Search

We report on the results of a search for a Weakly Interacting Massive Particle (WIMP) signal in low-energy data of the Cryogenic Dark Matter Search experiment using a maximum likelihood analysis. A background model is constructed using geant4 to simulate the surface-event background from Pb210 decay-chain events, while using independent calibration data to model the gamma background. Fitting this background model to the data results in no statistically significant WIMP component. In addition, we perform fits using an analytic ad hoc background model proposed by Collar and Fields, who claimed to find a large excess of signal-like events in our data. We confirm the strong preference for a signal hypothesis in their analysis under these assumptions, but excesses are observed in both single- and multiple-scatter events, which implies the signal is not caused by WIMPs, but rather reflects the inadequacy of their background model.

While the standard model of particle physics does not include free particles with fractional charge, experimental searches have not ruled out their existence. We report results from the Cryogenic Dark Matter Search (CDMS II) experiment that give the first direct-detection limits for cosmogenically produced relativistic particles with electric charge lower than e/6. A search for tracks in the six stacked detectors of each of two of the CDMS II towers finds no candidates, thereby excluding new parameter space for particles with electric charges between e/6 and e/200.

We report a first search for weakly interacting massive particles (WIMPs) using the background rejection capabilities of SuperCDMS. An exposure of 577 kg days was analyzed for WIMPs with mass

SuperCDMS is an experiment designed to directly detect weakly interacting massive particles (WIMPs), a favored candidate for dark matter ubiquitous in the Universe. In this Letter, we present WIMP-search results using a calorimetric technique we call CDMSlite, which relies on voltage-assisted Luke-Neganov amplification of the ionization energy deposited by particle interactions. The data were collected with a single 0.6 kg germanium detector running for ten live days at the Soudan Underground Laboratory. A low energy threshold of 170  eVee (electron equivalent) was obtained, which allows us to constrain new WIMP-nucleon spin-independent parameter space for WIMP masses below 6  GeV/c2.

We report results of a search for weakly interacting massive particles (WIMPS) with the silicon detectors of the CDMS II experiment. This blind analysis of 140.2 kg day of data taken between July 2007 and September 2008 revealed three WIMP-candidate events with a surface-event background estimate of 0.41(-0.08)(+0.20)(stat)(-0.24)(+0.28)(syst). Other known backgrounds from neutrons and 206Pb are limited to

The SuperCDMS experiment in the Soudan Underground Laboratory searches for dark matter with a 9-kg array of cryogenic germanium detectors. Symmetric sensors on opposite sides measure both charge and phonons from each particle interaction, providing excellent discrimination between electron and nuclear recoils, and between surface and interior events. Surface event rejection capabilities were tested with two 210Pb sources producing ∼130 beta decays/hr. In ∼800 live hours, no events leaked into the 8-115 keV signal region, giving upper limit leakage fraction 1.7 × 10-5 at 90% C.L., corresponding to < 0.6 surface event background in the future 200-kg SuperCDMS SNOLAB experiment. © 2013 AIP Publishing LLC.

We report results of a search for weakly interacting massive particles (WIMPs) with the Si detectors of the CDMS II experiment. This report describes a blind analysis of the first data taken with CDMS II's full complement of detectors in 2006-2007; results from this exposure using the Ge detectors have already been presented. We observed no candidate WIMP-scattering events in an exposure of 55.9 kg-days before analysis cuts, with an expected background of ∼1.1 events. The exposure of this analysis is equivalent to 10.3 kg-days over a recoil energy range of 7-100 keV for an ideal Si detector and a WIMP mass of 10 GeV/c2. These data set an upper limit of 1.7×10-41 cm2 on the WIMP-nucleon spin-independent cross section of a 10 GeV/c2 WIMP. These data exclude parameter space for spin-independent WIMP-nucleon elastic scattering that is relevant to recent searches for low-mass WIMPs. © 2013 American Physical Society.

In non-clinical studies, the proteasome inhibitor ixazomib inhibits cell growth in a broad panel of solid tumor cell lines in vitro. In contrast, antitumor activity in xenograft tumors is model-dependent, with some solid tumors showing no response to ixazomib. In this study we examined factors responsible for ixazomib sensitivity or resistance using mouse xenograft models. A survey of 14 non-small cell lung cancer (NSCLC) and 6 colon xenografts showed a striking relationship between ixazomib activity and KRAS genotype; tumors with wild-type (WT) KRAS were more sensitive to ixazomib than tumors harboring KRAS activating mutations. To confirm the association between KRAS genotype and ixazomib sensitivity, we used SW48 isogenic colon cancer cell lines. Either KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cells to generate cells that stably express activated KRAS. SW48 KRAS WT tumors, but neither SW48-KRAS-G13D tumors nor SW48-KRAS-G12V tumors, were sensitive to ixazomib in vivo. Since activated KRAS is known to be associated with metabolic reprogramming, we compared metabolite profiling of SW48-WT and SW48-KRAS-G13D tumors treated with or without ixazomib. Prior to treatment there were significant metabolic differences between SW48 WT and SW48-KRAS-G13D tumors, reflecting higher oxidative stress and glucose utilization in the KRAS-G13D tumors. Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors. Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types. However, changes in lipid beta oxidation were observed in only the KRAS WT tumors. The non-clinical data presented here show a correlation between KRAS genotype and ixazomib sensitivity in NSCLC and colon xenografts and provide new evidence of regulation of key metabolic pathways by proteasome inhibition.

Inflammation is a fundamental defensive response to harmful stimuli. However, it can cause damage if it does not subside. To avoid such damage, organisms have developed a mechanism called resolution of inflammation. Here we applied an untargeted metabolomics approach to a sterile and self-resolving animal model of acute inflammation, namely zymosan-induced peritonitis in mice, to examine the effect of inflammation and resolution on the metabolomic profiles. Significant and time-dependent changes in metabolite profiles after zymosan administration were observed in both peritoneal wash fluid (PWF) and plasma. These metabolomic changes correlated well with inflammatory chemokine or cytokine production. In PWF, most of metabolites that could detected increased in zymosan-treated mice, which is suggestive of inflammation, oxidative stress and increased energy demands. In plasma, most metabolites in the central metabolic pathway (glycolysis and TCA cycle) were significantly downregulated after zymosan administration. The concentration of the ketone body 3-hydroxybutyric acid (3-HB) in plasma and PWF increased in zymosan-injected animals indicating upregulation of fatty acid β-oxidation. Increased 3-HB level was observed in the cells that infiltrated into the peritoneal cavity and these infiltrated cells might contribute, at least in part, to the production of 3-HB in the peritoneal cavity.

"Suffering" is a central concept within bioethics and often a crucial consideration in medical decision making. As used in practice, however, the concept risks being uninformative, ambiguous, or even misleading. In this paper, we consider a series of cases in which "suffering" is invoked and analyze them in light of prominent theories of suffering. We then outline ethical hazards that arise as a result of imprecise usage of the concept and offer practical recommendations for avoiding them. Appeals to suffering are often getting at something ethically important. But this is where the work of ethics begins, not where it ends.

How should clinical ethicists be trained? Scholars have stated that clinical ethics fellowships create well-trained, competent ethicists. While this appears intuitive, few features of fellowship programs have been publicly discussed, let alone debated. In this paper, we examine how fellowships can foster effective mentoring relationships. These relationships provide the foundation for the fellow's transition from novice to competent professional. In this essay, we begin by discussing our pedagogical commitments. Next, we describe the structures our program has created to assist our fellows in becoming competent ethicists. We then outline the kinds of knowledge, skills, and professional attributes mentors should possess. Following this, we focus on the knowledge, skills, and professional attributes that fellows develop as they co-create effective mentoring relationships. We will not prescribe a single approach to fellowship training; instead, our perspective will, we hope, become a catalyst for further conversation on training and mentoring clinical ethics fellows., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

While it is not explicitly included in capacity assessment tools, "consistency" has come to feature as a central concern when assessing patients' capacity. In order to determine whether inconsistency indicates incapacity, clinicians must determine the source of the inconsistency with respect to the process or content of a patient's decision-making. In this paper, we outline common types of inconsistency and analyze them against widely accepted elements of capacity. We explore the question of whether inconsistency necessarily entails a deficiency in a patient's capacity. While inconsistency may count as prima facie evidence of incapacity-enough evidence to justify a closer look-when making such determinations, it is important for clinicians to slow down, inquire about the reasons underlying the inconsistency and clearly show which of the elements of capacity the patient fails to satisfy., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Palliative interventions are intended to alleviate suffering and improve quality, not quantity, of life and are not intended to cure illness. In psychiatry, uncertainty about which interventions count as palliative stems from the fact that psychiatry generally prioritizes symptom management irrespective of diagnosis or specific pathophysiology of illness. This commentary on a case considers how distinctions between palliative and other psychiatric interventions might not be all that helpful in resolving clinical and ethical questions about which interventions are-and when they are-appropriate., (Copyright 2023 American Medical Association. All Rights Reserved.)

Extracorporeal membrane oxygenation (ECMO) is typically viewed as a time-limited intervention-a bridge to recovery or transplant-not a destination therapy. However, some patients with decision-making capacity request continued ECMO support despite a poor prognosis for recovery and lack of viability as a transplant candidate. In response, critical care teams have asked for guidance regarding the ethical permissibility of unilateral withdrawal over the objections of a capacitated patient. In this article, we evaluate several ethical arguments that have been made in favor of withdrawal, including distributive justice, quality of life, patients' rights, professional integrity, and the Equivalence Thesis. We find that existing justifications for unilateral withdrawal of ECMO support in capacitated patients are problematic, which leads us to conclude that either: (1) additional ethical arguments are necessary to defend this approach or (2) the claim that it is not appropriate to use ECMO as a destination therapy should be questioned.

While experience often affords important knowledge and insight that is difficult to garner through observation or testimony alone, it also has the potential to generate conflicts of interest and unrepresentative perspectives. We call this tension the paradox of experience . In this paper, we first outline appeals to experience made in debates about access to unproven medical products and disability bioethics, as examples of how experience claims arise in bioethics and some of the challenges raised by these claims. We then motivate the idea that experience can be an asset by appealing to themes in feminist and moral epistemology, distinguishing between epistemic and justice-based appeals. Next, we explain the concern that experience may be a liability by appealing to empirical work on cognitive biases and theoretical work about the problem of partial representation. We conclude with preliminary recommendations for addressing the paradox and offer several questions for future discussion.

This Letter presents the results from the MiniBooNE experiment within a full "3+1" scenario where one sterile neutrino is introduced to the three-active-neutrino picture. In addition to electron-neutrino appearance at short baselines, this scenario also allows for disappearance of the muon-neutrino and electron-neutrino fluxes in the Booster Neutrino Beam, which is shared by the MicroBooNE experiment. We present the 3+1 fit to the MiniBooNE electron-(anti)neutrino and muon-(anti)neutrino data alone and in combination with MicroBooNE electron-neutrino data. The best-fit parameters of the combined fit with the exclusive charged-current quasielastic analysis (inclusive analysis) are Δm^{2}=0.209  eV^{2}(0.033  eV^{2}), |U&#95;{e4}|^{2}=0.016(0.500), |U&#95;{μ4}|^{2}=0.500(0.500), and sin^{2}(2θ&#95;{μe})=0.0316(1.0). Comparing the no-oscillation scenario to the 3+1 model, the data prefer the 3+1 model with a Δχ^{2}/d.o.f.=24.7/3(17.3/3), a 4.3σ(3.4σ) preference assuming the asymptotic approximation given by Wilks's theorem.

Bodily imagery elicits strong affective responses and is highly salient, potentially altering viewers' decision making. When clinicians engage surrogates in video calls showing the patient's body, several competing ethical issues must be considered. On the one hand, surrogates may require visual information to make informed decisions, and video technology closes crucial information gaps. On the other, video technology puts an increased amount of control in the hands of clinicians over how the patient's condition is perceived. This article explores some situations that can result in manipulation due to the affective impact of bodily images and the potential for selectivity and framing. Focusing on goals of care, the paper outlines the foremost ethical considerations for clinicians and provides recommendations for clinicians on how to reduce possible manipulation when making these video calls., (Copyright 2022 American Medical Association. All Rights Reserved.)

Patients who experience difficulty making medical decisions are often referred to as "ambivalent." However, the current lack of attention to the nuances between a cluster of phenomena that resemble ambivalence means that we are not always recognizing what is really going on with a patient. Importantly, different kinds of "ambivalence" may call for different approaches. In this paper, we present a taxonomy of ambivalence-related phenomena, provide normative analysis of some of the effects of-and common responses to-such mental states, and sketch some practical strategies for addressing ambivalence. In applying lessons from the philosophical literature and decision theory, our aim is to provide ethicists and clinicians with the tools to better understand and effectively intervene in cases of ambivalence.

The range of decisions considered permissible in pediatrics is typically understood to involve a balance between patient interests and parental or surrogate authority. In this article, we argue that there is a distinct set of considerations relevant to pediatric decision-making that is often neglected or unacknowledged in pediatrics-namely, considerations related to patient authenticity. The standard of pediatric authenticity asks not what is best for the patient or what the patient would choose but, rather, what is most consistent with who the patient is. We begin the article with an overview of the best interest standard and suggest that authenticity can elucidate considerations that fall between a child's strictly medical interests and broader familial or relational interests. Next, we discuss authenticity in greater detail, noting the limits of applying certain philosophical conceptions of authenticity in pediatrics. We then sketch our own account of pediatric authenticity and distinguish it from the related concepts of subjective interests and assent. We conclude with a discussion of three cases illustrating the normative significance of authenticity in a range of situations arising in pediatric medicine., (© 2022 The Hastings Center.)

Critical care professionals in the United States are experiencing distress and frustration during the recent delta-wave of the coronavirus disease 2019 pandemic. This wave feels different because most, although not all, patients suffering with the sequelae from coronavirus disease 2019 who enter ICUs are unvaccinated. Since vaccines in the United States are safe, effective, and widely available for people 12 and older, severe cases of coronavirus disease 2019 are now considered preventable. However, even when a disease is preventable, critical care professionals still have remaining role-based, ethical obligations to their patients. Developing additional mechanisms for reflection and resilience, in spite of accumulated frustrations from otherwise preventable mortality, may help the professional and those they care for. In this essay, we propose a number of questions that recognize the existential frustrations critical care professionals experience, while also uncovering the ethical obligations that remain. Rather than becoming comfortable with silence or frustration, these reflections intend to bridge the gap between feeling frustrated and building relationships that benefit both the patient and the critical care professional during this pandemic., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

"Bring your whole self to work" remains a common mantra of supporters of workplace diversity, equity, and inclusion ("DEI").1 For example, disability rights advocates have long contended that hiding or downplaying one's disability from one's colleagues at work "create[s] an invisible layer of additional work for the individual" in being accepted at the job and negatively affects productivity.2 LGBTQ+ rights advocates have raised similar points, noting that hiding or downplaying one's sexual orientation or gender identity from one's colleagues hinders internal advancement of LGBTQ+ workers.3 As recently as 2019, however, a Deloitte study found that sixty-one percent of workers hid or downplayed one or more of their identities from their colleagues at work.4.

Competing Interests: Competing interests: None declared.

By uncovering complex dynamics in the expression or localization of transcriptional regulators in single cells that were otherwise hidden at the population level, live cell imaging has transformed our understanding of how cells sense and orchestrate appropriate responses to changes in their internal state or extracellular environment. This has proved particularly true for the nuclear factor-kappaB (NF-κB) family of transcription factors, key regulators of the inflammatory response and innate immune function, which are capable of encoding information about the mode and intensity of stimuli in the dynamics of NF-κB nuclear accumulation and loss. While live cell imaging continues to serve as a useful tool in ongoing efforts to characterize the feedbacks that shape these dynamics and to connect dynamics to downstream gene expression, it is also proving invaluable for recent studies that seek to determine how intracellular pathogens subvert NF-κB signaling to survive and replicate within host cells by providing quantitative information about the pathogen and changes in NF-κB activity during different stages of an infection. Here, we provide a brief overview of NF-κB signaling in innate immune cells and review recent literature that uses live imaging to investigate the mechanisms by which bacterial and yeast pathogens modulate NF-κB in a variety of different host cell types to evade destruction or maintain the viability of an intracellular growth niche.

Spillover of lipoprotein lipase-generated fatty acids from chylomicrons into the plasma free fatty acid (FFA) pool is an important source of FFA and reflects inefficiency in dietary fat storage. We measured spillover in 13 people with type 2 diabetes using infusions of a [(3)H]triolein-labeled lipid emulsion and [U-(13)C]oleate during continuous feeding, before and after weight loss. Body fat was measured with dual energy X-ray absorptiometry and computed tomography. Participants lost ∼14% of body weight. There was an ∼38% decrease in meal-suppressed FFA concentration (P < 0.0001) and an ∼23% decrease in oleate flux (P = 0.007). Fractional spillover did not change (P = NS). At baseline, there was a strong negative correlation between spillover and leg fat (r = -0.79, P = 0.001) and a positive correlation with the trunk-to-leg fat ratio (R = 0.56, P = 0.047). These correlations disappeared after weight loss. Baseline leg fat (R = -0.61, P = 0.027) but not trunk fat (R = -0.27, P = 0.38) negatively predicted decreases in spillover with weight loss. These results indicate that spillover, a measure of inefficiency in dietary fat storage, is inversely associated with lower body fat in type 2 diabetes.

Plasma free fatty acid (FFA) kinetics in humans are often measured with only one tracer. In study 1, healthy volunteers received infusions of [U-¹³C]linoleate, [U-¹³C]oleate, and [U-¹³C]palmitate during continuous feeding with liquid meals low (n = 12) and high (n = 5) in palmitate and containing three labeled fatty acids to measure FFA appearance and fractional spillover of lipoprotein lipase-generated fatty acids. Study 2 used an intravenous lipid emulsion to increase FFA concentrations during infusion of linoleate and palmitate tracers. In study 1, there were no differences in spillover of the three fatty acids for the low-palmitate meal, but linoleate spillover was greater than oleate or palmitate for the high-palmitate meal. In studies 1 and 2, clearance was significantly greater for linoleate than for the other FFAs. There was a negative correlation between clearance and concentration for each fatty acid in the two studies. In study 1, concentration and spillover correlated positively for oleate and palmitate but negatively for linoleate. In conclusion, linoleate spillover is greater than that of other fatty acids under some circumstances. Linoleate clearance is greater than that of palmitate or oleate, indicating a need for caution when using a single FFA to infer the behavior of all fatty acids.

Elevated levels of blood lipids are well-documented risk factors for cardiovascular disease. Current classification schemes and treatment levels for hyperlipidemia are based on the National Cholesterol Education Panel's Adult Treatment Program-3 (ATP-III) guidelines. Extensive research over the past decade has raised the question whether or not ATP-III guidelines are sufficiently aggressive. New guidelines from ATP-IV are expected to be released in the near future, but in the meantime physicians are faced with uncertainty about how low to target low-density lipoprotein cholesterol, whether to pharmacologically treat high-density lipoprotein cholesterol and triglyceride levels, and how best to achieve target goals., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Spillover of fatty acids released by lipoprotein lipase hydrolysis of meal triglycerides may be a major contributor to the free fatty acid (FFA) pool. We studied lean (n = 6) and overweight and obese (n = 5) subjects during continuous feeding on two occasions: during intravenous infusion of niacin (2.8 mg/min) and saline. After establishment of steady-state chylomicronemia and suppression of adipose tissue lipolysis with a liquid meal, spillover was measured with infusions of [U-(13)C]oleate and [(3)H]triolein. Total FFA concentrations were lower during niacin infusion in both lean (50 ± 4 vs. 102 ± 7 μmol/L; P < 0.002) and obese (75 ± 6 vs. 143 ± 13 μmol/L; P < 0.01) subjects. Oleate appearance was lower during niacin infusion than during saline infusion in both lean (21 ± 2 vs. 32 ± 5 μmol/min; P = 0.07) and obese subjects (25 ± 3 vs. 46 ± 8 μmol/min; P < 0.02). Spillover was lower during niacin infusion than during saline infusion in lean (21 ± 4 vs. 29 ± 3%) and obese (21 ± 2 vs. 29 ± 5%) subjects (P < 0.03 for both). In summary, during meal absorption, niacin produces additional suppression of lipolysis and a reduction in fractional spillover compared with saline in both normal and obese subjects. Infusion of intravenous niacin provides a model for acutely improving dietary fat storage, perhaps by suppressing lipolysis in visceral adipose tissue.

Context: Spillover of chylomicron triglyceride fatty acids directly into the circulation as free fatty acids (FFAs) during lipoprotein lipase hydrolysis may contribute to the elevated total FFAs seen in insulin-resistant states., Objective: The objective of the study was to determine whether spillover is regulated by rates of intracellular lipolysis, we studied overweight and obese nondiabetic subjects (n = 7) on two occasions, during infusion of saline and insulin., Design: During insulin infusion (20 mU · m(-2) · min(-1)), plasma glucose was clamped at the concentration achieved during saline infusion. On both study days, subjects sipped 1-2 oz of a liquid mixed meal every 15 min for 6.5 h to achieve steady-state chylomicron and FFA concentrations. Spillover was measured with infusions of [(3)H]triolein and [U-(13)C] oleate., Results: Glucose concentrations were similar during saline compared with insulin (113 ± 2 vs. 113 ± 1 mg/dl, P = NS). Insulin levels during saline and insulin infusion were 18 ± 3 and 44 ± 5 μU/ml, respectively. Glucose infusion rate during insulin infusion was 5.5 ± 1.0 mg · kg fat-free mass(-1) · min(-1). Plasma FFA concentrations were lower during insulin compared with saline (75 ± 8 vs. 124 ± 13 μmol/liter, P = 0.002). Oleate rate of appearance was lower during insulin vs. saline (27 ± 3 vs. 36 ± 5 μmol/min, P = 0.004). Spillover was similar during saline and insulin (26 ± 2 vs. 25 ± 2%, P = 0.60)., Conclusions: These results indicate that suppression of intracellular lipolysis with insulin does not reduce lipoprotein lipase-mediated spillover in humans during meal absorption. It is possible that spillover did not decrease because of an impaired or absent antilipolytic effect of increased insulin concentrations in visceral fat.

The MiniBooNE experiment at Fermilab reports results from a search for ¯ν&#95;{μ}→¯ν&#95;{e} oscillations, using a data sample corresponding to 5.66×10²⁰ protons on target. An excess of 20.9±14.0 events is observed in the energy range 475

The MiniBooNE Collaboration reports initial results from a search for nu(mu)-->nu(e) oscillations. A signal-blind analysis was performed using a data sample corresponding to 3.39x10(20) protons on target. The data are consistent with background prediction across the full range of neutrino energy reconstructed assuming quasielastic scattering, 200

Using high statistics samples of charged-current numu interactions, the MiniBooNE [corrected] Collaboration reports a measurement of the single-charged-pion production to quasielastic cross section ratio on mineral oil (CH2), both with and without corrections for hadron reinteractions in the target nucleus. The result is provided as a function of neutrino energy in the range 0.4 GeV

The MiniBooNE Collaboration reports a search for nu&#95;{micro} and nu[over]&#95;{micro} disappearance in the Deltam;{2} region of 0.5-40 eV;{2}. These measurements are important for constraining models with extra types of neutrinos, extra dimensions, and CPT violation. Fits to the shape of the nu&#95;{micro} and nu[over]&#95;{micro} energy spectra reveal no evidence for disappearance at the 90% confidence level (C.L.) in either mode. The test of nu[over]&#95;{micro} disappearance probes a region below Deltam;{2} = 40 eV;{2} never explored before.

We report the first observation of off-axis neutrino interactions in the MiniBooNE detector from the NuMI beam line at Fermilab. The MiniBooNE detector is located 745 m from the NuMI production target, at 110 mrad angle (6.3 degrees) with respect to the NuMI beam axis. Samples of charged-current quasielastic numicro and nue interactions are analyzed and found to be in agreement with expectation. This provides a direct verification of the expected pion and kaon contributions to the neutrino flux and validates the modeling of the NuMI off-axis beam.

The MiniBooNE Collaboration observes unexplained electronlike events in the reconstructed neutrino energy range from 200 to 475 MeV. With 6.46x10;{20} protons on target, 544 electronlike events are observed in this energy range, compared to an expectation of 415.2+/-43.4 events, corresponding to an excess of 128.8+/-20.4+/-38.3 events. The shape of the excess in several kinematic variables is consistent with being due to either nu&#95;{e} and nu[over ]&#95;{e} charged-current scattering or nu&#95;{mu} neutral-current scattering with a photon in the final state. No significant excess of events is observed in the reconstructed neutrino energy range from 475 to 1250 MeV, where 408 events are observed compared to an expectation of 385.9+/-35.7 events.

The observation of neutrino oscillations is clear evidence for physics beyond the standard model. To make precise measurements of this phenomenon, neutrino oscillation experiments, including MiniBooNE, require an accurate description of neutrino charged current quasielastic (CCQE) cross sections to predict signal samples. Using a high-statistics sample of nu&#95;(mu) CCQE events, MiniBooNE finds that a simple Fermi gas model, with appropriate adjustments, accurately characterizes the CCQE events observed in a carbon-based detector. The extracted parameters include an effective axial mass, M&#95;(A)(eff)=1.23+/-0.20 GeV, that describes the four-momentum dependence of the axial-vector form factor of the nucleon, and a Pauli-suppression parameter, kappa=1.019+/-0.011. Such a modified Fermi gas model may also be used by future accelerator-based experiments measuring neutrino oscillations on nuclear targets.

Objective: Triglyceride-rich lipoproteins, primarily chylomicrons, can contribute to plasma free fatty acid (FFA) concentrations via spillover of fatty acids during intravascular hydrolysis into the venous effluent of some tissues. The present study was undertaken to determine whether spillover occurs in the splanchnic bed of humans., Research Design and Methods: Arterial and hepatic venous blood was sampled in postabsorptive (n = 6; study A) and postprandial (n = 5; study B) obese humans during infusion of carbon-labeled ((14)C or (13)C) oleate and (3)H triolein, the latter incorporated into a lipid emulsion as a surrogate for chylomicrons. Spillover was determined by measuring production of (3)H oleate., Results: Splanchnic spillover was higher than nonsplanchnic systemic spillover in both study A (60 +/- 7 vs. 24 +/- 6%; P < 0.01) and study B (54 +/- 3 vs. 16 +/- 5%; P < 0.005). Because portal vein sampling is not feasible in humans, assumptions regarding actual spillover in nonhepatic splanchnic tissues were required for the spillover calculation. A mathematical model was developed and demonstrated that nonhepatic splanchnic spillover rates in study A and study B of 69 and 80%, respectively, provided the best fit with the data. There was preferential splanchnic uptake of triglyceride fatty acids compared with FFAs in study B (fractional extraction 61 +/- 3 vs. 33 +/- 2%; P < 0.005)., Conclusions: These data confirm previous studies indicating that the transport of FFAs and triglyceride fatty acids are partitioned in tissues and indicate that splanchnic spillover from triglyceride-rich lipoproteins may be a significant source of both portal venous and systemic FFAs.

Free fatty acids are the major lipid fuel of the body. Dysregulation of adipose tissue lipolysis results in increased plasma free fatty acid concentrations, and via that mechanism contributes to insulin resistance in obesity and type 2 diabetes mellitus. Adipose tissue hormone sensitive lipase is thought to be responsible for the production of the majority of free fatty acids. However, a separate contribution comes from the action of endothelial lipases, especially lipoprotein lipase, on triglyceride-rich lipoproteins via a process known as spillover. The primary substrate for spillover appears to be chylomicrons derived from dietary fat. The spillover of fatty acids into the free fatty acid pool varies from one tissue to another. For example, spillover is low ( approximately 14%) in the forearm of healthy volunteers, suggesting that triglyceride fatty acid storage is relatively efficient in skeletal muscle. In contrast, spillover appears to be higher in adipose tissue and may also be higher in the splanchnic bed, based on preliminary data. If systemic spillover is increased in insulin resistant states such as diabetes, this could represent a mechanism contributing to the abnormal increases in plasma concentrations of free fatty acids in that condition.

The action of lipoprotein lipase on triglyceride-rich lipoproteins generates fatty acids that are either transported into tissues or mix with circulating free fatty acids (FFAs) via a process known as spillover. In the present study, arterial, portal vein, and hepatic vein sampling catheters were surgically placed in nine mongrel dogs. The animals were subsequently studied after a 42-h fast during infusion of [14C]oleate and a lipid emulsion containing [3H]triolein; the emulsion was used as a surrogate for the study of chylomicron metabolism. More than one-half of splanchnic [3H]triglyceride uptake occurred in the liver, and substantial fractional spillover of [3H]oleate was observed in both liver and nonhepatic tissues (approximately 50% each). There was a significant correlation between FFA release from nonhepatic tissues (presumably visceral fat) and nonhepatic fractional spillover (R = 0.81, P < 0.01), consistent with a model in which the rate of intracellular lipolysis influences spillover by determining the direction of net fatty acid flow between the cell and the interstitium. There was a significant correlation between "true" and "net" splanchnic spillover (R = 0.84, P < 0.005), the latter representing calculation of spillover between arterial and hepatic venous blood without portal venous data. Metabolism of chylomicron triglycerides in visceral fat may be an important source of portal venous FFAs.

The MiniBooNE Collaboration reports first results of a search for nu e appearance in a nu mu beam. With two largely independent analyses, we observe no significant excess of events above the background for reconstructed neutrino energies above 475 MeV. The data are consistent with no oscillations within a two-neutrino appearance-only oscillation model.

Animal studies indicate that oversupply of fatty acids derived from the action of cardiac lipoprotein lipase (LPL) on plasma lipoproteins may contribute to myocardial dysfunction. However, the contribution of circulating triglycerides to myocardial fatty acid supply in humans is not known. Six postabsorptive nondiabetic subjects who were scheduled for diagnostic coronary angiography were studied. (14)C oleate and a lipid emulsion labeled with (3)H triolein were infused to assess myocardial uptake of free fatty acids (FFAs) and triglycerides, as well as myocardial spillover of LPL-generated fatty acids. Six paired blood samples were taken from the femoral artery and the coronary sinus. Coronary sinus concentrations of unlabeled triglycerides were slightly, but not significantly, lower than arterial (P = 0.12), whereas labeled triglyceride concentrations were significantly lower in the coronary sinus than in the artery (P < 0.05; extraction fraction congruent with 11%). Triglycerides and FFAs accounted for approximately 17% and approximately 83%, respectively, of myocardial fatty acid uptake. Systemic and myocardial fractional spillover of LPL-generated fatty acids was 49.0 +/- 7% and 34.7 +/- 13%, respectively. The myocardium was a minor contributor to systemic triglyceride uptake ( approximately 3%) and a trivial contributor to systemic FFA production ( approximately 0.5%). These results indicate that circulating triglycerides may be a significant source of fatty acids for myocardial respiration.