for motor-manipulative responses.