918 research outputs found
Sea Ice Meltwater and Circumpolar Deep Water Drive Contrasting Productivity in Three Antarctic Polynyas
In the Southern Ocean, polynyas exhibit enhanced rates of primary productivity and represent large seasonal sinks for atmospheric CO2. Three contrasting east Antarctic polynyas were visited in late December to early January 2017: the Dalton, Mertz, and Ninnis polynyas. In the Mertz and Ninnis polynyas, phytoplankton biomass (average of 322 and 354mg chlorophyll a (Chl a)/m(2), respectively) and net community production (5.3 and 4.6mol C/m(2), respectively) were approximately 3 times those measured in the Dalton polynya (average of 122mg Chl a/m(2) and 1.8mol C/m(2)). Phytoplankton communities also differed between the polynyas. Diatoms were thriving in the Mertz and Ninnis polynyas but not in the Dalton polynya, where Phaeocystis antarctica dominated. These strong regional differences were explored using physiological, biological, and physical parameters. The most likely drivers of the observed higher productivity in the Mertz and Ninnis were the relatively shallow inflow of iron-rich modified Circumpolar Deep Water onto the shelf as well as a very large sea ice meltwater contribution. The productivity contrast between the three polynyas could not be explained by (1) the input of glacial meltwater, (2) the presence of Ice Shelf Water, or (3) stratification of the mixed layer. Our results show that physical drivers regulate the productivity of polynyas, suggesting that the response of biological productivity and carbon export to future change will vary among polynyas
See-saw neutrino masses and large mixing angles in the vortex background on a sphere
In the vortex background on a sphere, a single 6-dimensional fermion family
gives rise to 3 zero-modes in the 4-dimensional point of view, which may
explain the replication of families in the Standard Model. Previously, it had
been shown that realistic hierarchical mass and mixing patterns can be
reproduced for the quarks and the charged leptons. Here, we show that the
addition of a single heavy 6-dimensional field that is gauge singlet, unbound
to the vortex, and embedded with a bulk Majorana mass enables to generate 4D
Majorana masses for the light neutrinos through the see-saw mechanism. The
scheme is very predictive. The hierarchical structure of the fermion zero-modes
leads automatically to an inverted pseudo-Dirac mass pattern, and always
predicts one maximal angle in the neutrino see-saw matrix. It is possible to
obtain a second large mixing angle from either the charged lepton or the
neutrino sector, and we demonstrate that this model can fit all observed data
in neutrino oscillations experiments. Also, U_{e3} is found to be of the order
~0.1.Comment: 23 pages, 1 figur
Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review.
Osteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment
Enduring efficacy and tolerability of daratumumab in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (GEN503): final results of an open-label, phase 1/2 study
Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells
The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al
Dynamical R-parity Breaking at the LHC
In a class of extensions of the minimal supersymmetric standard model with
(B-L)/left-right symmetry that explains the neutrino masses, breaking R-parity
symmetry is an essential and dynamical requirement for successful gauge
symmetry breaking. Two consequences of these models are: (i) a new kind of
R-parity breaking interaction that protects proton stability but adds new
contributions to neutrinoless double beta decay and (ii) an upper bound on the
extra gauge and parity symmetry breaking scale which is within the large hadron
collider (LHC) energy range. We point out that an important prediction of such
theories is a potentially large mixing between the right-handed charged lepton
() and the superpartner of the right-handed gauge boson (), which leads to a brand new class of R-parity violating interactions of
type and \widetilde{d^c}^\dagger\u^c
e^c. We analyze the relevant constraints on the sparticle mass spectrum and
the LHC signatures for the case with smuon/stau NLSP and gravitino LSP. We note
the "smoking gun" signals for such models to be lepton flavor/number violating
processes: (or ) and
(or ) without
significant missing energy. The predicted multi-lepton final states and the
flavor structure make the model be distinguishable even in the early running of
the LHC.Comment: 30 pages, 13 figures, 6 tables, reference adde
Seesaw Neutrino Signals at the Large Hadron Collider
We discuss the scenario with gauge singlet fermions (right-handed neutrinos)
accessible at the energy of the Large Hadron Collider. The singlet fermions
generate tiny neutrino masses via the seesaw mechanism and also have sizable
couplings to the standard-model particles. We demonstrate that these two facts,
which are naively not satisfied simultaneously, are reconciled in the
five-dimensional framework in various fashions, which make the seesaw mechanism
observable. The collider signal of tri-lepton final states with transverse
missing energy is investigated for two explicit examples of the observable
seesaw, taking account of three types of neutrino mass spectrum and the
constraint from lepton flavor violation. We find by showing the significance of
signal discovery that the collider experiment has a potential to find signals
of extra dimensions and the origin of small neutrino masses.Comment: 27 pages, 4 figure
Keratocyte loss in corneal infection through apoptosis: a histologic study of 59 cases
BACKGROUND: Keratocyte loss by apoptosis following epithelial debridement is a well-recognized entity. In a study of corneal buttons obtained from patients of corneal ulcer undergoing therapeutic keratoplasty, we observed loss of keratocytes in the normal appearing corneal stroma, surrounding the zone of inflammation. Based on these observations, we hypothesized that the cell loss in the inflammatory free zone of corneal stroma is by apoptosis that could possibly be a non-specific host response, independent of the nature of infectious agent. METHODS: To test our hypothesis, in this study, we performed Terminal deoxyribonucleotidyl transferase-mediated d-Uridine 5" triphosphate Nick End Labelling (TUNEL) staining on 59 corneal buttons from patients diagnosed as bacterial, fungal, viral and Acanthamoeba keratitis. The corneal sections were reviewed for morphologic changes in the epithelium, stroma, type, degree and depth of inflammation, loss of keratocytes in the surrounding stroma (posterior or peripheral). TUNEL positivity was evaluated in the corneal sections, both in the zone of inflammation as well as the surrounding stroma. A correlation was attempted between the keratocyte loss, histologic, microbiologic and clinical features. RESULTS: The corneal tissues were from 59 patients aged between 16 years and 85 years (mean 46 years) and included fungal (22), viral (15), bacterial (14) and Acanthamoeba (8) keratitis. The morphological changes in corneal tissues noted were: epithelial ulceration (52, 88.1%), destruction of Bowman's layer (58, 99%), mild to moderate (28; 47.5%) to severe inflammation (31; 52.5%). Morphologic evidence of disappearance or reduced number of keratocytic nuclei in the corneal stroma was noted in 49 (83%) cases; while the TUNEL positive brown cells were identified in all cases 53/54 (98%), including cases of fungal (19), bacterial (14), viral (13), and Acanthamoeba keratitis. TUNEL staining was located mostly in the deeper stroma and in few cases the peripheral stroma. TUNEL positivity was also noted with the polymorphonuclear infiltrates and in few epithelial cells (10 of 59, 17%) cases, more with viral infections (6/10; 60%). CONCLUSIONS: We report apoptotic cell death of keratocytes in the corneal stroma in infectious keratitis, a phenomenon independent of type of infectious agent. The inflammatory cells in the zone of inflammation also show evidence of apoptotic cell death. It could be speculated that the infective process possibly triggers keratocyte loss of the surrounding stroma by apoptosis, which could possibly be a protective phenomenon. It also suggests that necrotic cell death and apoptotic cell deaths could occur simultaneously in infective conditions of the cornea
A comparison of location of acute symptomatic vs. 'silent' small vessel lesions
Background: Acute lacunar ischaemic stroke, white matter hyperintensities, and lacunes are all features of cerebral small vessel disease. It is unclear why some small vessel disease lesions present with acute stroke symptoms, whereas others typically do not.
Aim: To test if lesion location could be one reason why some small vessel disease lesions present with acute stroke, whereas others accumulate covertly.
Methods: We identified prospectively patients who presented with acute lacunar stroke symptoms with a recent small subcortical infarct confirmed on magnetic resonance diffusion imaging. We compared the distribution of the acute infarcts with that of white matter hyperintensity and lacunes using computational image mapping methods.
Results: In 188 patients, mean age 67 ± standard deviation 12 years, the lesions that presented with acute lacunar ischaemic stroke were located in or near the main motor and sensory tracts in (descending order): posterior limb of the internal capsule (probability density 0·2/mm3), centrum semiovale (probability density = 0·15/mm3), medial lentiform nucleus/lateral thalamus (probability density = 0·09/mm3), and pons (probability density = 0·02/mm3). Most lacunes were in the lentiform nucleus (probability density = 0·01–0·04/mm3) or external capsule (probability density = 0·05/mm3). Most white matter hyperintensities were in centrum semiovale (except for the area affected by the acute symptomatic infarcts), external capsules, basal ganglia, and brainstem, with little overlap with the acute symptomatic infarcts (analysis of variance, P < 0·01).
Conclusions: Lesions that present with acute lacunar ischaemic stroke symptoms may be more likely noticed by the patient through affecting the main motor and sensory tracts, whereas white matter hyperintensity and asymptomatic lacunes mainly affect other areas. Brain location could at least partly explain the symptomatic vs. covert development of small vessel disease
Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study
Objective The FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) trial assessed efficacy and safety of the potential disease-modifying osteoarthritis drug (DMOAD) sprifermin in patients with knee osteoarthritis. Here, we report 5-year efficacy and safety results.
Methods Patients were randomised to intra-articular sprifermin 100 µg or 30 µg every 6 months (q6mo) or 12 months, or placebo, for 18 months. The primary analysis was at year 2, with follow-up at years 3, 4 and 5. Additional post hoc exploratory analyses were conducted in patients with baseline minimum radiographic joint space width 1.5–3.5 mm and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain 40–90, a subgroup at risk (SAR) of progression.
Results 378 (69%) patients completed the 5-year follow-up. A significant dose-response in total femorotibial joint cartilage thickness with sprifermin (trend test, p<0.001) and a 0.05 mm mean difference with sprifermin 100 µg q6mo versus placebo (95% CI 0.00 to 0.10; p=0.015) were sustained to year 5. WOMAC pain scores improved ~50% from baseline in all groups. No patient in the 100 µg q6mo group had replacement of the treated knee. 96%–98% of patients receiving sprifermin and 98% placebo reported adverse events, most were mild or moderate and deemed unrelated to treatment. Adverse event-related study withdrawals were <10%. Differentiation in WOMAC pain between sprifermin 100 µg q6mo and placebo in the SAR (n=161) at year 3 was maintained to year 5 (−10.08; 95% CI −25.68 to 5.53).
Conclusion In the longest DMOAD trial reported to date, sprifermin maintained long-term structural modification of articular cartilage over 3.5 years post-treatment. Potential translation to clinical benefit was observed in the SAR.
Trial registration number NCT0191916
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