The present invention provides methods for assessing whether a subject is at risk of developing a neurological disorder, diagnosing or confirming whether a subject is afflicted with a neurological disorder, assessing whether PD has progressed in a subject afflicted with PD, assessing whether a neurological disorder is developing in a subject who has been identified as being at risk of developing the neurological disorder, assessing whether a subject afflicted with a neurological disorder is likely to benefit from a therapy, assessing whether a subject afflicted with a neurological disorder has benefited from a therapy, treating a subject afflicted with a neurological disorder, and prophylactically treating a subject who has been identified as being at risk of developing a neurological disorder. The present invention also provides epitopes, compounds and compositions relating to these methods.

Provided herein are systems and methods for biomass digestion and products formed thereof. The products include one or more biogases, U.S. Environmental Protection Agency classified Class A Biosolids, and pathogen reduced organic liquid fertilizer. Through the digestion of waste materials using sequential phases in an efficient digestion process, enhanced biomass conversion efficiency and improved output of products (in quantity and/or quality) are obtained with a significant reduction in dwell time in each phase.

A method for treating a synthesis gas from a gasification step. The synthesis gas is cooled to condense heavy organic impurities and water. At the end of the cooling step, light organic impurities and inorganic impurities are adsorped by at least one adsorption bed. The water and heavy tars are separated by decantation from the step of cooling the synthesis gas. At least one adsorption bed is regenerated by temperature-modulated or pressure-modulated desorption.

A harvesting system and method providing a row insensitive plant cutting and gathering capability, suitable for harvesting tall, stalky plants such as sweet sorghum, cane, and the like, in high volume, which also billet cuts the harvested plants. Multiple plants are cut simultaneously on a continuous basis at any locations across a header of the system, and the cut plants are gathered into a continuous overlapping flow having a vertical extent or thickness of several stalks or canes and their associated foliage. The flow is then vertically compacted into a mat of reduced thickness while being conveyed into a billet cutter, which cuts the stalks or canes into billets of a desired length and discharges the billets to a desired location, all while the harvester is moving through a field harvesting. The system can be incorporated into a conventional sugarcane harvester in place of conventional base cutters and row dividers.

An apparatus for forming a water storage material from a biomass input material using supercritical or subcritical fluid processing, the water storage material capable of absorbing a liquid and releasing the liquid. The apparatus utilizes supercritical fluid processing, subcritical fluid processing, charring, or a combination thereof. The apparatus includes a controller configured to control the apparatus. The apparatus further including a processing station configured to hold the biomass input material, and to use the biomass input material for processing into the water storage material.

Described herein are systems and methods for achieving fast pyrolysis of wood and other carbonaceous solids in rotary reactors. Novel heating, feeding and condensing methods result in high oil yields near those currently achieved with more complicated fast pyrolysis systems. High intensity burners are arranged and controlled to produce high heating rates and uniform temperature of the rotating cylindrical walls of the reactors. The feeding system delays the onset of pyrolysis until the solids fall onto the heated kiln walls. The pyrolysis gases and vapors are rapidly withdrawn and quenched with recycled liquids. The first condenser incorporates a clean out nozzle. Char products are readily separated and discharged into a heat exchanger where heat is recovered and used together with heat from reactor flue gas to dry the solids prior to being fed to the reactor.

A method for producing synthetic gas from biomass by: a) grinding the biomass, feeding the biomass into a pyrolysis furnace while spraying a first superheated water vapor into the pyrolysis furnace, controlling the temperature of the pyrolysis furnace at 500-800° C., contacting the biomass with the first superheated water vapor for a pyrolysis reaction to yield crude synthetic gas and ash including coke; b) cooling the ash, and separating the coke from the ash; c) transporting the crude synthetic gas and the coke into a gasifier, spraying a second superheated water vapor into the gasifier, controlling the gasifier at an operating temperature of 1200-1600° C., contacting the biomass with the second superheated water vapor for a gasification reaction to yield primary synthetic gas; and d) cooling, removing dust, deacidifying, and desiccating the primary synthetic gas to obtain clean synthetic gas.

The disclosed embodiments provide systems for the removal and use of tar from a biomass gasification system. For example, in one embodiment, a biomass gasification system includes a reactor configured to gasify a biomass fuel in the presence of air to generate a producer gas. The system also includes an absorber configured to receive a mixture of the producer gas and tar and to absorb the tar into an organic solvent to produce treated producer gas and a rich solvent mixture containing at least a portion of the tar. The system further includes a recycle line configured to direct the rich solvent mixture to a biomass gasifier.

Light-addressable potentiometric sensing units are provided. A light-addressable potentiometric sensing unit comprises a conductive substrate, a metal oxide semiconductor layer, and a sensing layer. The metal oxide semiconductor layer is made of indium gallium zinc oxide, indium gallium oxide, indium zinc oxide, indium oxide co-doped with tin and zinc, tin oxide, or zinc oxide. The wide-band gap characteristic of the metal oxide semiconductor layer enables the light-addressable potentiometric sensing unit to resist the interference from visible light. The light-addressable potentiometric sensing unit therefore exhibits a more stable performance.

Embodiments presented herein describe an apparatus and method to control the conversion of carbonaceous materials, particularly biomass and those biomass resources, into a high performance solid fuel. This method, and the apparatus described as the means to accomplish this method, provides a process having a control system that enables the system to produce a fuel of uniform quality, even with a change in biomass supply.

A two-stage reactor is disclosed for the conversion of solid particulate biomass material. The reactor is designed to maximize conversion of the solid biomass material, while limiting excess cracking of primary reaction products. The two-stage reactor comprises a first stage reactor, in which solid biomass material is thermally pyrolyzed to primary reaction products. The primary reaction products are catalytically converted in a second stage reactor.

A process is provided comprising subjecting a quantity of plant biomass fibers to a pretreatment to cause at least a portion of lignin contained within each fiber to move to an outer surface of said fiber, wherein a quantity of pretreated tacky plant biomass fibers is produced; and densifying the quantity of pretreated tacky plant biomass fibers to produce one or more densified biomass particulates, wherein said biomass fibers are densified without using added binder.

The present invention refers to a process for classifying tumor samples of unknown and/or uncertain primary origin, specifically including the steps of obtaining patterns of biological activity modulation of tumor of unknown and/or uncertain primary origin and comparing them to an specific and unique group of biomarkers which determine the profiles of biological activity modulation of known origin tumors. The present invention belongs to the molecular biology and genetics field.

The present invention provides detection methods for detecting a pre-cancerous epithelial cell signature. The present invention further provides reagents for use in the detection methods. A subject detection method is useful in various imaging, diagnostic, prognostic, and patient monitoring methods, which are also provided.

A system and method for detecting a biomarker in exhaled breath condensate nanodroplets comprises noninvasively collecting exhaled breath condensate nanodroplets of a subject, and analyzing said nanodroplets utilizing immuno-quantitative polymerase chain reaction to detect one or more target biomarkers.

The present invention relates to methods of determining if a subject has an increased risk of suffering from memory impairment. The methods comprise analyzing at least one sample from the subject to determine a value of the subject's exosomal profile or combined biomarker profile (lipids plus exosomal cargo) and comparing the value of the subject's exosomal or combined biomarker profile with the value of a normal exosomal or biomarker profile, respectively. A change in the value of the subject's exosomal or combined biomarker profile, including a change in the subject's exosomal or combined biomarker profile, over normal values is indicative that the subject has an increased risk of suffering from memory impairment compared to a normal individual.

A system includes a gas turbine system having a turbine combustor, a turbine driven by combustion products from the turbine combustor, and an exhaust gas compressor driven by the turbine. The exhaust gas compressor is configured to compress and supply an exhaust gas to the turbine combustor. The gas turbine system also has an exhaust gas recirculation (EGR) system. The EGR system is configured to recirculate the exhaust gas along an exhaust recirculation path from the turbine to the exhaust gas compressor. The system further includes a main oxidant compression system having one or more oxidant compressors. The one or more oxidant compressors are separate from the exhaust gas compressor, and the one or more oxidant compressors are configured to supply all compressed oxidant utilized by the turbine combustor in generating the combustion products.

Currently, owing to the ongoing lockdown, kirana (corner) stores on JioMart serve limited inventory. But that will be a thing of the past once restrictions are lifted.

Currently, owing to the ongoing lockdown, kirana (corner) stores on JioMart serve limited inventory. But that will be a thing of the past once restrictions are lifted.

Shares of Biomerica Inc. (BMRA) are surging over 28% in pre-market today, after the company announced that it has received a CE mark and launched a new high-volume production version of its COVID-19 IgG/IgM Rapid Test (a finger prick blood test with results in 10 minutes, that can be performed by trained professionals anywhere) being sold in countries outside the US.

Fisheries science with indigenous perspective, slippery surface and seasons on other planets

Some koalas may be pickier eaters than others due to the mix of microbes in their lower gastrointestinal tract, but faecal transplants could help them diversify their diet, a new study suggests.

Axiom is a smart work assistant that saves you time by making the complex straightforward.

(United States Ninth Circuit) - In a civil procedure action, arising from a copyright infringement action brought by plaintiffs, American companies in the natural foods industry, against defendant, a UK limited company, after defendant sent an email newsletter containing plaintiffs' logos to 343 email addresses, the district court's dismissal for lack of personal jurisdiction is affirmed where defendant's suit-related conduct did not create a substantial connection with California.

(United States Ninth Circuit) - In a civil procedure action, arising from a copyright infringement action brought by plaintiffs, American companies in the natural foods industry, against defendant, a UK limited company, after defendant sent an email newsletter containing plaintiffs' logos to 343 email addresses, the district court's dismissal for lack of personal jurisdiction is affirmed where defendant's suit-related conduct did not create a substantial connection with California.

В новом интервью с SiriusXM "Trunk Nation" у легендарного гитариста Tony Iommi спросили, доволен ли он тем, как прошёл прощальный тур BLACK SABBATH "The End", на что он ответил:

«Было здорово иметь возможность отправиться в последний тур. Честно говоря, я чувствовал себя неважно [из-за] этого, потому что в основном это был мой выбор, моя вина, потому что турне для меня в некоторой степени было в физическом плане не самой лучшей идеей. Я имею в виду, что приходилось возвращаться в часа утра после концерта — ты отыграл концерт, а потом летишь обратно в отель — это было много возвращений поздними ночами. Я находился в таких же условиях, как когда мне было 20. Несмотря на то, что мы путешествовали [на] лучших [условиях] — у нас был собственный самолет, у нас были потрясающие отели, и нас разместили в Нью-Йорке или Лос-Анджелесе на 10 дней, или где-то ещё, это было вот так. Выходили из отеля, летели на самолёте, давали концерт, возвращались, но к тому времени, как мы заканчивали, возвращались в отель и ложились спать, уже было три-четыре часа. А для меня это было трудно, и мой доктор сказал мне попробовать немного успокоиться. И в то время это казалось правильным.

Особенно после всего, что случилось с Ронни [Джеймсом Дио], мне очень понравился тот период [с HEAVEN & HELL], когда мы были снова с Дио, мы очень сблизились с этой группой, и это была отличная группа. А потом мы решили заново собрать SABBATH с Ozz'ом [Ozzy Osbourne'ом], и это было круто для завершения карьеры. Но я думаю, что если бы Ронни был жив, я бы, наверное, делал что-нибудь с ним сейчас».

Iommi также ответил на вопрос, возможны ли разовые выступления группы:

«Думаю, это было бы неплохо, ну если мы сможем это сделать. Сложность в том, по крайней мере с SABBATH, что это всё серьёзное предприятие, ты не можешь просто взять и отыграть, так как нужны техники, полная линейка оборудования и всё такое. И это должен быть год или полтора тура... Я не против чего-то такого, я просто хотел бы всё сделать иначе». #Black_Sabbath #BlackSabbath #HardRock #Hard_Rock #HeavyMetal #Heavy_Metal

I was skeptical of an email asking for a lung cancer link

El 67% de los usuarios en todo el mundo se siente actualmente cómodo utilizando tecnologías biométricas (lectura de huella dactilar, escaneado de retina y reconocimiento facial o de voz) para acceder a sus aplicaciones, según el estudio IBM Security Future of Identity elaborado por IBM.

Researchers have uncovered a potential means to profile and track online users using a novel approach that combines device identifiers with their biometric information. The details come from a newly published research titled "Nowhere to Hide: Cross-modal Identity Leakage between Biometrics and Devices" by a group of academics from the University of Liverpool, New York University, The Chinese

Welcome to part 1112 of the blog.continued from cracker in melaka ...The morning after the hindu procession i awoke to find Reuben and Livia had backed their bags and left for Cherating. After moving into a single room across the hall I went for s

An array of scientific evidence suggest that in some cases, the bacteria in your gut–your microbiome–could be tied to neurological and psychological disorders and differences, from anxiety and autism to Parkinson's and schizophrenia. The journal Science published a survey of the field and the Cambridge, Massachusetts start-up Holobiome that hopes to use insight into this "psychobiome" to develop treatments for depression, insomnia, and other conditions with a neurological side to them. From Science:

For example, many people with irritable bowel syndrome are also depressed, people on the autism spectrum tend to have digestive problems, and people with Parkinson’s are prone to constipation.

Researchers have also noticed an increase in depression in people taking antibiotics—but not antiviral or antifungal medications that leave gut bacteria unharmed. Last year, Jeroen Raes, a microbiologist at the Catholic University of Leuven, and colleagues analyzed the health records of two groups—one Belgian, one Dutch—of more then 1000 people participating in surveys of their types of gut bacteria. People with depression had deficits of the same two bacterial species, the authors reported in April 2019 in Nature Microbiology.

Researchers see ways in which gut microbes could influence the brain. Some may secrete messenger molecules that travel though the blood to the brain. Other bacteria may stimulate the vagus nerve, which runs from the base of the brain to the organs in the abdomen. Bacterial molecules might relay signals to the vagus through recently discovered “neuropod” cells that sit in the lining of the gut, sensing its biochemical milieu, including microbial compounds.

Purpose: The aim of this retrospective multicentric study was to develop and evaluate a prognostic FDG PET/CT radiomics signature in early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic radiotherapy (SBRT). Material and Methods: Patients from 3 different centers (n = 27, 29 and 8) were pooled to constitute the training set, whereas the patients from a fourth center (n = 23) were used as the testing set. The primary endpoint was local control (LC). The primary tumour was semi-automatically delineated in the PET images using the Fuzzy locally adaptive Bayesian algorithm, and manually in the low-dose CT images. A total of 184 IBSI-compliant radiomic features were extracted. Seven clinical and treatment parameters were included. We used ComBat to harmonize radiomic features extracted from the four institutions relying on different PET/CT scanners. In the training set, variables found significant in the univariate analysis were fed into a multivariate regression model and models were built by combining independent prognostic factors. Results: Median follow-up was 21.1 (1.7 – 63.4) and 25.5 (7.7 – 57.8) months in training and testing sets respectively. In univariate analysis, none of the clinical variables, 2 PET and 2 CT features were significantly predictive of LC. The best predictive models in the training set were obtained by combining one feature from PET, namely information correlation 2 (IC2) and one from CT (Flatness), reaching a sensitivity of 100% and a specificity of 96%. Another model combining 2 PET features (IC2 and Strength), reached sensitivity of 100% and specificity of 88%, both with an undefined hazard ratio (HR) (p<0.001). The latter model obtained an accuracy of 0.91 (sensitivity 100%, specificity 81%), with a HR undefined (P = 0.023) in the testing set, however other models relying on CT radiomics features only or the combination of PET and CT features failed to validate in the testing set. Conclusion: We showed that two radiomic features derived from FDG PET were independently associated with LC in patients with NSCLC undergoing SBRT and could be combined in an accurate predictive model. This model could provide local relapse-related information and could be helpful in clinical decision-making.

[S-Methyl-¹¹C](±)-7-methoxy-3-(4-(4-(methylthio)phenyl)butyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol (¹¹C-NR2B-SMe) and its enantiomers were synthesized as candidates for imaging the NR2B subunit within the N-methyl-D-aspartate receptor with positron emission tomography (PET). Methods: Brains were scanned with PET for 90 min after intravenous injection of one of the candidate radioligands into rats. To detect any NR2B specific binding of radioligand in brain, various pre-blocking or displacing agents were evaluated for their impact on the PET brain imaging data. Radiometabolites from brain and other tissues were measured ex vivo and in vitro. Results: Each radioligand gave high early whole brain uptake of radioactivity, followed by a brief fast decline and then a slow final decline. ¹¹C-(S)-NR2B-SMe was studied extensively. Ex vivo measurements showed that radioactivity in rat brain at 30 min after radioligand injection was virtually unchanged radioligand. Only less lipophilic radiometabolites appeared in plasma. High-affinity NR2B ligands, Ro-25-6981, ifenprodil, and CO10124, showed increasing preblock of whole brain radioactivity retention with increasing dose (0.01 to 1.25 mg/kg, i.v.). Five 1 antagonists (FTC146, BD1407, F3, F4, and NE100) and four 1 agonists ((+)-pentazocine, (±)-PPCC, PRE-084, (+)-SKF10047) were ineffective preblocking agents, except FTC146 and F4 at high dose. Two potent 1 receptor agonists, TC1 and SA4503, showed dose-dependent preblocking effects in the presence or absence of pharmacological 1 receptor blockade with FTC146. Conclusion: ¹¹C-(S)-NR2B-SMe has adequate NR2B-specific PET signal in rat brain to warrant further evaluation in higher species. TC1 and SA4503 likely have off-target binding to NR2B in vivo.

Purpose: PET using O-(2-[¹⁸F]Fluoroethyl)-L-tyrosine (¹⁸F-FET) is useful to detect residual tumor tissue after glioma resection. Recent animal experiments detected reactive changes of ¹⁸F-FET uptake at the rim of the resection cavity within the first two weeks after resection of gliomas. In the present study, we evaluated pre- and postoperative ¹⁸F-FET PET scans of glioma patients with particular emphasis on the identification of reactive changes after surgery. Methods: Forty-three patients with cerebral gliomas (9 low-grade, 34 high-grade; 9 primary tumors, 34 recurrent tumors) who had preoperative (time before surgery, median 23 d, range 6-44 d) and postoperative ¹⁸F-FET-PET (time after surgery, median 14, range 5–28 d) were included. PET scans (20-40 min p.i.) were evaluated visually for complete or incomplete resection (CR, IR) and compared with MRI. Changes of ¹⁸F-FET-uptake in residual tumor were evaluated by tumor-to-brain ratios (TBRmax) and in the vicinity of the resection cavity by maximum lesion-to-brain ratios (LBRmax). Results: Visual analysis of ¹⁸F-FET PET scans revealed CR in 16/43 patients and IR in the remaining patients. PET results were concordant with MRI in 69% of the patients. LBRmax of ¹⁸F-FET uptake in the vicinity of the resection cavity was significantly higher compared with preoperative values (1.59 ± 0.36 versus 1.14 ± 0.17; n = 43, p<0.001). In 11 patients (26%) a "flare phenomenon" was observed with a considerable increase of ¹⁸F-FET uptake compared with preoperative values in either the residual tumor (n = 5) or in areas remote from tumor in the preoperative PET scan (n = 6) (2.92 ± 1.24 versus 1.62 ± 0.75; p<0.001). Further follow-up in five patients showed decreasing ¹⁸F-FET uptake in the flare areas in four and progress in one case. Conclusion: Our study confirms that ¹⁸F-FET PET provides valuable information for assessing the success of glioma resection. Postoperative reactive changes at the rim of the resection cavity appear to be mild. However, in 23 % of the patients, a postoperative "flare phenomenon" was observed that warrants further investigation.

Cancer Survival is related to tumor volume. FDG PET measurement of tumor volume holds promise but is not yet a clinical tool. Measurements come in two forms: the total lesion volume (TLV) based on the number of voxels in the tumor and secondly the total lesion glycolysis (TLG) which is the TLV multiplied by the average SUL per voxel of the tumor (SUL is the standardize uptake value normalized for lean mass). In this study we measured tumor volume in patients with malignant pleural mesothelioma (MPM). METHODS: A threshold-based program in IDL was developed to measure tumor volume in FDG PET images. 19 patients with malignant pleural mesothelioma (MPM) were studied before and after two cycles (6 weeks) of chemo-immunotherapy. Measurements included the total lesion volume (TLV), Total Lesion Glycolysis (TLG), the sum of the SULs in the tumor (SUL- total), a measure of total FDG uptake, and the average SUL per voxel. RESULTS: Baseline MPM volumes (TLV) ranged from 11 to 2610 cc. TLG values ranged from 32 to 8552 SUL-cc and were strongly correlated with TLV. While tumor volumes ranged over 3 orders of magnitude, the average SUL per voxel, SUL-average, stayed within a narrow range of 2.4 to 5.3 units. Thus, TLV was the major component of TLG while SUL-average was a minor component and was essentially constant. Further evaluation of SUL-average showed that in this cohort it’s two components SUL-total and tumor volume changed in parallel and were strongly correlated, r= 0.99, p<.01. Thus, whether the tumors were large or small, the FDG uptake as measured by SUL-total was proportional to the total tumor volume. Conclusion: TLG equals TLV multiplied by the average SUL per voxel, essentially TLV multiplied by a constant. Thus TLG, commonly considered a measure of "metabolic activity" in tumors, is also in this cohort a measure of tumor volume. The constancy of SUL per voxel is due to FDG uptake being proportional to tumor volume. Thus, in this study, the FDG uptake was also a measure of volume.

Prostate specific membrane antigen (PSMA) targeting Positron Emission Tomography (PET) imaging is becoming the reference standard for prostate cancer (PC) staging, especially in advanced disease. Yet, the implications of PSMA-PET derived whole-body tumor volume for overall survival are poorly elucidated to date. This might be due to the fact that (semi-) automated quantification of whole-body tumor volume as PSMA-PET biomarker is an unmet clinical challenge. Therefore, a novel semi-automated software is proposed and evaluated by the present study, which enables the semi-automated quantification of PSMA-PET biomarkers such as whole-body tumor volume. Methods: The proposed quantification is implemented as a research prototype (MI Whole Body Analysis Suite, v1.0, Siemens Medical Solutions USA, Inc., Knoxville, TN). PSMA accumulating foci were automatically segmented by a percental threshold (50% of local SUV_max). Neural networks were trained to segment organs in PET-CT acquisitions (training CTs: 8,632, validation CTs: 53). Thereby, PSMA foci within organs of physiologic PSMA uptake were semi-automatically excluded from the analysis. Pretherapeutic PSMA-PET-CTs of 40 consecutive patients treated with ¹⁷⁷Lu-PSMA-617 therapy were evaluated in this analysis. The volumetric whole-body tumor volume (PSMATV50), SUV_max, SUVmean and other whole-body imaging biomarkers were calculated for each patient. Semi-automatically derived results were compared with manual readings in a sub-cohort (by one nuclear medicine physician using syngo.MM Oncology software, Siemens Healthineers, Knoxville, TN). Additionally, an inter-observer evaluation of the semi-automated approach was performed in a sub-cohort (by two nuclear medicine physicians). Results: Manually and semi automatically derived PSMA metrics were highly correlated (PSMATV50: R2=1.000; p<0.001; SUV_max: R2=0.988; p<0.001). The inter-observer agreement of the semi-automated workflow was also high (PSMATV50: R2=1.000; p<0.001; ICC=1.000; SUV_max: R2=0.988; p<0.001; ICC=0.997). PSMATV50 [ml] was a significant predictor of overall survival (HR: 1.004; 95%CI: 1.001-1.006, P = 0.002) and remained so in a multivariate regression including other biomarkers (HR: 1.004; 95%CI: 1.001-1.006 P = 0.004). Conclusion: PSMATV50 is a promising PSMA-PET biomarker that is reproducible and easily quantified by the proposed semi-automated software. Moreover, PSMATV50 is a significant predictor of overall survival in patients with advanced prostate cancer that receive ¹⁷⁷Lu-PSMA-617 therapy.

The use of protein biomarkers as surrogates for clinical endpoints requires extensive multilevel validation including development of robust and sensitive assays for precise measurement of protein concentration. Multiple reaction monitoring (MRM) is a well-established mass-spectrometric method that can be used for reproducible protein-concentration measurements in biological specimens collected via microsampling. The dried blood spot (DBS) microsampling technique can be performed non-invasively without the expertise of a phlebotomist, and can enhance analyte stability which facilitate the application of this technique in retrospective studies while providing lower storage and shipping costs, because cold-chain logistics can be eliminated. Thus, precise, sensitive, and multiplexed methods for measuring protein concentrations in DBSs can be used for de novo biomarker discovery and for biomarker quantification or verification experiments. To achieve this goal, MRM assays were developed for multiplexed concentration measurement of proteins in DBSs.

The lower limit of quantification (LLOQ) was found to have a median total coefficient of variation (CV) of 18% for 245 proteins, whereas the median LLOQ was 5 fmol of peptide injected on column, and the median inter-day CV over 4 days for measuring endogenous protein concentration was 8%. The majority (88%) of the assays displayed parallelism, whereas the peptide standards remained stable throughout the assay workflow and after exposure to multiple freeze-thaw cycles. For 190 proteins, the measured protein concentrations remained stable in DBS stored at ambient laboratory temperature for up to 2 months. Finally, the developed assays were used to measure the concentration ranges for 200 proteins in twenty same sex, same race and age matched individuals.

Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.

Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. In our previous study, we surveyed both IgG and IgM-bound serological biomarkers and validated a panel of IgG-bound autoantigens for early LC diagnosis with 50% sensitivity at 90% specificity. To further improve the performance of these serological biomarkers, we surveyed HuProt arrays, comprised of 20,240 human proteins, for IgA-bound autoantigens because IgAs are a major immunoglobulin isotype in the lung. Integrating with IgG-bound autoantigens, we discovered and validated a combined biomarker panel using ELISA-format tests. Specifically, in Phase I, we obtained IgA-based autoimmune profiles of 69 early stage LC patients, 30 healthy subjects and 25 patients with lung benign lesions (LBL) on HuProt arrays and identified 28 proteins as candidate autoantigens that were significantly associated with early stage LC. In Phase II, we re-purified the autoantigens and converted them into an ELISA-format testing to profile an additional large cohort, comprised of 136 early stage LC patients, 58 healthy individuals, and 29 LBL patients. Integration of IgG autoimmune profiles allowed us to identify and validate a biomarker panel of three IgA autoantigens (i.e. BCL7A, and TRIM33 and MTERF4) and three IgG autoantigens (i.e. CTAG1A, DDX4 and MAGEC2) for diagnosis of early stage LC with 73.5% sensitivity at >85% specificity. In Phase III, the performance of this biomarker panel was confirmed with an independent cohort, comprised of 88 early stage LC patients, 18 LBL patients, and 36 healthy subjects. Finally, a blind test on 178 serum samples was conducted to confirm the performance of the biomarker panel. In summary, this study demonstrates for the first time that an integrated panel of IgA/IgG autoantigens can serve as valuable biomarkers to further improve the performance of early diagnosis of LC.

Sandi M. Azab
Mar 31, 2020; 0:jlr.D120000630v1-jlr.D120000630
Methods

Haibo Jiang
Apr 2, 2020; 0:jlr.ILR120000783v1-jlr.ILR120000783
Images in Lipid Research

We return like a nerdy phoenix for episode 66, where Henry Burrell leads David Price and Dominic Preston down the tech rabbit hole to discuss the week's news. Amazon Prime Day came and went, but what does it really mean for consumers and the media? Did you buy anything? Did you need it? The team then discuss the odd ongoing story of the man who lost copyright of an image of a monkey to... the monkey that allegedly took it. PETA got involved. It's weird. It's good to be back.  

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Join Henry Burrell as he asks Davids Price why Snopes, the fact checking website, has run into trouble and how crowdfunding could save the day. Is it still important in this age of fake news? Then Scott Carey commentates on the bout between Mark Zuckerberg and Elon Musk. Who knows the most about AI? When will the killer robots descend upon us? Does Mark do all his online Q & A’s in front of a cooking brisket? All this answered and more.  

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Oh boy what a meaty session we have for you as Christina Mercer, Somrata Sarkar, David Price and Henry Burrell tackle three whopics (whopping topics) head on.

Somrata takes us into the sometimes scary thoughts of our own digital afterlives. Should we be worried that we'll end up as misrepresentative chat bots one day? Who will have the authority to police the companies that harvest our data?

Then Christina explains the knife edge America is on when it comes to net neutrality. Despite recent hope, there's still a chance the web across the pond will be ruthlessly metered and segmented.

Finally David asks us if we've checked our unused email accounts recently, as there might be a lot of desperate noodle companies in there begging you to stay on their mailing lists.

See acast.com/privacy for privacy and opt-out information.

Nutritional studies rely on various biological specimens for fatty acid (FA) determination, yet it is unclear how levels of serum non-esterified FA (NEFAs) correlate with other circulating lipid pools. Here, we used a high throughput method (< 4 min/sample) based on multisegment injection-non-aqueous-capillary electrophoresis–mass spectrometry (MSI-NACE-MS) to investigate whether specific serum NEFAs have utility as biomarkers of dietary fat intake in women. We first  identified circulating NEFAs correlated with long-term/habitual food intake among pregnant women with contrasting dietary patterns (n=50). Acute changes in serum NEFA trajectories were also studied in non-pregnant women (n=18) following high-dose (5 g/day) fish oil (FO) supplementation or isoenergetic sunflower oil placebo over 56 days. In the cross-sectional study, serum omega-3 (-3) FA correlated with self-reported total -3 daily intake, notably eicosapentaenoic acid (EPA) as its NEFA (r=0.46; p=0.001), whereas pentadecanoic acid was associated with full-fat dairy intake (r=0.43; p=0.002), outcomes consistent with results from  total FA serum hydrolysates. In the intervention cohort, serum -3 NEFAs increased 2.5-fold from baseline within 28 days following FO supplementation, and this increase was most pronounced for EPA (p=0.0004). Unlike for docosahexaenoic acid, circulating EPA as its NEFA also strongly correlated to EPA concentrations measured from erythrocyte phospholipid hydrolysates (r=0.66; p=4.6 x 10-10), and was better suited to detect dietary non-adherence. We conclude that MSI-NACE-MS offers a rapid method to quantify serum NEFAs and objectively monitor dietary fat intake in women that is complementary to diet records or food frequency questionnaires.

Sepsis is defined as the systemic, dysregulated host immune response to an infection that leads to injury to host organ systems, and, often, death. Complex interactions between pathogens and their hosts elicit microcirculatory dysfunction. Neutrophil myeloperoxidase (MPO) is critical for combating pathogens, but MPO-derived hypochlorous acid (HOCl) can react with host molecular species as well. Plasmalogens are targeted by HOCl, leading to the production of 2-chlorofatty acids (2-CLFAs). 2-CLFAs are associated with human sepsis mortality, decrease in vitroendothelial barrier function, and activate human neutrophil extracellular trap formation. Here, we sought to examine 2-CLFAs in an in vivorat sepsis model. Intraperitoneal cecal slurry sepsis with clinically relevant rescue therapies led to ~73% mortality and evidence of microcirculatory dysfunction. Plasma concentrations of 2-CLFAs assessed 8h after sepsis induction were lower in rats that survived sepsis than in non-survivors. 2-CLFA levels were elevated in kidney, liver, spleen, lung, colon and ileum in septic animals. In vivo, exogenous 2-CLFA treatments increased kidney permeability, and in in vitroexperiments 2-CLFA also increased epithelial surface expression of vascular cell adhesion molecule 1 and decreased epithelial barrier function. Collectively, these studies support a role of free 2-CLFAs as biomarkers of sepsis mortality, potentially mediated, in part, by 2-CLFA-elicited endothelial and epithelial barrier dysfunction.

This article has been withdrawn by the authors. We discovered an error after this manuscript was published as a Paper in Press. Specifically, we learned that the structures of glycans presented for the PD-L1 peptide were drawn and labeled incorrectly. We wish to withdraw this article and submit a corrected version for review.

Cardiac glucose uptake and oxidation are reduced in diabetes despite hyperglycemia. Mitochondrial dysfunction contributes to heart failure in diabetes. It is unclear if these changes are adaptive or maladaptive. To directly evaluate the relationship between glucose delivery and mitochondrial dysfunction in diabetic cardiomyopathy we generated transgenic mice with inducible cardiomyocyte-specific expression of the glucose transporter (GLUT4). We examined mice rendered hyperglycemic following low-dose streptozotocin prior to increasing cardiomyocyte glucose uptake by transgene induction. Enhanced myocardial glucose in non-diabetic mice decreased mitochondrial ATP generation and was associated with echocardiographic evidence of diastolic dysfunction. Increasing myocardial glucose delivery after short-term diabetes onset, exacerbated mitochondrial oxidative dysfunction. Transcriptomic analysis revealed that the largest changes, driven by glucose and diabetes, were in genes involved in mitochondrial function. This glucose-dependent transcriptional repression was in part mediated by O-GlcNAcylation of the transcription factor Sp1. Increased glucose uptake induced direct O-GlcNAcylation of many electron transport chain subunits and other mitochondrial proteins. These findings identify mitochondria as a major target of glucotoxicity. They also suggest reduced glucose utilization in diabetic cardiomyopathy might defend against glucotoxicity and caution that restoring glucose delivery to the heart in the context of diabetes could accelerate mitochondrial dysfunction by disrupting protective metabolic adaptations.

23 February 2017

Although most renewable energy policy frameworks treat biomass as carbon-neutral at the point of combustion, biomass emits more carbon per unit of energy than most fossil fuels.