C2 C6 Research Articles

Selective extraction of high-added value carboxylic acids from aqueous fermentative effluents with new hydrophobic eutectic solvents (HES)

SummaryRecovering these carboxylic acids from the fermentative streams in a sustainable, green, and economical way is a significant challenge. This work assessed hydrophobic eutectic solvents (HES) – water-immiscible – for the selective recovery of carboxylic acids via liquid–liquid extraction. Different trioctylphosphine oxide (TOPO) mixtures with menthol and thymol were studied and deeply characterized by 1H and 31P NMR to yield stable eutectic solvents, including a novel experiment of 31P NMR at variable temperatures for the first time. Those stable eutectic solvents were tested in the liquid extraction of complex aqueous mixtures containing C2–C6 carboxylic acids and simple sugars (glucose and xylose). The back-extraction of the carboxylic acids for the recovery of the HES was optimized, being necessary in three stages for the complete cleaning of the eutectic solvent using NaOH 0.1 M. The eutectic mixture of TOPO and thymol in a molar ratio of 1:2 exhibited an overall recovery of C5 and C6 carboxylic acids over 70 %, allowing its selective extraction from the rest of the compounds in the complex mixture. Likewise, this HES (after back extraction) was successfully reused in a second extraction cycle, keeping the performance of the fresh one. Therefore, this study demonstrated that HES can have a high extraction selectivity for carboxylic acids of ≥C5. Moreover, these solvents were stable and allowed reusability, reducing the environmental impact and process costs.

Biochar facilitated Biological CO2 conversion to C2-C6 alcohols and fatty acids

Microbial CO2 utilization reduces the carbon footprint, providing economic potential. Biochar, rich in minerals and trace metals, can enhance microbial activity. This study investigates poultry litter and switchgrass biochars produced at 350 and 700 °C (PLB350, PLB700, SGB350 and SGB700, respectively) affect CO2 conversion to C2–C6 alcohols and acids by Clostridium muellerianum P21, C. ragsdalei P11 and C. carboxidivorans P7. Fermentations were in 250-mL bottles containing H2:CO2:N2 (60:20:20) shaken at 125 rpm and 37 °C. SGB350 increased alcohol titers by 1.1–2.1 fold, and PLB350 enhanced acid concentrations by 1.2–1.7 fold compared to the control without biochar. About 2.0–3.3 fold more ethanol was formed by strain P11 compared to strains P7 and P21 with SGB350. However, strain P21 produced 2.4-fold more butanol than strain P7 with SGB350, including unique hexanol production. These results highlight the potential of biochar in enhancing C2–C6 alcohol production from CO2, thereby boosting process feasibility.

Stopping Power and Range Calculations of electrons interaction with C2 H4, C6 H6 and CH3CHO

Stopping Power and Range Calculations of electrons interaction with C2 H4, C6 H6 and CH3CHO

Synthesis and quantification of short-chain fatty acid esters of hydroxy fatty acids in rat intestinal contents and fecal samples by LC-MS/MS

Short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs) are a new class of endogenous lipids belonging to the fatty acid esters of the hydroxy fatty acid family. We previously uncovered their chemical structure and discussed their potential biological significance. We anticipate an increased need for SFAHFA measurements as markers of metabolic and inflammatory health. In this study, we synthesized sixty isomeric SFAHFAs by combining 12 hydroxy fatty acids (C16–C24) and five short-chain fatty acids (C2–C6) including a labelled internal standard. SFAHFA enrichment was achieved by solid-phase extraction and established a sensitive method for their quantitation by targeted LC-MS/MS. The method was applied to profile SFAHFAs in intestinal contents and fecal samples collected from rats fed a high-fat diet (HFD). The results demonstrated a significant decrease in SFAHFAs in the intestinal contents of the HFD group compared with the control group. The fecal time course (0–8 weeks) profile of SFAHFAs showed significant downregulation of acetic and propanoic acid esters in just 2 weeks after HFD administration. This study offers the first synthesis and quantitation method for SFAHFAs, demonstrating their potential use in elucidating SFAHFA sources, their role in various diseases, and potential biochemical signalling pathways.

Glofitamab + Pola-R-CHP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL): Results from a phase Ib study.

7549 Background: Polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin and prednisone (Pola-R-CHP) has shown a significant progression-free survival benefit versus R-CHOP as first line (1L) therapy for DLBCL (Tilly et al. 2022). Glofitamab is a bispecific antibody with a novel 2:1 (CD20:CD3) format; bivalency for CD20 on B cells enables combination with anti-CD20 antibodies, including rituximab. Glofitamab monotherapy induced durable responses in patients (pts) with relapsed/refractory DLBCL and its incorporation in the 1L setting may further improve outcomes (Dickinson et al. 2022). We present results from the expansion stage of an ongoing Phase Ib study (NCT03467373) of glofitamab (Glofit) + Pola-R-CHP in pts with 1L DLBCL. Methods: Pts received Pola-R-CHP on Day (D) 1 of each 21-day cycle (C; max. 6 cycles) and glofitamab in C2‒C6 (C2 step-up dosing [2.5mg C2D8, 10mg C2D15]; target dose [30mg] C3D8 and onwards). Response was assessed by PET-CT using Lugano criteria (Cheson et al. 2014). Efficacy-evaluable pts were those that reached end of treatment (EOT), progressed or died by data cut-off (EOT population). Cytokine release syndrome (CRS) events were graded by ASTCT criteria (Lee et al. 2019) and other adverse events (AEs) by CTCAE (v4.0). Results: As of Nov 14, 2022, 24 pts had enrolled and received study treatment (safety population). Median age was 65 years (range: 32–85), 96% of pts had stage III–IV disease and median IPI score was 3 (IPI 1: 4% [1/24], IPI 2: 33% [8/24], IPI 3: 38% [9/24], IPI 4: 25% [6/24]). Of 24 pts, 17 were efficacy evaluable. After a median follow up of 5.1 (range: 3–8) months, complete metabolic response rate was 76.5% (13/17) and overall response rate was 100% in the EOT population (best overall response). In safety-evaluable pts, Grade (Gr) ≥3 AEs occurred in 15 (63%) pts and Gr ≥3 AEs related to glofitamab in 9 (38%) pts. One Gr 5 AE was reported (acute respiratory distress syndrome, unrelated to study treatment). Serious AEs (SAEs) were reported in 12 (50%) pts and SAEs related to glofitamab in 4 (17%) pts. AEs leading to glofitamab dose interruption occurred in 5 (21%) pts; median dose intensity was 100% for all Glofit + Pola-R-CHP components. Only Gr 1 CRS (n = 3, 13%) was reported, with no treatment or hospitalization required. Neurological AEs (NAEs) occurred in 11 (46%) pts and were mostly Gr 1/2 (10 pts, 42%); one patient had a Gr 3 NAE (hypomania). No NAEs potentially consistent with immune effector cell-associated neurotoxicity syndrome were reported. Neutropenia was reported in 12 (50%) pts (Gr 3, n = 6; Gr 4, n = 6), febrile neutropenia in 2 (8.3%) pts and Gr 3/4 infection in 4 (17%) pts (Gr 3, n = 2; Gr 4, n = 2). Conclusions: Early data suggest that Glofit + Pola-R-CHP has promising efficacy and a similar safety profile to Pola-R-CHP and Glofit + R-CHOP for 1L DLBCL treatment. Glofit + Pola-R-CHP dose intensity was maintained in all pts. Updated data will be presented. Clinical trial information: NCT03467373 .

One-pot synthesis of cellulose ester–graft–polylactide copolymers in an ionic liquid and the effect of graft-chain composition on their thermoplasticities and enzymatic degradabilities

With the aim of developing polymers having controlled thermoplasticities and biodegradabilities, a series of cellulose ester–graft–polylactide copolymers was synthesized using a homogeneous one-pot system in which the reaction medium was the ionic liquid 1-ethyl-3-methylimidazolium diethylphosphate (EmimDEP). The structures and compositions of the copolymers were controlled by varying the feed ratio of the carboxylic anhydride (acetic (C2), propionic (C3), or hexanoic (C6)) and L-lactide. In terms of side-chain substitution, the copolymers exhibited DSAcyl values of 0.7–2.7 and MSPLA values of 3.2–14.2. With increasing DSAcyl, the copolymers presented enhanced thermal stability and thermoplasticity due to the intermolecular interactions between the acyl groups and polylactide side-chains. The effect of graft-chain composition on mechanical properties and biodegradability was investigated using homogeneous cast films prepared with the copolymers. The mechanical properties were found to be affected by the carbon number of the acyl group (C2–C6), with higher carbon numbers imparting better plasticization. To investigate biodegradability, a two-step enzymatic degradation was performed using proteinase K and then cellulase. The copolymers with DSAcyl values below 1.3 exhibited enzymatic biodegradability with weight losses in the range 15.2%–34.6% (cf. 58.4% for polylactide).

Dual-Bed Plasma/Catalytic Synergy for Methane Transformation into Aromatics

Direct conversion of methane to aromatics (benzene, toluene, and xylene, briefly BTX) remains a formidable challenge. Here, we demonstrate that CH4 can be efficiently transformed into BTX through the coupling of a dielectric barrier discharge (DBD) plasma reactor with a thermocatalytic aromatization reactor (at temperatures ≤ 550 °C). With the assistance of DBD plasma, methane can be activated by the energetic electrons to form various radicals, which are recombined to produce a mixture of C2–C6 light alkanes and alkenes. With a plasma power deposition of 12 W, the conversion of CH4 is up to 50% dependent upon the partial pressure. The energy efficiency is between 0.3 to 1.5 mol/(kW h) dependent upon the power deposition. The C2–C6 light hydrocarbons from the plasma reactor can be transformed into BTX over various catalysts at temperatures ≤ 550 °C. With the Ga/HZSM-5 catalyst, the selectivity of total BTX is up to 70% dependent upon the reaction conditions (temperature, partial pressure, and catalyst loading). With such a dual-bed plasma/catalytic tandem system, CH4 conversion and BTX yield only slightly deactivated with time-on-stream up to 1000 min and can be 100% regenerated through coke burnoff. We suggest that the dual-bed plasma/catalytic reaction system could be interesting for small-scale onsite flare gas or biogas conversion.

Estimation of the minimum miscibility pressure for CO2–crude-oil systems by molecular dynamics simulation

CO2 injection is an effective enhanced oil recovery technique for energy security with the benefits of carbon neutrality. To reach the maximum oil recovery, the miscible condition between CO2 and oil needs to be maintained in the reservoir, which requires the operation pressure to be higher than the minimum miscibility pressure (MMP). There are two types of MMPs: the first-contact MMP (FC-MMP) and the multi-contact MMP (MC-MMP). In this study, molecular dynamics simulations were performed for the CO2–oil interface system using two simplified digital oil models: a Bakken dead oil with four lumping components and a live-crude-oil model with 50 types of oil molecules but with no asphaltenes and heavy oil fractions. The vanishing interfacial tension method was used to predict the MMP. Different CO2–oil volume ratios were considered to mimic the different degrees of vaporization. To estimate the MMP accurately and rapidly, the interfacial tension in the low-pressure regime was used for the prediction. Consequently, different MMPs were obtained, where the MMP value increased with increasing CO2–oil volume ratio. FC-MMP can be predicted when the CO2–oil volume ratio is sufficiently high. When the CO2–oil volume ratio was approximately 9–10, MMP was closest to the actual MC-MMP value. The condensing and vaporizing mechanism was also studied at the molecular scale. Because pure CO2 was used, only the vaporizing effect on MMP occurred. It was found that the intermediate C2–C6 components have the main effect on the MMP calculation. This study can help to establish a computational protocol to estimate FC-MMP and MC-MMP, which are widely used in reservoir engineering.

Carbon isotopic composition of methane and its origin in natural gas from the Petišovci-Dolina oil and gas field (Pannonian Basin System, NE Slovenia) – a preliminary study

The carbon isotopic composition of methane (δ13CCH4) in natural gas from the Petišovci-Dolina oil and gas field (NE Slovenia) was measured for the first time in August and September 2021. The gas samples from different depths were taken from three wells: Dolina-deep (Pg-6) from the depth interval 3102–3104 m, Petišovci-deep (Pg-5) from the depth interval 2772–2795 m, and Petišovci-shallow (D-5) from the depth interval 1212–1250 m. According to the available composition dataset of gas, available from the Petrol Geo d.o.o. documentation, the “deep” gases sampled from the Pg-6 and Pg-5 wells consist of 85 % methane (C1), 11 % hydrocarbons heavier than methane (C2–C6) and 4 % CO2. The “shallow” gas from well D-5 contains more than 89 % methane, up to 11 % C2–C6 gases, while the CO2 content is negligible. The “deep« gas from the Pg-6 and Pg-5 wells has δ13CCH4 -36.7 ‰ and -36.6 ‰, respectively, while the “shallow” gas from the D-5 well has the δ13CCH4 of -38.6 ‰. The methane from the “shallow” gas is slightly enriched in the lighter 12C isotope. δ13CCH4 in the range from -38.6 to -36.6 ‰ clearly indicates the thermogenic origin of methane formed during the catagenesis phase of gas formation.

Total chemocatalytic cascade conversion of lignocellulosic biomass into biochemicals

Because of its complexity, selective conversion of lignocellulosic biomass into platform chemicals presents significant challenges. Herein, we converted birch wood into high-yield lignin-derived phenolic monomers and dimers and holocellulose-derived polyols and monocarboxylic acids via a two-step cascade reaction using 0.1 wt% Pd on N-doped carbon (Pd0.1/CNx) and passivated alumina-coated Ni on activated carbon (Ni2 @Al2O3/AC) catalysts. The catalytic fractionation of birch sawdust using Pd0.1/CNx produced 11.1 wt% monomers, 5.6% dimers, and 63.4 wt% pulp-rich solid (PRS) based on feed weight. The subsequent conversion of PRS over passivated Ni2 @Al2O3/AC produced 21.6 wt% C2–C6 polyols and 7.9 wt% monocarboxylic acids. After the whole biomass conversion reaction, the Pd0.1/CNx and Ni2 @Al2O3/AC catalysts were separated using their different magnetic responses and reused three times without activity loss. The structure–performance relationships of the Pd0.1/CNx catalysts synthesized using different methods and effect of passivation on the performance of the Ni2 @Al2O3/AC catalyst were analyzed.

Response to Comment on Hydrogen and C2-C6 Alkane Sensing in Complex Fuel Gas Mixtures with Fiber-Enhanced Raman Spectroscopy.

Response to Comment on Hydrogen and C2-C6 Alkane Sensing in Complex Fuel Gas Mixtures with Fiber-Enhanced Raman Spectroscopy.

Comment on Hydrogen and C2-C6 Alkane Sensing in Complex Fuel Gas Mixtures with Fiber-Enhanced Raman Spectroscopy.

Comment on Hydrogen and C2-C6 Alkane Sensing in Complex Fuel Gas Mixtures with Fiber-Enhanced Raman Spectroscopy.

Saturated Vapor Pressures and Enthalpies of Vaporization of Diesters of Neopentyl Glycol and Linear C2–C6 Acids

Saturated Vapor Pressures and Enthalpies of Vaporization of Diesters of Neopentyl Glycol and Linear C2–C6 Acids

Hydrogen and C2-C6 Alkane Sensing in Complex Fuel Gas Mixtures with Fiber-Enhanced Raman Spectroscopy.

Power-to-gas is a heavily discussed option to store surplus electricity from renewable sources. Part of the generated hydrogen could be fed into the gas grid and lead to fluctuations in the composition of the fuel gas. Consequently, both operators of transmission networks and end users would need to frequently monitor the gas to ensure safety as well as optimal and stable operation. Currently, gas chromatography-based analysis methods are the state of the art. However, these methods have several downsides for time-resolved and distributed application and Raman gas spectroscopy is favorable for future point-of-use monitoring. Here, we demonstrate that fiber-enhanced Raman gas spectroscopy (FERS) enables the simultaneous detection of all relevant gases, from major (methane, CH4; hydrogen, H2) to minor (C2-C6 alkanes) fuel gas components. The characteristic peaks of H2 (585 cm-1), CH4 (2917 cm-1), isopentane (765 cm-1), i-butane (798 cm-1), n-butane (830 cm-1), n-pentane (840 cm-1), propane (869 cm-1), ethane (993 cm-1), and n-hexane (1038 cm-1) are well resolved in the broadband spectra acquired with a compact spectrometer. The fiber enhancement achieved in a hollow-core antiresonant fiber enables highly sensitive measurements with limits of detection between 90 and 180 ppm for different hydrocarbons. Both methane and hydrogen were quantified with high accuracy with average relative errors of 1.1% for CH4 and 1.5% for H2 over a wide concentration range. These results show that FERS is ideally suited for comprehensive fuel gas analysis in a future, where regenerative sources lead to fluctuations in the composition of gas.

Uptake and translocation of perfluoroalkyl acids with different carbon chain lengths (C2-C8) in wheat (Triticum acstivnm L.) under the effect of copper exposure.

The co-contamination by perfluoroalkyl acids (PFAAs) and heavy metals (HMs) is ubiquitous in the surface environment subjected to sewage irrigation and land application of sludge. However, the joint effects of HMs and PFAAs on plant roots are not well clarified. This study explored the root uptake and acropetal translocation behaviors of C2-C8 PFAAs by wheat (Triticum acstivnm L.) under the co-exposure of copper (Cu). The underlying uptake mechanisms of PFAAs were verified in a defective root system. The results showed that excessive Cu (100-400μmol/L) damaged the cell membrane of wheat root to increase electrolytic leakage. In the defective root system, the root concentrations of PFAAs decreased by 6%-73% and the decrease rates were negatively associated with the carbon chain length of PFAAs. Along with the decrease in root concentrations of PFAAs, the amount of ultrashort-chain (C2-C3) and short-chain (C4-C6) PFAAs translocated to the shoot also decreased by 45%-84%. In contrast, the acropetal translocation of long-chain (C8) PFAAs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), was enhanced under Cu exposure due to the increase in root permeability as observed by increased electrolytic leakage. The shoot concentrations of PFOA and PFOS under Cu exposure were up to 5.5 and 11 times higher than those in the control, respectively. These results suggested that PFOA and PFOS could enter wheat root more easily through the breaks caused by Cu exposure and thereby their acropetal transportation to shoot was enhanced. Therefore, the risk of plant accumulation of long-chain PFAAs can be potentially underestimated if without considering the co-contamination with HMs in the environment.

Influence of Culture Conditions on the Bioreduction of Organic Acids to Alcohols by Thermoanaerobacter pseudoethanolicus.

Thermoanaerobacter species have recently been observed to reduce carboxylic acids to their corresponding alcohols. The present investigation shows that Thermoanaerobacter pseudoethanolicus converts C2–C6 short-chain fatty acids (SCFAs) to their corresponding alcohols in the presence of glucose. The conversion yields varied from 21% of 3-methyl-1-butyrate to 57.9% of 1-pentanoate being converted to their corresponding alcohols. Slightly acidic culture conditions (pH 6.5) was optimal for the reduction. By increasing the initial glucose concentration, an increase in the conversion of SCFAs reduced to their corresponding alcohols was observed. Inhibitory experiments on C2–C8 alcohols showed that C4 and higher alcohols are inhibitory to T. pseudoethanolicus suggesting that other culture modes may be necessary to improve the amount of fatty acids reduced to the analogous alcohol. The reduction of SCFAs to their corresponding alcohols was further demonstrated using 13C-labelled fatty acids and the conversion was followed kinetically. Finally, increased activity of alcohol dehydrogenase (ADH) and aldehyde oxidation activity was observed in cultures of T. pseudoethanolicus grown on glucose as compared to glucose supplemented with either 3-methyl-1-butyrate or pentanoate, using both NADH and NADPH as cofactors, although the presence of the latter showed higher ADH and aldehyde oxidoreductase (ALDH) activity.

Perceptual Quality of Nonesterified Fatty Acids Varies with Fatty Acid Chain Length.

Nonesterified fatty acids (NEFA) are effective taste stimuli. The quality they impart has not been well characterized. Sourness, and "fattiness" have been reported, but an irritation component has also been described and how these transition with gradations of aliphatic chain length has not been systematically studied. This study examined intensity and quality ratings of NEFA ranging from C2 to C18. Oral sites and the time course of sensations were also monitored. Given all NEFA contain carboxylic acid moieties capable of donating hydrogen ions, the primary stimulus for sour taste, testing was conducted with and without sour adaptation to explore the contribution of sour taste across the range of NEFA. Short-chain NEFA (C2-C6) were rated as predominantly sour, and this was diminished in C2 and C4 by sour adaptation. Medium-chain NEFA (C8-C12) were rated as mainly irritating with long-chain NEFA (C18) described mostly as bitter. The latter may reflect the lack of "fatty" lexicon to describe the sensation. Short-chain NEFA were mostly localized to the anterior tongue and were of rapid onset. The sensation from medium-chain NEFA was attributed to the lateral tongue, whereas medium- and long-chain NEFA sensations were predominantly localized to the back of the tongue and throat and had a longer lag time. The findings indicate there is a systematic transition of NEFA taste quality and irritation with increments in chain length and this is consistent with multiple modes of transduction.

Heterogeneous alkane dehydrogenation catalysts investigated via a surface organometallic chemistry approach.

The selective conversion of light alkanes (C2–C6 saturated hydrocarbons) to the corresponding alkene is an appealing strategy for the petrochemical industry in view of the availability of these feedstocks, in particular with the emergence of Shale gas. Here, we present a review of model dehydrogenation catalysts of light alkanes prepared via surface organometallic chemistry (SOMC). A specific focus of this review is the use of molecular strategies for the deconvolution of complex heterogeneous materials that are proficient in enabling dehydrogenation reactions. The challenges associated with the proposed reactions are highlighted, as well as overriding themes that can be ascertained from the systematic study of these challenging reactions using model SOMC catalysts.

Inferior selective crossectomy for great saphenous vein incompetence: Our experience.

To describe the mid-term outcome after inferior selective crossectomy in a subset of patients with symptomatic chronic venous disease and both great saphenous vein and suprasaphenic valve incompetence.Methodsː Retrospective analysis of prospectively collected data was conducted. During an eight-year period, 1095 ligations of all saphenofemoral junction inferior tributaries and great saphenous vein stripping were performed in 814 Clinical, Etiology, Anatomy, Pathophysiology C2-C6 patients. Duplex ultrasound follow-up examinations were performed after 30 days, 6 months, and 2 years, and saphenofemoral junction hemodynamic patterns and varicose veins recurrence rates were evaluated. Two hundred and twenty patients completed the two-year follow-up period. At the 30-day Duplex ultrasound evaluations, two different hemodynamic patterns were described. Type 1, with physiological drainage of saphenofemoral junction superior tributaries, was observed in 214 patients. Type 2, without flow in saphenofemoral junction superior tributaries, was observed in six patients. Overall varicose vein recurrence rates were 0, 2.3, and 2.7% at the 30-day, 6-month, and 2-year follow-up examinations, respectively. At the two-year follow-up, Type 1 patients showed 0% varicose vein recurrence, while Type 2 patients showed 100%.Conclusionsː Inferior selective crossectomy seems to be a valid and safe option in case of both suprasaphenic valve and great saphenous vein incompetence. Duplex ultrasound evaluation, according to our protocol, allows us to identify two different saphenofemoral junction hemodynamic patterns that could predict varicose vein recurrence at mid-term. An optimal stump washing after inferior selective crossectomy, warranted by patency and large caliber saphenofemoral junction superior tributaries, seems to be the key point in preventing varicose vein recurrence in this context. However, large prospective studies regarding saphenofemoral junction modifications and varicose vein recurrence are needed to confirm these preliminary observations.

Detailed Analysis of Sewage Sludge Pyrolysis Gas: Effect of Pyrolysis Temperature

Conventional methods of sewage sludge disposal are often limited by their environmental impact and economic demands. Pyrolysis has been studied as a viable method for sewage sludge disposal and transformation into usable products. Pyrolytic products may have various uses, and their complex characteristics shall be described to assess their potential for safe utilization. Here, we studied slow pyrolysis of stabilized sewage sludge in a fixed bed reactor at 400–800 °C to describe the composition of the pyrolysis gas and the condensate fraction. We found that condensate elemental composition was practically independent of pyrolysis temperature. On the other hand, the composition of the pyrolysis gas was strongly temperature-dependent regarding both the share of major components (H2, CO, CO2, CH4) and C2–C6 hydrocarbons speciation (which as a sum attributed to 7–9 vol. % of the gas). The increase in pyrolysis temperature also resulted in increasing the N2 content of the gas, whereas the sulfur containing gas compounds were substantially diluted in the increasing gas volume.