Does encouraging a belief in determinism increase cheating? Reconsidering the value of believing in free will.

A key source of support for the view that challenging people's beliefs about free will may undermine moral behavior is two classic studies by Vohs and Schooler (2008). These authors reported that exposure to certain prompts suggesting that free will is an illusion increased cheating behavior. In the present paper, we report several attempts to replicate this influential and widely cited work. Over a series of five studies (sample sizes of N = 162, N = 283, N = 268, N = 804, N = 982) (four preregistered) we tested the relationship between (1) anti-free-will prompts and free will beliefs and (2) free will beliefs and immoral behavior. Our primary task was to closely replicate the findings from Vohs and Schooler (2008) using the same or highly similar manipulations and measurements as the ones used in their original studies. Our efforts were largely unsuccessful. We suggest that manipulating free will beliefs in a robust way is more difficult than has been implied by prior work, and that the proposed link with immoral behavior may not be as consistent as previous work suggests.

Identification and classification of cathinone unknowns by statistical analysis processing of direct analysis in real time-high resolution mass spectrometry-derived "neutral loss" spectra.

An approach to the rapid determination of the structures of novel synthetic cathinone designer drugs, also known as bath salts, is reported. While cathinones fragment so extensively by electron impact mass spectrometry that their mass spectra often cannot be used to identify the structure, collision-induced dissociation (CID) direct analysis in real time-high resolution mass spectrometry (DART-HRMS) experiments furnished spectra that provided diagnostic fragmentation patterns for the analyzed cathinones. From this data, neutral loss spectra, which reflect the presence of specific chemical moieties, could be acquired. These spectra showed striking similarities between cathinones sharing structural features such as pyrrolidine rings and methylenedioxy moieties. Principle component analysis (PCA) of the neutral loss spectra of nine synthetic cathinones of various types including ethcathinones, those containing a methylenedioxy moiety appended to the benzene ring, and pyrrolidine-containing structures, illustrated that cathinones falling within the same class clustered together and could be distinguished from those of other classes. Furthermore, hierarchical clustering analysis of the neutral loss data of a model set derived from 44 synthetic cathinones, furnished a dendrogram in which structurally similar cathinones clustered together. The ability of this model system to facilitate structure determination was tested using 4-fluoroethcathinone, 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP), and ethylone, which fall into the ethcathinone, pyrrolidine-containing, and methylenedioxy-containing subclasses respectively. The results showed that their neutral loss spectra correctly fell within the ethcathinone, pyrrolidine-containing and methylenedioxy-containing cathinone clades of the dendrogram, and that the neutral loss information could be used to infer the structures of these compounds. The analysis and data processing steps are rapid and samples can be analyzed in their native form without any sample processing steps. The robustness of the dendrogram dataset can be readily increased by continued addition of newly discovered structures. The approach can be broadly applied to structure determination of unknowns, and would be particularly useful for analyses where sample amounts are limited.

Variations in judgments of intentional action and moral evaluation across eight cultures.

Individuals tend to judge bad side effects as more intentional than good side effects (the Knobe or side-effect effect). Here, we assessed how widespread these findings are by testing eleven adult cohorts of eight highly contrasted cultures on their attributions of intentional action as well as ratings of blame and praise. We found limited generalizability of the original side-effect effect, and even a reversal of the effect in two rural, traditional cultures (Samoa and Vanuatu) where participants were more likely to judge the good side effect as intentional. Three follow-up experiments indicate that this reversal of the side-effect effect is not due to semantics and may be linked to the perception of the status of the protagonist. These results highlight the importance of factoring cultural context in our understanding of moral cognition.

What kinds of alternative possibilities are required of the folk concept(s) of choice?

Our concept of choice is integral to the way we understand others and ourselves, especially when considering ourselves as free and responsible agents. Despite the importance of this concept, there has been little empirical work on it. In this paper we report four experiments that provide evidence for two concepts of choice-namely, a concept of choice that is operative in the phrase having a choice and another that is operative in the phrase making a choice. The experiments indicate that the two concepts of choice can be differentiated from each other on the basis of the kind of alternatives to which each is sensitive. The results indicate that the folk concept of choice is more nuanced than has been assumed. This new, empirically informed understanding of the folk concept of choice has important implications for debates concerning free will, responsibility, and other debates spanning psychology and philosophy.

Detection of "bath salt" synthetic cathinones and metabolites in urine via DART-MS and solid phase microextraction.

A rapid and sensitive method, direct analysis in real time mass spectrometry (DART-MS) was applied to the characterization and semiquantitative analysis of synthetic cathinones and their metabolites in urine. DART-MS was capable of detecting three different cathinones and three metabolites down to sub-clinical levels directly without any sample preparations. The process produced a spectrum within seconds because no extraction or derivatization was required for analysis and the high mass accuracy of the instrumentation allowed analysis without the need for lengthy chromatographic separations. The use of solid phase microextration demonstrated a relative increase in the detectability of both drugs and metabolites, improving the detection signal on average more than an order of magnitude over direct detection, while providing cleaner spectra devoid of the major peaks associated with urine that oftentimes dominate such samples.

DART-MS in-source collision induced dissociation and high mass accuracy for new psychoactive substance determinations.

The influx of new psychoactive substances is a problem that is challenging the analytical capabilities of enforcement agencies. Cathinone designer drugs are less likely to be included in routine drug screens and typical drug formulations are commonly mixtures with continually shifting components. Ambient ionization mass spectrometry employs relatively mild conditions to desorb and ionize solid samples, imparting much less energy than that associated with conventional mass spectrometry methods. Direct analysis in real time mass spectrometry (DART-MS) is an ambient ionization method that was employed to rapidly screen cathinones, alone and in mixtures, readily enabling differentiation of the active drug(s) from various cutting agents. Accurate mass determinations provided preliminary identification of the various components of drug mixtures. The data generated in forensic mass spectrometry can be used for both elemental composition formulations and isotope abundance calculations for determination of unknown psychoactive substances, and we demonstrate how this data could be applied to the presence of new drugs as the active components shift in response to regulations. Isotope abundance calculations were used to develop a candidate pool of possible molecular formulas associated with cathinones as a specific class of designer drugs. Together, the combination of a time-of-flight (TOF) mass analyzer along with in-source collision-induced dissociation (CID) spectra were used to drastically narrow the pool of candidates to a single molecular formula. The [M+H](+) and product ion peaks provided data for presumptive analysis of various substituted synthetic cathinones in a manner that is complementary to conventional GC-MS analysis of new psychoactive substances.

It's OK if 'my brain made me do it': people's intuitions about free will and neuroscientific prediction.

In recent years, a number of prominent scientists have argued that free will is an illusion, appealing to evidence demonstrating that information about brain activity can be used to predict behavior before people are aware of having made a decision. These scientists claim that the possibility of perfect prediction based on neural information challenges the ordinary understanding of free will. In this paper we provide evidence suggesting that most people do not view the possibility of neuro-prediction as a threat to free will unless it also raises concerns about manipulation of the agent's behavior. In Experiment 1 two scenarios described future brain imaging technology that allows perfect prediction of decisions and actions based on earlier neural activity, and this possibility did not undermine most people's attributions of free will or responsibility, except in the scenario that also allowed manipulation. In Experiment 2 the scenarios increased the salience of the physicalist implications of neuro-prediction, while in Experiment 3 the scenarios suggested dualism, with perfect prediction by mindreaders. The patterns of results for these two experiments were similar to the results in Experiment 1, suggesting that participants do not understand free will to require specific metaphysical conditions regarding the mind-body relation. Most people seem to understand free will in a way that is not threatened by perfect prediction based on neural information, suggesting that they believe that just because "my brain made me do it," that does not mean that I didn't do it of my own free will.

Recent advances in forensic drug analysis by DART-MS.

Mass spectrometry methods play a major role in many forensic applications. While gas chromatography-mass spectrometry methods are commonly used in crime laboratories and enforcement agencies, a variety of advanced techniques are now available that can improve upon standard methods and address emerging issues in forensic science. New mass spectrometry technologies include more versatile ionization sources, allowing the next generation of instrumentation to be more multipurpose and adaptable to the needs of the discipline. Direct analysis in real-time mass spectrometry is an ambient ionization method that allows direct testing of gas, liquid and solid samples without the need for any preparation or extraction, based on thermal desorption and ionization directly from the sample surface. This Review will provide an in-depth description of direct analysis in real-time time-of-flight mass spectrometry as applied to samples relevant to forensic science, with a focus on analysis and characterization related to forensic drug chemistry.

The free will inventory: measuring beliefs about agency and responsibility.

In this paper, we present the results of the construction and validation of a new psychometric tool for measuring beliefs about free will and related concepts: The Free Will Inventory (FWI). In its final form, FWI is a 29-item instrument with two parts. Part 1 consists of three 5-item subscales designed to measure strength of belief in free will, determinism, and dualism. Part 2 consists of a series of fourteen statements designed to further explore the complex network of people's associated beliefs and attitudes about free will, determinism, choice, the soul, predictability, responsibility, and punishment. Having presented the construction and validation of FWI, we discuss several ways that it could be used in future research, highlight some as yet unanswered questions that are ripe for interdisciplinary investigation, and encourage researchers to join us in our efforts to answer these questions.

DART-MS for rapid, preliminary screening of urine for DMAA.

Dimethylamylamine (DMAA) is a sympathomimetic amine found in weight-loss/workout supplements or used as an appetite suppressant. DMAA is a stimulant that is banned by the World Anti-Doping Agency (WADA). Adverse health effects as well as fatalities have been implicated with its use. Direct analysis in real time mass spectrometry (DART-MS) is an ambient ionization method that was employed to rapidly identify the presence of DMAA in various samples without any extraction or preparations whatsoever. DMAA was first identified in supplements, sampled directly in their solid forms. Furthermore, DMAA was detected directly in urine over 48 h as a means of indicating recent abuse of the substance. DART-MS analysis is instantaneous, and coupled with the high mass accuracy associated with the time-of-flight mass analyzer, results in unequivocal identification of the presence of DMAA. These features demonstrate DART-MS as an attractive potential alternative screening method for the presence of drugs and medications or for toxicological investigations.

DART-MS as a preliminary screening method for "herbal incense": chemical analysis of synthetic cannabinoids.

Direct analysis in real time mass spectrometry (DART-MS) served as a method for rapid high-throughput screening of six commercially available "Spice" products, detecting various combinations of five synthetic cannabinoids. Direct analysis in real time is an ambient ionization process that, along with high mass accuracy time-of-flight (TOF)-MS to 0.0001 Da, was employed to establish the presence of cannabinoids. Mass spectra were acquired by simply suspending a small portion of sample between the ion source and the mass spectrometer inlet. The ability to test minute amounts of sample is a major advantage when very limited amounts of evidentiary material are available. In addition, reports are widespread regarding the testing backlogs that now exist because of the large influx of designer drugs. This method circumvents time-consuming sample extraction, derivatization, chromatographic, and other sample preparative steps required for analysis by more conventional mass spectrometric methods. Accordingly, the synthetic cannabinoids AM-2201, JWH-122, JWH-203, JWH-210, and RCS-4 were identified in commercially available herbal Spice products, singly and in tandem, at concentrations within the range of 4-141 mg/g of material. Direct analysis in real time mass spectrometry decreases the time necessary to triage analytical evidence, and therefore, it has the potential to contribute to backlog reduction and more timely criminal prosecution.

Direct analysis in real time mass spectrometry (DART-MS) of "bath salt" cathinone drug mixtures.

Rapid and versatile direct analysis in real time mass spectrometry (DART-MS) methods were developed for detection and characterization of synthetic cathinone designer drugs, also known as "bath salts". The speed and efficiency associated with DART-MS testing of such highly unpredictable samples demonstrate the technique as an attractive alternative to conventional GC-MS and LC-MS methods. A series of isobaric and closely related synthetic cathinones, alone and in mixtures, were differentiated using high mass accuracy and in-source collision induced dissociation (CID). Crime laboratories have observed a dramatic rise in the use of these substances, which has caused sample testing backlogs, particularly since the myriad of structurally related compounds are challenging to efficiently differentiate. This challenge is compounded by the perpetual emergence of new structural variants as soon as older generation derivatives become scheduled. Because of the numerous chemical substances that fall into these categories, along with the varying composition and complexity of mixtures of these drugs, DART-MS CID has the potential to dramatically streamline sample analysis, minimize the number of sample preparation steps, and enable rapid characterization of emerging structural analogs.

Direct analysis in real time mass spectrometry with collision-induced dissociation for structural analysis of synthetic cannabinoids.

RATIONALE: The emergence of numerous cannabinoid designer drugs has been tied to large spikes in emergency room visits and overdoses. Identifying these substances is difficult for the following reasons: (1) the compounds are novel, closely structurally related, and do not usually test positive in drug screens; (2) novel analogs rapidly appear on the market; (3) no standard protocols exist for their identification; and (4) customized and extensive sample preparation/extraction and analysis procedures are required to demonstrate their presence. METHODS: Direct analysis in real time mass spectrometry (DART-MS) employing collision-induced dissociation (CID) provided confirmatory structural information that was useful in characterizing the various cannabinoid analogs, including those contained in mixtures. CID analysis illustrated that, although closely related compounds fragment in a similar fashion, their structural differences still resulted in multiple diagnostic peaks that provided additional confidence towards structural identification. RESULTS: DART-MS spectra were acquired under CID conditions to rapidly differentiate among five synthetic cannabinoids contained within 'herbal' products purchased locally in New York State (USA). The spectra exhibited [M+H](+) ions and product ions unique to each cannabinoid that corresponded to major structural features. Five different cannabinoid analogs, alone and as mixtures of at least two cannabinoids, were identified in six herbal products and differentiated by their CID product ion patterns. CONCLUSIONS: Illicit synthetic cannabinoid products continue to be readily available despite national and international restrictions. These products contain a wide range of active components, and, in many cases, multiple active ingredients. DART-MS allows rapid analyses of these synthetic cannabinoids based on the exact masses of their [M+H](+) ions and product ion peaks generated using CID.

Direct analysis in real time mass spectrometry for analysis of sexual assault evidence.

RATIONALE: Sexual assault crimes are vastly underreported and suffer from alarmingly low prosecution and conviction rates. The key scientific method to aid in prosecution of such cases is forensic DNA analysis, where biological evidence such as semen collected using a rape test kit is used to determine a suspect's DNA profile. However, the growing awareness by criminals of the importance of DNA in the prosecution of sexual assaults has resulted in increased condom use by assailants as a means to avoid leaving behind their DNA. Thus, other types of trace evidence are important to help corroborate victims' accounts, exonerate the innocent, link suspects to the crime, or confirm penetration. METHODS: Direct Analysis in Real Time Mass Spectrometry (DART-MS) was employed for the comprehensive characterization of non-DNA trace evidence associated with sexual assault. The ambient ionization method associated with DART-MS is extremely rapid and samples are processed instantaneously, without the need for extraction, sample preparation, or other means that might compromise forensic evidence for future analyses. RESULTS: In a single assay, we demonstrated the ability to identify lubricant formulations associated with sexual assault, such as the spermicide nonoxynol-9, compounds used in condom manufacture, and numerous other trace components as probative evidence. In addition, the method can also serve to identify compounds within trace biological residues, such as fatty acids commonly identified in latent fingerprints. CONCLUSIONS: Characterization of lubricant residues as probative evidence serves to establish a connection between the victim and the perpetrator, and the availability of these details may lead to higher rates of prosecution and conviction, as well as more severe penalties. The methodology described here opens the way for the adoption of a comprehensive, rapid, and sensitive analysis for use in crime labs, while providing knowledge that can inform and guide criminal justice policy and practice.

Rapid identification of synthetic cannabinoids in herbal samples via direct analysis in real time mass spectrometry.

RATIONALE: Dozens of synthetic cannabinoid analogs purposefully meant to circumvent legal restrictions associated with controlled substances continue to be manufactured and promoted as producing 'legal highs'. These designer drugs are difficult to identify in conventional drug screens not only because routine protocols have not been developed for their detection, but also because their association with complex plant matrices during manufacture generally requires labor-intensive extraction and sample preparation for analysis. To address this new and important challenge in forensic chemistry, Direct Analysis in Real Time Mass Spectrometry (DART-MS) is applied to the analysis of these designer drugs. METHODS: DART-MS was employed to sample synthetic cannabinoids directly on botanical matrices. The ambient ionization method associated with DART-MS permitted the analysis of solid herbal samples directly, without the need for extraction or sample preparation. The high mass resolution time-of-flight analyzer allowed identification of these substances despite their presence within a complex matrix and enabled differentiation of closely related analogs. RESULTS: DART-MS was performed to rapidly identify the synthetic cannabinoids AM-251 and JWH-015. For each cannabinoid, three hundred micrograms (300 µg) of material was easily detected within an excess of background matrix by mass. CONCLUSIONS: New variations of herbal blends containing a wide range of base components and laced with synthetic cannabinoids are being produced, making their presence difficult to track by conventional methods. DART-MS permits rapid identification of trace synthetic cannabinoids within complex biological matrices, with excellent sensitivity and specificity compared with standard methods.

Detection of the spermicide nonoxynol-9 via GC-MS.

The spermicide nonoxynol-9 is actually a complex mixture of dozens of closely related amphiphilic compounds, and the chemical properties of this assortment significantly hamper its characterization by GC-MS. The inability to perform routine GC-MS testing on nonoxynol-9 has limited its evidentiary value in forensic casework, which relies heavily on this technique for analysis. A disturbing trend in sexual assault is the use of condoms by assailants, to avoid leaving behind DNA evidence that can connect a perpetrator to a victim. This observation necessitates the development of alternative methods for the analysis of trace evidence that can show causal links between a victim and a suspect. Detection of lubricants associated with sexual assault is one such way to establish this connection. The development of GC-MS methods that permit facile detection of both nonoxynol-9 alone and nonoxynol-9 extracted from other complex matrices that have potential as trace evidence in sexual assault is reported. A detection limit of 2.14 µg of nonoxynol-9 is demonstrated, and a detailed mass spectral profile that elaborates on what is known of its structure is provided.

Abrupt and dynamic changes in gene expression revealed by live cell arrays.

A description of the noise associated with gene expression is presented, based on a simplified form of the combined multistep processes of transcription and translation. These processes are influenced by numerous factors, including the accessibility of promoter regions to the transcriptional machinery, the kinetics of assembly of the transcription complexes, and the synthesis and degradation of both mRNA and proteins, among others. Ultimately, stochasticity in cellular processes results in variation in protein levels. Here we constructed a rationally designed RNA-based transcriptional activator to reduce these variables and provide a cleaner, more detailed portrayal of cellular noise. Functioning at a level comparable to natural transcription activation, this activator is isolated to a lacZ reporter gene in yeast cells to quantitatively describe the efficiency of the combined processes of transcription and translation. By employing single-cell array techniques to monitor individual cells simultaneously and in real time, a statistical approach to investigate noise inherent in gene expression is possible. Live cell arrays enabled cell populations to be characterized temporally at the individual cell level. The array platform allowed for a relative measure of protein production in real time and could characterize protein bursts with variable size and random timing, such that bursts occurred in a temporally indiscriminate fashion. The inherent variability and randomness of these processes is characterized, with almost half (47%) of cells experiencing bursting behavior at least once over the course of the experiment. We demonstrate that cells identified on the upper periphery of activity exhibit behaviors that are substantially different from the majority of the population, and such variable activities within a population will provide a more accurate characterization of the population.

Cellular heterogeneity and live cell arrays.

In the past decade, the tendency to move from a global, one-size-fits-all treatment philosophy to personalized medicine is based, in part, on the nuanced differences and sub-classifications of disease states. Our knowledge of these varied states stems from not only the ability to diagnose, classify, and perform experiments on cell populations as a whole, but also from new technologies that allow interrogation of cell populations at the individual cell level. Such departures from conventional thinking are driven by the recognition that clonal cell populations have numerous activities that manifest as significant levels of non-genetic heterogeneity. Clonal populations by definition originate from a single genetic origin so are regarded as having a high level of homogeneity as compared to genetically distinct cell populations. However, analysis at the single cell level has revealed a different phenomenon; cells and organisms require an inherent level of non-genetic heterogeneity to function properly, and in some cases, to survive. The growing understanding of this occurrence has lead to the development of methods to monitor, analyze, and better characterize the heterogeneity in cell populations. Following the trend of DNA- and protein microarrays, platforms capable of simultaneously monitoring each cell in a population have been developed. These cellular microarray platforms and other related formats allow for continuous monitoring of single live cells and simultaneously generate individual cell and average population data that are more descriptive and information-rich than traditional bulk methods. These technological advances have helped develop a better understanding of the intricacies associated with biological processes and afforded greater insight into complex biological systems. The associated instruments, techniques, and reagents now allow for highly multiplexed analyses, which enable multiple cellular activities, processes, or pathways to be monitored simultaneously. This critical review will discuss the paradigm shift associated with cellular heterogeneity, speak to the key developments that have lead to our better understanding of systems biology, and detail the future directions of the discipline (281 references).

Quantum dots for positional registration in live cell-based arrays.

For a better understanding of complex biological processes, it is desirable to simultaneously follow the dynamics of multiple components in living cells or organisms in real time. An encoding scheme was developed that enables the observation of multiple cell populations with single-cell resolution. Specifically, different yeast cell types were labeled with quantum dots and added to an array of microwells, where they randomly self-assemble into the complementary-sized cavities. Quantum dots conjugated to cells externally, internally, or in combination generated unique optical patterns to differentiate various cell types in the array. For the model system described herein, cells were monitored for their lacZ expression levels through the processing of a fluorescent precursor by ss-galactosidase. The encoding schemes employed were independent of the reporter emission and had no affect on the cellular activity. The live cell array platform allowed analysis of hundreds of individual cells simultaneously and continuously in real time. By coupling this platform with quantum dot cell labeling, the utility of this array format is extended to mixed cellular populations.

An RNA-based transcription activator derived from an inhibitory aptamer.

According to the recruitment model of transcriptional activation, an activator helps initiate transcription by bringing the RNA polymerase to a specific location on the DNA through interaction with components of the transcriptional machinery. However, it is difficult to isolate and define the activities of specific activator-target pairs experimentally through rearranging existing protein parts. Here we designed and constructed an RNA-based transcriptional activator to study specificity from both sides of the activator-target interface. Utilizing a well-characterized site-specific RNA aptamer for TFIIB, we were able to delineate some key features of this process. By rationally converting an inhibitory aptamer into the activation domain of the activator, we also introduced a new source of submolecular building blocks to synthetic biology.