Simultaneous precise editing of multiple genes in human cells

Abstract. When double-strand breaks are introduced in a genome by CRISPR they are repaired either by non-homologous end joining (NHEJ), which often results i

Field evaluation of controlled traffic farming in central Europe using commercially available machinery

The progressive increase in the size and weight of farm machinery causes concerns due to the increased risk of soil compaction that arises from non-organized vehicle traffic. Controlled traffic farming (CTF) offers an effective means to manage compaction by confining all load-bearing wheels to the least possible area of permanent traffic lanes. Although CTF is relatively well-established in Australia and in some countries in Northern Europe, its benefits and suitability for Central European conditions have not been demonstrated. A long-term experimental site was established in 2010 in Nitra, Slovakia, using a 6 m 'OutTrac-CTF' system with shallow non-inversion tillage practices. The 16 ha experimental field of loam soil is representative of land used for arable cropping in Central Europe. Four traffic intensities (non-trafficked, one traffic event per year with a single pass, multiple passes with permanent traffic lanes, and random traffic) were evaluated using two traffic systems: controlled (CTF) and non-controlled traffic farming (referred to as random traffic farming or RTF). This article reports the findings derived from the first four years of the project and focuses on the effects of traffic systems on yields observed in cereal crops (winter wheat, spring barley, and maize) grown at the site in a rotation cycle. Significant differences (p < 0.1) in yield are reported due to the heterogeneity of the field and the seasonal effect of weather. The results of this investigation suggest that CTF systems have potential to increase production sustainably in arable farming systems in Central Europe. Well-designed CTF systems using commercially available machinery allow for reductions in the area affected by traffic of up to 50% compared with random, non-organized traffic systems. Results also show that in years when soil moisture was not limiting, the yield penalty from a single (annual) machine pass was relatively small (~5%). However, in dry years, compaction caused by multiple machinery passes may lead to yield losses of up to 33%. When considering the ratio of non-trafficked to trafficked area within the different CTF systems evaluated in this study, yield improvements of up to 0.5 t ha-1 for cereals are possible when converting from RTF to CTF. Given the assumptions made in the analyses, such yield increases translate into increased revenues of up to 117 USD ha-1 (1 Euro= 1.1 USD). For Central European farming systems, the main benefit of CTF appears to be improved efficiency and enhanced agronomic stability, especially in dry seasons, where the significant yield penalty from machinery passes is likely

Primary malignant melanoma of the stomach: report of a case

We report a case of primary malignant melanoma (MM) of the stomach. The patient, a 73-year-old man, was referred to our hospital for investigation of an elevated lesion in the stomach, detected by gastroscopy. On admission, physical examinations and laboratory data were unremarkable. Gastroscopy revealed a pigmented, elevated tumor, approximately 2 cm in diameter, in the posterior wall of the stomach. A biopsy was taken, which resulted in a diagnosis of MM, based on the presence of melanin in tumor cells. F-18 fluorodeoxyglucose positron emission tomography showed no accumulation of tracer except for the tumor in the stomach, indicating that it was a primary MM of the stomach. The patient underwent distal gastrectomy, but died of recurrence 1 year later. Very few cases of primary MM of the stomach have been reported. Thus, we report this case, followed by a review of the literature

Multiple Core and Vibronic Coupling Effects in Attosecond Stimulated X-Ray Raman Spectroscopy

Attosecond Stimulated X-ray Raman Spectroscopy (SXRS) is a promising technique for investigating molecular electronic structure and photochemical processes with high spatial and temporal resolution. We present a theoretical study of SXRS from multiple core excitation sites of the same element. Two issues are addressed: interference between pathways contributing the signals from different sites; and how nuclear vibrations influence the signals. Taking furan as a model system, which contains two types of carbons Cα and Cβ, we performed time-dependent density functional theory calculations and computed the SXRS signals with two pulses tuned at the carbon K-edge. Our simulations demonstrate that the SXRS signal from the Cα and Cβ sites are non-additive, owing to the significant mixed contributions (Cα 1s excitations by the pump pulse followed by Cβ 1s excitations by the probe, or vice verse). Harmonic vibrations linearly coupled to the electronic transitions are incorporated using the cumulant expansion. The nuclei act as a bath for electronic transitions which accelerate the decay of time-domain signal. The frequency-domain spectrum is modified by a small red shift and high-resolution fine-structure features are introduced

Surveillance of Midazolam Infusions in ICU

ABSTRACTIn order to determine the utilization of midazolam (MDM) infusions and to assess for the development of tachyphylaxis and withdrawal reactions with MDM, 17 mechanically-ventilated patients who received 18 courses of MDM infusions during their stay in ICU were studied retrospectively.With a mean age of 52 years (range: 22-78), the average starting, maintenance and peak infusion rates were 1.0 ± 0.6, 1.9 ± 1.3, and 3.8 ± 4.6 mcg/kg/min, respectively. Patients received the infusion for a mean of 9.1 days (range: 0.6-16.1).An inverse relationship was found between age and mean lowest daily Glasgow Coma Scale (GCS) scores (r=-0.60, n=14, p=0.02). Increases in the mean daily MDM infusion rate, suggestive of tachyphylaxis, were also noted (n=18, p&lt;0.01). Ten patients were studied for use of CNS drugs after MDM discontinuation. Three patients who required haloperidol during the 24 hours following MDM discontinuation received larger doses of MDM than the remaining seven patients (3.6 ± 1.8 versus 1.2 ± 0.6 mcg/kg/min, n=10, p=0.05). Concurrent use of diazepam during the 24 hours prior to MDM discontinuation was documented in seven of ten patients.The inverse relationship between age and GCS scores is suggestive of decreased clearance or enhanced sensitivity to MDM in older patients. Concurrent use of diazepam, possible development of tachyphylaxis and withdrawal reactions to MDM were also found. These findings may be useful in developing guidelines for use of MDM infusions.RÉSUMÉUne étude rétrospective de 17 patients mis sous ventilation assistée et ayant reçu 18 perfusions de midazolam (MDM) durant leur séjour aux soins intensifs a été effectuée pour que l'on puisse définir l'utilisation des perfusions de MDM et évaluer les conditions de survenue de tachyphylaxie et de réactions de sevrage associées au MDM.Les patients étaient âgés en moyenne de 52 ans (écart de 22 à 78 ans). Les vitesses de perfusion initiale, de maintien et maximale étaient de 1,0 ± 0,6, de 1,9 ± 1,3 et de 3,8 ± 4,6 μg/kg/min, respectivement. Les perfusions ont été administrées en moyenne durant 9,1 jours (écart de 0,6 à 16,1).Un rapport inverse a été observé entre l'âge et les scores quotidiens moyens les plus faibles (r = 0,60; n = 14; p = 0,02) à l'échelle de «coma» de Glasgow (GCS). On a aussi remarqué que des augmentations de la vitesse moyenne quotidienne de la perfusion de MDM pouvaient laisser prévoir la tachyphylaxie (n = 18; p &lt; 0,01).Dix patients ont été évalués relativement à l'utilisation de dépresseurs du SNC après le retrait du MDM. Les trois patients qui ont eu besoin d'halopéridol dans les 24 heures suivant le retrait du MDM avaient reçu de plus fortes doses de MDM que les sept autres patients (3,6 ± 1,8 versus 1,2 ± 0,6 μg/kg/min : n = 10, p = 0,05). L'usage concomitant de diazépam dans les 24 heures précédant le retrait du MDM a été documenté chez sept des dix patients.Le rapport inverse entre l'âge et les scores à l'échelle GCS semble indiquer une clairance réduite ou une sensibilité accrue au MDM chez les patients plus âgés. On a également noté un usage concomitant de diazépam, un risque de tachyphylaxie et des réactions de sevrage associés au MDM. Ces résultats pourraient être utiles dans l'élaboration de lignes directrices sur l'utilisation des perfusions de MDM