The mutation process on the ancestral line under selection.

We consider the Moran model of population genetics with two types, mutation, and selection, and investigate the line of descent of a randomly-sampled individual from a contemporary population. We trace this ancestral line back into the distant past, far beyond the most recent common ancestor of the population (thus connecting population genetics to phylogeny), and analyse the mutation process along this line. To this end, we use the pruned lookdown ancestral selection graph (Lenz et al., 2015), which consists of a set of potential ancestors of the sampled individual at any given time. Relative to the neutral case (that is, without selection), we obtain a general bias towards the beneficial type, an increase in the beneficial mutation rate, and a decrease in the deleterious mutation rate. This sheds new light on previous analytical results. We discuss our findings in the light of a well-known observation at the interface of phylogeny and population genetics, namely, the difference in the mutation rates (or, more precisely, mutation fluxes) estimated via phylogenetic methods relative to those observed in pedigree studies.

Two-Loop Four-Graviton Scattering Amplitudes.

We present the analytic form of the two-loop four-graviton scattering amplitudes in Einstein gravity. To remove ultraviolet divergences we include counterterms quadratic and cubic in the Riemann curvature tensor. The two-loop numerical unitarity approach is used to deal with the challenging momentum dependence of the interactions. We exploit the algebraic properties of the integrand of the amplitude in order to reduce it to a minimal basis of Feynman integrals. Analytic expressions are obtained from numerical evaluations of the amplitude. Finally, we show that four-graviton scattering observables depend on fewer couplings than naïvely expected.

Analytic Form of Planar Two-Loop Five-Gluon Scattering Amplitudes in QCD.

We present the analytic form of the planar two-loop five-gluon scattering amplitudes in QCD for a complete set of independent helicity configurations of external gluons. These include the first analytic results for five-point two-loop amplitudes relevant for the computation of next-to-next-to-leading-order QCD corrections at hadron colliders. The results were obtained by reconstructing analytic expressions from numerical evaluations. The complexity of the computation is reduced by exploiting physical and analytical properties of the amplitudes, employing a minimal basis of so-called pentagon functions that have recently been classified.

Two-Loop Four-Gluon Amplitudes from Numerical Unitarity.

We present the first numerical computation of two-loop amplitudes based on the unitarity method. As a proof of principle, we compute the four-gluon process in the leading-color approximation. We discuss the new method, analyze its numerical properties, and apply it to reconstruct the analytic form of the amplitudes. The numerical method is universal, and can be automated to provide multiscale two-loop computations for phenomenologically relevant signatures at hadron colliders.

[Peranal bleeding and elevated liver function tests in a 33­year-old refugee from Nigeria]. / Peranaler Blutabgang und erhöhte Leberwerte bei einem 33­jährigen Flüchtling aus Nigeria.

A 33-year-old refugee from Nigeria, who had been living in Germany for 1 year, was admitted to the hospital due to pelvic pain, peranal hemorrhage, and an unexplained increase in transaminase levels. As the liver screening tests, sonography findings, and colonoscopy were normal, a liver biopsy was performed that revealed Schistosoma mansoni worm eggs as an unexpected diagnostic finding. Serological tests for specific antibodies and parasitological egg detection in the stool confirmed the diagnosis. After only temporary response to a short-term and low-dose treatment with praziquantel, a 3-day high-dose (40 mg/kg body weight) treatment with praziquantel finally led to long-lasting symptom relief.

A novel machine-learning framework based on early embryo morphokinetics identifies a feature signature associated with blastocyst development.

BACKGROUND: Artificial Intelligence entails the application of computer algorithms to the huge and heterogeneous amount of morphodynamic data produced by Time-Lapse Technology. In this context, Machine Learning (ML) methods were developed in order to assist embryologists with automatized and objective predictive models able to standardize human embryo assessment. In this study, we aimed at developing a novel ML-based strategy to identify relevant patterns associated with the prediction of blastocyst development stage on day 5. METHODS: We retrospectively analysed the morphokinetics of 575 embryos obtained from 80 women who underwent IVF at our Unit. Embryo morphokinetics was registered using the Geri plus® time-lapse system. Overall, 30 clinical, morphological and morphokinetic variables related to women and embryos were recorded and combined. Some embryos reached the expanded blastocyst stage on day 5 (BL Group, n = 210), some others did not (nBL Group, n = 365). RESULTS: The novel EmbryoMLSelection framework was developed following four-steps: Feature Selection, Rules Extraction, Rules Selection and Rules Evaluation. Six rules composed by a combination of 8 variables were finally selected, and provided a predictive power described by an AUC of 0.84 and an accuracy of 81%. CONCLUSIONS: We provided herein a new feature-signature able to identify with an high performance embryos with the best developmental competence to reach the expanded blastocyst stage on day 5. Clear and clinically relevant cut-offs were identified for each considered variable, providing an objective tool for early embryo developmental assessment.

Four-jet production at the Large Hadron Collider at next-to-leading order in QCD.

We present the cross sections for production of up to four jets at the Large Hadron Collider, at next-to-leading order in the QCD coupling. We use the BLACKHAT library in conjunction with SHERPA and a recently developed algorithm for assembling primitive amplitudes into color-dressed amplitudes. We adopt the cuts used by ATLAS in their study of multijet events in pp collisions at √s=7 TeV. We include estimates of nonperturbative corrections and compare to ATLAS data. We store intermediate results in a framework that allows the inexpensive computation of additional results for different choices of scale or parton distributions.

Precise predictions for W+4-jet production at the large hadron collider.

We present the next-to-leading order (NLO) QCD results for W+4-jet production at hadron colliders. This is the first hadron-collider process with five final-state objects to be computed at NLO. It represents an important background to many searches for new physics at the energy frontier. Total cross sections, as well as distributions in the jet transverse momenta, are provided for the initial LHC energy of √s = 7 TeV. We use a leading-color approximation, known to be accurate to 3% for W production with fewer jets. The calculation uses the BLACKHAT library along with the SHERPA package.

Deep sequencing evidence from single grapevine plants reveals a virome dominated by mycoviruses.

We have characterized the virome in single grapevines by 454 high-throughput sequencing of double-stranded RNA recovered from the vine stem. The analysis revealed a substantial set of sequences similar to those of fungal viruses. Twenty-six putative fungal virus groups were identified from a single plant source. These represented half of all known mycoviral families including the Chrysoviridae, Hypoviridae, Narnaviridae, Partitiviridae, and Totiviridae. Three of the mycoviruses were associated with Botrytis cinerea, a common fungal pathogen of grapes. Most of the rest appeared to be undescribed. The presence of viral sequences identified by BLAST analysis was confirmed by sequencing PCR products generated from the starting material using primers designed from the genomic sequences of putative mycoviruses. To further characterize these sequences as fungal viruses, fungi from the grapevine tissue were cultured and screened with the same PCR probes. Five of the mycoviruses identified in the total grapevine extract were identified again in extracts of the fungal cultures.

Stereoselective approach to hydroxyindolizidines: protection/deprotection of the nitrone functionality via cycloaddition/retrocycloaddition.

The enantiomerically pure indolizidine (-)-21 has been synthesized starting from L-malic acid. The key intermediate 20 has been assembled through an intramolecular 1,3-dipolar cycloaddition of a nitrone generated in situ by retrocycloaddition from isoxazolidine 17 or 18. The configuration of the new three stereocenters was set up with complete control in the cycloaddition step. The presented synthetic route provides a general and highly selective methodology toward indolizidines having the [1,8a]-cis configuration.

Total synthesis of (-)-rosmarinecine by intramolecular cycloaddition of (S)-malic acid derived pyrroline N-oxide.

[reaction in text] Straightforward total syntheses of (-)-rosmarinecine have been achieved from L-malic acid derived pyrroline N-oxides by two novel useful cascade processes, which join the family of domino reactions. Both strategies, which furnished the target alkaloid in enantioenriched and enantiopure forms, respectively, allow complete control of configuration at all the three newly created contiguous stereogenic centers.

Design and synthesis of a new bicyclic dipeptide isostere.

The synthesis of a new Gly-Pro turn mimetic and the computational study of its ability to induce beta-turn is reported.

Synthesis of taurine analogues from alkenes: preparation of 2-aminocycloalkanesulfonic acids.

(+/-)trans 2-Aminocyclohexanesulfonic acid and (+/-)trans 2-aminocyclopentanesulfonic acid were prepared from cyclohexene and cyclopentene respectively by sulfur monochloride addition, followed by oxidation to 2-chlorosulfonic acid and substitution of chlorine.

[Purulent meningitis in the elderly. Incidence in our area]. / Meningitis purulenta en el anciano. Incidencia en nuestro medio.

A retrospective study in patients over 65 years old with acute bacterial meningitis admitted to the internal medicine department of the "Hospital Provincial de Zamora" over the last 25 years, is presented. 43 cases (26.87%) over 65 years old were found, out of 160 cases admitted with ABM during this period. This high prevalence is partially explained because of the large elderly population in this area. The frequent atypical clinical features than can result in the diagnosis being confused with neurological pathology such as CVA (which is common at this age) is noteworthy. The most frequent etiology was meningococos (41.86%), followed by pneumococos (4.6%) and E. Coli (4.6%). We highlight the good prognosis of ABM in the elderly, early diagnosis and the right therapy necessary to achieve it.

[Alternatives for closure of the rectal "stump" in Hartmann's operation. A comparative experimental study which includes the resorbable mechanical suture (polysorb)]. / Alternativas de cierre de "muñón" rectal en la operación de Hartmann. Estudio experimental comparativo que incluye sutura mecánica reabsorbible (polisorb).

Five different kinds of sutures which can be used for closure of the rectal stump in Hartmann's operation are evaluated in the same animal. They are compared at six different phases of the cicatrization process: 7-30-45-60-90 and 150 days. In the analysis, the degree of complete cicatrization is considered as well as the thickness of the cicatriced tissue, and other factors such as persistence of suture material and the result of it. All of the sutures involved accomplished the goal of a good joint of the planes of intestinal suture. Although, two of them, the metal stapler and Polyglactin (Vicryl) in extramucosal surgery fulfill almost in an ideal way the goals concerning security, rare reaction to suture material, and consequently less thickness in the cicatriced tissue (2 x 2 and 1 x 1 mm respectively) as well as complete cicatrization in ninety days. Stapler is performed quicker and in a more aseptic way, but the scar resulting from Polyglactin is smaller. In separate extramucosal points, silk produces a more important tissue reaction with a thicker scar (3 x 3 mm) coming to an end in 150 days. "Albert Lembert" type suture is really far away from being a good mean because it creates an important tissue reaction with a thick scar (3 x 3 mm), with late consolidation (150 days) and granulomatous reaction. Resorbable stapler--Polisorb--has a considerable volume and it causes an important tissue reaction which determines a very thick (4.5 x 4.5 mm) and "unfinished" scar within 150 days; really far away for practical use.

[Venereal granuloma. Its clinical manifestation in the genitals and other parts of the body]. / Granuloma venéreo. Su manifestación clinica en genitales y otras partes del organismo.

Ten patients with granuloma inguinale (venereum), were studied and treated in the "Institute of Dermatology" of Guatemala city, and the high incidence of this venereal desease is noted by the author. Also, there is the detailed description of two cases which were complicated with dissemination of the granuloma inguinate to distant organs of the body; one shows knee joint lesions and the other the invasion of the lungs. 9 cases were successfully treated with a semisynthetic Tetracycline drug alone and one patient, received the combined treatment of Tetracycline and Streptomycine, with spectacularly good results.

D(-)lentiginosine-induced apoptosis involves the intrinsic pathway and is p53-independent.

We have recently found that D(-)lentiginosine, a synthetic iminosugar exerting glucosidase inhibitory activity, but not its natural enantiomer lentiginosine, is endowed with an unexpected, pro-apoptotic activity. Here, we investigated mechanisms involved in apoptosis induced by D(-)lentiginosine in MOLT-3, HT-29 and SH-SY5Y tumour cell lines. The results showed that D(-)lentiginosine increased caspase 9 expression at 18 h in all the cell lines from 1.5-3.1 folds. Cytochrome c in the cytoplasm was found to be increased from 2.3-2.6 folds in treated cells with respect to control cells. These effects were accompanied by a remarkable collapse of the mitochondrial membrane potential and by the downregulation of anti-apoptotic genes, as well as the upregulation of pro-apoptotic genes of the Bcl-2 family. U937Bcl-2 transfectants, highly expressing Bcl-2, were reluctant to undergo apoptosis even following treatment with 500 µM D(-)lentiginosine, whereas apoptosis by D(-)lentiginosine was induced also in U937 cells, naturally deficient in P53. Thus, our study establishes that the enantiomer of a natural iminosugar is endowed with a possible anti-tumorigenic effect that might be ascribed not only to their capacity to inhibit glycosidases but also to other unknown mechanisms. These data encourage further investigation on similar compounds to make them an interesting platform for the generation of new anticancer drugs.

Octahedral tilting, monoclinic phase and the phase diagram of PZT.

Anelastic and dielectric spectroscopy measurements on PbZr(1-x)Ti(x)O(3) (PZT) close to the morphotropic (MPB) and antiferroelectric boundaries provide new insight into some controversial aspects of its phase diagram. No evidence is found of a border separating monoclinic (M) from rhombohedral (R) phases, in agreement with recent structural studies supporting a coexistence of the two phases over a broad composition range x<0.5, with the fraction of M increasing toward the MPB. It is also discussed why the observed maximum of elastic compliance appears to be due to a rotational instability of the polarization linearly coupled to shear strain. Therefore it cannot be explained by extrinsic softening from finely twinned R phase alone, but indicates the presence also of M phase, not necessarily homogeneous.A new diffuse transition is found within the ferroelectric phase near x ~ 0.1, at a temperature T(IT) higher than the well established boundary T(T) to the phase with tilted octahedra. It is proposed that around T(IT) the octahedra start rotating in a disordered manner and finally become ordered below T(T). In this interpretation, the onset temperature for octahedral tilting monotonically increases up to the antiferroelectric transition of PbZrO(3), and the depression of T(T)(x) below x=0.18 would be a consequence of the partial relief of the mismatch between the average cation radii with the initial stage of tilting below T(IT).