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Discovery of analgesics void of abuse liability is critical to battle the opioid crisis in the United States. Among many strategies to achieve this goal, targeting more than one opioid receptor seems promising to minimize this unwanted side effect while achieving a reasonable therapeutic profile. In the process of understanding the structure-activity relationship of nalfurafine, we identified a potential analgesic agent, NMF, as a dual kappa opioid receptor/delta opioid receptor agonist with minimum abuse liability. Further characterizations, including primary in vitro ADMET studies (hERG toxicity, plasma protein binding, permeability, and hepatic metabolism), and in vivo pharmacodynamic and toxicity profiling (time course, abuse liability, tolerance, withdrawal, respiratory depression, body weight, and locomotor activity) further confirmed NMF as a promising drug candidate for future development.

Background Opioid withdrawal is a key driver of opioid addiction and an obstacle to recovery. However, withdrawal effects on opioid reinforcement and mesolimbic neuroadaptation are understudied, and the role of sex is largely unknown. Methods Male (n = 13) and female (n = 12) rats responded under a fentanyl-versus-food choice procedure during daily 2-hour sessions. In addition to the daily choice sessions, rats were provided extended access to fentanyl during 12-hour self-administration sessions. After 2 weeks of this self-administration regimen, the nucleus accumbens and ventral tegmental area of a subset of rats were subjected to RNA sequencing. In the remaining rats, a third week of this self-administration regimen was conducted, during which methadone effects on fentanyl-versus-food choice were determined. Results Before opioid dependence, male and female rats similarly allocated responding between fentanyl and food. Abstinence from extended fentanyl access elicited similar increases in somatic withdrawal signs in both sexes. Despite similar withdrawal signs and extended-access fentanyl intake, opioid withdrawal was accompanied by a maladaptive increase in fentanyl choice in males, but not females. Behavioral sex differences corresponded with a greater number of differentially expressed genes in the nucleus accumbens and ventral tegmental area of opioid-withdrawn females relative to males. Methadone blocked withdrawal-associated increases in fentanyl choice in males but failed to further decrease fentanyl choice in females. Conclusions These results provide foundational evidence of sex-specific neuroadaptations to opioid withdrawal, which may be relevant to the female-specific resilience to withdrawal-associated increases in opioid choice and aid in the identification of novel therapeutic targets.

Species distribution models have been used to assist decision-making in many different aspects of conservation, restoration, and environmental management. However, to apply species distribution models effectively, we need to discriminate between suitable and unsuitable environments and the models need to be developed at fine scales (i.e. covering small areas at a fine resolution). These characteristics allow more precise decision-making for heterogeneous environments in smaller areas, such as biomes. We also need to understand the potential limiting factors in relation to these models better, including the effects of sample bias in species occurrence records and the potential mismatch between the scale at which the models were built and the scale at which the predictor variables interact with species occurrence. Here we evaluate the effects of two methods used to reduce bias (geographic vs. environmental filters) and three predictor variable types (climactic, local and biotic) on model predictions. We explore these issues for the hyacinth macaw (Anodorhynchus hyacinthinus), a globally vulnerable species in the Pantanal biome of central South America. We consider broad-scale variables, local-scale habitat associations, and the interactions of the macaw with two plant species that provide its food and nesting location. Our results show that using broad-scale climate variables for local-scale models (i.e., models with a fine resolution with a small extent) can generate predictive distribution models that underpredict suitability. Using local and biotic variables generates more accurate models with predictions consistent with the known distribution of the bird species. Although not commonly used, local-scale variables strongly affect model performance by increasing accuracy, reducing omission error, and leading to more conservative predictions. On the other hand, these methods lead to variable results in relation to bias reduction, with their efficiency depending on the amount of sampling bias in the occurrence records. In conclusion, local variables and the method of bias reduction play an important role in species distribution models. Fine resolution models constructed at the local scale for small areas show the greatest skill in predicting species distribution.

Recent studies have shown that social interaction can serve as an alternative reinforcer to opioid self-administration under a choice context in rats. However, additional parametric studies are needed to evaluate the sensitivity of opioid-vs.-social interaction procedures relative to more established opioid-vs.-food procedures. The current study evaluated the sensitivity of a novel fentanyl-vs.-social interaction choice procedure to environmental and pharmacological manipulations previously shown to affect fentanyl-vs.-food choice. Male and female rats (responder rats; n = 6/sex) were trained to respond in a discrete-trial choice procedure for either 30-s access to a same-sex "partner" rat or an intravenous fentanyl infusion. Once trained, the effects of fentanyl unit dose (0, 0.32-10 μg/kg/inf), partner rat presence, opioid-dependence status, chronic naltrexone administration (0.032, 0.1 mg/kg/h), and response requirement for fentanyl self-administration (fixed ratio 1-320) were determined across weeks. The fentanyl-vs.-social interaction choice procedure was sensitive to the unit dose of fentanyl, chronic naltrexone treatment, and fentanyl response requirement. However, the magnitude of these effects on fentanyl choice was smaller than those reported in published fentanyl-vs.-food choice studies. Furthermore, fentanyl-vs.-social interaction choice was not sensitive to removal of the partner rat or opioid-dependence status. Minimal sex differences were detected. These results suggest that this fentanyl-vs.-social interaction choice procedure is less sensitive to environmental and pharmacological interventions than previously established opioid-vs.-food choice procedures. The observed discrepancy in sensitivity between the procedures suggests that social interaction may have qualitatively different reinforcing properties compared to more commonly assessed alternative reinforcers such as food (preclinical) or money (human laboratory).

RationaleStrategies are needed to decrease the abuse liability of mu opioid receptor (MOR) agonists. One strategy under consideration is to combine MOR agonists with kappa opioid receptor (KOR) agonists.ObjectivesThe effects of KOR-agonists (U50488, nalfurafine) on fentanyl-versus-food choice were compared under conditions where the KOR agonists were added to the self-administered fentanyl (contingent delivery) or administered as pretreatments (non-contingent delivery) in male and female rats. The effects of increasing and decreasing the magnitude of the alternative food reinforcer were also determined.MethodsRats were trained to respond under a concurrent schedule of fentanyl (0, 0.32-10 μg/kg/infusion) and food reinforcement. In Experiment 1, U50488 and nalfurafine were co-administered with fentanyl as fixed-proportion mixtures (contingent administration). In Experiment 2, U50488 (1-10 mg/kg) and nalfurafine (3.2-32 μg/kg) were administered as acute pretreatments (non-contingent administration). nor-BNI (32 mg/kg) was administered prior to contingent and non-contingent KOR-agonist treatment in Experiment 3. Experiment 4 evaluated the effects of increasing and decreasing the magnitude of the non-drug reinforcer.ResultsBoth U50488 and nalfurafine decreased fentanyl choice when administered contingently, demonstrating that KOR agonists punish opioid choice. Non-contingent U50488 and nalfurafine administration decreased rates of fentanyl and food self-administration without altering fentanyl choice. Both contingent and non-contingent U50488 and nalfurafine effects on fentanyl choice were attenuated by nor-BNI. Fentanyl choice was sensitive to increases and decreases in the magnitude of the non-drug reinforcer.ConclusionsThese results demonstrate that the effects of KOR agonists on fentanyl reinforcement are dependent upon the contingencies under which they are administered.

Opioid-targeted vaccines represent an emerging treatment strategy for opioid use disorder. To determine whether concurrent vaccination against two commonly abused opioids (fentanyl and heroin) would confer broader spectrum opioid coverage, the current study evaluated dual fentanyl/heroin conjugate vaccine effectiveness using a warm water tail-withdrawal and a fentanyl/heroin-vs-food choice procedure in male and female rats across a 105-day observation period. Vaccine administration generated titers of high-affinity antibodies to both fentanyl and heroin sufficient to decrease the antinociceptive potency of fentanyl (25-fold), heroin (4.6-fold), and a 1:27 fentanyl/heroin mixture (7.5-fold). Vaccination did not alter the antinociceptive potency of the structurally dissimilar opioid agonist methadone. For comparison, continuous treatment with a naltrexone dose (0.032 mg/kg/h) shown previously to produce clinically relevant plasma-naltrexone levels decreased the antinociceptive potency of fentanyl, heroin, and the 1:27 fentanyl/heroin mixture by approximately 20-fold. Naltrexone treatment also shifted the potency of 1:27 fentanyl/heroin mixture in a drug-vs-food choice self-administration procedure 4.3-fold. In contrast, vaccination did not attenuate 1:27 fentanyl/heroin mixture self-administration in the drug-vs-food choice procedure. These data demonstrate that a vaccine can simultaneously attenuate the thermal antinociceptive effects of two structurally dissimilar opioids. However, the vaccine did not attenuate fentanyl/heroin mixture self-administration, suggesting a greater magnitude of vaccine responsiveness is required to decrease opioid reinforcement relative to antinociception.

The high efficacy mu-opioid receptor (MOR) agonist methadone is an effective opioid use disorder (OUD) medication used exclusively in opioid-dependent patients. However, methadone has undesirable effects that limit its clinical efficacy. Intermediate efficacy MOR agonists may treat OUD with fewer undesirable effects. We compared the effects of methadone with the intermediate efficacy MOR agonist TRV130 (oliceridine) on fentanyl-vs.-food choice and somatic withdrawal signs in opioid-dependent and post-opioid-dependent rats. Male rats (n = 20) were trained under a fentanyl-vs.-food choice procedure. Rats were then provided extended fentanyl (3.2 µg/kg/infusion) access (6 p.m.-6 a.m.) for 10 days to produce opioid dependence/withdrawal. Rats were treated with vehicle (n = 7), TRV130 (3.2 mg/kg; n = 8), or methadone (3.2 mg/kg; n = 5) three times per day after each extended-access session (8:30 a.m., 11 a.m., 1:30 p.m.). Withdrawal sign scoring (1:55 p.m.) and choice tests (2-4 p.m.) were conducted daily. Vehicle, TRV130, and methadone effects on fentanyl choice were redetermined in post-opioid-dependent rats. Vehicle-, TRV130-, and methadone-treated rats had similar fentanyl intakes during extended access. Vehicle-treated rats exhibited increased withdrawal signs and decreased bodyweights. Both methadone and TRV130 decreased these withdrawal signs. TRV130 was less effective than methadone to decrease fentanyl choice and increase food choice in opioid-dependent rats. Neither methadone nor TRV130 decreased fentanyl choice in post-opioid-dependent rats. Results suggest that higher MOR activation is required to reduce fentanyl choice than withdrawal signs in fentanyl-dependent rats. Additionally, given that TRV130 did not precipitate withdrawal in opioid-dependent rats, intermediate efficacy MOR agonists like TRV130 may facilitate the transition of patients with OUD from methadone to lower efficacy treatments like buprenorphine.

Laser ultrasonics is a remote nondestructive evaluation technique suitable for real-time monitoring of fabrication processes in semiconductor metrology, advanced manufacturing, and other applications where non-contact, high fidelity measurements are required. Here we investigate laser ultrasonic data processing approaches to reconstruct images of subsurface side drilled holes in aluminum alloy specimens. We demonstrate through simulation that the model-based linear sampling method (LSM) can perform accurate shape reconstruction of single and multiple holes and produce images with well-defined boundaries. We experimentally confirm that LSM produces images that represent the internal geometric features of an object, some of which may be missed by conventional imaging.

This study explores the evolutionary history of ecological niche characters in the Eurasian snowfinch lineage. Specifically, we use new analytical approaches to reconstruct ecological niche evolution, taking uncertainty in knowledge of the ecological niche limits into account. We found an overall pattern of niche conservatism in relation to both temperature and precipitation characteristics of niches, but for one dramatic niche evolution event, in Montifringilla nivalis. Interestingly, this species is also that which has by far the broadest geographic distribution among snowfinches. We conclude that an evolutionary change in niche characteristics perhaps within M. nivalis (i.e., present in some and not all of its populations) made possible the broad, westward range expansion of that species, thus changing the distributional potential of the snowfinch lineage dramatically.

Biodiversity remains relatively unknown and understudied in many parts of the developing world with significant information gaps, in stark contrast to many areas in the developed world, where knowledge about biodiversity can approach encyclopedic. Access to resources, such as funding, data, information, expertise, and biological collections (often collected by colonial-era scientists from across the developing world), is often quite limited for developing-world scientists. The life of a biodiversity scientist in the developing world is therefore one of manifold dilemmas and challenges, as well as numerous opportunities. Although collaborations exist between developing-world scientists and developed-world scientists, too many of those collaborations are not deep or permanent, and developing-world scientists are too often relegated to a subordinate role. The focus in this contribution is on providing suggestions for how to open and build access to resources for developing-world scientists. Everyone benefits if developing-world and developed-world scientists work together collaboratively to pose interesting and novel questions, generate new data, update existing data, carry out analyses, and arrive at interesting insights and interpretations. In this way, the biodiversity science community can replace “parachute” science with “global science.”

Lens-coupled X-ray computed tomography (X-ray CT) using a transparent scintillator imaged on a CCD camera obtains higher spatial resolution than the more commonly employed phosphor-enhanced amorphous silicon (A-Si) panels. A-Si panels are limited to resolution typically greater than ~200 microns, have a limited working life due to degradation with dose, and provide intrinsically low efficiency with thin (few hundred microns thick) phosphor coatings. Demanding applications such as imaging the interior of complex additively manufactured components require high throughput and high resolution, best achieved with a lens-coupled system. However, for large fields-of-view, very large area but thin transparent scintillators are required – a format difficult to fabricate with high light yield single crystals – therefore, glass scintillators with both modest X-ray interaction and light yield have been used for years. We have developed a new polycrystalline transparent ceramic scintillator, Gd0.3Lu1.6Eu0.1O3, or “GLO,” that offers excellent stopping power and light yield for improved contrast in sizes up to 14” x 14” plates, with thicknesses in the 2-10 mm range, and we are implementing it in systems to increase imaging throughput for 9 MeV Bremsstrahlung X-ray CT. CT imaging performance will be described.

Fast neutron Computed Tomography (nCT) is a powerful and non-invasive imaging modality that can be used to examine features and defects within low Z elements (such as plastic) hidden or shielded by high Z elements (such as tungsten, lead, or even stainless steel). This study built a fast neutron radiography and nCT system and explored various multi-material complex objects utilizing a fast neutron beam at The Ohio State University Research Reactor (OSURR), which provides ~5.4 x 10^7 n·cm-2·s-1 neutron flux at 1.6 MeV (median energy). The lens-based system includes an Electron Multiplying (EM) CCD camera, a light-tight enclosure, and a high light yield 1 cm thick Polyvinyl Toluene (PVT) scintillator provided by Lawrence Livermore National Laboratory (LLNL). A variety of test exemplars were scanned, with the number of projections for each scan ranging from 90 to 180, covering either 180 or 360 degrees. The exposure time for each projection ranged down to one minute, enabling a full nCT scan within a few hours of operation at a 500-kW low power research reactor. 3D tomograms were constructed using Octopus reconstruction software. Results showed that not only could nCT projection data be successfully constructed into volume data, but good contrast between HDPE and a millimeter-sized tungsten ball could be obtained. The 3D tomography presents high contrast to clearly discern HDPE features and voids inside tungsten shielding that are not discernable using 2D radiography.

Orphan legume crops play an important role in smallholder farmers’ food systems. Though less documented, they have the potential to contribute to adequate nutrition in vulnerable communities. Unfortunately, data are scarce about the potential of those crops to withstand current and future climate variations. Using Macrotyloma geocarpum as an example, we used genetically informed ecological niche models to explore the role of ecology on the current and future distributions of genetic populations of Kersting’s groundnut. Three main conclusions emerged: i) the models had good predictive power, indicating that M. geocarpum’s distribution was correlated with both climatic and soil layers; ii) identity and similarity tests revealed that the two genetic groups while overlapping, are each, locally adapted and display differences in climate suitability; iii) by integrating the genetic information in niche modeling, niches projections show divergence in the response of the species and genetic populations to ongoing climate change. This study highlights the importance of incorporating genetic data into ENM approaches to obtain a finer information of species’ future distribution, and explores the implications for agricultural adaptation, with a particular focus on identifying priority actions in orphan crops conservation and breeding.

Background and Purpose: Maintenance treatment with opioid agonists (buprenorphine, methadone) decreases opioid use and relapse. We recently modelled maintenance treatment in rats and found that chronic delivery of buprenorphine or the μ opioid receptor partial agonist TRV130 decreased relapse to oxycodone seeking and taking. Here, we tested the buprenorphine analogue BU08028 on different heroin relapse-related measures and heroin versus food choice. Experimental Approach: For relapse assessment, we trained male and female rats to self-administer heroin (6 h·day−1, 14 days) in Context A and then implanted osmotic minipumps containing BU08028 (0, 0.03 or 0.1 mg·kg−1·d−1). Effects of chronic BU08028 delivery were tested on (1) incubation of heroin-seeking in a non-drug Context B, (2) extinction responding reinforced by heroin-associated discrete cues in Context B, (3) reinstatement of heroin-seeking induced by re-exposure to Context A and (4) re-acquisition of heroin self-administration in Context A. For choice assessment, we tested the effect of chronic BU08028 delivery on heroin versus food choice. Key Results: Chronic BU08028 delivery decreased incubation of heroin seeking. Unexpectedly, BU08028 increased re-acquisition of heroin self-administration selectively in females. Chronic BU08028 had minimal effects on context-induced reinstatement and heroin versus food choice in both sexes. Finally, exploratory post hoc analyses suggest that BU08028 decreased extinction responding selectively in males. Conclusions and Implications: Chronic BU08028 delivery had both beneficial and detrimental, sex-dependent, effects on different triggers of heroin relapse and minimal effects on heroin choice in both sexes. Results suggest that BU08028 would not be an effective opioid maintenance treatment in humans.

Fast neutrons accessible from 14-MeV D-T neutron generators have higher transmission through high-Z materials compared to radiography X-rays due to a more uniform attenuation as a function of material Z. These neutrons can therefore image low-Z materials even when shielded by high-Z materials. The constraints in portable fast-neutron digital imaging systems include limited neutron output, limited light produced by neutron imaging scintillators, and lower resolution images due to large source spot size and required scintillator thickness. In addition, digital panel dark-noise counts can be 100x higher than the image signal, and variations across the panel can also be comparable to this signal. We will discuss recent efforts to develop a portable neutron-radiography system, including improved neutron scintillator, mitigation of digital panel noise, and new portable D-T neutron generators. We will also present MCNP efforts to model the system, including neutron scattering effects.

Additive Manufacturing (AM) presents significant industry-specific advantages allowing the creation of complex geometries and internal features that cannot be produced using conventional manufacturing processes. However, a current limitation of AM is the degraded dimensional control and surface integrity of specific surfaces. The parts are constructed through layer-by-layer approach, each layer presenting a characteristic ‘fingerprint’. The functional performance of the final part is influenced by the morphology of the outer surface as well as by the surface quality introduced at intermediate layers. Surface texture metrology therefore can play an enabling role in AM-related manufacture and research. The use of optical topography measurement instrumentation allows for a high level of detail in the acquisition of topographic information. Some of the most commonly used optical measuring instruments are Vertical Scanning Interferometry (CSI), Imaging Confocal Microscopy (CONF), and Focus Variation (FV), each one has benefits and drawbacks in terms of acquisition time and measurement resolution. AM surfaces overall present complex topographical features, requiring the acquisition of large surface areas and large z-scans which considerably increases the acquisition time. Speed is a key factor in industrial practice, and time optimization is required for quality control and surface analysis before down-stream processes. This paper reports on the measurement and characterisation of the surface texture of metal powder bed fusion AM parts. All measurements were performed in the same SENSOFAR S-NEOX instrument using the commonly used optical technologies (CSI, CONF, and FV) and the latest step in confocal measurement technology called Continuous Confocal (C-CONF). The resolution and acquisition time of each technique is analysed in order to check the suitability of each method to characterize and describe the AM surface microstructures in a time-efficient way.

We review the biology and ecology of the endemic New Zealand genus Alseuosmia A. Cunn. The taxonomy of the genus has a complicated history with considerable debate about both its relationsh...

Characterisation of freeform surfaces is an increasingly importance area of metrology. Currently the characterisation of surfaces is performed using data that can be represented by a height map. Modern measurement devices allow the acquisition of surfaces with complex shapes that cannot properly be analysed using the current texture parameters definition. In this paper a method to characterise both freeform surfaces and surfaces with re-entrant features is proposed. Two surface approximation methods are investigated: triangular mesh and Bezier surface. The proposed method will be compared with a method able to extract the ISO 25178-2 areal texture parameters from a triangular mesh.

Hass avocado cultivation in Colombia has grown rapidly in area in recent years. It is being planted in marginal areas, which leads to low yields, and in many cases is related to diseases. Ecological niche modeling (ENM) can offer a view of the potential geographic and environmental distribution of diseases, and thus identify areas with suitable or unsuitable conditions for their development. The aim of the study was to assess current and potential distribution of the major diseases on Hass avocado in Colombia. Areas planted with Hass avocado in Antioquia, Colombia were sampled for diseases including the following pathogens: Phytophthora cinnamomi, Verticillium sp., Lasiodiplodia theobromae, Phytophthora palmivora, Colletotrichum gloeosporioides sensu lato, Pestalotia sp., and Capnodium sp., and one disorder hypoxia-anoxia. These pathogens were selected based on their relevance (incidence-severity) and capacity to cause damage in different tissues of avocado plants. Severity and incidence of each disease were related to environmental information from vegetation indices and topographic variables using maximum entropy modeling approaches (MaxEnt). Models were calibrated only across areas sampled, and then transferred more broadly to areas currently planted, and to potential zones for planting. Combinations of best performance and low omission rates were the basis for model selection. Results show that Hass avocado has been planted in areas highly conducive for many pathogens, particularly for Phytophthora cinnamomi and hypoxia-anoxia disorder. Ecological niche modeling approaches offer an alternative toolset for planning and making assessments that can be incorporated into disease management plans.

The transition for new head teachers (school principals) can be a difficult and unpredictable one. This article outlines a case of a deputy (assistant principal) in the United Kingdom as he takes up his first headship. We describe some of the challenges involved and prompt readers to consider strategies that could be used and support that may be accessed to negotiate this challenging period. In particular, this illustrative case shows how the lead-in period between appointment and formal assumption of the role can be productively used. This article would be of use to readers aspiring to take on a senior leadership roles. But it would also be relevant for people working at district level and others involved in recruiting, appointing, and supporting senior leaders.

The current opioid crisis remains a significant public health issue and there is a critical need for biomedical research to develop effective and easily deployable candidate treatments. One emerging treatment strategy for opioid use disorder includes immunopharmacotherapies or opioid-targeted vaccines. The present study determined the effectiveness of a fentanyl-tetanus toxoid conjugate vaccine to alter fentanyl self-administration using a fentanyl-vs.-food choice procedure in male and female rats under three experimental conditions. For comparison, continuous 7-day naltrexone (0.01–0.1 mg/kg/h) and 7-day clonidine (3.2–10 μg/kg/h) treatment effects were also determined on fentanyl-vs.-food choice. Male and female rats responded for concurrently available 18% diluted Ensure® (liquid food) and fentanyl (0–10 μg/kg/infusion) infusions during daily sessions. Under baseline and saline treatment conditions, fentanyl maintained a dose-dependent increase in fentanyl-vs.-food choice. First, fentanyl vaccine administration significantly blunted fentanyl reinforcement and increased food reinforcement for 15 weeks in non-opioid dependent rats. Second, surmountability experiments by increasing the unit fentanyl dose available during the self-administration session 10-fold empirically determined that the fentanyl vaccine produced an approximate 22-fold potency shift in fentanyl-vs.-food choice that was as effective as the clinically approved treatment naltrexone. Clonidine treatment significantly increased fentanyl-vs.-food choice. Lastly, fentanyl vaccine administration prevented the expression of withdrawal-associated increases in fentanyl-vs.-food choice following introduction of extended 12 h fentanyl access sessions. Overall, these results support the potential and further consideration of immunopharmacotherapies as candidate treatments to address the current opioid crisis.

Clinical evidence suggest that men are more sensitive than women to the abuse-related effects of mu-opioid agonists. In contrast, preclinical studies suggest the opposite sex difference. The aim of the present study was to clarify this discrepancy using a fentanyl vs. diluted Ensure® choice procedure to assess sex differences in opioid reinforcement. Sex differences in intravenous (IV) fentanyl self-administration were examined under a fixed-ratio (FR5) schedule, a multi-day progressive-ratio (PR) schedule for behavioral economic analysis, and a concurrent (choice) schedule of fentanyl and diluted Ensure® reinforcement in Sprague–Dawley male and female rats. The fentanyl dose-effect function under the FR5 schedule was significantly shifted upward in females compared to males. Similarly, the reinforcing effectiveness of both fentanyl (3.2 and 10 µg/kg per injection, IV) and diluted Ensure® (18 and 56%) were greater in females than in males as assessed using behavioral economic analysis, irrespective of dose or concentration. However, under a fentanyl vs. foodchoice procedure, males chose 3.2 µg/kg per injection fentanyl injections over 18%, but not 56%, diluted Ensure® at a higher percentage compared to females. Overall, these results suggest that the expression of sex differences in opioid reinforcement depends upon the schedule of reinforcement and that preclinical opioid vs. food choice procedures provide a translationally relevant measure (i.e., behavioral allocation) consistent with the direction of sex differences reported in the clinical literature.

Megavolt x-ray computed tomography (CT) is a powerful tool for three-dimensional characterization. However, its utility is limited for large objects composed of high-atomic number (Z) materials, where x rays fail to penetrate. Information from fast neutron CT (FNCT) can complement x-ray CT reconstructions since fast neutrons can more readily penetrate high-Z objects. Here, we demonstrate a method for combining FNCT and x-ray CT data to create a single reconstruction, more accurate than could be achieved with either x rays or fast neutrons alone. The algorithm was tested on an exemplar comprising multiple concentric, nested cylinders of different materials. Simulated and empirical x-ray CT data were acquired for the exemplar using a 9 MV bremsstrahlung spectrum. Additional simulated and empirical FNCT data were acquired using an accelerator based fast neutron source. The FNCT data were used to synthesize x-ray CT data and augment the x-ray CT data missing due to lack of penetration. This approach mitigates artifacts that would otherwise negatively affect the accuracy and resolution of a single-modality reconstructed volume.

Production of nitric oxide (NO) has been demonstrated in several malignancies, however its role remains not fully understood, specifically in relation to the metabolic and functional implications that it may have on immune cells participating in tumorigenesis. Here, we show that inducible NO synthase (iNOS) is expressed in cancers of the colon and the prostate, mainly by tumour cells, and NO generation is evidenced by widespread nitrotyrosine (NT) staining in tumour tissue. Furthermore, presence of NT is observed in the majority of tumour-associated macrophages (TAMs), despite low iNOS expression by these cells, suggesting that NO from the tumour microenvironment affects TAMs. Indeed, using a co-culture model, we demonstrate that NO produced by colon and prostate cancer cells is sufficient to induce NT formation in neighbouring macrophages. Moreover, exposure to exogenous NO promotes mitochondria-dependent and -independent changes in macrophages, which orientate their polarity towards an enhanced pro-inflammatory phenotype, whilst decreasing antigen-presenting function and wound healing capacity. Abrogating endogenous NO generation in murine macrophages, on the other hand, decreases their pro-inflammatory phenotype. These results suggest that the presence of NO in cancer may regulate TAM metabolism and function, favouring the persistence of inflammation, impairing healing and subverting adaptive immunity responses.

Orphan legume crops play an important role in smallholder farmers’ food systems. Though less documented, they have the potential to contribute to adequate nutrition in vulnerable communities. Unfortunately, data are scarce about the potential of those crops to withstand current and future climate variations. Using Macrotyloma geocarpum as an example, we used ecological niche modeling to explore the role of ecology on the current and future distributions of genetic populations of Kersting’s groundnut. Our findings showed that: (1) the models had good predictive power, indicating that M. geocarpum’s distribution was correlated with both climatic and soil layers; (2) identity and similarity tests revealed that the two genetic groups have identical and similar environmental niches; (3) by integrating the genetic information in niche modeling, niches projections show divergence in the response of the species and genetic populations to ongoing climate change. This study highlights the importance of incorporating genetic data into Ecological Niche Modeling (ENM) approaches to obtain a finer information of species’ future distribution, and explores the implications for agricultural adaptation, with a particular focus on identifying priority actions in orphan crops conservation and breeding.