Measured proton electromagnetic structure deviates from theoretical predictions.

The visible world is founded on the proton, the only composite building block of matter that is stable in nature. Consequently, understanding the formation of matter relies on explaining the dynamics and the properties of the proton's bound state. A fundamental property of the proton involves the response of the system to an external electromagnetic field. It is characterized by the electromagnetic polarizabilities1 that describe how easily the charge and magnetization distributions inside the system are distorted by the electromagnetic field. Moreover, the generalized polarizabilities2 map out the resulting deformation of the densities in a proton subject to an electromagnetic field. They disclose essential information about the underlying system dynamics and provide a key for decoding the proton structure in terms of the theory of the strong interaction that binds its elementary quark and gluon constituents. Of particular interest is a puzzle in the electric generalized polarizability of the proton that remains unresolved for two decades2. Here we report measurements of the proton's electromagnetic generalized polarizabilities at low four-momentum transfer squared. We show evidence of an anomaly to the behaviour of the proton's electric generalized polarizability that contradicts the predictions of nuclear theory and derive its signature in the spatial distribution of the induced polarization in the proton. The reported measurements suggest the presence of a new, not-yet-understood dynamical mechanism in the proton and present notable challenges to the nuclear theory.

A small proton charge radius from an electron-proton scattering experiment.

Elastic electron-proton scattering (e-p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, rp. In 2010, a new method using muonic hydrogen atoms1 found a substantial discrepancy compared with previous results2, which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen3,4. Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e-p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e-p experiments and enabled measurements at very small forward-scattering angles. Our result, rp = 0.831 ± 0.007stat ± 0.012syst femtometres, is smaller than the most recent high-precision e-p measurement5 and 2.7 standard deviations smaller than the average of all e-p experimental results6. The smaller rp we have now measured supports the value found by two previous muonic hydrogen experiments1,7. In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant8-one of the most accurately evaluated fundamental constants in physics.

Measurements of Nonsinglet Moments of the Nucleon Structure Functions and Comparison to Predictions from Lattice QCD for Q

We present extractions of the nucleon nonsinglet moments utilizing new precision data on the deuteron F_{2} structure function at large Bjorken-x determined via the Rosenbluth separation technique at Jefferson Lab Experimental Hall C. These new data are combined with a complementary set of data on the proton previously measured in Hall C at similar kinematics and world datasets on the proton and deuteron at lower x measured at SLAC and CERN. The new Jefferson Lab data provide coverage of the upper third of the x range, crucial for precision determination of the higher moments. In contrast to previous extractions, these moments have been corrected for nuclear effects in the deuteron using a new global fit to the deuteron and proton data. The obtained experimental moments represent an order of magnitude improvement in precision over previous extractions using high x data. Moreover, recent exciting developments in lattice QCD calculations provide a first ever comparison of these new experimental results with calculations of moments carried out at the physical pion mass, as well as a new approach that first calculates the quark distributions directly before determining moments.

Biodegradable polymerized simvastatin stimulates bone formation.

Previous research from our labs demonstrated the synthesis of polymerized simvastatin by ring-opening polymerization and slow degradation with controlled release of simvastatin in vitro. The objective of the present study was to evaluate the degradation and intramembranous bone-forming potential of simvastatin-containing polyprodrugs in vivo using a rat calvarial onlay model. Poly(ethylene glycol)-block-poly(simvastatin) and poly(ethylene glycol)-block-poly(simvastatin)-ran-poly(glycolide) were compared with simvastatin conventionally encapsulated in poly(lactic-co-glycolic acid) (PLGA) and pure PLGA. The rate of degradation was higher for PLGA with and without simvastatin relative to the simvastatin polyprodrugs. Significant new bone growth at the circumference of poly(ethylene glycol)-block-poly(simvastatin) disks was observed beginning at 4 weeks, whereas severe bone resorption (4 weeks) and bone loss (8 weeks) were observed for PLGA loaded with simvastatin. No significant systemic effects were observed for serum total cholesterol and body weight. Increased expression of osteogenic (BMP-2, Runx2, and ALP), angiogenic (VEGF), and inflammatory cytokines (IL-6 and NF-ĸB) genes was seen with all polymers at the end of 8 weeks. Poly(ethylene glycol)-block-poly(simvastatin), with slow degradation and drug release, controlled inflammation, and significant osteogenic effect, is a candidate for use in bone regeneration applications. STATEMENT OF SIGNIFICANCE: Traditional drug delivery systems, e.g., drug encapsulated in poly(lactic-co-glycolic acid) (PLGA), are typically passive and have limited drug payload. As an alternative, we polymerized the drug simvastatin, which has multiple physiological effects, into macromolecules ("polysimvastatin") via ring-opening polymerization. We previously demonstrated that the rate of degradation and drug (simvastatin) release can be adjusted by copolymerizing it with other monomers. The present results demonstrate significant new bone growth around polysimvastatin, whereas severe bone loss occurred for PLGA loaded with simvastatin. This degradable biomaterial with biofunctionality integrated into the polymeric backbone is a useful candidate for bone regeneration applications.

Revealing Color Forces with Transverse Polarized Electron Scattering.

The Spin Asymmetries of the Nucleon Experiment measured two double spin asymmetries using a polarized proton target and polarized electron beam at two beam energies, 4.7 and 5.9 GeV. A large-acceptance open-configuration detector package identified scattered electrons at 40° and covered a wide range in Bjorken x (0.3

Vancomycin- and Poly(simvastatin)-Loaded Scaffolds with Time-Dependent Development of Porosity.

Biodegradable scaffolds are widely use in drug delivery and tissue engineering applications. The scaffolds can be modified to provide the necessary mechanical support for tissue formation and to deliver one or more drugs to stimulate tissue formation or for the treatment of a specific condition. In the current study, we developed biodegradable scaffolds that have the potential for dual drug delivery. The scaffolds consisted of simvastatin-containing prodrug, poly(simvastatin) entrapped in poly(ß-amino ester) (PBAE) porogen particles and vancomycin encapsulated in poly(lactic-co-glycolic acid) (PLGA) microspheres, which were fused together around the PBAE porogens to create a slow-degrading matrix. Upon hydrolysis, poly(simvastatin) releases simvastatin acid, which has angiogenic and osteogenic properties, while the PLGA microspheres release vancomycin as an antibacterial agent. Degradation of PBAE porogens through hydrolysis of ester linkages led to the development of porosity in a controlled manner and led to water penetration that facilitated hydrolysis of PLGA. Higher porogen loading (~60% by weight) gave rise to ~70% interconnected porosity with pore spacing of ~180 µm. This open volume facilitated simvastatin acid release upon hydrolysis and entrapped vancomycin release via diffusion through and degradation of PLGA. During the study, ~162 µg of simvastatin acid and ~18 mg vancomycin were released from the highest porosity scaffolds. Bioactivity studies showed that released simvastatin acid stimulated preosteoblastic activity, indicating that scaffold fabrication did not damage the polymeric prodrug. Regarding mechanical properties, compressive modulus, failure strain, and failure stress decreased with increasing PBAE porogen content. These dual drug releasing scaffolds with controlled development of microarchitecture can be useful in bone tissue engineering applications.

Biodegradable Simvastatin-Containing Polymeric Prodrugs with Improved Drug Release.

Simvastatin was previously converted to a polymeric prodrug with higher drug loading, but the hydrophobic nature of the poly(simvastatin) component of the block copolymer led to slow release of the drug in vitro. In this study, we hypothesized that degradation could be accelerated by chemically modifying the polymer backbone by introducing glycolide and lactide comonomers. Copolymers were formed by ring-opening polymerization using 5 kDa monomethyl ether poly(ethylene glycol) as the microinitiator in presence of triazabicyclodecene catalyst. In addition to simvastatin, modified reaction mixtures contained lactide or glycolide. Incorporation of the less hydrophobic glycolide comonomer led to in vitro degradation of up to two times greater mass loss, release of up to ~7 times more simvastatin, and a 2-3 times increase in compressive modulus compared to the lactide-containing and parent polymers.

Factors that determine body composition of female systemic lupus erythematosus (SLE) patients in Sri Lanka: a comparative study using dual-energy x-ray absorptiometry.

Studies on body composition and its determinants among SLE patients are limited. Estimation of body composition, analysis of determinants and associations of different body compartments are important in planning long-term care of these patients. The aim of the study was to identify the changes in body composition among SLE patients and assess the effect of corticosteroid use, patient and disease-related variables on body composition. We compared lean mass, fat mass, bone mineral density (BMD), and bone mineral content (BMC) determined by dual-energy x-ray absorptiometry technology, in a group of premenopausal women with SLE (n = 27) and an age-matched healthy group of women (n = 27). The median (IQR) duration of SLE was 3 (2-5) years while median (IQR) duration and dose of prednisolone therapy were 108 (88 - 172) weeks and 9730 (6160-15360) mg, respectively. No significant difference was observed in body mass index (BMI) or total fat mass between the two groups. SLE patients, however, had significantly lower lean mass (p < 0.001), BMD (p < 0.001) and BMC (p < 0.005) than healthy controls. Among cases, compared with lean mass, total body fat content showed stronger associations with total body BMD (r = 0.49, p < 0.01) and total body BMC (r = 0.63, p < 0.01). When a stepwise regression model was fitted, lean mass among controls and total fat mass among cases emerged as the best predictors of BMC/BMD. No significant correlations were found between the disease duration or cumulative glucocorticosteroid dose and total body BMD, total body BMC, lean mass or total fat content in SLE patients.

Tibial dyschondroplasia-associated proteomic changes in chicken growth plate cartilage.

Tibial dyschondroplasia (TD) is a poultry leg problem that affects the proximal growth plate of the tibia, preventing its transition to bone. To understand the disease-induced proteomic changes, we compared the protein extracts of cartilage from normal and TD-affected growth plates. TD was induced by feeding thiram to chickens 2 wk before tissue harvest. Proteins were extracted from whole tissues and from conditioned media (CM) prepared by incubating appropriate growth plate tissues in serum-free culture medium for 48 hr. The extracts were prefractionated to contain proteins ranging between 10 and 100 kD. Equal amounts of proteins were subjected to 2D gel electrophoresis with three individual samples per group. The gels were silver stained, and digital images were compared and analyzed with Melanie software to determine differentially expressed protein spots. On comparison of two sets of gels, 47 matching spots were detected in tissue extracts and 27 in CM extracts. Among the matching spots, 12 were determined to be down-regulated in tissue extracts (P < or = 0.05) and two in CM extracts (P < or = 0.05) of TD-affected growth plates. Altogether, 32 protein spots could be identified in both tissue and CM extracts by in-gel trypsin digestion, followed by peptide mass fingerprinting and mass spectrometry (MS)/MS fragmentation. The down-regulated proteins included alpha-enolase, G protein, origin recognition complex, peptidyl prolyl isomerase, calumenin, type II collagen precursor, and the expressed sequence tag pgm2n.pk014.f20, a protein with homology to human reticulocalbin-3 (RCN3). Most of the downregulated proteins are associated with signal transduction, energy metabolism, and secretory functions that are integral to cell viability. Consistent with our earlier findings that the TD chondrocytes are nonviable, the current results suggest that thiram very likely interferes with basic metabolic functions of chondrocytes, leading to their death and, consequently, to the pathogenesis of TD.

Management and outcome of residual bile duct stones following cholecystectomy at a tertiary referral centre in Sri Lanka.

BACKGROUND: In spite of the advent of pre- and per-operative imaging techniques, the problem of residual bile duct stones following laparoscopic or open cholecystectomy still exists with a reported frequency of 2-10%. Endoscopic stone extraction is a minimally invasive technique which is fast becoming popular in the management of residual ductal stones. OBJECTIVE: To review the experience in our unit with regard to clinical presentation and the outcome following endoscopic management of residual bile duct stones. DESIGN: Retrospective descriptive study. SETTING: Patients referred to a tertiary referral centre with suspected residual bile duct stones following open or laparoscopic cholecystectomy from 5 March 2002 to 31 December 2006. PATIENTS AND METHOD: 56 patients with suspected residual bile duct stones were reviewed with regard to clinical presentation, stone profile, success rate and outcome. RESULTS: Mean age of the sample was 43.2 years. Female to male ratio was 34/22. 4 (73.3%). Main presenting symptom was epigastric or right hypochondrial pain (39.2%). Presence of residual stones or gravel noted in 91% (51) during ERCP. Complete stone extraction was achieved in 83.9% (47). All these patients became completely asymptomatic. Four patients had ERCP related morbidity. There were no deaths. Longest follow up was 38 months and the shortest 1.5 months. CONCLUSIONS: Endoscopic approach is a safe and effective method in the diagnosis and treatment of residual bile duct stones.