Guiding the Eye: A Non-photorealistic Solution for Controlling Viewer Interest

In film and still photography, depth of field control is often employed to control viewer interest in an image. This technique is also used in computer animation, but, in a medium where artists have near infinite control, must we rely on replicating photorealism? This research is a viable, non-photorealistic solution to the problem of directing viewer interest. Vision is directed by reducing superfluous visual information from parts of the image, which do not directly affect the depictive meaning of that image. This concept is applied to images and animations rendered from three-dimensional, computergenerated scenes, where detail is defined as visual information pertaining to the surface properties of a given object. A system is developed to demonstrate this concept. The system uses distance from a user-defined origin as the main mechanism to modulate detail. This solution is implemented within a modeling and shading environment to serve as a non-photorealistic, functional alternative for depth of field. This approach is conceptually based on a model of human vision, specifically, the relationship between foveal and peripheral vision, and is artistically driven by various works in the disciplines of painting and illustration, that through the careful manipulation of detail, control interest and understanding within the image. The resulting images and animations produced by this system provide viable evidence that detail modulation can be used to control effectively viewer interest in an image eliminating the need to use photographic techniques like depth of field

Nitric oxide metabolites as biomarkers for influenza-like acute respiratory infections presenting to the emergency room

Aims: Nitric oxide (NO) is increased in the respiratory tract in pulmonary infections. The aim was to determine whether nasal wash NO metabolites could serve as biomarkers of viral pathogen and disease severity in children with influenza-like illness (ILI) presenting to the emergency department (ED) during the 2009 influenza A H1N1 pandemic. Methods: Children ≤18 years old presenting to the ED with ILI were eligible. Nasal wash specimens were tested for NO metabolites, nitrate and nitrite, by HPLC and for respiratory viruses by real-time PCR. Results: Eighty-nine patients with ILI were prospectively enrolled during Oct-Dec, 2009. In the entire cohort, nasal wash nitrite was low to undetectable (interquartile range [IQR], 0 - 2 μM), while median nitrate was 3.4 μM (IQR 0-8.6). Rhinovirus (23%), respiratory syncytial virus (RSV) (20%), novel H1N1 (19%), and adenovirus (11%) were the most common viruses found. Children with RSV subtype B-associated ILI had higher nitrate compared to all other viruses combined (P=0.002). Conclusion: Concentration of NO-derived nitrate in nasal secretions in children in the ED is suggestive of viral pathogen causative for ILI, and thus might be of clinical utility. Predictive potential of this putative biomarker for ILI needs further evaluation in sicker patients in a prospective manner

Antigenic Site-Specific Competitive Antibody Responses to the Fusion Protein of Respiratory Syncytial Virus Were Associated With Viral Clearance in Hematopoietic Cell Transplantation Adults

Background: Recent studies of human sera showed that the majority of the respiratory syncytial virus (RSV) neutralizing antibodies are directed against pre-fusion conformation of the fusion (F) protein of RSV and revealed the importance of pre-fusion antigenic site Ø specific antibodies. However, detailed analysis of multiple antigenic site-specific competitive antibody responses to RSV F protein and their contribution to virus clearance in humans are lacking.Methods: We prospectively enrolled a cohort of RSV infected hematopoietic cell transplantation (HCT) adults (n = 40). Serum samples were collected at enrollment (acute, n = 40) and 14 to 60 days post-enrollment (convalescent, n = 40). Antigenic site-specific F protein antibodies were measured against pre-fusion site Ø, post-fusion site I, and sites II and IV present in both the pre-fusion and post-fusion F protein conformations utilizing four different competitive antibody assays developed with biotinylated monoclonal antibodies (mAb) D25, 131-2A, palivizumab, and 101F, respectively. The lower limit of detection were 7.8 and 1.0 μg/mL for the competitive antibody assays that measured site Ø specific response, as well as sites I, II, and IV specific responses, respectively. Neutralizing antibody titers to RSV A and B subgroups was determined by microneutralization assays.Results: The overall findings in RSV infected HCT adults revealed: (1) a significant increase in antigenic site-specific competitive antibodies in convalescent sera except for site Ø competitive antibody (p < 0.01); (2) comparable concentrations in the acute and convalescent serum samples of antigenic site-specific competitive antibodies between RSV/A and RSV/B infected HCT adults (p > 0.05); (3) significantly increased concentrations of the antigenic site-specific competitive antibodies in HCT adults who had genomic RSV detected in the upper respiratory tract for <14 days compared to those for ≥14 days (p < 0.01); and (4) statistically significant correlation between the antigenic site-specific competitive antibody concentrations and neutralizing antibody titers against RSV/A and RSV/B (r ranged from 0.33 to 0.83 for acute sera, and 0.50–0.88 for convalescent sera; p < 0.05).Conclusions: In RSV infected HCT adults, antigenic site-specific antibody responses were induced against multiple antigenic sites found in both the pre-fusion and post-fusion F conformations, and were associated with a more rapid viral clearance and neutralizing antibody activity. However, the association is not necessarily the cause and the consequence

Multiple RSV strains infecting HEp-2 and A549 cells reveal cell line-dependent differences in resistance to RSV infection

Background: Respiratory syncytial virus (RSV) is the major viral driver of a global pediatric respiratory disease burden disproportionately borne by the poor1. Thus, RSV, like SARS-CoV-2, combines with congenital and environmental and host-history-dependent factors to create a spectrum of disease with greatest severity most frequently occurring in those least able to procure treatment. Methods: Here we apply whole genome sequencing and a suite of other molecular biological techniques to survey host-virus dynamics in infections of two distinct cell lines (HEp2 and A549) with four strains representative of known RSV genetic diversity. Results: We observed non-gradient patterns of RSV gene expression and a single major difference in transcriptional readthrough correlating with a deep split in the RSV phylogenetic tree. We also observed increased viral replication in HEp2 cells along with a pro-inflammatory host-response; and decreased viral replication in A549 cells with a more potent antiviral response in host gene expression and levels of secreted cytokines. Conclusions: Our findings suggest HEp2 and A549 cell lines can be used as complementary models of host response leading to more or less severe RSV disease. In vitro perturbations inspired by actual environmental and host-history-dependent factors associated with greater disease can be tested for their ability to shift the antiviral response of A549 cells to the more pro-inflammatory response of HEp2 cells. Such studies would help illuminate the tragic costs of poverty and suggest public health-level interventions to reduce the global disease burden from RSV and other respiratory viruses

A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats

ABSTRACT Although respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (ΔSH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-ΔSH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log 10 total PFU and 2.7 log 10 PFU/g of tissue, respectively, compared to those in unvaccinated animals ( P < 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity. IMPORTANCE RSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV-naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by incorporating a low-fusion, subgroup B F protein in the genetic background of codon-deoptimized nonstructural protein genes and a deleted small hydrophobic protein gene. The resultant vaccine candidate, DB1, was attenuated, highly immunogenic, and protective against RSV challenge in cotton rats

A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation

Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization and there remains no pediatric vaccine. RSV live-attenuated vaccines (LAVs) have a history of safe testing in infants; however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we seek to engineer an RSV LAV with enhanced immunogenicity. Genetic mapping identifies strain line 19 fusion (F) protein residues that correlate with pre-fusion antigen maintenance by ELISA and thermal stability of infectivity in live RSV. We generate a LAV candidate named OE4 which expresses line 19F and is attenuated by codon-deoptimization of non-structural (NS1 and NS2) genes, deletion of the small hydrophobic (SH) gene, codon-deoptimization of the attachment (G) gene and ablation of the secreted form of G. OE4 (RSV-A2-dNS1-dNS2-ΔSH-dGm-Gsnull-line19F) exhibits elevated pre-fusion antigen levels, thermal stability, immunogenicity, and efficacy despite heavy attenuation in the upper and lower airways of cotton rats

Measurement of the Lifetime Difference Between B_s Mass Eigenstates

We present measurements of the lifetimes and polarization amplitudes for B_s --> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and light (L) mass eigenstates in the B_s system are separately measured for the first time by determining the relative contributions of amplitudes with definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07 +{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s and average Gamma_s, of the decay rates of the two eigenstates, the results are DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47 +{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters on 16 March 2005; revisions are for length and typesetting only, no changes in results or conclusion

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study

Background: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). Methods: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxyterminal telopeptide of type I collagen (b-CTX) were analysed. Results: Patients with RCC who died or progressed had higher baseline b-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline b-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that b-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. Conclusion: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOLNovartis Oncology Spain for supporting this stud

Search for higgsinos decaying to two Higgs bosons and missing transverse momentum in proton-proton collisions at √s = 13 TeV

Results are presented from a search for physics beyond the standard model in proton-proton collisions at s? = 13 TeV in channels with two Higgs bosons, each decaying via the process H ? bb¯¯¯ , and large missing transverse momentum. The search uses a data sample corresponding to an integrated luminosity of 137 fb?1 collected by the CMS experiment at the CERN LHC. The search is motivated by models of supersymmetry that predict the production of neutralinos, the neutral partners of the electroweak gauge and Higgs bosons. The observed event yields in the signal regions are found to be consistent with the standard model background expectations. The results are interpreted using simplified models of supersymmetry. For the electroweak production of nearly mass-degenerate higgsinos, each of whose decay chains yields a neutralino (??01) that in turn decays to a massless goldstino and a Higgs boson, (??01) masses in the range 175 to 1025 GeV are excluded at 95% confidence level. For the strong production of gluino pairs decaying via a slightly lighter (??02) to H and a light (??01) , gluino masses below 2330 GeV are excluded.We congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC and thank the technical and administrative staffs at CERN and at other CMS institutes for their contributions to the success of the CMS effort. In addition, we gratefully acknowledge the computing center s and personnel of the Worldwide LHC Computing Grid and other center s for delivering so effectively the computing infrastructure essential to our analyses. Finally, we acknowledge the enduring support for the construction and operation of the LHC, the CMS detector, and the supporting computing infrastructure provided by the following funding agencies: BMBWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, FAPERGS, and FAPESP (Brazil); MES and BNSF (Bulgaria); CERN; CAS, MoST, and NSFC (China); MINCIENCIAS (Colombia); MSES and CSF (Croatia); RIF (Cyprus); SENESCYT (Ecuador); MoER, ERC PUT and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRI (Greece); NKFIA (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); MSIP and NRF (Republic of Korea); MES (Latvia); LAS (Lithuania); MOE and UM (Malaysia); BUAP, CINVESTAV, CONACYT, LNS, SEP, and UASLP-FAI (Mexico); MOS (Montenegro); MBIE (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Dubna); MON, RosAtom, RAS, RFBR, and NRC KI (Russia); MESTD (Serbia); MCIN/AEI and PCTI (Spain); MOSTR (Sri Lanka); Swiss Funding Agencies (Switzerland); MST (Taipei); ThEPCenter, IPST, STAR, and NSTDA (Thailand); TUBITAK and TAEK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (U.S.A.). Individuals have received support from the Marie-Curie program and the European Research Council and Horizon 2020 Grant, contract Nos. 675440, 724704, 752730, 758316, 765710, 824093, 884104, and COST Action CA16108 (European Union); the Leventis Foundation; the Alfred P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium); the F.R.S.-FNRS and FWO (Belgium) under the “Excellence of Science — EOS” — be.h project n. 30820817; the Beijing Municipal Science & Technology Commission, No. Z191100007219010; the Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Deutsche Forschungsgemeinschaft (DFG), under Germany’s Excellence Strategy — EXC 2121 “Quantum Universe” — 390833306, and under project number 400140256-GRK2497; the Lendület (“Momentum”) Program and the János Bolyai Research Scholarship of the Hungarian Academy of Sciences, the New National Excellence Program ÚNKP, the NKFIA research grants 123842, 123959, 124845, 124850, 125105, 128713, 128786, and 129058 (Hungary); the Council of Science and Industrial Research, India; the Latvian Council of Science; the Ministry of Science and Higher Education and the National Science Center, contracts Opus 2014/15/B/ST2/03998 and 2015/19/B/ST2/02861 (Poland); the Fundação para a Ciência e a Tecnologia, grant CEECIND/01334/2018 (Portugal); the National Priorities Research Program by Qatar National Research Fund; the Ministry of Science and Higher Education, projects no. 0723- 2020-0041 and no. FSWW-2020-0008, and the Russian Foundation for Basic Research, project No. 19-42-703014 (Russia); MCIN/AEI/10.13039/501100011033, ERDF “a way of making Europe”, and the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2017-0765 and Programa Severo Ochoa del Principado de Asturias (Spain); the Stavros Niarchos Foundation (Greece); the Rachadapisek Sompot Fund for Postdoctoral Fellowship, Chulalongkorn University and the Chulalongkorn Academic into Its 2nd Century Project Advancement Project (Thailand); the Kavli Foundation; the Nvidia Corporation; the SuperMicro Corporation; the Welch Foundation, contract C-1845; and the Weston Havens Foundation (U.S.A.)

Observation of forward neutron multiplicity dependence of dimuon acoplanarity in ultraperipheral Pb-Pb collisions at √ S-NN=5.02 TeV

The first measurement of the dependence of γγ → μ+μ− production on the multiplicity of neutrons emitted very close to the beam direction in ultraperipheral heavy ion collisions is reported. Data for lead-lead interactions at √sNN = 5.02 TeV, with an integrated luminosity of approximately 1.5 nb−¹, are collected using the CMS detector at the LHC. The azimuthal correlations between the two muons in the invariant mass region 8 8.3. The back-to-back correlation structure from leading-order photon-photon scattering is found to be significantly broader for events with a larger number of emitted neutrons from each nucleus, corresponding to interactions with a smaller impact parameter. This observation provides a data-driven demonstration that the average transverse momentum of photons emitted from relativistic heavy ions has an impact parameter dependence. These results provide new constraints on models of photon-induced interactions in ultraperipheral collisions. They also provide a baseline to search for possible final-state effects on lepton pairs caused by traversing a quark-gluon plasma produced in hadronic heavy ion collisions.We congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC and thank the technical and administrative staffs at CERN and at other CMS institutes for their contributions to the success of the CMS effort. In addition, we gratefully acknowledge the computing centers and personnel of the Worldwide LHC Computing Grid for delivering so effectively the computing infrastructure essential to our analyses. Finally, we acknowledge the enduring support for the construction and operation of the LHC and the CMS detector provided by the following funding agencies: BMBWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, FAPERGS, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES and CSF (Croatia); RIF (Cyprus); SENESCYT (Ecuador); MoER, ERC PUT, and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); NKFIA (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); MSIP and NRF (Republic of Korea); MES (Latvia); LAS (Lithuania); MOE and UM (Malaysia); BUAP, CINVESTAV, CONACYT, LNS, SEP, and UASLP-FAI (Mexico); MOS (Montenegro); MBIE (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Dubna); MON, RosAtom, RAS, RFBR, and NRC KI (Russia); MESTD (Serbia); SEIDI, CPAN, PCTI, and FEDER (Spain); MOSTR (Sri Lanka); Swiss Funding Agencies (Switzerland); MST (Taipei); ThEPCenter, IPST, STAR, and NSTDA (Thailand); TUBITAK and TAEK (Turkey); NASU (Ukraine); STFC(United Kingdom); DOE and NSF (U.S.)