Journal: PLoS computational biology
The negative effects of extremely competitive academic and research environments on the performance and health of researchers are well known and common worldwide. The prevalence of these effects, particularly among early career researchers, calls for a more humane and people-centered way of working within research labs. Although there is growing concern about the urgent need for a better life-work balance when doing science, there are not many examples about how this could be achieved in practice. In this article, I introduce 10 simple rules to make the working environment of research labs more nurturing, collaborative, and people-centered. These rules are directed towards existing and future principal investigators (PIs) but will be of interest to anyone working in a research lab and/or dealing with how to improve working conditions for scientists.
There is a popular belief in neuroscience that we are primarily data limited, and that producing large, multimodal, and complex datasets will, with the help of advanced data analysis algorithms, lead to fundamental insights into the way the brain processes information. These datasets do not yet exist, and if they did we would have no way of evaluating whether or not the algorithmically-generated insights were sufficient or even correct. To address this, here we take a classical microprocessor as a model organism, and use our ability to perform arbitrary experiments on it to see if popular data analysis methods from neuroscience can elucidate the way it processes information. Microprocessors are among those artificial information processing systems that are both complex and that we understand at all levels, from the overall logical flow, via logical gates, to the dynamics of transistors. We show that the approaches reveal interesting structure in the data but do not meaningfully describe the hierarchy of information processing in the microprocessor. This suggests current analytic approaches in neuroscience may fall short of producing meaningful understanding of neural systems, regardless of the amount of data. Additionally, we argue for scientists using complex non-linear dynamical systems with known ground truth, such as the microprocessor as a validation platform for time-series and structure discovery methods.
The primary immunological target of COVID-19 vaccines is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface and mediates viral entry into the host cell. To identify possible antibody binding sites, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation, and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for structure-based vaccine design. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics. The protective glycan shield and the high flexibility of its hinges give the stalk overall low epitope scores. Our computational epitope-mapping procedure is general and should thus prove useful for other viral envelope proteins whose structures have been characterized.
Human menopause is an unsolved evolutionary puzzle, and relationships among the factors that produced it remain understood poorly. Classic theory, involving a one-sex (female) model of human demography, suggests that genes imparting deleterious effects on post-reproductive survival will accumulate. Thus, a ‘death barrier’ should emerge beyond the maximum age for female reproduction. Under this scenario, few women would experience menopause (decreased fertility with continued survival) because few would survive much longer than they reproduced. However, no death barrier is observed in human populations. Subsequent theoretical research has shown that two-sex models, including male fertility at older ages, avoid the death barrier. Here we use a stochastic, two-sex computational model implemented by computer simulation to show how male mating preference for younger females could lead to the accumulation of mutations deleterious to female fertility and thus produce a menopausal period. Our model requires neither the initial assumption of a decline in older female fertility nor the effects of inclusive fitness through which older, non-reproducing women assist in the reproductive efforts of younger women. Our model helps to explain why such effects, observed in many societies, may be insufficient factors in elucidating the origin of menopause.
The link between object perception and neural activity in visual cortical areas is a problem of fundamental importance in neuroscience. Here we show that electrical potentials from the ventral temporal cortical surface in humans contain sufficient information for spontaneous and near-instantaneous identification of a subject’s perceptual state. Electrocorticographic (ECoG) arrays were placed on the subtemporal cortical surface of seven epilepsy patients. Grayscale images of faces and houses were displayed rapidly in random sequence. We developed a template projection approach to decode the continuous ECoG data stream spontaneously, predicting the occurrence, timing and type of visual stimulus. In this setting, we evaluated the independent and joint use of two well-studied features of brain signals, broadband changes in the frequency power spectrum of the potential and deflections in the raw potential trace (event-related potential; ERP). Our ability to predict both the timing of stimulus onset and the type of image was best when we used a combination of both the broadband response and ERP, suggesting that they capture different and complementary aspects of the subject’s perceptual state. Specifically, we were able to predict the timing and type of 96% of all stimuli, with less than 5% false positive rate and a ~20ms error in timing.
The primate visual system achieves remarkable visual object recognition performance even in brief presentations, and under changes to object exemplar, geometric transformations, and background variation (a.k.a. core visual object recognition). This remarkable performance is mediated by the representation formed in inferior temporal (IT) cortex. In parallel, recent advances in machine learning have led to ever higher performing models of object recognition using artificial deep neural networks (DNNs). It remains unclear, however, whether the representational performance of DNNs rivals that of the brain. To accurately produce such a comparison, a major difficulty has been a unifying metric that accounts for experimental limitations, such as the amount of noise, the number of neural recording sites, and the number of trials, and computational limitations, such as the complexity of the decoding classifier and the number of classifier training examples. In this work, we perform a direct comparison that corrects for these experimental limitations and computational considerations. As part of our methodology, we propose an extension of “kernel analysis” that measures the generalization accuracy as a function of representational complexity. Our evaluations show that, unlike previous bio-inspired models, the latest DNNs rival the representational performance of IT cortex on this visual object recognition task. Furthermore, we show that models that perform well on measures of representational performance also perform well on measures of representational similarity to IT, and on measures of predicting individual IT multi-unit responses. Whether these DNNs rely on computational mechanisms similar to the primate visual system is yet to be determined, but, unlike all previous bio-inspired models, that possibility cannot be ruled out merely on representational performance grounds.
Computers are now essential in all branches of science, but most researchers are never taught the equivalent of basic lab skills for research computing. As a result, data can get lost, analyses can take much longer than necessary, and researchers are limited in how effectively they can work with software and data. Computing workflows need to follow the same practices as lab projects and notebooks, with organized data, documented steps, and the project structured for reproducibility, but researchers new to computing often don’t know where to start. This paper presents a set of good computing practices that every researcher can adopt, regardless of their current level of computational skill. These practices, which encompass data management, programming, collaborating with colleagues, organizing projects, tracking work, and writing manuscripts, are drawn from a wide variety of published sources from our daily lives and from our work with volunteer organizations that have delivered workshops to over 11,000 people since 2010.
Standard theories of decision-making involving delayed outcomes predict that people should defer a punishment, whilst advancing a reward. In some cases, such as pain, people seem to prefer to expedite punishment, implying that its anticipation carries a cost, often conceptualized as ‘dread’. Despite empirical support for the existence of dread, whether and how it depends on prospective delay is unknown. Furthermore, it is unclear whether dread represents a stable component of value, or is modulated by biases such as framing effects. Here, we examine choices made between different numbers of painful shocks to be delivered faithfully at different time points up to 15 minutes in the future, as well as choices between hypothetical painful dental appointments at time points of up to approximately eight months in the future, to test alternative models for how future pain is disvalued. We show that future pain initially becomes increasingly aversive with increasing delay, but does so at a decreasing rate. This is consistent with a value model in which moment-by-moment dread increases up to the time of expected pain, such that dread becomes equivalent to the discounted expectation of pain. For a minority of individuals pain has maximum negative value at intermediate delay, suggesting that the dread function may itself be prospectively discounted in time. Framing an outcome as relief reduces the overall preference to expedite pain, which can be parameterized by reducing the rate of the dread-discounting function. Our data support an account of disvaluation for primary punishments such as pain, which differs fundamentally from existing models applied to financial punishments, in which dread exerts a powerful but time-dependent influence over choice.
Postdocs are a critical transition for early-career researchers. This transient period, between finishing a PhD and finding a permanent position, is when early-career researchers develop independent research programs and establish collaborative relationships that can make a successful career. Traditionally, postdocs physically relocate-sometimes multiple times-for these short-term appointments, which creates challenges that can disproportionately affect members of traditionally underrepresented groups in science, technology, engineering, and mathematics (STEM). However, many research activities involving analytical and quantitative work do not require a physical presence in a lab and can be accomplished remotely. Other fields have embraced remote work, yet many academics have been hesitant to hire remote postdocs. In this article, we present advice to both principal investigators (PIs) and postdocs for successfully navigating a remote position. Using the combined experience of the authors (as either remote postdocs or employers of remote postdocs), we provide a road map to overcome the real (and perceived) obstacles associated with remote work. With planning, communication, and creativity, remote postdocs can be a fully functioning and productive member of a research lab. Further, our rules can be useful for research labs generally and can help foster a more flexible and inclusive environment.
Echolocation is the ability to use sound-echoes to infer spatial information about the environment. Some blind people have developed extraordinary proficiency in echolocation using mouth-clicks. The first step of human biosonar is the transmission (mouth click) and subsequent reception of the resultant sound through the ear. Existing head-related transfer function (HRTF) data bases provide descriptions of reception of the resultant sound. For the current report, we collected a large database of click emissions with three blind people expertly trained in echolocation, which allowed us to perform unprecedented analyses. Specifically, the current report provides the first ever description of the spatial distribution (i.e. beam pattern) of human expert echolocation transmissions, as well as spectro-temporal descriptions at a level of detail not available before. Our data show that transmission levels are fairly constant within a 60° cone emanating from the mouth, but levels drop gradually at further angles, more than for speech. In terms of spectro-temporal features, our data show that emissions are consistently very brief (~3ms duration) with peak frequencies 2-4kHz, but with energy also at 10kHz. This differs from previous reports of durations 3-15ms and peak frequencies 2-8kHz, which were based on less detailed measurements. Based on our measurements we propose to model transmissions as sum of monotones modulated by a decaying exponential, with angular attenuation by a modified cardioid. We provide model parameters for each echolocator. These results are a step towards developing computational models of human biosonar. For example, in bats, spatial and spectro-temporal features of emissions have been used to derive and test model based hypotheses about behaviour. The data we present here suggest similar research opportunities within the context of human echolocation. Relatedly, the data are a basis to develop synthetic models of human echolocation that could be virtual (i.e. simulated) or real (i.e. loudspeaker, microphones), and which will help understanding the link between physical principles and human behaviour.