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In 1969 Joseph Bogen, a colleague of Roger Sperry and the neurosurgeon who performed commissurotomy on Sperry’s “split-brain” study participants, wrote an article subtitled “The Corpus Callosum and Creativity.” The article argued for the critical role of the corpus callosum and hemispheric specialization in creativity. Building on a four-stage model of creativity (learning, incubation, illumination, refinement) and Sperry’s innovative studies, the Bogens posited that in the intact brain, creativity relies on two opposing functions of the corpus callosum: (a) interhemispheric inhibition to facilitate simultaneous and independent activity of uniquely-specialized processing centers during learning and incubation and (b) interhemispheric facilitation to support the increased bi-hemispheric integration and coordination which produces illumination. This article revisits the Bogens’ theory considering scientific discoveries over the past 50 years. We begin by reviewing relevant findings from split-brain studies, and then briefly consider findings from studies that examine the association of creativity with callosal structure and function in neurotypical participants. Finally, we provide an in-depth discussion of creativity in persons with agenesis of the corpus callosum (ACC)—the congenital absence of the corpus callosum. These three lines of inquiry strongly support the theory suggested by Bogen and Bogen in 1969 and provide further clarification regarding the critical and unique role of the corpus callosum in creative cognition.

Abstract Background Epilepsy is the fourth-most common neurological disorder, affecting an estimated 50 million patients globally. Nearly 40% of patients have uncontrolled seizures yet incur 80% of the cost. Anti-epileptic drugs commonly result in resistance and reversion to uncontrolled drug-resistant epilepsy and are often associated with significant adverse effects. This has led to a trial-and-error system in which physicians spend months to years attempting to identify the optimal therapeutic approach. Objective To investigate the potential clinical utility from the context of optimal therapeutic prediction of characterizing cellular electrophysiology. It is well-established that genomic data alone can sometimes be predictive of effective therapeutic approach. Thus, to assess the predictive power of electrophysiological data, machine learning strategies are implemented to predict a subject’s genetically defined class in an in silico model using brief electrophysiological recordings obtained from simulated neuronal networks. Methods A dynamic network of isogenic neurons is modeled in silico for 1-s for 228 dynamically modeled patients falling into one of three categories: healthy, general sodium channel gain of function, or inhibitory sodium channel loss of function. Data from previous studies investigating the electrophysiological and cellular properties of neurons in vitro are used to define the parameters governing said models. Ninety-two electrophysiological features defining the nature and consistency of network connectivity, activity, waveform shape, and complexity are extracted for each patient network and t-tests are used for feature selection for the following machine learning algorithms: Neural Network, Support Vector Machine, Gaussian Naïve Bayes Classifier, Decision Tree, and Gradient Boosting Decision Tree. Finally, their performance in accurately predicting which genetic category the subjects fall under is assessed. Results Several machine learning algorithms excel in using electrophysiological data from isogenic neurons to accurately predict genetic class with a Gaussian Naïve Bayes Classifier predicting healthy, gain of function, and overall, with the best accuracy, area under the curve, and F1. The Gradient Boosting Decision Tree performs the best for loss of function models indicated by the same metrics. Conclusions It is possible for machine learning algorithms to use electrophysiological data to predict clinically valuable metrics such as optimal therapeutic approach, especially when combining several models.

Neuroscience, the fastest growing scientific discipline for decades, has affected numerous aspects of Western culture. Thus, one should expect it to have influences on religion as well. This article treats one of the points of intersection with Christianity, the basic metaphysical makeup of humans. The two most prevalent views in the tradition are body-soul dualism and holism or physicalism. This article describes four developments in neuroscience that have consequences for Christian practice and understanding: (1) agenesis of the corpus callosum (the millions of neurons connecting the right and left cerebral hemispheres); (2) the large frontal lobes of the cerebral cortex, which have massive connections with other regions of the brain; (3) somatic markers, which provide subtle emotional reactions to contemplated actions; and (4) mirror neurons, which have been found to subserve both the performance of an action and understanding of the actions of others. Because various forms of physicalism are more compatible with the ever tightening connections between neural processes and beliefs and practices, the article begins with biblical and theological considerations showing that some forms of physicalism are acceptable options for Christians. However, in the philosophical world a number of physicalists are content with simply reducing to mere brain processes the higher mental capacities that enable understanding and practice of Christian life. So the article attempts to show why physicalism need not entail this sort of reductionism.

Summary: CD8+ T cell exhaustion (TEX) impairs the ability of T cells to clear chronic infection or cancer. While TEX are hypofunctional, some TEX retain effector gene signatures, a feature associated with killer lectin-like receptor (KLR) expression. Although KLR+ TEX (TKLR) may improve control of chronic antigen, the signaling molecules regulating this population are poorly understood. Using single-cell RNA sequencing (scRNA-seq), flow cytometry, RNA velocity, and single-cell T cell receptor sequencing (scTCR-seq), we demonstrate that deleting the pseudokinase Trib1 shifts TEX toward CX3CR1+ intermediates with robust enrichment of TKLR via clonal T cell expansion. Adoptive transfer studies demonstrate this shift toward CD8+ TKLR in Trib1-deficient cells is CD8 intrinsic, while CD4-depletion studies demonstrate CD4+ T cells are required for improved viral control in Trib1 conditional knockout mice. Further, Trib1 loss augments anti-programmed death-ligand 1 (PD-L1) blockade to improve viral clearance. These data identify Trib1 as an important regulator of CD8+ TEX whose targeting enhances the TKLR effector state and improves checkpoint inhibitor therapy.

Modelling of aggressive lymphomas, such as double hit lymphoma, has been challenging. Here the authors engineer a CRISPR activation mouse to enable the generation of these aggressive lymphomas and identify the pro-survival BCL-2 protein A1 as a venetoclax resistance factor.

Rift Valley fever is a zoonotic haemorrhagic fever with complex transmission dynamics influenced by environmental variables and animal movements. Here, the authors develop a metapopulation model incorporating these factors and use it to identify the main drivers of transmission in the Comoros archipelago.

New antitubercular agents with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new arylated quinoline carboxylic acids (QCAs) having activity against replicating and non-replicating Mycobacterium tuberculosis (Mtb), the causative agent of TB. Thus, the synthesis, characterization, and in vitro screening (MABA and LORA) of 48 QCAs modified with alkyl, aryl, alkoxy, halogens, and nitro groups in the quinoline ring led to the discovery of two QCA derivatives, 7i and 7m, adorned with C-2 2-(naphthalen-2-yl)/C-6 1-butyl and C-2 22-(phenanthren-3-yl)/C-6 isopropyl, respectively, as the best Mtb inhibitors. DNA gyrase inhibition was shown to be exhibited by both, with QCA 7m illustrating better activity up to a 1 μM test concentration. Finally, a docking model for both compounds with Mtb DNA gyrase was developed, and it showed a good correlation with in vitro results.

In lymphopenic environments, secondary lymphoid organs regulate the size of B and T cell compartments by supporting the homeostatic proliferation of mature lymphocytes. The molecular mechanisms underlying these responses and their functional consequences remain incompletely understood. To evaluate homeostasis of the mature B cell pool during lymphopenia, we turned to an adoptive transfer model of purified follicular B cells into Rag2–/– mouse recipients. Highly purified follicular B cells transdifferentiated into marginal zone–like B cells when transferred into Rag2–/– lymphopenic hosts but not into wild-type hosts. In lymphopenic spleens, transferred B cells gradually lost their follicular phenotype and acquired characteristics of marginal zone B cells, as judged by cell surface phenotype, expression of integrins and chemokine receptors, positioning close to the marginal sinus, and an ability to rapidly generate functional plasma cells. Initiation of follicular to marginal zone B cell transdifferentiation preceded proliferation. Furthermore, the transdifferentiation process was dependent on Notch2 receptors in B cells and expression of Delta-like 1 Notch ligands by splenic Ccl19-Cre+ fibroblastic stromal cells. Gene expression analysis showed rapid induction of Notch-regulated transcripts followed by upregulated Myc expression and acquisition of broad transcriptional features of marginal zone B cells. Thus, naive mature B cells are endowed with plastic transdifferentiation potential in response to increased stromal Notch ligand availability during lymphopenia.

Fragment-based drug discovery employs screening of small polar compounds typically exhibiting low affinity towards protein targets. Here, the authors combine the use of protein-based binding pharmacophores with the theory of protein hotspots to develop a design protocol for fragment libraries, called SpotXplorer, and validate their approach on common and emerging drug targets.

Abstract Necroptosis is a pro-inflammatory cell death program executed by the terminal effector, mixed lineage kinase domain-like (MLKL). Previous studies suggested a role for the necroptotic machinery in platelets, where loss of MLKL or its upstream regulator, RIPK3 kinase, impacted thrombosis and haemostasis. However, it remains unknown whether necroptosis operates within megakaryocytes, the progenitors of platelets, and whether necroptotic cell death might contribute to or diminish platelet production. Here, we demonstrate that megakaryocytes possess a functional necroptosis signalling cascade. Necroptosis activation leads to phosphorylation of MLKL, loss of viability and cell swelling. Analyses at steady state and post antibody-mediated thrombocytopenia revealed that platelet production was normal in the absence of MLKL, however, platelet activation and haemostasis were impaired with prolonged tail re-bleeding times. We conclude that MLKL plays a role in regulating platelet function and haemostasis and that necroptosis signalling in megakaryocytes is dispensable for platelet production.

Necroptosis is a regulated form of inflammatory cell death driven by activated MLKL. Here, the authors identify a mutation in the brace region that confers constitutive activation, leading to lethal inflammation in homozygous mutant mice and providing insight into human mutations in this region.

B cell development is tightly regulated in a stepwise manner to ensure proper generation of repertoire diversity via somatic gene rearrangements. Here, the authors show that a transcription factor, Erg, functions at the earliest stage to critically control two downstream factors, Ebf1 and Pax5, for modulating this gene rearrangement process.

The slow neutron capture process (s-process) is responsible for producing about half of the elemental abundances heavier than iron in the universe. Neutron capture cross sections on stable isotopes are a key nuclear physics input for s-process studies. The 72Ge(n, γ) Maxwellian-Averaged Cross Section (MACS) has an important influence on the production of isotopes between Ge and Zr in the weak s-process in massive stars and so far only theoretical estimations are available. An experiment was carried out at the neutron time-of-flight facility n_TOF at CERN to measure the 72Ge(n, γ) reaction for the first time at stellar neutron energies. The capture measurement was performed using an enriched 72GeO2 sample at a flight path length of 184 m, which provided high neutron energy resolution. The prompt gamma rays produced after neutron capture were detected with a set of liquid scintillation detectors (C6D6). The neutron capture yield is derived from the counting spectra taking into account the neutron flux and the gamma-ray detection efficiency using the Pulse Height Weighting Technique. Over 70 new neutron resonances were identified, providing an improved resolved reaction cross section to calculate experimental MACS values for the first time. The experiment, data analysis and the new MACS results will be presented including their impact on stellar nucleosynthesis, which was investigated using the post-processing nucleosynthesis code mppnp for a 25 solar mass model.

Summary: The suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling required to prevent excessive cellular responses. In particular, SOCS3 is involved in the regulation of metabolic syndromes, such as obesity and diabetes, by suppressing leptin and insulin signals. SOCS3 also suppresses the inflammatory response associated with metabolic stress, but this specific role remains undefined. Wild-type mice on a high-fat diet (HFD) exhibited only fatty liver, whereas systemic deletion of SOCS3 resulted in excessive myeloid hematopoiesis and hepatic inflammation. In addition, depletion of the gut microbiota resulted in considerable improvement in excess granulopoiesis and splenomegaly, halting the progression of systemic inflammation in SOCS3KO mice on the HFD. This result suggests that intestinal dysbiosis is involved in inflammation associated with SOCS3KO. Although contributing to diet-induced obesity and fatty liver, SOCS3 is nevertheless critical to suppress excess myeloid hematopoiesis and severe systemic inflammation associated with intestinal dysbiosis on HFD.

This study comprehensively examines the effects of the COVID-19 pandemic on energy consumption in the United States. The purpose of the study is to quantify the effects of lockdowns and pandemic disruptions on energy consumption trends in order to inform policymakers and utilities on how to prepare for such events in the future. The study focuses on 2020 data collected by the Federal government. The effects are quantified using descriptive statistics. State-wise and sector-wise data have been presented using plots and heat maps. Related metrics like COVID case data, GDP, emissions, and expenditures were also presented. The total energy consumption fell by 7.5% in 2020. Besides Alaska, every state saw a decrease in energy, with some as high as 26%. The residential sector had the most states that saw an increase in energy, stemming from lockdowns and working from home. Similarly, petroleum consumption saw a decrease of 11.4% as a result of a decrease in travel. Biomass-related renewable energy generation fell by 23% due to decreased demand, while all other sources increased by 7.3%. Carbon dioxide emissions fell by 10.4%, methane by 2.8%, and nitric oxide by 6.7%. The overall per capita energy expenditure for the country dropped by 18.5%. There was a stronger correlation between GDP and energy consumption than between GDP and COVID case counts. The pandemic did not affect each state or sector evenly. The statistics and correlations presented here can be used in the ongoing effort to study the global impact of the pandemic and prepare for future challenges.

Summary: Emerging single-cell epigenomic assays are used to investigate the heterogeneity of chromatin activity and its function. However, identifying cells with distinct regulatory elements and clearly visualizing their relationships remains challenging. To this end, we introduce TooManyPeaks to address the need for the simultaneous study of chromatin state heterogeneity in both rare and abundant subpopulations. Our analyses of existing data from three widely used single-cell assays for transposase-accessible chromatin using sequencing (scATAC-seq) show the superior performance of TooManyPeaks in delineating and visualizing pure clusters of rare and abundant subpopulations. Furthermore, the application of TooManyPeaks to new scATAC-seq data from drug-naive and drug-resistant leukemic T cells clearly visualizes relationships among these cells and stratifies a rare “resistant-like” drug-naive sub-clone with distinct cis-regulatory elements.

Abstract Background The treatment paradigm for metastatic hormone-sensitive prostate cancer (mHSPC) patients is evolving. PET/CT now offers improved sensitivity and accuracy in staging. Recent randomized trial data supports escalated hormone therapy, local primary tumor therapy, and metastasis-directed therapy. The impact of combining such therapies into a multimodal approach is unknown. This Phase II single-arm clinical trial sponsored and funded by Veterans Affairs combines local, metastasis-directed, and systemic therapies to durably render patients free of detectable disease off active therapy. Methods Patients with newly-diagnosed M1a/b prostate cancer (PSMA PET/CT staging is permitted) and 1–5 radiographically visible metastases (excluding pelvic lymph nodes) are undergoing local treatment with radical prostatectomy, limited duration systemic therapy for a total of six months (leuprolide, abiraterone acetate with prednisone, and apalutamide), metastasis-directed stereotactic body radiotherapy (SBRT), and post-operative fractionated radiotherapy if pT ≥ 3a, N1, or positive margins are present. The primary endpoint is the percent of patients achieving a serum PSA of

The diversity of fibroblasts contributing to wound healing is unclear. Here, the authors use single-cell RNA-sequencing to identify heterogeneity among murine fibroblasts in the wound and find that recruited myeloid cells contribute to adipocyte regeneration during healing.

There is increasing effort to improve the signal sensitivity and explore the hyperpolarization dynamics. Here the authors demonstrate the parahydrogen spin transfer dynamics in compounds containing 15N using SABRE hyperpolarization technique with different strengths of the magnetic field.

Defense mechanisms are mental functions which facilitate coping when real or imagined events challenge personal wishes, needs, and feelings. Whether defense mechanisms have a specific neural basis is unknown. The present research tested the hypothesis that interhemispheric integration plays a critical role in defense mechanism development, by studying a unique sample of patients born without the corpus callosum (agenesis of the corpus callosum; AgCC). Adults with AgCC (N = 27) and matched healthy volunteers (N = 30) were compared on defense mechanism use across increasing levels of developmental maturity (denial, least; projection, intermediate; identification, most). Narratives generated in response to Thematic Apperception Test images were scored according to the Defense Mechanism Manual. Greater use of denial and less identification was found in persons with AgCC, compared to healthy comparisons. This difference emerged after age 18 when full maturation of defenses among healthy individuals was expected. The findings provide clinically important characterization of social and emotional processing in persons with AgCC. More broadly, the results support the hypothesis that functional integration across the hemispheres is important for the development of defense mechanisms.

Gain-of-function Notch mutations are recurrent in mature small B cell lymphomas such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), but the Notch target genes that contribute to B cell oncogenesis are largely unknown. We performed integrative analysis of Notch-regulated transcripts, genomic binding of Notch transcription complexes, and genome conformation data to identify direct Notch target genes in MCL cell lines. This B cell Notch regulome is largely controlled through Notch-bound distal enhancers and includes genes involved in B cell receptor and cytokine signaling and the oncogene MYC, which sustains proliferation of Notch-dependent MCL cell lines via a Notch-regulated lineage-restricted enhancer complex. Expression of direct Notch target genes is associated with Notch activity in an MCL xenograft model and in CLL lymph node biopsies. Our findings provide key insights into the role of Notch in MCL and other B cell malignancies and have important implications for therapeutic targeting of Notch-dependent oncogenic pathways.

Hematopoiesis is a multistage process involving the differentiation of stem and progenitor cells into distinct mature cell lineages. Here we present Haemopedia, an atlas of murine gene-expression data containing 54 hematopoietic cell types, covering all the mature lineages in hematopoiesis. We include rare cell populations such as eosinophils, mast cells, basophils, and megakaryocytes, and a broad collection of progenitor and stem cells. We show that lineage branching and maturation during hematopoiesis can be reconstructed using the expression patterns of small sets of genes. We also have identified genes with enriched expression in each of the mature blood cell lineages, many of which show conserved lineage-enriched expression in human hematopoiesis. We have created an online web portal called Haemosphere to make analyses of Haemopedia and other blood cell transcriptional datasets easier. This resource provides simple tools to interrogate gene-expression-based relationships between hematopoietic cell types and genes of interest.

We have measured the capture cross section of the 155Gd and 157Gd isotopes between 0.025 eV and 1 keV. The capture events were recorded by an array of 4 C6D6 detectors, and the capture yield was deduced exploiting the total energy detection system in combination with the Pulse Height Weighting Techniques. Because of the large cross section around thermal neutron energy, 4 metallic samples of different thickness were used to prevent problems related to self-shielding. The samples were isotopically enriched, with a cross contamination of the other isotope of less than 1.14%. The capture yield was analyzed with an R-Matrix code to describe the cross section in terms of resonance parameters. Near thermal energies, the results are significantly different from evaluations and from previous time-of-flight experiments. The data from the present measurement at n_TOF are publicly available in the experimental nuclear reaction database EXFOR.

An accurate measurement of the 235U(n,f) cross section from thermal to 170 keV of neutron energy has recently been performed at n_TOF facility at CERN using 6Li(n,t)4He and 10B(n,α)7Li as references. This measurement has been carried out in order to investigate a possible overestimation of the 235U fission cross section evaluation provided by most recent libraries between 10 and 30 keV. A custom experimental apparatus based on in-beam silicon detectors has been used, and a Monte Carlo simulation in GEANT4 has been employed to characterize the setup and calculate detectors efficiency. The results evidenced the presence of an overestimation in the interval between 9 and 18 keV and the new data may be used to decrease the uncertainty of 235U(n,f) cross section in the keV region.

Neutron-induced fission cross sections of isotopes involved in the nuclear fuel cycle are vital for the design and safe operation of advanced nuclear systems. Such experimental data can also provide additional constraints for the adjustment of nuclear model parameters used in the evaluation process, resulting in the further development of fission models. In the present work, the 237Np(n,f) cross section was studied at the EAR2 vertical beam-line at CERN's n_TOF facility, over a wide range of neutron energies, from meV to MeV, using the time-of-flight technique and a set-up based on Micromegas detectors, in an attempt to provide accurate experimental data. Preliminary results in the 200 keV – 14 MeV neutron energy range as well as the experimental procedure, including a description of the facility and the data handling and analysis, will be presented.

233U is the fissile nuclei in the Th-U fuel cycle with a particularily small neutron capture cross setion which is on average about one order of magnitude lower than its fission cross section. Hence, the measurement of the 233U(n, γ) cross section relies on a method to accurately distinguish between capture and fission γ-rays. A measurement of the 233U α-ratio has been performed at the n_TOF facility at CERN using a so-called fission tagging setup, coupling n_TOF 's Total Absorption Calorimeter with a novel fission chamber to tag the fission γ-rays. The experimental setup is described and essential parts of the analysis are discussed. Finally, a preliminary 233U α-ratio is presented.

The design and operation of innovative nuclear systems requires a better knowledge of the capture and fission cross sections of the Pu isotopes. For the case of capture on 242Pu, a reduction of the uncertainty in the fast region down to 8-12% is required. Moreover, aiming at improving the evaluation of the fast energy range in terms of average parameters, the OECD NEA High Priority Request List (HPRL) requests high-resolution capture measurements with improved accuracy below 2 keV. The current uncertainties also affect the thermal point, where previous experiments deviate from each other by 20%. A fruitful collaboration betwen JGU Mainz and HZ Dresden-Rossendorf within the EC CHANDA project resulted in a 242Pu sample consisting of a stack of seven fission-like targets making a total of 95(4) mg of 242Pu electrodeposited on thin (11.5 μm) aluminum backings. This contribution presents the results of a set of measurements of the 242Pu(n, γ) cross section from thermal to 500 keV combining different neutron beams and techniques. The thermal point was determined at the Budapest Research Reactor by means of Neutron Activation Analysis and Prompt Gamma Analysis, and the resolved (1 eV - 4 keV) and unresolved (1 - 500 keV) resonance regions were measured using a set of four Total Energy detectors at the CERN n_TOF-EAR1.

There has been significant growth in non-invasive screening techniques for evaluating abnormal tissue. Vibroacoustography (VA), an imaging modality based on ultrasound-stimulated acoustic emission and non-linear scattering characteristics of the target, has previously been used to generate relative real-time, pathology-specific image contrast between abnormal tissue and normal surrounding tissue; however, an in-depth tissue assessment has yet to be completed. VA utilizes two non-destructive low MHz ultrasound tones to produce an acoustic beat frequency in the low kHz range. The acoustic radiation force perturbs the target as a function of its mechanical and acoustic properties and the emissive acoustic waves are detected by a nearby hydrophone to form an image based on the viscoelastic characteristics of the target. We have previously reported that our VA imaging system can distinguish suspect tissue from normal tissue in tissue-mimicking phantoms (TMPs) and ex vivo models with high image contrast; however, the goal of this work is to assess the measurement performance and resolution capabilities of this system in pre-clinical models, specifically TMPs in tissue assessment. Lateral and axial resolution, as well as material characterization, studies were performed on isotropic two-layered and multiple-layered TMP targets. The resolution studies resulted in ∼1 mm lateral and ∼12 mm axial, which were confirmed and validated for a confocal transducer geometry. The system showed sufficient measurement performance to detect regions with elastic moduli difference of at least 10 kPa and lateral width of at least 4 mm. This result, coupled with high imaging contrast, supports the utilization of VA for potential applications in in vivo medical imaging and tissue assessment for intraoperative applications.

233U is of key importance among the fissile nuclei in the Th-U fuel cycle. A particularity of 233U is its small neutron capture cross-section, which is on average about one order of magnitude lower than the fission cross-section. The accuracy in the measurement of the 233U capture cross-section depends crucially on an efficient capture-fission discrimination, thus a combined set-up of fission and γ-detectors is needed. A measurement of the 233U capture cross-section and capture-to-fission ratio was performed at the CERN n_TOF facility. The Total Absorption Calorimeter (TAC) of n_TOF was employed as γ-detector coupled with a novel compact ionization chamber as fission detector. A brief description of the experimental set-up will be given, and essential parts of the analysis procedure as well as the preliminary response of the set-up to capture are presented and discussed.

We introduce an in vivo spectroscopic method to assess the effects of diet on fatty acid composition of the predominant chemical constituent of adipocytes in mice. To do this, we make use of a nonlinear NMR signal that, unlike a standard NMR signal, is intrinsically insensitive to local magnetic field inhomogeneities and which naturally suppresses the large water signal from nonfatty tissues. Our method yields fat composition information from fat depots distributed over large sample volumes in a single experiment, without requiring the use of tedious shimming procedures, voxel selection, or water suppression. Our results suggest that this method can reveal clear differences in adipose tissue composition of mice fed a standard chow diet compared with mice fed a diet rich in polyunsaturated fatty acids. With further developments this method could be used to obtain information on human lipid composition noninvasively and to track changes in lipid composition induced by diet intervention, pharmaceutical drugs, and exercise.

A major challenge in cancer biology is to monitor and understand cancer metabolism in vivo with the goal of improved diagnosis and perhaps therapy. Because of the complexity of biochemical pathways, tracer methods are required for detecting specific enzyme-catalyzed reactions. Stable isotopes such as 13C or 15N with detection by nuclear magnetic resonance provide the necessary information about tissue biochemistry, but the crucial metabolites are present in low concentration and therefore are beyond the detection threshold of traditional magnetic resonance methods. A solution is to improve sensitivity by a factor of 10,000 or more by temporarily redistributing the populations of nuclear spins in a magnetic field, a process termed hyperpolarization. Although this effect is short-lived, hyperpolarized molecules can be generated in an aqueous solution and infused in vivo where metabolism generates products that can be imaged. This discovery lifts the primary constraint on magnetic resonance imaging for monitoring metabolism—poor sensitivity—while preserving the advantage of biochemical information. The purpose of this report was to briefly summarize the known abnormalities in cancer metabolism, the value and limitations of current imaging methods for metabolism, and the principles of hyperpolarization. Recent preclinical applications are described. Hyperpolarization technology is still in its infancy, and current polarizer equipment and methods are suboptimal. Nevertheless, there are no fundamental barriers to rapid translation of this exciting technology to clinical research and perhaps clinical care.

The slow neutron capture process (s-process) is responsible for producing about half of the elemental abundances heavier than iron in the universe. Neutron capture cross sections on stable isotopes are a key nuclear physics input for s-process studies. The 72Ge(n, γ) cross section has an important influence on production of isotopes between Ge and Zr during s-process in massive stars and therefore experimental data are urgently required. 72Ge(n, γ) was measured at the neutron time-of-flight facility n_TOF (CERN) for the first time at stellar energies. The measurement was performed using an enriched 72GeO2 sample at a flight path of 185m with a set of liquid scintillation detectors (C6D6). The motivation, experiment and current status of the data analysis are reported.

Monte Carlo (MC) simulations are an essential tool to determine fundamental features of a neutron beam, such as the neutron flux or the γ-ray background, that sometimes can not be measured or at least not in every position or energy range. Until recently, the most widely used MC codes in this field had been MCNPX and FLUKA. However, the Geant4 toolkit has also become a competitive code for the transport of neutrons after the development of the native Geant4 format for neutron data libraries, G4NDL. In this context, we present the Geant4 simulations of the neutron spallation target of the n_TOF facility at CERN, done with version 10.1.1 of the toolkit. The first goal was the validation of the intra-nuclear cascade models implemented in the code using, as benchmark, the characteristics of the neutron beam measured at the first experimental area (EAR1), especially the neutron flux and energy distribution, and the time distribution of neutrons of equal kinetic energy, the so-called Resolution Function. The second goal was the development of a Monte Carlo tool aimed to provide useful calculations for both the analysis and planning of the upcoming measurements at the new experimental area (EAR2) of the facility.

Neutron-induced reaction cross sections are important for a wide variety of research fields ranging from the study of nuclear level densities, nucleosynthesis to applications of nuclear technology like design, and criticality and safety assessment of existing and future nuclear reactors, radiation dosimetry, medical applications, nuclear waste transmutation, accelerator-driven systems and fuel cycle investigations. Simulations and calculations of nuclear technology applications largely rely on evaluated nuclear data libraries. The evaluations in these libraries are based both on experimental data and theoretical models. CERN’s neutron time-of-flight facility n_TOF has produced a considerable amount of experimental data since it has become fully operational with the start of its scientific measurement programme in 2001. While for a long period a single measurement station (EAR1) located at 185 m from the neutron production target was available, the construction of a second beam line at 20 m (EAR2) in 2014 has substantially increased the measurement capabilities of the facility. An outline of the experimental nuclear data activities at n_TOF will be presented.

The Cosmological Lithium Problem refers to the large discrepancy between the abundance of primordial 7Li predicted by the standard theory of Big Bang Nucleosynthesis and the value inferred from the so-called “Spite plateau” in halo stars. A possible explanation for this longstanding puzzle in Nuclear Astrophysics is related to the incorrect estimation of the destruction rate of 7Be, which is responsible for the production of 95% of primordial Lithium. While charged-particle induced reactions have mostly been ruled out, data on the 7Be(n,α) and 7Be(n,p) reactions are scarce or completely missing, so that a large uncertainty still affects the abundance of 7Li predicted by the standard theory of Big Bang Nucleosynthesis. Both reactions have been measured at the n_TOF facility at CERN, providing for the first time data in a wide neutron energy range.

The 33S(n,α)30Si cross section measurement, using 10B(n,α) as reference, at the n_TOF Experimental Area 2 (EAR2) facility at CERN is presented. Data from 0.01 eV to 100 keV are provided and, for the first time, the cross section is measured in the range from 0.01 eV to 10 keV. These data may be used for a future evaluation of the cross section because present evaluations exhibit large discrepancies. The 33S(n,α)30Si reaction is of interest in medical physics because of its possible use as a cooperative target to boron in Neutron Capture Therapy (NCT).

An important experimental program on Nuclear Astrophysics is being carried out at the n_TOF since several years, in order to address the still open issues in stellar and primordial nucleosynthesis. Several neutron capture reactions relevant to s-process nucleosynthesis have been measured so far, some of which on important branching point radioisotopes. Furthermore, the construction of a second experimental area has recently opened the way to challenging measurements of (n, charged particle) reactions on isotopes of short half-life. The Nuclear Astrophysics program of the n_TOF Collaboration is here described, with emphasis on recent results relevant for stellar nucleosynthesis, stellar neutron sources and primordial nucleosynthesis.

The CERN n_TOF neutron beam facility is characterized by a very high instantaneous neutron flux, excellent TOF resolution at the 185 m long flight path (EAR-1), low intrinsic background and coverage of a wide range of neutron energies, from thermal to a few GeV. These characteristics provide a unique possibility to perform high-accuracy measurements of neutron-induced reaction cross-sections and angular distributions of interest for fundamental and applied Nuclear Physics. Since 2001, the n_TOF Collaboration has collected a wealth of high quality nuclear data relevant for nuclear astrophysics, nuclear reactor technology, nuclear medicine, etc. The overall efficiency of the experimental program and the range of possible measurements has been expanded with the construction of a second experimental area (EAR-2), located 20 m on the vertical of the n_TOF spallation target. This upgrade, which benefits from a neutron flux 30 times higher than in EAR-1, provides a substantial extension in measurement capabilities, opening the possibility to collect data on neutron cross-section of isotopes with short half-lives or available in very small amounts. This contribution will outline the main characteristics of the n_TOF facility, with special emphasis on the new experimental area. In particular, we will discuss the innovative features of the EAR-2 neutron beam that make possible to perform very challenging measurements on short-lived radioisotopes or sub-mg samples, out of reach up to now at other neutron facilities around the world. Finally, the future perspectives of the facility will be presented.

The accurate knowledge of the neutron-induced fission cross-sections of actinides and other isotopes involved in the nuclear fuel cycle is essential for the design of advanced nuclear systems, such as Generation-IV nuclear reactors. Such experimental data can also provide the necessary feedback for the adjustment of nuclear model parameters used in the evaluation process, resulting in the further development of nuclear fission models. In the present work, the 240Pu(n,f) cross-section was measured at CERN's n_TOF facility relative to the well-known 235U(n,f) cross section, over a wide range of neutron energies, from meV to almost MeV, using the time-of-flight technique and a set-up based on Micromegas detectors. This measurement was the first experiment to be performed at n_TOF's new experimental area (EAR-2), which offers a significantly higher neutron flux compared to the already existing experimental area (EAR-1). Preliminary results as well as the experimental procedure, including a description of the facility and the data handling and analysis, are presented.