Recent Submissions

  • Human HspB1, HspB3, HspB5 and HspB8: Shaping these disease factors during vertebrate evolution

    Institute for Genomics and Evolutionary Medicine (iGEM) (Temple University) (2024-01-04)
    Small heat shock proteins (sHSPs) emerged early in evolution and occur in all domains of life and nearly in all species, including humans. Mutations in four sHSPs (HspB1, HspB3, HspB5, HspB8) are associated with neuromuscular disorders. The aim of this study is to investigate the evolutionary forces shaping these sHSPs during vertebrate evolution. We performed comparative evolutionary analyses on a set of orthologous sHSP sequences, based on the ratio of non-synonymous: synonymous substitution rates for each codon. We found that these sHSPs had been historically exposed to different degrees of purifying selection, decreasing in this order: HspB8 > HspB1, HspB5 > HspB3. Within each sHSP, regions with different degrees of purifying selection can be discerned, resulting in characteristic selective pressure profiles. The conserved α-crystallin domains were exposed to the most stringent purifying selection compared to the flanking regions, supporting a 'dimorphic pattern' of evolution. Thus, during vertebrate evolution the different sequence partitions were exposed to different and measurable degrees of selective pressures. Among the disease-associated mutations, most are missense mutations primarily in HspB1 and to a lesser extent in the other sHSPs. Our data provide an explanation for this disparate incidence. Contrary to the expectation, most missense mutations cause dominant disease phenotypes. Theoretical considerations support a connection between the historic exposure of these sHSP genes to a high degree of purifying selection and the unusual prevalence of genetic dominance of the associated disease phenotypes. Our study puts the genetics of inheritable sHSP-borne diseases into the context of vertebrate evolution.
  • To go or not to go: multiple identities and the effects of ambivalence

    Yu, Qionglei; Huang, Yu-An; Li, Xiang (Robert); Ren, Zhimin (2022-05-22)
    This study unpacks how a person’s multiple identities affect their decision making when selecting a tourism destination. We propose that different aspects of identity yield distinct yet competing emotions. For instance, perceived social audience admiration combined with animosity might produce ambivalence, leading to greater decision-making uncertainty. Findings show that tourists with greater ambivalence towards particular destination countries are more likely to cancel or postpone their travel decisions. Additionally, the destination country’s economic development and a tourist’s pursuit of material happiness interact as moderators in the relationships between identities, emotions, and travel intention. Recommendations are provided for tourism product development and marketing communications for destination countries.
  • Updated QCD global analysis of single transverse-spin asymmetries: Extracting ˜H, and the role of the Soffer bound and lattice QCD

    Gamberg, Leonard; Malda, Michel; Miller, Joshua A.; Pitonyak, Daniel; Prokudin, Alexei; Sato, Nobuo (2022-08-12)
    We present an update to the QCD global analysis of single transverse-spin asymmetries presented in [J. Cammarota et al. (Jefferson Lab Angular Momentum Collaboration), Phys. Rev. D 102, 054002 (2020).] (JAM3D-20). JAM3D-20 simultaneously included transverse momentum dependent and collinear twist-3 observables, both of which are sensitive to quark-gluon-quark correlations in hadrons. In this study we extract for the first time the twist-3 chiral odd fragmentation function ˜H by incorporating the sinϕs modulation data from semi-inclusive deep-inelastic scattering along with its contribution to the single transverse-spin asymmetry in pion production from proton-proton collisions. We also explore the impact of lattice QCD tensor charge calculations and the Soffer bound on our global analysis. We find that both constraints can be accommodated within our results, with ˜H playing a key role in maintaining agreement with the data from proton-proton collisions.
  • Context-dependent amygdala-prefrontal connectivity in youths with autism spectrum disorder

    Christian, Isaac Ray; Liuzzi, Michael T.; Yu, Qiongru; Kryza-Lacombe, Maria; Monk, Christopher S.; Jarcho, Johanna; Wiggins, Jillian Lee (2022-01-17)
    Background: The amygdala-prefrontal cortex circuit is involved in processing socio-emotional cues and may partially mediate social impairment in autism spectrum disorder (ASD). Past task-based fMRI studies in ASD indicate a mix of hypo- and hyper-connectivity in response to socio-emotional stimuli whereas resting state studies report hypoconnectivity between these regions. However, it is still unknown whether ASD-related alterations in amygdala-prefrontal circuitry are present across socio-emotional tasks and resting state contexts within the same sample or instead, depend on context. Method: ASD (n = 47) and typically developing individuals (TD; n = 72) underwent fMRI during an implicit emotional face processing task and during rest, and whole-brain amygdala connectivity was calculated to determine patterns that differed by context and diagnosis. Results: Relative to TD, the ASD group demonstrated weaker left amygdala connectivity with the medial frontal gyrus and the left superior frontal gyrus during rest, but stronger connectivity during task. Furthermore, across both contexts, ASD vs. TD had stronger right amygdala connectivity with the left insula/superior temporal gyrus. Conclusion: Findings suggest some alterations in amygdala connectivity of ASD may depend on context while others are pervasive across task and rest conditions. Understanding context-dependent brain alterations in ASD may help disambiguate the mechanisms subserving social impairment and provide targets for treatment.
  • Studies of the symmetric binding mode of daclatasvir and analogs using a new homology model of HCV NS5A GT-4a

    Institute for Computational Molecular Science (Temple University) (2022-12-29)
    Context: Egypt has a high prevalence of the hepatitis C virus (HCV) genotype 4a (GT-4a). Unfortunately, the high resistance it exhibited still was not given the deserved attention in the scientific community. There is currently no consensus on the NS5A binding site because the crystal structure of HCV NS5A has not been resolved. The prediction of the binding modes of direct-acting antivirals (DAA) with the NS5A is a point of controversy due to the fact that several research groups presented different interaction models to elucidate the NS5A binding site. Consequently, a 3D model of HCV NS5A GT-4a was constructed and evaluated using molecular dynamics (MD) simulations. The generated model implies an intriguing new orientation of the AH relative to domain I. Additionally, the probable binding modes of marketed NS5A inhibitors were explored. MD simulations validated the stability of the predicted protein–ligand complexes. The suggested model predicts that daclatasvir and similar drugs bind symmetrically to HCV NS5A GT-4a. This will allow for the development of new NS5A-directed drugs, which may result in reduced resistance and/or a wider range of effectiveness against HCV. Methods: The 3D model of HCV NS5A GT-4a was constructed using the comparative modeling approach of the web-based application Robetta. Its stability was tested with 200-ns MD simulations using the Desmond package of Schrodinger. The OPLS2005 force field was assigned for minimization, and the RMSD, RMSF, and rGyr were tracked throughout the MD simulations. Fpocket was used to identify druggable protein pockets (cavities) over the simulation trajectories. The binding modes of marketed NS5A inhibitors were then generated and refined with the aid of docking predictions made by FRED and AutoDock Vina. The stability of these drugs in complex with GT-4a was investigated by using energetic and structural analyses over MD simulations. The Prime MM-GBSA (molecular mechanics/generalized Born surface area) method was used as a validation tool after the docking stage and for the averaged clusters after the MD simulation stage. We utilized PyMOL and VMD to visualize the data.
  • ATHENA detector proposal — a totally hermetic electron nucleus apparatus proposed for IP6 at the Electron-Ion Collider

    Kunnath, A.; Nam, Jae; Posik, M.; Surrow, Bernd; The ATHENA Collaboration; Nam|0000-0003-1893-5237; Surrow|0000-0001-5839-707X (2022-10-10)
    ATHENA has been designed as a general purpose detector capable of delivering the full scientific scope of the Electron-Ion Collider. Careful technology choices provide fine tracking and momentum resolution, high performance electromagnetic and hadronic calorimetry, hadron identification over a wide kinematic range, and near-complete hermeticity. This article describes the detector design and its expected performance in the most relevant physics channels. It includes an evaluation of detector technology choices, the technical challenges to realizing the detector and the R&D required to meet those challenges.
  • Burkhardt-Cottingham-type sum rules for light-cone and quasi-PDFs

    Bhattacharya, Shohini; Metz, Andreas; Bhattacharya|0000-0001-8536-082X (2022-03-25)
    The Burkhardt-Cottingham (BC) sum rule connects the twist-3 light-cone parton distribution function (PDF) gT(x) to the twist-2 helicity PDF g1(x). The chiral-odd counterpart of the BC sum rule relates the twist-3 light-cone PDF hL(x) to the twist-2 transversity PDF h1(x). These BC-type sum rules can also be derived for the corresponding quasi-PDFs. We perform a perturbative check of the BC-type sum rules in the quark target model and the Yukawa model, by going beyond the ultraviolet (UV) divergent terms. We employ dimensional regularization (DR) and cutoff schemes to regulate UV divergences, and show that the BC-type sum rules hold for DR, while they are generally violated when using a cutoff. This violation can be traced back to the breaking of rotational invariance. We find corresponding results for the sum rule relating the mass of the target to the twist-3 PDF e(x). Moreover, we supplement our analytical results with numerical calculations.
  • How bad is crime for business? Evidence from consumer behavior

    Fe, Hao; Sanfelice, Viviane; Sanfelice|0000-0003-0942-1138 (2022-03-30)
    Understanding how consumers respond to crime offers evidence of how safety perception impacts individuals daily choices and has important implications for economic development of communities. This paper investigates the impact of local crime on subsequent consumer visits to food and entertainment retails using a novel longitudinal dataset with point-specific crime and consumer visit data. We leverage the richness of our data to account for unobserved heterogeneity and time variant confounders through temporal and geographical variation. Our results show that consumers respond more strongly to property and street crimes. The response concentrates on the venue visit decision rather than the intensity of consumption (i.e. duration) in the venue.
  • The geographical dispersion of inventor networks in peripheral economies

    Cano-Kollmann, Marcelo; Mudambi, Ram; Tavares-Lehmann, Ana Teresa; Mudambi|0000-0002-5396-5602 (2022-05-07)
    In this paper we explore patenting activity in two peripheral economies (Portugal and Greece), to analyze the dispersion of inventor networks. Inventor networks are key conduits through which knowledge flows. Therefore, they can be critical in the catch-up process of peripheral economies – economies that belong to the group of rich countries but have weaker innovation systems. As global value chains fragment into geographically dispersed activities, opportunities arise for peripheral economies to participate in global innovation processes. However, different types of innovation activities have distinct network properties. More codifiable innovative activities can be carried out through collaboration by internationally dispersed teams. On the other hand, activities that are more dependent on tacit knowledge are likely to require the co-location of knowledge workers. This implies that innovation that relies mostly on tacit knowledge will provide limited connectivity benefits for peripheral economies’ innovation systems. We hypothesize that, while this is generally true, “leading” innovative multinational enterprises may possess more sophisticated capabilities for transnational collaboration than less innovative firms. Therefore, innovation in activities involving tacit knowledge may show different network characteristics depending on who performs them: leading firms or “laggards”. Our results, based on data from Portugal and Greece are consistent with our hypotheses.
  • Modeling of Dynamic Mechanical Response of Li-Ion cells with Homogenized Electrolyte-Solid Interactions

    Electric Vehicle Safety Lab (EVSL) (Temple Unviersity) (2022-01-25)
    Several recent studies have revealed substantial strain-rate dependence of lithium-ion batteries subjected to dynamic mechanical loadings. This behavior has been shown to be strongly dependent on the cell type, geometry, and setting. While still far from being fully understood, this dependence is believed to be connected to the solid-liquid interactions between the porous solid materials inside the electrodes and separators and the liquid electrolyte. This understanding has been supported by tests on dry cells revealing a significantly simpler behavior, being determined primarily by the constitutive material properties as compared to wet cells. This paper provides a modeling approach for the fluid-solid interaction inside battery cells by utilizing a pore fluid movement feature originally developed for geo-materials. By applying this module to the dry cell structure, the essentials of the peculiar load displacement patterns observed with active cells could be reproduced for two types of cells, a prismatic and a pouch cell. It is believed that this procedure, elucidating the underlying physics, and yet being simple, effective, and less time consuming than potential alternative techniques, will be exceedingly useful for evaluating crash behavior of electric vehicles. It allows making realistic calculations feasible based on experiments performed only on dry cells quasi-statically.
  • Effects of Intimate Partner Violence During COVID-19 and Pandemic-Related Stress on the Mental and Physical Health of Women Veterans

    Iverson, Katherine M.; Dardis, Christina M.; Cowlishaw, Sean; Webermann, Aliya R.; Shayani, Danielle R.; Dichter, Melissa E.; Mitchell, Karen S.; Mattocks, Kristin M.; Gerber, Megan R.; Portnoy, Galina R. (2022-08-30)
    Background: Little is known about women veterans’ intimate partner violence (IPV) experiences during the COVID-19 pandemic or the impacts of pandemic-related stress on their mental and physical health. Objectives: To identify IPV experiences among women veterans prior to and during the pandemic, pandemic-related stressors, and examine their respective contributions to mental and physical health. Design: National sample of women veterans drawn from a larger web-based longitudinal study. Relationships between recent IPV and pandemic-related stressors were tested with linear regressions, controlling for pre-pandemic IPV and mental and physical health symptoms, demographic, and military-related covariates. Participants: One hundred forty-two women veterans (Mage=58.8 years). Main Measures: We assessed IPV (CTS-2), PTSD (PCL-5), depression (CESD), anxiety (DASS-A), physical health (PHQ-15), and physical health–related quality of life (SF-12) prior to the pandemic (June 2016–December 2016/January 2017) and during the pandemic study period (March 2020–December 2020/January 2021). We assessed pandemic-related stressors (EPII) during the pandemic study period. Key Results: Over a third (38.7%) of participants experienced IPV during the pandemic study period (psychological: 35.9%, physical: 9.9%, sexual: 4.2%). Overall rates, frequency, and severity of IPV experience did not significantly differ between the pre-pandemic and pandemic study periods. Few participants tested positive for COVID-19 (4.2%); however, most participants reported experiencing pandemic-related stressors across life domains (e.g., social activities: 88%, physical health: 80.3%, emotional health: 68.3%). IPV during the pandemic and pandemic-related stressors were both associated with greater PTSD and depressive symptoms. Pandemic-related stressors were associated with worse anxiety and physical health symptoms. Neither IPV during the pandemic nor pandemic-related stressors were associated with physical health–related quality of life. Conclusions: IPV experiences during the pandemic were common among women veterans, as were pandemic-related stressors. Although IPV did not increase in the context of COVID-19, IPV experiences during the pandemic and pandemic-related stressors were linked with poorer mental and physical health.
  • First Measurement of High-Energy Reactor Antineutrinos at Daya Bay

    Daya Bay Collaboration; Jones|0000-0003-0299-2210 (2022-07-18)
    This Letter reports the first measurement of high-energy reactor antineutrinos at Daya Bay, with nearly 9000 inverse beta decay candidates in the prompt energy region of 8–12 MeV observed over 1958 days of data collection. A multivariate analysis is used to separate 2500 signal events from background statistically. The hypothesis of no reactor antineutrinos with neutrino energy above 10 MeV is rejected with a significance of 6.2 standard deviations. A 29% antineutrino flux deficit in the prompt energy region of 8–11 MeV is observed compared to a recent model prediction. We provide the unfolded antineutrino spectrum above 7 MeV as a data-based reference for other experiments. This result provides the first direct observation of the production of antineutrinos from several high-Qβ isotopes in commercial reactors.
  • Autistic-Delivered Peer Support: A Feasibility Study

    Shea, Lindsay L.; Wong, Mi-Yeet; Song, Wei; Kaplan, Katy; Uppal, Disha; Salzer, Mark S.; Song|0000-0001-5625-514X (2022-11-12)
    Peer support has been an undeveloped pathway for filling the service gap and to generate employment opportunities for autistic individuals. Peer supports have been deployed widely in mental health and among veterans and understanding the utility of this service modality among autistic individuals illuminates opportunities for research, policy, and practice. This study examined characteristics of participants in an autistic-delivered peer support program and reports on use of and satisfaction with the program. Half of autistic participants had a co-occurring mental health diagnosis. Participants reported multiple areas of unmet needs and participant satisfaction with the program was high (90%). The findings of this study point toward autistic-delivered peer support as a promising avenue for future development.
  • Vibrational Dynamics at Aqueous–Mineral Interfaces

    Center for Complex Materials from First Principles (CCM) (Temple University) (2022-01-31)
    The dynamics of water at mineral surfaces has attracted much attention due to the marked differences, compared to the bulk, in the ability of interfacial water populations to redistribute vibrational energy, largely due to perturbations in the local hydrogen-bonding environments at interfaces. However, many unanswered questions persist regarding these geochemically and technologically relevant systems. The evolution of our understanding and current state-of-the-art interpretation are reviewed for three important mineral/aqueous interfaces (Al2O3, SiO2, and CaF2). While we focus on time-resolved vibrational Sum Frequency Generation (vSFG), as it is inherently surface specific, we include complementary time-resolved techniques such as IR and THz spectroscopies, which combined can provide a broader picture of interfacial dynamics at mineral surfaces. We show that vibrational dynamics are uniquely positioned to inform on structure at interfaces, which could be missed using conventional static vibrational spectra. Insights presented here shine light on previous successes and suggest future avenues for transient vibrational spectroscopy at mineral/aqueous interfaces.
  • Functional remodelling of perinuclear mitochondria alters nucleoplasmic Ca2+ signalling in heart failure

    Cardiovascular Research Center (Temple University) (2022-10-03)
    Mitochondrial dysfunction in cardiomyocytes is a hallmark of heart failure development. Although initial studies recognized the importance of different mitochondrial subpopulations, there is a striking lack of direct comparison of intrafibrillar (IF) versus perinuclear (PN) mitochondria during the development of HF. Here, we use multiple approaches to examine the morphology and functional properties of IF versus PN mitochondria in pressure overload-induced cardiac remodelling in mice, and in non-failing and failing human cardiomyocytes. We demonstrate that PN mitochondria from failing cardiomyocytes are more susceptible to depolarization of mitochondrial membrane potential, reactive oxygen species generation and impairment in Ca2+ uptake compared with IF mitochondria at baseline and under physiological stress protocol. We also demonstrate, for the first time to our knowledge, that under normal conditions PN mitochondrial Ca2+ uptake shapes nucleoplasmic Ca2+ transients (CaTs) and limits nucleoplasmic Ca2+ loading. The loss of PN mitochondrial Ca2+ buffering capacity translates into increased nucleoplasmic CaTs and may explain disproportionate rise in nucleoplasmic [Ca2+] in failing cardiomyocytes at increased stimulation frequencies. Therefore, a previously unidentified benefit of restoring the mitochondrial Ca2+ uptake may be normalization of nuclear Ca2+ signalling and alleviation of altered excitation–transcription, which could be an important therapeutic approach to prevent adverse cardiac remodelling. This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.
  • Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa

    Institute for Genomics and Evolutionary Medicine (iGEM) (Temple University), NGS-SA Consortium (2022-06-27)
    Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern predominantly drove South Africa’s fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and similar to BA.2 except for the addition of 69–70 deletion (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild-type amino acid at Q493. The two lineages differ only outside of the spike region. The 69–70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimated growth advantages for BA.4 and BA.5 of 0.08 (95% confidence interval (CI): 0.08–0.09) and 0.10 (95% CI: 0.09–0.11) per day, respectively, over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.
  • First Extraction of Polarized Sea Asymmetry from Weak Boson Production in Proton–Proton Collisions

    Cocuzza, Christopher; Metz, Andreas (2022-03-15)
    We present a global QCD analysis of spin-dependent parton distribution functions (PDFs) that includes the latest polarized W-lepton production data from the STAR collaboration at RHIC. These data allow the first data-driven extraction of a nonzero polarized light quark sea asymmetry Δu¯−Δd¯ within a global QCD framework with minimal theoretical assumptions.
  • Generalized parton distributions from lattice QCD with asymmetric momentum transfer: Unpolarized quarks

    Bhattacharya, Shohini; Cichy, Krzysztof; Constantinou, Martha; Dodson, Jack; Gao, Xiang; Metz, Andreas; Mukherjee, Swagato; Scapellato, Aurora; Steffens, Fernanda; Zhao, Yong; Constantinou|0000-0002-6988-1745; Scapellato|0000-0002-3891-1411 (2022-12-26)
    Traditionally, lattice QCD computations of generalized parton distributions (GPDs) have been carried out in a symmetric frame, where the transferred momentum is symmetrically distributed between the incoming and outgoing hadrons. However, such frames are inconvenient since they require a separate calculation for each value of the momentum transfer, increasing significantly the computational cost. In this work, by focusing on the quasidistribution approach, we lay the foundation for faster and more effective lattice QCD calculations of GPDs exploiting asymmetric frames, with freedom in the transferred momentum distribution. An important ingredient of our approach is the Lorentz covariant parametrization of the matrix elements in terms of Lorentz-invariant amplitudes, which allows one to relate matrix elements in different frames. We also use this amplitude approach to propose a new definition of quasi-GPDs that is frame independent and, more importantly, may lead to smaller power corrections in the matching relations to the light-cone GPDs. We demonstrate the efficacy of the formalism through numerical calculations using one ensemble of Nf=2+1+1 twisted-mass fermions with a clover improvement. The value of the light-quark masses lead to a pion mass of about 260 MeV. Concentrating on the proton, and limiting ourselves to a vanishing longitudinal momentum transfer to the target, we extract the invariant amplitudes from matrix element calculations in both the symmetric and asymmetric frame and obtain results for the twist-2 light-cone GPDs for unpolarized quarks, that is, H and E.
  • The role of PET in the management of sarcoidosis

    Temple University. Hospital (2022-07-16)
    Purpose of review: PET has emerged as method to determine the location and extent of disease activity in sarcoidosis. As most clinicians do not routinely utilize PET in the management of sarcoidosis, an understanding of the imaging technique is needed to comprehend the impact that PET abnormalities have on diagnosis, prognosis, and treatment. Recent findings: Although PET can detect inflammation because of sarcoidosis throughout the body, it is most often utilized for the diagnosis of cardiac sarcoidosis for which it may provide information about prognosis and adverse events. Whenever PET is combined with cardiac magnetic resonance (CMR), clinicians may be able to increase the diagnostic yield of imaging. Furthermore, PET abnormalities have the potential to be utilized in the reduction or augmentation of therapy based on an individual's response to treatment. Although various biomarkers are used to monitor disease activity in sarcoidosis, an established and reproducible relationship between PET and biomarkers does not exist. Summary: PET has the potential to improve the diagnosis of sarcoidosis and alter treatment decisions but prospective trials are needed to define the role of PET while also standardizing the performance and interpretation of the imaging modality.

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