To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with ...dendritic cells (DC) pulsed with either MHC class I (MHC-I)-restricted epitopes alone or both MHC class I and II (MHC-I/II)-restricted epitopes. We enrolled 33 stage III and IV HLA-A*02:01-positive patients with melanoma in this study, of whom 29 were evaluable for immunologic response. Patients received intranodal vaccinations with cytokine-matured DCs loaded with keyhole limpet hemocyanin and MHC-I alone or MHC-I/II-restricted tumor-associated antigens (TAA) of tyrosinase and gp100, depending on their HLA-DR4 status. In 4 of 15 patients vaccinated with MHC-I/II-loaded DCs and 1 of 14 patients vaccinated with MHC-I-loaded DCs, we detected TAA-specific CD8(+) T cells with maintained IFN-γ production in skin test infiltrating lymphocyte (SKIL) cultures and circulating TAA-specific CD8(+) T cells. If TAA-specific CD4(+) T-cell responses were detected in SKIL cultures, it coincided with TAA-specific CD8(+) T-cell responses. In 3 of 13 patients tested, we detected TAA-specific CD4(+)CD25(+)FoxP3(-) T cells with high proliferative capacity and IFN-γ production, indicating that these were not regulatory T cells. Vaccination with MHC-I/II-loaded DCs resulted in improved clinical outcome compared with matched control patients treated with dacarbazine (DTIC), median overall survival of 15.0 versus 8.3 months (P = 0.089), and median progression-free survival of 5.0 versus 2.8 months (P = 0.0089). In conclusion, coactivating TAA-specific CD4(+) T-helper cells with DCs pulsed with both MHC class I and II-restricted epitopes augments TAA-specific CD8(+) T-cell responses, contributing to improved clinical responses.
Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the ...design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.
We report the beam energy (sqrtsNN=7.7-200 GeV) and collision centrality dependence of the mean (M), standard deviation (σ), skewness (S), and kurtosis (κ) of the net-proton multiplicity ...distributions in Au+Au collisions. The measurements are carried out by the STAR experiment at midrapidity (|y|<0.5) and within the transverse momentum range 0.4<pT<0.8 GeV/c in the first phase of the Beam Energy Scan program at the Relativistic Heavy Ion Collider. These measurements are important for understanding the quantum chromodynamic phase diagram. The products of the moments, Sσ and κσ2, are sensitive to the correlation length of the hot and dense medium created in the collisions and are related to the ratios of baryon number susceptibilities of corresponding orders. The products of moments are found to have values significantly below the Skellam expectation and close to expectations based on independent proton and antiproton production. The measurements are compared to a transport model calculation to understand the effect of acceptance and baryon number conservation and also to a hadron resonance gas model.
During protein crystallization and purification, proteins are commonly found in concentrated salt solutions. The exact interplay of the hydration shell, the salt ions, and proteinprotein interactions ...under these conditions is far from being understood on a fundamental level, despite the obvious practical relevance. We have studied a model globular protein (bovine serum albumin, BSA) in concentrated salt solutions by small-angle neutron scattering (SANS). The data are also compared to previous studies using SAXS. The SANS results for dilute protein solutions give an averaged volume of BSA of 91700
3
, which is about 37% smaller than that determined by SAXS. The difference in volume corresponds to the contribution of a hydration shell with a hydration level of 0.30 g g
1
protein. The forward intensity
I
(0) determined from Guinier analysis is used to determine the second virial coefficient,
A
2
, which describes the overall protein interactions in solution. It is found that
A
2
follows the reverse order of the Hofmeister series,
i.e.
(NH
4
)
2
SO
4
< Na
2
SO
4
< NaOAc < NaCl < NaNO
3
< NaSCN. The dimensionless second virial coefficient
B
2
, corrected for the particle volume and molecular weight, has been calculated using different approaches, and shows that
B
2
with corrections for hydration and the non-spherical shape of the protein describes the interactions better than those determined from the bare protein. SANS data are further analyzed in the full
q
-range using liquid theoretical approaches, which gives results consistent with the
A
2
analysis and the experimental structure factor.
The second virial coefficient,
A
2
, obtained by SANS for proteins in concentrated salt solutions, follows the reverse Hofmeister series.
In this clinical trial, patients who had a rheumatic disease and were receiving glucocorticoids were given either daily alendronate and alfacalcidol placebo or daily alfacalcidol and alendronate ...placebo. Alendronate was more effective than alfacalcidol in the prevention of glucocorticoid-induced bone loss in the lumbar spine.
In patients who had a rheumatic disease and were receiving glucocorticoids, alendronate was more effective than alfacalcidol in the prevention of glucocorticoid-induced bone loss in the lumbar spine.
Glucocorticoids are frequently used in patients with rheumatic diseases and are associated with increased bone loss and a risk of fracture.
1
–
3
An important effect of glucocorticoids on bone is the inhibition of bone formation by decreasing the number of osteoblasts and hampering their function.
4
,
5
Glucocorticoids also increase the rate of bone resorption by stimulating the formation and action of osteoclasts. Furthermore, glucocorticoids decrease intestinal absorption of calcium and increase renal calcium excretion.
5
–
8
Although daily doses of prednisone of 7.5 mg or more have been associated with glucocorticoid-induced osteoporosis,
9
,
10
lower doses of the drug have also been . . .
The dynamics of living organisms are organized across many spatial scales. However, current cost-effective imaging systems can measure only a subset of these scales at once. We have created a ...scalable multi-camera array microscope (MCAM) that enables comprehensive high-resolution recording from multiple spatial scales simultaneously, ranging from structures that approach the cellular scale to large-group behavioral dynamics. By collecting data from up to 96 cameras, we computationally generate gigapixel-scale images and movies with a field of view over hundreds of square centimeters at an optical resolution of 18 µm. This allows us to observe the behavior and fine anatomical features of numerous freely moving model organisms on multiple spatial scales, including larval zebrafish, fruit flies, nematodes, carpenter ants, and slime mold. Further, the MCAM architecture allows stereoscopic tracking of the z-position of organisms using the overlapping field of view from adjacent cameras. Overall, by removing the bottlenecks imposed by single-camera image acquisition systems, the MCAM provides a powerful platform for investigating detailed biological features and behavioral processes of small model organisms across a wide range of spatial scales.
Localizing Parts of Faces Using a Consensus of Exemplars Belhumeur, Peter N.; Jacobs, David W.; Kriegman, David J. ...
IEEE transactions on pattern analysis and machine intelligence,
12/2013, Letnik:
35, Številka:
12
Journal Article
Recenzirano
We present a novel approach to localizing parts in images of human faces. The approach combines the output of local detectors with a nonparametric set of global models for the part locations based on ...over 1,000 hand-labeled exemplar images. By assuming that the global models generate the part locations as hidden variables, we derive a Bayesian objective function. This function is optimized using a consensus of models for these hidden variables. The resulting localizer handles a much wider range of expression, pose, lighting, and occlusion than prior ones. We show excellent performance on real-world face datasets such as Labeled Faces in the Wild (LFW) and a new Labeled Face Parts in the Wild (LFPW) and show that our localizer achieves state-of-the-art performance on the less challenging BioID dataset.
Early thrombus removal might prevent post-thrombotic syndrome by preserving venous function and restoring flow. Previous trials comparing additional catheter-directed thrombolysis to standard ...treatment showed conflicting outcomes. We aimed to assess the benefit of additional ultrasound-accelerated catheter-directed thrombolysis for the prevention of post-thrombotic syndrome compared with standard therapy in patients with iliofemoral deep-vein thrombosis.
We did a multicentre, randomised, single-blind, allocation-concealed, parallel group, superiority trial in 15 hospitals in the Netherlands. Patients aged 18-85 years with a first-time acute iliofemoral deep-vein thrombosis and symptoms for no more than 14 days were randomly assigned (1:1) to either standard treatment with additional ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. Randomisation was done with a web-based automatic programme and a random varying block size (2-12), stratified by age and centre. Standard treatment included anticoagulant therapy, compression therapy (knee-high elastic compression stockings; 30-40 mmHg), and early ambulation. Additional ultrasound-accelerated catheter-directed thrombolysis was done with urokinase with a starting bolus of 250 000 international units (IU) in 10 mL NaCl followed by a continuous dose of 100 000 IU/h for a maximum of 96 h through the Ekos Endowave-system. Adjunctive percutaneous transluminal angioplasty, thrombosuction, or stenting was performed at the discretion of the physician who performed the intervention. The primary outcome was the proportion of patients with post-thrombotic syndrome at 12 months diagnosed according to the original Villalta criteria-a Villalta-score of at least 5 on two consecutive occasions at least 3 months apart or the occurrence of venous ulceration-and was assessed in a modified intention-to-treat population of all randomly assigned patients who passed screening and started treatment. The safety analysis was assessed in the same modified intention-to-treat population. This study is complete and is registered at ClinicalTrials.gov, NCT00970619.
Between May 28, 2010, and Sept 18, 2017, 184 patients were randomly assigned to either additional ultrasound-accelerated catheter-directed thrombolysis (n=91) or standard treatment alone (n=93). Exclusion because of screening failure or early withdrawal of informed consent resulted in 77 patients in the intervention group and 75 in the standard treatment group starting allocated treatment. Median follow-up was 12·0 months (IQR 6·0-12·0). 12-month post-thrombotic syndrome occurred in 22 (29%) patients allocated to additional treatment versus 26 (35%) patients receiving standard treatment alone (odds ratio 0·75 95% CI 0·38 to 1·50; p=0·42). Major bleeding occurred in four (5%) patients in the intervention group, with associated neuropraxia or the peroneal nerve in one patient, and no events in the standard treatment group. No serious adverse events occurred. None of the four deaths (one 1% in the intervention group vs three 4% in the standard treatment group) were treatment related.
This study showed that additional ultrasound-accelerated catheter-directed thrombolysis does not change the risk of post-thrombotic syndrome 1 year after acute iliofemoral deep-vein thrombosis compared with standard therapy alone. Although this trial is inconclusive, the outcome suggests the possibility of a moderate beneficial effect with additional ultrasound-accelerated catheter-directed thrombolysis. Further research is therefore warranted to better understand this outcome in the context of previous trials, preferably by combining the available evidence in an individual patient data meta-analysis.
The Netherlands Organisation for Health Research and Development (ZonMw), Maastricht University Medical Centre, BTG-Interventional Medicine.
Abstract
Objectives
To summarize the epidemiologic, clinical, and laboratory characteristics of autoimmune hemolytic anemia (AIHA) secondary to severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2) infection or vaccination.
Methods
We conducted a systematic review using standardized keyword search to identify all reports of SARS-CoV-2 infection or vaccination and AIHA across PubMed, Web of Science, Scopus, and Google Scholar through September 24, 2021.
Results
Fifty patients (mean SD age, 50.8 21.6 years) diagnosed with coronavirus disease 2019 (COVID-19) and AIHA were identified. AIHA subtypes and number of patients were as follows: cold AIHA (n = 18), warm AIHA (n = 14), mixed-type AIHA (n = 3), direct antiglobulin test (DAT)–negative AIHA (n = 1), DAT-negative Evans syndrome (n = 1), Evans syndrome (n = 3), and subtype not reported (n = 10). Mean (SD) hemoglobin at AIHA diagnosis was 6.5 2.8 g/dL (95% confidence interval, 5.7-7.3 g/dL). Median time from COVID-19 symptom onset to AIHA diagnosis was 7 days. In total, 19% (8/42) of patients with COVID-19–associated AIHA with reported outcomes were deceased. Four patients (mean SD age, 73.5 16.9 years) developed AIHA following SARS-CoV-2 vaccination: Pfizer-BioNTech BNT162b2 vaccine (n = 2); Moderna mRNA-1273 vaccine (n = 1); undisclosed mRNA vaccine (n = 1). AIHA occurred after 1 dose in 3 patients (median, 5 days).
Conclusions
SARS-CoV-2 infection and vaccination are associated with multiple AIHA subtypes, beginning approximately 7 days after infectious symptoms and 5 days after vaccination.
Lambertian reflectance and linear subspaces Basri, R.; Jacobs, D.W.
IEEE transactions on pattern analysis and machine intelligence,
02/2003, Letnik:
25, Številka:
2
Journal Article
Recenzirano
We prove that the set of all Lambertian reflectance functions (the mapping from surface normals to intensities) obtained with arbitrary distant light sources lies close to a 9D linear subspace. This ...implies that, in general, the set of images of a convex Lambertian object obtained under a wide variety of lighting conditions can be approximated accurately by a low-dimensional linear subspace, explaining prior empirical results. We also provide a simple analytic characterization of this linear space. We obtain these results by representing lighting using spherical harmonics and describing the effects of Lambertian materials as the analog of a convolution. These results allow us to construct algorithms for object recognition based on linear methods as well as algorithms that use convex optimization to enforce nonnegative lighting functions. We also show a simple way to enforce nonnegative lighting when the images of an object lie near a 4D linear space. We apply these algorithms to perform face recognition by finding the 3D model that best matches a 2D query image.
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