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.

First Measurement of Near-Threshold J/ψ Exclusive Photoproduction off the Proton.

We report on the measurement of the γp→J/ψp cross section from E_{γ}=11.8 GeV down to the threshold at 8.2 GeV using a tagged photon beam with the GlueX experiment. We find that the total cross section falls toward the threshold less steeply than expected from two-gluon exchange models. The differential cross section dσ/dt has an exponential slope of 1.67±0.39 GeV^{-2} at 10.7 GeV average energy. The LHCb pentaquark candidates P_{c}^{+} can be produced in the s channel of this reaction. We see no evidence for them and set model-dependent upper limits on their branching fractions B(P_{c}^{+}→J/ψp) and cross sections σ(γp→P_{c}^{+})×B(P_{c}^{+}→J/ψp).

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.

[Use of analgesia and sedation in dental implantology in patients with concomitant hypertension].

Dental implants surgery in patients with hypertension increases the risk of vascular complications. The aim of the study was to examine the effect of analgesia and sedation on blood pressure and postoperative pain in dental implantology. In 76 patients with hypertension implant surgery was performed under local anesthesia only (40 patients) or under local anesthesia with propofol sedation and pre-emptive analgesia with ketorolac (36 patients). Intraoperative systolic blood pressure in the second group was 20% less than in the first group while the intensity of pain in the postoperative period in the second group was three times less than in the first one. Propofol sedation in dental implantology provides hemodynamic stability in patients with concomitant hypertension and preemptive analgesia with ketorolac allows minimizing postoperative pain.

[Long-term dental interventions in mentally retarded children under general anesthesia with sevoflurane].

Dental procedures in mentally retarded children is challenging for both dentist and for anesthesiologist. The aim of the study was to evaluate the efficacy and safety of dental care procedures under general anesthesia with sevoflurane by means of laryngeal mask in mentally retarded children. The randomized controlled study included 65 mentally retarded children with ASA 2-3 who underwent dental treatment. All patients had multiple caries. The children were divided into two groups. The first group included 35 children with normal body weigh while the second one - 30 obese children. All patients received a rapid induction with sevoflurane with the subsequent installation of the laryngeal mask. In the second group the signs of hypoventilation recorded an average of 10 ± 4 minutes after induction of anesthesia, which was manifested in increasing Pсо2greater than 50 mm Hg. In the first group, the signs of hypoventilation marked an average of 18 ± 3.5 minutes from the start of induction of anesthesia. All patients were transferred to the artificial lung ventilation through the LMA. By dental treatment under general anesthesia with sevoflurane and laryngeal mask all mentally retarded children had respiratory depression with increased levels of carbon dioxide greater than 50 mmHg, but obese children developed these signs of hypoventilation twice as fast. Conducting long dental treatment in mentally retarded children require artificial lung ventilation.

Observation of the (Λ)(7)He hypernucleus by the (e, e'K+) reaction.

An experiment with a newly developed high-resolution kaon spectrometer and a scattered electron spectrometer with a novel configuration was performed in Hall C at Jefferson Lab. The ground state of a neutron-rich hypernucleus, (Λ)(7)He, was observed for the first time with the (e, e'K+) reaction with an energy resolution of ~0.6 MeV. This resolution is the best reported to date for hypernuclear reaction spectroscopy. The (Λ)(7)He binding energy supplies the last missing information of the A = 7, T = 1 hypernuclear isotriplet, providing a new input for the charge symmetry breaking effect of the ΛN potential.

Depletion of COPI in cancer cells: the role of reactive oxygen species in the induction of lipid accumulation, noncanonical lipophagy and apoptosis.

The coatomer protein complex 1 (COPI) is a multisubunit complex that coats intracellular vesicles and is involved in intracellular protein trafficking. Recently we and others found that depletion of COPI complex subunits zeta (COPZ1) and delta (ARCN1) preferentially kills tumor cells relative to normal cells. Here we delineate the specific cellular effects and sequence of events of COPI complex depletion in tumor cells. We find that this depletion leads to the inhibition of mitochondrial oxidative phosphorylation and the elevation of reactive oxygen species (ROS) production, followed by accumulation of lipid droplets (LDs) and autophagy-associated proteins LC3-II and SQSTM1/p62 and, finally, apoptosis of the tumor cells. Inactivation of ROS in COPI-depleted cells with the mitochondrial-specific quencher, mitoquinone mesylate, attenuated apoptosis and markedly decreased both the size and the number of LDs. COPI depletion caused ROS-dependent accumulation of LC3-II and SQSTM1 which colocalizes with LDs. Lack of double-membrane autophagosomes and insensitivity to Atg5 deletion suggested an accumulation of a microlipophagy complex on the surface of LDs induced by depletion of the COPI complex. Our findings suggest a sequence of cellular events triggered by COPI depletion, starting with inhibition of oxidative phosphorylation, followed by ROS activation and accumulation of LDs and apoptosis.

New Measurement of the π0 radiative decay width.

High precision measurements of the differential cross sections for π0 photoproduction at forward angles for two nuclei, 12C and 208Pb, have been performed for incident photon energies of 4.9-5.5 GeV to extract the π0→γγ decay width. The experiment was done at Jefferson Lab using the Hall B photon tagger and a high-resolution multichannel calorimeter. The π0→γγ decay width was extracted by fitting the measured cross sections using recently updated theoretical models for the process. The resulting value for the decay width is Γ(π0→γγ)=7.82±0.14(stat)±0.17(syst) eV. With the 2.8% total uncertainty, this result is a factor of 2.5 more precise than the current Particle Data Group average of this fundamental quantity, and it is consistent with current theoretical predictions.

Search for a new gauge boson in electron-nucleus fixed-target scattering by the APEX experiment.

We present a search at the Jefferson Laboratory for new forces mediated by sub-GeV vector bosons with weak coupling α' to electrons. Such a particle A' can be produced in electron-nucleus fixed-target scattering and then decay to an e + e- pair, producing a narrow resonance in the QED trident spectrum. Using APEX test run data, we searched in the mass range 175-250 MeV, found no evidence for an A'→ e+ e- reaction, and set an upper limit of α'/α ~/= 10(-6). Our findings demonstrate that fixed-target searches can explore a new, wide, and important range of masses and couplings for sub-GeV forces.

Precision measurement of the neutral pion lifetime.

The explicit breaking of the axial symmetry by quantum fluctuations gives rise to the so-called axial anomaly. This phenomenon is solely responsible for the decay of the neutral pion π0 into two photons (γγ), leading to its unusually short lifetime. We precisely measured the decay width Γ of the [Formula: see text] process. The differential cross sections for π0 photoproduction at forward angles were measured on two targets, carbon-12 and silicon-28, yielding [Formula: see text], where stat. denotes the statistical uncertainty and syst. the systematic uncertainty. We combined the results of this and an earlier experiment to generate a weighted average of [Formula: see text] Our final result has a total uncertainty of 1.50% and confirms the prediction based on the chiral anomaly in quantum chromodynamics.

Appearance of differentiation characteristics (induction of Ah-receptor-dependent genes) during cultivation of transformed cell clone K8 from embryonic rat fibroblasts.

The differentiation status of fibroblasts can be characterized by their ability to induce Ah-receptor-dependent genes. The ability to induce Ah-receptor-dependent genes encoding cytochrome P450 isoforms, Ah-receptor repressor, and NADPH-quinine oxidoreductase were studied in the transformed cell clone K8 obtained from immortalized embryonic rat fibroblasts by treatment with benzo(a)pyrene and in the parental clone F27. Treatment with benz(a)anthracene did not induce the genes in the transformed clone K8 on passages 4-14, but the induction was recorded in the transformed clone beginning from the 16th passage and later, whereas in F27 cells the induction was observed throughout the experiment. Induction levels of mRNA of the induction-regulating genes encoding the Ah-receptor and Ah receptor nuclear translocator were similar in F27 cells and in the transformed cell clone K8 in both early and late passages. Electrophoretic mobility shift assay showed that in clone K8 transmission of the induction signal was disturbed in the early passages before interaction of the activated Ah-receptor with the recognizing region of DNA. Possible mechanisms responsible for the absence of induction in the early passages in the transformed cells are discussed.

Effects of IKK inhibitor PS1145 on NF-kappaB function, proliferation, apoptosis and invasion activity in prostate carcinoma cells.

A key antiapoptotic transcription factor, nuclear factor kappa-B (NF-kappaB), is known to be critically important for tumor cell growth, angiogenesis and development of metastatic lesions. We and others showed previously that NF-kappaB transcription factor was constitutively activated in androgen-independent prostate carcinoma (PC) cell lines due to the upregulated activity of inhibitor of NF-kappaB kinases (IKK). In this work, using luciferase assay, electrophoretic mobility shift assay and Northern blot analysis of expression of endogenous kappaB-responsive genes, we demonstrate that a novel highly specific small-molecule IKK inhibitor, PS1145, efficiently inhibited both basal and induced NF-kappaB activity in PC cells. We found that PS1145 induced caspase 3/7-dependent apoptosis in PC cells and significantly sensitized PC cells to apoptosis induced by tumor necrosis factor alpha. We also showed that PS1145 inhibited PC cell proliferation. Effects of PS1145 on proliferation and apoptosis correlated with inhibition of interleukin (IL)-6, cyclin D1, D2, inhibitor of apoptosis (IAP)-1 and IAP-2 gene expression and decreased IL-6 protein level. In addition, we found that incubation with PS1145 inhibited the invasion activity of highly invasive PC3-S cells in invasion chamber assay in a dose-dependent manner. Overall, this study provides the framework for development of a novel therapeutic approach targeting NF-kappaB transcription factor to treat advanced PC.

Simultaneous detection of genetic and immunological markers in non-small cell lung cancer: prediction of metastatic potential of tumor.

The restriction fragment length polymorphism of c-Ha-ras-1 and L-myc genes and expression of cell surface effector molecules were studied to determine their potential utility as markers for assessing risk of metastasis in 84 lung cancer patients. We performed a comparative study of primary lung carcinomas, metastases, adjacent tissues and blood samples in a group of patients with lung cancer of different histological types, grade of differentiation and presence of regional and distant metastasis. No differences in the frequency of c-Ha-ras-1 rare alleles were found between lung cancer patients and unaffected controls. The detection of common a4-allele seems to be associated with metastasis and low differentiation of lung carcinomas. S-allele of L-myc was observed in 82.6% of patients with metastatic lesions. Homozygosity of L-allele patients was not evidence for distant metastasis and only 17.4% of these patients have metastatic lesions of the lymph nodes. The expression of HLA class I and receptor of transferrin (TrRec) were tested immunohistochemically in the same patients. In the group of squamous cell carcinomas with regional metastases the expression of HLA class I antigens was decreased [7/21 (33.3%) positive staining tumors versus 13/20 (65.0%) in the group without metastases]. The opposite situation was observed for TrRec. The data of restriction fragment length polymorphism of oncogenes and expression of two cell surface effector molecules, identified in the same patients, were combined. The registration of more than one poor marker, tested in individuals with squamous cell carcinoma, closely correlated with dissemination and advanced stage of the disease. Nearly 90% (20/22) of patients with well and moderately differentiated tumor revealed metastatic lesions versus 6.6% (1/15) of patients with manifestation of a single poor marker. Finally, proposals could be made for the development of a risk group that incorporates both clinical and molecular biology features in the prediction of metastasis.

[Molecular mechanisms of photoreception. V. Reconstitution of a sodium channel on an artificial lipid membrane modified by bovine rod outer segment components]. / Molikuliarnye mekhanizmy fotoretseptsii. V. Popytka modelirovaniia tsitoplazmaticheskoi membrany fotoretseptora na iskusstvennoi lipidnoi membrane, modifitsirovannoi komponentami naruzhnykh segmentov palochek setchatki byka.

An attempt is made to reconstitute the Na+-conductivity elements of rod outer segment (ROS) plasma membrane on the artificial lipid membrane (ALM). ALM were modified by preparation with bovine ROS plasma membrane fragments. Discrete fluctuations of the ALM conductivity were observed at addition of this preparation to the ALM bathing solutions to a final concentration of 0.1--1.0 microgram/ml. The magnitude of these fluctuations was about 25 pS at 140 mM NaCl. The modified ALM possessed preferentially the Na+-conductivity, which was at least five times as great as that for K+ or Li+. The modified ALM showed practically no conductivity for Cl-. The Na+-channels were voltage-dependent. The Na+-channels were "sensitive to visible light" at some experimental conditions. The optimal conditions were obtained for reconstitution of Na+-channel on the ALM. The temporal and termal stabilities of the modified preparation were investigated. It was shown that the frequency of the modified ALM conductivity fluctuations are dependent on temperature and on lipids composition of ALM. The data obtained in our work are in a good agreement with the results of electrophysiological studies of photoreceptor cells. It may be indicated, that the investigated ALM contains the Na+-channel of the ROS plasma membranes. It is suggested that the reconstituted system will be useful for studying the principles of regulation of ROS plasma membrane sodium conductivity and the nature of a mediator in a photoreceptor transduction mechanism.

[Fast photo-induced changes in the light scattering of vertebrate photoreceptor membrane preparations. Study of suspensions of vesicles obtained by ultrasonic treatment of the outer segments of retinal rods]. / Bystrye fotoindutsirovannye izmeneniia svetorasseianiia preparatov fotoretseptornykh membran pozvonochnykh. Izuchenie suspenzii vezikul, poluchennykh pri ul'trazvukovoi obrasbotke naruzhnykh segmentov palochek setchatki.

By light scattering method it was shown, that vesicles, obtained by sonication of rod outer segment membranes in different ionic media rapidly and irreversibly increased their volume under bleaching of rhodopsin. Apparently, this volume change was caused by the increase in the amount of free ions in vesicles under illumination. The photoinduced volume change was practically the same in all cases studied (equal ionic constitutions inside and outside of vesicles; in the presence of penetrating anion SCN-; under ionic gradients on vesicle membranes; in the presence of ionophores which induce the permeability for K+ and H+) and corresponds to the appearance of no more than one ion inside the vesicle under bleaching of one rhodopsin molecule. The obtained results testify against the hypothesis, that bleaching of rhodopsin induce essential increase in ionic permeability of rod outer segment disk membranes.

[Fast photo-induced changes in the light scattering of vertebrate photoreceptor membrane preparations. Study of a suspension of retinal outer rod segments]. / Bystrye fotoindutsirovannye izmeneniia svetorasseianiia preparatov fotoretseptornykh membran pozvonochnykh, izuchenie suspenzii naruzhnykh segmentov palochek setchatki.

It has been found that light induced a fast decrease of light scattering of suspensions of retinal rod outer segments. This decrease coincides in time with the decay of metarhodopsin I. Evidence is presented that this effect is conditioned by an increase of the interdisc volume due to a photoinduced increase of ion numbers in them. The value of the effect was practically independent of pH, ionic composition and osmomolarity of the medium. The effect amplitude was small (10% to the value of light scattering change induced by hypertonic shock) and in proportion to the value of bleached rhodopsin. Calculations in the basis of these data have shown that bleaching of a rhodopsin molecule brings about the appearance of no more than one ion in the interdisc volume. The results obtained are used to analyzed the validity of our proposition concerning the existence of ionic photoconductivity in the disc membranes of rod outer segments.

[The course and outcome of tuberculous meningoencephalomyelitis]. / Techenie i iskhody tuberkuleznogo meningoéntsefalomielita.

Nineteen patients aged 8 months to 62 years suffering from tuberculous meningoencephalomyelitis were followed up from 1968 to 1987. The given pattern of tuberculous meningitis was established to occur mostly in adults. In children and adolescents the disease onset was mostly acute or subacute, whereas in adults, it was progressive. It was also established that as a rule children and adolescents manifested a descending pattern of meningoencephalomyelitis whereas adults an ascending one. The disease was marked by clinical polymorphism, creating certain difficulties for early diagnosis. Tuberculous meningoencephalomyelitis still remains the most rarely occurring and severe disease involving the meninges and central nervous system. It is not infrequently associated with the development of irreversible complications, thus being a cause of disability and high enough lethality.