Pfs230 Domain 7 is targeted by a potent malaria transmission-blocking monoclonal antibody.

Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that block Plasmodium parasite development in the mosquito midgut, thus preventing mosquitoes from becoming infectious. While the Pro-domain and first of fourteen 6-Cysteine domains (Pro-D1) of the Plasmodium gamete surface protein Pfs230 are known targets of transmission-blocking antibodies, no studies to date have discovered other Pfs230 domains that are functional targets. Here, we show that a murine monoclonal antibody (mAb), 18F25.1, targets Pfs230 Domain 7. We generated a subclass-switched complement-fixing variant, mAb 18F25.2a, using a CRISPR/Cas9-based hybridoma engineering method. This subclass-switched mAb 18F25.2a induced lysis of female gametes in vitro. Importantly, mAb 18F25.2a potently reduced P. falciparum infection of Anopheles stephensi mosquitoes in a complement-dependent manner, as assessed by standard membrane feeding assays. Together, our data identify Pfs230 Domain 7 as target for transmission-blocking antibodies and provide a strong incentive to study domains outside Pfs230Pro-D1 as TBV candidates.

Bioaerosols are the dominant source of warm-temperature immersion-mode INPs and drive uncertainties in INP predictability.

Ice-nucleating particles (INPs) are rare atmospheric aerosols that initiate primary ice formation, but accurately simulating their concentrations and variability in large-scale climate models remains a challenge. Doing so requires both simulating major particle sources and parameterizing their ice nucleation (IN) efficiency. Validating and improving model predictions of INP concentrations requires measuring their concentrations delineated by particle type. We present a method to speciate INP concentrations into contributions from dust, sea spray aerosol (SSA), and bioaerosol. Field campaign data from Bodega Bay, California, showed that bioaerosols were the primary source of INPs between -12° and -20°C, while dust was a minor source and SSA had little impact. We found that recent parameterizations for dust and SSA accurately predicted ambient INP concentrations. However, the model did not skillfully simulate bioaerosol INPs, suggesting a need for further research to identify major factors controlling their emissions and INP efficiency for improved representation in models.

Effect of Predeparture Testing on Postarrival SARS-CoV-2-Positive Test Results Among International Travelers - CDC Traveler-Based Genomic Surveillance Program, Four U.S. Airports, March-September 2022.

Beginning December 6, 2021, all international air passengers boarding flights to the United States were required to show either a negative result from a SARS-CoV-2 viral test taken ≤1 day before departure or proof of recovery from COVID-19 within the preceding 90 days (1). As of June 12, 2022, predeparture testing was no longer mandatory but remained recommended by CDC (2,3). Various modeling studies have estimated that predeparture testing the day before or the day of air travel reduces transmission or importation of SARS-CoV-2 by 31%-76% (4-7). Postarrival SARS-CoV-2 pooled testing data from CDC's Traveler-based Genomic Surveillance program were used to compare SARS-CoV-2 test results among volunteer travelers arriving at four U.S. airports during two 12-week periods: March 20-June 11, 2022, when predeparture testing was required, and June 12-September 3, 2022, when predeparture testing was not required. In a multivariable logistic regression model, pooled nasal swab specimens collected during March 20-June 11 were 52% less likely to be positive for SARS-CoV-2 than were those collected during June 12-September 3, after adjusting for COVID-19 incidence in the flight's country of origin, sample pool size, and collection airport (adjusted odds ratio [aOR] = 0.48, 95% CI = 0.39-0.58) (p<0.001). These findings support predeparture testing as a tool for reducing travel-associated SARS-CoV-2 transmission and provide important real-world evidence that can guide decisions for future outbreaks and pandemics.

Early Detection of Severe Acute Respiratory Syndrome Coronavirus 2 Variants Using Traveler-based Genomic Surveillance at 4 US Airports, September 2021-January 2022.

We enrolled arriving international air travelers in a severe acute respiratory syndrome coronavirus 2 genomic surveillance program. We used molecular testing of pooled nasal swabs and sequenced positive samples for sublineage. Traveler-based surveillance provided early-warning variant detection, reporting the first US Omicron BA.2 and BA.3 in North America.

Early detection of SARS-CoV-2 variants using traveler-based genomic surveillance at four US airports, September 2021- January 2022

We enrolled arriving international air travelers in SARS-CoV-2 genomic surveillance, using molecular testing of pooled nasal swabs, and sequencing positive samples for viral lineage. Traveler-based genomic surveillance provided early warning variant detection; we reported the first U.S. Omicron BA.2 and first BA.3 in North America, weeks before next reported detection.

Null Geodesic Congruences, Asymptotically-Flat Spacetimes and Their Physical Interpretation.

A priori, there is nothing very special about shear-free or asymptotically shear-free null geodesic congruences. Surprisingly, however, they turn out to possess a large number of fascinating geometric properties and to be closely related, in the context of general relativity, to a variety of physically significant effects. It is the purpose of this paper to try to fully develop these issues. This work starts with a detailed exposition of the theory of shear-free and asymptotically shear-free null geodesic congruences, i.e., congruences with shear that vanishes at future conformal null infinity. A major portion of the exposition lies in the analysis of the space of regular shear-free and asymptotically shear-free null geodesic congruences. This analysis leads to the space of complex analytic curves in an auxiliary four-complex dimensional space, [Formula: see text]-space. They in turn play a dominant role in the applications. The applications center around the problem of extracting interior physical properties of an asymptotically-flat spacetime directly from the asymptotic gravitational (and Maxwell) field itself, in analogy with the determination of total charge by an integral over the Maxwell field at infinity or the identification of the interior mass (and its loss) by (Bondi's) integrals of the Weyl tensor, also at infinity. More specifically, we will see that the asymptotically shear-free congruences lead us to an asymptotic definition of the center-of-mass and its equations of motion. This includes a kinematic meaning, in terms of the center-of-mass motion, for the Bondi three-momentum. In addition, we obtain insights into intrinsic spin and, in general, angular momentum, including an angular-momentum-conservation law with well-defined flux terms. When a Maxwell field is present, the asymptotically shear-free congruences allow us to determine/define at infinity a center-of-charge world line and intrinsic magnetic dipole moment.

Trends in use and yield of chest computed tomography with angiography for diagnosis of pulmonary embolism in a Connecticut hospital emergency department.

RATIONALE: We hypothesize that the ready availability of chest computed tomography (CT) scan, with angiography (CTA), for pulmonary embolism (PE) has resulted in its increased use in the emergency department (ED) with an associated decrease in positive studies. RESULTS: CTA for diagnosis of PE increased over 13-fold from 2000 to 2005. The diagnostic yield of CTA for PE decreased from 14% in 2000 to a mean (SD) of 7.2 (.91)% during subsequent years (P =.007). No significant change in yield occurred after 2001 (P = 0.51). Significantly more segmental and subsegmental embolisms were observed with the 16-slice CT in years 2004-2005 when compared to the single-slice CT used in years 2000-2003. CONCLUSIONS: CTA for PE in our hospital ED has a low-positive yield rate, suggesting overutilization. However, the positive-yield rate remained steady despite increasing numbers of CTA, suggesting increased detection of PE and/or false-positive CTA.

Null Geodesic Congruences, Asymptotically-Flat Spacetimes and Their Physical Interpretation.

A priori, there is nothing very special about shear-free or asymptotically shear-free null geodesic congruences. Surprisingly, however, they turn out to possess a large number of fascinating geometric properties and to be closely related, in the context of general relativity, to a variety of physically significant effects. It is the purpose of this paper to try to fully develop these issues. This work starts with a detailed exposition of the theory of shear-free and asymptotically shear-free null geodesic congruences, i.e., congruences with shear that vanishes at future conformal null infinity. A major portion of the exposition lies in the analysis of the space of regular shear-free and asymptotically shear-free null geodesic congruences. This analysis leads to the space of complex analytic curves in an auxiliary four-complex dimensional space, [Formula: see text]-space. They in turn play a dominant role in the applications. The applications center around the problem of extracting interior physical properties of an asymptotically-flat spacetime directly from the asymptotic gravitational (and Maxwell) field itself, in analogy with the determination of total charge by an integral over the Maxwell field at infinity or the identification of the interior mass (and its loss) by (Bondi's) integrals of the Weyl tensor, also at infinity. More specifically, we will see that the asymptotically shear-free congruences lead us to an asymptotic definition of the center-of-mass and its equations of motion. This includes a kinematic meaning, in terms of the center-of-mass motion, for the Bondi three-momentum. In addition, we obtain insights into intrinsic spin and, in general, angular momentum, including an angular-momentum-conservation law with well-defined flux terms. When a Maxwell field is present, the asymptotically shear-free congruences allow us to determine/define at infinity a center-of-charge world line and intrinsic magnetic dipole moment.

Computed tomography and magnetic resonance imaging of inferior vena caval thrombus associated with metastasis to the kidney.

The computed tomography and magnetic resonance imaging findings in 2 cases of inferior vena caval thrombus associated with metastases to the kidney are presented. In both cases, the radiologic findings were suggestive of renal cell carcinoma. Recognition that metastases to the kidney can be associated with inferior vena caval thrombus broadens the differential diagnosis in a patient with a renal mass, an inferior vena caval filling defect, and a known primary malignancy, potentially altering the diagnostic approach.

Direct observation of lipoprotein cholesterol ester degradation in lysosomes.

We have investigated whether pyrene-labelled cholesterol esters (PyrnCEs) (n indicates the number of aliphatic carbons in the pyrene-chain) can be used to observe the degradation of low-density lipoprotein (LDL)-derived cholesterol esters (CEs) in the lysosomes of living cells. To select the optimal substrates, hydrolysis of the PyrnCE species by lysosomal acid lipase (LAL) in detergent/phospholipid micelles was compared. The rate of hydrolysis varied markedly depending on the length of the pyrenyl chain. Pyr10CE was clearly the best substrate, while Pyr4CE was practically unhydrolysed. Pyr10CE and [3H]cholesteryl linoleate, the major CE species in LDL, were hydrolysed equally by LAL when incorporated together into reconstituted LDL (rLDL) particles, thus indicating that Pyr10CE is a reliable reporter of the lysosomal degradation of native CEs. When rLDL particles containing Pyr4CE or Pyr10CE were incubated with fibroblasts, the accumulation of bright intracellular vesicular fluorescence was observed with the former fluorescent derivative, but not with the latter. However, when the cells were treated with chloroquine, an inhibitor of lysosomal hydrolysis, or when cells with defective LAL were employed, Pyr10CE also accumulated in vesicular structures. HPLC analysis of cellular lipid extracts fully supported these imaging results. It is concluded that PyrnCEs can be used to observe degradation of CEs directly in living cells. This should be particularly useful when exploring the mechanisms responsible for the accumulation of lipoprotein-derived CEs in complex systems such as the arterial intima.