High-Precision Measurement of the 238Pu/239Pu Isotope Ratio by TIMS.

With an aim to improve the precision of isotopic standards of special nuclear materials like uranium and plutonium, National Bureau of Standards (NBS) undertook the recertification of isotopic standards prepared between 1960 and 1970. In a recent initiative, Lawrence Livermore National Laboratory (LLNL) in collaboration with New Brunswick Laboratory Program Office (NBL PO) undertaken efforts to recertify SRM 946, SRM 947, and SRM 948. The primary goal of this drive is to lower the uncertainties associated with the isotopic compositions of plutonium standards. The drive is also aims to minimize the uncertainty associated with measurement of the 238Pu content from 2% to ∼0.3%. In this connection, our laboratory at the Fuel Chemistry Division, Bhabha Atomic Research Centre, proposes a novel indicator "minima in the (RMO254/(i + 16))/(RM238/i) curve" (where i = m/z 233 or 235 amu), which is the ratio of the isotope ratio of metal oxides (238M16O/iM16O) to that of metal ions (238M/iM) of uranium in determining the accurate 238Pu content by thermal ionization mass spectrometry. Various enriched uranium spikes have been employed to study the efficacy of the minima in the (RMO(254)/(i + 16))/(RM238/i) curve. With the combination of monitoring the minima in the (RMO(254)/(i + 16))/(RM238/i) curve and the application of the 233U spike (with an isotope abundance of 238U ∼ 0.05%), an external precision of 0.2% has been achieved in the determination of the 238Pu/239Pu isotope ratio for isotopic standard SRM 947.

Impact of the COVID-19 Pandemic on Blood Donation Patterns: A Systematic Review and Meta-Analysis.

Blood centers, which are arguably the backbone of every hospital, depend on blood donors for a constant and regular supply of blood. Like many other fields, the COVID-19 pandemic severely affected blood donations. In this article, we aim to systematically search the studies done on blood donation during the COVID-19 pandemic period, analyze the pandemic's effect on blood donation, and examine the methodology used to overcome the problem. We performed a systematic review and meta-analysis to investigate the effect of the COVID-19 pandemic on blood donation. Two independent reviewers searched different databases, such as PubMed, ProQuest, Scopus, and Google Scholar. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Joanna Briggs Institute critical appraisal checklist for overall study characteristics. We included a total of 15 studies. There was an overall decrease in blood donation of 25%, with some regions showing a decrease of as much as 71%. However, some regions were able to experience a 2-10% increase in blood donation after taking stringent and early measures to prevent such decreases. The COVID-19 pandemic and consequent lockdown greatly affected blood transfusion services, resulting in a progressive decline in blood donations that threatened the lives of many patients who were fully dependent on blood transfusion. However, by making appropriate and early decisions and taking action, policymakers and the rest of society can prevent such shortages, potentially saving millions of lives.

Unraveling the paleo-marine signature in saline thermal waters of Cambay rift basin, Western India: Insights from geochemistry and multi isotopic (B, O and H) analysis.

Cambay rift basin is the only geothermal province in India that hosts several saline thermal water manifestations having EC values varying from 525 to 10,860 µS/cm. Various ionic ratios (Na/Cl, Br/Cl, Ca/(SO4 + HCO3), SO4/Cl) as well as boron isotopic composition (δ11B = 40.5 to 46 ‰) clearly ascribes the presence of fossil (relics of evaporated seawater) seawater as origin of increased salinity in the majority of thermal waters. Depleted isotopic (δ18O, δ2H) composition of these thermal waters also substantiates the presence of paleowater in these systems. In rest of the thermal waters, agricultural return flow is found to be source of dissolved solutes as confirmed from different bivariate plots such as B/Cl vs. Br/Cl and δ11B vs. B/Cl as well as from ionic ratios. This study thus provides the diagnostic tools to elucidate the source of variable salinity in the thermal waters circulating in the Cambay rift basin, India.

Task-Specific Supported Liquid Membrane for Actinide Assay in Aqueous Streams by Thermal Ionization Mass Spectrometry.

Thermal ionization mass spectrometry is the most commonly used technique for the determination of Pu isotopic composition and concentration in complex matrices but involves multiple steps including sample pretreatment, removal of matrix, preconcentration of Pu, and loading on a rhenium filament for TIMS analysis. The present work reports the synthesis of the N,N'-dioctyl-α-hydroxyacetamide (DOHA) functionalized supported liquid membrane that offered dual functions: (i) matrix elimination and/or preconcentration of actinides from complex aqueous samples and (ii) served as a loading substrate for TIMS analysis. The ligand composition in the membrane can be tuned aiming either for selective preconcentration of Pu from an aqueous matrix or for bulk removal of actinides. The membrane, impregnated with 0.2 M DOHA in dodecane, showed very high selectivity for PuIV in acidic medium, in the presence of other competing actinides, viz., AmIII, UVI, and NpV. The membrane based loading in TIMS improved the sample utilization efficiency and ionization efficiency compared to the conventional solution loading technique, offering Pu analysis from a single Re filament, that served as both vaporization and ionization filament and direct determination of 238Pu in the presence of 238U, eliminating the requirement of alpha spectrometry. It was possible to achieve >80% reduction in analysis time and >95% reduction in secondary waste generation by the SLM-TIMS method, compared to conventional TIMS involving Pu purification by anion exchange resin. Pu concentrations in seawater and groundwater samples, synthetic urine, and dissolver solution of irradiated fuel were determined by SLM-TIMS, employing the isotope dilution (ID) technique, with very good accuracy and precision. The membrane, impregnated with 2 M DOHA in dodecane, showed strong affinity for actinides and was successfully employed for the removal of bulk actinides from aqueous samples with more than 96% recovery.

A Concerted Synchronous [2 + 2] Cycloreversion Repair Catalyzed by Two Electrons.

The current understanding of photoenzyme-catalyzed [2 + 2] cycloreversion repair of cyclobutane pyrimidine dimer (CPD) is that a photogenerated electron from the photolyase enzyme catalyzes the repair. This one-electron catalyzed repair is a sequential two-bond breaking cycloreversion of the cyclobutane center and involves a negative ion radical as an intermediate. Here, by resonantly capturing two exogenous low-energy electrons into the molecular field of a CPD, we show that the concerted synchronous two-bond breaking reaction, which is intermediate-free, and hence a safe repair, is feasible through two-electron catalysis.

Robotic-assisted laparoscopy in reproductive surgery: a contemporary review.

Robotic surgery is a conceptual fusion of the conventional open surgery and the minimally invasive laparoscopic surgery. We reviewed the current role of robotic-assisted laparoscopy in the field of reproductive surgery by a literature search in PubMed database. We analyzed the reported advantages and limitations of the use of robotics in reproductive surgeries like myomectomy, tubal reanastomosis, endometriosis, ovarian tissue cryopreservation, and ovarian transposition. Overall, robotic assistance in reproductive surgery resulted in decreased blood loss, less post-operative pain, shorter hospital stay, and faster convalescence, whereas reproductive outcomes were similar to open/laparoscopic approaches. The main drawbacks of robotic surgery were higher cost and longer operating times. It is as safe and effective as the conventional laparoscopy and represents a reasonable alternate to abdominal approach. Procedures that are technically challenging with the conventional laparoscopy can be performed with robotic assistance. It has advantages of improved visualization and Endowrist™ movements allowing precise suturing. This helps to overcome the limitations of laparoscopy, especially in complicated procedures, and may shorten the steep learning curve in minimal invasive surgery. Randomized controlled trials looking at both short- and long-term outcomes are warranted to strengthen the role of robotic surgery in the field of reproductive surgery.

Association of homocysteine with global DNA methylation in vegetarian Indian pregnant women and neonatal birth anthropometrics.

OBJECTIVE: The present study was designed to evaluate if plasma maternal folate, vitamin B-12 and homocysteine levels had an effect on maternal global DNA methylation and neonatal anthropometrics in Indian pregnant women. METHODS: A total of 49 participants having completed ≥36 weeks of pregnancy were enrolled in the study. Estimation of folate was by Ion capture assay, vitamin B-12 by microparticle enzyme immunoassay, total homocysteine by fluorescence polarization immunoassay and global DNA methylation using Cayman's DNA methylation enzyme immunoassay (EIA) kit. RESULTS: Folate and vitamin B-12 were inversely correlated to homocysteine in pregnant women consuming vegetarian and non-vegetarian diet. No difference in global DNA methylation was found between the vegetarian and non-vegetarian pregnant women. Folate and vitamin B-12 did not show association with global DNA methylation, however plasma total homocysteine of the vegetarian group showed significant correlation to global DNA methylation (r(2 )= 0.49, p = 0.011). Plasma total homocysteine was inversely related to tricep skinfold (r(2 )= -0.484, p = 0.01) and chest circumference (r(2 )= -0.104, p = 0.04) of neonates in vegetarian group. CONCLUSION: Moderate vitamin B-12 deficiency in vegetarian pregnant women might be the cause of hyperhomocystinemia, hypermethylation when compared to vitamin B-12 sufficient non-vegetarian group.

Cryopreservation of testicular and epididymal sperm: techniques and clinical outcomes of assisted conception.

The introduction of the technique of intracytoplasmic sperm injection to achieve fertilization, especially using surgically retrieved testicular or epididymal sperm from men with obstructive or non-obstructive azoospermia, has revolutionized the field of assisted reproduction. The techniques for the retrieval of spermatozoa vary from relatively simple percutaneous sperm aspiration to open excision (testicular biopsy) and the more invasive Micro-TESE. The probability of retrieving spermatozoa can be as high as 100% in men with obstructive azoospermia (congenital bilateral absence of the vas deferens, status post-vasectomy). However, in nonobstructive azoospermia, successful sperm retrieval has been reported in 10-100% of cases by various investigators. The surgical retrieval and cryopreservation of sperm, especially in men with non-obstructive azoospermia, to some extent ensures the availability of sperm at the time of intracytoplasmic sperm injection. In addition, this strategy can avoid unnecessary ovarian stimulation in those patients intending to undergo in vitro fertilization-intracytoplasmic sperm injection with freshly retrieved testicular sperm when an absolute absence of sperm in the testis is identified. Several different methods for the cryopreservation of testicular and epididymal sperm are available. The choice of the container or carrier may be an important consideration and should take into account the number or concentration of the sperm in the final preparation. When the number of sperm in a testicular biopsy sample is extremely low (e.g., 1-20 total sperm available), the use of an evacuated zona pellucida to store the cryopreserved sperm has been shown to be an effective approach.

Cryopreservation of testicular and epididymal sperm: techniques and clinical outcomes of assisted conception

The introduction of the technique of intracytoplasmic sperm injection to achieve fertilization, especially using surgically retrieved testicular or epididymal sperm from men with obstructive or non-obstructive azoospermia, has revolutionized the field of assisted reproduction. The techniques for the retrieval of spermatozoa vary from relatively simple percutaneous sperm aspiration to open excision (testicular biopsy) and the more invasive Micro-TESE. The probability of retrieving spermatozoa can be as high as 100% in men with obstructive azoospermia (congenital bilateral absence of the vas deferens, status post-vasectomy). However, in nonobstructive azoospermia, successful sperm retrieval has been reported in 10-100% of cases by various investigators. The surgical retrieval and cryopreservation of sperm, especially in men with non-obstructive azoospermia, to some extent ensures the availability of sperm at the time of intracytoplasmic sperm injection. In addition, this strategy can avoid unnecessary ovarian stimulation in those patients intending to undergo in vitro fertilization-intracytoplasmic sperm injection with freshly retrieved testicular sperm when an absolute absence of sperm in the testis is identified. Several different methods for the cryopreservation of testicular and epididymal sperm are available. The choice of the container or carrier may be an important consideration and should take into account the number or concentration of the sperm in the final preparation. When the number of sperm in a testicular biopsy sample is extremely low (e.g., 1-20 total sperm available), the use of an evacuated zona pellucida to store the cryopreserved sperm has been shown to be an effective approach.

Network analysis has diverse roles in drug discovery.

Computational biologists use network analysis to uncover relationships between various data types of interest for drug discovery. For example, signalling and metabolic pathways are commonly used to understand disease states and drug mechanisms. However, several other flavours of network analysis techniques are also applicable in a drug discovery context. Recent advances include networks that encompass relationships between diseases, molecular mechanisms and gene targets. Even social networks that mirror interactions within the scientific community are helping to foster collaborations and novel research. We review how these different types of network analysis approaches facilitate drug discovery and their associated challenges.

Differential producibility analysis (DPA) of transcriptomic data with metabolic networks: deconstructing the metabolic response of M. tuberculosis.

A general paucity of knowledge about the metabolic state of Mycobacterium tuberculosis within the host environment is a major factor impeding development of novel drugs against tuberculosis. Current experimental methods do not allow direct determination of the global metabolic state of a bacterial pathogen in vivo, but the transcriptional activity of all encoded genes has been investigated in numerous microarray studies. We describe a novel algorithm, Differential Producibility Analysis (DPA) that uses a metabolic network to extract metabolic signals from transcriptome data. The method utilizes Flux Balance Analysis (FBA) to identify the set of genes that affect the ability to produce each metabolite in the network. Subsequently, Rank Product Analysis is used to identify those metabolites predicted to be most affected by a transcriptional signal. We first apply DPA to investigate the metabolic response of E. coli to both anaerobic growth and inactivation of the FNR global regulator. DPA successfully extracts metabolic signals that correspond to experimental data and provides novel metabolic insights. We next apply DPA to investigate the metabolic response of M. tuberculosis to the macrophage environment, human sputum and a range of in vitro environmental perturbations. The analysis revealed a previously unrecognized feature of the response of M. tuberculosis to the macrophage environment: a down-regulation of genes influencing metabolites in central metabolism and concomitant up-regulation of genes that influence synthesis of cell wall components and virulence factors. DPA suggests that a significant feature of the response of the tubercle bacillus to the intracellular environment is a channeling of resources towards remodeling of its cell envelope, possibly in preparation for attack by host defenses. DPA may be used to unravel the mechanisms of virulence and persistence of M. tuberculosis and other pathogens and may have general application for extracting metabolic signals from other "-omics" data.

The application of next-generation sequencing technologies to drug discovery and development.

Next-generation sequencing (NGS) technologies represent a paradigm shift in sequencing capability. The technology has already been extensively applied to biological research, resulting in significant and remarkable insights into the molecular biology of cells. In this review, we focus on current and potential applications of the technology as applied to the drug discovery and development process. Early applications have focused on the oncology and infectious disease therapeutic areas, with emerging use in biopharmaceutical development and vaccine production in evidence. Although this technology has great potential, significant challenges remain, particularly around the storage, transfer and analysis of the substantial data sets generated.

HIV-1 enhancing effect of prostatic acid phosphatase peptides is reduced in human seminal plasma.

We recently reported that HIV-1 infection can be inhibited by innate antimicrobial components of human seminal plasma (SP). Conversely, naturally occurring peptidic fragments from the SP-derived prostatic acid phosphatase (PAP) have been reported to form amyloid fibrils called "SEVI" and enhance HIV-1 infection in vitro. In order to understand the biological consequence of this proviral effect, we extended these studies in the presence of human SP. PAP-derived peptides were agitated to form SEVI and incubated in the presence or absence of SP. While PAP-derived peptides and SEVI alone were proviral, the presence of 1% SP ablated their proviral activity in several different anti-HIV-1 assays. The anti-HIV-1 activity of SP was concentration dependent and was reduced following filtration. Supraphysiological concentrations of PAP peptides and SEVI incubated with diluted SP were degraded within hours, with SP exhibiting proteolytic activity at dilutions as high as 1:200. Sub-physiological concentrations of two prominent proteases of SP, prostate-specific antigen (PSA) and matriptase, could degrade physiological and supraphysiological concentrations of PAP peptides and SEVI. While human SP is a complex biological fluid, containing both antiviral and proviral factors, our results suggest that PAP peptides and SEVI may be subject to naturally occurring proteolytic components capable of reducing their proviral activity.

High precision isotope ratio measurements on by thermal ionization mass spectrometry using ion.

Studies were carried out to determine the 10B/11B isotope ratio by positive thermal ionization mass spectrometry (P-TIMS) analyzing boron as rubidium borate ions. Of the 36 different ionic species formed, the boron and rubidium isotope ratios were obtained from the ion intensity ratios of the most suitable ion pairs corresponding to masses 212, 213 and 215, 213 respectively. The investigations were carried out to explore the possibility of correcting the observed isotope ratio of boron by using a modified internal normalization technique based on the observed Rb isotope ratio. The method is based on the relation of isotopic fractionation of boron as a function of the rubidium (natural isotopic composition) isotopes fractionation obtained during TIMS analysis from the same filament loading. The application of the methodology to improve the precision of the observed 10B/11B isotope ratio during analysis of irradiated boron alloy samples is demonstrated. Improvement in precision from 0.25% to better than 0.05% was demonstrated using this approach.

Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma.

Mucosal surfaces of the reproductive tract as well as their secretions have important roles in preventing sexual transmission of HIV-1. In the current study, the majority of the intrinsic anti-HIV-1 activity of human seminal plasma (SP) was determined to reside in the cationic polypeptide fraction. Antiviral assays utilizing luciferase reporter cells and lymphocytic cells revealed the ability of whole SP to prevent HIV-1 infection, even when SP was diluted 3200-fold. Subsequent fractionation by continuous flow acid-urea (AU)-PAGE and antiviral testing revealed that cationic polypeptides within SP were responsible for the majority of anti-HIV-1 activity. A proteomic approach was utilized to resolve and identify 52 individual cationic polypeptides that contribute to the aggregate anti-HIV-1 activity of SP. One peptide fragment of semenogelin I, termed SG-1, was purified from SP by a multistep chromatographic approach, protein sequenced, and determined to exhibit anti-HIV-1 activity against HIV-1. Anti-HIV-1 activity was transient, as whole SP incubated for prolonged time intervals exhibited a proportional decrease in anti-HIV-1 activity that was directly attributed to the degradation of semenogelin I peptides. Collectively, these results indicate that the cationic polypeptide fraction of SP is active against HIV-1, and that semenogelin-derived peptides contribute to the intrinsic anti-HIV-1 activity of SP.

A bent electrostatic ion beam trap for simultaneous measurements of fragmentation and ionization of cluster ions.

We describe a bent electrostatic ion beam trap in which cluster ions of several keV kinetic energy can be stored on a V-shaped trajectory by means of an electrostatic deflector placed between two electrostatic mirrors. While maintaining all the advantages of its linear counterpart [Zajfman et al., Phys. Rev. A 55, R1577 (1997); Dahan et al., Rev. Sci. Instrum. 69, 76 (1998)], such as long storage times, straight segments, and a field-free region for merged or crossed beam experiments, the bent trap allows for simultaneous measurement of charged and neutral fragments and determination of the average kinetic energy released in the fragmentation. These unique properties of the bent trap are illustrated by first results concerning the competition between delayed fragmentation and ionization of Al(n) (-) clusters after irradiation by a short laser pulse.

Selection of objective function in genome scale flux balance analysis for process feed development in antibiotic production.

Using flux variability analysis of a genome scale metabolic network of Streptomyces coelicolor, a series of reactions were identified, from disparate pathways that could be combined into an actinorhodin-generating mini-network. Candidate process feed nutrients that might be expected to influence this network were used in process simulations and in silico predictions compared to experimental findings. Ranking potential process feeds by flux balance analysis optimisation, using either growth or antibiotic production as objective function, did not correlate with experimental actinorhodin yields in fed processes. However, the effect of the feeds on glucose assimilation rate (using glucose uptake as objective function) ranked them in the same order as in vivo antibiotic production efficiency, consistent with results of a robustness analysis of the effect of glucose assimilation on actinorhodin production.

Electrostatic ion trap and Fourier transform measurements for high-resolution mass spectrometry.

We report on the development of an electrostatic ion trap for high-resolution mass spectrometry. The trap works on purely electrostatic fields and hence trapping and storing of ions is not mass restrictive, unlike other techniques based on Penning, Paul, or radio frequency quadrupole ion traps. It allows simultaneous trapping and studying of multiple mass species over a large mass range. Mass spectra were recorded in "dispersive" and "self-bunching" modes of ions. Storage lifetimes of about 100 ms and mass resolving power of about 20,000 could be achieved from the fifth harmonic Fourier transform spectrum of Xe ions recorded in the self-bunching mode.

Size-dependent electron-impact detachment of internally cold Cn- and Aln- clusters.

The cross sections for electron detachment of internally cold Cn- and Aln- clusters were measured using an electrostatic ion beam trap fitted with an internal electron target. The measured electron-impact detachment cross sections for the Cn- (n = 1-9) clusters exhibit even-odd oscillations reflecting the binding energy trend, namely, higher cross sections for weaker binding. Surprisingly, however, these cross sections increase on the average with cluster size, n, in spite of the increase in electron binding. In contrast, the Aln- (n = 2-5) clusters follow the known scaling laws for electron detachment. We suggest that the size-dependent polarizability of these clusters is responsible for the observed behavior.

A randomized parallel trial of topical aspirin-moisturizer solution vs. oral aspirin for acute herpetic neuralgia.

BACKGROUND: In this study, the efficacy of oral aspirin vs. topical aspirin in moisturizer (Vaseline Intensive Care Lotion) was studied in an open, randomized, parallel trial in patients with acute herpetic neuralgia. METHODS: Thirty patients were evaluated in the trial, with 15 in each group. The patients were randomized to receive either oral aspirin, 375-750 mg three times a day, or 75 mg topical aspirin/mL of moisturizer (5-10 mL, depending on the extent of involvement), three times a day, for 21 days. Pain was assessed daily by means of a self-rating visual analog scale and physician assessment. In addition, the skin and plasma levels of aspirin were measured in both groups. RESULTS: The mean time to onset of pain relief was 44 min with topical aspirin and 110 min with oral aspirin. The mean duration of pain relief after a single application of topical aspirin was 5.4 h, whereas it was 3.5 h with oral aspirin. The mean visual analog scale scores for pain with oral aspirin decreased from 68.2 +/- 6.1 on day zero to 43.1 +/- 8.7 on day 21, which was not significant compared with the baseline score. With topical aspirin, the baseline pain score was 77.5 +/- 3.7 and decreased to 6.8 +/- 3 on day 21 (P < 0.001 compared to the baseline score and compared to oral aspirin). The mean plasma and skin levels of aspirin following oral administration were 16.21 +/- 1.1 microg/mL and 1.97 +/- 0.3 microg/mm2, respectively. After topical administration, the mean plasma level of aspirin was 2.29 +/- 0.5 microg/mL (P < 0.01 vs. oral aspirin) and the skin level was 5.96 +/- 0.4 microg/mm2 (P < 0.05 vs. oral aspirin). Treatment tolerance was excellent in both groups. CONCLUSIONS: This trial has demonstrated that topical aspirin in moisturizer is clearly superior to oral aspirin in relieving the pain of acute herpetic neuralgia, and that the analgesic activity of aspirin is largely due to its local effect.