The asymmetry of antimatter in the proton.

The fundamental building blocks of the proton-quarks and gluons-have been known for decades. However, we still have an incomplete theoretical and experimental understanding of how these particles and their dynamics give rise to the quantum bound state of the proton and its physical properties, such as its spin1. The two up quarks and the single down quark that comprise the proton in the simplest picture account only for a few per cent of the proton mass, the bulk of which is in the form of quark kinetic and potential energy and gluon energy from the strong force2. An essential feature of this force, as described by quantum chromodynamics, is its ability to create matter-antimatter quark pairs inside the proton that exist only for a very short time. Their fleeting existence makes the antimatter quarks within protons difficult to study, but their existence is discernible in reactions in which a matter-antimatter quark pair annihilates. In this picture of quark-antiquark creation by the strong force, the probability distributions as a function of momentum for the presence of up and down antimatter quarks should be nearly identical, given that their masses are very similar and small compared to the mass of the proton3. Here we provide evidence from muon pair production measurements that these distributions are considerably different, with more abundant down antimatter quarks than up antimatter quarks over a wide range of momenta. These results are expected to revive interest in several proposed mechanisms for the origin of this antimatter asymmetry in the proton that had been disfavoured by previous results4, and point to future measurements that can distinguish between these mechanisms.

Deeply Virtual Compton Scattering Cross Section at High Bjorken x_{B}.

We report high-precision measurements of the deeply virtual Compton scattering (DVCS) cross section at high values of the Bjorken variable x_{B}. DVCS is sensitive to the generalized parton distributions of the nucleon, which provide a three-dimensional description of its internal constituents. Using the exact analytic expression of the DVCS cross section for all possible polarization states of the initial and final electron and nucleon, and final state photon, we present the first experimental extraction of all four helicity-conserving Compton form factors (CFFs) of the nucleon as a function of x_{B}, while systematically including helicity flip amplitudes. In particular, the high accuracy of the present data demonstrates sensitivity to some very poorly known CFFs.

Deep Exclusive Electroproduction of π

We report measurements of the exclusive neutral pion electroproduction cross section off protons at large values of x_{B} (0.36, 0.48, and 0.60) and Q^{2} (3.1 to 8.4 GeV^{2}) obtained from Jefferson Lab Hall A experiment E12-06-014. The corresponding structure functions dσ_{T}/dt+εdσ_{L}/dt, dσ_{TT}/dt, dσ_{LT}/dt, and dσ_{LT^{'}}/dt are extracted as a function of the proton momentum transfer t-t_{min}. The results suggest the amplitude for transversely polarized virtual photons continues to dominate the cross section throughout this kinematic range. The data are well described by calculations based on transversity generalized parton distributions coupled to a helicity flip distribution amplitude of the pion, thus providing a unique way to probe the structure of the nucleon.

Interference Effect between ϕ and Λ(1520) Production Channels in the γp→K

The ϕ-Λ(1520) interference effect in the γp→K^{+}K^{-}p reaction has been measured for the first time in the energy range from 1.673 to 2.173 GeV. The relative phases between ϕ and Λ(1520) production amplitudes were obtained in the kinematic region where the two resonances overlap. The measurement results support strong constructive interference when K^{+}K^{-} pairs are observed at forward angles but destructive interference for proton emission at forward angles. Furthermore, the observed interference effect does not account for the sqrt[s]=2.1 GeV bump structure in forward differential cross sections for ϕ photoproduction. This fact suggests possible exotic structures such as a hidden-strangeness pentaquark state, a new Pomeron exchange, or rescattering processes via other hyperon states.

Protocol paper: Multi-site, cluster-randomized clinical trial for optimizing functional outcomes of older cancer survivors after chemotherapy.

BACKGROUND: Cancer survivors over the age of 65 have unique needs due to the higher prevalence of functional and cognitive impairment, comorbidities, geriatric syndromes, and greater need for social support after chemotherapy. In this study, we will evaluate whether a Geriatric Evaluation and Management-Survivorship (GEMS) intervention improves functional outcomes important to older cancer survivors following chemotherapy. METHODS: A cluster-randomized trial will be conducted in approximately 30 community oncology practices affiliated with the University of Rochester Cancer Center (URCC) National Cancer Institute Community Oncology Research Program (NCORP) Research Base. Participating sites will be randomized to the GEMS intervention, which includes Advanced Practice Practitioner (APP)-directed geriatric evaluation and management (GEM), and Survivorship Health Education (SHE) that is combined with Exercise for Cancer Patients (EXCAP©®), or usual care. Cancer survivors will be recruited from community oncology practices (of participating oncology physicians and APPs) after the enrolled clinicians have consented and completed a baseline survey. We will enroll 780 cancer survivors aged 65 years and older who have completed curative-intent chemotherapy for a solid tumor malignancy within four weeks of study enrollment. Cancer survivors will be asked to choose one caregiver to also participate for a total up to 780 caregivers. The primary aim is to compare the effectiveness of GEMS for improving patient-reported physical function at six months. The secondary aim is to compare effectiveness of GEMS for improving patient-reported cognitive function at six months. Tertiary aims include comparing the effectiveness of GEMS for improving: 1) Patient-reported physical function at twelve months; 2) objectively assessed physical function at six and twelve months; and 3) patient-reported cognitive function at twelve months and objectively assessed cognitive function at six and twelve months. Exploratory health care aims include: 1) Survivor satisfaction with care, 2) APP communication with primary care physicians (PCPs), 3) completion of referral appointments, and 4) hospitalizations at six and twelve months. Exploratory caregiver aims include: 1) Caregiver distress; 2) caregiver quality of life; 3) caregiver burden; and 4) satisfaction with patient care at six and twelve months. DISCUSSION: If successful, GEMS would be an option for a standardized APP-led survivorship care intervention. TRIAL REGISTRATION: ClinicalTrials.govNCT05006482, registered on August 9, 2021.

SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda.

BACKGROUND: Mal de Meleda (MDM) is palmoplantar erythrokeratoderma with an autosomal recessive inheritance and is caused by a mutation in the gene encoding SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1). SLURP-1 is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis. In addition, murine studies have shown that nAchR signalling is important for the regulation of T-cell function. Among the family members, patients with the homozygous SLURP1 (previously known as ARS component B) mutation are prone to melanoma and viral infection, which might link to defective T-cell function as well as a derangement of epidermal homeostasis. OBJECTIVES: To investigate the association of the SLURP1 gene mutation with T-cell activation in a Taiwanese family with MDM. To test that SLURP-1 is essential for T-cell activation. METHODS: Human peripheral blood mononuclear cells (PBMCs) were isolated from a Taiwanese MDM family bearing the G to A substitution in nucleotide 256 in the SLURP1 gene, corresponding to a glycine to arginine substitution at amino acid 86 (G86R) in the SLURP-1 protein. PBMCs from homozygotes and wild-type controls were stimulated with anti-CD3/anti-CD28 antibodies and the level of T-cell activation was determined by the stimulation index. RESULTS: PBMCs with the heterozygous and homozygous SLURP-1 G86R mutation had defective T-cell activation. This was restored by the addition of 0·5 µg mL(-1) recombinant human SLURP-1 protein. CONCLUSIONS: Patients with MDM with the homozygous SLURP-1 G86R mutation may have an impaired T-cell activation. The presence of wild-type SLURP-1 is essential for normal T-cell activation.

Localization and activity of myosin light chain kinase isoforms during the cell cycle.

Phosphorylation on Ser 19 of the myosin II regulatory light chain by myosin light chain kinase (MLCK) regulates actomyosin contractility in smooth muscle and vertebrate nonmuscle cells. The smooth/nonmuscle MLCK gene locus produces two kinases, a high molecular weight isoform (long MLCK) and a low molecular weight isoform (short MLCK), that are differentially expressed in smooth and nonmuscle tissues. To study the relative localization of the MLCK isoforms in cultured nonmuscle cells and to determine the spatial and temporal dynamics of MLCK localization during mitosis, we constructed green fluorescent protein fusions of the long and short MLCKs. In interphase cells, localization of the long MLCK to stress fibers is mediated by five DXRXXL motifs, which span the junction of the NH(2)-terminal extension and the short MLCK. In contrast, localization of the long MLCK to the cleavage furrow in dividing cells requires the five DXRXXL motifs as well as additional amino acid sequences present in the NH(2)-terminal extension. Thus, it appears that nonmuscle cells utilize different mechanisms for targeting the long MLCK to actomyosin structures during interphase and mitosis. Further studies have shown that the long MLCK has twofold lower kinase activity in early mitosis than in interphase or in the early stages of postmitotic spreading. These findings suggest a model in which MLCK and the myosin II phosphatase (Totsukawa, G., Y. Yamakita, S. Yamashiro, H. Hosoya, D.J. Hartshorne, and F. Matsumura. 1999. J. Cell Biol. 144:735-744) act cooperatively to regulate the level of Ser 19-phosphorylated myosin II during mitosis and initiate cytokinesis through the activation of myosin II motor activity.

Anti-escaping of incident laser in rare-earth doped fluoride ceramics with glass forming layer.

Adaptive fluoride ceramic with glass forming layer (GCZBL-Er) used in laser anti-escaping has been prepared by one-step synthesis, and the thickness of glass layer is identified as ~0.41 mm. Blue, green and red emissions of Er3+/Yb3+ codoped fluoride ceramic (CZBL-Er) and glass layer (GZBL-Er) have been investigated under ~980 nm laser pumping. With the forming of thin glass layer on ceramic surface, the absorption intensities on diffuse reflection of GCZBL-Er at 974 nm and 1.53 µm increase by 48% and 53% than those of CZBL-Er. Excited by a 979 nm laser, the presence of the glass layer increases the absolute absorption rate in spectral power from 75% in CZBL-Er to 83% in GCZBL-Er, which is consistent with the improvement in the absorbed photon number. In addition, the quantum yield of GCZBL-Er complex is raised by 28.4% compared to the case of ceramic substrate by photon quantification. Intense absorption-conversion ability and efficient macroscopical anti-escaping effect confirm the superiority of ingenious structure in the fluoride ceramics with glass forming layer, which provides a new approach for developing the absorption-conversion materials of anti-NIR laser detection.

Population balance modeling of the conidial aggregation of Aspergillus niger.

Numerous biotechnological production processes are based on the submerse cultivation of filamentous fungi. Process design, however, is often hampered by the complex growth pattern of these organisms. In the morphologic development of coagulating filamentous fungi, like Aspergillus niger, conidial aggregation is the first step of filamentous morphogenesis. For a proper description of this phenomenon it is necessary to characterize conidial populations. Kinetic studies performed with an in-line particle size analyzer suggested that two distinct aggregation steps have to be considered. The first step of conidial aggregation starts immediately after inoculation. Both the rate constants of formation and disintegration of aggregates have been determined by measuring the concentration of conidia at the beginning of the cultivation and the concentration of particles at steady state during the first hours of cultivation. In contrast to the first aggregation step, where the collision of conidia is presumed to be responsible for the process, the second aggregation step is thought to be initiated by germination of conidia. Growing hyphae provide additional surface for the attachment of non- germinated conidia, which leads to a strong decrease in particle concentration. The specific hyphal length growth rate and the ratio of particle concentration to the growing adhesion hyphal surface are decisive matters of the second aggregation step. Both aggregation steps can be described by population dynamics and simulated using the program package PARSIVAL (PARticle SIze eVALution) for the treatment of general particle population balances.

Impaired endothelium-dependent relaxation after cardiac global ischemia and reperfusion: role of warm blood cardioplegia.

OBJECTIVES: Experiments were designed to determine whether coronary endothelial dysfunction after cardiac global ischemia and reperfusion could be prevented by warm blood cardioplegic solution. BACKGROUND: The coronary endothelium produces endothelium-derived relaxing factor (EDRF) to prevent vasospasm and thrombosis. After ischemia and reperfusion, endothelium-dependent relaxation (EDR) is diminished as a result of G-protein dysfunction. METHODS: Dogs were exposed to extracorporeal circulation in 37 degrees C (group 1) or 28 degrees C (groups 2 and 3). The heart was ischemic for 120 min while continuous warm blood cardioplegic solution (group 1) or intermittent cold (4 degrees C) crystalloid cardioplegic solution was not used in group 3 animals. The heart was then allowed to function for 60 min of reperfusion. RESULTS: Endothelium-derived relaxation in response to acetylcholine, adenosine diphosphate and sodium fluoride of the coronary rings of group 1 was significantly different from that of groups 2 and 3 but was not significantly different from that of group 4. In contrast, EDR in response to the receptor-independent calcium ionophore agonist A23187 was not significantly different between the four groups. Scanning electron microscopic studies showed that platelet adhesion and aggregation, area of microthrombi, disruption of endothelial cells and separation of the intercellular junction could be found in coronary segments of groups 2 and 3 but not in vessels of groups 1 and 4. CONCLUSIONS: These experiments suggest that cardiac global ischemia and reperfusion impair receptor-mediated release of EDRF from the coronary endothelium with G-protein dysfunction. This type of coronary endothelial dysfunction can be prevented by continuous anterograde infusion of warm blood cardioplegic solution during global ischemia.

Characteristics of recombinant W501S mutated human gamma-glutamyl carboxylase.

A mutation (W501S) in the vitamin K-dependent gamma-glutamyl carboxylase (VKC) that leads to a congenital bleeding disorder was recently discovered in two patients. To characterize the enzyme defect, recombinant VKC-W501S was expressed in and purified from insect cells. The major effect of the mutation appears to be to decrease the affinity of the carboxylase for the propeptide of its substrates. This observation agrees with recent data that place part of the propeptide binding site within residues 495-513 of VKC. Additionally, we demonstrate that the affinity between descarboxy osteocalcin (d-OC) and VKC remains unaffected by the W501S mutation. This confirms earlier data that the high-affinity site for d-OC is not located on the propeptide binding domain of VKC. Two properties of the enzyme suggest an explanation for the observation that vitamin K supplementation ameliorates the effects of the mutation: (i) since full carboxylation requires the propeptide to remain bound to the enzyme sufficiently long for full carboxylation, a reduced affinity can cause its premature release before carboxylation is complete; (ii) propeptide binding results in a decrease of the KM for vitamin K hydroquinone in wild-type, but not in mutant carboxylase, resulting in increased vitamin K requirement of affected subjects.

Identification of a gene encoding a typical gamma-carboxyglutamic acid domain in the tunicate Halocynthia roretzi.

We report the identification of a gene capable of encoding a novel Gla (gamma-carboxyglutamic acid) protein from the tunicate Halocynthia roretzi, a primitive member of the phylum Chordata. We call this new hypothetical protein Gla-RTK; it has a Gla domain typical of human vitamin K-dependent coagulation factors, a transmembrane domain, and a receptor tyrosine kinase domain. The receptor tyrosine kinase domain is very similar to the ARK (adhesion-related kinase) family of receptor tyrosine kinases. The ARK family includes Axl, Tyro3, and c-Mer. This gene also encodes a propeptide that binds to the human gamma-glutamyl carboxylase within a range of affinities observed for mammalian propeptides. The cDNA for this putative protein is found distributed throughout the oocyte and embryo but the cDNA is apparently not transcribed except during oogenesis. One of the most interesting aspects of this hypothetical protein is that its Gla domain is highly homologous to the Gla domain of Gas6, a ligand for Axl, while its receptor tyrosine kinase domain is highly homologous to Axl.

Enhancement of endothelium-dependent contraction of the canine coronary artery by UW solution.

University of Wisconsin (UW) solution has been used almost routinely in the preservation of the hepatic, pancreatic, renal, and cardiac allografts. However, its effect on vascular endothelium is unknown. Experiments were designed to evaluate its effect on canine coronary endothelium. Canine coronary arteries (n = 8 in each group) were preserved in cold (4 degrees C) UW solution (group 1) and physiological solution (group 2) for 6 hr immediately after harvesting. Segments of preserved and control (group 3) coronary arteries with or without endothelium were then suspended in organ chambers to measure isometric force. Perfusate hypoxia (pO2 30 +/- 5 mmHg) caused endothelium-dependent contraction in the arteries of all 3 groups. However, vascular segments with endothelium of group 1 exhibited hypoxic contractions (107 +/- 26% of the initial tension contracted by prostaglandin F2 alpha 2 x 10(-6) mol/L, P < 0.05) that were significantly greater than those of the group 2 and group 3 segments with endothelium (25 +/- 5% and 20 +/- 4%). The hypoxic contraction in arteries of group 1 could be attenuated by NG-monomethyl-L-arginine (L-NMMA), the blocker of endothelial cell synthesis of the nitric oxide from L-arginine. The action of L-NMMA could be reversed by L-arginine but not D-arginine. Endothelium-dependent relaxation of coronary endothelium to acetylcholine and adenosine diphosphate and endothelium-independent relaxation and contraction of coronary smooth muscle were not altered by the UW solution. After preservation with the UW solution, endothelium-dependent contraction of the canine coronary arteries, occurs by L-arginine-dependent pathway, is enhanced. This augmentation by the UW solution would favor vasospasm after transplantation.

On-line multiplane transesophageal echocardiography for balloon mitral commissurotomy.

This study describes in detail the technique and results of on-line multiplane transesophageal echocardiographic guidance of balloon mitral commissurotomy in 150 consecutive patients with symptomatic mitral stenosis. The mitral valve area improved significantly and there were no in-hospital deaths, strokes, or emergency valve operations.

Frequency of Epstein-Barr virus-associated gastric adenocarcinoma in Taiwan.

Eighty-two gastric adenocarcinomas (32 intestinal and 50 diffuse type) were investigated for the presence of Epstein-Barr virus (EBV) DNA by amplifying the 78-bp fragment from the EBNA1 gene with polymerase chain reaction. EBV was detected in 17 (20.7%) of the 82 gastric tumorous specimens. Of these 17 EBV-positive cases, only one was EBV-positive in the adjacent non-tumorous tissue. EBV-positive gastric adenocarcinoma was present in 15.6 and 24.0% of the intestinal and diffuse type tumors, respectively, but within the two classes there was significant non-homogeneity by type. EBV was found more frequently in adenocarcinomas of the tubular (25%) and poorly differentiated (30.3%) types. EBV involvement was found more in male than in female patients. Eighty of the 82 tumors were also checked for the prevalence of p53 gene mutation. Of the 17 EBV-positive gastric adenocarcinomas, only two showed p53 gene mutations. The p53 mutation rate was lower in EBV-positive tumors (11.8%) than in EBV-negative tumors (25.4%).

Reversal of refractory hypotension in septic shock by inhibitor of nitric oxide synthase.

Septic shock is a life-threatening condition that results from exposure to bacterial endotoxin. It is mediated by the release of cytokines. Some of these cytokines cause the release of vasoactive substances. We report the case of a 62-year-old male patient who received redo operation for replacement of the degenerative porcine aortic and mitral prostheses. High cardiac output shock developed on the seventh postoperative day with severe metabolic acidosis and oliguria. Systemic vascular resistance and mean arterial pressure elevated within 5 min and stabilized 60 min after the start of a single dose of intravenous administration of NG-monomethyl-L-arginine (50 mg), a potent and selective inhibitor of nitric oxide synthesis. These findings indicate that nitric oxide overproduction is an important contributor to refractory hypotension in high cardiac output septic shock. Our findings suggested the utilization of nitric oxide synthase inhibitor in the treatment of septic shock in humans.

Time course and extent of recovery of endothelium-dependent contractions and relaxations after direct arterial injury.

To determine the time course of the return of endothelium-dependent relaxations and contractions during intimal regeneration, we performed balloon endothelial denudation of the thoracic and abdominal aorta of male Lewis rats and examined smooth muscle function and endothelium-dependent responses in vitro at 1, 2, 4, and 8 weeks after aortic injury. At each study interval during endothelial cell regeneration, vascular smooth muscle contracted and relaxed normally to direct stimulation with norepinephrine and sodium nitroprusside. Endothelium-dependent contractions to serotonin returned to normal at 1 week and developed into a hypercontractile response at 8 weeks. Endothelium-dependent relaxations to acetylcholine returned to normal at 8 weeks, but endothelium-dependent relaxations to adenosine diphosphate remained impaired. These experiments demonstrate that regenerating endothelium regains the ability to produce contracting factor before relaxing factor, and it even exhibits potentiated contractile activity 8 weeks after injury. Thus, after direct arterial injury, regenerating endothelium has abnormal endothelium-dependent function that predisposes the vessel to vasospasm and thrombosis.

Global myocardial ischemia and reperfusion impair endothelium-dependent relaxations to aggregating platelets in the canine coronary artery. A possible cause of vasospasm after cardiopulmonary bypass.

Experiments were designed to determine whether endothelial cell injury contributes to increased coronary vascular tone after global cardiac ischemia and reperfusion. Canine hearts were exposed to global ischemia for 45 minutes and were reperfused for 60 minutes. Rings (5 to 6 mm long) of the left anterior descending coronary artery from reperfused hearts and from normal (control) hearts were suspended for isometric force measurement in organ chambers containing physiologic salt solution (37 degrees C, and 95% oxygen and 5% carbon dioxide). After contraction with prostaglandin F2 alpha, reperfused coronary arteries had significant impairment of endothelium-dependent relaxations to aggregating platelets (52% +/- 12% relaxation versus 102% +/- 11% for control segments; p less than 0.05). Reperfused arterial rings also exhibited impaired endothelium-dependent relaxations to the receptor-dependent agonist acetylcholine and the platelet-derived compounds adenosine diphosphate and serotonin. Importantly, endothelium-dependent relaxations to the non-receptor-dependent agonist A23187 were normal after ischemia and reperfusion. Quiescent (noncontracted) reperfused arterial rings lost the ability to counteract the constrictive effect of aggregating platelets on the coronary vascular smooth muscle (24% +/- 7% contraction versus 5% +/- 2% relaxation for control segments; p less than 0.05). Endothelium-independent contractions to potassium chloride and prostaglandin F2 alpha were similar in reperfused and normal arteries. Also, endothelium-independent relaxations to nitric oxide and isoproterenol were comparable in reperfused arteries and normal vessels. Thus global cardiac ischemia and reperfusion impair the normal endothelium-dependent relaxations to aggregating platelets and other receptor-dependent vasoactive drugs. This impairment of platelet-mediated coronary vasodilation may explain increased coronary vascular tone after cardiopulmonary bypass and could be an important pathophysiologic mechanism of postoperative coronary vasospasm.

Superoxide anion mediates the endothelium-dependent contractions to serotonin by regenerated endothelium.

The endothelium modulates vascular tone by releasing a variety of vasoactive compounds that relax or contract the underlying vascular smooth muscle. We have previously demonstrated that regenerated endothelium exhibits endothelium-dependent hypercontraction to the platelet-derived compound serotonin (or 5-HT). To determine if this hypercontraction is mediated by superoxide anion produced by the endothelium, we performed balloon catheter denudation on the thoracic and abdominal aorta of male Lewis rats. Eight weeks after arterial injury, endothelium-dependent responses to serotonin were examined in tissue bath experiments. Vascular rings (5 mm in length), with and without endothelium, were contracted with norepinephrine and then exposed to serotonin (10(-9) to 3 x 10(-5) mol/L). Vascular rings with regenerated endothelium exhibited hypercontraction to serotonin (251% +/- 25% of initial norepinephrine contraction; p less than 0.05 compared with control rings, 175% +/- 13%). Removal of the endothelium (133% +/- 6%) or treatment with superoxide dismutase (184% +/- 7%), with or without catalase, prevented the endothelium-dependent constrictor effect of the serotonin. Ketanserin suppressed the vasoconstrictor effect of serotonin on control (93% +/- 15%) and regenerated (105% +/- 9%) rings with endothelium, indicating that the serotonin effect is mediated through the 5-HT2-serotonergic receptor. Deferoxamine or heat-inactivated superoxide dismutase did not modify the response. These observations support the hypothesis that superoxide anion is an endothelium-derived contracting factor produced by regenerated endothelium after intimal injury.