Nucleon Structure Functions from Operator Product Expansion on the Lattice.

Deep-inelastic scattering, in the laboratory and on the lattice, is most instructive for understanding how the nucleon is built from quarks and gluons. The long-term goal is to compute the associated structure functions from first principles. So far this has been limited to model calculations. In this Letter we propose a new method to compute the structure functions directly from the virtual, all-encompassing Compton amplitude, utilizing the operator product expansion. This overcomes issues of renormalization and operator mixing, which so far have hindered lattice calculations of power corrections and higher moments.

Electric Dipole Moment of the Neutron from 2+1 Flavor Lattice QCD.

We compute the electric dipole moment d(n) of the neutron from a fully dynamical simulation of lattice QCD with 2+1 flavors of clover fermions and nonvanishing θ term. The latter is rotated into a pseudoscalar density in the fermionic action using the axial anomaly. To make the action real, the vacuum angle θ is taken to be purely imaginary. The physical value of dd(n) is obtained by analytic continuation. We find d(n)=-3.9(2)(9)×10(-16) θ e cm, which, when combined with the experimental limit on d(n), leads to the upper bound |θ|≲7.4×10(-11).

Playing Tic-Tac-Toe with a Sugar-Based Molecular Computer.

Today, molecules can perform Boolean operations and circuits at a level of higher complexity. However, concatenation of logic gates and inhomogeneous inputs and outputs are still challenging tasks. Novel approaches for logic gate integration are possible when chemical programming and software programming are combined. Here it is shown that a molecular finite automaton based on the concatenated implication function (IMP) of a fluorescent two-component sugar probe via a wiring algorithm is able to play tic-tac-toe.

Discovery of 40Mg and 42Al suggests neutron drip-line slant towards heavier isotopes.

A fundamental question in nuclear physics is what combinations of neutrons and protons can make up a nucleus. Many hundreds of exotic neutron-rich isotopes have never been observed; the limit of how many neutrons a given number of protons can bind is unknown for all but the lightest elements, owing to the delicate interplay between single particle and collective quantum effects in the nucleus. This limit, known as the neutron drip line, provides a benchmark for models of the atomic nucleus. Here we report a significant advance in the determination of this limit: the discovery of two new neutron-rich isotopes--40Mg and 42Al--that are predicted to be drip-line nuclei. In the past, several attempts to observe 40Mg were unsuccessful; moreover, the observation of 42Al provides an experimental indication that the neutron drip line may be located further towards heavier isotopes in this mass region than is currently believed. In stable nuclei, attractive pairing forces enhance the stability of isotopes with even numbers of protons and neutrons. In contrast, the present work shows that nuclei at the drip line gain stability from an unpaired proton, which narrows the shell gaps and provides the opportunity to bind many more neutrons.

Evidence for the ground-state resonance of 26O.

Evidence for the ground state of the neutron-unbound nucleus (26)O was observed for the first time in the single proton-knockout reaction from a 82 MeV/u (27)F beam. Neutrons were measured in coincidence with (24)O fragments. (26)O was determined to be unbound by 150(-150)(+50) keV from the observation of low-energy neutrons. This result agrees with recent shell-model calculations based on microscopic two- and three-nucleon forces.

First observation of ground state dineutron decay: 16Be.

We report on the first observation of dineutron emission in the decay of 16Be. A single-proton knockout reaction from a 53 MeV/u 17B beam was used to populate the ground state of 16Be. 16Be is bound with respect to the emission of one neutron and unbound to two-neutron emission. The dineutron character of the decay is evidenced by a small emission angle between the two neutrons. The two-neutron separation energy of 16Be was measured to be 1.35(10) MeV, in good agreement with shell model calculations, using standard interactions for this mass region.

Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN).

BACKGROUND: Schizophrenia is a severe and often difficult to treat psychiatric illness. In many patients, negative symptoms dominate the clinical picture. Meta-analysis has suggested moderate, but significant effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on these symptoms. For treatment of depression a much shorter protocol - intermittent theta burst stimulation (iTBS) - has shown to be non-inferior to conventional high-frequency rTMS. This randomized, sham-controlled, rater-blinded clinical trial assesses the effects of conventional HF-rTMS as well as of iTBS of the left dorsolateral prefrontal cortex in comparison with sham. METHODS: The study will be conducted at two psychiatric university hospitals in Germany and at two in the Czech Republic. Assuming an effect size of 0.64 to be detected with a power of 80%, the calculated sample size is 90 patients. Primary outcome will be the difference in the Scale for the Assessment of Negative Symptoms (SANS) score between each active arm and the sham arm at end of treatment.In addition, the trial investigates effects on depressive symptoms, cognitive performance and cigarette smoking. Recording magnetic resonance imaging (MRI) and electroencephalography (EEG) data will serve to assess whether treatment success can be predicted by neural markers and is related to specific neurobiological changes. DISCUSSION: This is a clinical trial directly comparing 10 Hz-rTMS and iTBS in a sham-controlled manner in treating negative symptoms of schizophrenia. If successful, this would present an interesting treatment option for a chronic and severe condition that can be applied at most psychiatric hospitals and only takes up a few minutes per day. TRIAL REGISTRATION NUMBER: This trial has been registered at clinicaltrials.gov, Identifier: NCT04318977. DATA DISSEMINATION: Results from the trial shall be published in peer-reviewed journals and presented at meetings and conferences.

Burden of disease - prevalence and incidence of ESRD in selected European regions and populations.

Rates of renal replacement therapy (RRT) vary markedly between Eastern and Western European countries. This review aims to establish the characteristics of healthcare systems and renal services that are independently associated with rates of initiation of RRT in these countries. The incidence of RRT varied from 12 to 455 per million populations (pmp); the only general population indicator independently associated with RRT incidence was aged 65+. Economic and financial conditions could also play an important role. Gross Domestic Product (GDP) per capita and the proportion of GDP spent on healthcare independently predicted RRT incidence. Each increase in hemodialysis (HD) facilities and competition between providers is associated with higher RRT incidence. In this context, macroeconomic and potentially modifiable renal service organizational factors appear more important determinants of provision of RRT than measurable medical factors. The economic, financial or medical conditions could also play an important role in treatment strategy. The proportion of patients receiving HD, peritoneal dialysis (PD) or transplantation shows marked variation in Europe. The East Europeans use more HD and less RTx as compared to West Europeans; the use of PD is similar. Treatment of anemia and mineral metabolism disorders also varies from one region to another. The mean baseline hemoglobin level and the prevalence of patients reaching this value are higher in West Europeans. Regarding mineral metabolism, the percent of patients achieving all four parameters (Ca, P, CaxP and PTH) was also higher in Western Europe. The adherence to EBPG (European Best Practice Guidelines) was also higher in these countries.

Pancreatic and gastric heterotopic tissue presenting as a symptomatic gallbladder mass: A case report and literature review.

Pancreatic and gastric heterotopia is an uncommon congenital anomaly in which gastric and/or pancreatic tissue is found outside of its anatomic location. In the majority of patients, lesions are found incidentally because they tend to be asymptomatic. However, lesions may become symptomatic when inflammation, obstruction, and bleeding occurs. Depending on tissue size and location they can harvest a landscape of nonspecific symptoms, causing a delay in diagnosis. Heterotopic tissue of either gastric or pancreatic origin have been reported in literature, however the presence of combined gastric and pancreatic heterotopic tissue is exceedingly rare. We report a case of an 18-year-old female with polypoid gastric and pancreatic heterotopia and focal intestinal metaplasia of the gallbladder with clinical findings of acute cholecystitis. In this literature review, we synthesize the clinical significance, histopathological features, diagnosis and management of pancreatic and gastric heterotopic tissue.

Differential activation of pituitary hormone genes by human Lhx3 isoforms with distinct DNA binding properties.

Lhx3 is a LIM homeodomain transcription factor essential for pituitary development and motor neuron specification in mice. We identified two isoforms of human Lhx3, hLhx3a and hLhx3b, which differ in their ability to trans-activate pituitary gene targets. These factors are identical within the LIM domains and the homeodomain, but differ in their amino-terminal sequences preceding the LIM motifs. Both isoforms are localized to the nucleus and are expressed in the adult human pituitary, but gene activation studies demonstrate characteristic functional differences. Human Lhx3a trans-activated the alpha-glycoprotein subunit promoter and a reporter construct containing a high-affinity Lhx3 binding site more effectively than the hLhx3b isoform. In addition, hLhx3a synergized with the pituitary POU domain factor, Pit-1, to strongly induce transcription of the TSHbeta-subunit gene, while hLhx3b did not. We demonstrate that the differences in gene activation properties between hLhx3a and hLhx3b correlate with their DNA binding to sites within these genes. The short hLhx3b-specific amino-terminal domain inhibits DNA binding and gene activation functions of the molecule. These data suggest that isoforms of Lhx3 may play distinct roles during development of the mammalian pituitary gland and other neuroendocrine systems.

Detection and developmental changes of the 1,25-(OH)2-D3 receptor concentration in mouse skin and intestine.

We investigated [3H]1,25-dihydroxyvitamin D3-specific binding activity in fetal, neonatal, and adult mouse skin to determine (a) during which stage in development the skin develops the capacity to respond to this hormone and (b) whether the hormone binding activity changed during development and maturation. A macromolecule with properties similar to those of the chick intestinal 1,25-dihydroxyvitamin D3 receptor was detected in the skin and intestine of mouse pups at 17 days of fetal life. 1,25-Dihydroxyvitamin D3-specific binding activity from both tissues sedimented on linear sucrose gradients at 3.5-3.7S and eluted from DNA cellulose at 0.22 M KCl. At earlier stages of fetal life (12-14 days) receptor-like activity was detected in cytosols prepared from whole-mouse fetuses. 1,25-Dihydroxyvitamin D3-specific binding activity was quantitated in the skin and intestine throughout development using a chromatin binding assay. Scatchard analysis of saturation binding data showed that the concentration of binding activity in skin increased rapidly after birth and reached a maximum when the mice were 10-19 days old. By contrast, the binding activity that was detected in the fetal and neonatal whole intestine remained low until the mice were weaned. The affinity (Kd) of the binding activity was similar in skin and intestine at all ages studied. It is concluded that 1,25-dihydroxyvitamin D3-specific binding activity appears in both skin and intestine of the mouse prior to birth and increases in these two tissues during different stages in development.

Androgen deficiency in women with hypopituitarism.

Androgen deficiency in men is associated with severe osteopenia, alterations in body composition including an increase in fat mass, and decreased libido. Little is known about the pathophysiology, metabolic consequences, or gender-specific effects of androgen deficiency in women. Acquired hypopituitarism in women is characterized by central hypogonadism and/or hypoadrenalism and therefore may affect critical sources of androgen production in women. We hypothesized that serum androgen levels would be decreased in women with hypopituitarism. We therefore determined serum androgen levels in 55 women with hypopituitarism and 92 controls. This included 4 subsets of hypopituitary women: 1) women less than 50 yr old not receiving estrogen, 2) women less than 50 yr old receiving estrogen, 3) women more than 50 yr old not receiving estrogen, and 4) women more than 50 yr old receiving estrogen. Premenopausal controls with regular menstrual cycles were studied in the early follicular phase, midcycle, and luteal phase during one cycle. All other subjects were studied 3 times during the month at comparable intervals to mimic these 3 time points of the normal menstrual cycle. Serum testosterone, free testosterone, androstenedione, and dehydroepiandrosterone sulfate levels were markedly reduced in all 4 groups of women with hypopituitarism compared with controls (P < 0.0001). Moreover, serum testosterone, free testosterone, and androstenedione levels were lower in women with central hypoadrenalism and hypogonadism than in subjects with hypoadrenalism or hypogonadism alone (P < 0.025). Mean DHEAS levels were decreased in hypopituitary women with both hypogonadism and hypoadrenalism compared with those in women with hypogonadism alone (P < 0.0001). These data demonstrate hypoandrogenemia in women with hypopituitarism. The physiological consequences of low androgen levels in this population remain to be determined.

Role of the LIM domains in DNA recognition by the Lhx3 neuroendocrine transcription factor.

LIM homeodomain transcription factors regulate many aspects of development in multicellular organisms. Such factors contain two LIM domains in their amino terminus and a DNA-binding homeodomain. To better understand the mechanism of gene regulation by these proteins, we studied the role of the LIM domains in DNA interaction by Lhx3, a protein that is essential for pituitary development and motor neuron specification in mammals. By site selection, we demonstrate that Lhx3 binds at high affinity to an AT-rich consensus DNA sequence that is similar to sequences located within the promoters of some pituitary hormone genes. The LIM domains reduce the affinity of DNA binding by Lhx3, but do not affect the specificity. Lhx3 preferentially binds to the consensus site as a monomer with minor groove contacts. The Lhx3 binding consensus site confers Lhx3-dependent transcriptional activation to heterologous promoters. Further, DNA molecules containing the consensus Lhx3 binding site are bent to similar angles in complexes containing either wild type Lhx3 or Lhx3 lacking LIM domains. These data are consistent with Lhx3 having the properties of an architectural transcription factor. We also propose that there are distinct classes of LIM homeodomain transcription factors in which the LIM domains play different roles in modulating interactions with DNA sites in target genes.

The liver in hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease).

The livers of four patients with hereditary hemorrhagic telangiectasia--including the original case of Osler--were examined at autopsy. Characteristic random focal fibrovascular lesions were found in all. The importance of recognizing the apparently common and seemingly benign hepatic involvement in this disease is emphasized in view of its possible confusion with more serious types of liver disease that may complicate the condition.

Parallel DNA template preparation using a vacuum filtration sample transfer device.

Solid-phase techniques have facilitated the handling of biochemical analytes. This has stimulated the development of systems by which large sample panels can be analyzed with high levels of security and quality. We describe a sample transfer device based on the principle of vacuum filtration, which enables parallel handling of 96 samples of analytes bound to Sepharose beads. The tool was employed for strand separation of DNA samples, by attracting the beads to filter probes while passing them between the reagent solutions. The samples were analyzed using Pyrosequencing technology and proved to yield genotyping results of high quality. The presented sample preparation procedure provides an important link in the development of integrated systems for rapid genetic analysis at a low cost. In addition, the same filter could be reused extensively with very low risk for detectable cross-contamination between assays and without any reduction in processing capacity, thus further reducing the cost per analyzed sample.

Freeze-fracture autoradiography. Progress towards a routine technique.

Freeze-fracture autoradiography was introduced in 1976 as a new technique for the autoradiography of diffusible compounds at the electron microscope level. With the original approach coating of the frozen replicated specimens was performed in a cryostat at atmospheric pressure. Ice contamination of the specimen surface acting as an outstanding source of artifacts was thereby not excluded. With the use of a specially designed coating device and volatile spreading substances it was made possible to coat the frozen replicated specimens in the maintained vacuum of the freeze-fracture plant. In this complicated technique we have recently extended the freeze-fracture autoradiography to labeled frozen-dried "half" membranes of red blood cells.

Biochemical and genetic characterization of the porcine Prophet of Pit-1 pituitary transcription factor.

Prophet of Pit-1 (Prop-1) is a paired class homeodomain transcription factor that is specifically expressed in the pituitary gland. Mutations in the Prop-1 gene cause compound pituitary diseases in mouse models and human patients. We have cloned and analyzed the porcine ortholog of Prop-1. Analysis of cDNAs revealed that the porcine Prop-1 sequence is similar to the mouse and human proteins within the homeodomain and carboxyl terminus, but the amino terminus is poorly conserved. The Prop-1 gene consists of three exons and two introns and spans 3.8 kilobases of genomic DNA. In addition, we mapped Prop-1 to the q arm of pig chromosome two. During development, Prop-1 is expressed at the time of pituitary organogenesis. In the adult, expression was observed at low levels only in the pituitary gland. The porcine Prop-1 protein displays similar biochemical, DNA binding, and transcriptional activities to human PROP-1. We conclude that, although the structural divergence between the porcine and human PROP-1 molecules may indicate some distinct functions, the porcine Prop-1 gene encodes a pituitary transcription factor with similar overall activities to the human ortholog.

Extraosseous osteosarcoma presenting with intestinal hemorrhage: case report and literature review.

A 23-year-old man presented with intestinal bleeding due to an extraosseous osteosarcoma of the jejunum. A lesion was also found in the deltoid muscle, and other metachronous soft tissue sites developed subsequently. The presence of malignant osteoid was documented by immunohistochemical studies of one of the lesions. The patient died of metastatic disease 19 months after diagnosis, despite surgical resections and adjuvant chemotherapy. This unique presentation is discussed, and the literature concerning extraosseous osteosarcoma is reviewed.

Cellular dyscohesion in fine-needle aspiration of breast carcinoma. Prognostic indicator for axillary lymph node metastases?

The role of fine-needle aspiration (FNA) in the diagnosis of breast carcinoma is established. We evaluated whether the degree of cellular dyscohesion and the nuclear grade in FNA material of breast carcinomas are reliable prognostic predictors for ipsilateral axillary lymph node metastasis. FNA specimens from 98 women with infiltrating ductal and infiltrating lobular carcinomas were evaluated by 2 observers for degree of cellular dyscohesion and nuclear grade. Follow-up specimens from lumpectomy and/or mastectomy with axillary dissection were available for each patient. By univariate analysis, degree of cellular dyscohesion and nuclear grade were not predictive of axillary lymph node metastasis regardless of tumor size. High histologic grade, size greater than 2 cm, and patient age younger than 52 years were significant predictors of metastasis. By multivariate analysis, size greater than 2 cm and age younger than 52 years were statistically significant for lymph node metastasis. In contrast with a published study, the results of the present study fail to show cellular dyscohesion in FNA specimens as predictive of lymph node metastasis; however, the scoring method for determining the degree of cellular dyscohesion is reproducible between 2 independent observers.