Closed-cycle, low-vibration 4 K cryostat for ion traps and other applications

In-vacuo cryogenic environments are ideal for applications requiring both low temperatures and extremely low particle densities. This enables reaching long storage and coherence times for example in ion traps, essential requirements for experiments with highly charged ions, quantum computation, and optical clocks. We have developed a novel cryostat continuously refrigerated with a pulse-tube cryocooler and providing the lowest vibration level reported for such a closed-cycle system with 1 W cooling power for a <5 K experiment. A decoupling system suppresses vibrations from the cryocooler by three orders of magnitude down to a level of 10 nm peak amplitudes in the horizontal plane. Heat loads of about 40 W (at 45 K) and 1 W (at 4 K) are transferred from an experimental chamber, mounted on an optical table, to the cryocooler through a vacuum-insulated massive 120 kg inertial copper pendulum. The 1.4 m long pendulum allows installation of the cryocooler in a separate, acoustically isolated machine room. In the laser laboratory, we measured the residual vibrations using an interferometric setup. The positioning of the 4 K elements is reproduced to better than a few micrometer after a full thermal cycle to room temperature. Extreme high vacuum on the $10^{-15}$ mbar level is achieved. In collaboration with the Max-Planck-Intitut f\"ur Kernphysik (MPIK), such a setup is now in operation at the Physikalisch-Technische Bundesanstalt (PTB) for a next-generation optical clock experiment using highly charged ions

Sapucaia nut (Lecythis pisonis Cambess) and its by-products: a promising and underutilized source of bioactive compounds. Part II: phenolic compounds profile.

In this study, the profile of the bioactive compounds of sapucaia nut (Lecythis pisonis Cambess) and its byproducts have been investigated. The phenolic profile by LC-ESI-MS/MS, the total phenolic content, the condensed tannins and the antioxidant activity of the sapucaia nut and shell were determined. 14 phenolic compounds were identified in the sapucaia nut extract, primarily phenolic acids and flavonoids. Catechin, epicatechin, myricetin, ellagic acid and ferulic acid presented significant correlation to the antioxidant activity. The sapucaia shell contained 22 phenolic compounds, 13 of which were quantified. The sapucaia shell extract showed a high content of total phenolic compounds, a high condensed tannins content, and high antioxidant activity. The higher antioxidant activity of the shell can be associated with a higher content of phenolics. Overall, it can be concluded that the sapucaia nut is a raw material rich in phenolic compounds that present high antioxidant activity. The nuts and the cake may be used as a promising raw material for the food industry, while the shells could be an alternative source of natural antioxidants. Further use in the cosmetics and pharmaceutical industry may also be envisaged. 1. Introduction Lecythis pisonis

Sensitivity to New Physics of Isotope Shift Studies using the Coronal Lines of Highly Charged Calcium Ions

Promising searches for new physics beyond the current Standard Model (SM) of particle physics are feasible through isotope-shift spectroscopy, which is sensitive to a hypothetical fifth force between the neutrons of the nucleus and the electrons of the shell. Such an interaction would be mediated by a new particle which could in principle be associated with dark matter. In so-called King plots, the mass-scaled frequency shifts of two optical transitions are plotted against each other for a series of isotopes. Subtle deviations from the expected linearity could reveal such a fifth force. Here, we study experimentally and theoretically six transitions in highly charged ions of Ca, an element with five stable isotopes of zero nuclear spin. Some of the transitions are suitable for upcoming high-precision coherent laser spectroscopy and optical clocks. Our results provide a sufficient number of clock transitions for -- in combination with those of singly charged Ca$^+$ -- application of the generalized King plot method. This will allow future high-precision measurements to remove higher-order SM-related nonlinearities and open a new door to yet more sensitive searches for unknown forces and particles

Determination of catechin in green tea using a catechol oxidase biomimetic sensor

A catechol oxidase biomimetic sensor, based on a novel copper(II) complex, was developed for the determination of catechin in green tea and the results were compared with those obtained by capillary electrophoresis. The dinuclear copper(II) complex, [Cu2(HL)(µ-CH3COO)](ClO4), containing the ligand N,N-[bis-(2-pyridylmethyl)]-N',N'-[(2-hydroxybenzyl)(2-hydroxy-3,5-di-tert-butylbenzyl)]-1,3-propanediamine-2-ol (H3L), was synthesized and characterized by IR, ¹H NMR and elemental analysis. The best conditions for the optimization of the biomimetic sensor were established by square wave voltammetry. The best performance for this sensor was obtained in 75:15:10% (m/m/m) of the graphite powder:nujol:copper(II) complex, 0.05 mol L-1 phosphate buffer solution (pH 7.5) and frequency, pulse amplitude, scan increment at 30 Hz, 80 mV, 3.3 mV, respectively. The analytical curve was linear in the concentration range 4.95 × 10-6 to 3.27 × 10-5 mol L-1 (r = 0.9993) with a detection limit of 2.8 × 10-7 mol L-1. This biomimetic sensor demonstrated long-term stability (9 months; 800 determinations) and reproducibility with a relative standard deviation of 3.5%. The recovery of catechin from green tea samples ranged from 93.8 to 106.9% and the determination, compared with that obtained using capillary electrophoresis, was found to be acceptable at the 95% confidence level

Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (>75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P<0.001). Using specific thresholds, patients with ⩾25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P<0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease

Importance of Magnesium Status in COVID-19

A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, cellular, and physiological roles required for cardiovascular, immunological, respiratory, and neurological functions. Both low serum and dietary Mg have been associated with the severity of COVID-19 outcomes, including mortality; both are also associated with COVID-19 risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular disease, hypertension, and asthma. In addition, populations with high rates of COVID-19 mortality and hospitalization tend to consume diets high in modern processed foods, which are generally low in Mg. In this review, we review the research to describe and consider the possible impact of Mg and Mg status on COVID-19 showing that (1) serum Mg between 2.19 and 2.26 mg/dL and dietary Mg intakes &gt; 329 mg/day could be protective during the disease course and (2) inhaled Mg may improve oxygenation of hypoxic COVID-19 patients. In spite of such promise, oral Mg for COVID-19 has thus far been studied only in combination with other nutrients. Mg deficiency is involved in the occurrence and aggravation of neuropsychiatric complications of COVID-19, including memory loss, cognition, loss of taste and smell, ataxia, confusion, dizziness, and headache. Potential of zinc and/or Mg as useful for increasing drug therapy effectiveness or reducing adverse effect of anti-COVID-19 drugs is reviewed. Oral Mg trials of patients with COVID-19 are warranted

A Gestational High Protein Diet Affects the Abundance of Muscle Transcripts Related to Cell Cycle Regulation throughout Development in Porcine Progeny

BACKGROUND: In various animal models pregnancy diets have been shown to affect offspring phenotype. Indeed, the underlying programming of development is associated with modulations in birth weight, body composition, and continual diet-dependent modifications of offspring metabolism until adulthood, producing the hypothesis that the offspring's transcriptome is permanently altered depending on maternal diet. METHODOLOGY/PRINCIPAL FINDINGS: To assess alterations of the offspring's transcriptome due to gestational protein supply, German Landrace sows were fed isoenergetic diets containing protein levels of either 30% (high protein--HP) or 12% (adequate protein--AP) throughout their pregnancy. Offspring muscle tissue (M. longissimus dorsi) was collected at 94 days post conception (dpc), and 1, 28, and 188 days post natum (dpn) for use with Affymetrix GeneChip Porcine Genome Arrays and subsequent statistical and Ingenuity pathway analyses. Numerous transcripts were found to have altered abundance at 94 dpc and 1 dpn; at 28 dpn no transcripts were altered, and at 188 dpn only a few transcripts showed a different abundance between diet groups. However, when assessing transcriptional changes across developmental time points, marked differences were obvious among the dietary groups. Depending on the gestational dietary exposure, short- and long-term effects were observed for mRNA expression of genes related to cell cycle regulation, energy metabolism, growth factor signaling pathways, and nucleic acid metabolism. In particular, the abundance of transcripts related to cell cycle remained divergent among the groups during development. CONCLUSION: Expression analysis indicates that maternal protein supply induced programming of the offspring's genome; early postnatal compensation of the slight growth retardation obvious at birth in HP piglets resulted, as did a permanently different developmental alteration and responsiveness to the common environment of the transcriptome. The transcriptome modulations are interpreted as the molecular equivalent of developmental plasticity of the offspring that necessitates adaptation and maintenance of the organismal phenotype

Transcriptional profiling of degraded RNA in cryopreserved and fixed tissue samples obtained at autopsy

BACKGROUND: Traditional multiplexed gene expression methods require well preserved, intact RNA. Such specimens are difficult to acquire in clinical practice where formalin fixation is the standard procedure for processing tissue. Even when special handling methods are used to obtain frozen tissue, there may be RNA degradation; for example autopsy samples where degradation occurs both pre-mortem and during the interval between death and cryopreservation. Although specimens with partially degraded RNA can be analyzed by qRT-PCR, these analyses can only be done individually or at low levels of multiplexing and are laborious and expensive to run for large numbers of RNA targets. METHODS: We evaluated the ability of the cDNA-mediated Annealing, Selection, extension, and Ligation (DASL) assay to provide highly multiplexed analyses of cryopreserved and formalin fixed, paraffin embedded (FFPE) tissues obtained at autopsy. Each assay provides data on 1536 targets, and can be performed on specimens with RNA fragments as small as 60 bp. RESULTS: The DASL performed accurately and consistently with cryopreserved RNA obtained at autopsy as well as with RNA extracted from formalin-fixed paraffin embedded tissue that had a cryopreserved mirror image specimen with high quality RNA. In FFPE tissue where the cryopreserved mirror image specimen was of low quality the assay performed reproducibly on some but not all specimens. CONCLUSION: The DASL assay provides reproducible results from cryopreserved specimens and many FFPE specimens obtained at autopsy. Gene expression analyses of these specimens may be especially valuable for the study of non-cancer endpoints, where surgical specimens are rarely available