Quantum Kinks: Solitons at Strong Coupling

We examine solitons in theories with heavy fermions. These ``quantum'' solitons differ dramatically from semi-classical (perturbative) solitons because fermion loop effects are important when the Yukawa coupling is strong. We focus on kinks in a $(1+1)$--dimensional $\phi^4$ theory coupled to fermions; a large-$N$ expansion is employed to treat the Yukawa coupling $g$ nonperturbatively. A local expression for the fermion vacuum energy is derived using the WKB approximation for the Dirac eigenvalues. We find that fermion loop corrections increase the energy of the kink and (for large $g$) decrease its size. For large $g$, the energy of the quantum kink is proportional to $g$, and its size scales as $1/g$, unlike the classical kink; we argue that these features are generic to quantum solitons in theories with strong Yukawa couplings. We also discuss the possible instability of fermions to solitons.Comment: 21 pp. + 2 figs., phyzzx, JHU-TIPAC-92001

Real-Time Image Guided Ablative Prostate Cancer Radiation Therapy: Results From the TROG 15.01 SPARK Trial.

PurposeKilovoltage intrafraction monitoring (KIM) is a novel software platform implemented on standard radiation therapy systems and enabling real-time image guided radiation therapy (IGRT). In a multi-institutional prospective trial, we investigated whether real-time IGRT improved the accuracy of the dose patients with prostate cancer received during radiation therapy.Methods and materialsForty-eight patients with prostate cancer were treated with KIM-guided SABR with 36.25 Gy in 5 fractions. During KIM-guided treatment, the prostate motion was corrected for by either beam gating with couch shifts or multileaf collimator tracking. A dose reconstruction method was used to evaluate the dose delivered to the target and organs at risk with and without real-time IGRT. Primary outcome was the effect of real-time IGRT on dose distributions. Secondary outcomes included patient-reported outcomes and toxicity.ResultsMotion correction occurred in ≥1 treatment for 88% of patients (42 of 48) and 51% of treatments (121 of 235). With real-time IGRT, no treatments had prostate clinical target volume (CTV) D98% dose 5% less than planned. Without real-time IGRT, 13 treatments (5.5%) had prostate CTV D98% doses 5% less than planned. The prostate CTV D98% dose with real-time IGRT was closer to the plan by an average of 1.0% (range, -2.8% to 20.3%). Patient outcomes showed no change in the 12-month patient-reported outcomes compared with baseline and no grade ≥3 genitourinary or gastrointestinal toxicities.ConclusionsReal-time IGRT is clinically effective for prostate cancer SABR

Homogeneous Bubble Nucleation driven by local hot spots: a Molecular Dynamics Study

We report a Molecular Dynamics study of homogenous bubble nucleation in a Lennard-Jones fluid. The rate of bubble nucleation is estimated using forward-flux sampling (FFS). We find that cavitation starts with compact bubbles rather than with ramified structures as had been suggested by Shen and Debenedetti (J. Chem. Phys. 111:3581, 1999). Our estimate of the bubble-nucleation rate is higher than predicted on the basis of Classical Nucleation Theory (CNT). Our simulations show that local temperature fluctuations correlate strongly with subsequent bubble formation - this mechanism is not taken into account in CNT

Melanocortin receptors in GtoPdb v.2021.3

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development

Melanocortin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [36]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development

Melanocortin receptors in GtoPdb v.2023.1

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test. setmelanotide was approved by the US FDA for weight management in patients with POMC, PCSK1 or LEPR defiency, bremelanotide was approved by the US FDA for generalized hypoactive sexual desire disorder in premenopausal women, and NDP-MSH (afamelanotide) was approved by the EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development

Dairy consumption and cardiometabolic diseases: systematic review and updated meta-analyses of prospective cohort studies

Purpose of Review Dairy products contain both beneficial and harmful nutrients in relation to cardiometabolic diseases. Here, we provide the latest scientific evidence regarding the relationship between dairy products and cardiometabolic diseases by reviewing the literature and updating meta-analyses of observational studies. Recent Findings We updated our previous meta-analyses of cohort studies on type 2 diabetes, coronary heart disease (CHD), and stroke with nine studies and confirmed previous results. Total dairy and low-fat dairy (per 200 g/d) were inversely associated with a 3–4% lower risk of diabetes. Yogurt was non-linearly inversely associatedwith diabetes (RR = 0.86, 95%CI: 0.83–0.90 at 80 g/ d). Total dairy and milk were not associated with CHD (RR~1.0). An increment of 200 g of daily milk intake was associated with an 8% lower risk of stroke. Summary The latest scientific evidence confirmed neutral or beneficial associations between dairy products and risk of cardiometabolic diseases

The long-term effects of an implantable drop foot stimulator on gait in hemiparetic patients

Drop foot is a frequent abnormality in gait after central nervous system lesions. Different treatment strategies are available to functionally restore dorsal extension during swing phase in gait. Orthoses as well as surface and implantable devices for electrical stimulation of the peroneal nerve may be used in patients who do not regain good dorsal extension. While several studies investigated the effects of implanted systems on walking speed and gait endurance, only a few studies have focussed on the system’s impact on kinematics and long-term outcomes. Therefore, our aim was to further investigate the effects of the implanted system ActiGait on gait kinematics and spatiotemporal parameters for the first time with a 1-year follow-up period. 10 patients were implanted with an ActiGait stimulator, with 8 patients completing baseline and follow-up assessments. Assessments included a 10-m walking test, video-based gait analysis and a Visual Analogue Scale (VAS) for health status. At baseline, gait analysis was performed without any assistive device as well as with surface electrical stimulation. At follow-up patients walked with the ActiGait system switched off and on. The maximum dorsal extension of the ankle at initial contact increased significantly between baseline without stimulation and follow-up with ActiGait (p = 0.018). While the spatio-temporal parameters did not seem to change much with the use of ActiGait in convenient walking speed, patients did walk faster when using surface stimulation or ActiGait compared to no stimulation at the 10-m walking test at their fastest possible walking speed. Patients rated their health better at the 1-year follow-up. In summary, a global improvement in gait kinematics compared to no stimulation was observed and the long-term safety of the device could be confirmed

Idiopathic radiographic apical root resorption in wind instrument players

Root resorption of the permanent teeth involves an elaborate interaction among inflammatory cells resulting in loss of dental hard tissues. This report describes three clinical cases where idiopathic root resorption occurred in wind instrument playing patients. These patients produce adequate non-orthodontic forces, while playing their instruments, to expose their teeth to root resorbing force. Careful clinical monitoring of patients' teeth should be undertaken, as the additive effects of orthodontic treatment and musical habits are unknown

Crossing borders to bind proteins—a new concept in protein recognition based on the conjugation of small organic molecules or short peptides to polypeptides from a designed set

A new concept for protein recognition and binding is highlighted. The conjugation of small organic molecules or short peptides to polypeptides from a designed set provides binder molecules that bind proteins with high affinities, and with selectivities that are equal to those of antibodies. The small organic molecules or peptides need to bind the protein targets but only with modest affinities and selectivities, because conjugation to the polypeptides results in molecules with dramatically improved binder performance. The polypeptides are selected from a set of only sixteen sequences designed to bind, in principle, any protein. The small number of polypeptides used to prepare high-affinity binders contrasts sharply with the huge libraries used in binder technologies based on selection or immunization. Also, unlike antibodies and engineered proteins, the polypeptides have unordered three-dimensional structures and adapt to the proteins to which they bind. Binder molecules for the C-reactive protein, human carbonic anhydrase II, acetylcholine esterase, thymidine kinase 1, phosphorylated proteins, the D-dimer, and a number of antibodies are used as examples to demonstrate that affinities are achieved that are higher than those of the small molecules or peptides by as much as four orders of magnitude. Evaluation by pull-down experiments and ELISA-based tests in human serum show selectivities to be equal to those of antibodies. Small organic molecules and peptides are readily available from pools of endogenous ligands, enzyme substrates, inhibitors or products, from screened small molecule libraries, from phage display, and from mRNA display. The technology is an alternative to established binder concepts for applications in drug development, diagnostics, medical imaging, and protein separation