Fiber-delivered heterodyne spectroscopy with a mid-infrared frequency comb.

By exploiting the excellent short-term phase stability between consecutive pulses from a free-running optical parametric oscillator frequency comb, we report the first example of hollow-core fiber-delivered heterodyne spectroscopy in the 3.1-3.8 µm wavelength range. The technique provides a means of spectroscopically interrogating a sample situated at the distal end of a fiber, with all electronics and light sources situated at the proximal end and with an inherent capability to suppress spectroscopically interfering features present in the free-space and in-fiber delivery path. Using a silica anti-resonant, hollow-core delivery fiber, we demonstrate high quality transmission and attenuated total reflectance spectroscopy of a plastic sample for fiber lengths of up to 40 m, significantly exceeding the few-meter lengths typically possible using solid-core fibers. The technique opens a route to implementing multi-species spectroscopic monitoring in remote and / or hostile industrial environments and medical applications.

Three-element, self-starting Kerr-lens-modelocked 1-GHz Ti:sapphire oscillator pumped by a single laser diode.

We present a Kerr-lens-modelocked, three-element, diode-pumped Ti:sapphire laser producing 111-fs pulses at a repetition frequency of 1.02 GHz. Self-starting soliton-modelocked operation with an output power of 106 mW was obtained when the laser was pumped at 1.0 W with a single 527-nm laser diode. The output exhibits a relative intensity noise of 0.06% (1 Hz - 1 MHz) and locking of the repetition rate to an external reference is demonstrated with a phase error of 1.7 mrad (1 Hz-1 MHz). The simplicity of the laser makes it an attractive candidate as a module for integration into larger systems.

Hollow-core fiber delivery of broadband mid-infrared light for remote spectroscopy.

High-resolution multi-species spectroscopy is achieved by delivering broadband 3-4-µm mid-infrared light through a 4.5-meter-long silica-based hollow-core optical fiber. Absorptions from H37Cl, H35Cl, H2O and CH4 present in the gas within the fiber core are observed, and the corresponding gas concentrations are obtained to 5-ppb precision using a high-resolution Fourier-transform spectrometer and a full-spectrum multi-species fitting algorithm. We show that by fully fitting the narrow absorption features of these light molecules their contributions can be nulled, enabling further spectroscopy of C3H6O and C3H8O contained in a Herriott cell after the fiber. As a demonstration of the potential to extend fiber-delivered broadband mid-infrared spectroscopy to significant distances, we present a high-resolution characterization of the transmission of a 63-meter length of hollow-core fiber, fully fitting the input and output spectra to obtain the intra-fiber gas concentrations. We show that, despite the fiber not having been purged, useful spectroscopic windows are still preserved which have the potential to enable hydrocarbon spectroscopy at the distal end of fibers with lengths of tens or even hundreds of meters.

Easy One-Step Amplification and Labeling Procedure for Copy Number Variation Detection.

BACKGROUND: The specific characteristics of copy number variations (CNVs) require specific methods of detection and characterization. We developed the Easy One-Step Amplification and Labeling procedure for CNV detection (EOSAL-CNV), a new method based on proportional amplification and labeling of amplicons in 1 PCR. METHODS: We used tailed primers for specific amplification and a pair of labeling probes (only 1 labeled) for amplification and labeling of all amplicons in just 1 reaction. Products were loaded directly onto a capillary DNA sequencer for fragment sizing and quantification. Data obtained could be analyzed by Microsoft Excel spreadsheet or EOSAL-CNV analysis software. We developed the protocol using the LDLR (low density lipoprotein receptor) gene including 23 samples with 8 different CNVs. After optimizing the protocol, it was used for genes in the following multiplexes: BRCA1 (BRCA1 DNA repair associated), BRCA2 (BRCA2 DNA repair associated), CHEK2 (checkpoint kinase 2), MLH1 (mutL homolog 1) plus MSH6 (mutS homolog 6), MSH2 (mutS homolog 2) plus EPCAM (epithelial cell adhesion molecule) and chromosome 17 (especially the TP53 [tumor protein 53] gene). We compared our procedure with multiplex ligation-dependent probe amplification (MLPA). RESULTS: The simple procedure for CNV detection required 150 min, with <10 min of handwork. After analyzing >240 samples, EOSAL-CNV excluded the presence of CNVs in all controls, and in all cases, results were identical using MLPA and EOSAL-CNV. Analysis of the 17p region in tumor samples showed 100% similarity between fluorescent in situ hybridization and EOSAL-CNV. CONCLUSIONS: EOSAL-CNV allowed reliable, fast, easy detection and characterization of CNVs. It provides an alternative to targeted analysis methods such as MLPA.

Characterization of a carrier-envelope-offset-stabilized blue- and green-diode-pumped Ti:sapphire frequency comb.

Diode-pumping of Ti:sapphire provides a low-cost route to high-quality frequency-comb sources, exploiting the potential of direct diode modulation for wideband control of the carrier-envelope-offset frequency. We present here an fREP- and fCEO-locked, directly diode-pumped Ti:sapphire frequency comb, producing 66-fs pulses at 800 nm and employing f-to-2f interferometry and current modulation of a 462-nm blue laser diode to achieve a stabilization bandwidth extending to ∼70 kHz. Characterizations of the fREP and fCEO phase noise are compared to relative intensity noise spectra of the pump diodes to provide insights into how the diode design and performance transfer into the comb stability, suggesting a lower contribution to fREP and fCEO noise from the blue laser diode than from the green diode.

Correction: Memory hierarchy characterization of SPEC CPU2006 and SPEC CPU2017 on the Intel Xeon Skylake-SP.

[This corrects the article DOI: 10.1371/journal.pone.0220135.].

Mucorales and Mucormycosis: Recent Insights and Future Prospects.

The classification of Mucorales encompasses a collection of basal fungi that have traditionally demonstrated an aversion to modern genetic manipulation techniques. This aversion led to a scarcity of knowledge regarding their biology compared to other fungal groups. However, the emergence of mucormycosis, a fungal disease caused by Mucorales, has attracted the attention of the clinical field, mainly because available therapies are ineffective for decreasing the fatal outcome associated with the disease. This revitalized curiosity about Mucorales and mucormycosis, also encouraged by the recent COVID-19 pandemic, has spurred a significant and productive effort to uncover their mysteries in recent years. Here, we elaborate on the most remarkable breakthroughs related to the recently discovered genetic advances in Mucorales and mucormycosis. The utilization of a few genetic study models has enabled the identification of virulence factors in Mucorales that were previously described in other pathogens. More notably, recent investigations have identified novel genes and mechanisms controlling the pathogenic potential of Mucorales and their interactions with the host, providing fresh avenues to devise new strategies against mucormycosis. Finally, new study models are allowing virulence studies that were previously hampered in Mucorales, predicting a prolific future for the field.

Volume alterations of the hippocampus and amygdala in patients with schizophrenia and persistent auditory hallucinations.

INTRODUCTION: Auditory hallucinations (AH) are one of the most prevalent symptoms of schizophrenia. They might cause several brain alterations, especially changes in the volumes of hippocampus and amygdala, regions related to the relay and processing of auditory cues and emotional memories. MATERIAL AND METHODS: We have recruited 41 patients with schizophrenia and persistent AH, 35 patients without AH, and 55 healthy controls. Using their MRIs, we have performed semiautomatic segmentations of the hippocampus and amygdala using Freesurfer. We have also performed bilateral correlations between the total PSYRATS score and the volumes of affected subregions and nuclei. RESULTS: In the hippocampus, we found bilateral increases in the volume of its hippocampal fissure and decreases in the right fimbria in patients with and without AH. The volume of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus were decreased in patients with AH. In the amygdala, we found its left total volume was shrunk, and there was a decrease of its left accessory basal nucleus in patients with AH. CONCLUSIONS: We have detected volume alterations of different limbic structures likely due to the presence of AH. The volumes of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus, and total volume of the amygdala and its accessory basal nucleus, were only affected in patients with AH. Bilateral volume alterations in the hippocampal fissure and right fimbria seem inherent of schizophrenia and due to traits not contemplated in our research.

Compressed Sparse FM-Index: Fast Sequence Alignment Using Large K-Steps.

The FM-index is a data structure used in genomics for exact search of input sequences over large reference genomes. Algorithms based on the FM-index show an irregular memory access pattern, resulting in a memory bound problem. We analyze a recent implementation of the FM-index and highlight existing throughput-memory trade-offs, showing that memory requirements limit implementation of large k-steps. We propose COFI, a COmpressed FM-Index for large K-steps. COFI enables a 15-step FM-index using less than 16 GB for a human genome reference of 3 giga base pairs. An algorithm based on this new layout is evaluated on both a Knights Landing (KNL) and an Skylake-based system (SKX). We achieve average speed-ups of 1.46× and 1.39×, respectively, with respect to an state-of-the-art FM-index implementation that is already well optimized.

Harnessing of Diluted Methane Emissions by Direct Partial Oxidation of Methane to Methanol over Cu/Mordenite.

The upgrading of diluted methane emissions into valuable products can be accomplished at low temperatures (200 °C) by the direct partial oxidation of methanol over copper-exchanged zeolite catalysts. The reaction has been studied in a continuous fixed-bed reactor loaded with a Cu-mordenite catalyst, according to a three-step cyclic process: adsorption of methane, desorption of methanol, and reactivation of the catalyst. The purpose of the work is the use of methane emissions as feedstocks, which is challenging due to their low methane concentration and the presence of oxygen. Methane concentration had a marked influence on methane adsorption and methanol production (decreased from 164 µmol/g Cu for pure methane to 19 µmol/g Cu for 5% methane). The presence of oxygen, even in low concentrations (2.5%), reduced methane adsorption drastically. However, methanol production was only affected slightly (average decrease of 9%), concluding that methane adsorbed on the active centers yielding methanol is not influenced by oxygen.

Accelerating Sequence Alignments Based on FM-Index Using the Intel KNL Processor.

FM-index is a compact data structure suitable for fast matches of short reads to large reference genomes. The matching algorithm using this index exhibits irregular memory access patterns that cause frequent cache misses, resulting in a memory bound problem. This paper analyzes different FM-index versions presented in the literature, focusing on those computing aspects related to the data access. As a result of the analysis, we propose a new organization of FM-index that minimizes the demand for memory bandwidth, allowing a great improvement of performance on processors with high-bandwidth memory, such as the second-generation Intel Xeon Phi (Knights Landing, or KNL), integrating ultra high-bandwidth stacked memory technology. As the roofline model shows, our implementation reaches 95 percent of the peak random access bandwidth limit when executed on the KNL and almost all of the available bandwidth when executed on other Intel Xeon architectures with conventional DDR memory. In addition, the obtained throughput in KNL is much higher than the results reported for GPUs in the literature.

Memory hierarchy characterization of SPEC CPU2006 and SPEC CPU2017 on the Intel Xeon Skylake-SP.

SPEC CPU is one of the most common benchmark suites used in computer architecture research. CPU2017 has recently been released to replace CPU2006. In this paper we present a detailed evaluation of the memory hierarchy performance for both the CPU2006 and single-threaded CPU2017 benchmarks. The experiments were executed on an Intel Xeon Skylake-SP, which is the first Intel processor to implement a mostly non-inclusive last-level cache (LLC). We present a classification of the benchmarks according to their memory pressure and analyze the performance impact of different LLC sizes. We also test all the hardware prefetchers showing they improve performance in most of the benchmarks. After comprehensive experimentation, we can highlight the following conclusions: i) almost half of SPEC CPU benchmarks have very low miss ratios in the second and third level caches, even with small LLC sizes and without hardware prefetching, ii) overall, the SPEC CPU2017 benchmarks demand even less memory hierarchy resources than the SPEC CPU2006 ones, iii) hardware prefetching is very effective in reducing LLC misses for most benchmarks, even with the smallest LLC size, and iv) from the memory hierarchy standpoint the methodologies commonly used to select benchmarks or simulation points do not guarantee representative workloads.

Low-energy/pulse response and high-resolution-CMOS camera for spatiotemporal femtosecond laser pulses characterization @ 1.55 µm.

In this work, we present a commercial CMOS (Complementary Metal Oxide Semiconductor) Raspberry Pi camera implemented as a Near-Infrared detector for both spatial and temporal characterization of femtosecond pulses delivered from a femtosecond Erbium Doped Fiber laser (fs-EDFL) @ 1.55 µm, based on the Two Photon Absorption (TPA) process. The capacity of the device was assessed by measuring the spatial beam profile of the fs-EDFL and comparing the experimental results with the theoretical Fresnel diffraction pattern. We also demonstrate the potential of the CMOS Raspberry Pi camera as a wavefront sensor through its a nonlinear response in a Shack-Hartmann array and for the temporal characterization of the femtosecond pulses delivered from the fs-EDFL through TPA Intensity autocorrelation measurements. The direct pulse detection and measurement, through the nonlinear response with a CMOS, is proposed as a novel and affordable high-resolution and high-sensitivity alternative to costly detectors such as CCDs, wavefront sensors and beam profilers @ 1.55 µm. The measured fluence threshold, down to 17.5 µJ/cm2, and pJ/pulse energy response represents the lowest reported values applied as a beam profiler and a TPA Shack-Hartmann wavefront sensor, to our knowledge.

Non-invasive diagnostic of cardiac allograft vasculopathy by 31P magnetic resonance chemical shift imaging.

BACKGROUND: Coronary angiography is still the gold standard for the diagnosis of cardiac allograft vasculopathy (CAV) for which alternative non-invasive diagnostic approaches are currently investigated. In this study, we assessed whether 31P magnetic resonance chemical shift imaging can diagnose CAV by studying variations in cardiac high-energy phosphates in a population of adult heart transplant recipients. METHODS AND RESULTS: CAV was defined by coronary angiography as the presence of diffuse coronary irregularities with significant concentric narrowing on epicardial or distal coronary arteries. Eight patients with CAV (group A), and 18 patients without CAV (group B) were included in this study and compared to nine healthy volunteers (group C). Patients and volunteers underwent 31P three-dimensional chemical shift imaging to determine the ratio of phosphocreatine (PCr) and adenosine tri-phosphate (ATP). PCr/ATP was significantly lower in group A (1.51+/-0.50) than in groups B and C (1.98+/-0.53 (p=0.003) and 2.14+/-0.31 (p=0.001)), respectively. Time from transplant, number of episodes of acute rejection, and left ventricular ejection fraction (LVEF) were not significantly different between patient groups. A PCr/ATP value of 1.59 was the optimal cut-off value to predict CAV (specificity and sensitivity of 100% and 72%, respectively). CONCLUSION: Clinically, in vivo 31P chemical shift imaging is a promising, non-invasive method to detect the potential modifications of high-energy phosphates related to CAV and to better screen indications for coronary angiograms. This may be relevant for coronary angiography follow-up and adjustments of immunotherapy regimen.

Webcam autofocus mechanism used as a delay line for the characterization of femtosecond pulses.

In this work, we present an electromagnetic focusing mechanism (EFM), from a commercial webcam, implemented as a delay line of a femtosecond laser pulse characterization system. The characterization system consists on a second order autocorrelator based on a two-photon-absorption detection. The results presented here were performed for two different home-made femtosecond oscillators: Ti:sapph @ 820 nm and highly chirped pulses generated with an Erbium Doped Fiber @ 1550 nm. The EFM applied as a delay line represents an excellent alternative due its performance in terms of stability, resolution, and long scan range up to 3 ps. Due its low power consumption, the device can be connected through the Universal Serial Bus (USB) port. Details of components, schematics of electronic controls, and detection systems are presented.

Parsonnet's risk score predicts late survival but not late functional results after aortic valve replacement in octogenarians.

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess whether outcome after aortic valve replacement (AVR) in octogenarians can be anticipated by their preoperative clinical status. METHODS: Early and late results of 101 consecutive patients operated on for AVR between 1988 and 1998 in the authors' department were reviewed. Data were compared for two patient groups determined by Parsonnet's risk score (PRS) values: group A (n = 42), PRS <30, and group B (n = 59), PRS > or =30. RESULTS: Hospital mortality was 7.1% in group A and 16.9% in group B (p = NS). Follow up was complete (total 268 patient-years; mean 2.7 years per patient). Five- and eight-year survival rates were 76% and 39% in group A, and 57% and 16% in group B (p <0.05). Late mortality was mainly related to non-cardiac causes. Among 61 survivors on completion of follow up, functional results (mean NYHA class and mean Karnofsky score) were 1.5+/-0.8 versus 1.5+/-0.7 and 61+/-18 versus 61+/-17 in groups A and B, respectively. Among survivors, 24/31 from group A versus 22/30 from group B were still living in their own home. CONCLUSION: These results indicated that the PRS overestimated the operative risk of AVR in octogenarians. PRS also appeared to be related to late survival in these patients, but did not predict any postoperative functional benefits.

[Genetic polymorphisms of the renin-angiotensin system and essential hypertension]. / Polimorfismos genéticos del sistema renina-angiotensina e hipertensión arterial esencial.

BACKGROUND: The renin-angiotensin system (RAS) is known to regulate the blood pressure (BP). Several RAS polymorphisms have been associated with essential hypertension (EH), but there is uncertainty about this association. We examined whether the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene, and the M235T polymorphism of the angiotensinogen (AGT) gene were associated with EH in a sample of Spanish hipertensive patients. PATIENTS AND METHOD: We studied 1,204 patients with EH (BP > 140/90 mmHg): 668 males, aged 50.8 (13.6) years with systolic BP 151.7 (19.1) and diastolic BP 94.3 (13) mmHg [mean (SD)] and 536 females, aged 52.4 (13.9) years with systolic BP 155.1 (19.8) and diastolic BP 94.5 (12.3) mmHg. As a control group, 367 men and 280 women with no family history of cardiovascular disease who had a normal blood pressure were included. Polymorphisms were determined by PCR amplification of genomic DNA, followed by enzyme digestion for the AGT gene polymorphism. RESULTS: The genotype distribution and allele frequencies of the two RAS polymorphisms were similar in hypertensive and control subjects. Similarly, there were no differences in BP level with regard to the genotype in male or female patients. In addition, we did not find any compound effect of the I/D ACE gene and M235T AGT gene polymorphisms on BP levels in hypertensive subjects. CONCLUSIONS: This study suggests that in the population studied, the contribution of the ACE I/D polymorphism and the AGT M235T polymorphism in the development of EH is less important than previously estimated.

Mid-term results of laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass in adolescent patients.

The prevalence and severity of obesity in children and adolescents has been increasing in recent years at an unprecedented rate. Morbidly obese children will almost certainly develop severe comorbidities as they progress to adulthood, and bariatric surgery may provide the only alternative for achieving a healthy weight. The aim of this study was to assess the long-term outcomes and safety of laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) as new treatment modalities for morbidly obese adolescents. We conducted a retrospective review of a prospectively collected database of all adolescent patients who underwent LSG and RYGB under IRB protocol at the Bariatric and Metabolic Institute in Cleveland Clinic Florida between 2002 and 2011. Patients were also contacted by phone, adhering to HIPAA regulations, and were asked to answer a survey. Eighteen adolescents had a bariatric procedure performed at this institution. The mean age was 17.5 years, the average weight was 293.1 lbs, and the average BMI was 47.2 kg/m2. The mean follow-up period consisted of 55.2 months. The postoperative weight at 55 months follow-up was 188.4 lbs and average BMI was 30.1 kg/m2. Fifteen of the patients were available for follow-up. Thirteen out of 16 (81%) comorbidities in patients available for follow-up were in remission following rapid weight loss. The long-term follow-up and perioperative morbidity shown in this study suggest that LSG and LRYGB appear to be safe and effective operations in morbidly obese adolescents.

Genomic and metabolomic profile associated to microalbuminuria.

To identify factors related with the risk to develop microalbuminuria using combined genomic and metabolomic values from a general population study. One thousand five hundred and two subjects, Caucasian, more than 18 years, representative of the general population, were included. Blood pressure measurement and albumin/creatinine ratio were measured in a urine sample. Using SNPlex, 1251 SNPs potentially associated to urinary albumin excretion (UAE) were analyzed. Serum metabolomic profile was assessed by 1H NMR spectra using a Brucker Advance DRX 600 spectrometer. From the total population, 1217 (mean age 54 ± 19, 50.6% men, ACR>30 mg/g in 81 subjects) with high genotyping call rate were analysed. A characteristic metabolomic profile, which included products from mitochondrial and extra mitochondrial metabolism as well as branched amino acids and their derivative signals, were observed in microalbuminuric as compare to normoalbuminuric subjects. The comparison of the metabolomic profile between subjects with different UAE status for each of the genotypes associated to microalbuminuria revealed two SNPs, the rs10492025_TT of RPH3A gene and the rs4359_CC of ACE gene, with minimal or no statistically significant differences. Subjects with and without microalbuminuria, who shared the same genotype and metabolomic profile, differed in age. Microalbuminurics with the CC genotype of the rs4359 polymorphism and with the TT genotype of the rs10492025 polymorphism were seven years older and seventeen years younger, respectively as compared to the whole microalbuminuric subjects. With the same metabolomic environment, characteristic of subjects with microalbuminuria, the TT genotype of the rs10492025 polymorphism seems to increase and the CC genotype of the rs4359 polymorphism seems to reduce risk to develop microalbuminuria.