Auxiliary gauge mediation: a new route to mini-split supersymmetry

The discovery of a standard-model-like Higgs at 126 GeV and the absence of squark signals thus far at the LHC both point towards a mini-split spectrum for supersymmetry. Within standard paradigms, it is non-trivial to realize a mini-split spectrum with heavier sfermions but lighter gauginos while simultaneously generating Higgs sector soft terms of the correct magnitude, suggesting the need for new models of supersymmetry breaking and mediation. In this paper, we present a new approach to mini-split model building based on gauge mediation by “auxiliary groups”, which are the anomaly-free continuous symmetries of the standard model in the limit of vanishing Yukawa couplings. In addition to the well-known flavor SU(3) [subscript F] and baryon-minus-lepton U(1) [subscript B−L] groups, we find that an additional U(1) [subscript H] acting on the Higgs doublets alone can be used to generate Higgs soft masses and B-terms necessary for a complete model of mini-split. Auxiliary gauge mediation is a special case of Higgsed gauge mediation, and we review the resulting two-loop scalar soft terms as well as three-loop gaugino masses. Along the way, we present a complete two-loop calculation of A-terms and B-terms in gauge mediation, which — contrary to a common misconception — includes a non-zero contribution at the messenger threshold which can be sizable in models with light gauginos. We present several phenomenologically acceptable mini-split spectra arising from auxiliary gauge mediation and highlight a complete minimal model which realizes the required spectrum and Higgs sector soft terms with a single U(1) [subscript X] auxiliary gauge symmetry. We discuss possible experimental consequences.United States. Dept. of Energy (Cooperative Research Agreement DE-FG02-05ER-41360)National Science Foundation (U.S.). Graduate Research Fellowship ProgramSimons Foundation (Postdoctoral Fellowship)United States. Dept. of Energy (Early Career Research Program DE-FG02-11ER-41741

Mine closure of pit lakes as terminal sinks: best available practice when options are limited?

In an arid climate, pit lake evaporation rates can exceed influx rates, causing the lake to function as a hydraulic terminal sink, with water levels in the pit remaining below surrounding groundwater levels. We present case studies from Western Australia for two mines nearing closure. At the first site, modelling indicates that waste dump covers for the potentially acid forming (PAF) material would not be successful over the long term (1,000 years or more). The second site is a case study where PAF management is limited by the current waste rock dump location and suitable cover materials. Pit lake water balance modelling using Goldsim software indicated that both pit lakes would function as hydraulic terminal sinks if not backfilled above long-term equilibrium water levels. Poor water quality will likely develop as evapoconcentration increases contaminant concentrations, providing a potential threat to local wildlife. Even so, the best current opportunity to limit the risk of contaminant migration and protect regional groundwater environments may be to limit backfill and intentionally produce a terminal sink pit lake

Purpose in life predicts better emotional recovery from negative stimuli

Purpose in life predicts both health and longevity suggesting that the ability to find meaning from life’s experiences, especially when confronting life’s challenges, may be a mechanism underlying resilience. Having purpose in life may motivate reframing stressful situations to deal with them more productively, thereby facilitating recovery from stress and trauma. In turn, enhanced ability to recover from negative events may allow a person to achieve or maintain a feeling of greater purpose in life over time. In a large sample of adults (aged 36-84 years) from the MIDUS study (Midlife in the U.S., http://www.midus.wisc.edu/), we tested whether purpose in life was associated with better emotional recovery following exposure to negative picture stimuli indexed by the magnitude of the eyeblink startle reflex (EBR), a measure sensitive to emotional state. We differentiated between initial emotional reactivity (during stimulus presentation) and emotional recovery (occurring after stimulus offset). Greater purpose in life, assessed over two years prior, predicted better recovery from negative stimuli indexed by a smaller eyeblink after negative pictures offset, even after controlling for initial reactivity to the stimuli during the picture presentation, gender, age, trait affect, and other well-being dimensions. These data suggest a proximal mechanism by which purpose in life may afford protection from negative events and confer resilience is through enhanced automatic emotion regulation after negative emotional provocation

Breeding for increased nitrogen-use efficiency: a review for wheat (T. aestivum L.)

Nitrogen fertilizer is the most used nutrient source in modern agriculture and represents significant environmental and production costs. In the meantime, the demand for grain increases and production per area has to increase as new cultivated areas are scarce. In this context, breeding for an efficient use of nitrogen became a major objective. In wheat, nitrogen is required to maintain a photosynthetically active canopy ensuring grain yield and to produce grain storage proteins that are generally needed to maintain a high end-use quality. This review presents current knowledge of physiological, metabolic and genetic factors influencing nitrogen uptake and utilization in the context of different nitrogen management systems. This includes the role of root system and its interactions with microorganisms, nitrate assimilation and its relationship with photosynthesis as postanthesis remobilization and nitrogen partitioning. Regarding nitrogen-use efficiency complexity, several physiological avenues for increasing it were discussed and their phenotyping methods were reviewed. Phenotypic and molecular breeding strategies were also reviewed and discussed regarding nitrogen regimes and genetic diversity

Acquired resistance to oxaliplatin is not directly associated with increased resistance to DNA damage in SK-N-ASrOXALI4000, a newly established oxaliplatin-resistant sub-line of the neuroblastoma cell line SK-N-AS

The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-ASrOXALI4000 cells exhibited a stable resistance phenotype that was not affected by culturing the cells for 10 weeks in the absence of oxaliplatin. Interestingly, SK-N-ASrOXALI4000 cells showed no cross resistance to gemcitabine and increased sensitivity to doxorubicin and UVC radiation, alternative treatments that like platinum drugs target DNA integrity. Notably, UVC-induced DNA damage is thought to be predominantly repaired by nucleotide excision repair and nucleotide excision repair has been described as the main oxaliplatin-induced DNA damage repair system. SK-N-ASrOXALI4000 cells were also more sensitive to lysis by influenza A virus, a candidate for oncolytic therapy, than SK-N-AS cells. In conclusion, we introduce a novel oxaliplatin resistance model. The oxaliplatin resistance mechanisms in SK-N-ASrOXALI4000 cells appear to be complex and not to directly depend on enhanced DNA repair capacity. Models of oxaliplatin resistance are of particular relevance since research on platinum drugs has so far predominantly focused on cisplatin and carboplatin

A Robotic Wide-Angle H-Alpha Survey of the Southern Sky

We have completed a robotic wide-angle imaging survey of the southern sky (declination less than +15 degrees) at 656.3 nm wavelength, the H-alpha emission line of hydrogen. Each image of the resulting Southern H-Alpha Sky Survey Atlas (SHASSA) covers an area of the sky 13 degrees square at an angular resolution of approximately 0.8 arcminute, and reaches a sensitivity level of 2 rayleigh (1.2 x 10^-17 erg cm^-2 s^-1 arcsec^-2) per pixel, corresponding to an emission measure of 4 cm^-6 pc, and to a brightness temperature for microwave free-free emission of 12 microkelvins at 30 GHz. Smoothing over several pixels allows features as faint as 0.5 rayleigh to be detected.Comment: LATEX, 33 pages, 15 figures. Accepted for publication in PASP, 113, November 2001. Further information at http://amundsen.swarthmore.edu/SHASSA

Macrophage-Derived Mlkl in Alcohol-Associated Liver Disease: Regulation of Phagocytosis

BACKGROUND AND AIMS: Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays a role in intracellular vesicle trafficking that is critical for regulating liver inflammation and injury in alcohol-associated liver disease (ALD). Although receptor interacting protein kinase 3 (Rip3)-/- mice are completely protected from ethanol-induced liver injury, Mlkl-/- mice are only partially protected. Therefore, we hypothesized that cell-specific functions of MLKL may contribute to ethanol-induced injury. APPROACH AND RESULTS: Bone marrow transplants between Mlkl-/- mice and littermates were conducted to distinguish the role of myeloid versus nonmyeloid Mlkl in the Gao-binge model of ALD. Ethanol-induced hepatic injury, steatosis, and inflammation were exacerbated in Mlkl-/- →wild-type (WT) mice, whereas Mlkl deficiency in nonmyeloid cells (WT→ Mlkl-/- ) had no effect on Gao-binge ethanol-induced injury. Importantly, Mlkl deficiency in myeloid cells exacerbated ethanol-mediated bacterial burden and accumulation of immune cells in livers. Mechanistically, challenging macrophages with lipopolysaccharide (LPS) induced signal transducer and activator of transcription 1-mediated expression and phosphorylation of MLKL, as well as translocation and oligomerization of MLKL to intracellular compartments, including phagosomes and lysosomes but not plasma membrane. Importantly, pharmacological or genetic inhibition of MLKL suppressed the phagocytic capability of primary mouse Kupffer cells (KCs) at baseline and in response to LPS with/without ethanol as well as peripheral monocytes isolated from both healthy controls and patients with alcohol-associated hepatitis. Further, in vivo studies revealed that KCs of Mlkl-/- mice phagocytosed fewer bioparticles than KCs of WT mice. CONCLUSION: Together, these data indicate that myeloid MLKL restricts ethanol-induced liver inflammation and injury by regulating hepatic immune cell homeostasis and macrophage phagocytosis

Automated Large Vessel Occlusion Detection Software and Thrombectomy Treatment Times: a Cluster Randomized Clinical Trial

IMPORTANCE: The benefit of endovascular stroke therapy (EVT) in large vessel occlusion (LVO) ischemic stroke is highly time dependent. Process improvements to accelerate in-hospital workflows are critical. OBJECTIVE: to determine whether automated computed tomography (CT) angiogram interpretation coupled with secure group messaging can improve in-hospital EVT workflows. DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized stepped-wedge clinical trial took place from January 1, 2021, through February 27, 2022, at 4 comprehensive stroke centers (CSCs) in the greater Houston, Texas, area. All 443 participants with LVO stroke who presented through the emergency department were treated with EVT at the 4 CSCs. Exclusion criteria included patients presenting as transfers from an outside hospital (n = 158), in-hospital stroke (n = 39), and patients treated with EVT through randomization in a large core clinical trial (n = 3). INTERVENTION: Artificial intelligence (AI)-enabled automated LVO detection from CT angiogram coupled with secure messaging was activated at the 4 CSCs in a random-stepped fashion. Once activated, clinicians and radiologists received real-time alerts to their mobile phones notifying them of possible LVO within minutes of CT imaging completion. MAIN OUTCOMES AND MEASURES: Primary outcome was the effect of AI-enabled LVO detection on door-to-groin (DTG) time and was measured using a mixed-effects linear regression model, which included a random effect for cluster (CSC) and a fixed effect for exposure status (pre-AI vs post-AI). Secondary outcomes included time from hospital arrival to intravenous tissue plasminogen activator (IV tPA) bolus in eligible patients, time from initiation of CT scan to start of EVT, and hospital length of stay. In exploratory analysis, the study team evaluated the impact of AI implementation on 90-day modified Rankin Scale disability outcomes. RESULTS: Among 243 patients who met inclusion criteria, 140 were treated during the unexposed period and 103 during the exposed period. Median age for the complete cohort was 70 (IQR, 58-79) years and 122 were female (50%). Median National Institutes of Health Stroke Scale score at presentation was 17 (IQR, 11-22) and the median DTG preexposure was 100 (IQR, 81-116) minutes. In mixed-effects linear regression, implementation of the AI algorithm was associated with a reduction in DTG time by 11.2 minutes (95% CI, -18.22 to -4.2). Time from CT scan initiation to EVT start fell by 9.8 minutes (95% CI, -16.9 to -2.6). There were no differences in IV tPA treatment times nor hospital length of stay. In multivariable logistic regression adjusted for age, National Institutes of Health Stroke scale score, and the Alberta Stroke Program Early CT Score, there was no difference in likelihood of functional independence (modified Rankin Scale score, 0-2; odds ratio, 1.3; 95% CI, 0.42-4.0). CONCLUSIONS AND RELEVANCE: Automated LVO detection coupled with secure mobile phone application-based communication improved in-hospital acute ischemic stroke workflows. Software implementation was associated with clinically meaningful reductions in EVT treatment times. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05838456

Automated Large Vessel Occlusion Detection Software and Thrombectomy Treatment Times: A Cluster Randomized Clinical Trial

Importance The benefit of endovascular stroke therapy (EVT) in large vessel occlusion (LVO) ischemic stroke is highly time dependent. Process improvements to accelerate in-hospital workflows are critical. Objective To determine whether automated computed tomography (CT) angiogram interpretation coupled with secure group messaging can improve in-hospital EVT workflows. Design, Setting, and Participants This cluster randomized stepped-wedge clinical trial took place from January 1, 2021, through February 27, 2022, at 4 comprehensive stroke centers (CSCs) in the greater Houston, Texas, area. All 443 participants with LVO stroke who presented through the emergency department were treated with EVT at the 4 CSCs. Exclusion criteria included patients presenting as transfers from an outside hospital (n = 158), in-hospital stroke (n = 39), and patients treated with EVT through randomization in a large core clinical trial (n = 3). Intervention Artificial intelligence (AI)–enabled automated LVO detection from CT angiogram coupled with secure messaging was activated at the 4 CSCs in a random-stepped fashion. Once activated, clinicians and radiologists received real-time alerts to their mobile phones notifying them of possible LVO within minutes of CT imaging completion. Main Outcomes and Measures Primary outcome was the effect of AI-enabled LVO detection on door-to-groin (DTG) time and was measured using a mixed-effects linear regression model, which included a random effect for cluster (CSC) and a fixed effect for exposure status (pre-AI vs post-AI). Secondary outcomes included time from hospital arrival to intravenous tissue plasminogen activator (IV tPA) bolus in eligible patients, time from initiation of CT scan to start of EVT, and hospital length of stay. In exploratory analysis, the study team evaluated the impact of AI implementation on 90-day modified Rankin Scale disability outcomes. Results Among 243 patients who met inclusion criteria, 140 were treated during the unexposed period and 103 during the exposed period. Median age for the complete cohort was 70 (IQR, 58-79) years and 122 were female (50%). Median National Institutes of Health Stroke Scale score at presentation was 17 (IQR, 11-22) and the median DTG preexposure was 100 (IQR, 81-116) minutes. In mixed-effects linear regression, implementation of the AI algorithm was associated with a reduction in DTG time by 11.2 minutes (95% CI, −18.22 to −4.2). Time from CT scan initiation to EVT start fell by 9.8 minutes (95% CI, −16.9 to −2.6). There were no differences in IV tPA treatment times nor hospital length of stay. In multivariable logistic regression adjusted for age, National Institutes of Health Stroke scale score, and the Alberta Stroke Program Early CT Score, there was no difference in likelihood of functional independence (modified Rankin Scale score, 0-2; odds ratio, 1.3; 95% CI, 0.42-4.0). Conclusions and Relevance Automated LVO detection coupled with secure mobile phone application-based communication improved in-hospital acute ischemic stroke workflows. Software implementation was associated with clinically meaningful reductions in EVT treatment times