2,937 research outputs found
Rovibrational Polaritons in Gas-Phase Methane
Polaritonic states arise when a bright optical transition of a molecular
ensemble is resonantly matched to an optical cavity mode frequency. Here, we
lay the groundwork to study the behavior of polaritons in clean, isolated
systems by establishing a new platform for vibrational strong coupling in
gas-phase molecules. We access the strong coupling regime in an intracavity
cryogenic buffer gas cell optimized for the preparation of simultaneously cold
and dense ensembles, and report a proof-of-principle demonstration in gas-phase
methane. We strongly cavity-couple individual rovibrational transitions and
probe a range of coupling strengths and detunings. We reproduce our findings
with classical cavity transmission simulations in the presence of strong
intracavity absorbers. This infrastructure provides a new testbed for benchmark
studies of cavity-altered chemistry
A versatile platform for gas-phase molecular polaritonics
Strong cavity coupling of gas-phase molecules will enable studies of
benchmark chemical processes under strong light-matter interactions with a high
level of experimental control and no solvent effects. We recently demonstrated
the formation of gas-phase molecular polaritons by strongly coupling a bright
rovibrational transition of methane to a Fabry-P\'erot optical cavity mode
inside a cryogenic buffer gas cell. Here, we further explore the flexible
capabilities of this infrastructure. We show that we can greatly increase the
collective coupling strength of the molecular ensemble to the cavity by
increasing the intracavity methane number density. In doing so, we access a
multimode coupling regime in which many nested polaritonic states arise as the
Rabi splitting approaches the cavity mode spacing. We explore polariton
formation for cavity geometries of varying length, finesse, and mirror radius
of curvature. We also report a proof-of-principle demonstration of
rovibrational gas-phase polariton formation at room temperature. This
experimental flexibility affords a great degree of control over the properties
of molecular polaritons and opens up a wider range of simple molecular
processes to future interrogation under strong cavity-coupling. We anticipate
that ongoing work in gas-phase polaritonics will facilitate convergence between
experimental results and theoretical models of cavity-altered chemistry and
physics
Divergent evolution of protein conformational dynamics in dihydrofolate reductase.
Molecular evolution is driven by mutations, which may affect the fitness of an organism and are then subject to natural selection or genetic drift. Analysis of primary protein sequences and tertiary structures has yielded valuable insights into the evolution of protein function, but little is known about the evolution of functional mechanisms, protein dynamics and conformational plasticity essential for activity. We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family. Despite structural similarity, Escherichia coli and human DHFRs use different dynamic mechanisms to perform the same function, and human DHFR cannot complement DHFR-deficient E. coli cells. Identification of the primary-sequence determinants of flexibility in DHFRs from several species allowed us to propose a likely scenario for the evolution of functionally important DHFR dynamics following a pattern of divergent evolution that is tuned by cellular environment
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Associations between palliative chemotherapy and adult cancer patients’ end of life care and place of death: prospective cohort study
Objectives: To determine whether the receipt of chemotherapy among terminally ill cancer patients months before death was associated with patients’ subsequent intensive medical care and place of death. Design: Secondary analysis of a prospective, multi-institution, longitudinal study of patients with advanced cancer. Setting: Eight outpatient oncology clinics in the United States. Participants: 386 adult patients with metastatic cancers refractory to at least one chemotherapy regimen, whom physicians identified as terminally ill at study enrollment and who subsequently died. Main outcome measures Primary outcomes: intensive medical care (cardiopulmonary resuscitation, mechanical ventilation, or both) in the last week of life and patients’ place of death (for example, intensive care unit). Secondary outcomes: survival, late hospice referrals (≤1 week before death), and dying in preferred place of death. Results: 216 (56%) of 386 terminally ill cancer patients were receiving palliative chemotherapy at study enrollment, a median of 4.0 months before death. After propensity score weighted adjustment, use of chemotherapy at enrollment was associated with higher rates of cardiopulmonary resuscitation, mechanical ventilation, or both in the last week of life (14% v 2%; adjusted risk difference 10.5%, 95% confidence interval 5.0% to 15.5%) and late hospice referrals (54% v 37%; 13.6%, 3.6% to 23.6%) but no difference in survival (hazard ratio 1.11, 95% confidence interval 0.90 to 1.38). Patients receiving palliative chemotherapy were more likely to die in an intensive care unit (11% v 2%; adjusted risk difference 6.1%, 1.1% to 11.1%) and less likely to die at home (47% v 66%; −10.8%, −1.0% to −20.6%), compared with those who were not. Patients receiving palliative chemotherapy were also less likely to die in their preferred place, compared with those who were not (65% v 80%; adjusted risk difference −9.4%, −0.8% to −18.1%). Conclusions: The use of chemotherapy in terminally ill cancer patients in the last months of life was associated with an increased risk of undergoing cardiopulmonary resuscitation, mechanical ventilation or both and of dying in an intensive care unit. Future research should determine the mechanisms by which palliative chemotherapy affects end of life outcomes and patients’ attainment of their goals
Epithelial Outgrowths from Tissue Cultures of Basal Cell Epitheliomas This Work Received A Bronx Dermatological Society Henry Silver Award June, 1963
Nectar chemistry modulates the impact of an invasive plant on native pollinators
1. Invasive species are considered a main driver of pollinator declines, yet the direct effects of invasive alien plants on pollinators are poorly understood.
2. Abundant, invasive plant species can provide a copious nectar resource for native pollinators. However, the nectar of some plants contains secondary compounds, usually associated with defence against herbivores. The impacts of these compounds on pollinators are often unknown.
3. We compared how consumption of grayanotoxin I and III, natural secondary compounds in the nectar of invasive Rhododendron ponticum L., affected three native bee species: a honeybee, (Apis mellifera L.), a solitary mining bee (Andrena carantonica, Pérez) and a bumblebee, (Bombus terrestris, L.).
4. Survival of the solitary bee and the bumblebee species was not affected by either grayanotoxin, but honeybees were ∼20× more likely to die when fed solutions containing grayanotoxin I. Furthermore, solitary bees were deterred from feeding and exhibited malaise behaviours indicative of sublethal toxicity in response to consumption of grayanotoxin I. In contrast, grayanotoxins did not affect bumblebee survival or behaviour, even when bees were subjected to multiple stressors (parasite infection or food stress).
5. Our experiments suggest that while R. ponticum provides abundant floral nectar, it is only available as a food resource to pollinators that tolerate grayanotoxins. Pollinators whose health is negatively affected by grayanotoxins may experience negative impacts from R. ponticum invasion directly (if they consume R. ponticum nectar) or indirectly (if native floral resources are replaced by R. ponticum).
6. Our study makes a novel comparison of the effects of a natural nectar secondary compound on three pollinator species and clearly demonstrates drastic variation in the responses of different key pollinator taxa to a nectar toxin. Our findings are thus in congruence with literature demonstrating the varying effects of invasive plant chemistry on native foliar herbivores, and our work demonstrates that nectar chemistry should be taken into account when determining the impacts of plant invasion for native pollinators
PDT in the Thoracic Cavity: Spectroscopic Methods and Fluence Modeling for Treatment Planning
PDT for the thoracic cavity provides a promising cancer treatment modality, but improvements in treatment planning, particularly in PDT dosimetry, can be made to improve uniformity of light delivery. When a cavity of arbitrary geometry is illuminated, the fluence increases due to multiple-scattered photons, referred to as the Integrating Sphere Effect (ISE). Current pleural PDT treatment protocol at the University of Pennsylvania monitors light fluence (hereafter simply fluence, measured in W/cm2) via seven isotropic detectors sutured at different locations in thoracic cavity of a patient. This protocol monitors light at discrete locations, but does not provide a measurement of fluence for the thoracic cavity as a whole. Current calculation of light fluence includes direct light only and thus does not account for the unique optical properties of each tissue type present, which in turn affects the accuracy of the calculated light distribution in the surrounding tissue and, in turn, the overall cell death and treatment efficacy.
Treatment planning for pleural PDT can be improved, in part, by considering the contribution of scattered light, which is affected by the two factors of geometry and in vivo optical properties. We expanded the work by Willem Star in regards to the ISE in a spherical cavity. A series of Monte Carlo (MC) simulations were run for semi-infinite planar, spherical, and ellipsoidal geometries for a range of optical properties. The results of these simulations are compared to theory and numerical solutions for fluence in the cavity and at the cavity-medium boundary. The development via MC simulations offers a general method of calculating the required light fluence specialized to each patient, based on the treatment surface area.
The scattered fluence calculation is dependent on in vivo optical properties (μa and μs\u27) of the tissues treated. Diffuse reflectance and fluorescence spectroscopy methods are used to determine the optical properties and oxygenation (reflectance measurements) and drug concentration (fluorescence measurements) of different tissues in vivo, before and after treatment, in patients enrolled the Phase I HPPH study ongoing at the University of Pennsylvania.
This work aims to provide the building blocks essential to pleural PDT treatment planning by more accurately calculating the required fluence using a model that accounts for the effects of treatment geometry and optical properties measured in vivo
Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes:linear and nonlinear Mendelian randomization analyses
Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes:linear and nonlinear Mendelian randomization analyses
BACKGROUND: Observational studies have reported maternal short/long sleep duration to be associated with adverse pregnancy and perinatal outcomes. However, it remains unclear whether there are nonlinear causal effects. Our aim was to use Mendelian randomization (MR) and multivariable regression to examine nonlinear effects of sleep duration on stillbirth (MR only), miscarriage (MR only), gestational diabetes, hypertensive disorders of pregnancy, perinatal depression, preterm birth and low/high offspring birthweight. METHODS: We used data from European women in UK Biobank (N=176,897), FinnGen (N=~123,579), Avon Longitudinal Study of Parents and Children (N=6826), Born in Bradford (N=2940) and Norwegian Mother, Father and Child Cohort Study (MoBa, N=14,584). We used 78 previously identified genetic variants as instruments for sleep duration and investigated its effects using two-sample, and one-sample nonlinear (UK Biobank only), MR. We compared MR findings with multivariable regression in MoBa (N=76,669), where maternal sleep duration was measured at 30 weeks. RESULTS: In UK Biobank, MR provided evidence of nonlinear effects of sleep duration on stillbirth, perinatal depression and low offspring birthweight. Shorter and longer duration increased stillbirth and low offspring birthweight; shorter duration increased perinatal depression. For example, longer sleep duration was related to lower risk of low offspring birthweight (odds ratio 0.79 per 1 h/day (95% confidence interval: 0.67, 0.93)) in the shortest duration group and higher risk (odds ratio 1.40 (95% confidence interval: 1.06, 1.84)) in the longest duration group, suggesting shorter and longer duration increased the risk. These were supported by the lack of evidence of a linear effect of sleep duration on any outcome using two-sample MR. In multivariable regression, risks of all outcomes were higher in the women reporting <5 and ≥10 h/day sleep compared with the reference category of 8–9 h/day, despite some wide confidence intervals. Nonlinear models fitted the data better than linear models for most outcomes (likelihood ratio P-value=0.02 to 3.2×10(−52)), except for gestational diabetes. CONCLUSIONS: Our results show shorter and longer sleep duration potentially causing higher risks of stillbirth, perinatal depression and low offspring birthweight. Larger studies with more cases are needed to detect potential nonlinear effects on hypertensive disorders of pregnancy, preterm birth and high offspring birthweight. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02494-y
Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease.
BACKGROUND: Global gene expression profiling can provide insight into the underlying pathophysiology of disease processes. Kawasaki disease (KD) is an acute, self-limited vasculitis whose etiology remains unknown. Although the clinical illness shares certain features with other pediatric infectious diseases, the occurrence of coronary artery aneurysms in 25% of untreated patients is unique to KD. METHODS: To gain further insight into the molecular mechanisms underlying KD, we investigated the acute and convalescent whole blood transcriptional profiles of 146 KD subjects and compared them with the transcriptional profiles of pediatric patients with confirmed bacterial or viral infection, and with healthy control children. We also investigated the transcript abundance in patients with different intravenous immunoglobulin treatment responses and different coronary artery outcomes. RESULTS: The overwhelming signature for acute KD involved signaling pathways of the innate immune system. Comparison with other acute pediatric infections highlighted the importance of pathways involved in cell motility including paxillin, relaxin, actin, integrins, and matrix metalloproteinases. Most importantly, the IL1β pathway was identified as a potential therapeutic target. CONCLUSION: Our study revealed the importance of the IL-1 signaling pathway and a prominent signature of innate immunity and cell migration in the acute phase of the illness
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