Measurement of B_{s}^{0} meson production in pp and PbPb collisions at \sqrt{SNN}

The production cross sections of B_{s}^{0} mesons and charge conjugates are measured in proton-proton (pp) and PbPb collisions via the exclusive decay channel B_{s}^{0}→J/ψϕ→μ^{+}μ^{−}K^{+}K^{−} at a center-of-mass energy of 5.02 TeV per nucleon pair and within the rapidity range |y|<2.4 using the CMS detector at the LHC. The pp measurement is performed as a function of transverse momentum (p_{T}) of the B_{s}^{0} mesons in the range of 7 to 50 GeV/c and is compared to the predictions of perturbative QCD calculations. The B_{s}^{0} production yield in PbPb collisions is measured in two p_{T} intervals, 7 to 15 and 15 to 50 GeV/c, and compared to the yield in pp collisions in the same kinematic region. The nuclear modification factor (R_{AA}) is found to be 1.5±0.6(stat)±0.5(syst) for 7–15 GeV/c, and 0.87±0.30(stat)±0.17(syst) for 15–50 GeV/c, respectively. Within current uncertainties, the B_{s}^{0} results are consistent with models of strangeness enhancement, and suppression by parton energy loss, as observed for the B+ mesons

Hepatic stellate cells:central modulators of hepatic carcinogenesis

Hepatocellular carcinoma (HCC) represents the second most common cause of cancer-related death worldwide, and is increasing in incidence. Currently, our therapeutic repertoire for the treatment of HCC is severely limited, and therefore effective new therapies are urgently required. Recently, there has been increasing interest focusing on the cellular and molecular interactions between cancer cells and their microenvironment. HCC represents a unique opportunity to study the relationship between a diseased stroma and promotion of carcinogenesis, as 90 % of HCCs arise in a cirrhotic liver. Hepatic stellate cells (HSC) are the major source of extracellular proteins during fibrogenesis, and may directly, or via secreted products, contribute to tumour initiation and progression. In this review we explore the complex cellular and molecular interplay between HSC biology and hepatocarcinogenesis. We focus on the molecular mechanisms by which HSC modulate HCC growth, immune cell evasion and angiogenesis. This is followed by a discussion of recent progress in the field in understanding the mechanistic crosstalk between HSC and HCC, and the pathways that are potentially amenable to therapeutic intervention. Furthermore, we summarise the exciting recent developments in strategies to target HSC specifically, and novel techniques to deliver pharmaceutical agents directly to HSC, potentially allowing tailored, cell-specific therapy for HCC

Early behavioural facilitation by temporal expectations in complex visual-motor sequences

In daily life, temporal expectations may derive from incidental learning of recurring patterns of intervals. We investigated the incidental acquisition and utilisation of combined temporal-ordinal (spatial/effector) structure in complex visual-motor sequences using a modified version of a serial reaction time (SRT) task. In this task, not only the series of targets/responses, but also the series of intervals between subsequent targets was repeated across multiple presentations of the same sequence. Each participant completed three sessions. In the first session, only the repeating sequence was presented. During the second and third session, occasional probe blocks were presented, where a new (unlearned) spatial-temporal sequence was introduced. We first confirm that participants not only got faster over time, but that they were slower and less accurate during probe blocks, indicating that they incidentally learned the sequence structure. Having established a robust behavioural benefit induced by the repeating spatial-temporal sequence, we next addressed our central hypothesis that implicit temporal orienting (evoked by the learned temporal structure) would have the largest influence on performance for targets following short (as opposed to longer) intervals between temporally structured sequence elements, paralleling classical observations in tasks using explicit temporal cues. We found that indeed, reaction time differences between new and repeated sequences were largest for the short interval, compared to the medium and long intervals, and that this was the case, even when comparing late blocks (where the repeated sequence had been incidentally learned), to early blocks (where this sequence was still unfamiliar). We conclude that incidentally acquired temporal expectations that follow a sequential structure can have a robust facilitatory influence on visually-guided behavioural responses and that, like more explicit forms of temporal orienting, this effect is most pronounced for sequence elements that are expected at short inter-element intervals

Reprint of: Early behavioural facilitation by temporal expectations in complex visual-motor sequences

In daily life, temporal expectations may derive from incidental learning of recurring patterns of intervals. We investigated the incidental acquisition and utilisation of combined temporal-ordinal (spatial/effector) structure in complex visual-motor sequences using a modified version of a serial reaction time (SRT) task. In this task, not only the series of targets/responses, but also the series of intervals between subsequent targets was repeated across multiple presentations of the same sequence. Each participant completed three sessions. In the first session, only the repeating sequence was presented. During the second and third session, occasional probe blocks were presented, where a new (unlearned) spatial-temporal sequence was introduced. We first confirm that participants not only got faster over time, but that they were slower and less accurate during probe blocks, indicating that they incidentally learned the sequence structure. Having established a robust behavioural benefit induced by the repeating spatial-temporal sequence, we next addressed our central hypothesis that implicit temporal orienting (evoked by the learned temporal structure) would have the largest influence on performance for targets following short (as opposed to longer) intervals between temporally structured sequence elements, paralleling classical observations in tasks using explicit temporal cues. We found that indeed, reaction time differences between new and repeated sequences were largest for the short interval, compared to the medium and long intervals, and that this was the case, even when comparing late blocks (where the repeated sequence had been incidentally learned), to early blocks (where this sequence was still unfamiliar). We conclude that incidentally acquired temporal expectations that follow a sequential structure can have a robust facilitatory influence on visually-guided behavioural responses and that, like more explicit forms of temporal orienting, this effect is most pronounced for sequence elements that are expected at short inter-element intervals

Reprint of: Early behavioural facilitation by temporal expectations in complex visual-motor sequences

In daily life, temporal expectations may derive from incidental learning of recurring patterns of intervals. We investigated the incidental acquisition and utilisation of combined temporal-ordinal (spatial/effector) structure in complex visual-motor sequences using a modified version of a serial reaction time (SRT) task. In this task, not only the series of targets/responses, but also the series of intervals between subsequent targets was repeated across multiple presentations of the same sequence. Each participant completed three sessions. In the first session, only the repeating sequence was presented. During the second and third session, occasional probe blocks were presented, where a new (unlearned) spatial-temporal sequence was introduced. We first confirm that participants not only got faster over time, but that they were slower and less accurate during probe blocks, indicating that they incidentally learned the sequence structure. Having established a robust behavioural benefit induced by the repeating spatial-temporal sequence, we next addressed our central hypothesis that implicit temporal orienting (evoked by the learned temporal structure) would have the largest influence on performance for targets following short (as opposed to longer) intervals between temporally structured sequence elements, paralleling classical observations in tasks using explicit temporal cues. We found that indeed, reaction time differences between new and repeated sequences were largest for the short interval, compared to the medium and long intervals, and that this was the case, even when comparing late blocks (where the repeated sequence had been incidentally learned), to early blocks (where this sequence was still unfamiliar). We conclude that incidentally acquired temporal expectations that follow a sequential structure can have a robust facilitatory influence on visually-guided behavioural responses and that, like more explicit forms of temporal orienting, this effect is most pronounced for sequence elements that are expected at short inter-element intervals

Temporal alignment of anticipatory motor cortical beta lateralisation in hidden visual-motor sequences

Performance improves when participants respond to events that are structured in repeating sequences, suggesting that learning can lead to proactive anticipatory preparation. Whereas most sequence‐learning studies have emphasised spatial structure, most sequences also contain a prominent temporal structure. We used MEG to investigate spatial and temporal anticipatory neural dynamics in a modified serial reaction time (SRT) task. Performance and brain activity were compared between blocks with learned spatial‐temporal sequences and blocks with new sequences. After confirming a strong behavioural benefit of spatial‐temporal predictability, we show lateralisation of beta oscillations in anticipation of the response associated with the upcoming target location and show that this also aligns to the expected timing of these forthcoming events. This effect was found both when comparing between repeated (learned) and new (unlearned) sequences, as well as when comparing targets that were expected after short vs. long intervals within the repeated (learned) sequence. Our findings suggest that learning of spatial‐temporal structure leads to proactive and dynamic modulation of motor cortical excitability in anticipation of both the location and timing of events that are relevant to guide action

Temporal alignment of anticipatory motor cortical beta lateralisation in hidden visual-motor sequences

Performance improves when participants respond to events that are structured in repeating sequences, suggesting that learning can lead to proactive anticipatory preparation. Whereas most sequence‐learning studies have emphasised spatial structure, most sequences also contain a prominent temporal structure. We used MEG to investigate spatial and temporal anticipatory neural dynamics in a modified serial reaction time (SRT) task. Performance and brain activity were compared between blocks with learned spatial‐temporal sequences and blocks with new sequences. After confirming a strong behavioural benefit of spatial‐temporal predictability, we show lateralisation of beta oscillations in anticipation of the response associated with the upcoming target location and show that this also aligns to the expected timing of these forthcoming events. This effect was found both when comparing between repeated (learned) and new (unlearned) sequences, as well as when comparing targets that were expected after short vs. long intervals within the repeated (learned) sequence. Our findings suggest that learning of spatial‐temporal structure leads to proactive and dynamic modulation of motor cortical excitability in anticipation of both the location and timing of events that are relevant to guide action

Dissecting beta-state changes during timed movement preparation in Parkinson’s disease

An emerging perspective describes beta-band (15−28 Hz) activity as consisting of short-lived high-amplitude events that only appear sustained in conventional measures of trial-average power. This has important implications for characterising abnormalities observed in beta-band activity in disorders like Parkinson’s disease. Measuring parameters associated with beta-event dynamics may yield more sensitive measures, provide more selective diagnostic neural markers, and provide greater mechanistic insight into the breakdown of brain dynamics in this disease. Here, we used magnetoencephalography in eighteen Parkinson’s disease participants off dopaminergic medication and eighteen healthy control participants to investigate beta-event dynamics during timed movement preparation. We used the Hidden Markov Model to classify event dynamics in a data-driven manner and derived three parameters of beta events: (1) beta-state amplitude, (2) beta-state lifetime, and (3) beta-state interval time. Of these, changes in beta-state interval time explained the overall decreases in beta power during timed movement preparation and uniquely captured the impairment in such preparation in patients with Parkinson’s disease. Thus, the increased granularity of the Hidden Markov Model analysis (compared with conventional analysis of power) provides increased sensitivity and suggests a possible reason for impairments of timed movement preparation in Parkinson’s disease