Solutions to the MiniBooNE Anomaly from New Physics in Charged Meson Decays.

We point out that production of new bosons by charged meson decays can greatly enhance the sensitivity of beam-focused accelerator-based experiments to new physics signals. This enhancement arises since the charged mesons are focused and their three-body decays do not suffer from helicity suppression in the same way as their usual two-body decays. As a realistic application, we attempt to explain the MiniBooNE low energy excess utilizing this overlooked mechanism, uniquely realizing dark-sector interpretations as plausible solutions to the excess. As proof of the principle, we consider two well-motivated classes of dark-sector models, models of vector-portal dark matter and models of long-lived (pseudo)scalar. We argue that the model parameter values to accommodate the excess are consistent with existing limits and that they can be tested at current and future accelerator-based neutrino experiments.

Laparoscopic cholecystectomy in patients with previous upper midline abdominal surgery: comparison of laparoscopic cholecystectomy after gastric surgery and non-gastric surgery using propensity score matching.

BACKGROUND: Previous upper midline abdominal surgery is a reported relative contraindication to laparoscopic cholecystectomy. We aimed to investigate the effects of previous upper abdominal surgery on the feasibility and safety of laparoscopic cholecystectomy; we evaluated the effects of the previous upper abdominal surgery type on laparoscopic cholecystectomy with respect to complications and conversion to open surgery. METHODS: We prospectively evaluated 1,258 patients who underwent laparoscopic cholecystectomy, including those who underwent upper midline abdominal surgery previously, at a single tertiary referral center. The perioperative and postoperative outcomes-open conversion rate, operation time, intraoperative and postoperative complications, and length of hospital stay-were evaluated. Patients were grouped according to the previous surgical method into the gastric (n = 77), non-gastric (n = 40), and control (n = 1141) groups. Patients in the gastric + non-gastric groups (n = 117) were 1:1 matched with those in the control group (n = 117) using propensity score matching (PSM). RESULTS: Before PSM, age, sex, open conversion rate, gallbladder status, port number, overall morbidity, and postoperative hospital stay duration did not significantly differ between the gastric and non-gastric groups; the body mass index (22.3 ± 3.4 versus 24.1 ± 3.8 kg/m2, p = 0.009) and operation time (129.9 ± 63.6 versus 97.9 ± 51.1 min, p = 0.004) significantly differed. After PSM, age, sex, body mass index, and American Society of Anesthesiology score did not significantly differ between gastric + non-gastric (n = 117) and conventional groups (n = 117; the operation time (118.9 ± 61.3 versus 75.8 ± 37.1 min, p < 0.001), open conversion rate (n = 6, 5.1% versus n = 0, 0.0%, p = 0.013), port number, overall morbidities (n = 26, 22.2% versus n = 10, 8.5%, p = 0.004), and postoperative hospital stay duration (6.7 ± 4.3 versus 5.5 ± 3.2 days, p = 0.031) significantly differed. CONCLUSION: Previous upper midline abdominal surgery was not contraindicative to safe laparoscopic cholecystectomy. Patients with previous upper midline abdominal surgery undergoing laparoscopic cholecystectomy should be informed preoperatively of the probability of conversion to open surgery, lengthened duration, and associated morbidities.

Plasma Aldo-Keto Reductase Family 1 Member B10 as a Biomarker Performs Well in the Diagnosis of Nonalcoholic Steatohepatitis and Fibrosis.

We found several blood biomarkers through computational secretome analyses, including aldo-keto reductase family 1 member B10 (AKR1B10), which reflected the progression of nonalcoholic fatty liver disease (NAFLD). After confirming that hepatic AKR1B10 reflected the progression of NAFLD in a subgroup with NAFLD, we evaluated the diagnostic accuracy of plasma AKR1B10 and other biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) and fibrosis in replication cohort. We enrolled healthy control subjects and patients with biopsy-proven NAFLD (n = 102) and evaluated the performance of various diagnostic markers. Plasma AKR1B10 performed well in the diagnosis of NASH with an area under the receiver operating characteristic (AUROC) curve of 0.834 and a cutoff value of 1078.2 pg/mL, as well as advanced fibrosis (AUROC curve value of 0.914 and cutoff level 1078.2 pg/mL), with further improvement in combination with C3. When we monitored a subgroup of obese patients who underwent bariatric surgery (n = 35), plasma AKR1B10 decreased dramatically, and 40.0% of patients with NASH at baseline showed a decrease in plasma AKR1B10 levels to below the cutoff level after the surgery. In an independent validation study, we proved that plasma AKR1B10 was a specific biomarker of NAFLD progression across varying degrees of renal dysfunction. Despite perfect correlation between plasma and serum levels of AKR1B10 in paired sample analysis, its serum level was 1.4-fold higher than that in plasma. Plasma AKR1B10 alone and in combination with C3 could be a useful noninvasive biomarker for the diagnosis of NASH and hepatic fibrosis.

Axionlike Particles at Future Neutrino Experiments: Closing the Cosmological Triangle.

Axionlike particles (ALPs) provide a promising direction in the search for new physics, while a wide range of models incorporate ALPs. We point out that future neutrino experiments, such as DUNE, possess competitive sensitivity to ALP signals. The high-intensity proton beam impinging on a target can not only produce copious amounts of neutrinos, but also cascade photons that are created from charged particle showers stopping in the target. Therefore, ALPs interacting with photons can be produced (often energetically) with high intensity via the Primakoff effect and then leave their signatures at the near detector through the inverse Primakoff scattering or decays to a photon pair. Moreover, the high-capability near detectors allow for discrimination between ALP signals and potential backgrounds, improving the signal sensitivity further. We demonstrate that a DUNE-like detector can explore a wide range of parameter space in ALP-photon coupling g_{aγ} vs ALP mass m_{a}, including some regions unconstrained by existing bounds; the "cosmological triangle" will be fully explored and the sensitivity limits would reach up to m_{a}∼3-4 GeV and down to g_{aγ}∼10^{-8} GeV^{-1}.

Exosomes released from Shiga toxin 2a-treated human macrophages modulate inflammatory responses and induce cell death in toxin receptor expressing human cells.

Shiga toxins (Stxs) produced by Stx-producing Escherichia coli are the primarily virulence factors of hemolytic uremic syndrome and central nervous system (CNS) impairment. Although the precise mechanisms of toxin dissemination remain unclear, Stxs bind to extracellular vesicles (EVs). Exosomes, a subset of EVs, may play a key role in Stx-mediated renal injury. To test this hypothesis, we isolated exosomes from monocyte-derived macrophages in the presence of Stx2a or Stx2 toxoids. Macrophage-like differentiated THP-1 cells treated with Stxs secreted Stx-associated exosomes (Stx-Exo) of 90-130 nm in diameter, which induced cytotoxicity in recipient cells in a toxin receptor globotriaosylceramide (Gb3 )-dependent manner. Stx2-Exo engulfed by Gb3 -positive cells were translocated to the endoplasmic reticulum in the human proximal tubule epithelial cell line HK-2. Stx2-Exo contained pro-inflammatory cytokine mRNAs and proteins and induced more severe inflammation than purified Stx2a accompanied by greater death of target cells such as human renal or retinal pigment epithelial cells. Blockade of exosome biogenesis using the pharmacological inhibitor GW4869 reduced Stx2-Exo-mediated human renal cell death. Stx2-Exo isolated from human primary monocyte-derived macrophages activated caspase 3/7 and resulted in significant cell death in primary human renal cortical epithelial cells. Based on these results, we speculate that Stx-containing exosomes derived from macrophages may exacerbate cytotoxicity and inflammation and trigger cell death in toxin-sensitive cells. Therapeutic interventions targeting Stx-containing exosomes may prevent or ameliorate Stx-mediated acute vascular dysfunction.

New Directions for Axion Searches via Scattering at Reactor Neutrino Experiments.

Searches for pseudoscalar axionlike-particles (ALPs) typically rely on their decay in beam dumps or their conversion into photons in haloscopes and helioscopes. We point out a new experimental direction for ALP probes via their production by the intense gamma ray flux available from megawatt-scale nuclear reactors at neutrino experiments through Primakoff-like or Compton-like channels. Low-threshold detectors in close proximity to the core will have visibility to ALP decays and inverse Primakoff and Compton scattering, providing sensitivity to the ALP-photon and ALP-electron couplings. We find that the sensitivity to these couplings at the ongoing MINER and various other reactor based neutrino experiments, e.g., CONNIE, CONUS, ν-cleus, etc., exceeds existing limits set by laboratory experiments and, for the ALP-electron coupling, we forecast the world's best laboratory-based constraints over a large portion of the sub-MeV ALP mass range.

Dark Matter Signals from Timing Spectra at Neutrino Experiments.

We propose a novel strategy to search for new physics in timing spectra at low-energy neutrino experiments using a pulsed beam, envisioning the situation in which a new particle comes from the decay of its heavier partner with a finite particle width. The timing distribution of events induced by the dark matter (DM) candidate particle scattering at the detector may populate in a relatively narrow range, forming a "resonancelike" shape. Because of this structural feature, the signal may be isolated from the backgrounds, in particular when the backgrounds are uniformly distributed in energy and time. For proof of the principle, we investigate the discovery potential for DM from the decay of a dark photon in the ongoing COHERENT experiment and show the exciting prospects for exploring the associated parameter space with this experiment. We analyze the existing CsI detector data with a timing cut and an energy cut, and we find, for the first time, an excess in the timing distribution that can be explained by such DM. We compare the sensitivity to the kinetic mixing parameter (ε) for current and future COHERENT experiments with the projected limits from LDMX and DUNE.

Efficient Multimodal MRI Evaluation for Endovascular Thrombectomy of Anterior Circulation Large Vessel Occlusion.

BACKGROUND: MRI and CT modalities are both current standard-of-care options for initial imaging in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). MR provides greater lesion conspicuity and spatial resolution, but few series have demonstrated multimodal MR may be performed efficiently. METHODS: In a prospective comprehensive stroke center registry, we analyzed all anterior circulation LVO thrombectomy patients between 2012-2017 who: (1) arrived directly by EMS from the field, and (2) had initial NIHSS ≥6. Center imaging policy was multimodal MRI (including DWI/GRE/MRA w/wo PWI) as the initial evaluation in all patients without contraindications, and multimodal CT (including CT with CTA, w/wo CTP) in the remainder. RESULTS: Among 106 EMS-arriving endovascular thrombectomy patients, initial imaging was MRI 62.3%, CT in 37.7%. MRI and CT patients were similar in age (72.5 vs 71.3), severity (NIHSS 16.4 v 18.2), and medical history, though MRI patients had longer onset-to-door times. Overall, door-to-needle (DTN) and door-to-puncture (DTP) times did not differ among MR and CT patients, and were faster for both modalities in 2015-2017 versus 2012-2014. In the 2015-2017 period, for MR-imaged patients, the median DTN 42m (IQR 34-55) surpassed standard (60m) and advanced (45m) national targets and the median DTP 86m (IQR 71-106) surpassed the standard national target (90m). CONCLUSIONS: AIS-LVO patients can be evaluated by multimodal MR imaging with care speeds faster than national recommendations for door-to-needle and door-to-puncture times. With its more sensitive lesion identification and spatial resolution, MRI remains a highly viable primary imaging strategy in acute ischemic stroke patients, though further workflow efficiency improvements are desirable.

Risk Factors for Recurrence of Right Colonic Diverticulitis.

BACKGROUND: Right colonic diverticulitis (RCD) is more common in Asian countries than in Western countries, and the risk factors for recurrence of RCD are not fully understood. The objective of this study was to assess the risk factors for recurrence of RCD. METHODS: We analyzed 296 patients admitted for treatment of RCD in the Gachon University Gil Medical Center from December 2001 to October 2014. Gender, age, BMI, obesity, hypertension, diabetes mellitus, alcohol consumption, smoking, Hinchey classification, and hospital stay were investigated as risk factors for recurrence. RESULTS: Of the 296 patients with RCD, 31 patients recurred after conservative treatment. The median time interval between the initial episode and recurrence of diverticulitis was 10.4 months. In the univariate analysis, a high recurrence rate was observed in patients with a history of alcohol consumption, smoking, and long hospital stay. In the multivariate analysis, the recurrence rate was much higher (p < 0.001) in patients who stayed in the hospital for more than 10 days after the first attack. Smoking also elevated the recurrence rate (p = 0.011). CONCLUSION: Factors associated with recurrence of RCD may include smoking and the long hospital stay due to complexity when first diverticulitis occurs. Further prospective large-scale studies are needed to draw a definite conclusion.

Attachment of flagellin enhances the immunostimulatory activity of a hemagglutinin-ferritin nano-cage.

Hemagglutinin (HA) displayed on a ferritin nano-cage has been shown to be effective in generating a potent immune response against a broad range of influenza infections. Here, we showed that conjugation of flagellin together with HA to the exterior surface of the ferritin cage greatly enhanced not only the humoral immune response in mice but also antigen-specific T cell responses that include Th1 cytokine secretion. The effect of flagellin remained essentially unchanged when the molar ratio of flagellin to HA was reduced from 1:1 to 1:3. Injection of the ferritin-HA-flagellin cage provided protection against lethal virus challenge in mice. We used a small immunoglobulin fragment VL12.3 as a convenient method for attaching HA and flagellin to the ferritin cage. This attachment method can be used for rapid screening of a variety of protein cages and nano-assemblies to identify the most suitable carrier and adjuvant proteins for the target antigen.

MicroRNA-150 controls differentiation of intraepithelial lymphocytes through TGF-ß receptor II regulation.

BACKGROUND: Intraepithelial lymphocytes (IELs) in the intestines play pivotal roles in maintaining the integrity of the mucosa, regulating immune cells, and protecting against pathogenic invasion. Although several extrinsic factors, such as TGF-ß, have been identified to contribute to IEL generation, intrinsic regulatory factors have not been determined fully. OBJECTIVE: Here we investigated the regulation of IEL differentiation and the underlying mechanisms in mice. METHODS: We analyzed IELs and the expression of molecules associated with IEL differentiation in wild-type control and microRNA (miRNA)-150 knockout mice. Methotrexate was administered to mice lacking miR-150 and control mice. RESULTS: miR-150 deficiency reduced the IEL population in the small intestine and increased susceptibility to methotrexate-induced mucositis. Evaluation of expression of IEL differentiation-associated molecules showed that miR-150-deficient IELs exhibited decreased expression of TGF-ß receptor (TGF-ßR) II, CD103, CD8αα, and Runt-related transcription factor 3 in all the IEL subpopulations. The reduced expression of TGF-ßRII in miR-150-deficient IELs was caused by increased expression of c-Myb/miR-20a. Restoration of miR-150 or inhibition of miR-20a recovered the TGF-ßRII expression. CONCLUSION: miR-150 is an intrinsic regulator of IEL differentiation through TGF-ßRII regulation. miR-150-mediated IEL generation is crucial for maintaining intestinal integrity against anticancer drug-induced mucositis.

To Treat or Not to Treat?

Background and Purpose- The 2015 updated US Food and Drug Administration alteplase package insert altered several contraindications. We thus explored clinical factors influencing alteplase treatment decisions for patients with minor stroke. Methods- An expert panel selected 7 factors to build a series of survey vignettes: National Institutes of Health Stroke Scale (NIHSS), NIHSS area of primary deficit, baseline functional status, previous ischemic stroke, previous intracerebral hemorrhage, recent anticoagulation, and temporal pattern of symptoms in first hour of care. We used a fractional factorial design (150 vignettes) to provide unconfounded estimates of the effect of all 7 main factors, plus first-order interactions for NIHSS. Surveys were emailed to national organizations of neurologists, emergency physicians, and colleagues. Physicians were randomized to 1 of 10 sets of 15 vignettes, presented randomly. Physicians reported the subjective likelihood of giving alteplase on a 0 to 5 scale; scale categories were anchored to 6 probabilities from 0% to 100%. A conjoint statistical analysis was applied. Results- Responses from 194 US physicians yielded 156 with complete vignette data: 74% male, mean age 46, 80% neurologists. Treatment mean probabilities for individual vignettes ranged from 6% to 95%. Treatment probability increased from 24% for NIHSS score =1 to 41% for NIHSS score =5. The conjoint model accounted for 25% of total observed response variance. In contrast, a model accounting for all possible interactions accounted for 30% variance. Four of the 7 factors accounted jointly for 58% of total relative importance within the conjoint model: previous intracerebral hemorrhage (18%), recent anticoagulation (17%), NIHSS (13%), and previous ischemic stroke (10%). Conclusions- Four main variables jointly account for only a small fraction (<15%) of the total variance related to deciding to treat with intravenous alteplase, reflecting high variability and complexity. Future studies should consider other variables, including physician characteristics.

Correction to: Simultaneous detection of severe acute respiratory syndrome, Middle East respiratory syndrome, and related bat coronaviruses by real-time reverse transcription PCR.

Unfortunately, the concentration unit of plasmids was published incorrectly in the original publication of the article. The concentration unit, 'copies/ml' should be corrected to 'copies/µl'. This changes do not affect to the analytic sensitivity of the method because the detection limits of 50-100 copies/µL and 5-100 copies/µL using pUC57-SARS-pS2 (a template for SARS-CoV) and pGEM-MERS-S2 (a template for MERS-CoV), respectively, were as sensitive as other real-time PCR methods [1].

Virological and pathological characterization of an avian H1N1 influenza A virus.

Gene segments from avian H1N1 influenza A viruses have reassorted with other influenza viruses to generate pandemic strains over the past century. Nevertheless, little effort has been invested in understanding the characteristics of avian H1N1 influenza viruses. Here, we present the genome sequence and a molecular and virological characterization of an avian influenza A virus, A/wild bird/Korea/SK14/2014 (A/SK14, H1N1), isolated from migratory birds in South Korea during the winter season of 2014-2015. Full-genome sequencing and phylogenetic analysis revealed that the virus belongs to the Eurasian avian lineage. Although it retained avian-receptor binding preference, A/SK14 virus also exhibited detectable human-like receptor binding and was able to replicate in differentiated primary normal human bronchial epithelial cells. In animal models, A/SK14 virus was moderately pathogenic in mice, and virus was detected in nasal washes from inoculated guinea pigs, but not in direct-contact guinea pigs. Although A/SK14 showed moderate pathogenicity and no evidence of transmission in a mammalian model, our results suggest that the dual receptor specificity of A/SK14-like virus might allow for a more rapid adaptation to mammals, emphasizing the importance of further continuous surveillance and risk-assessment activities.

Dark Matter "Collider" from Inelastic Boosted Dark Matter.

We propose a novel dark matter (DM) detection strategy for models with a nonminimal dark sector. The main ingredients in the underlying DM scenario are a boosted DM particle and a heavier dark sector state. The relativistic DM impinged on target material scatters off inelastically to the heavier state, which subsequently decays into DM along with lighter states including visible (standard model) particles. The expected signal event, therefore, accompanies a visible signature by the secondary cascade process associated with a recoiling of the target particle, differing from the typical neutrino signal not involving the secondary signature. We then discuss various kinematic features followed by DM detection prospects at large-volume neutrino detectors with a model framework where a dark gauge boson is the mediator between the standard model particles and DM.

Simultaneous detection of severe acute respiratory syndrome, Middle East respiratory syndrome, and related bat coronaviruses by real-time reverse transcription PCR.

Since severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) share similar characteristics with respect to clinical signs, etiology, and transmission, methods for a rapid and accurate differential diagnosis are important. Therefore, the aim of this study was to develop a duplex real-time reverse transcription (RT)-PCR method for the simultaneous detection of these viruses. Primers and probes that target the conserved spike S2 region of human SARS-CoV, MERS-CoV, and their related bat CoVs were designed. The results of real-time RT-PCR showed specific reactions for each virus with adequate detection limits of 50-100 copies/mL and 5-100 copies/mL using pUC57-SARS-pS2 (a template for SARS-CoV) and pGEM-MERS-S2 (a template for MERS-CoV), respectively. In addition, this real-time RT-PCR system was able to detect the target viruses SARS-like bat CoV and MERS-CoV in bat fecal samples and sputum of MERS patients, respectively. Therefore, this newly developed real-time RT-PCR method is expected to detect not only SARS-CoV and MERS-CoV in humans but also several bat CoVs that are closely related to these viruses in bats.

IL-12p40 Homodimer Ameliorates Experimental Autoimmune Arthritis.

IL-23 is the key cytokine that induces the expansion of Th17 cells. It is composed of p19 and p40 subunits of IL-12. The p40 subunit binds competitively to the receptor of IL-23 and blocks its activity. Our aim was to assess the preventive and therapeutic effect of the IL-12p40 homodimer (p40)2 subunit in autoimmune arthritis animal models. In the current study, using IL-1R antagonist-knockout mice and a collagen-induced arthritis model, we investigated the suppressive effect of (p40)2 on inflammatory arthritis. We demonstrated that the recombinant adenovirus-expressing mouse (p40)2 model prevented the development of arthritis when given before the onset of arthritis. It also decreased the arthritis index and joint erosions in the mouse model if transferred after arthritis was established. (p40)2 inhibited the production of inflammatory cytokines and Ag-specific T cell proliferation. It also induced CD4(+)CD25(+)Foxp3 regulatory T (Treg) cells in vitro and in vivo, whereas the generation of retinoic acid receptor-related organ receptor γt and Th17 cells was suppressed. The induction of Treg cells and the suppression of Th17 cells were mediated via activated STAT5 and suppressed STAT3. Our data suggest that (p40)2 suppressed inflammatory arthritis successfully. This could be a useful therapeutic approach in autoimmune arthritis to regulate the Th17/Treg balance and IL-23 signaling.

Fluid-Attenuated Inversion Recovery Vascular Hyperintensity Topography, Novel Imaging Marker for Revascularization in Middle Cerebral Artery Occlusion.

BACKGROUND AND PURPOSE: In acute arterial occlusion, fluid-attenuated inversion recovery vascular hyperintensity (FVH) has been linked to slow flow in leptomeningeal collaterals and cerebral hypoperfusion, but the impact on clinical outcome is still controversial. In this study, we aimed to investigate the association between FVH topography or FVH-Alberta Stroke Program Early CT Score (ASPECTS) pattern and outcome in acute M1-middle cerebral artery occlusion patients with endovascular treatment. METHODS: We included acute M1-middle cerebral artery occlusion patients treated with endovascular therapy (ET). All patients had diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery before ET. Distal FVH-ASPECTS was evaluated according to distal middle cerebral artery-ASPECT area (M1-M6) and acute DWI lesion was also reviewed. The presence of FVH inside and outside DWI-positive lesions was separately analyzed. Clinical outcome after ET was analyzed with respect to different distal FVH-ASPECTS topography. RESULTS: Among 101 patients who met inclusion criteria for the study, mean age was 66.2±17.8 years and median National Institutes of Health Stroke Scale was 17.0 (interquartile range, 12.0-21.0). FVH-ASPECTS measured outside of the DWI lesion was significantly higher in patients with good outcome (modified Rankin Scale [mRS] score of 0-2; 8.0 versus 4.0, P<0.001). Logistic regression demonstrated that FVH-ASPECTS outside of the DWI lesion was independently associated with clinical outcome of these patients (odds ratio, 1.3; 95% confidence interval, 1.06-1.68; P=0.013). FVH-ASPECTS inside the DWI lesion was associated with hemorrhagic transformation (odds ratio, 1.3; 95% confidence interval, 1.04-1.51; P=0.019). CONCLUSIONS: Higher FVH-ASPECTS measured outside the DWI lesion is associated with good clinical outcomes in patients undergoing ET. FVH-ASPECTS measured inside the DWI lesion was predictive of hemorrhagic transformation. The FVH pattern, not number, can serve as an imaging selection marker for ET in acute middle cerebral artery occlusion.

Intranasal Introduction of Fc-Fused Interleukin-7 Provides Long-Lasting Prophylaxis against Lethal Influenza Virus Infection.

UNLABELLED: Influenza A virus (IAV) infection frequently causes hospitalization and mortality due to severe immunopathology. Annual vaccination and antiviral drugs are the current countermeasures against IAV infection, but they have a limited efficacy against new IAV variants. Here, we show that intranasal pretreatment with Fc-fused interleukin-7 (IL-7-mFc) protects mice from lethal IAV infections. The protective activity of IL-7-mFc relies on transcytosis via neonatal Fc receptor (FcRn) in the lung and lasts for several weeks. Introduction of IL-7-mFc alters pulmonary immune environments, leading to recruitment of T cells from circulation and their subsequent residency as tissue-resident memory-like T (TRM-like) cells. IL-7-mFc-primed pulmonary TRM-like cells contribute to protection upon IAV infection by dual modes. First, TRM-like cells, although not antigen specific but polyclonal, attenuate viral replication at the early phase of IAV infection. Second, TRM-like cells augment expansion of IAV-specific cytotoxic T lymphocytes (CTLs), in particular at the late phase of infection, which directly control viruses. Thus, accelerated viral clearance facilitated by pulmonary T cells, which are either antigen specific or not, alleviates immunopathology in the lung and mortality from IAV infection. Depleting a subset of pulmonary T cells indicates that both CD4 and CD8 T cells contribute to protection from IAV, although IL-7-primed CD4 T cells have a more prominent role. Collectively, we propose intranasal IL-7-mFc pretreatment as an effective means for generating protective immunity against IAV infections, which could be applied to a potential prophylaxis for influenza pandemics in the future. IMPORTANCE: The major consequence of a highly pathogenic IAV infection is severe pulmonary inflammation, which can result in organ failure and death at worst. Although vaccines for seasonal IAVs are effective, frequent variation of surface viral proteins hampers development of protective immunity. In this study, we demonstrated that intranasal IL-7-mFc pretreatment protected immunologically naive mice from lethal IAV infections. Intranasal pretreatment with IL-7-mFc induced an infiltration of T cells in the lung, which reside as effector/memory T cells with lung-retentive markers. Those IL-7-primed pulmonary T cells contributed to development of protective immunity upon IAV infection, reducing pulmonary immunopathology while increasing IAV-specific cytotoxic T lymphocytes. Since a single treatment with IL-7-mFc was effective in the protection against multiple strains of IAV for an extended period of time, our findings suggest a possibility that IL-7-mFc treatment, as a potential prophylaxis, can be developed for controlling highly pathogenic IAV infections.

750 GeV Diphoton Excess May Not Imply a 750 GeV Resonance.

We discuss nonstandard interpretations of the 750 GeV diphoton excess recently reported by the ATLAS and CMS Collaborations which do not involve a new, relatively broad resonance with a mass near 750 GeV. Instead, we consider the sequential cascade decay of a much heavier, possibly quite narrow, resonance into two photons along with one or more additional particles. The resulting diphoton invariant mass signal is generically rather broad, as suggested by the data. We examine three specific event topologies-the "antler," the "sandwich," and the two-step cascade decay-and show that they all can provide a good fit to the observed published data. In each case, we delineate the preferred mass parameter space selected by the best fit. In spite of the presence of extra particles in the final state, the measured diphoton p_{T} spectrum is moderate due to its anticorrelation with the diphoton invariant mass. We comment on the future prospects of discriminating with higher statistics between our scenarios, as well as from more conventional interpretations.